Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the American College of Physicians Use of Calcium Supplements, Vitamin D Supplements and Specific Osteoporosis Drugs Among French Women Aged 75–85 Years: Patterns of Use and Associated Factors Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation Dietary calcium and vitamin D intake in relation to osteoporotic fracture risk. 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Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence Low acceptance of treatment in the elderly for the secondary prevention of osteoporotic fracture in the acute rehabilitation setting Single-dose cholecalciferol suppresses the winter increase in parathyroid hormone concentrations in healthy older men and women: a randomized trial. The Women's Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. Dietary Protein and Vitamin D Intake and Risk of Falls: A Secondary Analysis of Postmenopausal Women from the Study of Osteoporotic Fractures Hypovitaminosis D and 'functional hypoparathyroidism'-the NoNoF (Nottingham Neck of Femur) study. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. Evaluating the cost-effectiveness of fall prevention programs that reduce fall-related hip fractures in older adults. Screening for Postmenopausal Osteoporosis: A Review of the Evidence for the U.S. Preventive Services Task Force [Optimization of calcium intake for the prevention of osteoporosis and osteoporotic fractures: a review of the evidence]. The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. Mortality after all major types of osteoporotic fracture in men and women: an observational study Determinants of bone mineral density in older men. Vitamin D3 and calcium to prevent hip fractures in elderly women. Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study Estrogen replacement therapy and fractures in older women. Study of Osteoporotic Fractures Research Group. Prescribing by general practitioners after an osteoporotic fracture Multivitamin and mineral supplementation is associated with the reduction of fracture risk and hospitalization rate in Chinese adult males: a randomized controlled study Effect of vitamin D(3) and calcium on fracture risk in 65- to 71-year-old women: a population-based 3-year randomized, controlled trial--the OSTPRE-FPS. Vitamin D and health in adults in Australia and New Zealand: a position statement. Osteoporosis prevalence and levels of treatment in primary care: the Australian BoneCare Study. Once-weekly risedronate for prevention of hip fracture in women with Parkinson's disease: a randomised controlled trial Type of dietary fat is associated with the 25-hydroxyvitamin D3 increment in response to vitamin D supplementation. Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care Osteoporosis and fractures in postmenopausal women using estrogen. An initial loading-dose vitamin D versus placebo after hip fracture surgery: randomized trial Consumption of yogurts fortified in vitamin D and calcium reduces serum parathyroid hormone and markers of bone resorption: a double-blind randomized controlled trial in institutionalized elderly women. Calcium-vitamin D3 supplementation is cost-effective in hip fractures prevention. Evaluation of Bone Mineral Density Loss in Morbidly Obese Women After Gastric Bypass: 3-Year Follow-Up Endometrial, breast and liver safety of soy isoflavones plus Lactobacillus sporogenes in post-menopausal women Risk of subsequent fracture after low-trauma fracture in men and women. Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules An initial loading-dose vitamin D versus placebo after hip fracture surgery: baseline characteristics of a randomized controlled trial (REVITAHIP) Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study. The Effect of Calcium and Vitamin D3 Supplementation on the Healing of the Proximal Humerus Fracture: A Randomized Placebo-Controlled Study Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS) Effect of Recombinant Human Parathyroid Hormone (1-84) on Vertebral Fracture and Bone Mineral Density in Postmenopausal Women with Osteoporosis Distribution and correlates of serum 25-hydroxyvitamin D levels in a sample of patients with hip fracture. Vitamin D Supplementation and Fracture Incidence in Elderly Persons Serum vitamin D and falls in older women in residential care in Australia. Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study VITAL-Bone Health: rationale and design of two ancillary studies evaluating the effects of vitamin D and/or omega-3 fatty acid supplements on incident fractures and bone health outcomes in the VITamin D and OmegA-3 TriaL (VITAL). Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women. Estimation of the optimum dose of vitamin D for disease prevention in older people: Rationale, design and baseline characteristics of the BEST-D trial Calcium plus vitamin D supplementation and the risk of fractures. Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group. Guidelines for the prevention of falls in people over 65 Fluoride Salts are no Better at Preventing New Vertebral Fractures than Calcium-Vitamin D in Postmenopausal Osteoporosis: The FAVOStudy Low fractional calcium absorption increases the risk for hip fracture in women with low calcium intake. Study of Osteoporotic Fractures Research Group. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores [Comparative study of dietary intake and nutritional status in elderly women with and without hip fracture]. Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO) Serum 25-OH vitamin D levels and risk of developing prostate cancer in older men Strontium ranelate prevents quality of life impairment in post-menopausal women with established vertebral osteoporosis Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group. Comparison of fracture, cardiovascular event, and breast cancer rates at 3 years in postmenopausal women with osteoporosis. Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. Alendronate and vitamin D2 for prevention of hip fracture in Parkinson's disease: a randomized controlled trial. Safety and efficacy of teriparatide in elderly women with established osteoporosis: bone anabolic therapy from a geriatric perspective. Postmenopausal bilateral oophorectomy is not associated with increased fracture risk in older women. Osteoporosis treatment in postmenopausal women after peripheral fractures: impact of information to general practitioners. Plasma phospholipid fatty acids and fish-oil consumption in relation to osteoporotic fracture risk in older adults: the Age, Gene/Environment Susceptibility Study. Association between self-reported prior wrist fractures and risk of subsequent hip and radiographic vertebral fractures in older women: a prospective study. Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post-hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial. Consumption of vitamin D-and calcium-fortified soft white cheese lowers the biochemical marker of bone resorption TRAP 5b in postmenopausal women at moderate risk of osteoporosis fracture. The Women's Health Initiative postmenopausal hormone trials: overview and baseline characteristics of participants. Combined Calcium and Vitamin D3 Supplementation in Elderly Women: Confirmation of Reversal of Secondary Hyperparathyroidism and Hip Fracture Risk: The Decalyos II Study Economic comparison of diagnostic approaches for evaluating osteoporosis in older women Teriparatide Improves Fracture Healing and Early Functional Recovery in Treatment of Osteoporotic Intertrochanteric Fractures Does vitamin D stop inpatients falling? A randomised controlled trial. Prevalence of osteoporosis in men and determinants of changes in bone mass in a non-selected Spanish population Thiazide diuretic agents and the incidence of hip fracture. Effects of risedronate alone or combined with vitamin K2 on serum undercarboxylated osteocalcin and osteocalcin levels in postmenopausal osteoporosis Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial. Evaluation of a fall-prevention program in older people after femoral neck fracture: a one-year follow-up Vitamin A intake and the risk of hip fracture in postmenopausal women: the Iowa Women’s Health Study Once-yearly zoledronic acid in older men compared with women with recent hip fracture. Response to teriparatide in patients with baseline 25-hydroxyvitamin D insufficiency or sufficiency. High-trauma fractures and low bone mineral density in older women and men. Bone mineral density and risk of breast cancer in older women: the study of osteoporotic fractures. Study of Osteoporotic Fractures Research Group. The association of consumption of fruits/vegetables with decreased risk of glaucoma among older African-American women in the study of osteoporotic fractures. A randomized controlled trial of mailed osteoporosis education to older adults Treatment of Osteoporosis in Australian Residential Aged Care Facilities: Update on Consensus Recommendations for Fracture Prevention. Injectable calcium phosphate bone cement Norian SRS for the treatment of intra-articular compression fractures of the distal radius in osteoporotic women Effect of long-term nutraceutical and dietary supplement use on cognition in the elderly: a 10-year systematic review of randomised controlled trials. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. Calcium and vitamin d supplementation decreases incidence of stress fractures in female navy recruits. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). Vitamin D insufficiency and health outcomes over 5 y in older women. Improving vision to prevent falls in frail older people: a randomized trial. Fracture incidence and characterization in patients on osteoporosis treatment: the ICARO study. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. Next steps for falls and fracture reduction. Predictors of Fractures in Elderly Women
 Older men with low serum IGF-1 have an increased risk of incident fractures: the MrOS Sweden study. Diuretic use and bone mineral density in older USA men: the osteoporotic fractures in men (MrOS) study. Effect of vitamin K supplementation on bone loss in elderly men and women. Risk factors for proximal humerus, forearm, and wrist fractures in elderly men and women: the Dubbo Osteoporosis Epidemiology Study. Calcium-Phosphate and Polymethylmethacrylate Cement in Long-term Outcome After Kyphoplasty of Painful Osteoporotic Vertebral Fractures Ultrasound Measurements for the Prediction of Osteoporotic Fractures in Elderly People
 Effects of Thiazide Diuretic Therapy on Bone Mass, Fractures, and Falls Physical activity and osteoporotic hip fracture risk in men. Weekly clodronate treatment prevents bone loss and vertebral fractures in women with subclinical Cushing’s syndrome Physical activity and decreased risk of clinical gallstone disease among post-menopausal women. Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women. Calcium, vitamin D supplementation, and physical function in the Women's Health Initiative. Two to three years of hormone replacement treatment in healthy women have long-term preventive effects on bone mass and osteoporotic fractures: the PERF study. Physical activity and osteoporotic fracture risk in older women. Study of Osteoporotic Fractures Research Group. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. Bone mineral density and bone markers in patients with a recent low-energy fracture: effect of 1 y of treatment with calcium and vitamin D. Dietary protein intake and risk of osteoporotic hip fracture in elderly residents of Utah. Between-meal risedronate does not alter bone turnover in nursing home residents. High‐Dose Monthly Vitamin D for Prevention of Acute Respiratory Infection in Older Long‐Term Care Residents: A Randomized Clinical Trial FokI polymorphism at translation initiation site of the vitamin D receptor gene predicts bone mineral density and vertebral fractures in postmenopausal Italian women. Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial Hip fracture prevention with a multifactorial educational program in elderly community-dwelling Finnish women Vitamin D supplementation improves neuromuscular function in older people who fall. Clinical Trials Express: Fracture Risk Reduction With Denosumab in Japanese Postmenopausal Women and Men With Osteoporosis: Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT) Calcium- and vitamin D3-fortified milk reduces bone loss at clinically relevant skeletal sites in older men: a 2-year randomized controlled trial. Relation of aromatase gene polymorphism and hormone replacement therapy to serum estradiol levels, bone mineral density, and fracture risk in early postmenopausal women* Homocysteine levels and the risk of osteoporotic fracture.
The National Institutes of Health 's consensus conference ( 1 ) defined osteoporosis as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk for fracture . Bone strength reflects the integration of two main features : bone density and bone quality .Bone quality refers to architecture , turnover , damage accumulation ( e.g. , microfractures ) , and mineralization . Although osteoporosis can affect any bone , the hip , spine , and wrist are most likely to be affected . Osteoporosis affects an estimated 44 million Americans or 55 % of people 50 years of age or older . Another 34 million Americans are estimated to have low bone mass , meaning that they are at an increased risk for osteoporosis . Osteoporosis can be diagnosed by the occurrence of fragility fracture . In patients without fragility fracture , osteoporosis is often diagnosed by low bone density .  Dual x-ray absorptiometry ( DXA ) is the current gold st and ard test for diagnosing osteoporosis in people without an osteoporotic fracture .  Dual x-ray absorptiometry results are scored as st and ard deviations ( SDs ) from a young healthy norm ( usually female ) and reported as T-scores . For example , a T-score of 2 indicates a bone mineral density that is 2 SDs below the comparative norm . The international reference st and ard for the description of osteoporosis in postmenopausal women and in men age 50 years or older is a femoral neck bone mineral density of 2.5 SD or more below the young female adult mean ( 2 ) . Low bone density , as measured by DXA , is an imperfect predictor of fracture risk , identifying fewer than half the people who go on to have an osteoporotic fracture . Screening guidelines for women are well established ( 3 ) , and the American College of Physicians ( ACP ) recently published guidelines on screening for men ( 4 ) . This guideline presents the available evidence on various pharmacologic treatments to prevent fractures in men and women with low bone density or osteoporosis . Medications used to treat osteoporosis may affect different parts of the skeletal system differently , and efficacy for vertebral fractures does not necessarily imply efficacy for nonvertebral fractures . The target audience for this guideline is all clinicians and the target patient population is all adult men and women with low bone density or osteoporosis . These recommendations are based on the systematic evidence review by MacLean and colleagues ( 5 ) and the Agency for Healthcare Research and Quality sponsored Southern California Evidence -Based Practice Center evidence report ( 6 ) . The drugs currently approved for prevention of osteoporosis include alendronate , ib and ronate , risedronate , zoledronic acid , estrogen , and raloxifene . The drugs currently approved for treatment of osteoporosis include alendronate , ib and ronate , risedronate , calcitonin , teriparatide , zoledronic acid ( in postmenopausal women ) , and raloxifene . Testosterone , pamidronate , and etidronate are not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Methods The literature search done by MacLean and colleagues for the systematic review ( 5 ) included studies from MEDLINE ( 1966 to December 2006 ) , the ACP Journal Club data base , the Cochrane Central Register of Controlled Trials ( no date limits ) , the Cochrane Data base of Systematic Review s ( no date limits ) , Web sites of the United Kingdom National Institute of Health and Clinical Excellence ( no date limits ) , and the United Kingdom Health Technology Assessment Program ( January 1998 to December 2006 ) . The review ers limited their search to English- language publications and human studies . They derived evidence for comparative benefits of various treatments exclusively from r and omized , controlled trials , whereas they included evidence from other types of studies for short- and long-term harms . Two physicians independently abstract ed data about study population s , interventions , follow-up , and outcome ascertainment by using a structured form . For each group within a r and omized trial , a statistician extracted the sample size and number of persons reporting fractures . Two review ers , under the supervision of the statistician , independently abstract ed information about adverse events . The statistician or the principal investigator resolved disagreements . This guideline is based on an evaluation of 76 r and omized , controlled trials , 4 of which were identified in the up date d search , and 24 meta-analyses that were included in the efficacy analyses . The analyses of adverse events included 491 articles , representing 417 r and omized trials , 25 other controlled clinical trials , 11 open-label trials , 31 large observational studies , and 9 case reports of osteonecrosis among bisphosphonate users . MacLean and colleagues ' background article ( 5 ) includes details about the methods used for the systematic evidence review . The ACP rates the evidence and recommendations by using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) system with minor modifications ( Table 1 ) . In addition , the evidence review ers used predefined criteria to assess the quality of systematic review s and r and omized trials , based on internal and external validity assessment s detailed in the Quality of Reporting of Meta-Analyses ( QUOROM ) statement ( 7 ) . Table 1 . The American College of Physicians ' Guideline Grading System The objective of this guideline is to synthesize the evidence for the following questions : What are the comparative benefits in fracture reduction among and also within the following treatments for low bone density :  bisphosphonates , specifically alendronate , risedronate , etidronate , ib and ronate , pamidronate , and zoledronic acid ; calcitonin ; estrogen for women ; teriparatide ; selective estrogen receptor modulators ( SERMs ) , specifically raloxifene and tamoxifen ; testosterone for men ; vitamins and minerals , specifically vitamin D and calcium ; and the combination of calcium plus vitamin D ? How does fracture reduction result ing from treatments vary among individuals with different risks for fracture as determined by bone mineral density ( borderline , low , or severe ) , previous fractures ( prevention vs. treatment ) , age , sex , glucocorticoid use , and other factors ( such as community-dwelling vs. institutionalized or vitamin Ddeficient vs. not ) ? What are the short- and long-term harms ( adverse effects ) of these therapies , and do these vary by specific sub population s ? Comparative Benefits of Drugs versus Placebo in Fracture Reduction Evidence from 24 meta-analyses ( 830 ) and 35 additional r and omized trials published after the meta-analyses ( 3165 ) described the effect of 9 of the 14 agents ( alendronate , etidronate , risedronate , calcitonin , estrogen , teriparatide , raloxifene , calcium , and vitamin D ) on fracture incidence . For 4 agents ( ib and ronate , pamidronate , zoledronic acid , and tamoxifen ) , the review ers found no meta-analyses and instead gathered the evidence from 14 r and omized trials ( 6679 ) . No studies were found that reported fracture rates for testosterone . Three r and omized trials ( 35 , 80 , 81 ) and 1 meta- analysis ( 82 ) evaluated the combination of calcium plus vitamin D  on fractures .  Bisphosphonates Good- quality evidence showed that alendronate , etidronate , ib and ronate , and risedronate prevent vertebral fractures . In addition , evidence from good- quality studies demonstrated that both alendronate and risedronate prevent nonvertebral and hip fractures . Two large r and omized trials showed that zoledronic acid prevents vertebral and nonvertebral fractures in high-risk population s and reduces the risk for hip fracture ( 67 , 74 ) . Ib and ronate has not been shown to reduce nonvertebral fractures ( 68 ) . Of the 6 fairly small trials that looked at vertebral fractures , 1 demonstrated a statistically significant reduction in fractures with pamidronate relative to placebo ( 0.14 [ 95 % CI , 0.03 to 0.72 ] ) ( 73 ) . However , after these data were pooled , the pooled risk estimate for fractures for pamidronate relative to placebo was not significant ( 0.52 [ CI , 0.21 to 1.24 ] ) ( 6 ) . Calcitonin Fair- quality evidence shows that calcitonin reduces vertebral fractures ( 83 , 84 ) . Good- quality evidence indicates that calcitonin does not reduce nonvertebral fractures ( 13 , 16 ) . Estrogen Good- quality evidence shows that estrogen reduces the incidence of vertebral ( 29 , 85 ) , nonvertebral ( 86 ) , and hip fractures ( 85 ) . Teriparatide Good- quality evidence shows that teriparatide prevents vertebral fractures . The evidence related to teriparatide preventing nonvertebral fractures is mixed ; 1 large r and omized trial showed a reduction in nonvertebral fractures ( 34 ) but 2 small trials did not ( 87 , 88 ) . SERMs Good- quality evidence shows that raloxifene prevents vertebral fractures , but that tamoxifen has no effect on vertebral fractures ( 8991 ) . In addition , both raloxifene and tamoxifen had no effect on hip fractures ( 91 ) . Tamoxifen is not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Testosterone No studies reported fracture rates for testosterone . Calcium and Vitamin D In the studies evaluated by MacLean and colleagues ( 5 ) , the evidence for the effect of calcium alone on reduction of fractures is complex . Most studies of pharmacologic agents for osteoporosis include calcium and vitamin D as part of the treatment regimen . Evidence from 1 meta- analysis ( 27 ) and several r and omized trials ( 35 , 48 , 51 , 92 ) showed no significant difference between calcium and placebo in preventing vertebral , nonvertebral , and hip fractures in postmenopausal women . However , nonadherence to therapy may influence this result , and 1 trial with a prespecified analysis of adherent patients found a reduction in fracture risk ( 48 ) . A recent meta- analysis ( 82 ) concluded that the relative risk ( RR ) for fracture with calcium alone was 0.90 ( CI , 0.80 to 1.00 ) , but it did not include a modestly large trial with negative results ( 35 ) . MacLean and colleagues ( 5 ) Background Despite the availability of effective preventive and curative medications for osteoporosis , and guidelines for its diagnosis and management , few individuals are treated for osteoporosis , even among those who have already had a fracture . Objectives Our objective was to describe the patterns of use of medication for osteoporosis , i.e. , calcium supplements , vitamin D supplements , and specific anti-osteoporotic drugs , such as bisphosphonates , in a large sample of French older women living at home , and to identify individual factors associated with use of these medications overall and in two specific clinical situations . Methods Cross-sectional analysis of data from 4,221 women aged 75–85 years who participated in a balance and mobility examination as part of the screening procedure for the Ossébo study , a r and omized controlled trial testing the effectiveness of exercise for the prevention of fall-related injuries .  Electoral rolls  were used to invite women in 16 towns to participate ( participation rate 10.3 % ) . Information collected through question naires included current medication use and , in particular , use of osteoporosis medications ( specific osteoporosis drugs , calcium and vitamin D supplementation ) in the past 6 months , and history of fracture since the age of 50 , including fracture locations . Fractures were categorized in three groups : no fracture , major osteoporotic fracture ( hip , humerus , wrist , pelvis , and vertebra ) , and other fracture . Results Nearly 48 % of the participants reported they did not take calcium or vitamin D supplements or any specific  osteoporosis drugs  . Of the 2,133 women who reported using osteoporosis medication , 85 % used  vitamin D supplements ( 25 % as the sole medication against this disease ) , 59 % calcium supplements , and 42 % a specific anti-osteoporotic drug ( 75 % of them combining it with vitamin D supplementation ) . The use of any osteoporosis medication was significantly associated ( p < 0.001 ) with a history of a major osteoporotic fracture , lower weight , dual-energy X-ray absorptiometry ( DXA ) bone-density measurement in the past 5 years , a cancer-screening examination in the past 5 years , and a positive attitude toward medication use in general . Living alone was associated with a lower likelihood of using a specific anti-osteoporotic drug  , and a higher education level was associated with a higher likelihood of vitamin D supplementation . Of the 1,553 women who had already had a major osteoporotic fracture , one-third ( 34.8 % ) were not taking any osteoporosis medication . In this subgroup , use of this medication was associated with the same factors as in the overall study population . In particular , neither older age nor a history of falls in the previous 12 months was associated with a higher likelihood of using osteoporosis medication . Among the 909 women who reported using a specific osteoporosis drug , vitamin D use was associated with a higher educational level and a more frequent preventive attitude . Conclusion In France , as in other western countries , women aged 75 years and over are not managed according to guidelines . Further studies should address the barriers encountered in improving quality of care in osteoporosis management Description This guideline up date s the 2008 American College of Physicians ( ACP ) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women . This guideline is endorsed by the American Academy of Family Physicians . Methods The ACP Clinical Guidelines Committee based these recommendations on a systematic review of r and omized controlled trials ; systematic review s ; large observational studies ( for adverse events ) ; and case reports ( for rare events ) that were published between 2 January 2005 and 3 June 2011 . The review was up date d to July 2016 by using a machine-learning method , and a limited up date to October 2016 was done . Clinical outcomes evaluated were fractures and adverse events . This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density , including pharmaceutical prescriptions , calcium , vitamin D , and estrogen . Evidence was grade d according to the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) system . Target Audience and Patient Population The target audience for this guideline includes all clinicians . The target patient population includes men and women with low bone density and osteoporosis . Recommendation 1 ACP recommends that clinicians offer pharmacologic treatment with alendronate , risedronate , zoledronic acid , or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis . ( Grade : strong recommendation ; high- quality evidence ) . Recommendation 2 ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 3 ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinical ly recognized osteoporosis . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 4 ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 5 ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women . ( Grade : strong recommendation ; moderate- quality evidence ) . Recommendation 6 ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences , fracture risk profile , and benefits , harms , and costs of medications . ( Grade : weak recommendation ; low- quality evidence ) Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community  Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33 Introduction Osteoporotic fractures in older people are a major and increasing public health problem . We examined the effect of vitamin D supplementation on fracture rate in people living in sheltered accommodation . Methods In a pragmatic double blind r and omised controlled trial of 3 years duration , we examined 3,440 people ( 2,624 women and 816 men ) living in residential or care home . We used four-monthly oral supplementation using 100,000 IU vitamin D2 ( ergocalciferol ) . As a main outcome measure , we used the incidence of first fracture using an intention to treat analysis . This was a multicentre study in 314 care homes or sheltered accommodation complexes in South Wales , UK . Results The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , 205 first fractures occurred in the intervention group during a total of 2,846 person years of follow-up ( 7 fractures per 100 people per year of follow-up ) , with 218 first fractures in the control group over 2,860 person years of follow-up . The hazard ratio of 0.95 ( 95 % confidence interval 0.79–1.15 ) for intervention compared to control was not statistically significant . ConclusionS upplementation with four-monthly 100,000 IU of oral vitamin D2 is not sufficient to affect fracture incidence among older people living in institutional care The etiologic role of dietary calcium and vitamin D intake in primary prevention of  osteoporotic fractures is uncertain , despite considerable research efforts . With the aim to examine these associations with an improved precision , we used data from a large population -based prospect i ve cohort study in central Sweden . We estimated nutrient intake from a self-administered food-frequency question naire filled in by 60,689 women , aged 40 - 74 years at baseline during 1987 - 1990 . During follow-up , we observed 3986 women with a fracture at any site and 1535 with a hip fracture .  Rate ratio of fractures ( RR ) and 95 % CI were estimated using Cox proportional hazards models . We found no dose-response association between dietary calcium intake and fracture risk . The age-adjusted RR of hip fracture was 1.01 ( 95 % CI 0.96 - 1.06 ) per 300 mg calcium/day and the corresponding risk of any osteoporotic fracture was 0.99 ( 95 % CI 0.96 - 1.03 ) . Furthermore , women with an estimated calcium intake below 400 mg/day and those with a calcium intake higher than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with intermediate calcium intakes : RR 1.07 ( 95 % CI 0.92 - 1.24 ) and RR 1.00 ( 95 % CI 0.79 - 1.27 ) , respectively . Vitamin D intake was not associated with fracture risk . Furthermore , women in the highest quintiles compared to the lowest quintiles of both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all fractures ( 95 % CI 0.88 - 1.17 ) . Dietary calcium or vitamin D intakes estimated at middle and older age do not seem to be of major importance for the primary prevention of osteoporotic fractures in women BACKGROUND Elevated plasma homocysteine concentrations are a risk factor for osteoporotic fractures . Lowering homocysteine with combined vitamin B-12 and folic acid supplementation may reduce fracture risk . OBJECTIVE This study [ B-vitamins for the PRevention Of Osteoporotic Fractures ( B-PROOF ) ] aim ed to determine whether vitamin B-12 and folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly individuals . DESIGN This was a double-blind , r and omized , placebo-controlled trial in 2919 participants aged ≥65 y with elevated homocysteine concentrations ( 12 - 50 μmol/L ) . Participants were assigned to receive daily 500 μg vitamin B-12 plus 400 μg folic acid or placebo supplementation for 2 y. Both intervention and placebo tablets also contained 600 IU vitamin D3 . The primary endpoint was time to first osteoporotic fracture . Exploratory prespecified subgroup analyses were performed in men and women and in individuals younger than and older than age 80 y. Data were analyzed according to intention-to-treat and per- protocol principles . RESULTS Osteoporotic fractures occurred in 61 persons ( 4.2 % ) in the intervention group and 75 persons ( 5.1 % ) in the placebo group . Osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses ( HR : 0.84 ; 95 % CI : 0.58 , 1.21 ) or per- protocol analyses ( HR : 0.81 ; 95 % CI : 0.54 , 1.21 ) . For persons aged > 80 y , in per- protocol analyses , osteoporotic fracture risk was lower in the intervention group than in the placebo group ( HR : 0.27 ; 95 % CI : 0.10 , 0.74 ) . The total number of adverse events ( including mortality ) did not differ between groups . However , 63 and 42 participants in the intervention and placebo groups , respectively , reported incident cancer ( HR : 1.56 ; 95 % CI : 1.04 , 2.31 ) . CONCLUSIONS These data show that combined vitamin B-12 and folic acid supplementation had no effect on osteoporotic fracture incidence in this elderly population . Exploratory subgroup analyses suggest a beneficial effect on osteoporotic fracture prevention in compliant persons aged > 80 y. However , treatment was also associated with increased incidence of cancer , although the study was not design ed for assessing cancer outcomes . Therefore , vitamin B-12 plus folic acid supplementation can not be recommended at present for fracture prevention in elderly people . The B-PROOF study was registered with the Netherl and s Trial Register ( trialregister.nl ) as NTR1333 and at clinical trials.gov as NCT00696414 For a 50-year old caucasian woman today , the risk of a hip fracture over her remaining lifetime is about 17 % . Tomorrow the situation will clearly be worse because the continual increase in life expectancy will cause a 3-fold rise in worldwide fracture incidence over the next 60 years , particularly in women , but also in men . In addition , a secular increase in the incidence of hip fractures in individuals of the same age has been noted in both sexes by several investigators , and the cost of hip fractures is expected to dramatically increase in the next decades . Consequently , preventive strategies are urgently required . A great deal has been learned in recent years about the risk factors for hip fracture , the pathophysiology of this fracture , and the prediction of fracture risk , particularly through bone mass measurements on the hip and biochemical evaluations of parathyroid and vitamin D status . The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility . A substantial femoral bone loss continues throughout the old age , with a continuous and exponential increase in the risk of hip fracture , and any reduction or arrest of this loss will induce an important reduction in the incidence of hip fractures . A preventive effect on the risk of hip fracture may be partly achieved by using long term estrogen replacement therapy after menopause , but also by using vitamin D and calcium supplements for a late prevention in elderly people .  Vitamin D insufficiency and deficit in calcium intake are very common in elderly people living either in institutions or at home , particularly in Europe where dairy products are not fortified with vitamin D. The cumulative response to this deficit in calcium intake and low vitamin D status is a negative calcium balance which stimulates parathyroid hormone secretion . In 300 residents of nursing homes , we recently found a significant negative correlation between serum 25 OHD and log serum PTH after age-adjustment . In addition , in 446 elderly women living at home in 5 French cities and selected from the voting lists , we also found an age-adjusted relationship between serum 25 OHD and PTH concentrations . This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements . We have shown in a 3-year controlled prospect i ve study that the daily use of these supplements ( 1.2 g of calcium and 800 IU of vitamin D3 ) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced of 23 % ( intention-to-treat analysis ) the number of hip fractures and other non vertebral fractures . In parallel , serum perathyroid hormone concentration was reduced of 28 % and low serum 25-hydroxyvitamin D concentration returned to normal values . After 18 months of treatment the bone density of the total proximal femoral region had increased 2.7 % the vitamin D3-calcium group and decreased 4.6 % in the placebo group ( p < 0.001 ) . This prevention is safe and can be recommended in people living in institutions . It could be also useful in other elderly subjects particularly at risk because of a low calcium intake , an absence of solar exposure and a previous history of falls . From the data of our study we assessed the economic consequences in terms of medical cost of this prevention . In case of treatment of all women living in nursing homes in France , this would saved FF 150000000 per year , the economic balance of prevention becoming positive as soon as the age of the beginning of the prevention reaches 73.5 years . It is now possible to partly stop bone loss in elderly people and it is never too late to prevent hip fractures with calcium and vitamin D supplements UNLABELLED This study of 9605 community-dwelling residents supports that vitamin D and calcium supplementation may prevent  osteoporotic fractures in elderly in a northern European region known to be deficient in vitamin D , especially during winter periods . INTRODUCTION We evaluated the effect of two programs for the prevention of osteoporotic fractures leading to acute hospital admission in a population of elderly community-dwelling residents . MATERIAL S AND METHODS This was a factorial , cluster-r and omized , pragmatic , intervention study . We included 9605 community-dwelling residents aged 66 + years . We offered a prevention program of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU ( 10 microg ) of vitamin D3 to a total of 4957 participants . Another program with evaluation and suggestions for the improvement of the domestic environment was offered to a total of 5063 participants . Both programs included revision of the resident 's current pharmaceutical treatment . We achieved information on osteoporotic fractures in the study population from the Danish Hospital Registration Data base . We defined osteoporotic fractures as low energy fractures of the proximal humerus , distal forearm , vertebral column , pelvis , cervical femur , and intertrochanteric femur . RESULTS Active participation was 50.3 % in the Calcium and Vitamin D Program and 46.4 % in the Environmental and Health Program . We observed a 16 % reduction in fracture incidence rate ( relative risk [ RR ] , 0.84 ; CI , 0.72 - 0.98 ; p < 0.025 ) among male and female residents offered the Calcium and Vitamin D Program ( intention-to-prevent analysis ) . CONCLUSIONS This study supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in community-dwelling elderly people in a northern European region known to be deficient in vitamin D , especially during winter periods BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo .  Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo .  Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P<0.001 ) . The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures BACKGROUND Short trials of calcium supplementation show that it reduces loss of bone density in postmenopausal women ; longer observational studies do not generally find a lower risk of hip fracture with higher-calcium diets . Fewer studies have focused on vitamin D in preventing postmenopausal osteoporosis or fractures . OBJECTIVE We assessed relations between postmenopausal hip fracture risk and calcium , vitamin D , and milk consumption . DESIGN In an 18-y prospect i ve analysis in 72 337 postmenopausal women , dietary intake and nutritional supplement use were assessed at baseline in 1980 and up date d several times during follow-up . We identified 603 incident hip fractures result ing from low or moderate trauma .  Relative risks ( RRs ) from proportional hazards models were controlled for other dietary and nondietary factors . RESULTS Women consuming > or = 12.5 microg vitamin D/d from food plus supplements had a 37 % lower risk of hip fracture ( RR = 0.63 ; 95 % CI : 0.42 , 0.94 ) than did women consuming < 3.5 microg/d . Total calcium intake was not associated with hip fracture risk ( RR = 0.96 ; 95 % CI : 0.68 , 1.34 for > or = 1200 compared with < 600 mg/d ) . Milk consumption was also not associated with a lower risk of hip fracture ( P for trend = 0.21 ) . CONCLUSIONS An adequate vitamin D intake is associated with a lower risk of osteoporotic hip fractures in postmenopausal women . Neither milk nor a high-calcium diet appears to reduce risk . Because women commonly consume less than the recommended intake of vitamin D , supplement use or dark fish consumption may be prudent Background Osteoporosis is a major health problem , and the economic burden is expected to rise due to an increase in life expectancy throughout the world . Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk . As vitamin B12 and folate intake and status play a large role in homocysteine metabolism , it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration . Methods / Design The B-PROOF ( B-Vitamins for the PRevention Of Osteoporotic Fractures ) study is a r and omized double-blind placebo-controlled trial . The intervention comprises a period of two years , and includes 2919 subjects , aged 65 years and older , independently living or institutionalized , with an elevated homocysteine concentration ( ≥ 12 μmol/L ) . One group receives daily a tablet with 500 μg vitamin B12 and 400 μg folic acid and the other group receives a placebo tablet . In both tablets 15 μg ( 600 IU ) vitamin D is included . The primary outcome of the study is osteoporotic fractures . Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers , physical performance and physical activity including falls , nutritional intake and status , cognitive function , depression , genetics and quality of life . This large multi-center project is carried out by a consortium from the Erasmus MC ( Rotterdam , the Netherl and s ) , VUmc ( Amsterdam , the Netherl and s ) and Wageningen University , ( Wageningen , the Netherl and s ) , the latter acting as coordinator . Discussion To our best knowledge , the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population . We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013 . The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures . Trial Registration The B-PROOF study is registered with the Netherl and s Trial ( NTR NTR1333 ) and with Clinical Trials.gov ( NCT00696514 ) Background and aims : Given the high risk of subsequent fracture among elderly persons with fracture , it is important to initiate secondary treatment for osteoporosis . Acute rehabilitation centers may offer a unique opportunity to introduce treatment . Therefore , we evaluated willingness-to-participate and compliance with evidence -based interventions for the secondary prevention of  osteoporotic fracture in a non-r and omized study conducted in the acute rehabilitation setting . We also described differences in baseline characteristics between study participants and non- participants . Methods : All consecutive , community-dwelling admissions to an acute rehabilitation unit ( Boston , MA ) with the diagnosis of fracture were screened for enrollment . Eligible subjects were offered a free , 6-month supply of alendronate/cholecalciferol ( 70 mg/2800 IU weekly ) , calcium and vitamin D supplements , and fall prevention strategies . Six-month compliance ( ≥75 % consumption of medication or supplement ) with the interventions was determined at a home visit . Results : Among 62 eligible subjects , 25 agreed to participate . Non- participants were older than participants ( 86 vs 80 yrs , p<0.01 ) . There was no significant difference between other characteristics of participants and non- participants including sex , weight , type of fracture , cognitive status , and functional status . The most common reason for non-participation was reluctance to take another medication . Among participants , only 52 % were compliant with alendronate and 58 % were compliant with calcium and vitamin D supplementation at 6 months . Conclusions : Willingness-to-participate and compliance with secondary prevention strategies for osteoporosis was low in the acute rehabilitation setting , even when medications were provided free of cost . Educating individuals with fracture and their families on the consequences and treatment of osteoporosis may help to decrease the risk of sustaining a second fracture by accepting secondary preventive measures A r and omized double-blind controlled trial of a single oral dose of 2.5 mg ( 100,000 IU ) cholecalciferol ( vitamin D3 ) was conducted in the winter in 189 healthy free-living men and women aged 63 - 76 y. The mean baseline serum concentration for 25-hydroxyvitamin D was 34.5 nmol/L and for parathyroid hormone 3.18 pmol/L. After 5 wk , mean serum 25-hydroxyvitamin D concentrations were 60 % higher in the treated than in the placebo group ( P < 0.001 ) . There was a 12 % difference in parathyroid hormone concentrations in the treated compared with the placebo group ( P < 0.001 ) . No differences in serum calcium were seen . Findings suggest that 25-hydroxyvitamin D has a physiological role in the regulation of parathyroid secretion independent of serum calcium in healthy elderly people .  Parathyroid concentrations rise and 25-hydroxyvitamin D concentrations decline with age . These results may have implication s for the prevention of osteoporotic fractures that occur with increased frequency in winter and in elderly people Osteoporosis is a major public health issue leading to significant morbidity , loss of independence and excess loss of life . It has been estimated that 13 to 17 million postmenopausal women have low bone mass or osteoporosis ( 1 , 2 ) . This is associated with almost 1.5 million fractures annually , including 300,000 hip fractures ( 2 , 3 ) . A review of the evidence by Cumming in 1990 ( 4 ) and subsequently published r and omized clinical trials have shown that calcium and /or vitamin D supplements may play a role in the prevention and treatment of osteoporosis by slowing the rates of bone loss in postmenopausal and elderly women ( 5–9 ) . However , there are a limited number of calcium and /or vitamin D trials ( 10–13 ) and observational studies [ review of evidence by Cumming and Nevitt ( 14 ) and Kanis ( 15 ) ] , to support a role for calcium and vitamin D supplementation in the reduction of hip and other fractures . It has also been suggested that calcium and vitamin D supplementation may play a role in the reduction of colorectal cancer incidence ( 16–21 ) . To address these major health concerns of postmenopausal women , the Calcium-Vitamin D ( CaD ) trial of the Women ’s Health Initiative ( WHI ) was design ed to test the primary hypothesis that women who are r and omized to receive calcium and vitamin D supplementation will have a lower risk of hip fracture and secondarily , a lower risk of all fractures and colorectal cancer than women receiving corresponding placebo . The objective of this paper is More than 90 % of hip fractures in older Americans result from a fall . Inadequate intake of dietary protein and vitamin D are common in older adults , and diets in low these could contribute to loss of muscle mass and strength or coordination , in turn increasing the risk of falling . The objective of the study was to evaluate the relationship between protein and vitamin D intake with the occurrence of falls in older women in the Study of Osteoporotic Fracture , a prospect i ve cohort of more than 4000 postmenopausal women participating from January 1997 to September 1998 . Incident falls were ascertained for one year .  Protein and vitamin D intake  was assessed by a food frequency question naire ; associations with a reported fall were estimated with logistic regression , adjusted for fall-related covariates and energy . Protein and vitamin D were modeled separately because of high correlation ( rho = 0.55 , P < 0.001 ) . A total of 1429 women reported a fall within one year . In separate , unadjusted models  dietary protein  ( per 1 g/kg increase ) and  vitamin D  ( per 100 International Unit ( IU ) increase ) significantly increased the odds ratio ( OR ) of falling ( OR 1.35 95 % CI 1.15–1.59 , OR 1.11 95 % CI 1.03–1.19 , respectively ) . Once fall-related covariates were added to each model ,  dietary protein and vitamin D  were noncontributory to falls . While we could find no direct association between vitamin D and protein intake and fall prevention , adequate intake of these two nutrients are critical for musculoskeletal health in older adults BACKGROUND calcium and vitamin D deficiency are common in elderly people and lead to increased bone loss , with an enhanced risk of osteoporotic fractures . Although hip fractures are a serious consequence , few therapeutic measures are given for primary or secondary prevention . A combination of calcium and vitamin D may not be the most effective treatment for all patients . OBJECTIVE to investigate the effects of hypovitaminosis D on the calcium-parathyroid hormone endocrine axis , bone mineral density and fracture type , and the optimal role of combination calcium and vitamin D therapy after hip fracture in elderly patients . DESIGN a population -based , prospect i ve cohort study . METHODS 150 elderly subjects were recruited from the fast-track orthogeriatric rehabilitation ward within 7 days of surgery for hip fracture . This ward accepts people who live at home and are independent in activities of daily living . All subjects had a baseline medical examination , biochemical tests ( parathyroid hormone ,  25-hydroxyvitamin D  and  1,25-dihydroxyvitamin D ) and were referred for bone densitometry . RESULTS at 68 % , the prevalence of hypovitaminosis D ( 25-hydroxyvitamin D<30 nmol/l ) was high . However , only half the patients had evidence of secondary hyperparathyroidism , the rest having a low to normal level of parathyroid hormone ( ' functional hypoparathyroidism ' ) . Patients with secondary hyperparathyroidism and hypovitaminosis D had a higher mean corrected calcium , higher 1,25-dihydroxyvitamin D , lower hip bone mineral density and an excess of extracapsular over intracapsular fractures than the ' functional hypoparathyroid ' group ( P<0.01 ) . CONCLUSION there is a high prevalence of hypovitaminosis D in active , elderly people living at home who present with a hip fracture . However , secondary hyperparathyroidism occurs in only half of these patients . This subgroup attempts to maintain calcium homeostasis but does so at the expense of increased bone turnover , leading to amplified hip bone loss and an excess of extracapsular over intracapsular fractures .  Combination calcium and vitamin D treatment may be effective in preventing a second hip fracture in these patients , but its role in patients with hypovitaminosis D without secondary hyperparathyroidism and ' vitamin D-replete ' subjects needs further evaluation R and omized controlled trials have shown that a combination of vitamin D and calcium can prevent  fragility fractures in the elderly . Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known . We studied if an intervention with 10 microg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded r and omized controlled trial . Residents from 51 nursing homes were allocated r and omly to receive 5 ml of ordinary cod liver oil ( n = 569 ) or 5 ml of cod liver oil where vitamin D was removed ( n = 575 ) . During the study period of 2 years , fractures and deaths were registered , and the principal analysis was performed on the intention-to-treat basis . Biochemical markers were measured at baseline and after 1 year in a sub sample . Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a  hip fracture . The corresponding figures for all nonvertebral fractures were 76 persons ( control group ) and 69 persons ( vitamin D group ) . There was no difference in the incidence of hip fracture ( p = 0.66 , log-rank test ) , or in the incidence of all nonvertebral fractures ( p = 0.60 , log-rank test ) in the vitamin D group compared with the control group . Compared with the control group , persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter ( p = 0.001 ) . In conclusion , we found that an intervention with 10 microg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people OBJECTIVES To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient . DESIGN R and omized , placebo-controlled double-blind , trial of 2 years ' duration . SETTING Multicenter study in 60 hostels ( assisted living facilities ) and 89 nursing homes across Australia . PARTICIPANTS Six hundred twenty-five residents ( mean age 83.4 ) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L. INTERVENTION Vitamin D supplementation ( ergocalciferol , initially 10,000 IU given once weekly and then 1,000 IU daily ) or placebo for 2 years . All subjects received 600 mg of elemental calcium daily as calcium carbonate . MEASUREMENTS Falls and fractures recorded prospect ively in study diaries by care staff . RESULTS The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , the incident rate ratio for falling was 0.73 ( 95 % confidence interval (CI)=0.57 - 0.95 ) . The odds ratio for ever falling was 0.82 ( 95 % CI=0.59 - 1.12 ) and for ever fracturing was 0.69 ( 95 % CI=0.40 - 1.18 ) . An a priori subgroup analysis of subjects who took at least half the prescribed capsules ( n=540 ) , demonstrated an incident rate ratio for falls of 0.63 ( 95 % CI=0.48 - 0.82 ) , an odds ratio ( OR ) for ever falling of 0.70 ( 95 % CI=0.50 - 0.99 ) , and an OR for ever fracturing of 0.68 ( 95 % CI=0.38 - 1.22 ) . CONCLUSION Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient OBJECTIVES Low trauma fractures in older people incur enormous physical , social and economic costs . Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group . This strategy requires validation in a population setting . METHODS R and omized , double-blind , placebo-controlled trial of 300,000 IU intramuscular ( i.m . ) vitamin D2 ( ergocalciferol ) injection or matching placebo every autumn over 3 years . 9440 people ( 4354 men and 5086 women ) aged 75 yrs and over were recruited from general practice registers in Wessex , Engl and . Primary outcome measure was all non-vertebral fracture . Secondary outcomes were hip and wrist fractures , and all falls . RESULTS 585 subjects had incident non-spine fractures  ( hip 110 , wrist 116 , ankle 37 ) . Hazard ratios ( HRs ) for fracture in the vitamin D group were : 1.09 [ 95 % confidence interval ( CI ) 0.93 - 1.28 , P = 0.29 ] for any first fracture , 1.49 ( 95 % CI 1.02 - 2.18 , P = 0.04 ) for hip and 1.22 ( 95 % CI 0.85 - 1.76 , P = 0.28 ) for wrist . There was no effect on falls : HR 0.98 ( 0.93 - 1.04 ) . No protective effect was observed in any subgroup when the cohort was stratified by sex , age , previous fracture or mobility . CONCLUSIONS An annual i.m . injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population OBJECTIVES To model the incremental cost-utility of seven interventions reported as effective for preventing falls in older adults . DESIGN Mathematical epidemiological model populated by data based on direct clinical experience and a critical review of the literature . SETTING Model represents population level interventions . PARTICIPANTS No human subjects were involved in the study . MEASUREMENS : The last Cochrane data base review and meta-analyses of r and omized controlled trials categorized effective fall-prevention interventions into seven groups : medical management ( withdrawal ) of psychotropics , group tai chi , vitamin D supplementation , muscle and balance exercises , home modifications , multifactorial individualized programs for all elderly people , and multifactorial individualized treatments for high-risk frail elderly people . Fall-related hip fracture incidence was obtained from the literature . Salary figures for health professionals were based on Bureau of Labor Statistics data . Using an integrated healthcare system perspective , healthcare costs were estimated based on practice and studies on falls in older adults . Base case incremental cost utility ratios were calculated , and probabilistic sensitivity analyses were conducted . RESULTS Medical management of psychotropics and group tai chi were the least-costly , most-effective options , but they were also the least studied . Excluding these interventions , the least-expensive , most-effective options are  vitamin D supplementation and home modifications . Vitamin D supplementation costs less than home modifications , but home modifications cost only $ 14,794/ quality -adjusted life year ( QALY ) gained more than vitamin D. In probabilistic sensitivity analyses excluding management of psychotropics and tai chi , home modification is most likely to have the highest economic benefit when QALYs are valued at $ 50,000 or $ 100,000 . CONCLUSION Of single interventions studied , management of psychotropics and tai chi reduces costs the most . Of more-studied interventions , home modifications provide the best value . These results must be interpreted in the context of the multifactorial nature of falls Half of all postmenopausal women will have an osteoporosis-related fracture during their lives , including one quarter who will develop a vertebral deformity ( 1 ) and 15 % who will suffer a hip fracture ( 2 ) . Hip fractures are associated with high mortality rates and loss of independence ( 3 , 4 ) . Although many vertebral fractures are detected only incidentally on radiography , some cause severe pain , leading to 150 000 hospital admissions per year in persons older than 65 years of age , 161 000 physician office visits , and more than 5 million days of restricted activity in those 45 years of age or older ( 5 ) . Low bone density has been used to predict risk for fractures as well as to diagnose osteoporosis . Osteoporosis has been defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue , leading to enhanced bone fragility and a consequent increase in fracture risk ( 6 , 7 ) . This definition emphasizes that , in addition to bone mass , the structure of bone is an important factor in the pathogenesis of fractures . A World Health Organization working group ( 8) proposed that osteoporosis should be diagnosed in epidemiologic studies when  bone mineral density  is 2.5 SDs or more below the mean for healthy young adult women at the spine , hip , or wrist ( corresponding to a T-score 2.5 ) or when patients have a history of atraumatic fracture ( 9 ) . By the World Health Organization definition , up to 70 % of women older than 80 years of age have osteoporosis ( 10 ) . Age is also an important factor in the relationship between bone density and the absolute risk for fracture . Older women have a much higher fracture rate than younger women with the same bone density because of increasing risk from other factors , such as bone quality and tendency to fall ( 11 ) . Despite the high prevalence of osteoporosis and the effect of fractures on mortality , independence , and quality of life , it is not clear whether it is appropriate to screen asymptomatic postmenopausal women . Recent systematic review s and guidelines disagree about which women should be screened and when ( 12 - 20 ) . This disagreement reflects , in part , gaps in the evidence . For example , most guidelines recommend using risk factors to select patients for bone density testing , but because of inadequate data there is no consensus on which risk factors to use . As part of the U.S. Preventive Services Task Force up date of its 1996 recommendation ( 21 ) , we examined evidence on the benefits and harms of screening postmenopausal women for osteoporosis . Specifically , we addressed the role of risk factors in identifying high-risk women , techniques of bone density testing to identify fracture risks , effectiveness of treatment in reducing fracture risk , and harms of screening and treatment . Methods Additional methods used for this review , including determination of the quality of studies ( 22 ) , are detailed in Appendix Tables 1 , 2 , and 3 and in a separate report ( 23 ) . The analytic framework and key questions are detailed in the Appendix Figure . Relevant studies were identified from multiple search es of MEDLINE ( 1966 to May 2001 ) , HealthSTAR ( 1975 to May 2001 ) , and Cochrane data bases ; reference lists of systematic review s ; and experts . We also sent letters to manufacturers of bone density devices requesting additional information about the performance of their instruments , but we received no new data . Two review ers read each abstract to determine its eligibility . We included English- language abstract s that contained original data about postmenopausal women and osteoporosis and addressed screening or the effectiveness of risk factor assessment , bone density testing , or treatment . We considered screening to be the process of assessing postmenopausal women without known osteoporosis for risk of osteoporotic fractures by identification of risk factors , including low bone density . Postmenopausal women were those who had experienced surgical or natural menopause , regardless of age . Women with preexisting atraumatic fractures were not considered in the screening population because they had confirmed osteoporosis according to the World Health Organization definition . For studies of prediction , we selected articles that reported the relationship between risk factor assessment methods or bone density tests and bone density , bone loss , or fractures . We review ed studies of medications used for treatment and present results for bisphosphonates . We focused on r and omized , controlled trials of therapies reporting radiographically verified , nontraumatic fracture outcomes because fractures are a stronger measure of effectiveness than bone density . We excluded studies of primary prevention of osteoporosis , such as the role of nutrition , calcium consumption , and physical activity . We also excluded secondary causes of osteoporosis , such as corticosteroid use and certain chronic diseases , and studies that did not provide sufficient information to allow determination of the method for selecting patients and for analyzing data . Investigators read the full-text versions of the retrieved papers and reapplied the initial eligibility criteria . To assess the internal validity of individual studies , we applied a set of criteria developed by the third U.S. Preventive Services Task Force ( Appendix Table 1 ) ( 22 ) . In this paper , we highlight studies that are applicable to current practice st and ards , have high- quality internal validity ratings , and are most generalizable to the U.S. population of postmenopausal women under consideration for screening . We created an outcomes table to summarize the number of  hip and vertebral fractures  prevented based on age-specific prevalence rates and treatment effects obtained from results of the review ed studies . We conducted a sensitivity analysis to determine the influence of risk factors on the number needed to screen . This research was funded by the Agency for Healthcare Research and Quality under a contract to support the work of the U.S. Preventive Services Task Force . Agency staff and Task Force members participated in the initial design of the study and review ed interim analyses and the final manuscript . Additional reports were distributed for review to content experts and revised accordingly before preparation of this manuscript ( 23 , 24 ) . The authors are responsible for the content of the manuscript and the decision to su bmi t it for publication . Results Studies of Screening We identified no studies about the effectiveness of screening in reducing osteoporotic fractures . Without direct evidence from screening studies , recommendations about screening need to rely on evidence that risk factor assessment or bone density testing can adequately identify women who could ultimately benefit from treatment . Risk Factor Assessment Hundreds of studies report associations between risk factors and low bone density and fractures in postmenopausal women ( 24 ) . The most comprehensive study of risk factors in a U.S. population is the Study of Osteoporotic Fractures , a good- quality prospect i ve study of 9516 women 65 years of age and older ( 25 ) . In this study , 14 clinical risk factors were identified as significant predictors of hip fracture in multivariable models ( age ; maternal hip fracture ; no weight gain ; height ; poor self-rated health ; hyperthyroidism ; current use of benzodiazepines , anticonvulsants , or caffeine ; not walking for exercise ; lack of ambulation ; inability to rise from a chair ; poor scores on two measures of vision ; high resting pulse ; and any fracture since 50 years of age ) . The relative risk for hip fracture per decrease of 1 SD in calcaneal bone density was 1.6 ( 95 % CI , 1.3 to 1.9 ) . This was comparable to the magnitude of the relative risks of most of the other significant predictors in the model , which ranged from 1.2 to 2.0 . Women with at least 5 of the 14 risk factors had increased rates of hip fractures compared with those who had 0 to 2 risk factors at all levels of calcaneal bone density . To determine which risk factors could be important in women younger than 65 years of age , we review ed eight observational studies of risk factors and fractures of various types conducted in population s in which at least 50 % of participants were younger than 65 years of age . Table 1 lists risk factors that were statistically significant predictors for fractures in multivariable models ( 26 - 33 ) . These results could not be quantitatively combined because risk factors were defined differently in each study . Table 1 . Risk Factors for Fractures in Women 5065 Years of Age Results of risk factor studies have been used to assess risk in individuals . We identified 10 cross-sectional studies that described methods of determining risk for low bone density for individual women based on selected clinical risk factors ( Table 2 ) ( 34 - 43 ) . The most common method ologic limitations of these studies are lack of validation and lack of generalizability because of small numbers of patients or nonrepresentative patients . We also identified 8 studies of clinical risk factors to determine fracture risk ( Table 2 ) ( 44 - 51 ) . None of these studies received a good rating for internal validity . Four studies evaluated hip fracture outcomes , two evaluated vertebral fractures , and two evaluated all types of fractures . These studies described the association of risk factors with fractures known to have occurred already ( four casecontrol studies ) or how well they would predict fractures in the future ( four prospect i ve cohort studies ) . Table 2 . Studies of Risk Factor Assessment A recent study compared the performance of five clinical decision rules for bone density testing among 2365 postmenopausal women 45 years of age or older who were enrolled in a community-based study of osteoporosis in Canada ( 52 ) . These rules included guidelines from the National Osteoporosis Foundation ( 53 ) ; the Simple Calculated Osteoporosis Risk Estimation ( SCORE ) rule ( age , weight , ethnicity , estrogen use , One of the main focuses of lifestyle modification for the prevention of osteoporosis and osteoporotic fractures  in Japan is improvement in dietary calcium intake . However , virtually no r and omized controlled trial to assess the preventive effects of administration of calcium on the risk of fractures has been conducted in Japan . In this study , we review ed all the scientific papers currently available from medical literature data bases to propose evidence -based recommendations on the preventive procedures for osteoporosis . The result of the present systematic review gives the evidence showing that calcium supplementation or optimal dietary calcium intake increases bone density in childhood and adolescence and reduces the risk of fracture due to osteoporosis in the elderly people regardless of the gender . The evidence also supports the current health policy guiding the elderly to increase their dietary calcium intake in daily life Background Homocysteine has been postulated as a novel , potentially reversible risk factor for osteoporosis and related fractures . We evaluated whether homocysteine-lowering therapy with B-vitamins in patients with symptomatic cerebrovascular disease reduced the incidence of osteoporotic fractures . Methods VITAmins To Prevent Stroke ( VITATOPS ) was a prospect i ve r and omised double-blind placebo-controlled trial in which 8,164 patients with recent ( within 7 months ) stroke or transient ischemic attack were r and omly allocated to double-blind treatment with one tablet daily of either placebo ( n = 4,075 ) or B-vitamins ( folic acid 2 mg , vitamin B6 25 mg , vitamin B12 500 μg ; n = 4,089 ) . Patients were review ed every six months . Any osteoporotic fracture and osteoporotic hip fractures were secondary outcome events , and were review ed by a masked adjudication committee . Analysis was by intention to treat . Logistic regression was used to identify independent predictors of fracture . Results Participants had a mean age of 62.6 years ( SD 12.5 years ) and 64 % were male , 42 % of Western European descent and 75 % were functionally independent ( Oxford H and icap Scale of two or less ) . After a median duration of 2.8 years therapy and 3.4 years follow-up , there was no significant difference in the incidence of any osteoporotic fracture between participants assigned B-vitamins ( 67 [ 1.64 % ] ) and placebo ( 78 [ 1.91 % ] ; risk ratio [ RR ] 0.86 , 95 % confidence interval [ CI ] 0.62 - 1.18 ) or the incidence of hip fractures ( 34 [ 0.83 % ] B-vitamins vs. 36 [ 0.88 % ] placebo ; RR 0.94 , 95 % CI 0.59 - 1.5 ) . There was no significant impact of B-vitamin therapy on time to first fracture . Baseline homocysteine levels did not predict any osteoporotic fracture ( p = 0.43 ) . Independent predictors of any osteoporotic fracture were female sex , age > 64 years , Western European ethnicity and use of anti-osteoporosis medication at r and omization ( all p < 0.01 ) . Conclusions Once daily treatment with B-vitamins had no effect on incidence of osteoporotic fractures during a median of 3.4 years follow-up in patients with cerebrovascular disease . A modest effect of B-vitamin therapy is not excluded due to the low numbers of fracture outcome events . Trial registration Clinical trials.gov number : NCT00097669 and is rct n.org number : IS RCT N74743444 BACKGROUND Supplementation with calcium and vitamin D reduces bone loss and prevents fractures in elderly people , but it is not known whether any lasting benefit remains if the supplements are discontinued . OBJECTIVE The objective was to determine whether gains in bone mineral density ( BMD ) induced by calcium and vitamin D supplementation persist after supplement withdrawal . DESIGN Two-hundred ninety-five healthy , elderly men and women ( aged > /=68 y ) who had completed a 3-y r and omized , placebo-controlled trial of calcium and vitamin D supplementation were followed for an additional 2 y during which no study supplements were given .  BMD was measured by dual-energy X-ray absorptiometry , and biochemical variables related to calcium metabolism and bone turnover were measured . RESULTS In the 128 men , supplement-induced increases in spinal and femoral neck BMD were lost within 2 y of supplement discontinuation , but small benefits in total-body BMD remained . In the 167 women , there were no lasting benefits in total-body BMD or at any bone site . Consistent with the observations on BMD , the bone turnover rates in both men and women ( as measured by serum osteocalcin concentrations ) returned to their original higher concentrations within the same 2-y period . CONCLUSION Discontinued calcium and vitamin D supplementation has limited cumulative effect on bone mass in men and women aged > /=68 BACKGROUND Mortality increases after hip fractures  in women and more so in men . Little is known , however , about mortality after other fractures . We investigated the mortality associated with all fracture types in elderly women and men . METHODS We did a 5-year prospect i ve cohort study  in the semi-urban city of Dubbo , Australia , of all residents aged 60 years and older ( 2413 women and 1898 men ) . Low-trauma  osteoporotic fractures that occurred between 1989 and 1994 , confirmed by radiography  and personal interview , were classified as proximal femur , vertebral , and groupings of other major and minor fractures . We calculated st and ardised mortality rates from death certificates for people with fractures compared with the Dubbo population . FINDINGS 356 women and 137 men had low-trauma fractures . In women and men , mortality was increased in the first year after all major fractures . In women , age-st and ardised mortality ratios were 2.18 ( 95 % CI 2.03 - 2.32 ) for proximal femur , 1.66 ( 1.51 - 1.80 ) for vertebral , 1.92 ( 1.70 - 2.14 ) for other major , and 0.75 ( 0.66 - 0.84 ) for minor fractures . In men , these ratios were 3.17 ( 2.90 - 3.44 ) for proximal femur , 2.38 ( 2.17 - 2.59 ) for vertebral , 2.22 ( 1.91 - 2.52 ) for other major , and 1.45 ( 1.25 - 1.65 ) for minor fractures . There were excess deaths ( excluding minor fractures in women ) in all age-groups . INTERPRETATION All major fractures were associated with increased mortality , especially in men . The loss of potential years of life in the younger age-group shows that preventative strategies for fracture should not focus on older patients at the expense of younger women and of men Osteoporosis is a significant health problem and contributor to disability and premature mortality among older men . Incidence rates for hip fracture have stabilized in women , but continue to increase in men . A major risk factor for hip fracture is bone mineral density level . The determinants of bone mineral density ( BMD ) are well defined in women , but not in men . The primary goal of the current research was to increase our underst and ing of the determinants of BMD of the proximal femur in a large community-based sample of older male volunteers . Eligibility requirements included age of 50 years or older , ambulatory , and not having undergone a bilateral hip replacement . Five hundred twenty-three men , mean mean age 66.6 years , met all eligibility requirements and participated in the Study of Osteoporotic Risk in Men or STORM . Information on demographics , medical history , anthropometry , leisure-time and occupational physical activity , muscular strength , cigarette smoking , alcohol consumption , dietary calcium intake , and medication use ( thiazide diuretics and glucocorticoids ) were obtained by question naire , interview , and examination , BMD of the proximal femur ( femoral neck , greater trochanter , and Ward 's triangle ) was measured by dual-energy X-ray absorptiometry using the Hologic QDR-1000 and QDR-2000 . The cross-sectional determinants of BMD included age , blond hair color , current body weight , thiazide diuretic use , historical physical activity , and quadriceps strength . Several variables commonly thought to be determinants of BMD were not related to BMD in this population of older men , including current cigarette smoking , alcohol consumption , current leisure-time physical activity , dietary calcium intake , vitamin D use , and caffeine intake . However , failure to find associations among BMD and some of the potential determinants may be due to lack of statistical power . Identification of the determinants of BMD could lead to the development of interventions aim ed at maximizing BMD in men and could potentially decrease the risk of hip fractures BACKGROUND Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons .  Calcium and vitamin D supplements reduce this secondary hyperparathyroidism , but whether such supplements reduce the risk of hip fractures among elderly people is not known . METHODS We studied the effects of supplementation with vitamin D3 ( cholecalciferol ) and calcium on the frequency of hip fractures and other nonvertebral fractures , identified radiologically , in 3270 healthy ambulatory women ( mean [ + /- SD ] age , 84 + /- 6 years ) . Each day for 18 months , 1634 women received tricalcium phosphate ( containing 1.2 g of elemental calcium ) and 20 micrograms ( 800 IU ) of vitamin D3 , and 1636 women received a double placebo . We measured serial serum parathyroid hormone and 25-hydroxyvitamin D ( 25(OH)D ) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women . RESULTS Among the women who completed the 18-month study , the number of hip fractures was 43 percent lower ( P = 0.043 ) and the total number of nonvertebral fractures was 32 percent lower ( P = 0.015 ) among the women treated with vitamin D3 and calcium than among those who received placebo . The results of analyses according to active treatment and according to intention to treat were similar . In the vitamin D3-calcium group , the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months ( P < 0.001 ) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value ( P < 0.001 ) . The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group ( P < 0.001 ) . CONCLUSIONS Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women Osteoporosis is prevalent in men with an estimated one in eight men older than 50 years suffering from osteoporotic fracture , and a higher mortality rate after fracture among men compared with women . There are few approved therapies for osteoporosis in men . This observational study assesses the efficacy and safety of risedronate in the treatment of men with primary and secondary osteoporosis . A single-center , open label , r and omized , prospect i ve 1-year study was conducted in men with primary or secondary osteoporosis . Patients were r and omized to risedronate ( risedronate 5 mg/day plus calcium 1,000 mg/day and vitamin D 800 IU/day ) or control groups ( alfacalcidol 1 μg/day plus calcium 500 mg/day or vitamin D 1,000 IU/day plus calcium 800 mg/day ) . Bone mineral density ( BMD ) measurements , X-rays of the spine , a medical history and physical exam , and patient self- assessment s of back pain  were performed at baseline and 12 months . Blinded semi-quantitative fracture assessment was conducted by a radiologist . A total of 316 men with osteoporosis were enrolled in the trial  ( risedronate , n=158 ; control , n=158 ) . At 1 year lumbar spine BMD increased by 4.7 % in the risedronate group versus an increase of 1.0 % in the control group ( P<0.001 ) . Significant increases in BMD at the total hip and femoral neck were also observed with risedronate compared with the control group . The incidence of new vertebral fracture in the risedronate group was reduced by 60 % versus the control group ( P=0.028 ) . Daily treatment with risedronate for 12 months significantly increased BMD at the lumbar spine , femoral neck and total hip and significantly reduced the incidence of new vertebral fractures . This is the first prospect i ve , r and omized , controlled trial to demonstrate a significant reduction in vertebral fractures in 1 year in men with primary or secondary osteoporosis OBJECTIVE To determine the relation between estrogen replacement therapy and fractures . DESIGN Prospect i ve cohort study . SETTING Four clinical centers in Baltimore County , Maryl and ; Minneapolis , Minnesota ; Portl and , Oregon ; and the Monongahela Valley , Pennsylvania . PARTICIPANTS 9704 ambulatory , nonblack women 65 years of age or older . MEASUREMENTS  Estrogen use , medical history , and anthropometric data  were obtained by question naire , interview , and examination . Appendicular bone mass was measured by single-photon absorptiometry .  Incident fractures were vali date d by radiographic report . RESULTS After adjustment for potential confounders , current estrogen use was associated with a decrease in the risk for wrist fractures ( relative risk [ RR ] , 0.39 ; 95 % CI , 0.24 to 0.64 ) and for all nonspinal fractures ( RR , 0.66 ; CI , 0.54 to 0.80 ) when compared with no estrogen use . Results were similar for women using unopposed estrogen or estrogen plus progestin , for women younger or older than 75 years of age , and for current smokers or nonsmokers . The effect of estrogen remained after adjustment was made for appendicular bone mass . The relative risk for hip fracture tended to be lower among current users ( RR , 0.60 ; CI , 0.36 to 1.02 ) than among never-users . Estrogen was most effective in preventing hip fracture among those older than 75 years . Current users who started estrogen within 5 years of menopause had a decreased risk for hip fractures ( RR , 0.29 ; CI , 0.09 to 0.92 ) , wrist fractures ( RR , 0.29 ; CI , 0.13 to 0.68 ) , and all nonspinal fractures ( RR , 0.50 ; CI , 0.36 to 0.70 ) when compared with women who had never used estrogen . Previous use of estrogen for more than 10 years or use begun soon after menopause had no substantial effect on the risk for fractures . CONCLUSIONS Current use of estrogen appears to decrease the risk for fracture in older women . These results suggest that for protection against fractures , estrogen should be initiated soon after menopause and continued indefinitely OBJECTIVES Osteoporosis is a major cause of morbidity and cost . Patients sustaining one osteoporotic fracture are at increased risk of having another fracture . The objective of this study was to examine the use of “ bone drugs ” for the prevention of further osteoporotic fractures among patients who have had a “ typical ” osteoporotic fracture . METHODS This study took a r and om sample of 300 women aged 50 and over who had sustained either a vertebral , hip or Colles fracture in 1995 from the General Practice Research Data base ( GPRD ) and compared their use of bone drugs with 300 age and practice matched controls . RESULTS Compared with age and practice matched control patients only vertebral fracture patients showed a statistically significant increase in the use of bone drugs in the year after fracture ( 39 % and 2 % for cases and controls respectively ; 95 % CI of difference 27 % to 47 % ) . Etidronate was the most commonly used compound . CONCLUSION The majority of patients sustaining an osteoporotic fracture are not prescribed any pharmaceutical agents for the secondary prevention of fracture one year after a primary fracture Controversy exists in the literature regarding the efficacy of bone health-related nutrients , especially calcium and vitamin D , in preventing fractures . The aim of our present study was to determine the effect of multivitamin and mineral supplementation on fracture incidence among 3,318 participants from a nutritional intervention trial in Linxian , China . A total of 1,461 men and 1,857 women were enrolled and r and omized to daily supplementation with 26 vitamins and minerals tablet or placebo pills for 6 years , followed by a 16-year post-interventional follow-up . The date s , sites , and causes of the fractures were collected retrospectively via a st and ardized question naire . Cox proportional hazard model was used to estimate hazard ratios and 95 % confidence intervals of fracture incidence in the intervention versus the placebo group . A total of 221 fractures ( 57 in men and 164 in women ) occurred during the entire study period of 21 years and 9 months . In men , the supplement reduced the risk of fracture by 63 % during the trial period , and this protective effect was sustained and statistically significant when analysis included both the trial period and 5- or 10-year post-intervention follow-up ( years 0–11 , P = 0.04 ; years 0–16 , P = 0.02 , respectively ) . The protection against fracture was not apparent > 10 years after cessation of the intervention . In women , no significant effect of supplementation on fracture incidence was seen in any of the study periods . These results demonstrate that a 6-year multivitamin and mineral intervention was associated with significant reduction of fracture risk and fracture-related hospitalization in men , but not in women Antifracture efficacy of high-dose vitamin D ( 800 IU ) and calcium ( 1000 mg ) remains controversial . To determine whether daily 800 IU of vitamin D and 1000 mg of calcium supplementation prevents fractures , we r and omized 3432 women of the population -based Osteoporosis Risk Factor and Prevention ( OSTPRE ) Study cohort ( ages 65 to 71 years ) living in the region of northern Savonia , Finl and ( latitude 62 degrees to 64 degrees N ) for 3 years to receive 800 IU of cholecalciferol and 1000 mg of calcium as calcium carbonate or to a control group that did not receive placebo . The main outcome measure was incident fractures . Fracture data were collected in telephone interviews and vali date d. Data on 3195 women , 1586 in the intervention group and 1609 in the control group , were available for analysis . In adjusted Cox proportional hazards models , the risk of any fracture decreased in the vitamin D and calcium group by 17 % [ adjusted hazard ratio ( aHR ) = 0.83 ; 95 % confidence interval ( CI ) 0.61 - 1.12 ] , and the risk of any nonvertebral fracture decreased by 13 % ( aHR = 0.87 ; 95 % CI 0.63 - 1.19 ) . The risk of distal forearm fractures decreased by 30 % ( aHR = 0.70 ; 95 % CI 0.41 - 1.20 ) , and the risk of any upper extremity fractures decreased by 25 % ( aHR = 0.75 ; 95 % CI 0.49 - 1.16 ) , whereas the risk of lower extremity fractures remained essentially equal ( aHR = 1.02 ; 95 % CI 0.58 - 1.80 ) . None of these effects reached statistical significance . In conclusion , this study did not produce statistically significant evidence that vitamin D and calcium supplementation prevents fractures in a 65- to 71-year-old general population of postmenopausal women The prevalence of vitamin D deficiency varies , with the groups at greatest risk including housebound , community-dwelling older and /or disabled people , those in residential care , dark-skinned people ( particularly those modestly dressed ) , and other people who regularly avoid sun exposure or work indoors . Most adults are unlikely to obtain more than 5%-10 % of their vitamin D requirement from dietary sources . The main source of vitamin D for people residing in Australia and New Zeal and is exposure to sunlight . A serum 25-hydroxyvitamin D ( 25-OHD ) level of ≥ 50 nmol/L at the end of winter ( 10 - 20 nmol/L higher at the end of summer , to allow for seasonal decrease ) is required for optimal musculoskeletal health . Although it is likely that higher serum 25-OHD levels play a role in the prevention of some disease states , there is insufficient evidence from r and omised controlled trials to recommend higher targets . For moderately fair-skinned people , a walk with arms exposed for 6 - 7 minutes mid morning or mid afternoon in summer , and with as much bare skin exposed as feasible for 7 - 40 minutes ( depending on latitude ) at noon in winter , on most days , is likely to be helpful in maintaining adequate vitamin D levels in the body . When sun exposure is minimal , vitamin D intake from dietary sources and supplementation of at least 600 IU ( 15 µg ) per day for people aged ≤ 70 years and 800 IU ( 20 µg ) per day for those aged > 70 years is recommended . People in high-risk groups may require higher doses . There is good evidence that vitamin D plus calcium supplementation  effectively reduces fractures and falls in older men and women UNLABELLED The level of recognition and treatment of osteoporosis is not well characterized in primary care . In data from a large sample of postmenopausal women attending 927 primary care physicians , 29 % of women reported one or more fractures after menopause . The great majority ( 72 % ) were not on any osteoporosis-specific therapy . INTRODUCTION Osteoporosis is often first recognized at the time of a low-trauma fracture . However , by this stage , the risk of subsequent fractures has already risen substantially . Moreover , in many countries , only a small proportion of women , who have already sustained fractures , receive a treatment shown to reduce this increased risk of further fractures . MATERIAL S AND METHODS This project was initiated to examine the prevalence of osteoporotic fractures , risk factors for osteoporosis , and use of antifracture therapy among postmenopausal Australian women . More than 88,000 women from 927 primary care physicians returned over 69,358 surveys . Of these , 57,088 reported the presence of a postmenopausal fracture or risk factors . RESULTS Among these r and omly selected postmenopausal women , 29 % reported having had one or more low-trauma fractures after menopause ( 44 % substantiated in current records ) . One-third of these women reported multiple fractures . The prevalence of all types of fractures , except rib and ankle , increased with age and low body weight . Those who reported fractures were also more likely to report early menopause , corticosteroid use , and a family history of osteoporosis . Moreover , those with vertebral fractures were more likely to record height loss , kyphosis , and back pain . Physical inactivity , low calcium intake , and smoking had no consistent relationship with any fracture outcome . Of the women who reported a fracture after menopause , only 28 % were on any specific therapy for osteoporosis , and 7 % were on calcium alone . Of those who had been told they had osteoporosis by a doctor , 40 % were receiving specific osteoporosis therapy . CONCLUSIONS In this large study of postmenopausal Australian women attending primary care physicians , 29 % reported at least one low-trauma fracture after menopause . Less than one-third of these women were on specific treatment for osteoporosis , and only 40 % were ever told they had osteoporosis . Therefore , osteoporotic fractures are common in postmenopausal Australian women , and few , despite their substantially increased risk of further fractures , are on any specific anti-osteoporotic therapy . These data support the need for more effective education for the community and medical practitioners of the clinical significance of osteoporotic fractures and alternatives for treatment Background Incidence of a fracture , particularly in the hip joint , is high in Parkinson 's disease ( PD ) , owing to the immobilisation-induced bone resorption and vitamin D deficiency with reduced bone mineral density ( BMD ) . The authors previously demonstrated the lowered incidence of hip fractures in PD by daily administration of risedronate and vitamin D. Methods This r and omised , double-blind , placebo-controlled study was conducted to determine the efficacy of 17.5 mg once-weekly risedronate in the prevention of hip fracture in women with PD . Patients were r and omly assigned to 17.5 mg risedronate once a week ( n=136 ) or a placebo ( n=136 ) combined with daily 1000 IU of ergocalciferol .  Incidence of hip fractures was compared between the two groups during the 2-year follow-up . Results Hip fractures occurred in 15 patients in the placebo group and 3 patients in the risedronate group . The RR for hip fractures in the risedronate group as compared with the placebo group was 0.20 ( 95 % CI 0.06 to 0.66 ) . In the risedronate group , serum calcium levels decreased during the follow-up , while the levels in the placebo group increased . BMD increased by 3.4 % in the risedronate group and decreased by 3.2 % in the placebo group ( p<0.01 ) . Conclusions Treatment with once-weekly risedronate and ergocalciferol prevents hip fractures in older women with PD CONTEXT Mono- and polyunsaturated fats may have opposing effects on vitamin D absorption . OBJECTIVE The purpose of this study was to determine whether intakes of different dietary fats are associated with the increase in serum 25-hydroxyvitamin D ( 25OHD ) after supplementation with vitamin D(3 ) . DESIGN , SETTING , AND PARTICIPANTS This analysis was conducted in the active treatment arm of a r and omized , double-blind , placebo-controlled trial of vitamin D and calcium supplementation to prevent bone loss and fracture . Subjects included 152 healthy men and women age 65 and older who were assigned to 700 IU/d vitamin D(3 ) and 500 mg/d calcium .  Intakes of monounsaturated fatty acids ( MUFA ) , polyunsaturated fatty acids ( PUFA ) , and saturated fatty acids ( SFA ) were estimated by food frequency question naire . MAIN OUTCOME MEASURE The change in plasma 25OHD during 2 yr  vitamin D and calcium supplementation was assessed . RESULTS The change in plasma 25OHD ( nanograms per milliliter ) during vitamin D supplementation was positively associated with MUFA , ( β = 0.94 ; P = 0.016 ) , negatively associated with PUFA , ( β = -0.93 ; P = 0.038 ) , and positively associated with the MUFA/PUFA ratio ( β = 6.46 ; P = 0.014 ) . CONCLUSION The fat composition of the diet may influence the 25OHD response to supplemental vitamin D(3 ) . Diets rich in MUFA may improve and those rich in PUFA may reduce the effectiveness of vitamin D(3 ) supplements in healthy older adults . More studies are needed to confirm these findings Summary This trial compared the effects of daily treatment with vitamin D or placebo for 1 year on blood tests of vitamin D status . The results demonstrated that daily 4000 IU vitamin D3 is required to achieve blood levels associated with lowest disease risks , and this dose should be tested in future trials for fracture prevention . Introduction The aim of this trial was to assess the effects of daily supplementation with vitamin D3 4000 IU ( 100 μg ) , 2000 IU ( 50 μg ) or placebo for 1 year on biochemical markers of vitamin D status in preparation for a large trial for prevention of fractures and other outcomes . Methods This is a r and omized placebo-controlled trial in 305 community-dwelling people aged 65 years or older in Oxfordshire , UK . Outcomes included biochemical markers of vitamin D status ( plasma 25-hydroxy-vitamin D [ 25[OH]D ] , parathyroid hormone [ PTH ] , calcium and alkaline phosphatase ) , cardiovascular risk factors and tests of physical function . Results Mean ( SD ) plasma 25(OH)D levels were 50 ( 18 ) nmol/L at baseline and increased to 137 ( 39 ) , 102 ( 25 ) and 53 ( 16 ) nmol/L after 12 months in those allocated 4000 IU , 2000 IU or placebo , respectively ( with 88 % , 70 % and 1 % of these groups achieving the pre-specified level of > 90 nmol/L ) . Neither dose of vitamin D3 was associated with significant deviation outside the normal range of PTH or albumin-corrected calcium . The additional effect on 25(OH)D levels of 4000 versus 2000 IU was similar in all subgroups except for body mass index , for which the further increase was smaller in overweight and obese participants compared with normal-weight participants . Supplementation with vitamin D had no significant effects on cardiovascular risk factors or on measures of physical function . Conclusions After accounting for average 70 % compliance in long-term trials , doses of 4000 IU vitamin D3 daily may be required to achieve plasma 25(OH)D levels associated with lowest disease risk in observational studies BACKGROUND Previous studies demonstrate that postmenopausal women who use estrogen  are somewhat protected from bone loss and fractures compared with nonusers , but the extent to which estrogen users remain at risk for osteoporosis and fractures is uncertain . OBJECTIVE To determine long-term probabilities for incident fractures among postmenopausal estrogen users . METHODS We examined data from the Study of Osteoporotic Fractures , a prospect i ve cohort study with 10 years of follow-up ( 1986 - 1999 ) . This cohort includes 8816 women 65 years and older from community setting s in 4 areas of the United States . MAIN OUTCOME MEASURES Hip , wrist , vertebral , and nonvertebral fractures . RESULTS At baseline , using criteria developed by the World Health Organization , 40 % of continuous estrogen users were osteopenic and 13 % were osteoporotic at the hip or spine . Although women currently using estrogen lost less bone density than past users or those who never used estrogen , all user groups on average lost bone from the hip and calcaneus . During 10 years of observation , the adjusted probability of nonvertebral fractures was 19.6 % for continuous estrogen users , similar to current partial users and lower than past users and those who never used estrogen ( P<.05 ) . These comparisons were similar for hip , wrist , and vertebral fractures . CONCLUSIONS Although estrogen use is associated with reduced prevalence of low bone density , less bone loss , and lower probabilities for fractures , osteoporosis and fractures are common in older women who used estrogen continuously since menopause .  Estrogen users should be considered in strategies design ed to detect , prevent , and treat osteoporosis Background Improving vitamin D ( 25-OHD ) status may be an important modifiable factor that could reduce disability severity , fall-rates and mortality associated after hip fracture surgery . Providing a loading-dose post-surgery may overcome limitations in adherence to daily supplementation . Method In this r and omized , double-blind , placebo-controlled trial , 218 adults , aged 65-years or older , requiring hip fracture surgery were assigned to receive a single loading-dose of cholecalciferol ( 250,000 IU vitamin-D3 , the REVITAHIP - Replenishment of Vitamin D in Hip Fracture strategy ) or placebo , both receiving daily vitamin-D(800 IU ) and calcium ( 500 mg ) for 26-weeks . Outcome measures were 2.4 m gait-velocity , falls , fractures , death ( Week-4 ) , 25-OHD levels , quality -of-life measure ( EuroQoL ) and mortality at weeks-2 , 4 and 26 . Results Mean age of 218 participants was 83.9(7.2 ) years and 77.1 % were women .  Baseline mean 25-OHD was 52.7(23.5)nmol/L , with higher levels at Week-2 ( 73 vs 66 nmol/L ; p = .019 ) and Week-4 ( 83 vs 75 nmol/L ; p = .030 ) in the Active-group , but not at Week-26 . At week-4 , there were no differences in 2.4 m gait-velocity ( 0.42 m/s vs 0.39 m/s , p = .490 ) , fractures ( 2.7 % vs 2.8 % , p = .964 ) but Active participants reported less falls ( 6.3 % vs 21.1 % , χ2 = 4.327 ; p = 0.024 ) , with no significant reduction in deaths at week-4 ( 1 vs 3 , p = 0.295 ) , higher percentage reporting ‘ no pain or discomfort ’ ( 96.4 % vs 88.8 % , p = 0.037 ) , and trended for higher EuroQoL-scores ( p = 0.092 ) at week-26 . One case of hypercalcemia at week-2 normalised by week-4 . Conclusion Among older people after hip fracture surgery , the REVITAHIP strategy is a safe and low cost method of improving vitamin-D levels , reducing falls and pain levels . Trial registration The protocol for this study is registered with the Australian New Zeal and Clinical Trials Registry ANZCTRN ACTRN12610000392066 ( Date of registration : 14/05/2010 ) CONTEXT Nutritional prevention of bone deterioration with fortified foods seems particularly suitable in institutionalized elderly women at risk of vitamin D deficiency , secondary hyperparathyroidism , increased bone resorption , and osteoporotic fracture . OBJECTIVE The objective was to evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum PTH and bone resorption markers as compared with isocaloric and isoprotein dairy products in elderly women . DESIGN A r and omized double-blind controlled-trial , 56-day intervention was conducted in institutionalized women ( mean age 85.5 years ) consuming 2 125-g servings of either vitamin D- and calcium-fortified yogurt ( FY ) at supplemental levels of 10 μg/d vitamin D₃ and 800 mg/d calcium or nonfortified control yogurt ( CY ) providing 280 mg/d calcium . MAIN OUTCOMES The endpoints were serum changes from baseline ( day 0 ) to day 28 and day 56 in 25-hydroxyvitamin-D ( 25OHD ) , PTH , and bone resorption markers tartrate-resistant acid phosphatase isoform-5b ( TRAP5b ) , the primary outcome , and carboxyl-terminal cross-linked telopeptide of type I collagen ( CTX ) . RESULTS At day 56 , serum 25OHD increased ( mean ± SEM ) by 25.3 ± 1.8 vs 5.2 ± 2.5 nmol/L in FY ( n = 29 ) and CY ( n = 27 ) , respectively ( P < .0001 ) . The corresponding changes in PTH were -28.6 % ± 7.2 % vs -8.0 % ± 4.3 % ( P = .0003 ) ; in TRAP5b , -21.9 % ± 4.3 % vs 3.0 % ± 3.2 % ( P < .0001 ) ; and in CTX , -11.0 % ± 9.7 % vs -3.0 % ± 4.1 % ( P = .0146 ) , in FY and CY , respectively . At day 28 , these differences were less pronounced but already significant for 25OHD , PTH , and TRAP5b . CONCLUSIONS This study in institutionalized elderly at high risk for osteoporotic fracture suggests that fortification of dairy products with vitamin D₃ and calcium provides a greater prevention of accelerated bone resorption as compared with nonfortified equivalent foods OBJECTIVE To assess the cost implication s for a preventive treatment strategy for institutionalised elderly women with a combined 1200 mg/day calcium and 800 IU/day vitamin D(3 ) supplementation in seven European countries . DESIGN Retrospective cost effectiveness analysis based on a prospect i ve placebo-controlled r and omised clinical trial . DATA SOURCES Recently published cost studies in seven European countries . Clinical results from Decalyos , a 3-year placebo-controlled study in elderly institutionalised women . TRIALS Decalyos study , with 36 months follow-up of 3270 mobile elderly women living in 180 nursing homes , allocated to two groups . One group received 1200 mg/day elemental calcium in the form of tricalcium phosphate together with 800 IU/day ( 20 microg ) of cholecalciferol ( vitamin D(3 ) ) , the other placebo . RESULTS In the 36 months analysis of the Decalyos study , 138 hip fractures occurred in the group of 1176 women , receiving supplementation  and 184 hip fractures in the placebo group of 1127 women . The mean duration of treatment was 625.4 days . Adjusted to 1000 women , 46 hip fractures were avoided by the calcium and vitamin D(3 ) supplementation . For all countries , the total costs in the placebo group were higher than in the group receiving supplementation , result ing in a net benefit of 79000 - 711000 per 1000 women . CONCLUSION This analysis suggests that the supplementation strategy is cost saving . The results may underestimate the net benefits , as this treatment has also shown to be effective in decreasing the incidence of other non-vertebral fractures in elderly institutionalised women Studies that evaluate the influence of gastric bypass ( RYGP ) on bone mass are limited to short-term follow-up . We analysed changes in bone mineral density ( BMD ) three years after surgery and evaluated the main determinants of the development of bone disease . Prospect i ve study of 59 morbidly obese white women aged 46 ± 8 years . BMD scanning using DEXA and plasma determinations of calcium , parathyroid hormone , 25-hydroxyvitamin D and insulin-like growth factor-I were made prior , at 12 months and 3 years after surgery . In the first postoperative year BMD decreased at femoral neck ( FN ) 10.2 % and in the lumbar spine ( LS ) 3.2 % , in the third year it additionally decreased 2.7 % and 3.1 % , respectively . BMD at both sites remained above the values of women of the same age . In the follow-up , 1.7 % developed osteoporosis at FN and 6.8 % at LS . Patients with bone disease were older , the percentage of women with menopause was greater in this group and had lower initial and final values of lean mass . The percentage of BMD loss at FN remained positively associated with the percentage of lean mass loss [ β 0.304 , p = 0.045 ] , and menopause [ β 0.337 , p = 0.025 ] . Major osteoporotic fracture and hip fracture risk was low even in menopausal patients ( 3.1 % and 0.40 % , respectively ) . After RYGP menopausal women and those with greater lean mass loss are at higher risk of BMD loss but progression to osteoporosis is uncommon and the risk of fracture is low Objective : To assess the safety of a nutraceutical compound containing soy isoflavones and Lactobacillus sporogenes on endometrium , breast and liver function . Setting : Outpatient Menopausal Clinic . Study Design : 130 healthy postmenopausal women suffering from menopausal symptoms were r and omized to receive soy isoflavones 60 mg and Lactobacillus sporogenes 1 billion spores ( group E : 65 women ) or calcium and vitamin D3 ( group C : 65 women ) . Safety of the treatment was assessed at baseline and after 1 year taking into account endometrial thickness , mammographic density , serum levels of transaminases , γ-GT and bilirubin . Efficacy of the treatment was evaluated rating the score of menopausal symptoms at baseline and every 3 months . The statistical analysis was carried out with χ2 , Fisher exact ’s test and ANOVA . Results : After 12 months of treatment mammographic density , endometrial thickness and hepatic function did not show significant differences between groups , while menopausal symptoms were progressively and significantly reduced in severity and frequency during treatment with soy isoflavones plus Lactobacillus sporogenes versus calcium plus vitamin D3 . Conclusion : A 12 months treatment with a nutraceutical compound based on isoflavones and Lactobacillus sporogenes at the recommended doses is safe for endometrium , mammary gl and s and liver function in postmenopausal women CONTEXT There are few published long-term data on absolute risk of subsequent fracture ( refracture ) following initial low-trauma fracture in women and fewer in men . OBJECTIVE To examine long-term risk of subsequent fracture  following initial osteoporotic fracture in men and women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study ( Dubbo Osteoporosis Epidemiology Study ) in Australia of 2245 community-dwelling women and 1760 men aged 60 years or older followed up for 16 years from July 1989 through April 2005 . MAIN OUTCOME MEASURE Incidence of first ( initial ) fracture and incidence of subsequent fracture according to sex , age group , and time since first fracture . Relative risk was determined by comparing risk of subsequent fracture with risk of initial fracture . RESULTS There were 905 women and 337 men with an initial fracture , of whom 253 women and 71 men experienced a subsequent fracture . Relative risk ( RR ) of subsequent fracture in women was 1.95 ( 95 % confidence interval [ CI ] , 1.70 - 2.25 ) and in men was 3.47 ( 95 % CI , 2.68 - 4.48 ) . As a result , absolute risk of subsequent fracture was similar in women and men and at least as great as the initial fracture risk for a woman 10 years older . Thus , women and men aged 60 to 69 years had absolute refracture rates of 36/1000 person-years ( 95 % CI , 26 - 48/1000 ) and 37/1000 person-years ( 95 % CI , 23 - 59/1000 ) , respectively . The increase in absolute fracture risk remained for up to 10 years , by which time 40 % to 60 % of surviving women and men experienced a subsequent fracture . All fracture locations apart from rib ( men ) and ankle ( women ) result ed in increased subsequent fracture risk , with highest RRs following hip ( RR , 9.97 ; 95 % CI , 1.38 - 71.98 ) and clinical vertebral ( RR , 15.12 ; 95 % CI , 6.06 - 37.69 ) fractures in younger men . In multivariate analyses , femoral neck bone mineral density , age , and smoking were predictors of subsequent fracture in women and femoral neck bone mineral density , physical activity , and calcium intake were predictors in men . CONCLUSION After an initial low-trauma fracture , absolute risk of subsequent fracture was similar for men and women . This increased risk occurred for virtually all clinical fractures and persisted for up to 10 years An open-label study with blinded evaluation was performed to compare the preventive effect of a calcium supplement alone ( monotherapy ) or calcium supplement plus menatetrenone ( combined therapy ) on fracture in osteoporotic postmenopausal women aged 50 years or older . Patients were r and omized to receive monotherapy ( n = 2,193 ) or combined therapy ( n = 2,185 ) . Before r and omization , the subjects were stratified into a subgroup without vertebral fractures ( n = 2,986 ; no-fracture subgroup ) and a subgroup with at least one vertebral fracture ( n = 1,392 ; fracture subgroup ) . The incidence rate of new vertebral fractures during 36 months of treatment ( primary endpoint ) did not differ significantly between either subgroup of the two treatment groups . Although the cumulative 48-month incidence rate of new clinical fractures ( secondary endpoint ) was lower in the combined therapy group , the difference was not significant . There was a lower risk of new vertebral fractures in patients with at least five baseline fractures who received combined therapy . Also , the loss of height was less with combined therapy than with monotherapy  among patients 75 years of age or older at enrollment , those whose last menstrual period occurred 30 years or more before enrollment , and those with at least five vertebral fractures at enrollment .  Adverse events and adverse reactions were more frequent in the combined therapy group . In conclusion , menatetrenone therapy was not effective for preventing vertebral fractures in the full analysis set of this study , but the results suggested that it may prevent vertebral fractures in patients with more advanced osteoporosis Background Hypovitaminosis D is particularly common among older people with a proximal femoral ( hip ) fracture . There are currently no agreed strategies for vitamin D replenishment after hip fracture surgery . The REVITAHIP Study is a multisite , double-blinded r and omized-controlled trial investigating the effects of an oral vitamin D loading dose on gait velocity after hip fracture surgery . We describe the baseline characteristics of participants , aim ing to document hypovitaminosis D and its associations after hip fracture . Methods Participants , over 65 , recruited within 7 days following hip fracture surgery from 3 Australia hospitals , were r and omly allocated to receive a loading dose of vitamin D3 ( 250,000IU ) or placebo , followed by oral maintenance vitamin D3/calcium ( 800 IU/500 mg ) and the usual hip fracture rehabilitation pathway . Demographic and clinical data were collected , including surgical procedure , pre-fracture functional status , Mini Mental State Examination ( MMSE ) score , serum 25-hydroxyvitamin D ( 25-OHD ) , Verbal Rating Scale ( VRS ) for pain , grip strength and gait velocity . The associations of baseline 25-OHD levels with demographic and clinical data were assessed using Pearson ’s correlation , ANOVA and regression analyses . Results Two-hundred- and -eighteen people with hip fracture participated in the study . Mean age was 83.9+/-7.2 years , 77 % were women and 82 % lived in private homes . Fifty-six percent had a subcapital fracture . Mean comorbidity count was 3.13+/-2.0 . Mean MMSE was 26.1+/-3.9 . Forty-seven percent of participants had hypovitaminosis D ( < 50 nmol/L ) . Multivariate regression models demonstrated higher baseline vitamin D levels were significantly associated with higher premorbid Barthel index scores , lower post-operative VRS pain levels and use of vitamin D. Conclusion This study cohort shared similar demographic characteristics and comorbidities with other cohorts of people with hip fracture , with the probable exception of less cognitive impairment . Hypovitaminosis D was not as prevalent as previously documented . Patients taking vitamin D supplements and with higher premorbid Barthel index , reflecting greater independence and activity , tended to have higher 25-OHD levels at baseline . Further , lower VRS pain ratings following surgery were associated with higher vitamin D levels . Such associations will need further investigation to determine causation . ( ANZCTR number , ACTRN12610000392066).Trial registration The protocol for this study is registered with the Australian New Zeal and Clinical Trials Registry ANZCTRN ACTRN12610000392066 Context Vitamin D supplementation may help prevent fractures , but the relationship between blood vitamin D concentrations and fracture risk is unclear . Contribution These authors observed an increased risk for hip fracture among women with lower serum 25-hydroxyvitamin D [ 25(OH ) vitamin D ] concentrations that was independent of measures of frailty , body mass index , physical function , and falls . Caution The authors did not measure bone mineral density ( BMD ) , so they could not determine whether 25(OH ) vitamin D concentrations give different information about fracture risk than that offered by BMD . Implication Low serum 25(OH ) vitamin D concentrations seem to be associated with a higher hip fracture risk . The Editors Vitamin  D deficiency is common in older adults , especially during the winter ( 1 ) and in homebound population s ( 2 ) , general medical in patients ( 3 ) , and community-dwelling women admitted to the hospital with acute hip fracture ( 4 ) . A recently published evidence -based report on vitamin D and bone health ( 5 ) found the level of evidence for an association between serum 25-hydroxyvitamin D [ 25(OH ) vitamin D ] concentrations and fracture risk to be inconsistent ( 5 ) . Since publication of that review , 1 prospect i ve study ( 6 ) reported no relationship between serum 25(OH ) vitamin D concentrations and fractures , whereas another ( 7 ) reported a significantly lower risk for hip fracture with 25(OH ) vitamin D concentrations greater than 60 nmol/L. Vitamin D concentration could be associated with fractures in several ways . It could influence muscle strength and balance , both of which contribute to falls and disability ( 810 ) . The association between 25(OH ) vitamin D concentrations and fracture may also be influenced by renal function , because renal insufficiency has been linked to fracture ( 11 ) and to vitamin D deficiency ( 12 ) . Several interactions between vitamin D and estrogen receptors have been described ( 13 ) ; hormone therapy has been shown to reverse abnormalities in vitamin D metabolism ( 14 ) , and low vitamin D concentrations have also been linked to higher bone turnover ( 15 , 16 ) . Thus , sex-steroid hormones and bone turnover could contribute to the association between 25(OH ) vitamin D concentration and fractures . We conducted a nested casecontrol study within the WHI-OS ( Women 's Health Initiative Observational Study ) among 400 case- patients with adjudicated incident hip fracture and 400 control participants . We tested whether low serum 25(OH ) vitamin D concentrations are associated with a higher risk for hip fractures in community-dwelling women and whether this relationship may be mediated by poor physical functioning , frailty , falls , sex-steroid hormones , renal function , or bone turnover . Methods Study Population Our study population came from the WHI-OS , a prospect i ve cohort study that enrolled 93676 women between 1994 and 1998 at 40 U.S. clinical centers ( age range , 50 to 79 years ) . Study methods are described in detail elsewhere ( 17 ) . In brief , women were eligible if they were postmenopausal , were unlikely to move or die within 3 years , were not enrolled in the WHI clinical trials , and were not currently participating in any other clinical trial . The human subjects review committees from each participating institution approved the study . Follow-up and Outcome Ascertainment We sent women question naires annually to report any hospitalization and other outcomes , including fractures . As of August 2004 , median follow-up duration was 7.1 years ( range , 0.7 to 9.3 years ) . At that time , 3.7 % of participants had withdrawn or were lost to follow-up and 5.3 % had died . We review ed medical records to verify cases of hip fracture , and blinded central adjudicators confirmed the cases ( 18 ) . We excluded patients with pathologic hip fractures . Nested CaseControl Study Design The present study is a casecontrol study nested within the prospect i ve design of WHI-OS . We excluded women who had a history of hip fracture ; were receiving hormone therapy up to 1 year before enrollment ; or were currently receiving and rogens , selective estrogen receptor modulators , antiestrogens , or other osteoporosis treatments ( bisphosphonates , calcitonin , or parathyroid hormone ) . We also excluded women with insufficient serum stored or of unknown ethnicity , leaving 39793 eligible participants . Of these , 404 women had a hip fracture . We r and omly selected 400 of these women to form the incident hip fracture group . For each case-patient , we selected 1 control participant who was within 1 year of the case-patient 's age at screening , was of matching race or ethnicity , and had their blood drawn within 120 days of the case-patient 's blood draw date ; 99 % of case- patients and control participants were matched within 30 days . Baseline Clinical Variables We divided clinical centers into 3 geographic regions on the basis of latitude : northern ( > 40 N ) , middle ( 35 to 40 N ) , and southern ( < 35 N ) . We ascertained all covariates at baseline . Clinic interviewers recorded current use of prescription medications by direct inspection of medicine containers . We entered prescription names into the WHI data base and assigned drug codes by using Medispan software ( First Data Bank , San Bruno , California ) . Average amounts of elemental calcium and vitamin D preparations were entered directly from supplement containers . Dietary intakes of calcium and vitamin D were assessed by using a semiquantitative food-frequency question naire ( 19 ) . Total calcium and vitamin D intake was defined as the sum of diet and supplements . We used question naires to ascertain date of birth , race or ethnicity , age at menopause , history of any fracture after age 55 years , smoking , parental history of hip fracture , self-rated health status , and alcohol consumption . We classfied physical activity on the basis of frequency and duration of walking and mild , moderate , and strenuous activities in the previous week . We calculated kilocalories of energy expended in 1 week as the metabolic equivalent ( kcal hours/week per kg ) ( 20 ) . We measured physical function by using the R AND Short Form-36 physical function scale , which comprises 10 items measuring whether health now limits physical function in moderate or vigorous activity ( 2 items ) ; strength to lift , carry , stoop , bend , or stair climb ( 4 items ) ; ability to walk various distances without difficulty ( 3 items ) ; and self-care ( 1 item ) ( 21 ) . The scale is scored from 0 to 100 , with higher scores indicating better physical function . We compared women with a score greater than 90 versus those with a score less than or equal to 90 , a cutoff value corresponding to the median score . We computed a frailty score , which included self-reported muscle weakness and impaired walking speed ( R AND Short Form-36 physical function scale score < 75 ) , exhaustion ( R AND Short Form-36 vitality scale score < 55 ) , low physical activity ( lowest quartile of physical activity ) , and unintended weight loss between baseline and 3 years of follow-up ( 22 ) . A woman was considered frail if she reported 3 or more of these indicators . Weight was measured on a balance-beam scale with the participant dressed in indoor clothing without shoes . Height was measured by using a wall-mounted stadiometer . Body mass index was calculated as weight ( in kg ) divided by height ( in m2 ) . Laboratory Procedures Laboratory personnel blinded to casecontrol status obtained a 12-hour fasting blood sample at the baseline visit , which was processed and stored at 80C according to strict quality control procedures ( 23 ) . Serum 25(OH ) vitamin D concentrations and sex-steroid hormone levels were measured at the Reproductive Endocrine Research Laboratory at the University of Southern California .  25-Hydroxyvitamin vitamin D was measured by using a radioimmunoassay with DiaSorin reagents ( DiaSorin , Stillwater , Minnesota ) . The sensitivity of the assay was 3.75 nmol/L. The interassay coefficients of variation were 11.7 % , 10.5 % , 8.6 % , and 12.5 % at 14.0 , 56.8 , 82.5 , and 122.5 nmol/L , respectively . Estradiol and testosterone concentrations were quantified by using sensitive and specific radioimmunoassays after organic solvent extraction and celite column partition chromatography ( 2427 ) . The intra- and interassay coefficients of variation were 7.9 % and 8 % to 12 % , respectively , for estradiol and 6 % and 10 % to 12 % , respectively , for testosterone . We calculated bioavailable hormone concentrations by using mass action equations ( 2830 ) . We measured sex hormonebinding globulin by using a solid-phase , 2-site chemiluminescent immunoassay . The intra- and interassay coefficients of variation were 4.1 % to 7.7 % and 5.8 % to 13 % , respectively . Serum cystatin C , a marker of renal function that is independent of age and weight , was measured at Medical Research Laboratories International , Highl and Heights , Kentucky , by using the Dade Behring BN-II nephelometer and Dade Behring reagents ( Dade Behring , Ramsey , Minnesota ) in a particle-enhanced immunonepholometric assay . Serum C-terminal telopeptide of type I collagen and aminoterminal procollagen extensions propeptide were measured by immunoassay ( Synarc , Lyon , France ) . Statistical Analysis We used chi-square and t tests to compare baseline characteristics between case- patients with hip fracture and matched control participants . We assigned 25(OH ) vitamin D concentrations to quartile categories defined on the basis of the distribution in the control participants . To further assess confounding , we compared baseline characteristics across quartiles of 25(OH ) vitamin D concentrations in case- patients and control participants combined . We calculated the P values for trend by using logistic regression and coding the variable of interest as a continuous variable . We assessed the association between serum 25(OH ) vitamin D concentrations and incident hip fracture in conditional logistic regression models that retained the matched casecontrol design . We first examined the unadjusted associations and then adjusted for age , BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year The purpose of this study was to ( 1 ) quantify the healing process of the human osteoporotic proximal humerus fracture ( PHF ) expressed in terms of callus formation over the fracture region using BMD scanning , and ( 2 ) quantify the impact of medical intervention with vitamin D3 and calcium on the healing process of the human osteoporotic fracture . The conservatively treated PHF was chosen in order to follow the genuine fracture healing without influence of osteosynthetic material s or casts . Thirty women ( mean age = 78 years ; range = 58–88 ) with a PHF , osteoporosis or osteopenia ( based on a hip scan , WHO criteria ) , and not taking any drugs related to bone formation , including calcium or vitamin D supplementation  , were r and omly assigned to either oral 800 IU vitamin D3 plus 1 g calcium or placebo , in a double-blind prospect i ve study . We measured biochemical , radiographic , and bone mineral density effect parameters to evaluate the impact on the healing process . Scanning procedures of the fractured shoulder included use of a fixation device to obtain the highest possible precision . Double scans of the fractured shoulder revealed a coefficient of variation ( CV ) on BMD measurements that improved from 2.8 % immediately after fracture occurrence to 1.7 % at 12 weeks ( P = 0.003 ) approaching the 1.2 % levels observed over the healthy shoulder . BMD was similar in the two groups at baseline ( active 0.534 g/cm2 vs. placebo 0.518 g/cm2 ) , and both increased over the 12-week observation period , with peak levels in week 6 . By week 6 BMD levels were higher in the active group ( 0.623 g/cm2 ) compared with the placebo group ( 0.570 g/cm2 , P = 0.006 ) . Thirty seven percent of the patients presented with vitamin D levels below 30 nmol/l , indicative of mild vitamin D insufficiency . In conclusion , we have demonstrated that it is possible to quantify callus formation of the PHF with sufficiently high precision to demonstrate the positive influence of vitamin D3 and calcium over the first 6 weeks after fracture . Whether this results in more stable fractures , extends to other fracture types , or applies to other osteogenic bone agents such as bisphosphonates remains to be examined Summary Fall prevention is a key strategy for reducing  osteoporotic fractures . We investigated the association between vitamin D receptor ( VDR ) polymorphisms and reported  falls in postmenopausal women . Bsm1 polymorphisms were associated with falls , balance and muscle power measurements . These results may explain some of the excess fracture risk associated with VDR in some studies . Introduction Fall prevention is a key strategy for reducing osteoporotic fractures . It has been suggested that vitamin D supplementation may reduce the incidence of falls by reducing body sway and increasing muscle power . The vitamin D receptor gene is a well-studied c and i date gene for osteoporosis . We investigated the association between VDR polymorphisms and reported  falls in postmenopausal women . Methods Falls data were collected in two separate population cohorts . Five polymorphisms of the VDR gene were analysed ( Cdx-2 , Fok-1 , BsmI , Taq1 and Apa1 ) in the Aberdeen Prospect i ve Osteoporosis Screening Study ( APOSS ) cohort . Results found in APOSS were then vali date d in an independent cohort — the Osteoporosis and Ultrasound ( OPUS ) study ( Bsm1 and Fok1 only ) , where muscle power and balance were also measured . Results Carriers of the ‘ B ’ allele ( Bsm1 ) showed an increased risk for falls . In APOSS , this was statistically significant for visit 3 multiple falls ( p = 0.047 ) and for recurrent falls ( p = 0.043 ) . Similar results were found in OPUS for visit 1 falls ( p = 0.025 ) and visit 1 multiple falls ( p = 0.015 ) . Bsm1 polymorphisms were also associated with balance and muscle power measurements . Conclusions In conclusion , these results demonstrate an association between the Bsm1 polymorphism and risk of falling that may explain some of the excess fracture risk associated with VDR in some studies Context Research ers have not previously reported the efficacy and safety of parathyroid hormone ( 1 - 84 ) ( PTH ) for the primary prevention of osteoporotic fractures .  Contributions Among 2532 postmenopausal women with osteoporosis r and omly assigned to receive PTH or placebo , PTH decreased new vertebral fractures . The magnitude of the effect depended on assumptions about fractures in the one third of patients who withdrew from the trial prematurely . Adverse effects included hypercalciuria , hypercalcemia , and nausea . Caution Endogenous PTH and vitamin D levels could affect patients response to the drug but were not assessed in the study . Implication s Parathyroid hormone ( 1 - 84 ) effectively prevented new vertebral fractures but also increased hypercalciuria , hypercalcemia , and nausea . The Editors Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing patients to an increased risk for fracture ( 1 ) . Optimal treatment for osteoporosis should improve the amount , density , and quality of bone , thereby reducing skeletal fragility and fractures .  Antiresorptive agents , such as bisphosphonates , are commonly used for treating postmenopausal osteoporosis . Although these agents preserve bone architecture , they do not stimulate new bone formation or improve bone architecture . Anabolic or bone-forming agents are an alternative approach to the treatment of osteoporosis . Research ers have shown that parathyroid hormone ( PTH ) and certain peptide fragments of PTH increase bone mass and improve bone quality ( 2 , 3 ) . Teriparatide , a fragment of human PTH composed of its N-terminal 34 amino acids , has been approved for the treatment of postmenopausal women with osteoporosis who are at high risk for bone fracture . However , research ers have studied this agent only in women with prevalent vertebral fractures ( 4 ) , and data demonstrating prevention of the first vertebral fracture are lacking . We conducted the Treatment of Osteoporosis with Parathyroid Hormone ( TOP ) Study to examine the efficacy and safety of PTH ( 1 - 84 ) versus placebo for treating postmenopausal women with osteoporosis . We design ed the study to examine the change in incidence of all vertebral fractures between the treatment groups . We also design ed the study to examine the efficacy of this new bone-forming agent in preventing a first vertebral fracture in women without a vertebral fracture . Methods Study Participants We included postmenopausal women 45 to 54 years of age if bone mineral density ( BMD ) was 3.0 SDs or more ( T-score 3.0 ) below the mean peak bone mass of young adult women at the lumbar spine , femoral neck , or total hip with no prevalent vertebral fracture or if BMD T-score was2.5 and they had 1 to 4 vertebral fractures before enrollment . We included postmenopausal women 55 years of age or older if BMD T-score was2.5 and they had no vertebral fractures or if BMD T-score was2.0 and they had 1 to 4 vertebral fractures . We excluded women if baseline serum calcium level was greater than 2.66 mmol/L ( > 10.7 mg/dL ) or if urinary calciumcreatinine ratio was 1.0 or more . We included women with mild hypercalcemia ( serum calcium , 2.55 to 2.66 mmol/L [ 10.2 to 10.7 mg/dL ] ) and mild hypercalciuria ( 24-hour urine calcium7.6 mmol [ 302 mg ] ) at baseline . We did not measure baseline levels of serum PTH and vitamin D. We excluded women if they had taken bisphosphonates for a total of more than 12 months or for more than 90 days in the 12 months before enrollment . We allowed  previous estrogen therapy  if it had been discontinued for at least 4 weeks before the screening visit . We excluded women who had received PTH ( or a peptide fragment or analogue ) , PTH-related protein , fluoride , or strontium and those who had a history of metabolic bone disease ( other than osteoporosis ) , nephrolithiasis , or clinical ly significant hepatic or renal disorders . We also excluded women who were taking medications known to affect bone mineral metabolism . The ethics review committee for each center approved the study . All women provided written informed consent . An independent data and safety monitoring board review ed the progress and safety of the study . Study Design We conducted a r and omized , double-blind , placebo-controlled , parallel-group study in 168 centers in 9 countries . We r and omly assigned the study drug to blocks of 4 patients by using a computer-generated algorithm and shipped it in blocks of 4 to each study site . Women at each site were sequentially assigned the uniquely numbered , r and omly assigned study drug treatment kits by telephone . Women were stabilized for at least 2 weeks with supplemental calcium , 700 mg/d citrate salt , and vitamin D3 , 400 U/d , and then received 100 g of recombinant human PTH or placebo daily by subcutaneous injection for 18 months with continued calcium and vitamin D3 supplementation . Patients were instructed to administer the injection in the morning in the thigh or abdomen by using an injector pen . Study Conduct and Outcome Measures The primary end point was the occurrence of new or worsened vertebral fractures ( in all women and in women with and without a prevalent fracture ) identified by radiography at baseline , month 18 , or the final study visit . Radiologists assessed vertebral fractures in a blinded manner at a central reading organization by using a semiquantitative 4-point grading scale ( 5 ) . An incident vertebral fracture ( new or worsened ) was identified by a change in grade of 1 or more from baseline . Secondary outcomes included changes in BMD at lumbar spine , hip , whole body , and forearm ( distal one-third radius ) that we measured by using dual-energy x-ray absorptiometry with Hologic ( Hologic Inc. , Bedford , Massachusetts ) or Lunar ( GE Medical Systems , Madison , Wisconsin ) densitometers ( reported as percentage change from baseline to st and ardize instrumental differences in determining absolute BMD ) and stadiometric measurements of height . We measured whole body and forearm BMD only in a subset of approximately 300 women from selected sites with appropriate software . We reported nonvertebral clinical fractures and bone loss ( > 7 % at lumbar spine or > 9 % at total hip or femoral neck ) as adverse events . We did not distinguish between traumatic and fragility nonvertebral fractures . We used quantitative computed tomography ( 6 , 7 ) to evaluate the effects of PTH treatment at month 18 on volumetric cortical and trabecular BMD at lumbar vertebra ( L3 ) and the hip in 122 consenting women from a single center at which the technique was available . We assessed bone turnover markers ( serum bone-specific alkaline phosphatase and urinary N-telopeptides of type I collagen ) in the first 600 r and omly assigned women in the study . We measured bone-specific alkaline phosphatase by using the T and em R-Ostase immunoradiometric assay ( interassay coefficient of variation , 8 % ) ( Hybritech , San Diego , California ) . We measured N-telopeptides of type I collagen by using Osteomark enzyme-linked immunoabsorbent assay kits ( interassay coefficient of variation , 4.0 % ) ( Wampole Laboratories , Princeton , New Jersey ) normalized to urine creatinine concentrations . We made safety assessment s at months 1 , 3 , 6 , 9 , 12 , 15 , and 18 that included physical examinations , vital signs , electrocardiography ( months 1 , 12 , and 18 ) , adverse-event monitoring and central clinical laboratory assessment s consisting of chemistry ( including serum total calcium and creatinine ) , hematology , and urinalysis ( including 24-hour urine collection s and fasting , morning urinary calciumcreatinine ratios ) . Adverse events were reported spontaneously by patients , captured in a patients diary , or reported by a patient in response to an open-ended question from clinical study personnel . We used a central laboratory normal range for serum total calcium level of 2.15 to 2.55 mmol/L ( 8.6 to 10.2 mg/dL ) . We performed an analysis for antibodies to PTH with a vali date d electrochemiluminescent immunoassay by using biotinylated recombinant human PTH ( range , 26.3 to 2632.5 pmol/L ; intra-assay coefficient of variation , 8 % to 16 % ) ( Igen International , Inc. , Gaithersburg , Maryl and ) . We obtained iliac crest bone biopsy specimens at month 12 or 18 from a subset of 40 consenting women after tetracycline double-labeling ( 8) that we examined for abnormal bone structure . We anticipated that women might need to discontinue calcium supplementation and reduce the dosing frequency of the study drug to prevent excessive increases in serum calcium level , urinary calcium level , or both . We conservatively predefined hypercalcemia as a single , unconfirmed , predose serum total calcium value greater than 2.66 mmol/L ( > 10.7 mg/dL ) and hypercalciuria as a 24-hour urinary calcium value of 7.6 mmol or more ( 302 mg ) ( increased to > 9.0 mmol [ > 360 mg ] during the study ) or a fasting urinary calciumcreatinine ratio of 1.0 or more . If a woman developed hypercalcemia or hypercalciuria , we discontinued the daily calcium supplementation ; if either condition continued , we reduced the dosing frequency of the study drug . Statistical Analysis We estimated the sample size for our study by assuming that 67 % of the patients would not have a prevalent fracture ; that the 18-month vertebral fracture incidence for patients with and without a prevalent fracture who received placebo would be 10 % and 2.5 % , respectively ; and that 20 % of the patients in each group would discontinue the study early without a new or worsened fracture .  We expected a sample of 2600 patients ( 1300 per treatment group ) to provide at least 90 % power to detect a significant 60 % or greater reduction in vertebral fracture incidence in the PTH treatment group compared with the placebo group ( 2-sided level of 0.05 ) . We analyzed data by using SAS software , version 8.0 ( SAS Institute , Inc. , Cary , North Carolina ) . We used descriptive statistics to summarize demographic and other baseline variables . We assessed comparability of the treatment groups at baseline by using t-tests for continuous BACKGROUND Vitamin D deficiency is common in older population s , particularly during the winter months due to low levels of ultraviolet light exposure , and in nursing home residents . OBJECTIVE The main objective of the current study was to assess the distribution of serum 25-hydroxyvitamin D and its correlates in a sample of men and women with recent hip fractures who were part of a large clinical trial . METHODS This was a cross-sectional exploratory study of screened and ultimately r and omized patients with hip fractures . They were part of a multinational ( 115 clinical centers in 20 countries ) , r and omized , placebo-controlled , double-blind study testing the efficacy of a yearly IV bisphosphonate ( zoledronic acid ) in the prevention of new clinical fractures in patients with recent hip fracture repair .  Levels of 25-hydroxyvitamin D , calcium , alkaline phosphatase , creatinine clearance , and albumin were measured at a screening visit using blood serum . Demographic variables were assessed by patient self-report . Bone mineral density ( BMD ) was assessed by dual-energy x-ray absorptiometry of the nonfractured hip . RESULTS This report included 1174 screened patients ( 526 with vitamin D measured ) and 655 ( 385 with vitamin D measured ) patients r and omized before the protocol amendment . In screened patients , levels of 25-hydroxyvitamin D were low ( median , 14.7 ng/mL ; interquartilc range , 7.6 , 21.65 ) . Overall , 51 % were at or below the clinical ly meaningful threshold of 15 ng/mL. Among those patients r and omized , the level of 25-hydroxyvitamin D was significantly positively related to male sex ( rho , 0.13 ; P < 0.05 ) , serum calcium ( rho , 0.16 ; P < 0.01 ) , and BMD at the femoral neck ( rho , 0.22 ; P < 0.01 ) in bivariate analyses . Low serum 25-hydroxyvitamin D ( < 15 ng/mL ) was related only to low serum calcium ( odds ratio , 0.16 ; 95 % CI , 0.05 - 0.52 ) in multivariable logistic models controlling for sex , age , race , body mass index , living at home , alkaline phosphatase , and creatinine clearance . CONCLUSIONS We concluded that vitamin D insufficiency was a common problem in this population of elderly patients who had recently suffered a hip fracture . This insufficiency was related only to serum calcium in multivariable controlled models but can not be reliably identified or excluded by measuring serum calcium alone . Physicians should be encouraged to check and monitor patients ' serum levels of 25-hydroxyvitamin Vitamin D deficiency is common in elderly persons , especially those with hip fracture [ 1 , 2 ] . It is caused by low exposure to sunshine , decreased synthesis of vitamin D3 in the aging skin , and a diet low in vitamin D [ 3 , 4 ] . The mean vitamin D intake in elderly persons in the Netherl and s is about 100 IU/d , half that of elderly persons in the United States [ 5 ] . Most of this vitamin D comes from margarine , which is the only vitamin D-supplemented food in the Netherl and s ( 3 IU/g ) . In vitamin D deficiency , the low serum concentration of 25-hydroxyvitamin D [ 25(OH)D ] leads to a low 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] concentration and then to a higher serum parathyroid hormone concentration , especially in the winter [ 6 - 10 ] . Histologically , the increased parathyroid activity is associated with high bone turnover , leading to cortical bone loss and low density bone [ 5 , 11 ] , which may lead to hip fracture . We previously studied the effects of vitamin D supplementation in residents of a home for the elderly and residents of a nursing home [ 10 ] .  Vitamin D3 , 400 IU/d , led to an adequate increase of the serum 25(OH)D concentration , to a small but significant increase of the serum 1,25(OH)2D concentration , and to a decrease of the serum concentration of intact parathyroid hormone . It was recently observed [ 12 , 13 ] that bone mineral density at the hip is positively related to serum 25(OH)D concentration in postmenopausal and elderly women . Therefore , it might be expected that vitamin D supplementation would increase bone mineral density in elderly persons deficient in vitamin D. In line with this expectation , it was shown that vitamin D supplementation prevented bone loss from the spine during the winter in postmenopausal women [ 14 ] . These results suggest that vitamin D supplementation may reduce the incidence of hip fractures , because bone strength shows a strong correlation with bone mineral density [ 15 ] . However , increasing bone mineral density through a therapeutic intervention does not necessarily lead to increased bone strength , as has been shown with sodium fluoride [ 16 ] . Bone structure and bone quality are also determinants of bone strength [ 17 ] , and falls are a risk factor for hip fractures [ 18 ] . Therefore , hip fracture should be the outcome criterion in studies on the effect of vitamin D supplementation . Intervention studies on the prevention of osteoporotic fractures necessitate large numbers of patients , because the outcome has an annual incidence of 0.5 % to 4 % in the elderly population [ 19 ] . We report the results of a large-scale , prospect i ve study on the effect of vitamin D supplementation on the incidence of hip and other osteoporotic fractures . Methods Participants The study included 2578 persons ( 1916 women and 662 men ) 70 years of age and older ( mean age SD , 80 6 years ; range , 70 to 97 years ) . Participants were recruited from general practitioners , from apartment houses for elderly persons , and from homes for elderly persons in Amsterdam and its vicinity . Persons recruited from practitioners were living independently ; those recruited from apartment houses and homes were receiving some care , but less than they would have received in a nursing home . Participants had to be reasonably healthy and able to give informed consent . Persons with a history of hip fracture or total hip arthroplasty , known hypercalcemia , sarcoidosis , or recent urolithiasis ( < 5 years earlier ) were excluded . Patients who had diseases or who used medications that influence bone metabolism ( such as thyroid disease or glucocorticoid medication ) were not excluded . The spontaneous use of vitamin D supplements and multivitamins was discouraged , but the prescription practice s of the general practitioners were not altered . All vitamin use was carefully documented . The study was approved by the Ethical Review Board of the Vrije Universiteit Hospital , and all participants gave informed consent . Study Design After checking the inclusion and exclusion criteria and obtaining informed consent , the participants were r and omly assigned to receive either active treatment with vitamin D3 or placebo . The study was double-blind , and r and omization was done in blocks of 10 per general practice , apartment house , or home . R and omization lists were made using a computerized r and om-number generator . Lists in sealed envelopes were sent to the hospital pharmacy for assignment . Each participant took either one tablet per day that contained vitamin D3 , 400 IU , or one placebo tablet per day that was identical in appearance and taste to the vitamin tablet . After enrollment , the participants received the first container of tablets ( 210 tablets ) . The container was replaced every 6 months with a full container . All participants were also advised in writing to consume at least three servings of dairy products per day ( for example , 1 glass of milk , 1 cup of yogurt , and 1 slice of cheese ) to ensure a calcium intake of at least 800 to 1000 mg/d . The study was started in August 1988 . The last participant was enrolled in December 1990 , and all participants had stopped using study medication by December 1993 . The follow-up period had been planned to last no more than 3 years , but because the number of hip fractures during the study was lower than expected , a 6-month extension was planned . The study participants thus received medication for 3 to 3.5 years ; those who received it for 3.5 years were those who consented to the 6-month extension . Total follow-up was to a maximum of 4 years . Data collected at baseline included an  outdoor activity score  ( 1 equals going outdoors less than once a week ; 2 equals going outdoors 1 or 2 times per week ; and 3 equals going outdoors 3 times per week or more ) and a score for sunshine exposure ( when outside : 1 equals in the shade as much as possible ; 2 equals sometimes in sunshine ; 3 equals much exposure to sunshine ) . These scores show a positive relation with serum 25(OH)D concentration [ 3 ] . Mobility was estimated by a walking score that ranged from 1 ( unable to walk ) to 5 ( walks independently a fair distance on any surface ) [ 20 ] . The dietary calcium intake from dairy products was estimated in a subset of 348 women by using a question naire , as described previously [ 21 ] . The participants were evaluated annually with a question naire on hip fractures , other peripheral fractures , outdoor score , sunshine exposure score , use of vitamin supplements , and walking score . Each general practitioner or caretaker was asked to immediately report change of address , hip fracture , or death . Hip fracture and death were verified by the general practitioner . All participants were followed for the maximal period of 4 years if possible , even if they had stopped using the trial medication , had sustained a fracture , or had moved to another city . To investigate possible selection bias , 267 potential participants in a home for the elderly and its adjunct apartments ( all residents of the institution ) were studied for baseline characteristics , including age , sex , sunshine exposure score , outdoor score , walking score , and reasons for nonparticipation . Compliance was checked when the tablet containers were replaced ( every 6 months ) , by question naire ( every year ) , and by measurement of the serum 25(OH)D concentration . Serum 25(OH)D concentration was measured at baseline and after 1 year in 270 persons who participated in a sub study investigating the effect of vitamin D supplementation on bone mineral density and bone turnover variables . This sub study included a nonr and om sample of participants from several apartment houses and homes for the elderly and is described in detail elsewhere [ 21 ] . In the same sub study , dietary calcium intake from diary products was assessed . Serum 25(OH)D concentration was also estimated during the third year of the study in February and March in a r and om sample of 96 participants drawn from the remaining study population . These participants received a letter giving them an appointment within 10 days ; the blood sample s were drawn at home . Serum 25(OH)D concentration was measured by competitive protein binding assay after being purified by gradient high-pressure liquid chromatography . The intra- and interassay coefficients of variation were 5 % and 6 % , respectively [ 22 ] . Statistical Analysis Baseline data of the vitamin D group and the placebo group were compared using t-tests ( age , calcium intake ) , chi-square tests ( sex , residence ) , and Wilcoxon rank-sum tests ( scores ) . The serum 25(OH)D concentrations of both groups were compared using t-tests . Data on fractures and mortality were analyzed by survival analysis using log-rank tests , Cox proportional-hazards regression , and hazard rate ratios [ 23 ] . Hip fractures are presented using the Kaplan-Meier method . All participants were kept in the study as long as possible . The data were analyzed in two ways . The intention-to-treat analysis included all r and omly assigned participants for either the total follow-up period or until fracture , death , or loss to follow-up . The active treatment analysis included the participants as long as they stated that they were using the trial medication . Thus , the participants were included in the active treatment analysis until they stopped using the trial medication , regardless of whether a fracture occurred after they had stopped . Age , sex , and residence were added in both analyses as covariates to the Cox regression model . Because outdoor score , sunshine score , and walking score were interrelated ( correlation coefficients ranging from 0.21 to 0.59 ) and were likely to indicate general health or mobility , they were averaged over the years and added up to a sum score . For this purpose , the walking score was simplified ( 1 , 2 , or 3 equals 1 ; 4 equals 2 ; 5 equals 3 ) , because the lower walking scores applied to a few participants only . The result ing total score , ranging from 3 to 9 , was entered as a covariate in the model . The level of compliance ( weekly intake as reported on OBJECTIVES To determine the prevalence of vitamin D deficiency in older people in residential care and the influence that the level of vitamin D may have on their incidence of falls . DESIGN Prospect i ve cohort . SETTING Residential care facilities for older people in several states of Australia . PARTICIPANTS Six hundred sixty-seven women in low-level care and 952 women in high-level care , mean age 83.7 years . MEASUREMENTS  Serum 25-hydroxyvitamin D ( 25D ) levels and recognized risk factors for falls including current medication use , a history of previous fractures , weight , tibial length ( as a surrogate for height ) , cognitive function , walking ability , and frequency of going outdoors were determined . The women in low-level care and high-level care were followed for an average of 145 and 168 days , respectively . Falls were recorded prospect ively in diaries completed monthly by residential care staff . RESULTS  Vitamin D deficiency ( defined as a serum 25D level below 25 nmol/L ) was present in 144 ( 22 % ) women in low-level care and 428 ( 45 % ) in high-level care . After excluding 358 bed-bound residents and adjusting for weight , cognitive status , psychotropic drug use , previous Colles fracture , and the presence of w and ering behavior , log serum 25D level remained independently associated with time to first fall . The adjusted hazards ratio was 0.74 ( 95 % confidence interval=0.59 - 0.94 ; P=.01 ) , implying a 20 % reduction in the risk of falling with a doubling of the vitamin D level . CONCLUSION Vitamin D deficiency is common in residential care in Australia . A low level of serum vitamin D is an independent predictor of incident falls Objective To investigate associations between long term dietary intake of calcium and risk of fracture of any type , hip fractures , and osteoporosis . Design A longitudinal and prospect i ve cohort study , based on the Swedish Mammography Cohort , including a subcohort , the Swedish Mammography Cohort Clinical . Setting A population based cohort in Sweden established in 1987 . Participants 61 433 women ( born between 1914 and 1948 ) were followed up for 19 years . 5022 of these women participated in the subcohort . Main outcome measures Primary outcome measures were incident fractures of any type and hip fractures , which were identified from registry data . Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort . Diet was assessed by repeated food frequency question naires . Results During follow-up , 14 738 women ( 24 % ) experienced a first fracture of any type and among them 3871 ( 6 % ) a first hip fracture . Of the 5022 women in the subcohort , 1012 ( 20 % ) were measured as osteoporotic . The risk patterns with dietary calcium were non-linear . The crude rate of a first fracture of any type was 17.2/1000 person years at risk in the lowest quintile of calcium intake , and 14.0/1000 person years at risk in the third quintile , corresponding to a multivariable adjusted hazard ratio of 1.18 ( 95 % confidence interval 1.12 to 1.25 ) . The hazard ratio for a first hip fracture was 1.29 ( 1.17 to 1.43 ) and the odds ratio for osteoporosis was 1.47 ( 1.09 to 2.00 ) . With a low vitamin D intake , the rate of fracture in the first calcium quintile was more pronounced . The highest quintile of calcium intake did not further reduce the risk of fractures of any type , or of osteoporosis , but was associated with a higher rate of hip fracture , hazard ratio 1.19 ( 1.06 to 1.32 ) . Conclusion Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis RATIONALE Although vitamin D is widely used to promote skeletal health , definitive data on benefits and risks of supplemental vitamin D alone on bone are lacking . Results from large , r and omized controlled trials in the general population are sparse . Data on the effects of supplemental omega-3 fatty acids ( FAs ) on bone are also limited . DESIGN The VITamin D and OmegA-3 TriaL ( VITAL ) is a double-blind , placebo-controlled trial assessing the role of vitamin D3 ( 2000 IU/d ) and omega-3 FA ( 1g/d ) supplements in reducing risks of cancer and cardiovascular disease among U.S. men aged ≥50 and women aged ≥55 . To comprehensively test effects of supplemental vitamin D and /or omega-3 FAs on skeletal health , the VITAL : Effects on Fractures ancillary study is determining the effects of these supplements on incident fractures among 25,875 participants enrolled in the parent trial . Study investigators adjudicate fractures through a detailed review of medical records and radiological images ( hip and femur ) . In a complementary ancillary , VITAL : Effects on Structure and Architecture is determining the effects of supplemental vitamin D and /or omega-3 FAs on bone with detailed phenotyping during in-person visits . Comprehensive assessment s of bone density , turnover , structure/architecture , body composition , and physical performance are being performed at baseline and 2 years post-r and omization . CONCLUSION Results from these studies will clarify the relationship between supplemental vitamin D and /or omega-3 FAs on bone health outcomes , and inform clinical care and public health guidelines on the use of supplemental vitamin D for the primary prevention of fractures in women and men BACKGROUND Increased dietary calcium intake has been proposed as a population -based public health intervention to prevent osteoporotic fractures . We have examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action . METHODS Five-year , double-blind , placebo-controlled study of 1460 women recruited from the population and older than 70 years ( mean age , 75 years ) who were r and omized to receive calcium carbonate , 600 mg twice per day , or identical placebo .  The primary end points included clinical incident osteoporotic fractures , vertebral deformity , and adverse events ascertained in 5 years . Bone structure was also measured using dual x-ray absorptiometry of the hip and whole body , quantitative ultrasonography of the heel , and peripheral quantitative computed tomography of the distal radius . RESULTS Among our patients , 16.1 % sustained 1 or more clinical osteoporotic fractures . In the intention-to-treat analysis , calcium supplementation did not significantly reduce fracture risk ( hazard ratio , 0.87 ; 95 % confidence interval , 0.67 - 1.12 ) . However , 830 patients ( 56.8 % ) who took 80 % or more of their tablets ( calcium or placebo ) per year had reduced fracture incidence in the calcium compared with the placebo groups ( 10.2 % vs 15.4 % ; hazard ratio , 0.66 ; 95 % confidence interval , 0.45 - 0.97 ) . Calcium-treated patients had improved quantitative ultrasonography findings of the heel , femoral neck and whole-body dual x-ray absorptiometry data , and bone strength compared with placebo-treated patients . Of the 92 000 adverse events recorded , constipation was the only event increased by the treatment ( calcium group , 13.4 % ; placebo group , 9.1 % ) . CONCLUSION Supplementation with calcium carbonate tablets supplying 1200 mg/d is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance , but it is effective in those patients who are compliant Highlights • The BEST-D ( Biochemical Efficacy and Safety Trial of vitamin D ) trial will compare the biochemical and other effects of daily dietary supplementation with 100 μg or 50 μg vitamin D3 or placebo , when administered for 12 months , in 305 ambulant community-dwelling older people living in Oxfordshire , Engl and .• The primary analyses will compare 12-month mean plasma concentrations of 25(OH)D as well as the proportion of participants with a 12-month concentration > 90 nmol/L between participants allocated 100 μg and participants allocated 50 μg daily . Secondary analyses will compare the two active doses ( both separately and when combined ) with placebo.• Additional end-points include biochemical assessment s of safety , blood pressure , arterial stiffness , falls , fractures , heel and wrist bone density , grip strength and physical performance and echocardiographic assessment s of cardiac function in a r and om sample of participants .• The results of this trial will help determine the optimum dose of vitamin D to test in a larger trial investigating whether vitamin D supplementation can reduce the risk of fractures , cardiovascular disease or cancer BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo .  Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P<0.01 ) . Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . ) In postmenopausal women , the use of aromatase inhibitors increases bone turnover and induces bone loss at sites rich in trabecular bone at an average rate of 1 - 3 % per year leading to an increase in fracture incidence compared to that seen during tamoxifen use . The bone loss is much more marked in young women with treatment-induced ovarian suppression followed by aromatase inhibitor therapy ( average 7 - 8 % per annum ) . Pre-treatment with tamoxifen for 2 - 5 years may reduce the clinical significance of the adverse bone effects associated with aromatase inhibitors , particularly if this leads to a shortening in the duration of exposure to an aromatase inhibitor . However , skeletal status should still be assessed at the commencement of aromatase inhibitor therapy . The rate of bone loss in women who experience a premature menopause before the age of 45 or are receiving ovarian suppression therapy is accelerated by the concomitant use of aromatase inhibitors . These patients are considered to be at high risk of clinical ly important bone loss and should have a baseline dual energy X-ray absorptiometry ( DXA ) assessment of bone mineral density ( BMD ) . R and omised clinical trials in postmenopausal women indicate that bisphosphonates prevent the bone loss and accelerated bone turnover associated with aromatase inhibitor therapy and are a promising strategy for the prevention and treatment of osteoporosis in this setting . Treatment initiation recommendations are based on a combination of risk factors for osteoporotic fracture and BMD levels .  Bisphosphonates , along with a healthy lifestyle and adequate intake of calcium and vitamin D are the treatments of choice to prevent bone loss . Due to the rate of bone loss associated with breast cancer treatments , and uncertainties about the interaction between aromatase inhibitor use and BMD for fracture risk , the threshold for intervention has been set at a higher level than that generally recommended for postmenopausal osteoporosis . Management recommendations have been summarised in two algorithms , one for women experiencing a premature menopause and the other for postmenopausal women requiring adjuvant aromatase inhibitor therapy General practice p 994 Older people frequently fall . This is a serious public health problem , with a substantial impact on health and healthcare costs.1 These guidelines translate trial evidence about prevention of falls into recommendations that can be implemented in different setting s , with the aim of reducing the rate of falls and injurious falls in people over 65 ( see boxes 2 3 ) . # # # # Summary points Multifaceted interventions reduce falls in older people ( those over 65 ) Home assessment of older people at risk of falls without referral or direct intervention is not recommended Assessment of high risk residents in nursing homes with relevant referral is effective Evidence from well design ed single trials shows that assessment and modification of risk factors of older people who have presented to an accident and emergency department after a fall and the provision of hip protectors in residents of nursing homes are effective We up date d two previous systematic review s to include any new evidence up to March 1998 . 4 5 We electronically search ed Medline for all r and omised controlled trials and systematic review s by using the terms fall(s ) , accidental falls , fracture , elderly , aged , older , and senior . We followed up relevant references in papers , and we contacted research ers in prevention of falls for information about other trial evidence and about studies from journals not catalogued by the National Library of Medicine . For inclusion , studies had to be r and omised controlled trials of interventions design ed to minimise or prevent exposure to the risk factors for falling ( or fracture ) in people aged 65 years or over living in either community or residential care . Outcomes had to include the number of people who had fallen or the number of falls or fractures . We excluded drug or dietary treatments for the prevention of fractures . Trials that fulfilled the inclusion criteria were review ed and summarised Abstract . Although fluoride salts have been shown to be capable of linearly increasing spinal bone mineral density ( BMD ) in postmenopausal osteoporosis , the effects of this gain in density on the vertebral fracture rate remain controversial . We conducted a 2-year multicenter , prospect i ve , r and omized , double-masked clinical trial in 354 osteoporotic women with vertebral fractures ( mean age 65.7 years ) . They received either fluoride ( 208 patients ) , given as sodium fluoride ( 50 mg/day ) or as monofluorophosphate ( 200 mg/day or 150 mg/day ) , or a placebo ( 146 patients ) . All patients received daily supplements of 1 g of calcium ( Ca ) and 800 IU of vitamin D2 ( D ) . A 1-year open follow-up on Ca-D was obtained in 124 patients . After 2 years the fluoride group and the Ca-D group had increased their lumbar BMD by 10.8 % and 2.4 % respectively ( p = 0.0001 ) . However , the rate of patients with at least one new vertebral fracture , defined by semiquantitative assessment and evaluable on an intention-to-treat basis in 89 % of patients , was similar in the fluoride groups and the Ca-D group . No difference between the three fluoride regimens was found . The percentage of patients with nonvertebral fractures was not different in the fluoride and Ca-D groups ( 1.9 % and 1.4 % respectively for hip fractures ) . A lower limb pain syndrome occurred more frequently in the fluoride groups . In the 124 patients followed for 1 year after cessation of fluoride therapy , the percentage of patients with at least one new vertebral fracture after 36 months was identical to the percentages in the previous fluoride group and the Ca-D group . We conclude that flouride-Ca-D regimen was no more effective that Ca-D supplements for the prevention of new vertebral fractures in women with postmenopausal osteoporosis BACKGROUND Decreased ability to absorb calcium with age limits adaptation to low calcium intake and is thought to lead to secondary hyperparathyroidism and increased risk for hip and other fractures . However , the associations between fractional calcium absorption , dietary calcium intake , and risk for fracture have never been studied . OBJECTIVE To determine whether low fractional calcium absorption in women with low calcium intake increases the risk for subsequent hip and other nonspine  fractures . DESIGN Prospect i ve cohort study . SETTING Four clinical centers in Baltimore County , Maryl and ; Portl and , Oregon ; Minneapolis , Minnesota ; and the Monongahela Valley , Pennsylvania . PARTICIPANTS 5452 nonblack women 69 years of age or older participating in the fourth examination of the Study of Osteoporotic Fractures . MEASUREMENTS Fractional calcium absorption was measured by using a 3-hour single isotope ( 45Ca ) technique . Incident fractures were identified prospect ively and were confirmed by radiographic report . RESULTS During an average of 4.8 years , 729 women ( 13 % ) experienced at least one nonspine fracture  ;  153 of these women had hip fractures . After adjustment for age , women with lower fractional calcium absorption were at increased risk for hip fracture ( relative risk per 1-SD [ 7.7 % ] decrease in fractional calcium absorption , 1.24 [ 95 % CI , 1.05 to 1.48 ] ) . Women with low fractional calcium absorption and low calcium intake were at greatest risk for subsequent hip fracture ; among women whose dietary calcium intake was less than 400 mg/d , those who had fractional calcium absorption at or below the median value of 32.3 % had a 2.5-fold ( CI , 1.29-fold to 4.69-fold ) increase in risk for hip fracture compared with those who had greater absorption efficiency . Fractional calcium absorption was not related to risk for other nonspine fractures ( relative risk per 1-SD [ 7.7 % ] decrease in fractional calcium absorption , 1.05 [ CI , 0.96 to 1.14 ] ) . CONCLUSIONS In elderly women , low fractional calcium absorption in the setting of low calcium intake increases the risk for hip fracture . Our findings support the hypothesis of type II osteoporosis , which postulates that decreased calcium absorption is an important risk factor for hip fracture in older persons CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867 Objective To develop and vali date two new fracture risk algorithms ( QFractureScores ) for estimating the individual risk of osteoporotic fracture or hip fracture over 10 years . Design Prospect i ve open cohort study with routinely collected data from 357 general practice s to develop the scores and from 178 practice s to vali date the scores . Setting General practice s in Engl and and Wales . Participants 1 183 663 women and 1 174 232 men aged 30 - 85 in the derivation cohort , who contributed 7 898 208 and 8 049 306 person years of observation , respectively . There were 24 350 incident diagnoses of osteoporotic fracture in women and 7934 in men , and 9302 incident diagnoses of hip fracture in women and 5424 in men . Main outcome measures First ( incident ) diagnosis of osteoporotic fracture ( vertebral , distal radius , or hip ) and incident hip fracture recorded in general practice records . Results Use of hormone replacement therapy ( HRT ) , age , body mass index ( BMI ) , smoking status , recorded alcohol use , parental history of osteoporosis , rheumatoid arthritis , cardiovascular disease , type 2 diabetes , asthma , tricyclic antidepressants , corticosteroids , history of falls , menopausal symptoms , chronic liver disease , gastrointestinal malabsorption , and other endocrine disorders were significantly and independently associated with  risk of osteoporotic fracture in women . Some variables were significantly associated with risk of osteoporotic fracture but not with risk of hip fracture . The predictors for men for osteoporotic and hip fracture were age , BMI , smoking status , recorded alcohol use , rheumatoid arthritis , cardiovascular disease , type 2 diabetes , asthma , tricyclic antidepressants , corticosteroids , history of falls , and liver disease . The hip fracture algorithm had the best performance among men and women . It explained 63.94 % of the variation in women and 63.19 % of the variation in men . The D statistic values for discrimination were highest for hip fracture in women ( 2.73 ) and men ( 2.68 ) and were over twice the magnitude of the corresponding values for osteoporotic fracture . The ROC statistics for hip fracture were also high : 0.89 in women and 0.86 for men versus 0.79 and 0.69 , respectively , for the osteoporotic fracture outcome . The algorithms were well calibrated with predicted risks closely matching observed risks . The QFractureScore for hip fracture also had good performance for discrimination and calibration compared with the FRAX ( fracture risk assessment ) algorithm . Conclusions These new algorithms can predict risk of fracture in primary care population s in the UK without laboratory measurements and are therefore suitable for use in both clinical setting s and for self assessment ( www.qfracture.org ) . QFractureScores could be used to identify patients at high risk of fracture who might benefit from interventions to reduce their risk AIM To compare the nutritional status and dietary intake of elderly women admitted with hip fracture ( HF ) versus a control group without fracture and without known abnormalities of bone mineral density . DESIGN Descriptive and observational study . LOCATION Hospital Neurotraumatológico in Jaen ( Spain ) and three urban Primary Health Care centers in Jaen city ( San Felipe , Virgen de la Capilla and El Valle ) . PARTICIPANTS A total of 44 women with HF , which was considered osteoporotic , and a control group composed of 42 women with a similar age range , selected r and omly from the medical out patients who visit their Primary Health Care centers . MEASUREMENTS We record sociodemographic data . Dietary intake before the fracture and anthropometric variables  in the first 72hours after admission were assessed . RESULTS Patients with HF had lower weight ( 67.2±10.1 kg versus 72.0±10.1 kg , P<.05 ) , BMI ( 27.6±3.7kg/m(2 ) versus 31.3±4.6kg/m(2 ) , P<.001 ) , as well as lower arm and leg circumferences than the control patients . A significantly higher intake , in terms of macronutrients and energy consumption , was detected in the control group , as well as lower than recommended intake of calcium and vitamin D in both groups , which was more marked in patients with HF . Logistic regression found that the HF was associated with a lower BMI as well as lower intakes of protein , carbohydrates and calcium . CONCLUSIONS Adequate nutritional status and adequate intake of essential macro- and micronutrients seem to prevent osteoporotic HF Introduction Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures . A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects . Purpose and Methods Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have review ed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases , providing recommendations and guidelines for future studies in this field . Results and conclusions Robust mechanistic evidence is available from in vitro studies and in vivo animal studies , usually employing cholecalciferol , calcidiol or calcitriol in pharmacologic rather than physiologic doses . Although many cross-sectional and prospect i ve association studies in humans have shown that low 25-hydroxyvitamin D levels ( i.e. , < 50 nmol/L ) are consistently associated with chronic diseases , further strengthened by a dose-response relationship , several meta-analyses of clinical trials have shown contradictory results . Overall , large r and omized controlled trials with sufficient doses of vitamin D are missing , and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels  > 50 nmol/L , did not simultaneously assess multiple outcomes , and did not report overall safety ( e.g. , falls ) . Thus , no recommendations can be made to date for the use of vitamin D supplementation in general , parental compounds , or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases . Moreover , attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health can not be recommended based on current evidence , since safety has yet to be confirmed . Finally , the promising findings from mechanistic studies , large cohort studies , and small clinical trials obtained for autoimmune diseases ( including type 1 diabetes , multiple sclerosis , and systemic lupus erythematosus ) , cardiovascular disorders , and overall reduction in mortality require further confirmation Objective Multiple studies have shown clear evidence of vitamin D ’s anti-tumor effects on prostate cancer cells in laboratory experiments , but the evidence has not been consistent in humans . We sought to examine the association between vitamin D and prostate cancer risk in a cohort of older men . Methods We conducted a prospect i ve case-cohort study nested within the multicenter Osteoporotic Fractures in Men ( MrOS ) study .  Baseline serum 25-OH vitamin D  was measured in a r and omly selected sub-cohort of 1,433 men ≥65 years old without a history of prostate cancer and from all participants with an incident diagnosis of prostate cancer ( n = 297 ) . Cox proportional hazards models were used to evaluate the associations between quartiles of total 25-OH vitamin D and incident prostate cancer , as well as Gleason score . Results In comparison with the lowest quartile of 25-OH vitamin D , the hazard ratio for the highest quartile of 25-OH vitamin D was 1.22 ( CI 0.50–1.72 , p = 0.25 ) , no trend across quartiles ( p = 0.94 ) or association with Gleason score was observed . Adjustment for covariates did not alter the results . Conclusions In this prospect i ve cohort of older men , we found no association between serum 25-OH vitamin D levels and subsequent risk of prostate cancer Summary Strontium ranelate reduces the risk of fracture in post-menopausal osteoporotic women with prevalent fractures for whom quality of life is severely impaired . The SOTI study , which used the SF-36 ® question naire and disease-specific QUALIOST ® module , demonstrated that treatment with strontium ranelate improved osteoporotic women ’s quality of life compared with placebo . Introduction The Spinal Osteoporosis Therapeutic Intervention ( SOTI ) study demonstrated the effect of orally administered strontium ranelate versus placebo on the incidence of new vertebral fractures and compared impact on quality of life ( QoL ) . Methods QoL was assessed 6 monthly over 3 years using the QUALIOST ® and SF-36 ® question naires in post-menopausal osteoporotic women with prevalent fracture taking strontium ranelate or placebo  2 g/day . A total of 1,240 women were included ( strontium ranelate : n = 618 and placebo : n = 622 ) . Results The QUALIOST ® total score decreased in the strontium ranelate group , indicating preserved QoL compared with a deterioration in the placebo group ( P = 0.016 ) . Strontium ranelate patients had reduced QUALIOST ® emotional and physical dimension scores ( P = 0.019 and 0.032 , respectively , versus placebo ) , indicating beneficial effects on emotional and physical functioning . There was a trend towards better SF-36 ® scores in the strontium ranelate group , although there were no significant between-group differences . More strontium ranelate patients ( + 31 % ) were free from back pain over 3 years versus placebo ( P = 0.005 ) , with a significant effect from the first year of treatment ( P = 0.023 ) . ConclusionS trontium ranelate has beneficial effects on QoL  in women with post-menopausal osteoporosis compared with placebo The Women 's Health Initiative ( WHI ) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women , including cancer , cardiovascular disease , and osteoporotic fractures . The WHI was initiated in 1992 , with a planned completion date of 2007 . Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial ( CT ) that will include about 64,500 women or an observational study ( OS ) that will include about 100,000 women . The CT is design ed to allow r and omized controlled evaluation of three distinct interventions : a low-fat eating pattern , hypothesized to prevent breast cancer and colorectal cancer and , secondarily , coronary heart disease ; hormone replacement therapy , hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and , secondarily , to reduce the risk of hip and other fractures , with increased breast cancer risk as a possible adverse outcome ; and calcium and vitamin D supplementation , hypothesized to prevent hip fractures and , secondarily , other fractures and colorectal cancer . Overall benefit-versus-risk assessment is a central focus in each of the three CT components . Women are screened for participation in one or both of the components -- dietary modification ( DM ) or hormone replacement therapy (HRT)--of the CT , which will r and omize 48,000 and 27,500 women , respectively . Women who prove to be ineligible for , or who are unwilling to enroll in , these CT components are invited to enroll in the OS . At their 1-year anniversary of r and omization , CT women are invited to be further r and omized into the calcium and vitamin D ( CaD ) trial component , which is projected to include 45,000 women . The average follow-up for women in either CT or OS is approximately 9 years . Concerted efforts are made to enroll women of racial and ethnic minority groups , with a target of 20 % of overall enrollment in both the CT and OS . This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component . Some detail is provided on specific study design choices , including eligibility criteria , recruitment strategy , and sample size , with attention to the partial factorial design of the CT . Some aspects of the CT monitoring approach are also outlined . The scientific and logistic complexity of the WHI implies particular leadership and management challenges . The WHI organization and committee structure employed to respond to these challenges is also briefly described OBJECTIVES To compare event rates for osteoporotic fractures , cardiovascular events , and breast cancer in postmenopausal women with osteoporosis . DESIGN A prospect i ve , observational study of the placebo group in the double-blind , r and omized Multiple Outcomes of Raloxifene Evaluation trial . SETTING One hundred eighty clinical research centers in 25 countries . PARTICIPANTS Postmenopausal women ( n=2,565 , mean age=67 ) with osteoporosis were given calcium ( 500 mg/d ) and vitamin D ( 400 - 600 IU/d ) supplements . MEASUREMENTS The occurrence of at least one new fracture , cardiovascular event , or breast cancer diagnosis at 3 years was identified and adjudicated . RESULTS The occurrence of any fracture was the most common event in these women . In women without prevalent vertebral fractures ( n=1,627 ) , the event rates per 1,000 patient-years were 45.4 for any fracture , 15.2 for vertebral fracture , 4.7 for clinical vertebral fracture , 0.9 for hip fracture , 8.3 for any cardiovascular event , and 5.2 for all breast cancer . In women with prevalent vertebral fractures ( n=938 ) , the event rates per 1,000 patient-years were 117.4 for any new fracture , 77.1 for new vertebral fracture , 25.7 for clinical vertebral fracture , 5.8 for hip fracture , 15.1 for any cardiovascular event , and 2.6 for all breast cancer . The effect of prevalent fracture status on event rates was not dependent on whether women were older or younger than 65 , but women aged 65 and older had a 3.6 times greater occurrence of cardiovascular events than younger women , irrespective of prevalent fracture status . CONCLUSION These data on the relative incidence of clinical ly significant skeletal and extra-skeletal outcomes may be useful in choosing an agent for health maintenance for postmenopausal women with osteoporosis Abstract Objective To assess whether supplementation with calcium and cholecaliferol ( vitamin D3 ) reduces the risk of fracture in women with one or more risk factors for fracture of the hip . Design Pragmatic open r and omised controlled trial . Setting Practice nurse led clinics in primary care . Participants 3314 women aged 70 and over with one or more risk factors for hip fracture : any previous fracture , low body weight ( < 58 kg ) , smoker , family history of hip fracture , or fair or poor self reported health . Intervention Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls , or leaflet only ( control group ) . Main outcome measures Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment , falls , and quality of life ( measured with the SF-12 ) . Results 69 % of the women who completed the follow-up question naire at 24 months were still taking supplements ( 55 % with inclusion of r and omised participants known to be alive ) . After a median follow-up of 25 months ( range 18 to 42 months ) , clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures ( odds ratio for fracture in supplemented group 1.01 , 95 % confidence interval 0.71 to 1.43 ) . The odds ratio for hip fracture was 0.75 ( 0.31 to 1.78 ) . The odds of a woman having a fall at six and 12 months was 0.99 and 0.98 , respectively . Quality of life did not significantly differ between the groups . Conclusion We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture . Registration IS RCT N26118436 , controlled trials registry OBJECTIVES To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation . DESIGN A r and omised controlled trial of cluster design . SETTING AND SUBJECTS 223 Residential units ( mainly identical 30-bedded units ) , within 118 homes for elderly people throughout Britain , with 3,717 participating residents ( 76 % women , average age 85 years ) . The units provided mainly or entirely residential care ( 35 % of residents ) , nursing care ( 42 % ) or care for elderly mentally infirm ( EMI ) residents ( 23 % ) . METHODS Participants were r and omly allocated by residential unit ( cluster design ) to a treated group offered ergocalciferol 2.5 mg every 3 months ( equivalent to a daily dose of 1,100 IU ) , or to a control group .  Fractures were reported by staff and confirmed in hospital , and routinely collected data on reported falls were obtained . RESULTS After median follow-up of 10 months ( interquartile range 7 - 14 months ) , 64 ( 3.6 % ) of 1,762 vitamin D-treated residents and 51 ( 2.6 % ) of 1,955 controls had one or more non-vertebral fractures , and 24 ( 1.3 % ) and 20 ( 1.0 % ) , respectively , had a hip fracture . The proportion reporting at least one fall was 44 % in vitamin D-treated and 43 % in control residents . The differences between the vitamin D and control groups were not statistically significant . The incidence of all non-vertebral fractures in the care homes ( 3.2 % per year ) and of hip fractures ( 1.1 % per year ) was low , similar to rates in elderly people in sheltered accommodation , and the pre-treatment serum 25-hydroxy vitamin D concentration was high [ median 47 nmol/l , measured in a 1 % ( n = 18 ) sample ] . CONCLUSIONS We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures . A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites , bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a r and omized , double-blind , placebo-controlled trial . Bone mineral density ( BMD ) was measured by dual x-ray absorptiometry and bone structure by radiographs . Calcium biochemistry and bone turnover markers were measured in blood and urine . The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr . Baseline median calcium intake was 546 mg/day , and median serum 25OH vitamin D3 was 59 nmol/L. On placebo , loss of BMD at total hip was 2 % and femoral medulla expansion was 3 % over 4 yr . Calcium reduced bone loss , secondary hyperparathyroidism , and bone turnover . 25OH vitamin D3 was intermediate between placebo and calcium . Fracture rates and drop-out rates were similar among groups , and there were no serious adverse events with either supplement . A calcium supplement of 750 mg/day prevents loss of BMD , reduces femoral medullary expansion , secondary hyperparathyroidism , and high bone turnover . A supplement of 15 microg/day 25OH vitamin D3 is less effective , and because its effects are seen only at low calcium intakes , suggests that its beneficial effect is to reverse calcium insufficiency Incidence of a fracture , particularly in the hip joint , is high in elderly women with Parkinson 's disease ( PD ) , and this is due to the immobilization-induced bone resorption and vitamin D deficiency with reduced bone mineral density ( BMD ) . The objective of this study was to address the possibility that treatment with alendronate and vitamin D2 may reduce the incidence of hip fractures in elderly women with PD . PD patients were r and omly assigned to daily treatment with 5 mg alendronate ( n = 144 ) or a placebo combined with 1,000 IU of vitamin D2 ( n = 144 ) and followed for 2 years . Incidence of hip fractures in the two patient groups during the 2-year follow-up period was studied . At baseline , both groups of patients had low BMD with high levels of serum-ionized calcium and urinary deoxypyridinoline ( D-Pyr ) . Hip fractures occurred in 14 patients in the placebo group and 4 in the alendronate group . The relative risk for hip fractures in the alendronate group as compared with the placebo group was 0.29 ( 95 % CI , 0.10 - 0.85 ) . The number of hip fracture per 1,000 patient-years was 14 and 49 for the alendronate and placebo groups , respectively . In the alendronate group , serum calcium and urinary D-Pyr levels decreased significantly during the follow-up period , while the levels in the placebo group were increased . BMD increased by 3.1 % in the alendronate group and decreased by 2.8 % in the placebo group ( P < 0.01 ) . Treatment with alendronate and vitamin D2 increases BMD in elderly women with PD and leads to the prevention of hip fractures OBJECTIVES To assess the safety and efficacy of teriparatide in patients aged 75 and older and compare these findings with those of women younger than 75 using data from the Fracture Prevention Trial ( FPT ) . DESIGN The FPT was a r and omized , multicenter , double-blind , placebo-controlled study . SETTING The FPT multicenter international study . PARTICIPANTS Postmenopausal women aged 42 to 86 were r and omized to placebo ( N=544 ) or teriparatide 20 mug ( N=541 ) by daily self-injection for a median of 19 months . Patients received daily oral supplements of 1,000 mg calcium and 400 to 1,200 IU vitamin D. For this analysis , subgroups were defined according to patient age younger than 75 ( N=841 ) and 75 and older ( N=244 ) . MEASUREMENTS The effects of teriparatide on bone mineral density ( BMD ) of the lumbar spine and femoral neck ; the incidence of new vertebral and new nonvertebral fragility fractures ; bone turnover markers , including bone-specific alkaline phosphatase ; and urinary deoxypyridinoline corrected for creatinine clearance , as well as the safety of teriparatide , were investigated . RESULTS There were no significant treatment-by-age interactions for the bone turnover markers , femoral neck BMD , vertebral fractures , nonvertebral fragility fractures , height loss , hyperuricemia , or hypercalcemia . A significant treatment-by-age interaction for lumbar spine BMD ( P=.08 ) was due to an increase in BMD observed in the placebo group aged 75 and older . There were no treatment-by-age interactions for important treatment-emergent adverse events ( TEAEs ) , including back pain , nausea , leg cramps , and dizziness . The most important TEAEs in women aged 80 and older ( 23 patients from the placebo group and 25 patients from the teriparatide group ) were also review ed ; no unexpected TEAEs were found in the patients treated with teriparatide . These results indicate that the clinical effects of teriparatide were consistent in the older and younger women . CONCLUSION Age does not affect the safety and efficacy of teriparatide in postmenopausal women with osteoporosis UNLABELLED We studied whether oophorectomy performed after menopause is associated with an increased risk of hip or vertebral fractures in 6295 Study of Osteoporotic Fractures participants . There was no association between postmenopausal oophorectomy and the risk of hip or vertebral fractures . INTRODUCTION Bilateral oophorectomy after natural menopause has been associated with an increased risk of osteoporotic fractures , potentially because of a decline in serum estradiol and testosterone levels after the oophorectomy . We prospect ively tested this hypothesis in the Study of Osteoporotic Fractures ( SOF ) . MATERIAL S AND METHODS We studied 6295 white women 65 years of age participating in the SOF who were not taking estrogen therapy at baseline . Hip fracture analyses included 708 hip fractures ; vertebral fracture analyses included 267 incident vertebral fractures . Baseline serum estradiol and free testosterone values were available in a small subset of participants . RESULTS AND CONCLUSION There were no significant differences in age , weight , or BMD between the women who underwent postmenopausal oophorectomy ( n = 583 ) and those who did not ( n = 5712 ) . Free testosterone levels were significantly lower among women who had a postmenopausal oophorectomy . A history of postmenopausal oophorectomy was not associated with an increased risk of hip ( hazard ratio [ HR ] = 1.1 ; 95 % CI = 0.9 - 1.5 ) or vertebral fracture ( HR = 0.7 ; 95 % CI = 0.5 - 1.2 ) . The relationship between oophorectomy and hip fracture was not altered by adding serum estradiol level ( HR = 1.3 ; 95 % CI = 0.5 - 3.2 ) or serum free testosterone level ( HR = 1.7 ; 95 % CI = 0.8 - 3.7 ) to the model . In summary , postmenopausal oophorectomy was not associated with an increased risk of hip or vertebral fracture in this cohort . These results are in contrast to previous findings , suggesting that the relationship between postmenopausal oophorectomy and fractures is not fully eluci date d and that incidental oophorectomy after menopause should still be considered carefully in each potential patient UNLABELLED A low-impact fracture in a postmenopausal woman should prompt investigations for osteoporosis followed , if needed , by appropriate treatment . OBJECTIVES To evaluate the impact of information alerting general practitioners to the need for osteoporosis treatment in postmenopausal women with a recent history of peripheral fracture . METHODS We conducted a prospect i ve 7-month follow-up study of 78 postmenopausal women , with a mean age of 81.5 years , admitted to the emergency department for peripheral fractures . Three months after the fracture , we sent a letter to the general practitioner of each patient emphasizing the probable contribution of osteoporosis to the fracture and the need for osteoporosis treatment . Six months after the fracture , we interviewed the patients by telephone , and one month later we mailed a question naire to those physicians who had not followed the treatment recommendation . RESULTS At emergency room admission , 9 patients were receiving treatment for osteoporosis  (  hormone replacement therapy in one patient and calcium and vitamin D supplementation in eight patients ) . Admission to a ward was required in 66 ( 85 % ) patients . No treatment for osteoporosis was given at discharge . Six months after discharge , seven patients reported recent initiation of calcium and vitamin D supplementation , and none reported other osteoporosis treatments . The response rate to the physician question naire mailed 7 months after discharge was 54 % ( n=28 ) ; responses showed treatment of 11 additional patients , by calcium and vitamin D supplementation in six cases and by bisphosphonates with or without calcium and vitamin D supplementation in five cases . Treatment initiation rates were similar in patients younger and older than 80 years . CONCLUSIONS Despite information of general practitioners about the need for osteoporosis treatment , such treatment was initiated in only 30.5 % of patients . General practitioners may be reluctant to initiate osteoporosis treatment in patients who are very old or have multiple comorbidities BACKGROUND Polyunsaturated fatty acids ( PUFAs ) may play a role in fracture , but studies have been largely confined to estimates of dietary intake . OBJECTIVE We aim ed to examine associations between fatty acids measured in late life and fish-oil consumption in early life , midlife , and late life with  osteoporotic fracture risk .  DESIGN Osteoporotic fractures were determined from medical records over 5 - 9 y of follow-up in men and women aged 66 - 96 y. Data were analyzed from 1438 participants including 898 participants who were r and omly selected from the Age , Gene/Environment Susceptibility Study , which is an observational study , and 540 participants with incident fracture . Plasma phospholipid fatty acids were assessed by using gas chromatography .  Fish-oil consumption was assessed by using vali date d question naires as never ( referent ) , less than daily , or daily . HRs and 95 % CIs adjusted for age , education , height , weight , diabetes , physical activity , and medications were estimated by using Cox regression . RESULTS In men , the highest tertile of PUFAs , n-3 ( ω-3 ) , and eicosapentaenoic acid were associated with decreased fracture risk [ HRs ( 95 % CIs ) : 0.60 ( 95 % CI : 0.41 , 0.89 ) , 0.66 ( 0.45 , 0.95 ) , and 0.59 ( 0.41 , 0.86 ) , respectively ] . In women , PUFAs tended to be inversely associated with fracture risk ( P-trend = 0.06 ) , but tertiles 2 and 3 were not independently associated with risk . Tertile 2 of n-6 and arachidonic acid was associated with fracture risk in women [ HRs ( 95 % CIs ) : 1.43 ( 1.10 , 1.85 ) and 1.42 ( 1.09 , 1.85 ) , respectively ] . Daily  fish-oil consumption in late life was associated with lower fracture risk in men ( HR : 0.64 ; 95 % CI : 0.45 , 0.91 ) . Daily fish-oil consumption in midlife was associated with lower fracture risk in women ( HR : 0.75 ; 95 % CI : 0.58 , 0.98 ) . CONCLUSIONS Greater PUFA concentrations may be associated with lower osteoporotic fracture risk in older adults , particularly in men . Critical time periods for n-3 fatty acid consumption may differ by sex UNLABELLED In this large prospect i ve cohort study of elderly women , the relationships between prior wrist fracture and incident hip and radiographic vertebral fractures were significantly attenuated when adjusted for BMD . This study suggests that BMD thresholds for drug therapy to prevent osteoporotic fracture should be only modestly adjusted in those with prior wrist fracture compared with those without prior wrist fracture . Validation of such an approach would require intervention trials in patients with prior wrist fracture . INTRODUCTION Prior wrist fracture has been identified as a risk factor for incident hip and vertebral fractures and proposed as a criterion for determining who should be offered drug therapy to prevent osteoporotic fracture , even if their hip BMD T score is > -2.5 . Previously published studies of the relationships between prior wrist fracture and incident hip and vertebral fractures did not adjust for BMD . MATERIAL S AND METHODS We ascertained prior history of wrist fracture since age 50 , measured calcaneal and hip BMD  , and performed lateral spine films in a cohort of 9704 elderly community-dwelling women , and then followed them prospect ively for incident vertebral and hip fractures . Incident vertebral fractures were defined by morphometry using lateral  spine radiography at the first examination and an average of 3.7 years later . Incident hip fractures were confirmed with radiographic reports over a mean follow-up period of 10.1 years . RESULTS Prior wrist fracture was associated with an age-adjusted 72 % increased odds of incident radiographic vertebral fracture ( odds ratio [ OR ] , 1.72 ; 95 % CI , 1.31 - 2.25 ) . After adjustment for calcaneal BMD , the association of prior wrist fracture with incident radiographic vertebral fracture was attenuated ( OR , 1.39 ; 95 % CI , 1.05 - 1.83 ) . Prior wrist fracture was also associated with an age-adjusted 43 % excess rate of incident hip fracture ( hazards ratio [ HR ] , 1.43 ; 95 % CI , 1.17 - 1.74 ) . After adjustment for hip BMD , the association of prior wrist fracture with rate of incident hip fracture was no longer statistically significant ( HR , 1.12 ; 95 % CI , 0.92 - 1.38 ) . CONCLUSION In elderly women , prior wrist fracture is a risk factor for radiographic vertebral fracture independent of BMD . The association between prior wrist fracture and incident hip fracture is largely explained by hip BMD . Modest adjustment of BMD drug treatment thresholds for prevention of osteoporotic fractures in those with prior wrist fracture compared with those without prior wrist fracture may be reasonable , but validation of such an approach would require intervention trials in patients with prior wrist fracture BACKGROUND Adults with low concentrations of 25-hydroxyvitamin D ( 25[OH]D ) in blood have an increased risk of falls and fractures , but r and omised trials of vitamin D supplementation have had inconsistent results . We aim ed to assess the effect of high-dose vitamin D supplementation on fractures and falls . METHODS The Vitamin D Assessment ( ViDA ) Study was a r and omised , double-blind , placebo-controlled trial of healthy volunteers aged 50 - 84 years conducted at one centre in Auckl and , New Zeal and . Participants were r and omly assigned to receive either an initial oral dose of 200 000 IU ( 5·0 mg ) colecalciferol ( vitamin D3 ) followed by monthly 100 000 IU ( 2·5 mg ) colecalciferol or equivalent placebo dosing . The prespecified primary outcome was cardiovascular disease and secondary outcomes were respiratory illness and fractures . Here , we report secondary outcome data for fractures and post-hoc outcome data for falls . Cox proportional hazards models were used to estimate hazard ratios ( HRs ) for time to first fracture or time to first fall in individuals allocated vitamin D compared with placebo . The analysis of fractures included all participants who gave consent and was by intention-to-treat ; the analysis of falls included all individuals who returned one or more question naires . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12611000402943 . FINDINGS Between April 5 , 2011 , and Nov 6 , 2012 , 5110 participants were recruited and r and omly assigned either colecalciferol ( n=2558 ) or placebo ( n=2552 ) . Two participants allocated placebo withdrew consent after r and omisation ; thus , a total of 5108 individuals were included in the analysis of fractures . The mean age of participants was 65·9 years ( SD 8·3 ) and 2971 ( 58 % ) were men . The mean concentration of 25(OH)D in blood was 63 nmol/L ( SD 24 ) at baseline , with 1534 ( 30 % ) having 25(OH)D concentrations lower than 50 nmol/L. Follow-up was until July 31 , 2015 , with a mean treatment duration of 3·4 years ( SD 0·4 , range 2·5 - 4·2 ) . During follow-up , 2638 participants reported having a fall , 1312 ( 52 % ) of 2539 in the vitamin D group compared with 1326 ( 53 % ) of 2517 in the placebo group . The HR for falls-adjusted for age , sex , ethnic origin , history of recent fall , physical activity , and baseline 25(OH)D-was 0·99 ( 95 % CI 0·92 - 1·07 ; p=0·82 ) for vitamin D compared with placebo . Non-vertebral fractures were reported in 292 individuals , 156 ( 6 % ) of 2558 in the vitamin D group and 136 ( 5 % ) of 2550 in the placebo group . The adjusted HR for fractures was 1·19 ( 95 % CI 0·94 - 1·50 ; p=0·15 ) for vitamin D compared with placebo . 123 ( 2 % ) people died  during the trial , 65 assigned vitamin D and 58 allocated placebo ; the difference between treatment groups was not significant . INTERPRETATION High-dose bolus vitamin D supplementation of 100 000 IU colecalciferol monthly over 2·5 - 4·2 years did not prevent falls or fractures in this healthy , ambulatory , adult population . Further research is needed to ascertain the effects of daily vitamin D dosing , with or without calcium . FUNDING Health Research Council of New Zeal and and Accident Compensation Corporation of New Zeal and The prevention of increased bone remodeling in postmenopausal women at low 10-y risk of osteoporotic fractures essentially relies on reinforcement of environmental factors known to positively influence bone health , among which nutrition plays an important role . In institutionalized women in their mid-eighties , we previously found that consumption of fortified soft plain cheese increased vitamin D , calcium , and protein intakes , reduced bone resorption biochemical markers , particularly the serum bone specific acid phosphatase tartrate resistant acid phosphatase , isoform 5b ( TRAP 5b ) that reflects osteoclast activity , and stimulated the serum bone anabolic factor insulin-like growth factor-I ( IGF-I ) . Whether these effects occur in much younger women was tested in a prospect i ve control study . Seventy-one healthy postmenopausal women aged 56.6 ± 3.9 y ( mean ± SD ) with low spontaneous supply of both Ca and vitamin D were r and omized to consume daily ( treated , n = 36 ) or not ( controls , n = 35 ) two servings ( 2 × 100 g ) of skimmed-milk , soft plain cheese for 6 wk . The vitamin D and Ca-fortified dairy product provided daily : 661 kJ , 2.5 μg vitamin D , 400 mg calcium , and 13.8 g protein . At the end of the intervention , the decrease in TRAP 5b and the increase in IGF-I were greater in the treated than in the control group ( P < 0.02 ) . The changes in serum carboxy terminal crosslinked telopeptide of type I collagen did not differ significantly between the two groups . In conclusion , like in elderly women , consumption by healthy postmenopausal women of a vitamin D and calcium-fortified dairy product that also increases the protein intake , reduces the serum concentration of the bone resorption biomarker TRAP 5b . This response , combined with the increase in serum IGF-I , is compatible with a nutrition-induced reduction in postmenopausal bone loss rate The postmenopausal hormone therapy ( PHT ) component of the Women ’s Health Initiative ( WHI ) is composed of two r and omized , placebo-controlled , double-blind trials in postmenopausal women aged 50 to 79 years at initial screening , testing the effects of estrogen alone ( E-alone ) and estrogen plus progestin ( E P ) on coronary heart disease ( CHD ) as the primary outcome , hip and other fractures and colorectal cancer as secondary outcomes , and pulmonary embolism , breast and endometrial cancers as potential risks . The design and rationale of the PHT trials , including general eligibility and exclusion criteria and considerations regarding sample size and statistical power , have been described previously ( 1 ) . Postmenopausal hormones have been initiated in menopausal women for the treatment of vasomotor symptoms , mood disturbances , vaginal dryness , and prevention of rapid bone loss for several decades . Despite a paucity of data on effects of initiating hormone use in older women , postmenopausal hormones have also been promoted for the prevention of CHD , osteoporotic fractures , and other diseases that occur years after menopause ( 2 ) . It is generally recommended ( 2 ) that women with a uterus be prescribed a combination of estrogen and progestin to prevent Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people .  Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures , as proved by Decalyos I. Decalyos II is a 2-year , multicenter , r and omized , double-masked , placebo-controlled confirmatory study . The intention-to-treat population consisted of 583 ambulatory institutionalized women ( mean age 85.2 years , SD = 7.1 ) r and omized to the  calcium – vitamin D3  fixed combination group ( n= 199 ) ; the calcium plus vitamin D3 separate combination group ( n= 190 ) and the placebo group ( n= 194 ) . Fixed and separate combination groups received the same daily amount of calcium ( 1200 mg ) and vitamin D3 ( 800 IU ) , which had similar pharmacodynamic effects . Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent , with levels returning within the normal range after 6 months . In a subgroup of 114 patients  , femoral neck bone mineral density ( BMD ) decreased in the placebo group ( mean = –2.36 % per year , SD = 4.92 ) , while remaining unchanged in women treated with calcium-vitamin D3 ( mean = 0.29 % per year , SD = 8.63 ) . The difference between the two groups was 2.65 % ( 95 % CI = –0.44 , 5.75 % ) with a trend in favor of the active treatment group . No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis . The relative risk ( RR ) of HF in the placebo group compared with the active treatment group was 1.69 ( 95 % CI = 0.96 , 3.0 ) , which is similar to that found in Decalyos I ( RR = 1.7 ; 95 % CI = 1.0 , 2.8 ) . Thus , these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture  in elderly institutionalized women Of the technologies available , dual-energy X-ray absorptiometry of the hip or femoral neck ( DXA-FN ) is the best predictor of hip fractures . Diagnostic approaches utilizing measures of peripheral sites with office-based technology , such as calcaneal quantitative ultrasound ( QUS ) , may reduce costs although clinical and economic outcomes have not been evaluated . The objective was to compare three approaches for diagnosing osteoporosis in older women . The design was a decision-analytic model using diagnostic measures and clinical and economic outcomes from the Study of Osteoporotic Fractures , a prospect i ve cohort of older white women that measured BMD and QUS and assessed fracture outcomes . The setting and patients were a hypothetical cohort of older white women presenting for diagnosis of osteoporosis . For the diagnostic and treatment alternatives , three diagnostic approaches — DXA-FN alone , QUS alone and a sequential approach ( first QUS , then DXA-FN for those with low values for QUS)—were compared to no diagnosis . The outcome measures were the number of women identified for treatment , number of hip fractures prevented following diagnosis and subsequent treatment , number of women needed to treat to prevent one hip fracture and total direct medical costs . The sequential approach identified fewer women to treat , prevented more hip fractures and incurred lower total costs than using DXA alone . Diagnosis with QUS alone identified more women to treat and incurred higher total costs than DXA alone under most conditions . Compared to other approaches for diagnosing osteoporosis , sequential use of QUS followed by DXA result ed in fewer women treated and lower total costs Abstract Osteoporotic intertrochanteric fractures result in serious health problems and decrease health-related quality of life ( HRQoL ) . Faster time-to-union is important for early return to daily activities and reduction of complications . Teriparatide has been shown to accelerate fracture healing , but the literature is sparse on this topic . The aim of this study is to assess whether teriparatide accelerates fracture healing .  Between 2008 and 2014 , patients with osteoporotic intertrochanteric fractures who underwent surgical interventions were enrolled in this retrospective cohort study . Group 1 included patients who were not on any osteoporosis medication prior to fracture and who postoperatively received only calcium and vitamin D ; patients in Group 2 were not on any osteoporosis medication prior to fracture  , and received teriparatide and calcium and vitamin D postoperatively .  Patients in Group 3 were those who were on alendronate prior to fracture and postfracture received teriparatide as well as calcium and vitamin D.  Demographics , time-to-union , HRQoL ( short-form health survey [SF]-12 physical component summary [ PCS ] and SF-12 mental component summary [ MCS ] ) , morbidities , mortalities , and radiographic and functional outcomes between groups were compared . A total of 189 patients were enrolled in this study . There were 83 patients in Group 1 , 47 patients in Group 2 , and 59 patients in Group 3 . A significantly shorter time-to-union was found in the teriparatide-treated groups ( mean , 13.6 , 12.3 , and 10.6 weeks , respectively [ P = 0.002 ] ) . With regard to SF-12 PCS , the scores were significantly better in teriparatide-treated groups at 3 months ( mean , 19 , 28 , and 29 , respectively [ P = 0.002 ] ) and 6 months ( mean , 28 , 37 , and 38 , respectively [ P = 0.008 ] ) . Similar inter-group differences were noted when comparing the pain scores , the ability to get around the house , the ability to get out of the house , and the ability to go shopping at 3 and 6 months . Complications and mortality were also markedly reduced in the teriparatide-treated groups . Postoperative use of teriparatide for 6 months appears to be an effective adjunct therapy in the treatment of patients with osteoporotic intertrochanteric fractures . However , because of the limited power of the study , a prospect i ve , r and omized , large-scale cohort study is still required for determining the efficacy of teriparatide BACKGROUND Vitamin D deficiency is common in older people and may increase risk of falls and fracture .  Hospital in patients are at particular risk of falling . Previous studies suggest that vitamin D improves neuromuscular function and reduces falls . OBJECTIVE To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are in patients . DESIGN R and omised , double-blind , controlled study . PARTICIPANTS two hundred and five acute admissions > 65 years to a geriatric medical unit . METHODS Patients were r and omised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg , until discharge or death . RESULTS Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days ( IQR 14.75 - 71.00 ) . In a pre-selected sub-group ( 54/205 participants ) , median admission vitamin D level = 22.00 nmol/l ( IQR 15.00 - 30.50 ) . This did not significantly increase in the treatment versus control group . Median study drug adherence = 88 % , with no significant difference between study groups ( Mann-Whitney : P = 0.711 ) . Although there were fewer fallers in the vitamin D cohort , this did not reach statistical significance ( vitamin D : calcium = 36:45 fallers ; RR 0.82 ( CI 0.59 - 1.16 ) . Neither the mean number of falls  ( vitamin D : calcium = 1.040:1.155 ; Mann-Whitney P = 0.435 ) or time to first fall ( Log-rank test P = 0.377 ) differed between groups . CONCLUSIONS In a population of geriatric hospital in patients , vitamin D did not reduce the number of fallers . Routine supplementation can not be recommended to reduce falls in this group Osteoporotic studies conducted exclusively in men have been limited by the discrepancies in defining densitometric osteoporosis and , also , because osteoporosis has traditionally been associated only with women . The aims of this study were to describe the prevalence of  low bone mineral density ( BMD ) and osteoporotic fractures  as well as the rate of bone loss . The analysis of some risk factors for accelerated bone loss was also evaluated . Men aged 50 years and over , r and omly selected from the Oviedo municipal register ( n=308 ) , completed a question naire regarding risk factors related to osteoporosis ; they underwent two lateral radiographs of the dorsal and lumbar spine and a dual X-ray absorptiometry ( DXA ) study at the lumbar spine and hip . In the 4th year of the follow-up period , participants were invited to undergo repeats of the same tests that had been carried out in the initial study . The prevalence of densitometric osteoporosis  in men older than 50 years , st and ardized by age , was 8.1 % with regard to at least one of the four studied bone areas , with a slight increase with age . The prevalence of osteoporotic fracture , st and ardized by age , was 24.4 % , with a marked increase with age . Osteoporotic prevalent fracture was independently associated only with the rate of change in lumbar spine BMD . From all the osteoporotic risk factors analyzed , only low milk consumption and regular smoking were independently associated with loss of bone mass . In summary , prevalent osteoporotic fracture was independently associated with the rate of change in the lumbar spine BMD but not in the other segments studied . Avoiding smoking and ensuring an adequate milk intake might prevent the loss of bone mass in men Thiazide diuretic agents lower the urinary excretion of calcium . Their use has been associated with increased bone density , but their role in preventing hip fracture has not been established . We prospect ively studied the effect of thiazide diuretic agents on the incidence of hip fracture among 9518 men and women 65 years of age or older residing in three communities . At base line , 24 to 30 percent of the subjects were  thiazide users . In the subsequent four years , 242 subjects had hip fractures . The incidence rates of hip fracture were lower among thiazide users than nonusers in each community ; the Mantel-Haenszel relative risk of hip fracture , adjusted for community and age , was 0.63 ( 95 percent confidence interval , 0.46 to 0.86 ) . The protective effect of the use of thiazides was independent of sex , age , impaired mobility , body-mass index , and current and former smoking status ; the multivariate adjusted relative risk of hip fracture was 0.68 ( 95 percent confidence interval , 0.49 to 0.94 ) . Furthermore , the protective effect was specific to thiazide diuretic agents , since there was no association between the use of antihypertensive medications other than thiazides and the risk of hip fracture . These prospect i ve data suggest that in older men and women the use of thiazide diuretic agents is associated with a reduction of approximately one third in the risk of hip fracture Risedronate decreases osteoporotic fracture incidence ; however , its effects remain unclear in elderly osteoporotic patients . Vitamin K mediates carboxylation of osteocalcin ( OC ) , and high undercarboxylated osteocalcin ( ucOC ) levels indicate vitamin K deficiency and increased osteoporotic fracture risk . We aim ed to evaluate the effects of risedronate alone or combined with vitamin K2 on serum ucOC , OC , and incidence of vertebral fractures in elderly osteoporotic patients . A total of 101 women with postmenopausal osteoporosis aged > 60 years were r and omly stratified into two groups — R group ( n = 51 ) , treated with risedronate alone ; and R + K group ( n = 50 ) , treated with risedronate and vitamin K2 .  Serum ucOC , OC and incidence of vertebral fractures were evaluated before treatment and at 6 and 12 months post-treatment . Decreased ucOC rates at 6 and 12 months were not significant between groups . However , at 6 and 12 months , decreased OC rates in the R group ( p < 0.01 and 0.05 , respectively ) were significantly higher than in the R + K group , and ucOC/OC change rates in the R group ( p < 0.05 and 0.001 , respectively ) were significantly lower than in the R + K group . Vertebral fracture incidence was not significantly different between the groups at 6 and 12 months . ucOC levels in patients with incident vertebral fractures were significantly higher than in patients without incident vertebral fractures in the R group at 6 months ( p < 0.05 ) . Although no significant difference was observed for ucOC decrease rate and incidence of vertebral fractures between treatments , ucOC levels in patients with incident vertebral fractures were significantly greater than in patients without when using risedronate alone CONTEXT Stroke increases the risk of subsequent hip fracture by 2 to 4 times . Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly men and women . Treatment with folate and mecobalamin ( vitamin B12 ) may improve hyperhomocysteinemia . OBJECTIVE To investigate whether treatment with folate and vitamin B12 reduces the incidence of hip fractures in patients with hemiplegia following stroke . DESIGN , SETTING , AND PATIENTS A double-blind , r and omized controlled study of 628 consecutive patients aged 65 years or older with residual hemiplegia at least 1 year following first ischemic stroke , who were recruited from a single Japanese hospital from April 1 , 2000 , to May 31 , 2001 . Patients were assigned to daily oral treatment with 5 mg of folate and 1500 microg of mecobalamin , or double placebo ; 559 completed the 2-year follow-up . MAIN OUTCOME MEASURE Incidence of hip fractures in the 2 patient groups during the 2-year follow-up . RESULTS At baseline , patients in both groups had high levels of plasma homocysteine and low levels of serum cobalamin and serum folate . After 2 years , plasma homocysteine levels decreased by 38 % in the treatment group and increased by 31 % in the placebo group ( P<.001 ) . The number of hip fractures per 1000 patient-years was 10 and 43 for the treatment and placebo groups , respectively ( P<.001 ) . The adjusted relative risk , absolute risk reduction , and the number needed to treat for hip fractures in the treatment vs placebo groups were 0.20 ( 95 % confidence interval [ CI ] , 0.08 - 0.50 ) , 7.1 % ( 95 % CI , 3.6%-10.8 % ) , and 14 ( 95 % CI , 9 - 28 ) , respectively . No significant adverse effects were reported . CONCLUSION In this Japanese population with a high baseline fracture risk , combined treatment with folate and vitamin B12 is safe and effective in reducing the risk of a hip fracture in elderly patients following stroke Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) concludes that the evidence is insufficient to recommend for or against the use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . This is a grade I recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found poor evidence to determine whether supplementation with these vitamins reduces the risk for cardiovascular disease or cancer . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) The available evidence from r and omized trials is either inadequate or conflicting , and the influence of confounding variables on observed outcomes in observational studies can not be determined . As a result , the USPSTF could not determine the balance of benefits and harms of routine use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . The USPSTF recommends against the use of beta-carotene supplements , either alone or in combination , for the prevention of cancer or cardiovascular disease . This is a grade D recommendation . The USPSTF found good evidence that -carotene supplementation provides no benefit in the prevention of cancer or cardiovascular disease in middle-aged and older adults . In two trials restricted to heavy smokers , -carotene supplementation was associated with higher incidence of lung cancer and higher all-cause mortality . The USPSTF concludes that -carotene supplements are unlikely to provide important benefits and might cause harm in some groups . Clinical Considerations The USPSTF did not review evidence regarding vitamin supplementation for patients with known or potential nutritional deficiencies , including pregnant and lactating women , children , elderly persons , and people with chronic illnesses .  Dietary supplements may be appropriate for people whose diet does not provide the recommended dietary intake of specific vitamins . Individuals may wish to consult a health care provider to discuss whether dietary supplements are appropriate . With the exception of vitamins for which there is compelling evidence of net harm ( for example , beta-carotene supplementation in smokers ) , there is little reason to discourage people from taking vitamin supplements . Patients should be reminded that taking vitamins does not replace the need to eat a healthy diet . All patients should receive information about the benefits of a diet high in fruits and vegetables , as well as information on other foods and nutrients that should be emphasized or avoided in their diet ( see the 2002 USPSTF recommendations on counseling to promote a healthy diet [ 1 ] ) . Patients who choose to take vitamins  should be encouraged to adhere to the dosages recommended in the Dietary Reference Intakes of the Institute of Medicine . Some vitamins , such as A and D , may be harmful in higher doses ; therefore , doses greatly exceeding the Recommended Dietary Allowance or Adequate Intake should be taken with care while considering whether potential harms outweigh potential benefits . Vitamins and minerals sold in the United States are classified as dietary supplements , and there is a degree of quality control over content if they have a U.S. Pharmacopeia seal ( 2 ) . Nevertheless , imprecision in the content and concentration of ingredients could pose a theoretical risk not reflected in clinical trials using calibrated compounds . The adverse effects of beta-carotene on smokers have been observed primarily in those taking large supplemental doses . There is no evidence to suggest that beta-carotene is harmful to smokers at levels occurring naturally in foods . The USPSTF did not review evidence supporting folic acid supplementation among pregnant women to reduce neural tube defects . In 1996 , the USPSTF recommended folic acid for all women who are planning , or capable of , pregnancy ( see the 1996 USPSTF chapter on screening for neural tube defects [ 3 ] ) . Clinicians and patients should discuss the possible need for vitamin supplementation when taking certain medications ( for example , folic acid supplementation for patients taking methotrexate ) . Scientific Evidence The USPSTF review s ( 4 - 6 ) focused on the quality of the evidence regarding the effect of routine supplementation with certain vitamins on primary prevention of cancer and cardiovascular disease . These review s were undertaken because of the growing epidemiologic evidence that dietary factors may play a role in the etiology of these diseases ( 7 - 9 ) . The review s focused on prospect i ve trials of vitamin supplementation and observational studies of associations between the use of specific supplements and the risk for cancer or cardiovascular disease . The value of vitamins naturally occurring in food , the use of vitamin supplements for the prevention of other conditions ( for example , neural tube defects ) , and the use of vitamin supplements for the secondary prevention of complications in patients with existing disease were outside the scope of these review s. Vitamin A No prospect i ve trials have examined the effect of vitamin A supplements alone on the risk for cancer . Observational studies provide no evidence that such supplements prevent cancer in men . In women , observational studies have reported a statistically significant inverse association between use of vitamin A supplements and risk for colon and breast cancer ( 10 , 11 ) . Despite efforts to adjust for confounding variables , the observational , nonr and om design of these studies makes it difficult to assess the extent to which the reduced cancer risk is attributable to vitamin A or to other characteristics of women who take vitamin A supplements .  No evidence from prospect i ve trials is available regarding the benefits of vitamin A alone in preventing cardiovascular disease . One good- quality cohort study found no effect of vitamin A supplementation in reducing cardiovascular disease mortality ( 12 ) . Vitamin C No primary prevention trial of the effect of vitamin C supplementation alone on cancer or cardiovascular disease has been reported . Observational studies have generally shown no statistically significant associations between use of vitamin C supplements and risk for cancer of the breast , prostate , colon , or lung ( 12 - 14 ) . The observational cohort studies examining the effects of vitamin C on cardiovascular disease have produced inconsistent results ( 12 , 15 , 16 ) . Vitamin E Only a few trials have examined the effects of vitamin E on the primary prevention of cancer or cardiovascular disease . A r and omized , controlled trial ( RCT ) involving Finnish male smokers found that vitamin E supplementation is not protective against lung cancer but may have a beneficial impact on prostate cancer ( 14 ) . Because prostate cancer was not a primary end point of the trial and the trial had other limitations , further evidence is needed to confirm this finding . Observational studies have shown no statistically significant association between use of vitamin E supplements and risk for prostate , lung , or breast cancer ( 5 ) . One study suggested that vitamin E protects against colon cancer , but the influence of confounding variables can not be fully excluded ( 17 ) . Among primary prevention trials , two good- quality trials ( 14 , 18 ) and one fair- quality trial ( 19 ) found no statistically significant benefit of vitamin E supplementation in preventing cardiovascular disease ( 20 ) . Only one of seven trials of vitamin E supplementation for secondary prevention demonstrated a statistically significant reduction in cardiac events ( 4 ) . Some prospect i ve cohort studies have suggested a significant benefit , but the results are mixed and the influence of confounding variables can not be excluded ( 4 ) . -Carotene A consistent body of evidence from clinical trials suggests that beta-carotene supplementation does not decrease the risk for lung , prostate , colon , breast , or nonmelanoma skin cancer ( 14 , 21 - 25 ) . -Carotene supplements were associated with an increased risk for lung cancer among smokers , especially heavy smokers , in two RCTs ( 14 , 25 ) . Results from four RCTs demonstrated no reduced risk for cardiovascular events or death after beta-carotene supplementation ( 14 , 21 , 22 , 26 - 28 ) . Antioxidant Vitamin Combinations Studies of the effects of antioxidant vitamin combinations to prevent cancer have yielded mixed results . A recent RCT reported no statistically significant effect of daily supplementation with a combination of antioxidants : vitamin E , vitamin C , and beta-carotene ( 29 ) . Some studies have suggested an adverse effect of antioxidant combinations on cancer , but the results may have been confounded by the inclusion of beta-carotene ( 5 ) . Some observational studies of antioxidant vitamin combinations have suggested a benefit in preventing cardiovascular disease ( 13 , 30 , 31 ) , but other studies , including well- design ed RCTs , have shown no benefit ( 29 , 32 , 33 ) . One secondary prevention trial showed an increase in all-cause mortality among women taking antioxidant supplements  ( 34 ) . Multiple Vitamin Combinations The incremental benefit of taking supplemental doses of folic acid and B vitamins has been examined by comparing the outcomes of observational studies while controlling for the total intake of antioxidant vitamin supplements ( 35 ) . In these analyses , folic acid supplementation was associated with significantly decreased risk for colon cancer , but the protective effect requires confirmation in prospect i ve trials . There is conflicting evidence regarding the use of multivitamins and the risk for cardiovascular disease . Among cohort studies , one good- quality study reported a statistically significant reduction in coronary events ( 36 ) , two good- quality studies reported no statistically significant effect on mortality ( 16 , 37 ) , and one PURPOSE To evaluate whether use of a bisphosphonate ( risedronate ) in addition to calcium and vitamin D in male veterans with epilepsy who were taking antiepileptic drugs ( AEDs ) long term can prevent the loss of bone mass ( BMD , bone mineral density ) associated with AED use compared to patients who were treated with a placebo plus calcium and vitamin D. As a secondary end point we studied the incidence of new morphometric vertebral and nonvertebral fractures . METHODS Antiepileptic drug and osteoporosis prevention trial ( ADOPT ) was design ed as a prospect i ve 2-year double-blind , r and omized placebo controlled study involving 80 male veterans with epilepsy who were being treated with AEDs such as phenytoin , phenobarbital , sodium valproate , or carbamazepine for a minimum of 2 years . All enrolled participants received calcium and vitamin D supplementation , and were r and omized to risedronate or matching placebo .  Total body , bilateral proximal femora , and anteroposterior ( AP ) lumbar spine BMDs in addition to morphometric lateral vertebral assessment s ( LVAs ) were evaluated by a dual energy x-ray absorptiometry ( DXA ) instrument . Comparisons of BMDs were made between baseline , 1 year , and after 2 years of enrollment in the study . The incidence of new vertebral and nonvertebral fractures was secondary end point . KEY FINDINGS Of the 80 patients initially enrolled in the study , 53 patients completed the study . Baseline characteristics of the two groups were similar . At the end of the study , in the placebo plus calcium and vitamin D group , we observed a significant improvement in BMD at any of the evaluated sites when compared to their baseline scans in 69 % ( 18/26 ) of the participants . In the risedronate plus calcium and vitamin D group , we observed significant improvement of BMDs in 70 % ( 19/27 ) of the participants . At the end of the study , the risedronate group experienced a significant increase of BMD at the lumbar spine L1 - 4 ( 1.267 - 1.332 g/cm(2 ) ) , which was significantly larger than that seen in the placebo group ) ( 1.229 g/cm(2 ) vs. 1.245 g/cm(2 ) ; p = 0.0066).There were nonsignificant differences between the two groups regarding changes of total body BMD or at the proximal bilateral femora . Five new vertebral fractures and one nonvertebral fracture were observed only in the placebo group . SIGNIFICANCE Calcium and vitamin D supplementation or calcium and vitamin D supplementation in addition to risedronate improved BMD in more than 69 % of male veterans with epilepsy who were taking AEDs . In the group receiving risedronate plus calcium and vitamin D there was a significant improvement of BMD at the lumbar spine as compared to the placebo group , which also received calcium and vitamin D. The use of risedronate plus calcium and vitamin D prevented the incidence of new vertebral fractures and one nonvertebral fracture in this cohort Summary A r and omized , controlled fall-prevention study including 199 patients operated on for femoral neck fracture reduced inpatient falls and injuries . No statistically significant effects of the intervention program could be detected after discharge . It seems that fall-prevention must be part of everyday life in fall-prone old people . Introduction This study evaluates whether a postoperative multidisciplinary , multifactorial fall-prevention program performed by a geriatric team that reduced inpatient falls and injuries had any continuing effect after discharge . The intervention consisted of staff education , systematic assessment and treatment of fall risk factors and vitamin D and calcium supplementation . Methods The r and omized , controlled trial with a one-year follow-up at Umeå University Hospital , Sweden , included 199 patients operated on for femoral neck fracture , aged ≥70 years . Results After one year 44 participants had fallen 138 times in the intervention group compared with 55 participants and 191 falls in the control group . The crude postoperative fall incidence was 4.16/1,000 days in the intervention group vs. 6.43/1,000 days in the control group . The incidence rate ratio was 0.64 ( 95 % CI : 0.40–1.02 , p = 0.063 ) . Seven new fractures occurred in the intervention group and 11 in the control group . Conclusion A team applying comprehensive geriatric assessment and rehabilitation , including prevention and treatment of fall-risk factors , reduced inpatient falls and injuries , but no statistically significant effects of the program could be detected after discharge . It seems that fall-prevention must be part of everyday life in fall-prone elderly Excessive intake of vitamin A is postulated to have a detrimental effect on bone by inducing osteoporosis . This may lead to an increased risk of fracture , particularly in persons who are already at risk of osteoporosis . However , few studies have specifically examined the association of vitamin A intake through diet and supplement use , with fractures in a cohort of older , community-dwelling women . We prospect ively followed a cohort of 34,703 postmenopausal women from the Iowa Women ’s Health Study to determine if high levels of vitamin A and retinol intake through food and supplement use were associated with an increased risk of hip or all fractures . A semiquantitative food frequency question naire was used to obtain the participants ’ baseline vitamin A and retinol intake . Participants were followed for a mean duration of 9.5 years for incident self-reported hip and nonhip fractures . After multivariate adjustment , it was revealed that users of supplements containing vitamin A had a 1.18-fold increased risk of incident hip fracture ( n=525 ) compared with nonusers ( 95 % CI , 0.99 to 1.41 ) , but there was no evidence of an increased risk of all fractures ( n=6,502 ) among supplement users . There was also no evidence of a dose-response relationship in hip fracture risk with increasing amounts of vitamin A or retinol from supplements . Furthermore , our results showed no association between vitamin A or retinol intake from food and supplements , or food only , and the risk of hip or all fractures . In conclusion , we found little evidence of an increased risk of hip or all fractures with higher intakes of vitamin A or retinol among a cohort of older , postmenopausal women OBJECTIVES To assess the efficacy of once-yearly zoledronic acid ( ZOL ) 5 mg in increasing bone mineral density ( BMD ) in men with a recent hip fracture participating in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once- Yearly Recurrent Fracture Trial and to compare the efficacy with that in women from the same study . DESIGN R and omized , placebo-controlled , double-blind trial . SETTING International multicenter . PARTICIPANTS Five hundred and eight men and 1,619 women within 90 days of surgical repair of low-trauma hip fracture in the same study ( for comparison ) . INTERVENTION Once-yearly intravenous ( IV ) ZOL 5 mg ( n = 248 ) or placebo ( n = 260 ) , loading dose of vitamin D , daily calcium , and vitamin D supplements . MEASUREMENT Changes in BMD . RESULTS Percentage change from baseline in total hip BMD at Months 12 and 24 was significantly higher with ZOL than with placebo ( between-group difference , 2.0 % , P = .003 , and 3.8 % , P = .002 , respectively ) . Percentage change from baseline in femoral neck BMD at Month 24 was significantly higher with ZOL than with placebo ( 3.8 % , P = .003 ) . The BMD benefit was comparable with that observed in women in this study . New clinical fractures occurred in 36 ( 7.1 % ) participants ( ZOL , n = 16 ; placebo , n = 20 ; P = .64 ) . The  ZOL safety profile was comparable with that of placebo , with no significant differences in cardiovascular or long-term renal function and a trend toward lower mortality in ZOL-treated men . CONCLUSION Once-yearly IV ZOL 5 mg increases bone mass at the hip and femoral neck in men within 90 days of repair of a low-trauma hip fracture . Increases were of a similar magnitude to those observed in women in the same study CONTEXT Serum 25-hydroxyvitamin D ( 25OHD ) concentrations greater than 30 ng/ml have been recommended for lowering fracture risk . OBJECTIVE Our objective was to determine whether 25OHD sufficiency is a prerequisite for effective response to teriparatide ( TPTD ) . DESIGN AND PATIENTS Data were from 1620 osteoporotic postmenopausal women in the Fracture Prevention Trial . The response to TPTD was assessed in women subgrouped by having 25OHD insufficiency ( > 10 but < or=30 ng/ml ) or 25OHD sufficiency ( > 30 but < or=183 ng/ml ) at the baseline ( r and omization ) visit . An abnormal intact PTH was exclusionary . INTERVENTIONS At baseline , after at least 1 month of supplementation with calcium ( 1000 mg ) and vitamin D ( 400 - 1200 IU ) daily , women were r and omized to placebo or 20 or 40 microg TPTD by daily sc injection for a median of 19 months . Observation was for a median of 21 months . MAIN OUTCOME MEASURES Main outcome measures included vertebral and nonvertebral fractures , change in bone mineral density at the lumbar spine and femoral neck , change in bone formation marker amino-terminal extension peptide of procollagen type 1 , and the proportion of women with serum calcium at least 2.76 mmol/liter 4 - 6 h after dosing . RESULTS TPTD  reduced vertebral and nonvertebral fracture risk , increased lumbar spine and femoral neck bone mineral density , and increased amino-terminal extension peptide of procollagen type 1 relative to placebo in the two 25OHD subgroups . There were no significant differences in these endpoints between the subgroups ( each treatment by subgroup interaction , P > 0.10 ) . However , it should be noted that because of the limited number of fractures , this study does not exclude the possibility of differences in fracture outcome between the subgroups . CONCLUSIONS In postmenopausal women with osteoporosis and normal intact PTH , the responses to TPTD did not differ significantly in women with baseline 25OHD insufficiency or sufficiency CONTEXT It is widely believed that fractures result ing from high trauma are not osteoporotic ; however , this assumption has not been studied prospect ively . OBJECTIVE To examine the association between bone mineral density ( BMD ) and high-trauma fracture and between high-trauma fracture and  subsequent fracture in older women and men . DESIGN , SETTING , AND PARTICIPANTS Two prospect i ve US cohort studies in community-dwelling adults 65 years or older from geographically diverse sites . The Study of Osteoporotic Fractures followed up 8022 women for 9.1 years ( 1988 - 2006 ) . The Osteoporotic Fractures in Men Study followed up 5995 men for 5.1 years ( 2000 - 2007 ) . MAIN OUTCOME MEASURES Hip and spine BMD were assessed by dual-energy x-ray absorptiometry . Incident nonspine fractures were confirmed by radiographic report . Fractures were classified , without knowledge of BMD , as high trauma ( due to motor vehicle crashes and falls from greater than st and ing height ) or as low trauma ( due to falls from st and ing height and less severe trauma ) . RESULTS Overall , 264 women and 94 men sustained an initial high-trauma fracture and 3211 women and 346 men sustained an initial low-trauma fracture . For women , each 1-SD reduction in total hip BMD was similarly associated with an increased risk of high-trauma fracture ( multivariate relative hazard [ RH ] , 1.45 ; 95 % confidence interval [ CI ] , 1.23 - 1.72 ) and low-trauma fracture ( RH , 1.49 ; 95 % CI , 1.42 - 1.57 ) . Results were consistent in men ( high-trauma fracture RH , 1.54 ; 95 % CI , 1.20 - 1.96 ; low-trauma fracture RH , 1.69 ; 95 % CI , 1.49 - 1.91 ) . Risk of subsequent fracture was 34 % ( 95 % CI , 7%-67 % ) greater among women with an initial high-trauma fracture and 31 % ( 95 % CI , 20%-43 % ) greater among women with an initial low-trauma fracture , compared with women having no high- or low-trauma fracture , respectively . Risk of subsequent fracture was not modeled for men . CONCLUSIONS Similar to low-trauma nonspine fractures , high-trauma nonspine fractures are associated with low BMD and increased risk of subsequent fracture  in older adults . High-trauma nonspine fractures should be included as outcomes in osteoporosis trials and observational studies OBJECTIVE To test the hypothesis that bone  mineral density ( BMD ) is associated with the risk of developing breast cancer in older women . DESIGN Prospect i ve cohort study with mean ( SD ) follow-up of 3.2 ( 1.6 ) years . SETTING Four clinical centers , one each located in the following areas : Baltimore , Md ; Minneapolis , Minn ; Portl and , Ore ; and the Monongahela Valley in Pennsylvania . PARTICIPANTS A total of 6854 nonblack women who were 65 years of age or older and enrolled in the Study of Osteoporotic Fractures . MEASUREMENTS  Radius and calcaneus BMD  by single photon absorptiometry at baseline ; hip and spine BMD  by dual-energy x-ray absorptiometry 2 years later . MAIN OUTCOME MEASURE Breast cancer confirmed by medical record review . RESULTS A total of 97 women developed breast cancer . In the multivariate model , adjusting for age , the degree of obesity , and other important covariates , the risk of breast cancer was about 30 % to 50 % higher per 1 SD increase in BMD ( relative risk , distal radius BMD=1.50 ; 95 % confidence interval , 1.16 - 1.95 ) . The age-adjusted incidence rate of breast cancer per 1000 person-years among women in the lowest quartile of distal radius BMD was 2.46 , compared with 5.99 among women with the highest BMD . Women with BMD above the 25th percentile were at 2.0 to 2.5 times increased risk of breast cancer compared with women below the 25th percentile . Results were consistent across all BMD sites . CONCLUSIONS Bone mineral density predicts the risk of breast cancer in older women . The magnitude of the association is similar to that observed between BMD and all fractures . Our findings suggest a link between 2 of the most common conditions affecting a woman 's health . Identifying a common denominator for these conditions should substantially improve our underst and ing of their etiology and prevention PURPOSE To explore the association between consumption of fruits and vegetables and the presence of glaucoma in older African-American women . DESIGN Cross-sectional study . METHODS Disc photographs and suprathreshold visual fields were obtained from the 662 African-American participants in the Study of Osteoporotic Fractures . Masked , trained readers grade d all discs , and 2 glaucoma specialists review ed photographs and visual fields . The Block Food Frequency Question naire assessed food consumption . Relationships between selected fruit/vegetable/nutrient consumption and glaucoma were evaluated using logistic regression models after adjusting for potential confounders . RESULTS After excluding women missing Food Frequency Question naire and disc data , 584 African-American women ( 88.2 % of total African-American cohort ) were included . Glaucoma  was diagnosed in at least 1 eye in 77 subjects ( 13 % ) . Women who ate 3 or more servings/day of fruits/fruit juices were 79 % ( odds ratio [ OR ] = 0.21 ; 95 % confidence interval [ CI ] : 0.08 - 0.60 ) less likely to have glaucoma than women who ate less than 1 serving/day . Women who consumed more than 2 servings/week of fresh oranges ( OR = 0.18 ; 95 % CI : 0.06 - 0.51 ) and peaches ( OR = 0.30 ; 95 % CI : 0.13 - 0.67 ) had a decreased odds of glaucoma compared to those consuming less than 1 serving/week . For vegetables , > 1 serving/week compared to ≤1 serving/month of collard greens/kale decreased the odds of glaucoma by 57 % ( OR = 0.43 ; 95 % CI : 0.21 - 0.85 ) . There was a protective trend against glaucoma in those consuming more fruit/fruit juices ( P = .023 ) , fresh oranges ( P = .002 ) , fresh peaches ( P = .002 ) , and collard greens/kale ( P = .014 ) . Higher consumption of carrots ( P = .061 ) and spinach ( P = .094 ) also showed some associations . Individual nutrient intake from food sources found protective trends with higher intakes of vitamin A ( P = .011 ) , vitamin C ( P = .018 ) , and α-carotene ( P = .021 ) , and close to statistically significant trends with β-carotene ( P = .052 ) , folate ( P = .056 ) , and lutein/zeaxanthin ( P = .077 ) . CONCLUSION Higher intake of certain fruits and vegetables high in vitamins A and C and carotenoids may be associated with a decreased likelihood of glaucoma in older African-American women . R and omized controlled trials are needed to determine whether the intake of specific nutrients changes the risk of glaucoma Introduction Osteoporosis represents a growing public health concern ; however , current rates of management are sub-optimal . The aim of our study was to assess , in a r and omized controlled trial , the effect of a mailed educational intervention on older adults ’ knowledge , attitudes , and preventive behaviors regarding osteoporosis . The setting was a large publicly funded state pharmacy benefits program . The patients were 31,715 Medicare beneficiaries from Pennsylvania who participated in a drug benefits program for low-to-moderate income elderly people . Methods All women aged over 65 years , and all men and women with a history of fracture or long-term oral use of glucocorticoid , were included . Approximately half of the participants ( intervention group ) were r and omly selected to receive three mailings aim ed at improving knowledge of osteoporosis and enhancing preventive activities , such as using calcium and vitamin D , reducing fall risks in the home , obtaining a bone mineral density ( BMD ) test , and taking medications when necessary . The other participants did not receive the intervention mailings and served as controls . We surveyed a sample of intervention and control subjects to determine the effects of the intervention on knowledge , attitudes , self-efficacy ( confidence in one ’s ability to perform specific activities ) , and behavior regarding osteoporosis prevention and treatment . Six hundred r and omly selected participants in the intervention group and an equal number in the control group were invited to participate . Results Twenty-six had died and 636 of the remaining 1,185 ( 54 % ) completed the survey . Respondents and non-respondents did not differ significantly with respect to measured sociodemographic factors . All scales had good reliability ( all Cronbach ’s alphas > 0.65 ) . Knowledge of osteoporosis was generally very good and did not differ between intervention ( mean = 65 % correct responses ) and control subjects ( mean = 67 % correct ; P=0.4 ) . Perceived susceptibility to osteoporosis was relatively high and similar across groups ( P=0.4 ) . Self-efficacy for participating in osteoporosis prevention and treatment was very strong in both the intervention ( mean = 4.3 on a 0–5 scale ) and control ( mean = 4.2 , P=0.03 ) groups . On average , subjects in the intervention group reported participating in 3.5 of 6 preventive osteoporosis activities compared with 3.4 in the control group ( P=0.5 ) . Conclusions Compared with the controls , a mailed educational intervention for osteoporosis was not associated with better knowledge , higher perceived susceptibility , or performance of preventive measures among the at-risk older adults that we studied . The intervention group demonstrated a small increase in self-efficacy . More intensive patient interventions or intervention aim ed at other aspects of the care process may be required to bring about changes that lead to a reduction in fractures BACKGROUND Older people living in residential aged care facilities ( RACFs ) are at a higher risk of suffering fractures than the community-dwelling older population . The first Consensus Conference on Treatment of Osteoporosis in RACFs in Australia , held in Sydney in July 2009 , aim ed to address some of the issues relating to the treatment of older residents with osteoporosis in RACFs . Considering that the field of osteoporosis diagnosis and management has significantly advanced in the last 5 years and that new evidence has been generated from studies performed within RACFs , a Second Consensus Conference was held in Sydney in November 2014 . METHODS An expert panel met in November 2014 in Penrith , NSW , Australia in an attempt to reach a consensus on diverse issues related to the treatment of osteoporosis at RACFs . Participants were selected by the scientific committee on the basis of their practice in an RACF and /or major published articles . The co-chairs distributed topics r and omly to all participants , who then had to propose a statement on each topic for approval by the conference after a short , evidence -based presentation , when possible . RESULTS This article provides an up date on the most relevant evidence on osteoporosis  in older people living in RACFs grade d according to its level , quality , and relevance . CONCLUSION As with the first consensus , it is hoped that this statement will constitute an important guide to aid physicians in their decision making while practicing at RACFs Abstract Background . Distal radius fracture often presents a metaphyseal void which is more extended in elderly , osteoporotic patients . Bone graft and bone substitutes are reported to be beneficial in maintaining metaphyseal reduction . Methods . We performed a prospect i ve study on 52 menopausal , osteoporotic women with unstable intra-articular distal radius fractures to compare the outcome of percutaneous pinning and immobilisation in a cast for 6 weeks with that using injectable calcium phosphate bone cement ( Norian Skeletal Repair System , SRS ) to supplement pin and screw fixation and immobilisation in a cast for 3 weeks . All patients were review ed 2 years ( range 21–29 months ) after surgery . Results . Patients treated with SRS had better functional outcome , restoration of movement and grip strength ( p<0.001 ) . In this group there was 1 mm loss of radial length , 3 ° loss of radial inclination and 7 ° loss of palmar tilt . In the control group radial length decreased 3 mm , radial inclination decreased 11 ° and palmar tilt 12 ° . Loss of reduction was significantly higher in the control group ( p<0.001 ) . Conclusion . We conclude that the use of Norian SRS to supplement pin and screw fixation is effective in maintaining the reduction of unstable intra-articular distal radius fractures in osteoporotic patients and provides a better clinical outcome than percutaneous pinning Nutraceuticals have generated interest as a way to mitigate the cognitive decline in older adults . The aim of this systematic review was to determine the evidence for these cl aims from the scientific literature in r and omised , double-blinded , controlled trials ( duration : ≥1 year ; participants : n≥100 ; age(mean ) : ≥65 years ) . Following Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines , we search ed four electronic data bases ( PubMed , Scopus , CINAHL and Web of Science ) and identified twenty-five studies published between the 15·June·2006 and 14·June·2016 . Interventions included B-vitamins , n-3 fatty acids , antioxidant vitamins and herbs . Of the B-vitamin studies , four found benefits to cognition with supplementation . The first of these B-vitamin studies , in individuals with mild cognitive impairment ( n 266 ; duration = 2 years ) , included benefit to executive function ( P=0·015 ) and improvements in the Mini-Mental State Examination ( MMSE ) among participants with baseline homocysteine above 11·3 µmol/l ( P<0·001 ) . In the same sample , the second study found cognitive benefits  of B-vitamins dependent on the higher baseline plasma n-3 fatty acid status . The third B-vitamin study ( n 900 ; duration = 2 years ) reported improved performance in immediate ( P=0·046 ) and delayed recall ( P=0·013 ) , whereas the fourth study ( n 856 ; duration = 2 years ) reported slower rate of cognitive decline in the MMSE ( P=0·05 ) . One study investigating DHA treatment ( n 402 ; duration = 1·5 years ) revealed the slower rate of cognitive change in apoE e4 non-carriers ( P=0·03 ) . As only five included studies revealed notable benefits , presently based on the specific compounds explored here , there is not compelling evidence to support the use nutraceuticals to improve cognition in the elderly . Future long-term trials of nutraceuticals should investigate interactions with lifestyle , blood biomarkers and genetic risk factors BACKGROUND Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption . In a phase 2 clinical trial , strontium ranelate , an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption , has been shown to reduce the risk of vertebral fractures and to increase bone mineral density . METHODS To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial , we r and omly assigned 1649 postmenopausal women with osteoporosis ( low bone mineral density ) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years . We gave calcium and vitamin D supplements to both groups before and during the study . Vertebral radiographs were obtained annually , and measurements of bone mineral density were performed every six months . RESULTS New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group , with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period ( relative risk , 0.59 ; 95 percent confidence interval , 0.48 to 0.73 ) . Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck ( P<0.001 for both comparisons ) . There were no significant differences between the groups in the incidence of serious adverse events . CONCLUSIONS Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures INTRODUCTION Stress fractures ( SFx ) are one of the most common and debilitating overuse injuries seen in military recruits , and they are also problematic for nonmilitary athletic population s. The goal of this r and omized double-blind , placebo-controlled study was to determine whether a calcium and vitamin D intervention could reduce the incidence of SFx in female recruits during basic training . MATERIAL S AND METHODS We recruited 5201 female Navy recruit volunteers and r and omized them to 2000 mg calcium and 800 IU vitamin D/d or placebo .  SFx were ascertained when recruits reported to the Great Lakes clinic with symptoms . All SFx were confirmed with radiography or technetium scan according to the usual Navy protocol . RESULTS A total of 309 subjects were diagnosed with a SFx result ing in an incidence of 5.9 % per 8 wk . Using intention-to-treat analysis by including all enrolled subjects , we found that the calcium and vitamin D group had a 20 % lower incidence of SFx than the control group ( 5.3 % versus 6.6 % , respectively , p = 0.0026 for Fisher 's exact test ) . The per protocol analysis , including only the 3700 recruits who completed the study , found a 21 % lower incidence of fractures in the supplemented versus the control group ( 6.8 % versus 8.6 % , respectively , p = 0.02 for Fisher 's exact test ) . CONCLUSIONS Generalizing the findings to the population of 14,416 women who entered basic training at the Great Lakes during the 24 mo of recruitment , calcium and vitamin D supplementation for the entire cohort would have prevented approximately 187 persons from fracturing . Such a decrease in SFx would be associated with a significant decrease in morbidity and financial costs CONTEXT Vitamin D or calcium supplementation may have effects on  vascular disease and cancer .  OBJECTIVE Our objective was to investigate whether vitamin D or calcium supplementation affects mortality , vascular disease , and cancer in older people . DESIGN AND SETTING The study included long-term follow-up of participants in a two by two factorial , r and omized controlled trial from 21 orthopedic centers in the United Kingdom . PARTICIPANTS Participants were 5292 people ( 85 % women ) aged at least 70 yr with previous low-trauma fracture . INTERVENTIONS Participants were r and omly allocated to daily vitamin D(3 ) ( 800 IU ) , calcium ( 1000 mg ) , both , or placebo for 24 - 62 months , with a follow-up of 3 yr after intervention . MAIN OUTCOME MEASURES All-cause mortality , vascular disease mortality , cancer mortality , and cancer incidence were evaluated . RESULTS In intention-to-treat analyses , mortality [ hazard ratio ( HR ) = 0.93 ; 95 % confidence interval ( CI ) = 0.85 - 1.02 ] , vascular disease mortality ( HR = 0.91 ; 95 % CI = 0.79 - 1.05 ) , cancer mortality ( HR = 0.85 ; 95 % CI = 0.68 - 1.06 ) , and cancer incidence ( HR = 1.07 ; 95 % CI = 0.92 - 1.25 ) did not differ significantly between participants allocated vitamin D and those not . All-cause mortality ( HR = 1.03 ; 95 % CI = 0.94 - 1.13 ) , vascular disease mortality ( HR = 1.07 ; 95 % CI = 0.92 - 1.24 ) , cancer mortality ( HR = 1.13 ; 95 % CI = 0.91 - 1.40 ) , and cancer incidence ( HR = 1.06 ; 95 % CI = 0.91 - 1.23 ) also did not differ significantly between participants allocated calcium and those not . In a post hoc statistical analysis adjusting for compliance , thus with fewer participants , trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated , although all results remain nonsignificant . CONCLUSIONS Daily vitamin D or calcium supplementation did not affect mortality , vascular disease , cancer mortality , or cancer incidence BACKGROUND Vitamin D insufficiency was shown to be associated with adverse musculoskeletal and nonskeletal outcomes in numerous observational studies . However , some studies did not control for confounding factors such as age or seasonal variation of 25-hydroxyvitamin D [ 25(OH)D ] . OBJECTIVE We sought to determine the effect of vitamin D status on health outcomes . DESIGN Healthy community-dwelling women ( n = 1471 ) with a mean age of 74 y were followed in a 5-y trial of calcium supplementation .  25(OH)D was measured at baseline in all women .  Skeletal and nonskeletal outcomes were evaluated according to seasonally adjusted vitamin D status at baseline . RESULTS Fifty percent of women had a seasonally adjusted 25(OH)D concentration < 50 nmol/L. These women were significantly older , heavier , and less physically active and had more comorbidities than women with a seasonally adjusted 25(OH)D concentration > or = 50 nmol/L. Women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L had an increased incidence of stroke and cardiovascular events that did not persist after adjustment for between-group differences in age or comorbidities . Women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L were not at increased risk of adverse consequences for any musculoskeletal outcome , including fracture , falls , bone density , or grip strength or any nonskeletal outcomes , including death , myocardial infa rct ion , cancer , heart failure , diabetes , or adverse changes in blood pressure , weight , body composition , cholesterol , or glucose . CONCLUSIONS Vitamin D insufficiency is more common in older , frailer women . Community-dwelling older women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L were not at risk of adverse outcomes over 5 y after control for comorbidities . R and omized placebo-controlled trials are needed to determine whether vitamin D supplementation in individuals with vitamin D insufficiency influences health outcomes . This trial was registered at www.anzctr.org.au as ACTRN 012605000242628 OBJECTIVES To determine the efficacy of vision and eye examinations , with subsequent treatment of vision problems , for preventing falls and fractures in frail older people . DESIGN R and omized , controlled trial . SETTING Community in Sydney , Australia . PARTICIPANTS Six hundred sixteen men and women aged 70 and older ( mean age 81 ) recruited mainly from people attending outpatient aged care services . INTERVENTIONS The intervention group received comprehensive vision and eye examinations conducted by a study optometrist . The optometrist arranged for new eyeglasses  for 92 subjects and referred 24 for a home visit with an occupational therapist , 17 for glaucoma management , and 15 for  cataract surgery . The control group received usual care . MEASUREMENTS Falls and fractures during 12 months of follow-up were ascertained according to self-report using a monthly postcard system . RESULTS Fifty-seven percent of subjects fell at least once during follow-up . Falls occurred more frequently in the group r and omized to receive the vision intervention ( 65 % fell at least once ; 758 falls in total ) than in the control group ( 50 % fell at least once ; 516 falls in total ) . The falls rate ratio using the negative binomial model was 1.57 ( 95 % confidence interval (CI)=1.20 - 2.05 , P=.001 ) . Fractures were also more frequent in the intervention group ( 31 fractures ) than the control group ( 18 fractures ; relative risk from proportional hazards model 1.74 , 95 % CI=0.97 - 3.11 , P=.06 ) . CONCLUSION In frail older people , comprehensive vision and eye assessment , with appropriate treatment , does not reduce , and may even increase , the risk of falls and fractures UNLABELLED None of the available osteoporosis therapies have been shown to completely abolish the risk of fractures . In clinical practice , the outcome may be even poorer . In 880 patients prescribed with antiresorptives ( alendronate , risedronate , and raloxifene ) for > 1 year , a  fragility fracture  was recorded in 8.9%/year of them . This incidence is considerably higher than that observed in r and omized clinical trials , and it was significantly related to poor compliance and lack of supplementation with calcium and vitamin D. INTRODUCTION Osteoporotic fracture is one of the most important public health concerns among the elderly . Currently available therapies have been shown to significantly decrease the risk of fracture , although none of them completely abolishes this risk . In clinical practice , poor treatment response may also result from a number of other factors . MATERIAL S AND METHODS The Incidence and ChAracterization of inadequate clinical Responders in Osteoporosis ( ICARO ) is a multicenter , observational study carried out in Italy . It aim ed to analyze , in postmenopausal women with established osteoporosis , the risk factors for an " inadequate clinical response " to drug therapy , defined as the occurrence of new vertebral or nonvertebral fragility fractures in patients prescribed , for at least 1 year , alendronate , risedronate , or raloxifene , with a compliance > 50 % . RESULTS In 880 patients treated with antiresorptive agents  for a median of 2.0 years ( 95 % CI : 1.0 - 4.5 ) years , the " inadequate clinical responder ( ICR ) " subjects over the observation period were 220 ( 25 % ) , with an annual incidence of 8.9 % . ICRs , compared with " adequate clinical responders ( ACRs ) , " had more pretreatment fractures and were treated longer ( 2.8 versus 1.8 years ; p < 0.001 ) . After multiple adjustment for these confounding factors , significant determinants of inadequate clinical response were a poorer treatment compliance and a less frequent co-administration of calcium and vitamin D supplements . CONCLUSIONS The incidence of fractures during treatment with antiresorptive agents in a clinical setting is considerably higher than that observed in r and omized clinical trials . Inadequate compliance to treatment and lack of supplementation of calcium and vitamin D are major determinants of this poor response CONTEXT Type 2 diabetes mellitus ( DM ) is associated with higher bone mineral density ( BMD ) and paradoxically with increased fracture risk . It is not known if low BMD , central to fracture prediction in older adults , identifies fracture risk in patients with DM . OBJECTIVE To determine if femoral neck BMD T score and the World Health Organization Fracture Risk Algorithm ( FRAX ) score are associated with hip and nonspine fracture risk in older adults with type 2 DM . DESIGN , SETTING , AND PARTICIPANTS Data from 3 prospect i ve observational studies with adjudicated fracture outcomes ( Study of Osteoporotic Fractures [ December 1998-July 2008 ] ; Osteoporotic Fractures in Men Study [ March 2000-March 2009 ] ; and Health , Aging , and Body Composition study [ April 1997-June 2007 ] ) were analyzed in older community-dwelling adults ( 9449 women and 7436 men ) in the United States . MAIN OUTCOME MEASURE Self-reported incident fractures , which were verified by radiology reports . RESULTS Of 770 women with DM , 84 experienced a hip fracture and 262 a nonspine fracture during a mean ( SD ) follow-up of 12.6 ( 5.3 ) years . Of 1199 men with DM , 32 experienced a hip fracture and 133 a nonspine fracture during a mean ( SD ) follow-up of 7.5 ( 2.0 ) years . Age-adjusted hazard ratios ( HRs ) for 1-unit decrease in femoral neck BMD T score in women with DM were 1.88 ( 95 % confidence interval [ CI ] , 1.43 - 2.48 ) for hip fracture and 1.52 ( 95 % CI , 1.31 - 1.75 ) for nonspine fracture , and in men with DM were 5.71 ( 95 % CI , 3.42 - 9.53 ) for hip fracture and 2.17 ( 95 % CI , 1.75 - 2.69 ) for nonspine fracture . The FRAX score was also associated with fracture risk in participants with DM ( HRs for 1-unit increase in FRAX hip fracture score , 1.05 ; 95 % CI , 1.03 - 1.07 , for women with DM and 1.16 ; 95 % CI , 1.07 - 1.27 , for men with DM ; HRs for 1-unit increase in FRAX osteoporotic fracture score , 1.04 ; 95 % CI , 1.02 - 1.05 , for women with DM and 1.09 ; 95 % CI , 1.04 - 1.14 , for men with DM ) . However , for a given T score and age or for a given FRAX score , participants with DM had a higher fracture risk than those without DM . For a similar fracture risk , participants with DM had a higher T score than participants without DM . For hip fracture , the estimated mean difference in T score for women was 0.59 ( 95 % CI , 0.31 - 0.87 ) and for men was 0.38 ( 95 % CI , 0.09 - 0.66 ) . CONCLUSIONS Among older adults with type 2 DM , femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk ; however , in these patients compared with participants without DM , the fracture risk was higher for a given T score and age or for a given FRAX score In July the Department of Health ( DH ) in Engl and published a toolkit of re sources to promote more effective services to reduce the burden of  falls and fractures in older people . Unfortunately , there is plenty of evidence that the present provision of falls services is suboptimal . The toolkit is part of a ‘ Prevention Package ’ aim ed primarily at commissioners of care , in an attempt to achieve a more consistent and integrated approach to a range of prevention issues in older people [ 1 ] . Falls are a major international public health challenge because of the myriad effects on older individuals : direct physical and psychological injury ; fear of falling and activity limitation ; reduced social participation and quality of life ; increased dependence [ 2–5 ] ; and because of the economic impact on health and social care providers [ 6 , 7 ] . Studies from various countries have shown that about one third of people aged above 65 years fall each year . In UK primary care population s , the rate rises with age to over 60 % of nonagenarians , and is generally higher in women [ 8 ] and in socio-economically deprived population s [ 9 ] . Fragility fractures are the commonest significant injury , 300,000 annually in the UK including upwards of 70,000 hip fractures . Many falls go unreported , but nevertheless they account for 40 % of UK ambulance call-outs , with the variable proportion being conveyed to hospital accounting for one in ten Emergency Department ( ED ) attendances of the over 75s [ 6 ] , a third of whom are admitted , thus comprising about 14 % of emergency admissions . Identifying all falls related activity is challenging but recent estimates suggest that it accounts for between 10 % and 25 % of all local health and social care spending on older people [ 10 ] . Care of fragility fractures is particularly expensive , total health and social care costs in the UK being around £ 2 billion , most of which relates to hip fractures [ 11 ] . Current population and incidence projections suggest that by 2020 , this figure will rise by 50 % . Early in the development of geriatric medicine , falls were identified as a ‘ geriatric giant’—adverse in their own right but also a non-specific indicator of functional decompensation . Building on clarification of falls risk factors [ 12 ] , r and omised controlled trials demonstrated the effectiveness of risk factor based multi-factorial interventions [ 13 , 14 ] . This led to the notion of ‘ falls prevention services ’ . Based on international consensus about what constituted best clinical practice [ 15 ] , broadly similar policies have been developed by the responsible government departments of the four UK nations , and in Irel and [ 16 ] . The National Service Framework for Older People in Engl and ( NSF , 2001 ) [ 17 ] required health services and their local council partners to develop integrated services by April 2005 , incorporating case finding , assessment and referral systems and specialist falls and fragility fracture services . The NSF was launched without earmarked implementation funding , but there was plenty of activity , some enabled and directed by various government initiatives , encouraging community engagement . An independent postal question naire survey to health and social care agencies about their falls services in 2004 [ 18 ] reported most having made plans for an integrated service but implementation was patchy and focused on widely differing priorities . Only 30 % included systems for identifying high risk individuals and only 13 % of falls prevention programmes included exercise classes , the most effective prevention strategy [ 19 ] whilst interventions with little or no evidence base were promoted [ 20 ] . Implementation of these policies across Engl and , Wales and Northern Irel and has been monitored in a series of government funded national audits run by the Royal College of Physicians of London ( RCP ) . The first of these confirmed major gaps at the organisational level , particularly in case finding and referrals for secondary prevention [ 21 ] . A subsequent patient level clinical care audit of fragility fracture patients showed that most returning home from the Emergency Department were not offered a falls risk assessment and only one third were on appropriate treatment for osteoporosis 3 months later [ 22 ] . Despite intense interest among clinicians in the UK and appointment of many geriatricians with a focus on falls , syncope and orthogeriatrics , a repeat organisational audit showed that by 2008 there had been little improvement in service structure , capacity or processes [ 23 ] . Meanwhile the picture was clouded by the negative results of a DH funded systematic review with meta-analyses [ 24 ] . This suggested that the variable outcomes of clinical trials might be associated with the way that the multifactorial approach was organised . There are now several negative outcome trials employing the strategy of nurse led case finding linked to interventions intended to be provided by a range of unconnected professions acting on referral [ 25 ] . In clinical practice , it is likely that there is even more differential effectiveness depending on case finding and referral practice s and context ual differences in service delivery . Research evidence is still lacking on how to achieve much that the NSF aspired to , but there is sufficient evidence and examples of successful implementation to do much better than most are currently doing . So how will the latest government action help ? A key step is to clarify priorities and to put available re sources into the activities likely to make Abstract : In a prospect i ve study of 348 apparently healthy women , aged 70 years and over ( mean 80.3 years ) , we examined bone mineral density ( BMD ) , biochemical markers of bone metabolism , and some easily measurable predictors in relation to hip and osteoporotic fractures . In addition , we constructed risk profiles for hip and osteoporotic fractures . At baseline , BMD at both hips , using dual-energy X-ray absorptiometry , body height and body weight were measured . At the same time , serum and urine sample s were obtained for biochemical analysis . Serum sample s were analyzed for vitamin D metabolites , sex hormone binding globulin , serum intact parathyroid hormone , osteocalcin , alkaline phosphatase , phosphate , albumin , calcium and creatinine . In 2 h fasting urine , hydroxyproline , type I collagen crosslinked N-telopeptide ( NTx ) and calcium excretion were measured . Furthermore , easily measurable predictors , such as previous fracture , body mass index ( BMI ) and mobility were assessed . During the follow-up period ( mean duration 5.0 years ) , hip and any osteoporotic fracture ( wrist , humerus or hip fracture ) occurred in 16 and 33 participants , respectively . Data were analyzed using Cox regression analysis . BMD of the trochanter ( per 1 SD decrease ) and previous fracture were most strongly associated with hip fractures ( adjusted relative risk ( RR ) = 3.0 , 95 % confidence interval ( CI ) : 1.4–6.6 ; RR = 4.2 , 95 % CI : 1.5–11.6 , respectively ) and osteoporotic fractures ( RR = 1.8 , 95 % CI : 1.1–2.8 ; RR = 2.9 , 95 % CI : 1.5–5.7 , respectively ) . Previous fracture , BMI and mobility were identified as easily measurable predictors for hip fractures , whereas previous fracture , use of loop diuretics and age were predictors for osteoporotic fractures in the risk profile model . The risk of fractures can be predicted with three easily measurable predictors . This study confirms the importance of previous fracture as a predictor for hip fractures and other fractures . It also shows that the use of loop diuretics is a predictor for osteoporotic fractures Osteoporosis-related fractures constitute a major health concern not only in women but also in men .  Insulin-like growth factor 1 ( IGF-1 ) is a key determinant of bone mass , but the association between serum IGF-1 and incident fractures in men remains unclear . To determine the predictive value of serum IGF-1 for fracture risk in men , older men ( n = 2902 , mean age of 75 years ) participating in the prospect i ve , population -based Osteoporotic Fractures in Men ( MrOS ) Sweden study were followed for a mean of 3.3 years .  Serum IGF-1 was measured at baseline by radioimmunoassay .  Fractures occurring after the baseline visit were vali date d. In age-adjusted hazards regression analyses , serum IGF-1 associated inversely with risk of all fractures [ hazard ratio ( HR ) per SD decrease = 1.23 , 95 % confidence interval ( CI ) 1.07 - 1.41 ] , hip fractures ( HR per SD decrease = 1.45 , 95 % CI 1.07 - 1.97 ) , and clinical vertebral fractures ( HR per SD decrease = 1.40 , 95 % CI 1.10 - 1 - 78 ) . The predictive role of serum IGF-1 for fracture risk was unaffected by adjustment for height , weight , prevalent fractures , falls , and major prevalent diseases . Further adjustment for bone mineral density ( BMD ) result ed in an attenuated but still significant association between serum IGF-1 and fracture risk . Serum IGF-1 below but not above the median was inversely related to fracture incidence . The population -attributable risk proportion was 7.5 % for all fractures and 22.9 % for hip fractures . Taken together , older men with low serum IGF-1 have an increased fracture risk , especially for the two most important fracture types , hip and vertebral fractures . The association between serum IGF-1 and fracture risk is partly mediated via BMD SIR — It is estimated that 25–40 % of adults aged 65 years and over use diuretics [ 1 ] . The three major classes of diuretics have different effects on renal calcium balance .  Loop diuretics increase renal calcium excretion [ 2 ] , while thiazide and potassium-sparing diuretics exert a hypocalciuric effect . Thiazides facilitate the reabsorption of calcium in the early segment of the convoluted distal tubule , and potassium-sparing diuretics promote reabsorption of calcium in the late segment of the distal tubule [ 3–5 ] . Epidemiological data [ 6–14 ] and results from r and omised controlled trials [ 15–17 ] suggest that thiazide diuretic use is associated with a small increase in bone mineral density ( BMD ) or a decreased rate of bone loss . However , these associations were observed primarily among women . There are few data regarding the effects of loop diuretics on BMD and findings are not consistent across studies [ 18 , 19 ] . Although some studies have shown that loop diuretic use may be associated with an increased risk of hip and osteoporotic fractures [ 20–22 ] , it is uncertain whether this possibly elevated fracture risk was mediated by the effect of loop diuretics on bone or rather on fall-related mechanisms , such as dizziness and orthostasis . To our knowledge , no studies have specifically examined whether potassium-sparing diuretics have an independent effect on BMD . Therefore , we conducted a cross-sectional study among participants in the Osteoporotic Fractures in Men ( MrOS ) study , an ongoing prospect i ve study of community-dwelling men , to investigate the association between current diuretic use and BMD at multiple skeletal sites . We hypothesised that compared with diuretic non-users , loop diuretic users would have a lower mean BMD , while thiazide and potassium-sparing diuretic users would have a higher mean BMD CONTEXT Vitamin K has been implicated in bone health , primarily in observational studies . However , little is known about the role of phylloquinone supplementation on prevention of bone loss in men and women . OBJECTIVE The objective of this study was to determine the effect of 3-yr phylloquinone supplementation on change in bone mineral density ( BMD ) of the femoral neck bone in older men and women who were calcium and vitamin D replete . DESIGN , PARTICIPANTS , AND INTERVENTION In this 3-yr , double-blind , controlled trial , 452 men and women ( 60 - 80 yr ) were r and omized equally to receive a multivitamin that contained either 500 mug/d or no phylloquinone plus a daily calcium ( 600 mg elemental calcium ) and vitamin D ( 400 IU ) supplement . MAIN OUTCOME MEASURES Measurements of the femoral neck , spine ( L2-L4 ) , and total-body BMD , bone turnover , and vitamins K and D status were measured every 6 - 12 months . Intent-to-treat analysis was used to compare change in measures in 401 participants who completed the trial . RESULTS There were no differences in changes in BMD measurements at any of the anatomical sites measured between the two groups . The group that received the phylloquinone supplement had significantly higher phylloquinone and significantly lower percent undercarboxylated osteocalcin concentrations compared with the group that did not receive phylloquinone . No other biochemical measures differed between the two groups . CONCLUSIONS Phylloquinone supplementation in a dose attainable in the diet does not confer any additional benefit for bone health at the spine or hip when taken with recommended amounts of calcium and vitamin Fractures of the proximal humerus , forearm , and wrist account for approximately one third of total osteoporotic fractures in the elderly . Several risk factors for these fractures were evaluated in this prospect i ve study of 739 men and 1,105 women aged > or = 60 years in Dubbo , Australia . During follow-up ( 1989 - 1996 ) , the respective incidences of humerus and of forearm and wrist fractures , per 10,000 person-years , were 22.6 and 33.8 for men and 54.8 and 124.6 for women . Independent predictors of humerus fracture were femoral neck bone mineral density ( FNBMD ) ( relative risk ( RR ) = 2.3 , 95 % confidence interval ( CI ) : 1.2 , 4.5 ) in men and FNBMD ( RR = 2.4 , 95 % CI : 1.7 , 3.5 ) and height loss ( RR = 1.1 , 95 % CI : 1.0 , 1.2 ) in women . For forearm and wrist fractures , risk factors were FNBMD ( men : RR = 1.5 , 95 % CI : 1.0 , 2.3 ; women : RR = 1.5 , 95 % CI : 1.2 , 1.9 ) and height loss ( men : RR = 1.2 , 95 % CI : 1.0 , 1.3 ; women : RR = 1.1 , 95 % CI : 1.0 , 1.2 ) . In addition , dietary calcium ( men : RR = 2.0 , 95 % CI : 1.0 , 3.6 ) and a history of falls ( women : RR = 1.9 , 95 % CI : 1.4 , 2.6 ) were also significant . These data suggest that elderly men and women largely share common risk factors for upper limb fractures and that FNBMD is the primary risk factor Study Design . A comparative prospect i ve trial evaluating 3-year outcome . Objective . To compare clinical and morphologic outcomes as well as follow-up fractures after  kyphoplasty of painful osteoporotic vertebral fractures with calcium-phosphate ( CaP ) cement ( group 1 ) and with polymethylmethacrylate (PMMA)-cement ( group 2 ) . Summary of Background Data . CaP cements seem to be an alternative material for usage in kyphoplasty of vertebral fractures .  CaP cements are biodegradable and replaceable by newly formed bone after implantation . Concerns have been raised with regard to the stability of resorbable CaP-cements after implantation into vertebrae post kyphoplasty . Calcibon is a possible CaP cement , which exhibited adequate stability in short-term observations . Material s and Methods . Kyphoplasty was performed in 40 consecutive patients with primary osteoporosis and painful vertebral fractures , 20 received CaP-cement , 20 were treated with PMMA-cement . All patients received a pharmacological antiosteoporosis treatment ( 1000 mg calcium , 1000 IU vitamin D3 , and oral aminobisphosphonate ) , pain medication , and physiotherapy . Pain ( visual analog scale [ VAS ] ; range , 0–100 ) , mobility ( EVOS-score ; range , 0–100 ) and radiomorphologic measurements were assessed at baseline and after 6 , 12 , and 36 months . Results . There were no statistically significant differences between the CaP and PMMA-cement group regarding VAS-scores , EVOS-scores , or height-restoration at any time point . Furthermore , there was no significant difference in the occurrence of vertebral follow-up fractures between both groups during the 3-year follow-up period . Conclusion . CaP cement , e.g. , Calcibon , is as effective and safe as conventional PMMA-cement with regard to immediate and sustained pain reduction and improvement of mobility after kyphoplasty of patients with painful osteoporotic vertebral fractures . CaP cement has the potential of being resorbed and replaced by newly formed bone tissue ; thus , it seems to be a promising alternative for PMMA also in younger patients with painful vertebral fractures Abstract : In this prospect i ve study we investigated the predictive value of quantitative ultrasound ( QUS ) measurements and other potential predictors of osteoporotic fractures in the elderly . During a 1-year period , 710 participants ( 132 men and 578 women ) , aged 70 years and older ( mean age ± SD : 82.8 ± 5.9 ) , were recruited from seven homes and apartment houses for the elderly .  QUS measurements ( broadb and ultrasound attenuation ( BUA ) and speed of sound ( SOS ) )  were assessed with a clinical bone densitometer . A structured question naire was used to collect information on other potential predictors . Follow-up of fractures was done each half year by telephone interviews . During the study period ( median follow-up 2.8 years , maximum 3.7 years ) , 30 participants had a first hip fracture and 54 suffered from a first other nonspinal fracture . Cox regression analyses , adjusted for age and sex , showed that the relative risk ( RR ) of hip fracture for each st and ard deviation reduction was 2.3 ( 95 % CI , 1.4–3.7 ) for BUA and 1.6 ( 95 % CI , 1.1–2.3 ) for SOS . Slightly weaker relationships were found for any fracture ( BUA : RR , 1.6 ; 95 % CI , 1.2–2.1 ; SOS : RR , 1.3 ; 95 % CI , 1.0–1.6 ) . Multivariable analyses identified low BUA values and immobility as the strongest predictors for hip fractures and any fracture . Female gender proved to be the strongest predictor for other nonspinal fractures . It can be concluded that QUS measurements can predict the risk for hip fracture and any fracture in elderly people Osteoporosis is responsible for about 1.3 million fractures in the United States each year [ 1 ] . Further , recent research has shown that the risk for most types of fracture in elderly women is related to low bone mass ; thus , the public health impact of osteoporosis may , in fact , be much greater [ 2 ] and is projected to increase over the next several decades [ 3 ] . Postmenopausal estrogen replacement is the current recommended therapy for the prevention of osteoporosis [ 4 ] . However , the use of estrogen is not widespread among elderly women [ 5 ] . Clearly , more options for the prevention of osteoporosis and fracture need to be developed and explored . One option is the use of thiazide diuretics . Thiazide diuretics are known to reduce urinary excretion of calcium [ 6 , 7 ] and may also decrease bone resorption [ 6 ] and bone turnover [ 8 ] . The use of thiazide diuretics has been associated with a reduced risk for fracture , with risk ratios ranging from 0.3 to 0.8 [ 9 - 18 ] . For example , in a casecontrol study that excluded patients taking other drugs thought to affect bone mass , Ray and colleagues [ 15 ] found a 50 % reduction in the risk for hip fracture among patients who had used thiazide diuretics  for 6 years . In addition , LaCroix and colleagues [ 16 ] reported a 30 % lower risk for hip fracture in current users compared with nonusers . The Framingham Study also showed a lower risk for hip fracture among users of pure thiazide drugs when compared with those using agents that combined thiazide diuretics with other antihypertensive drugs [ 17 ] . However , all of these studies have been observational , which allows the possibility that users of thiazide diuretics have a lower risk for hip fracture because of other confounding factors . In addition , the more recent data of Heidrich and colleagues [ 19 ] conflict with these results . These investigators found a crude odds ratio for thiazide use and hip fracture of 1.1 , which is not statistically significant . However , when they adjusted for the potentially confounding effects of nursing-home residence ; previous hospitalizations ; history of stroke , alcoholism or organic brain syndrome ; body weight ; leg paralysis ; and use of phenobarbital , corticosteroids , or other diuretics , a significantly increased risk for hip fracture was found among women who reported current use of thiazide diuretics  [ 19 ] . No study has prospect ively evaluated the relation between thiazide diuretics and other types of fracture . The mechanism by which thiazide diuretics might protect against hip fracture is not known . Thiazide diuretics may decrease fracture risk by preserving bone mass [ 10 , 11 , 20 - 23 ] . Cross-sectional studies have shown that users of thiazide diuretics have slightly higher cortical and trabecular bone mass than nonusers . Two r and omized clinical studies of the effect of thiazide diuretics on bone loss had conflicting results [ 24 , 25 ] . If thiazide diuretics reduce the risk for hip fracture by slowing bone loss , then these agents should also protect against other types of fracture that are associated with reduced bone mass [ 2 ] . On the other h and , thiazide diuretics could increase the risk for fractures by increasing the risk for falls [ 26 ] . Thiazide diuretics might do this by causing dizziness or postural hypotension [ 27 ] , although the association of diuretic use with falling is not consistent [ 28 ] . More than 90 % of hip fractures are related to falls [ 29 ] . No previous study has included a comprehensive analysis of the effects of thiazide diuretics on bone mass , the risk for falls , and the risk for all fractures in a single population . In our prospect i ve study of 9704 women who were 65 years or older ( the Study of Osteoporotic Fractures ) , we assessed thiazide diuretic use and bone mass at baseline and conducted follow-up examinations every 4 months for the occurrence of fractures and falls . Methods Study Sample From September 1986 through October 1988 , women who were at least 65 years old were recruited for the Study of Osteoporotic Fractures in four areas of the United States : Portl and , Oregon ; Minneapolis , Minnesota ; Baltimore County , Maryl and ; and the Monongahela Valley region near Pittsburgh , Pennsylvania . Age-eligible women were recruited through several sources : health maintenance organizations ; lists of residents that had been compiled for other epidemiologic studies ; jury- selection lists ; voter- registration lists ; and lists of driver 's license holders [ 30 ] . We excluded black women because of their lower incidence of fractures , women who were unable to walk without the assistance of another person , and women who had bilateral hip replacements . Measurement of Bone Mass Bone mineral content ( g/cm ) and density ( g/cm2 ) were measured using single-photon absorptiometry ( OsteoAnalyzer , Siemens-Osteon , Wahiawa , Hawaii ) . Details of these methods have been reported elsewhere [ 30 ] . We scanned three sites : the distal radius , the proximal radius , and the calcaneus . The distal radius is composed of about 60 % cortical bone and 40 % trabecular bone , the proximal radius is about 99 % cortical bone [ 31 ] , and the calcaneus is about 97 % trabecular bone [ 32 ] . The reproducibility of the bone mass measurements , expressed as coefficients of variation , ranged from 1.3 % to 2.0 % among individuals and from 0.4 % to 1.2 % among scanners [ 30 ] . Diuretic Use Information on diuretic use was obtained at the baseline clinic interview . Participants were asked to bring all current medications to the clinic for verification . In addition , pictures of tablets were presented to participants to assist them in the re collection of previously prescribed diuretics . Diuretics , including combination drugs , were classified as thiazide diuretics according to the American Medical Association drug evaluations [ 33 ] . Separate histories were obtained from participants for use of thiazide and nonthiazide diuretics . Chlorthalidone was classified as a thiazide diuretic because its effects on calcium excretion are similar to those of thiazide diuretics . Analyses in which chlorthalidone was not considered as a thiazide diuretic yielded similar results . Women were asked whether they had ever taken diuretics ; at what age they had started taking diuretics ; whether they were currently using diuretics and , if not , when they had stopped ; whether they took diuretics the entire time or stopped for a few years ; and the name of the medication they were currently using . Duration of diuretic use was calculated as the total number of years that they reported using diuretics . No information was collected on dose at the baseline visit , but dose-related data were recorded at the first annual telephone interview . Information on duration of thiazide diuretic use was missing in 15 women . These women were excluded from all analyses . Other Measurements Reported health status , type of menopause , alcohol consumption , and cigarette smoking were assessed using a question naire that was review ed with the participant by a trained interviewer . Women were considered to have had a surgical menopause if they reported having had a bilateral oophorectomy at the age at which they stopped menstruating . Regarding alcohol consumption , participants were asked how much they had consumed during the past 30 days and how many times they had consumed three or more drinks per day and five or more drinks per day during the past 30 days . The measure of alcohol consumption used in our study was drinks per week , which was adjusted for atypical drinking , particularly heavy drinking over the last 30 days .  Dietary calcium  was assessed by a food frequency question naire and an interview using st and ardized food models to estimate portion sizes [ 34 ] . In our study , total calcium intake included dietary and supplemental calcium . Women were also asked if they had ever taken the following medications : thyroid hormones , medicine for seizures , vitamin D or multivitamins containing vitamin D , TUMS , calcium supplements , antacids , prednisone , cortisone , other steroid pills , birth control pills , estrogen pills , estrogen skin patches , estrogen vaginal cream or suppositories , estrogen injections , and progestins . Information was obtained on current use , duration of use , and specific drug and dosage used for the longest period . Functional status was measured by a respondent 's answers to questions about her ability to perform six instrumental activities of daily living by herself and without using special aids or equipment . These activities were as follows : walking two or three blocks outside on level ground ; climbing up 10 steps without stopping ; walking down 10 steps ; preparing one 's own meals ; doing heavy housework ; and doing one 's own shopping for groceries or clothes . The measure used in these analyses is the total number of activities ( ranging from 0 to 6 ) that a woman reported she was unable to do or had difficulty doing . Additionally , women were asked to rate their health status as very good , good , fair , poor , or very poor . During the clinic examination , body weight was measured ( after removal of shoes and heavy outer clothing ) using a balance beam scale . Height was measured ( after removal of shoes ) using a Harpenden stadiometer ( Holtain , Ltd. , Dyved , United Kingdom ) . Height and weight were used to calculate the body mass index ( kg/m2 ) . Ascertainment of Prevalent Vertebral Deformities The prevalence of vertebral deformities as shown by lateral thoracic and lumbar spine films was obtained on 2992 women ( 31 % of the cohort ) who were between 65 and 70 years old . The methods used to identify vertebral deformities have been described previously [ 35 ] . In summary , six points for each vertebral body , T4 through L4 , were marked with a translucent digitizer . We calculated three heights ( anterior , posterior , and middle ) and three ratios : anterior-to-posterior height ( wedge ) ; mid-to-posterior height ( endplate ) ; and the posterior height of each vertebra to the posterior height of the adjacent vertebrae ( crush ) . We classified a vertebral body BACKGROUND Physical activity has been related to reduced risk of osteoporotic hip fractures , but the evidence among men is weak . OBJECTIVE To determine the association between baseline leisure physical activity and future risk of osteoporotic hip fracture in men . METHODS At baseline in 1975 our prospect i ve study cohort included 3,262 men who were 44 years or older and did not have chronic disease restricting their ability to exercise .  At baseline , physical activity was assessed by a question naire . Hip fractures were followed for 21 years , or from the age of 50 years for subjects who were initially younger than 50 years . RESULTS The hazard ratio of osteoporotic hip fracture , adjusted for other possible predictors ( height , body mass index , baseline diseases , smoking , use of alcohol , work-related physical activity , and occupational group ) , in men participating in vigorous physical activity compared with men not participating was 0.38 ( 95 % confidence interval , 0.16 - 0.91 ) ( P = .03 ) . CONCLUSION These results provide further evidence that there is an inverse association between baseline physical activity  and future hip fracture risk among men Introduction : Chronic mild endogenous glucocorticoid excess has been shown to cause bone loss and to increase fracture risk in both post-menopausal and premenopausal women . Currently , it is unclear if patients with sub clinical Cushing ’s syndrome ( SCS ) with osteoporosis or osteopenia may benefit from antiresorptive treatment and the type of therapy to be given . Objective : This pilot r and omized study was aim ed at evaluating the effects of 12-month i m administration of clodronate ( 100 mg every week ) on vertebral and femoral bone mineral density ( BMD ) , bone turnover markers and on subjective pain in premenopausal women with SCS due to adrenal incidentalomas . Methods : Forty-six women ( age , 43.1 ±7.7 yr ) with SCS due to adrenal incidentaloma and osteoporosis/osteopenia were r and omized to receive clodronate plus supplement of Calcium ( 500 mg daily ) and Vitamin D3 ( 800 mg daily ) ( group 1 , no.=23 ) or supplements only ( group 2 , no.=23 ) . Both groups were similar in terms of age , body mass index , cortisol levels , BMD values , and bone turnover markers . All of the women were re-evaluated after 12 months . Results : After 12 months of treatment , in group 1 , a significant increase in lumbar BMD occurred ( p=0.04 ) , while bone turnover markers decreased by about one third ( p<0.05 ) . In group 2 , bone turnover markers did not change and BMD values slightly decreased ( p = ns ) . The differences in bone turnover markers and in lumbar BMD between the two groups were significant ( p<0.05 , all ) . No new vertebral fracture occurred in group 1 , while in group 2 the spine radiographies revealed 2 new fractures and a worsening of two pre-existent fractures . An improvement in subjective back pain , assessed by visual analogue scale pain score was observed in group 1 ( from 4.3±2.7 to 2.9±2.0 ; p<0.05 ) but not in group 2 ( from 4.4±3.1 to 4.2±3.4 ; p = ns ) . No significant changes occurred in cortisol secretion or clinical picture of the SCS during the study . Conclusions : Intramuscular administration of clodronate effectively increased lumbar BMD values , preserved bone mass at the femoral neck , stabilized vertebral fracture index , and decreased subjective back pain in pre-menopausal women with SCS . Since the untreated group continued to lose bone , antiresorptive treatment should be considered in patients with SCS , according to the prevision of surgical treatment , prevalent fractures , BMD values , age , concomitant morbidities , and desire for pregnancy BACKGROUND Physical activity may play a role in preventing gallstone disease . METHODS The activity/gallstone relationship was examined in post-menopausal women from the Study of Osteoporotic Fractures ( SOF ; 1986 - 1988 ) , a prospect i ve study of fracture risk factors in 8010 women ( mean age = 71.1 years , SD = 4.9 ) . RESULTS Multivariate logistic regression indicated women in the lowest two quartiles of physical activity , according to question naire , had a 59 % { OR = 1.59 ( 1.11 - 2.29 ) , P = 0.02 } and a 57 % higher risk { OR = 1.57 ( 1.11 - 2.23 ) , P = 0.01 } of developing gallstone disease compared to women in the highest quartile of activity ( PTrend = < 0.0001 ) . Additionally , this relationship was examined in a cohort of 182 post-menopausal women ( mean age 74.2 years , SD = 4.1 ) who participated in a r and omized controlled trial of a walking intervention . Women in the r and omized clinical trial in the lowest tertile of  physical activity  determined by a physical activity monitor had a higher risk of developing gallstone disease than women in the highest tertile of physical activity , 13 % { OR-1.13 ( 1.01 - 1.28 ) , P = 0.05 , PTrend = < 0.04}. CONCLUSION Physical activity appears to be inversely related to the development of gallstone disease  in post-menopausal women independent of body mass index BACKGROUND Seasonal Affective Disorder ( SAD ) is a sub-type of depression that only occurs during the winter months . A reduction in vitamin D may be linked to SAD . Since vitamin D deficiency has been reported to be common in older people , vitamin D supplementation may be expected to reduce seasonal mood disturbance in this group . OBJECTIVE To assess the effect of vitamin D supplementation on the mental health of older women . SETTING Primary care in three areas of the UK ( Herts , Newcastle , York ) . SUBJECTS Women aged 70 years or more recruited to the trial in the months May-October . INTERVENTION Eligible women were r and omised to receive calcium and vitamin D supplementation or no supplementation . OUTCOME MEASURE At baseline and the six monthly assessment the mental component score ( MCS ) , calculated from the SF-12 question naire was used to assess participants ' subjective psychological well-being . RESULTS A total of 2117 women recruited to the trial had their baseline measures taken between the months of May-October ( 1205 woman in the control group and 912 women in the intervention group ) . Of these women , 1621 had a  MCS score at baseline and six months . Comparison of the six month mean MCS scores , adjusting for baseline MCS score and age , showed there was no significant difference between the two scores ( p = 0.262 ) . CONCLUSIONS Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores OBJECTIVES The Women 's Health Initiative ( WHI ) r and omized trial of calcium/vitamin D supplementation found reduced bone loss with active treatment compared to placebo . Now we examine whether the treatment affected self-reported physical functioning and objective measures of physical functioning . DESIGN A r and omized , double-blind , placebo-controlled trial of 1,000 mg calcium carbonate plus 400 IU vitamin D(3 ) per day or matching placebo pills . SUBJECTS/ SETTING The study included 33,067 women ( 50 to 79 years old ) at 40 US study centers . MAIN OUTCOME MEASURES Physical functioning was assessed by question naire at enrollment in WHI , 1 year prior to calcium/vitamin D trial r and omization and at study close-out ( average follow-up 7.1 years ) . Objective physical performance and self-reported exercise measures were collected at WHI baseline ( 1 year prior to calcium/vitamin D enrollment ) and 2 years and 4 years after calcium/vitamin D trial enrollment in a sub sample ( n=3,137 ) . STATISTICAL ANALYSES PERFORMED Calcium/vitamin D effects were tested in unadjusted and interaction linear models for each of the physical function measures . Covariates were baseline total calcium intake , fracture risk score , treatment arm in the hormone therapy and dietary modification trials ( ie , active drug or placebo , low-fat diet intervention or usual diet , respectively ) and age . RESULTS Neither intention to treat nor high adherence analyses produced substantial effects of calcium/vitamin D  compared to placebo on physical functioning or performance . The interaction analyses also did not result in differences because of calcium/vitamin D. CONCLUSIONS As the first long-term r and omized trial to examine the effectiveness of calcium and vitamin D in protecting against decline of physical functioning in older women , the results did not support benefit Hormone replacement therapy ( HRT ) is often prescribed for a few years to suppress menopausal symptoms . Although its long-term use of HRT for the primary prevention of osteoporosis is not currently recommended , the long-term skeletal benefits of the limited therapy are of great interest . To determine whether administration of HRT for 2 - 3 years in the early postmenopausal years provides long-term benefits , such as prevention of bone loss and osteoporotic fractures , we studied a group of 347 healthy postmenopausal women with normal bone mass who had earlier completed one of four placebo-controlled HRT trials and who were reexamined 5 , 11 , or 15 years after stopping HRT .  Of these women , 263 received either  HRT or placebo for 2 - 3 years with no further bone-sparing treatment until follow-up , and the remaining 84 women reported either prolonged or current use of HRT at reexamination . Bone mineral density ( BMD ) at the spine ( L1-L4 ) and bone mineral content ( BMC ) in the forearm were measured at baseline , the end of the trials , and follow-up . At follow-up , we assessed the radiological presence of vertebral fracture and collected information on the new incidence of nonvertebral fractures . Compared with that of the placebo-treated women , the BMD and BMC of HRT-treated women continued to show significantly higher values ( > 5 % ) even many years after stopping HRT . After stopping treatment , the rate of bone loss returned to normal postmenopausal rates . The preservation of bone mass in the HRT group was accompanied by a significantly reduced risk of all osteoporotic fractures as compared with the placebo group [ OR = 0.48 ( 95 % CI , 0.26 - 0.88 ) ] . ' Fast losers ' on placebo had more than a 4-fold higher risk of fractures than had the women on limited HRT with a normal rate of bone loss after withdrawal . In conclusion , limited HRT administered in the early postmenopausal years offers long-lasting benefits for the prevention of postmenopausal bone loss and osteoporotic fracture BACKGROUND Physical activity has been related to enhanced bone mass and improved physical functioning and thus may reduce the risk for osteoporotic fracture .  OBJECTIVE To determine whether higher levels of physical activity are related to lower incidence of  hip , wrist , and vertebral fractures . DESIGN Prospect i ve cohort study . SETTING Four clinical centers in Baltimore , Maryl and ; Portl and , Oregon ; Minneapolis , Minnesota ; and the Monongahela Valley , Pennsylvania . PARTICIPANTS 9704 nonblack women 65 years of age or older . MEASUREMENTS  Physical activity  was assessed by question naire at baseline . Hip and wrist fractures were followed for an average of 7.6 years . The incidence of vertebral fracture was determined morphometrically by using radiography at baseline and an average of 3.7 years later . RESULTS Higher levels of leisure time , sport activity , and household chores and fewer hours of sitting daily were associated with a significantly reduced relative risk for hip fracture after adjustment for age , dietary factors , falls at baseline , and functional and health status . Very active women ( fourth and fifth quintiles ) had a statistically significant 36 % reduction in hip fractures ( relative risk , 0.64 [ 95 % CI , 0.45 to 0.891 ) compared with the least active women ( lowest quintile ) . The intensity of physical activity  was also related to fracture risk : Moderately to vigorously active women had statistically significant reductions of 42 % and 33 % in risk for hip and vertebral fractures , respectively , compared with inactive women . Total physical activity , hours of household chores per day , and hours of sitting per day were not significantly associated with wrist or vertebral fractures . CONCLUSIONS Among older community-dwelling women , physical activity is associated with a reduced risk for hip fracture but not wrist or vertebral fracture BACKGROUND Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospect i ve study . METHODS We assessed potential risk factors , including bone mass , in 9516 white women 65 years of age or older who had had no previous hip fracture . We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture . All reports of hip fractures were vali date d by review of x-ray films . RESULTS During the follow-up period , 192 women had first hip fractures not due to motor vehicle accidents . In multivariable age-adjusted analyses , a maternal history of hip fracture doubled the risk of hip fracture ( relative risk , 2.0 ; 95 percent confidence interval , 1.4 to 2.9 ) , and the increase in risk remained significant after adjustment for bone density . Women who had gained weight since the age of 25 had a lower risk . The risk was higher among women who had previous fractures of any type after the age of 50 , were tall at the age of 25 , rated their own health as fair or poor , had previous hyperthyroidism , had been treated with long-acting benzodiazepines or anticonvulsant drugs , ingested greater amounts of caffeine , or spent four hours a day or less on their feet . Examination findings associated with an increased risk included the inability to rise from a chair without using one 's arms , poor depth perception , poor contrast sensitivity , and tachycardia at rest . Low calcaneal bone density was also an independent risk factor . The incidence of hip fracture ranged from 1.1 ( 95 percent confidence interval , 0.5 to 1.6 ) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 ( 95 percent confidence interval , 20 to 34 ) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age . CONCLUSIONS Women with multiple risk factors and low bone density have an especially high risk of hip fracture . Maintaining body weight , walking for exercise , avoiding long-acting benzodiazepines , minimizing caffeine intake , and treating impaired visual function are among the steps that may decrease the risk BACKGROUND Low-energy fractures of the hip , forearm , shoulder , and spine are known consequences of osteoporosis . OBJECTIVE We evaluated the effect of 1 y of treatment with calcium and vitamin D on bone mineral density ( BMD ) and bone markers in patients with a recent low-energy fracture . DESIGN In a double-blinded design , patients with fracture of the hip ( lower-extremity fracture , or LEF ) or upper extremity ( UEF ) were r and omly assigned to receive 3000 mg calcium carbonate + 1400 IU cholecalciferol or placebo ( 200 IU cholecalciferol ) . BMD of the hip ( HBMD ) and lumbar spine ( LBMD ) were evaluated by dual-energy X-ray absorptiometry , and physical performance was assessed by the timed Up & Go test . Serum concentrations of 25-hydroxycholecalciferol , parathyroid hormone ( PTH ) , telepeptide of type I collagen ( ICTP ) , osteocalcin , and N-terminal propeptide of collagen type I were measured . RESULTS A total of 122 patients were included ( 84 % women ; x + /- SD age : 70 + /- 11 y ) ; 68 % completed the study . In an intention-to-treat analysis , LBMD increased in the intervention group and decreased in the placebo group , and the difference between the groups was significant after 12 mo : 0.931 + /- 0.211 compared with 0.848 + /- 0.194 ( P<0.05 ) . No significant change was shown for HBMD . The effect of treatment was more pronounced in patients aged < 70 y. The intervention decreased bone turnover . PTH was significantly lower in the intervention group ( P<0.01 ) for the LEF patients . ICTP and change in LBMD were significantly related to physical performance . CONCLUSIONS A 1-y intervention with calcium and vitamin D reduced bone turnover , significantly increased BMD in patients younger than 70 y , and decreased bone loss  in older patients . The effect of treatment was related to physical performance UNLABELLED The role of protein intake in osteoporosis is unclear . In a case-control study in Utah ( n = 2501 ) , increasing level of protein intake was associated with a decreased risk of hip fracture in men and women 50 - 69 years of age but not in those 70 - 89 years of age . Protein intake may be important for optimal bone health . INTRODUCTION Protein is an important component of bone , but the role of dietary protein intake in osteoporosis and fracture risk remains controversial . MATERIAL AND METHODS The role of dietary protein intake in osteoporotic hip fracture was evaluated in a statewide case-control study in Utah . Patients , 50 - 89 years of age , with hip fracture ( cases ) were ascertained through surveillance of 18 Utah hospitals during 1997 - 2001 . Age- and gender-matched controls were r and omly selected . Participants were interviewed in their place of residence , and diet was assessed using a picture-sort food frequency question naire previously reported to give a useful measure of usual dietary intake in the elderly Utah population . The association between  protein intake  and risk of hip fracture was examined across quartiles of protein intake and stratified by age group for 1167 cases ( 831 women , 336 men ) and 1334 controls ( 885 women , 449 men ) . RESULTS In logistic regression analyses that controlled for gender , body mass index , smoking status , alcohol use , calcium , vitamin D , potassium , physical activity , and estrogen use in women , the odds ratios ( OR ) of hip fracture decreased across increasing quartiles of total protein intake for participants 50 - 69 years of age ( OR : 1.0 [ reference ] ; 0.51 [ 95 % CI : 0.30 - 0.87 ] ; 0.53 [ 0.31 - 0.89 ] ; 0.35 [ 0.21 - 0.59 ] ; p < 0.001 ) . No similar associations were observed among participants 70 - 89 years of age . Results from analyses stratified by low and high calcium and potassium intake did not differ appreciably from the results presented above . CONCLUSION Higher total protein intake was associated with a reduced risk of hip fracture in men and women 50 - 69 years of age but not in men and women 70 - 89 years of age . The association between  dietary protein intake  and risk of hip fracture may be modified by age . Our study supports the hypothesis that adequate dietary protein is important for optimal bone health in the elderly 50 - 69 years of age OBJECTIVES To assess the effect of between-meal weekly risedronate and daily calcium 630 mg and vitamin D 400 IU on bone turnover markers . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Skilled nursing home ( NH ) . PARTICIPANTS Sixty skilled-NH residents ( 46 men , 14 women ) , mean age+/-st and ard deviation of 76+/-6 , were r and omized to receive risedronate 30 mg ( n=31 ) or matching placebo ( n=29 ) once weekly for 12 weeks . All received 315 mg calcium with 200 IU vitamin D twice daily . MEASUREMENTS Bone-specific alkaline phosphatase ( BSAP ) , N-telopeptide of type 1 collagen ( NTx ) , 25-hydroxyvitamin D ( 25OHD ) , and parathyroid hormone were measured at baseline and 6 and 12 weeks . RESULTS Risedronate reduced BSAP significantly more than placebo ( P<.05 ) at 6 weeks but not at 12 weeks ; no treatment effect on serum NTx was observed . Defining hypovitaminosis D as a serum 25OHD concentration below 32 ng/mL , 50 of 53 ( 94 % ) study participants were low at baseline ( mean 25OHD 19 ng/mL ) . Vitamin D levels remained insufficient in 74 % of participants after 12 weeks . CONCLUSION In this NH population , weekly risedronate administered using a between-meal dosing schedule reduced serum BSAP at 6 weeks of treatment ; this effect was not observed at 12 weeks . The overall lack of change in bone turnover markers suggests that this risedronate dose and schedule would not be expected to increase bone density or reduce fracture risk in this population . Hypovitaminosis D was common and not reliably corrected by 400 IU of vitamin D daily . Despite an extremely high osteoporotic fracture risk in NH residents , additional study is required to determine under which conditions pharmacological treatment is efficacious in this population and define approaches that assure vitamin D repletion OBJECTIVES To determine the efficacy and safety of high-dose vitamin D supplementation for prevention of acute respiratory infection ( ARI ) in older long-term care residents . DESIGN R and omized controlled trial investigating high-dose vs st and ard-dose vitamin D from 2010 to 2014 . SETTING Colorado long-term care facilities . PARTICIPANTS Long-term care residents aged 60 and older ( n = 107 ) . INTERVENTION The high-dose group received monthly supplement of vitamin D3 100,000 IU , the st and ard-dose group received a monthly placebo ( for participants taking 400 - 1,000 IU/d as part of usual care ) or a monthly supplement of 12,000 IU of vitamin D3 ( for participants taking < 400 IU/d as part of usual care ) . MEASUREMENTS The primary outcome was incidence of ARI during the 12-month intervention . Secondary outcomes were falls and fractures , 25-hydroxyvitamin D levels , hypercalcemia , and kidney stones . RESULTS Participants ( 55 high dose , 52 st and ard dose ) were r and omized and included in the final analysis . The high-dose group had 0.67 ARIs per person-year and the st and ard-dose group had 1.11 ( incidence rate ratio ( IRR ) = 0.60 , 95 % confidence interval ( CI ) = 0.38 - 0.94 , P = .02 ) . Falls were more common in the high-dose group ( 1.47 per person-year vs 0.63 in st and ard-dose group ; IRR = 2.33 , 95 % CI = 1.49 - 3.63 , P < .001 ) . Fractures were uncommon and similar in both groups ( high dose 0.10 vs st and ard dose 0.19 per person-year ; P = .31 ) . Mean trough 25-hydroxyvitamin D levels during the trial were 32 . ng/mL in the high-dose group and 25.1 ng/mL in the st and ard-dose group . There was no hypercalcemia or kidney stones in either group . CONCLUSION Monthly high-dose vitamin D3 supplementation reduced the incidence of ARI in older long-term care residents but was associated with a higher rate of falls without an increase in fractures A novel T/C polymorphism ( ATG to ACG ) at the translation initiation site of the vitamin D receptor ( VDR ) gene , defined by FokI restriction endonuclease , has been recently associated with variation in bone mineral density ( BMD ) and rates of bone loss in a group of postmenopausal Mexican-American women . The presence of the restriction site , design ated as f , allows protein translation to initiate from the first ATG , while the allele lacking the site , indicated as F , initiates translation at a second ATG . In this study , we investigated the role of FokI polymorphism in a group of 400 postmenopausal women of Italian descent stratified for BMD into osteoporotic ( n = 164 ) , osteopenic ( n = 117 ) , and normal ( n = 119 ) groups . There were 159 ( 41 % ) FF homozygotes , 55 ( 14 % ) ff homozygotes , and 186 ( 45 % ) Ff heterozygotes . In the whole population , we observed a weak association between FokI polymorphism and lumbar BMD ( p = 0.06 , analysis of covariance [ ANCOVA ] ) but not with femoral neck BMD ( p = 0.5 , ANCOVA ) . Interestingly , the effect of FokI genotypes on lumbar BMD was influenced by the years since menopause such that differences in BMD related to different VDR allelic variants were greater among women in the first 5 years of menopause ( p = 0.04 , ANCOVA ) , progressively declining afterward . In addition , a significantly higher prevalence of ff genotype in osteoporotic than in osteopenic and normal women was observed ( p = 0.04 , Chi-square test ) . Finally , ff genotype result ed significantly over-represented in the group of women with a vertebral fracture as compared with controls ( p = 0.003 , Chi-square test ) , equivalent to a relative risk of 2.58 ( 95 % confidence intervals 1.36 - 4.91 ) . We conclude that in this population , FokI polymorphism at the VDR gene locus accounts for a part of the heritable component of BMD at the lumbar spine UNLABELLED A 3-year prospect i ve , r and omized , placebo-controlled trial of oral clodronate 800 mg showed that the incidence of clinical fractures was decreased by 20 % in 5596 elderly women unselected for osteoporosis . The effect occurred in the absence of systematic calcium and vitamin D supplementation and was observed across a wide range of BMDs . INTRODUCTION To date , most studies with bisphosphonates have reported on their use in individuals selected to be at high risk for fracture usually by the presence of low BMD or a prior fragility fracture , usually of the spine . We wished to determine the effect of the bisphosphonate , clodronate , on the rate of fractures in women > or = 75 years of age living in the community . MATERIAL S AND METHODS Women > or = 75 years of age living in the general community in South Yorkshire and North Derbyshire , identified from general practice registers , were recruited by letter of invitation to a r and omized , double-blind , controlled trial of 800 mg oral clodronate ( Bonefos ) or matching placebo daily over 3 years . The main outcomes were the incidences of hip and any clinical fracture . RESULTS Of the 5579 elderly women included in the intention-to-treat analysis of efficacy , 114 had a new hip fracture during the 3-year treatment phase : 56 ( 2.0 % ) women in the clodronate group and 58 ( 2.1 % ) women in the placebo group ( hazard ration [ HR ] , 1.02 ; 95 % CI , 0.71 - 1.47 ) . Clodronate did , however , decrease the incidence of any clinical fracture by 20 % ( 264 women [ 9.5 % ] versus 337 [ 12.1 % ] in the placebo group ; HR , 0.80 ; 95 % CI , 0.68 - 0.94 ) . The incidence of osteoporosis-associated nonhip fractures was also significantly decreased by 29 % ( 5.2 % versus 7.4 % ; HR , 0.71 ; 95 % CI , 0.57 - 0.87 ) . The ability of clodronate to reduce the risk of osteoporotic fracture was independent of baseline BMD , but the number needed-to-treat was lower in the presence of osteoporosis . CONCLUSIONS Oral daily clodronate can prevent fractures without significant adverse effects in elderly women living in the general community . The effect on hip fracture risk is not significant , but an effect similar to that at other nonvertebral sites can not be excluded . This study suggests that antiresorptive therapies can reduce fracture incidence in high-risk individuals even in the presence of a normal or osteopenic BMD Importance Evidence suggests that low vitamin D status may increase the risk of cancer . Objective To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of  cancer among older women . Design , Setting , and Participants A 4-year , double-blind , placebo-controlled , population -based r and omized clinical trial in 31 rural counties ( June 24 , 2009 , to August 26 , 2015—the final date of follow-up ) . A total of 2303 healthy postmenopausal women 55 years or older were r and omized , 1156 to the treatment group and 1147 to the placebo group . Duration of treatment was 4 years . Interventions The treatment group ( vitamin D3 + calcium group ) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium ; the placebo group received identical placebos . Main Outcomes and Measures The primary outcome was the incidence of all-type cancer ( excluding nonmelanoma skin cancers ) , which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling . Results Among 2303 r and omized women ( mean age , 65.2 years [ SD , 7.0 ] ; mean baseline serum 25-hydroxyvitamin D level , 32.8 ng/mL [ SD , 10.5 ] ) , 2064 ( 90 % ) completed the study . At year 1 , serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group . A new diagnosis of cancer was confirmed in 109 participants , 45 ( 3.89 % ) in the vitamin D3 + calcium group and 64 ( 5.58 % ) in the placebo group ( difference , 1.69 % [ 95 % CI , −0.06 % to 3.46 % ] ; P = .06 ) . Kaplan-Meier incidence over 4 years was 0.042 ( 95 % CI , 0.032 to 0.056 ) in the vitamin D3 + calcium group and 0.060 ( 95 % CI , 0.048 to 0.076 ) in the placebo group ; P = .06 . In unadjusted Cox proportional hazards regression , the hazard ratio was 0.70 ( 95 % CI , 0.47 to 1.02 ) . Adverse events potentially related to the study included renal calculi ( 16 participants in the vitamin D3 + calcium group and 10 in the placebo group ) , and elevated serum calcium levels ( 6 in the vitamin D3 + calcium group and 2 in the placebo group ) . Conclusions and Relevance Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL , supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years . Further research is necessary to assess the possible role of vitamin D in cancer prevention . Trial Registration clinical trials.gov Identifier : Summary Guidelines suggest identification of women at fracture risk by bone density measurement and subsequently pharmacotherapy . However , most women who sustain a hip fracture do not have osteoporosis in terms of bone density . The present non-pharmacological intervention among elderly women unselected for osteoporosis reduced hip fracture risk by 55 % providing an alternative approach to fracture prevention . Introduction Hip fractures are expensive for society and cause disability for those who sustain them . We studied whether a multifactorial non-pharmacological prevention program reduces hip fracture risk in elderly women . Methods A controlled trial concerning 60- to 70-year-old community-dwelling Finnish women was undertaken . A r and om sample was drawn from the Population Information System and assigned into the intervention group ( IG ) and control group ( CG ) . Of the 2,547 women who were invited to the IG , 1,004 ( 39 % ) and of the 2,120 invited to the CG , 1,174 ( 55 % ) participated . The IG participated in a fracture prevention program for 1 week at a rehabilitation center followed by review days twice . The CG received no intervention . During the 10-year follow-up , both groups participated in survey question naire by mail . Outcome of interest was occurrence of hip fractures and changes in bone – health-related lifestyle . Results During the follow-up , 12 ( 1.2 % ) women in the IG and 29 ( 2.5 % ) in the CG sustained a hip fracture ( P = 0.039 ) . The determinants of hip fractures by stepwise logistic regression were baseline smoking ( odds ratio ( OR ) 4.32 ( 95 % confidence interval [ CI ] 2.14–8.71 ) , age OR 1.15/year ( 95 % CI 1.03–1.28 ) , fall history OR 2.7 ( 95 % CI 1.24–5.9 ) , stroke history OR 2.99 ( 95 % CI 1.19–7.54 ) and participating in this program OR 0.45 ( 95 % CI 0.22–0.93 ) . Starting vitamin D and calcium supplement use was more common in the IG compared with the CG . Conclusions The results suggest that this non-pharmacological fracture prevention program may reduce the risk of hip fractures in elderly Finnish women BACKGROUND vitamin D supplementation reduces the incidence of fractures in older adults . This may be partly mediated by effects of vitamin D on neuromuscular function . OBJECTIVE to determine the effects of vitamin D supplementation on aspects of neuromuscular function known to be risk factors for falls and fractures . DESIGN r and omised , double-blind , placebo-controlled study . SETTING falls clinic taking referrals from general practitioners and accident and emergency department . SUBJECTS 139 ambulatory subjects ( > /=65 years ) with a history of falls and 25-hydroxyvitamin D ( 25OHD ) < /=12 microg/l . INTERVENTION patients were r and omised to receive a single intramuscular injection of 600,000 i.u . ergocalciferol or placebo . OUTCOME MEASURES assessment s including biochemistry , postural sway , choice reaction time ( CRT ) , aggregate functional performance time ( AFPT ) , and quadriceps strength were carried out at baseline and 6 months post-intervention . RESULTS baseline characteristics were comparable between both groups . 25OHD in the treatment group increased significantly at 6 months . AFPT deteriorated in the control group and improved in the intervention group , representing a significant difference between groups ( + 6.6 s versus -2.0 s , t = 2.80 , P < 0.05 ) . Similar changes were observed for CRT ( -0.06 s versus + 0.41 s , t = -2.52 , P < 0.01 ) and postural sway ( + 0.0025 versus -0.0138 , t = 2.35 , P < 0.02 ) . There was no significant difference in muscle strength change between groups ( -10 N versus -2 N , t = -1.26 , ns ) . A significant correlation between change in AFPT and change in 25OHD levels was observed ( r = 0.19 , P = 0.03 ) . There was no significant difference in the number of falls ( 0.39 versus 0.24 , t = 1.08 , P = 0.28 ) or fallers ( 14 versus 11 , P = 0.52 ) between two groups . CONCLUSIONS vitamin D supplementation , in fallers with vitamin D insufficiency , has a significant beneficial effect on functional performance , reaction time and balance , but not muscle strength . This suggests that vitamin D supplementation improves neuromuscular or neuroprotective function , which may in part explain the mechanism whereby vitamin D reduces falls and fractures Context : Denosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral , nonvertebral , and hip fracture in predominantly Caucasian postmenopausal women with osteoporosis . Objective : The objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo . Design and Setting : A r and omized , double-blind , placebo-controlled trial with an open-label active comparator as a referential arm was conducted . Patients : Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older , who had one to four prevalent vertebral fractures . Intervention : Subjects were r and omly assigned to receive denosumab 60 mg sc every 6 months ( n = 500 ) , placebo for denosumab ( n = 511 ) , or oral alendronate 35 mg weekly ( n = 251 ) . All subjects received daily supplements of calcium and vitamin D. Main Outcome Measure : The primary endpoint was the 24-month incidence of new or worsening vertebral fracture  for denosumab vs placebo . Results : Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7 % , with incidences of 3.6 % in denosumab and 10.3 % in placebo at 24 months ( hazard ratio 0.343 ; 95 % confidence interval 0.194–0.606 , P = .0001 ) . No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study . Conclusion : These results provide evidence of the efficacy and safety  of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis UNLABELLED In this 2-year r and omized controlled study of 167 men > 50 years of age , supplementation with calcium-vitamin D3-fortified milk providing an additional 1000 mg of calcium and 800 IU of vitamin D3 per day was effective for suppressing PTH and stopping or slowing bone loss at several clinical ly important skeletal sites at risk for fracture . INTRODUCTION Low dietary calcium and inadequate vitamin D stores have long been implicated in age-related bone loss and osteoporosis . The aim of this study was to assess the effects of calcium and vitamin D3 fortified milk on BMD in community living men > 50 years of age . MATERIAL S AND METHODS This was a 2-year r and omized controlled study in which 167 men ( mean age + /- SD , 61.9 + /- 7.7 years ) were assigned to receive either 400 ml/day of reduced fat ( approximately 1 % ) ultra-high temperature ( UHT ) milk containing 1000 mg of calcium plus 800 IU of vitamin D3 or to a control group receiving no additional milk . Primary endpoints were changes in BMD , serum 25(OH)D , and PTH . RESULTS One hundred forty-nine men completed the study . Baseline characteristics between the groups were not different ; mean dietary calcium and serum 25(OH)D levels were 941 + /- 387 mg/day and 77 + /- 23 nM , respectively . After 2 years , the mean percent change in BMD was 0.9 - 1.6 % less in the milk supplementation compared with control group at the femoral neck , total hip , and ultradistal radius ( range , p < 0.08 to p < 0.001 after adjusting for covariates ) . There was a greater increase in lumbar spine BMD in the milk supplementation group after 12 and 18 months ( 0.8 - 1.0 % , p < or = 0.05 ) , but the between-group difference was not significant after 2 years ( 0.7 % ; 95 % CI , -0.3 , 1.7 ) . Serum 25(OH)D increased and PTH decreased in the milk supplementation relative to control group after the first year ( 31 % and -18 % , respectively ; both p < 0.001 ) , and these differences remained after 2 years . Body weight remained unchanged in both groups at the completion of the study . CONCLUSIONS Supplementing the diet of men > 50 years of age with reduced-fat calcium- and vitamin D3-enriched milk may represent a simple , nutritionally sound and cost-effective strategy to reduce  age-related bone loss  at several skeletal sites at risk for fracture in the elderly BACKGROUND . After the menopause , estrogen synthesis from and rogens and and rogen precursors by aromatase is the main source of circulating estrogens . AIM . To evaluate whether aromatase gene (CYP19)polymorphism affects circulating estradiol ( E[Formula : See Text])levels , bone mineral density ( BMD ) , BMD change or fracture risk . METHODS . A 5-year r and omized hormone replacement therapy ( HRT ) trial on 331 early postmenopausal women ( mean baseline age 52.7 ± 2.3 years ) . The participants consisted of two treatment groups : the HRT group ( n = 151 ) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D[Formula : See Text ] , 100 - 300 IU + 93 mg calcium as lactate/day , and the non-HRT group ( n = 180 ) received 93 mg calcium alone or in combination with vitamin D[Formula : See Text ] , 100 - 300 IU/day for 5 years . BMD was measured from lumbar spine and proximal femur ( DXA ) before and after the 5-year trial . All new symptomatic , radiographically defined fractures were recorded during the follow-up . The polymorphism ( intron 4 TTTA repeat ) of CYP19 was evaluated after PCR amplification of the polymorphic site . CYP19 polymorphism was divided into three repeat groups : short ( length of 7 or 8 in both alleles ; n = 135 ) , long ( length of 11 or higher in both alleles ; n = 47 ) , and medium ( rest of the values ; n = 149 ) . RESULTS . Of the baseline characteristics , only physical activity was associated with CYP19 polymorphism ( P = 0.04 ) and a borderline significance was observed with previous fractures ( P = 0.05 ) . In the HRT or non-HRT groups , the 5-year serum E[Formula : See Text ] change was not associated with CYP19 polymorphism ( P = 0.87 and 0.74 , respectively ) . Further , the polymorphism did not influence the calculated annual changes of lumbar or femoral neck BMD during the 5-year follow-up in the HRT ( P = 0.60 and 0.17 , respectively ) or non-HRT ( P = 0.92 and 0.80 , respectively ) groups . In all , 28 women sustained 33 fractures during the follow-up . The CYP19 polymorphism was not significantly associated with fracture risk ( P = 0.89 and 0.23 respectively ; Cox proportional hazards model ) in the HRT or non-HRT groups . CONCLUSIONS .CYP19 polymorphism was not associated with circulating E[Formula : See Text ] levels , BMD values , or fracture risk in these early postmenopausal Finnish women . If such an association exists in women , it may become apparent in older age groups BACKGROUND Very high plasma homocysteine levels are characteristic of homocystinuria , a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis . We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures . METHODS We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects , 55 years of age or older , who participated in two separate prospect i ve , population -based studies . In the Rotterdam Study , there were two independent cohorts : 562 subjects in cohort 1 , with a mean follow-up period of 8.1 years ; and 553 subjects in cohort 2 , with a mean follow-up period of 5.7 years . In the Longitudinal Aging Study Amsterdam , there was a single cohort of 1291 subjects , with a mean follow-up period of 2.7 years . Multivariate Cox proportional-hazards regression models were used for analysis of the risk of fracture , with adjustment for age , sex , body-mass index , and other characteristics that may be associated with the risk of fracture or with increased homocysteine levels . RESULTS During 11,253 person-years of follow-up , osteoporotic fractures occurred in 191 subjects . The overall multivariable-adjusted relative risk of fracture was 1.4 ( 95 percent confidence interval , 1.2 to 1.6 ) for each increase of 1 SD in the natural-log-transformed homocysteine level . The risk was similar in all three cohorts studied , and it was also similar in men and women . A homocysteine level in the highest age-specific quartile was associated with an increase by a factor of 1.9 in the risk of fracture ( 95 percent confidence interval , 1.4 to 2.6 ) . The associations between homocysteine levels and the risk of fracture appeared to be independent of bone mineral density and other potential risk factors for fracture . CONCLUSIONS An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women
There is high quality evidence that vitamin D plus calcium is associated with a statistically significant reduction in incidence of new non-vertebral fractures .
Vitamin D alone is unlikely to prevent fractures in the doses and formulations tested so far in older people .
Supplements of vitamin D and calcium may prevent hip or any type of fracture .
There was a small but significant increase in gastrointestinal symptoms and renal disease associated with vitamin D and calcium .
This review found that there was no increased risk of death from taking calcium and vitamin
BACKGROUND Vitamin D and related compounds have been used to prevent  osteoporotic fractures in older people .
This is the third up date of a Cochrane review first published in 1996 .
OBJECTIVES To determine the effects of vitamin D or related compounds , with or without calcium , for preventing  fractures in post-menopausal women and older men .