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 high-dose vitamin D3 supplementation on bone mineral density in subjects with prediabetes Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study No significant effect on bone mineral density by high doses of vitamin D3 given to overweight subjects for one year Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. 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 Factors Affecting Bone Loss in Female Endurance Athletes Vitamin D Supplementation and Fracture Incidence in Elderly Persons Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women Exercise and vitamin D in fall prevention among older women: a randomized clinical trial. Prevention of hip fractures by correcting calcium and vitamin D insufficiencies in elderly people. Estimation of the optimum dose of vitamin D for disease prevention in older people: Rationale, design and baseline characteristics of the BEST-D trial Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease [RETRACTED] Vitamin D3 and calcium to prevent hip fractures in elderly women. The Effect of High-Dose Vitamin D Supplementation on Calciotropic Hormones and Bone Mineral Density in Obese Subjects with Low Levels of Circulating 25-Hydroxyvitamin D: Results from a Randomized Controlled Study Calcium plus vitamin D supplementation and the risk of fractures. Positive effects of anabolic steroids, vitamin D and calcium on muscle mass, bone mineral density and clinical function after a hip fracture. A randomised study of 63 women. Vitamin D receptor gene polymorphisms are associated with the risk of fractures in postmenopausal women, independently of bone mineral density. Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women Investigation of Bone Health Subsequent to Vitamin D Supplementation in Children Following Burn Injury. An open-label trial comparing alendronate and alphacalcidol in reducing falls and hip fractures in disabled stroke patients. Hypovitaminosis D and 'functional hypoparathyroidism'-the NoNoF (Nottingham Neck of Femur) study. Risk factors for fractures of the distal forearm and proximal humerus. The Study of Osteoporotic Fractures Research Group. The effect of various vitamin D supplementation regimens in breast cancer patients Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study. Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial. Age-Related Changes in Serum Undercarboxylated Osteocalcin and its Relationships with Bone Density, Bone Quality, and Hip Fracture Effect of monthly high‐dose vitamin D on bone density in community‐dwelling older adults substudy of a randomized controlled trial Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. HipWatch: osteoporosis investigation and treatment after a hip fracture: a 6-month randomized controlled trial. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. Vitamin K, bone turnover, and bone mass in girls. 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). 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. Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D. The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis. Vitamin K intake and hip fractures in women: a prospective study. Improving evaluation and treatment for osteoporosis following distal radial fractures. A prospective randomized intervention. Benefits of oral protein supplementation in elderly patients with fracture of the proximal femur. Effects of exercise and nutrition on postural balance and risk of falling in elderly people with decreased bone mineral density: randomized controlled trial pilot study 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 Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial. Prophylactic Bisphosphonate Treatment Prevents Bone Fractures After Liver Transplantation Two-year outcomes on bone density and fracture incidence in patients with T2DM randomized to bariatric surgery versus intensive medical therapy. Vitamin D treatment in primary hyperparathyroidism: a randomized placebo controlled trial. The Effect of Calcium and Vitamin D3 Supplementation on the Healing of the Proximal Humerus Fracture: A Randomized Placebo-Controlled Study The effects of whole-body vibration training and vitamin D supplementation on muscle strength, muscle mass, and bone density in institutionalized elderly women: a 6-month randomized, controlled trial. Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: a randomized, double-blind, placebo controlled trial. Knee pain, knee osteoarthritis, and the risk of fracture. Effect of pamidronate on bone loss after kidney transplantation: a randomized trial. Effects of Vitamin D Supplementation on Bone Mineral Density and Bone Markers in HIV-Infected Youth Weekly risedronate in kidney transplant patients with osteopenia. Alendronate Prevents Postmenopausal Bone Loss in Women without Osteoporosis: A Double-Blind, Randomized, Controlled Trial Vitamin D supplementation after parathyroidectomy: effect on bone mineral density-a randomized double-blind study. Effects of 4-year treatment with once-weekly clodronate on prevention of corticosteroid-induced bone loss and fractures in patients with arthritis: evaluation with dual-energy X-ray absorptiometry and quantitative ultrasound. Effect of calcium and vitamin D supplementation on bone mineral density in women aged 65–71 years: a 3-year randomized population-based trial (OSTPRE-FPS) Effects of protein-rich supplementation and nandrolone on bone tissue after a hip fracture. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women Fall severity and bone mineral density as risk factors for hip fracture in ambulatory elderly. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. 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. Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial. Calcium and Vitamin D3 Supplementation Prevents Bone Loss in the Spine Secondary to Low-Dose Corticosteroids in Patients with Rheumatoid Arthritis Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the American College of Physicians Women’s Health Initiative clinical trials: interaction of calcium and vitamin D with hormone therapy Alendronate in combination with calcium and vitamin D prevents bone loss after orthotopic liver transplantation: a prospective single-center study. Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Protein Supplements Increase Serum Insulin-Like Growth Factor-I Levels and Attenuate Proximal Femur Bone Loss in Patients with Recent Hip Fracture Amelioration of osteopenia and hypovitaminosis D by 1α-hydroxyvitamin D3 in elderly patients with Parkinson’s disease Alendronate and vitamin D2 for prevention of hip fracture in Parkinson's disease: a randomized controlled trial. Effect of Chronic Alcohol Ingestion on Bone Mineral Density in Males without Liver Cirrhosis
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 Summary The rationale of this study was to determine the effect of high-dose vitamin D3 supplementation on bone mineral density ( BMD ) .  Prediabetic males given vitamin D had significantly less reduction in BMD at the femoral neck compared to the controls . The clinical implication s of our findings require further investigation . Introduction Type 2 diabetes mellitus is associated with increased fracture risk , and recent studies show crosstalk between bone and glucose metabolism . Few studies have investigated the effect of vitamin D supplementation on the bone without additional calcium . In the present study , we aim ed to determine whether a high dose of vitamin D3 could improve bone mass density ( BMD ) in prediabetic subjects . Methods The current study was conducted as a secondary research on a previously performed trial , in which 511 subjects with prediabetes were r and omized to vitamin D3 ( 20,000 IU per week ) versus placebo for 5 years  . BMD was measured using dual-energy X-ray absorptiometry ( DEXA ) . Results Two hundred and fifty-six subjects were r and omized to vitamin D and 255 to placebo . Mean baseline serum 25-hydroxyvitamin D ( 25(OH)D ) level was 60 nmol/L. Two hundred and two and 214 in the vitamin D and placebo groups , respectively , completed BMD measurements , whereas one in each group was excluded due to use of bisphosphonates . Males given vitamin D had significantly less reduction in BMD at the femoral neck measurement site compared to the controls ( 0.000 versus − 0.010 g/cm2 , p = 0.008 ) . No significant differences between intervention groups were seen at the total hip measurement site , regarding both males and females . Conclusions Vitamin D3 supplementation alone may be beneficial in males with prediabetes , but confirmatory studies are needed 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 Summary In this post hoc analysis of the VITdAL-ICU study , an RCT in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml  , vitamin D3 did not have a significant effect on β-Crosslaps and osteocalcin . Introduction Observational studies have shown accelerated bone loss in ICU survivors . A reversible contributor is vitamin D deficiency . In a post hoc analysis of the VITdAL-ICU study , we evaluated the effect of high-dose vitamin D3 on the bone turnover markers ( BTM ) β-Crosslaps ( CTX ) and osteocalcin ( OC ) . Methods The VITdAL-ICU study was a r and omized , double-blind , placebo-controlled trial in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml who received placebo or high-dose vitamin D3 ( a loading dose of 540,000 IU and starting 1 month after the loading dose five monthly maintenance doses of 90,000 IU ) . In this analysis on 289 survivors ( 209 telephone , 80 personal follow-up visits )  , BTM were analyzed on days 0 , 3 , 7 , 28 , and 180 ; self-reported falls and fractures were assessed . Bone mineral density ( BMD ) was measured after 6 months . Results At baseline , CTX was elevated ; OC was low in both groups — after 6 months , both had returned to normal . There were no differences between groups concerning BTM , BMD , falls , or fractures . In linear mixed effects models , CTX and OC showed a significant change over time ( p < 0.001 , respectively ) , but there was no difference between the vitamin D and placebo group ( p = 0.688 and p = 0.972 , respectively ) . Conclusions Vitamin D supplementation did not have a significant effect on BTM . Further studies should assess the effectiveness of vitamin D  on musculoskeletal outcomes in ICU survivors Background In meta-analyses supplementation with vitamin D appears to reduce incidence of fractures , and in cross-sectional studies there is a positive association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and bone mineral density ( BMD ) . However , the effect of supplementation with high doses of vitamin D on BMD is more uncertain and could in theory have both positive and negative effects . Methods The study was a one year , double blind placebo-controlled intervention trial performed at the University Hospital of North Norway . 421 subjects , 21 - 70 years old , were included and 312 completed the study . The subjects were r and omized to vitamin D3 40.000 IU per week ( DD group ) , vitamin D3 20.000 IU per week ( DP group ) , or placebo ( PP group ) . All subjects were given 500 mg calcium daily . Serum 25(OH)D , osteoprotegrin ( OPG ) , receptoractivator of nuclear factor-kappaB lig and ( RANKL ) , and BMD at the lumbar spine and the hip were measured before and at the end of the study . Results At baseline the mean serum 25(OH)D levels were 58 nmol/L ( all subjects ) and increased to 141 and 100 nmol/L in the DD and DP groups , respectively . After one year , no significant differences were found between the three groups regarding change in BMD , serum OPG or RANKL . Conclusions Supplementation with high doses of vitamin D for one year does not appear to have a negative effect on  BMD in healthy subjects . In order to disclose a positive effect , subjects with low BMD and /or low serum 25(OH)D levels need to be studied . Trial registration The trial was registered at Clinical Trials.gov ( NCT00243256 ) INTRODUCTION Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D(3 ) have yielded conflicting results . The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D ( 25-OH D ) , bone turnover markers , bone mineral density ( BMD ) , radius bone loss and incidence of fracture in postmenopausal women . METHODS 669 postmenopausal women ( mean age : 62.2 years ) belonging to a population -based cohort were followed prospect ively for a median of 11.2 years . At baseline , 25-OH D levels , BMD , bone turnover markers and clinical risk factors of osteoporosis were assessed . BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs . RESULTS 73 % and 35 % of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention . 11 % of women had levels below 30 nmol/l . Serum 25-OH D correlated modestly with intact PTH ( r(2)=0.023 , p<0.0001 ) , but not with bone turnover markers or BMD at the hip and radius after adjustment for age . When levels of 25-OH D were considered as a continuous variable , there was no significant association between 25-OH D levels and radius BMD loss or fracture risk . After adjustment for age , there was no significant difference in incidence of fracture , BMD , radius BMD loss , bone turnover markers , grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75 , 50 or 30 nmol/l . CONCLUSIONS In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency , vitamin D status may not be an important determinant of bone health 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 : Low bone mass leading to stress fractures is a well-known and yet unsolved problem among female athletes . Purpose : To quantify the rate of bone loss in healthy female athletes and investigate the effects of estrogen and vitamin K supplementation on bone loss . Study Design : Prospect i ve cohort study . Methods : We classified 115 female endurance athletes into amenorrheic , eumenorrheic , or estrogen-supplemented groups and r and omized them to receive either placebo or vitamin K1 . The bone mineral densities of the subjects ' femoral neck and lumbar spine were measured at baseline and after 2 years . Results : Bone mineral density in the lumbar spine remained constant , but bone density in the femoral neck had decreased significantly after 2 years in all three subgroups . The decrease was higher in amenorrheic ( —6.5 % ± 4.0 % ) than in eumenorrheic ( —3.2 % ± 4.1 % ) and estrogen-supplemented athletes ( —3.9 % ± 3.1 % ) . Supplementation with vitamin K did not affect the rate of bone loss . Conclusions : The rate of bone loss in all three subgroups of female athletes was unexpectedly high ; neither estrogen nor vitamin K supplementation prevented bone loss . Clinical Relevance : High-intensity training maintained over several years must be regarded in women as a risk factor for osteoporosis , and protocol s for optimal treatment should be developed 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 It has been reported that vitamin K supplementation effectively prevents fractures and sustains bone mineral density in osteoporosis . However , there are only limited reported data concerning the association between vitamin K nutritional status and bone mineral density ( BMD ) or fractures in Japan . The objectives were to evaluate the association between plasma phylloquinone ( K1 ) or menaquinone ( MK-4 and MK-7 ) concentration and BMD or fracture in Japanese women prospect ively . A total of 379 healthy women aged 30–88 years ( mean age , 63.0 years ) were consecutively enrolled .  Plasma K1 , MK-4 , MK-7 , and serum undercarboxylated osteocalcin ( ucOC ) concentrations , BMD , and incidence of vertebral fractures were evaluated . In stepwise multiple linear regression analyses , L2–4 BMD and a bone turnover marker , log K1 , concentrations were independently correlated with vertebral fracture incidence . When subjects were divided into low and high K1 groups by plasma K1 concentration , the incidence of vertebral fracture in the low K1 group ( 14.4 % ) was significantly higher than that in the high K1 group ( 4.2 % ) , and its age-adjusted RR was 3.58 ( 95 % CI , 3.26–3.93 ) . L2–4 BMD was not different between the two groups . These results suggest that subjects with  vitamin K1 insufficiency in bone have increased susceptibility for vertebral fracture independently from BMD IMPORTANCE While vitamin D supplementation and exercise are recommended for prevention of falls for older people , results regarding these 2 factors are contradictory . OBJECTIVE To determine the effectiveness of targeted exercise training and vitamin D supplementation in reducing falls and injurious falls among older women . DESIGN , SETTING , AND PARTICIPANTS A 2-year r and omized , double-blind , placebo-controlled vitamin D and open exercise trial conducted between April 2010 and March 2013 in Tampere , Finl and . Participants were 409 home-dwelling women 70 to 80 years old . The main inclusion criteria were at least 1 fall during the previous year , no use of vitamin D supplements , and no contraindication to exercise . INTERVENTIONS Four study groups , including placebo without exercise , vitamin D ( 800 IU/d ) without exercise , placebo and exercise , and vitamin D ( 800 IU/d ) and exercise . MAIN OUTCOMES AND MEASURES The primary outcome was monthly reported falls . Injurious falls and the number of fallers and injured fallers were reported as secondary outcomes . In addition , bone density , physical functioning ( muscle strength , balance , and mobility ) , and vitamin D metabolism were assessed . RESULTS Intent-to-treat analyses showed that neither vitamin D nor exercise reduced falls . Fall rates per 100 person-years were 118.2 , 132.1 , 120.7 , and 113.1 in the placebo without exercise , vitamin D without exercise , placebo and exercise , and vitamin D and exercise study groups , respectively ; however , injurious fall rates were 13.2 , 12.9 , 6.5 , and 5.0 , respectively . Hazard ratios for injured fallers were significantly lower among exercisers with vitamin D ( 0.38 ; 95 % CI , 0.17 - 0.83 ) and without vitamin D ( 0.47 ; 95 % CI , 0.23 - 0.99 ) . Vitamin D maintained femoral neck bone mineral density and increased tibial trabecular density slightly . However , only exercise improved muscle strength and balance .  Vitamin D did not enhance exercise effects on physical functioning . CONCLUSIONS AND RELEVANCE The rate of injurious falls and injured fallers more than halved with strength and balance training in home-dwelling older women , while neither exercise nor vitamin D affected the rate of falls . Exercise improved physical functioning . Future research is needed to determine the role of vitamin D in the enhancement of strength , balance , and mobility . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00986466 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 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 There is a high incidence of hip fractures in patients with Parkinson disease ( PD ) .  Bone mineral density ( BMD ) is decreased in patients with PD , correlating with the immobilization-induced bone resorption and hypovitaminosis D with compensatory hyperparathyroidism . OBJECTIVE To evaluate the effectiveness of risedronate , an inhibitor of bone resorption , on osteoporosis and the risk of hip fractures in elderly men with PD . METHODS This was a 2-year , r and omized , double-blind , placebo-controlled trial . In a prospect i ve study of patients with PD , 121 patients received a daily dose of 2.5 mg risedronate and vitamin D2 1,000 IU for 2 years , and the remaining 121 received placebo and vitamin D2  1,000 IU . Incidence of hip fractures was compared between the two groups . RESULTS Nine patients sustained hip fractures in the placebo group , and three hip fractures occurred in the risedronate group . The relative risk of a hip fracture in the risedronate group vs the placebo group was 0.33 ( 95 % CI , 0.09 to 1.20 ) . BMD increased by 2.2 % in the risedronate group and decreased by 2.9 % in the placebo group ( p < 0.0001 ) . Urinary deoxypyridinoline , a bone resorption marker , decreased by 46.7 % in the risedronate group and by 33.0 % in the placebo group . CONCLUSION Treatment with risedronate and vitamin D2 increases bone mineral density in elderly men with Parkinson disease and reduces 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 Low levels of 25-hydroxyvitamin D ( 25OHD ) are associated with increased bone turnover and risk of fractures . Plasma 25OHD is inversely related to body mass index , and vitamin D deficiency is common in obesity . We aim ed to determine whether vitamin D supplementation affects bone turnover and bone mineral density ( BMD ) in obese subjects . Fifty-two healthy obese men and women aged 18–50 years with plasma 25OHD levels below 50 nmol/L were r and omized to 7,000 IU of cholecalciferol daily or placebo for 26 weeks . We measured plasma levels of 25OHD , parathyroid hormone ( PTH ) , and markers of bone turnover , as well as BMD at the hip , spine , forearm , and whole body . Compared with placebo , treatment with cholecalciferol  increased mean plasma 25OHD from 35 to 110 nmol/L ( p < 0.00001 ) and significantly decreased PTH ( p < 0.05 ) . BMD increased significantly at the forearm by 1.6 ± 0.7 % ( p = 0.03 ) . The bone resorption marker C-terminal telopetide of type 1 collagen ( CTX ) decreased borderline significantly in the cholecalciferol group compared with the placebo group ( p = 0.07 ) . Changes in plasma 25OHD correlated inversely with changes in plasma levels of bone-specific alkaline phosphatase ( r = −0.38 , p = 0.01 ) and CTX ( r = −0.33 , p = 0.03 ) . Changes in CTX correlated inversely with changes in spine BMD ( r = −0.45 , p = 0.04 ) . Increasing circulating 25OHD levels by cholecalciferol treatment is of importance to bone health in young obese subjects as increased levels of 25OHD are associated with a decrease in both PTH and bone turnover and with an increase in BMD at the forearm 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 . ) A total of 63 women who had an operation for a fracture of the hip was r and omly allocated to one year of treatment either with anabolic steroids , vitamin D and calcium ( anabolic group ) or with calcium only ( control group ) . The thigh muscle volume was measured by quantitative CT . The bone mineral density of the hip , femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound . Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did ( p<0.01 ) . There was less bone loss in the proximal tibia in the anabolic group than in the control group . The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months . Anabolic steroids , even in this moderate dose , given in combination with vitamin D and calcium had a beneficial effect on muscle volume , bone mineral density and clinical function in this group of elderly women CONTEXT Osteoporosis is a systemic disease with a strong genetic component . Vitamin D receptor ( VDR ) gene polymorphisms explain only a small part of the genetic influence on the level of bone mineral density ( BMD ) , whereas their effect on fracture remains uncertain . OBJECTIVE The objective of this study was to investigate the relationships between VDR genotypes  and fracture risk . DESIGN A prospect i ve population -based cohort was studied . SUBJECTS A total of 589 postmenopausal women ( mean age , 62 yr ) were followed prospect ively during a median ( interquartile ) of 11 ( 1.1 ) yr . MAIN OUTCOME MEASURE The study measured incidents of vertebral and nonvertebral fractures . RESULTS VDR allele B was significantly and dose dependently overrepresented in women who fractured , including 34 and 86 women with first incident vertebral and nonvertebral fragility fractures , respectively . This corresponded to an odds ratio of 1.5 ( 95 % confidence interval , 0.95 - 2.40 ) for heterozygous carriers ( bB , n = 286 ) and 2.10 ( 95 % confidence interval , 1.16 - 3.79 ) for homozygous carriers ( BB , n = 90 ) of the B allele , compared with women with the bb genotype ( n = 213 ) . VDR genotype groups did not differ for demographics , physical activity , grip strength , personal and maternal history of fracture , and calcium intake . The association was independent of BMD of the spine , hip , and radius , and of the BMD loss at the radius . The relationship between VDR polymorphisms and fracture risk was not altered after adjustment for baseline circulating levels of bone turnover markers , estradiol , dehydroepi and rosterone sulfate , SHBG , IGF-I , intact PTH , and 25 hydroxyvitamin D. CONCLUSION VDR genotypes are associated with the risk of fracture  in postmenopausal women independently of BMD , rate of postmenopausal forearm BMD loss , bone turnover , and endogenous hormones . The mechanisms by which VDR genotypes influence bone strength remain to be determined Alendronate decreases the risk of femoral neck fracture by suppressing bone turnover , and also decreases the serum total osteocalcin level . A low serum carboxylated osteocalcin level or high undercarboxylated osteocalcin level could be risk factors for femoral neck fracture . Vitamin K mediates the carboxylation of osteocalcin , but the effect of alendronate therapy with or without vitamin K2 supplementation remains unknown . Forty-eight postmenopausal women were enrolled in a 1-year prospect i ve r and omized trial and assigned to alendronate monotherapy ( 5 mg/day ) ( group A , n = 26 ) or vitamin K2 ( 45 mg/day ) plus alendronate ( 5 mg/day ) ( group AK , n = 22 ) . Bone mineral density was measured by dual-energy X-ray absorptiometry at 0 and 12 months ; bone turnover parameters were measured at 0 , 3 , and 12 months . Four patients discontinued alendronate therapy , and we analyzed the remaining 44 patients ( 23 in group A and 21 in group AK ) who completed 1 year of treatment . Alendronate decreased undercarboxylated osteocalcin ; carboxylated osteocalcin was not affected . Addition of vitamin K2 enhanced the decrease of undercarboxylated osteocalcin levels and led to a greater increase of femoral neck bone mineral density .  Alendronate monotherapy does not decrease carboxylation of osteocalcin , and combination of vitamin K2 and alendronate brings further benefits on both osteocalcin carboxylation and BMD of femoral neck in postmenopausal women with osteoporosis BACKGROUND The effect of supplemental vitamin D on fracture occurrence following burn injuries is unclear . The objective of this study was to evaluate postintervention incidence of fractures in children during the rehabilitative phase postburn ( PB ) following participation in a r and omized clinical trial of vitamin D supplementation . MATERIAL S AND METHODS Follow-up for fracture evaluation was obtained in 39 of 50 patients r and omized to daily enteral vitamin D2 , D3 , or placebo throughout the acute burn course .  Serum 25-hydroxyvitamin D , 1,25-dihydroxyvitamin D , D2 , D3 , calcitonin , and bone alkaline phosphatase ( BAP ) measurements were obtained PB day 7 , midpoint , discharge , and 1-year PB . Urinary calcium was obtained PB day 7 and midpoint . Dual-energy x-ray absorptiometry ( DXA ) was performed at discharge and 1-year PB . RESULTS Fractures were reported in 6 of 39 respondents . Four fractures occurred in the placebo group , 2 in the D2 group , and none in the D3 group . Serum vitamin D , calcitonin , BAP , and urinary calcium were similar between fracture groups . The group with fracture morbidity had larger burn size ( 83.8 % ± 4.9 % vs 53.0 % ± 2.9 % , P < .0001 ) , greater full-thickness burn ( 69.7 % ± 9.4 % vs 39.4 % ± 4.1 % , P = .02 ) , and increased incidence of inhalation injury ( 33 % vs 6 % , P = .04 ) . Decreased bone mineral density z score was noted at discharge in the placebo fracture compared with no-fracture group ( P < .05 ) . CONCLUSION This preliminary report suggests there may be benefit of vitamin D3 in reducing postdischarge fracture risk . Results reaffirm the importance of monitoring bone health in pediatric patients postburn Although vitamin D supplementation has been suggested to reduce the risk of falling in ambulatory or institutionalized elderly persons , no study has examined whether it reduces the frequency of falling in immobilized stroke patients who have immobilization-induced hypercalcemia reflecting increased bone resorption leading to inhibited renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Bisphosphonate is known to reduce immobilization-induced hypercalcemia by inhibiting bone resorption of calcium . This study compared the efficacy of 2 drugs in reducing the risk of falling in patients with long-st and ing stroke . Eighty-two elderly patients with poststroke hemiparesis were followed for 1 year . The patients were r and omly assigned to one of 2 groups ; 41 patients received alendronate 35 mg once weekly , and 41 patients received alphacalcidiol 1 μg daily . The number of falls per person and incidence of hip fracture in the 2 groups were compared . At baseline , all patients had a low serum 1 , 25-[OH]2D level  . Alphacalcidol therapy enhanced immobilization-induced hypercalcemia by increasing intestinal calcium absorption , leading to a reduction of serum 1 , 25-[OH]2D level , while alendronate therapy enhanced 1 , 25-[OH]2D production by decreasing hypercalcemia  . Alendronate treatment accounted for a 55 % reduction in falls ( 95 % confidence interval [CI]=25 - 72 % ; P=.0021 ) . During the 1-year study period , hip fracture occurred in 1 of 41 subjects in the alphacalcidol group and in no subjects in the alendronate  group . Bone mineral density was increased by 3.2 % in the alendronate group and decreased by 0.1 % in the alphacalcidol group ( P<.0001 ) . Alendronate therapy increased serum 1 , 25-[OH]2D levels by improving immobilization-induced hypercalcemia , which may lead to decreased falling and subsequent hip fractures 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 The Study of Osteoporotic Fractures is a prospect i ve cohort study begun in 1986 that includes 9,704 women aged 65 years and older from Maryl and , Minnesota , Oregon , and Pennsylvania . A total of 171 women suffered fractures of the distal forearm , and 79 women had fractures of the proximal humerus during the first 2.2 years of follow-up . Most fractures at both sites occurred as a result of a fall . Low bone mineral density was a strong predictor of these fractures ; comparing those in the lowest quintile of bone mineral density in the distal radius with those in the highest quintile , the rate ratio was 4.1 for fractures of the distal forearm and 7.5 for fractures of the proximal humerus . Other factors associated with an increased rate of distal forearm fracture independently of low bone mineral density included poor visual acuity , number of falls in the year before baseline , and frequent walking . Factors that appeared to be independently associated with an increased rate of fracture of the proximal humerus included a recent decline in health status , insulin-dependent diabetes mellitus , infrequent walking , and several indicators of neuromuscular weakness such as inability to st and with feet in a t and em position for more than a few seconds . These data support the hypothesis that distal forearm fractures often occur as a result of a fall in women with low bone mineral density who are relatively healthy and active and have good neuromuscular function , while fractures of the proximal humerus tend to occur as a result of a fall in women with low bone mineral density who are less healthy and less active than average and who have poor neuromuscular function Vitamin D deficiency in the patients treated for breast cancer is associated with numerous adverse effects ( bone loss , arthralgia , and falls ) . The first aim of this study was to assess vitamin D status , determined by 25-OH vitamin D levels , among women diagnosed with breast cancer according to demographic/ clinical variables and bone mineral density ( BMD ) . The second aim of this study was to evaluate the effect of daily low-dose and weekly high-dose vitamin D supplementation on 25-OH vitamin D levels . This retrospective study included 224 women diagnosed with stage 0–III breast cancer who received treatment at the James P. Wilmot Cancer Center at the University of Rochester Medical Center . Total 25-OH vitamin D levels ( D2 + D3 ) were determined at baseline for all participants . Vitamin D deficiency was defined as a 25-OH vitamin D level < 20 ng/ml , insufficiency as 20–31 ng/ml , and sufficiency as ≥32 ng/ml . BMD was assessed during the period between 3 months before and 6 months following the baseline vitamin D assessment . Based on the participants ’ baseline levels , they received either no supplementation , low-dose supplementation ( 1,000 IU/day ) , or high-dose supplementation ( ≥50,000 IU/week ) , and 25-OH vitamin D was reassessed in the following 8–16 weeks . Approximately 66.5 % had deficient/insufficient vitamin D levels at baseline . Deficiency/insufficiency was more common among non-Caucasians , women with later-stage disease , and those who had previously received radiation therapy ( P < 0.05 ) . Breast cancer patients with deficient/insufficient 25-OH vitamin D levels had significantly lower lumbar BMD ( P = 0.03 ) . Compared to the no-supplementation group , weekly high-dose supplementation significantly increased 25-OH vitamin D levels , while daily low-dose supplementation did not significantly increase levels . Vitamin D deficiency and insufficiency were common among women with breast cancer and associated with reduced BMD in the spine . Clinicians should carefully consider vitamin D supplementation regimens when treating vitamin D deficiency/insufficiency in breast cancer patients PURPOSE To assess the comparative effectiveness of several medications on bone mineral density , biochemical bone markers , and the incidence of vertebral fractures in postmenopausal women with osteoporosis . METHODS A total of 396 postmenopausal women , aged 50 to 75 years , were allocated r and omly to six equal-sized groups : hormone replacement therapy , etidronate , eel calcitonin , alfacalcidol , vitamin K ( menatetrenone ) , or control ( no treatment ) .  Thoracic and lumbar spine radiographs , bone mineral density at the distal radius , and markers of bone turnover were assessed at baseline and every 3 months during the 2-year study . RESULTS Compared with baseline , the 2-year mean changes in bone mineral density were 2.0 % for hormone replacement therapy , -0.5 % for etidronate , 1.6 % for calcitonin , -3.6 % for alfacalcidol , -1.9 % for vitamin K , and -3.3 % for control . Seventeen ( 26 % ) of the 66 control patients developed new vertebral fractures . Compared with controls , the relative risks of vertebral fracture were 0.35 ( 95 % confidence interval [ CI ] : 0.14 to 0.83 ) for hormone replacement therapy , 0.40 ( 95 % CI : 0.17 to 0.92 ) for etidronate , 0.41 ( 95 % CI : 0.17 to 0.93 ) for calcitonin , 0.56 ( 95 % CI : 0.26 to 1.12 ) for alfacalcidol , and 0.44 ( 95 % CI : 0.20 to 0.99 ) for vitamin K. CONCLUSION We observed significant reductions in the incidence of vertebral fractures with hormone replacement therapy , etidronate , and calcitonin , and significant improvements in bone mineral density with hormone replacement therapy and calcitonin In women , the influence of and rogens on bone health is not clear . It has been suggested that the and rogen receptor ( AR ) genotype is associated with bone mineral density and serum and rogen levels in pre- and perimenopausal women , but the association between AR genotype , bone mineral density , and fracture risk has not been studied in postmenopausal women . Therefore , we studied whether AR polymorphism affects bone mineral density , bone mineral density change , or fracture risk in 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 D3 , 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 D3 , 100 - 300 IU/day for 5 years .  Bone mineral density 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 length of CAG repeat in exon 1 of AR gene was evaluated after polymerase chain reaction ( PCR ) amplification . The subjects were divided into three repeat groups according to AR alleles . None of the baseline characteristics were associated with AR gene polymorphism and HRT treatment . The polymorphism did not influence the calculated annual changes of lumbar or femoral neck bone mineral density during the 5-year follow-up in the HRT ( p = 0.926 and 0.146 , respectively ) or non-HRT ( p = 0.818 and 0.917 , respectively ) groups . In all , 28 women sustained 33 fractures during the follow-up . Thus , the numbers of fractures were limited . The AR repeat length variation was not significantly associated with fracture risk in the HRT or non-HRT groups ( p = 0.632 and 0.459 , respectively ; Cox proportional hazards model ) . In conclusion , AR gene polymorphism was not associated with baseline bone mineral density , 5-year bone mineral density change , or fracture risk in early postmenopausal Finnish women Abstract . The effect of the degree of carboxylation of osteocalcin ( OC ) on the properties of bone is unclear . The aim of this study was to relate serum concentrations of total OC ( tOC ) and undercarboxylated OC ( ucOC )  , measured with a two-site immunoassay , to bone mineral density ( BMD ) at the femoral neck and ultrasonic transmitted velocity ( UTV ) at the os calcis in 257 women aged 60–99 years , 22 of whom had sustained a hip fracture . There was an increase in tOC ( r = 0.19 , P= 0.003 ) and ucOC ( r = 0.20 , P= 0.002 ) with age . No significant difference in tOC or ucOC between subjects with and without hip fracture was found . Serum tOC was negatively correlated with femoral neck BMD ( r = −0.23 , P= 0.0001 ) and os calcis UTV ( r = −0.29 , P= 0.0001 ) and partial correlations indicated that these relationships were independent of age . Serum ucOC also correlated negatively with os calcis UTV ( r = −0.21 , P= 0.001 ) and less strongly with femoral neck BMD ( r = −0.13 , P= 0.052 ) . After adjusting for age , only the relationship between ucOC and os calcis UTV remained significant ( r = −0.16 , P= 0.017 ) . It is concluded that in women over 60 years , the increase in tOC reflects an age-related rise in bone remodeling , whereas the increase in ucOC reflects an age-related fall in vitamin K status . The stronger relationship of ucOC with UTV than BMD suggests that the rise in ucOC may perhaps relate more to changes in bone quality than mineral content . Higher serum ucOC concentrations in subjects with a history of hip fracture could not be confirmed BACKGROUND Severe vitamin D deficiency causes osteomalacia , yet trials of vitamin D supplementation in the community have not on average demonstrated benefit to bone mineral density ( BMD ) or fracture risk in adults . OBJECTIVE To determine whether monthly high-dose vitamin D supplementation influences BMD in the general population and in those with low 25-hydroxyvitamin D levels . METHODS Two-year sub study of a trial in older community-resident adults . A total of 452 participants were r and omized to receive monthly doses of vitamin D3 100 000 IU , or placebo . The primary end-point was change in lumbar spine BMD . Exploratory analyses to identify thresholds of baseline 25-hydroxyvitamin D for vitamin D effects on BMD were prespecified . RESULTS Intention-to-treat analyses showed no significant treatment effect in the lumbar spine ( between-groups difference 0.0071 g cm-2 , 95%CI : -0.0012 , 0.0154 ) or total body but BMD loss at both hip sites was significantly attenuated by ~1/2 % over 2 years . There was a significant interaction between baseline 25-hydroxyvitamin D and treatment effect ( P = 0.04 ) . With baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 ( n = 46 ) , there were between-groups BMD changes at the spine and femoral sites of ~2 % , significant in the spine and femoral neck , but there was no effect on total body BMD . When baseline 25-hydroxyvitamin D was > 30 nmol L-1 , differences were ~1/2 % and significant only at the total hip . CONCLUSIONS This sub study finds no clinical ly important benefit to BMD  from untargeted vitamin D supplementation of older , community-dwelling adults . Exploratory analyses suggest meaningful benefit in those with baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 . This represents a significant step towards a trial-based definition of vitamin D deficiency for bone health in older adults 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 OBJECTIVE We aim ed to determine whether a novel Patient Empowerment and Physician Alerting ( PEPA ) intervention would improve the proportion of seniors who were investigated and treated for osteoporosis after hip fracture . METHODS We undertook a 6-month r and omized controlled trial ( RCT ) in 48 women and men > /= 60 years old who had suffered a hip fracture and were admitted to a tertiary-care university hospital . The primary outcome measure was the proportion of participants offered one or more osteoporosis-specific ' best practice s ' measured using the Diagnosis and Management Question naire ( DMQ ) . Participant responses were vali date d in part by physician report . RESULTS In the PEPA intervention group , 19 ( 68 % ) were offered one or more components of best practice care  compared with 7 ( 35 % ) in the ' usual care ' group ( p < .05 ) . In the PEPA group , 15 ( 54 % ) ( p < .01 ) were prescribed  bisphosphonate therapy  , 8 ( 29 % ) ( p < .01 ) had a bone mineral density scan , 11 ( 39 % ) were prescribed calcium and vitamin D ( p = .32 ) , and 9 ( 32 % ) ( p < .01 ) were prescribed exercise .  In the usual care group , 0 ( 0 % ) were prescribed  bisphosphonate therapy , a  bone mineral density assessment , or exercise  and 6 ( 30 % ) were prescribed calcium and vitamin D. CONCLUSIONS This simple , inexpensive PEPA intervention result ed in far superior clinical management than did usual care in a population at high risk of future hip fracture 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 BACKGROUND Vitamin K has been suggested to have a role in bone metabolism , and low vitamin K intake has been related to low bone density and increased risk of osteoporotic fracture . OBJECTIVE The objective of this study was to determine whether phylloquinone ( vitamin K(1 ) ) intake and biochemical indicators of vitamin K status are related to bone mineral content ( BMC ) and markers of bone formation and bone resorption in girls . DESIGN Vitamin K status [ plasma phylloquinone concentration and percentage of undercarboxylated osteocalcin ( % ucOC ) ] was measured at baseline in a study of 245 healthy girls aged 3 - 16 y. Cross-linked N-telopeptide of type 1 collagen ( NTx ) breakdown , osteocalcin , and bone-specific alkaline phosphatase were measured to reflect bone resorption and formation . BMC of the total body , lumbar spine , and hip and dietary phylloquinone intake were measured annually for 4 y. RESULTS Phylloquinone intake ( median : 45 microg/d ) was not consistently associated with bone turnover markers or BMC . Better vitamin K status ( high plasma phylloquinone and low % ucOC ) was associated with lower bone resorption and formation . Plasma phylloquinone was inversely associated with NTx and osteocalcin concentrations ( P < 0.05 ) , and % ucOC was positively associated with NTx and bone-specific alkaline phosphatase concentrations ( P < 0.05 ) . Indicators of vitamin K status were not consistently associated with current BMC or gain in BMC over the 4-y study period . CONCLUSIONS Better vitamin K status was associated with decreased bone turnover in healthy girls consuming a typical US diet . R and omized phylloquinone supplementation trials are needed to further underst and the potential benefits of phylloquinone on bone acquisition in growing children 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 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 efficacy of calcium ( Ca ) in reducing bone loss is debated . In a r and omized placebo-controlled double-masked study , we investigated the effects of oral Ca supplements on femoral shaft ( FS ) , femoral neck ( FN ) and lumbar spine ( LS ) bone mineral density ( BMD ) , and on the incidence of vertebral fracture in vitamin-D-replete elderly . Ninety-three healthy subjects ( 72.1±0.6 years ) were r and omly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months . Sixty-three patients ( 78.4±1.0 years ) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo . FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group ( + 0.6±0.5 % v −1.2±0.7%,p<0.05 ) . There was no difference in effect between the two forms of Ca . The changes of + 0.7±0.8 % v −1.7±1.6 % in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance . In fractured patients , FS , FN and LS BMD changes were −1.3±0.8 , + 0.3±1.6 and + 3.1±1.2 % ( p<0.05 for the last ) . The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group , respectively , and 144.0 in Ca-supplemented fractured patients . Thus , oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly 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 A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side , correlating with the degree of paralysis and vitamin D deficiency due to malnutrition , sunlight deprivation , and immobilization-induced hypercalcemia , and increases the risk of hip fracture . We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [ 1alpha(OH)D3 ; vitamin D3 ] administration on bone mineral density preservation as compared with untreated controls . In a r and omized and prospect i ve study of 103 patients with hemiplegia after stroke ( the mean duration of illness was 4.8 yr ) , 68 ( 34 patients in each group ) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo , whereas the remaining 35 patients received no drug .  Bone mineral density on the hemiplegic side decreased by 1.4 % in the ipriflavone group , 3.8 % in the vitamin D3 group , and 5.4 % in the control group ( P < .0001 , ipriflavone v vitamin D3 and control ) . At baseline , all three groups of patients showed a 25-hydroxyvitamin D insufficiency , increased serum ionized calcium , and low levels of 1 , 25-dihydroxyvitamin D , suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1 , 25-dihydroxyvitamin D. After treatment , the serum 1 , 25-dihydroxyvitamin D level increased by 139.9 % in the ipriflavone group and by 26.9 % in the vitamin D3 group . Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen , and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group , whereas no changes occurred in the other two groups . One patient in the untreated group suffered a hip fracture , compared with none in the ipriflavone and vitamin D3 groups . These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1 , 25-dihydroxyvitamin D concentration In a recent study of women with postmenopausal osteoporosis , treatment with teriparatide for a median of 19 months increased bone mineral density and decreased the risk of vertebral and nonvertebral fractures . Using the same cohort , the current study evaluated the relationship between these therapeutic effects and the patient 's baseline age , vertebral bone mineral density , and prevalent vertebral fractures . In women over 65 years of age , treatment result ed in a greater increase in vertebral bone mineral density than in younger women ( treatment-by-age interaction , p = 0.037 ) , but baseline age had no effect on the relative risk reduction for vertebral fractures ( treatment-by-age interaction , p = 0.558 ) . In women receiving placebo ( with calcium and vitamin D ) , there was an inverse relationship between baseline vertebral bone mineral density and vertebral fracture risk . When compared across bone mineral density tertiles , the effects of teriparatide on the relative risk for developing new vertebral fractures and increase in vertebral bone mineral density did not differ significantly ( p = 0.817 and p = 0.615 , respectively ) . Teriparatide treatment significantly decreased vertebral fracture risk in patients with a vertebral bone mineral density T score of less than -33 or a score between -2.1 and -3.3 ( p < 0.001 and p = 0.027 , respectively ) and showed a trend toward reduced fracture risk in the group with a T score greater than -2.1 ( p = 0.115 ) . Placebo-treated women with two or more prevalent vertebral fractures had a significantly greater risk of developing new vertebral fractures than women with zero or one prevalent vertebral fracture ( p < 0.001 ) . When compared within prevalent vertebral fracture subgroups , the effects of teriparatide on the relative risk for developing new vertebral fractures were similar . The results of this study indicate that teriparatide offers clinical benefit to patients across a broad range of age and disease severity BACKGROUND Vitamin K mediates the gamma-carboxylation of glutamyl residues on several bone proteins , notably osteocalcin . High serum concentrations of undercarboxylated osteocalcin and low serum concentrations of vitamin K are associated with lower bone mineral density and increased risk of hip fracture . However , data are limited on the effects of dietary vitamin K. OBJECTIVE We investigated the hypothesis that high intakes of vitamin K are associated with a lower  risk of hip fracture in women . DESIGN We conducted a prospect i ve analysis within the Nurses ' Health Study cohort . Diet was assessed in 72327 women aged 38 - 63 y with a food-frequency question naire in 1984 ( baseline ) . During the subsequent 10 y of follow-up , 270 hip fractures result ing from low or moderate trauma were reported . RESULTS Women in quintiles 2 - 5 of vitamin K intake had a significantly lower age-adjusted relative risk ( RR : 0.70 ; 95 % CI : 0.53 , 0.93 ) of hip fracture than women in the lowest quintile ( < 109 microg/d ) . Risk did not decrease between quintiles 2 and 5 and risk estimates were not altered when other risk factors for osteoporosis , including calcium and vitamin D intakes , were added to the models . Risk of hip fracture was also inversely associated with lettuce consumption ( RR : 0.55 ; 95 % CI : 0.40 , 0.78 ) for one or more servings per day compared with one or fewer servings per week ) , the food that contributed the most to dietary vitamin K intakes . CONCLUSIONS Low intakes of vitamin K may increase the  risk of hip fracture in women . The data support the suggestion for a re assessment of the vitamin K requirements that are based on bone health and blood coagulation BACKGROUND Fragility fractures are associated with a significant increase in the risk of future fracture , but the rates of evaluation to identify osteoporosis after such injuries are low . The purpose of this study was to determine the rates of evaluation and treatment of osteoporosis following distal radial fractures and to test two interventions in the outpatient clinic to improve evaluation and treatment rates . METHODS In the first part of the study , the medical records of 298 consecutive patients treated for a fragility fracture of the distal part of the radius were review ed . Primary outcome measures were a bone mineral density examination and treatment with osteoporosis medication within six months after the fracture . In the second part of the study , fifty patients with a fragility fracture of the distal part of the radius were prospect ively r and omized to receive one of two interventions . These consisted of ( 1 ) the orthopaedic surgeon ordering a bone mineral density examination and forwarding the results to the primary care physician or ( 2 ) the orthopaedic surgeon sending a letter to the primary care physician outlining guidelines for osteoporosis screening . Patients were contacted at six months after the fracture to determine the rates of evaluation and treatment for osteoporosis . RESULTS The first part of the study revealed that , following a distal radial fracture , 21.3 % of 240 patients had a bone mineral density examination and 78.7 % were never screened . Osteopenia was the most common diagnosis among those screened ( 57 % ) . Most ( 72.5 % ) of the 240 patients received no medication , whereas 6.7 % received calcium and vitamin D ; 11.3 % , bisphosphonates ; 2.5 % , hormone replacement therapy ; and 7.1 % , a combination regimen . The treatment rate for the patients who had undergone a bone mineral density examination was 2.5-fold higher than the rate for those who had not had bone mineral density testing ( 53 % compared with 21 % , p < 0.001 ) . In the second part of the study , the patients r and omized to Intervention 1 had two to threefold greater rates of bone mineral density testing ( 93 % compared with 30 % , p < 0.001 ) , discussion of osteoporosis with their primary care physician ( 89 % compared with 35 % , p < 0.001 ) , and initiation of osteoporosis therapy ( 74 % compared with 26 % , p < 0.001 ) compared with patients r and omized to Intervention 2 . CONCLUSIONS Rates of evaluation and treatment for osteoporosis after fragility fractures remain low ( 21.3 % and 27.5 % , respectively ) . Patients who undergo a bone mineral density examination are more likely to receive treatment . Ordering a bone mineral density examination in the orthopaedic clinic can dramatically improve osteoporosis evaluation and treatment rates following fragility fractures of the distal part of the radius Malnutrition has been often suggested as contributing to both the high incidence of hip fracture in elderly people and its complications . In a recent prospect i ve controlled r and omized study , the clinical outcome of elderly patients with osteoporotic fracture of the proximal femur ( hip fracture ) improved by giving a simple oral dietary supplement . This study , however , did not prove that protein was responsible for the clinical improvement since the supplement also contained vitamins and minerals . We addressed this question by comparing the clinical outcome and bone mineral density ( BMD ) changes in elderly patients with hip fracture , receiving two different dietary supplements with different protein contents . Sixty-two patients ( mean age 82 ) admitted into the orthopedic ward for fracture of the proximal femur were r and omized into two groups . One group ( n = 33 ) received 250 ml/day of an oral nutritional supplement containing protein ( 20.4 g ) , mineral salts ( Ca : 0.525 g ) and vitamins A = 750 IU ; D3 = 25 IU ) for a mean of 38 days . A control group ( n = 29 ) received the same supplement dose , but with no protein , for the same period of time . The clinical course was significantly better in the group receiving protein , with 79 % having a favorable course as compared to 36 % ( p less than 0.02 ) in the control group during the stay in the recovery hospital . The rate of complications and deaths was also significantly lower in the protein-supplemented vs the control group ( 52 vs 80 % , p less than 0.05 ) 7 months after hip fracture . The median hospital stay was significantly lower in the protein-supplemented group ( 69 vs 102 days , p less than 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Objective : To compare the effect of calcium/vitamin D supplements with a combination of calcium/vitamin D supplements and exercise/protein on risk of falling and postural balance . Design : R and omized clinical trial . Setting : University hospital physiotherapy department . Subjects : Twenty-four independently living elderly females aged 65 years and older with osteopenia or osteoporosis and mean total hip T-score ( SD ) of —1.8 ( 0.8 ) . Interventions : A three-month programme consisting of exercise/protein including training of muscular strength , co-ordination , balance and endurance . Calcium/ vitamin D was supplemented in all participants for a 12-month period . Outcome measures : Assessment took place prior to and following the months 3 , 6 , 9 and at the end of the study ; primary dependent variables assessed were risk of falling ( Berg Balance Test ) and postural balance ( forceplate ) . Secondary measures included body composition , strength , activity level , number of falls , bone mineral content , biochemical indices , nutritional status and general health . Results : Significant reductions of risk of falling ( repeated measures ANOVA F = 8.90 , P = 0.008 ) , an increase in muscular strength ( ANOVA F = 3.0 , P = 0.03 ) , and an increase in activity level ( ANOVA F = 3.38 , P = 0.02 ) were found in the experimental group as compared to the control group . Further on , there was 89 % reduction of falls reported in the experimental group ( experimental pre/post 8/1 falls ; control group pre/post 5/6 falls ) . Conclusion : This study provides support for our intervention programme aim ed at reducing the risk of falling in elderly participants diagnosed with osteopenia or osteoporosis . The data obtained from the pilot study allow the calculation of the actual sample size needed for a larger r and omized trial 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 IMPORTANCE Experts debate optimal 25-hydroxyvitamin D ( 25[OH]D ) levels for musculoskeletal health . OBJECTIVE To compare the effects of placebo , low-dose cholecalciferol , and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption , bone mineral density , Timed Up and Go and five sit-to-st and tests , and muscle mass in postmenopausal women with vitamin D insufficiency . DESIGN , SETTING , AND PARTICIPANTS This r and omized , double-blind , placebo-controlled clinical trial was conducted at a single center in Madison , Wisconsin , from May 1 , 2010 , through July 31 , 2013 , and the final visit was completed on August 8 , 2014 . A total of 230 postmenopausal women 75 years or younger with baseline 25(OH)D levels of 14 through 27 ng/mL and no osteoporosis were studied . INTERVENTIONS Three arms included daily white and twice monthly yellow placebo ( n=76 ) , daily 800 IU vitamin D3 and twice monthly yellow placebo ( n=75 ) , and daily white placebo and twice monthly 50,000 IU vitamin D3 ( n=79 ) . The high-dose vitamin D regimen achieved and maintained 25(OH)D levels≥30 ng/mL. MAIN OUTCOMES AND MEASURES Outcome measures were 1-year change in total fractional calcium absorption using 2 stable isotopes , bone mineral density and muscle mass using dual energy x-ray absorptiometry , Timed Up and Go and five sit-to-st and tests , functional status ( Health Assessment Question naire ) , and physical activity ( Physical Activity Scale for the Elderly ) , with Benjamini-Hochberg correction of P values to control for the false discovery rate . RESULTS After baseline absorption was controlled for , calcium absorption increased 1 % ( 10 mg/d ) in the high-dose arm but decreased 2 % in the low-dose arm ( P = .005 vs high-dose arm ) and 1.3 % in the placebo arm ( P = .03 vs high-dose arm ) . We found no between-arm changes in spine , mean total-hip , mean femoral neck , or total-body bone mineral density , trabecular bone score , muscle mass , and Timed Up and Go or five sit-to-st and test scores . Likewise , we found no between-arm differences for numbers of falls , number of fallers , physical activity , or functional status . CONCLUSIONS AND RELEVANCE High-dose cholecalciferol therapy increased calcium absorption , but the effect was small and did not translate into beneficial effects on bone mineral density , muscle function , muscle mass , or falls . We found no data to support experts ' recommendations to maintain serum 25(OH)D levels of 30 ng/mL or higher in postmenopausal women . Instead , we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/mL. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00933244 A r and omized controlled prospect i ve open‐label single center trial was performed . At the time of transplantation patients were r and omly assigned to one of two treatment arms : The study group of 47 patients received zoledronic acid ( ZOL , 8 infusions at 4 mg during the first 12 months after LT ) , calcium ( 1000 mg/d ) and vitamin D ( 800 IE/d ) . The control group consisted of 49 patients who received calcium and vitamin D at same doses ( CON ) . The incidence of bone fractures or death was predefined as the primary endpoint . Secondary endpoints included bone mineral density ( BMD ) , serum biochemical markers of bone metabolism , parameters of trabecular bone histomorphometry and mineralization density distribution ( BMDD ) . Patients were followed up for 24 months . Analysis was performed on an intention‐to‐treat basis . The primary endpoint fracture or death was reached in 26 % of patients in the ZOL group and 46 % in the CON group ( p = 0.047 , log rank test ) . Densitometry results were different between the groups at the femoral neck at 6 months after LT ( mean+/‐SD BMD ZOL : 0.80 ± 0.19 g/cm2 vs. CON : 0.73 ± 0.14 g/cm2 , p = 0.036 ) . Mixed linear models of biochemical bone markers showed less increase of osteocalcin in the ZOL group and histomorphometry and BMDD indicated a reduction in bone turnover . Prophylactic treatment with the bisphosphonate zoledronic acid reduces bone turnover and fractures after liver transplantation OBJECTIVE To determine the 2-year outcomes of Roux-en-Y gastric bypass ( RYGB ) and sleeve gastrectomy ( SG ) vs. intensive medical therapy ( IMT ) on lean body mass , total bone mass , and bone mineral density ( BMD ) measures from the STAMPEDE trial . METHODS 54 subjects ( BMI : 36 ± 1 kg/m(2 ) , age : 48 ± 4 years ) with type 2 diabetes ( T2DM ) ( HbA1c : 9.7 ± 2 % ) were r and omized to IMT , RYGB , or SG and underwent DXA at baseline and at 1 and 2 years . RESULTS At 2 years , the reduction in BMI was similar after RYGB and SG and was greater than IMT ( P < 0.001 ) . Lean mass was reduced by ∼10 % , total bone mineral content reduced by ∼8 % , and hip BMD reduced by ∼9 % in both surgical groups and was significantly greater than IMT despite increases in vitamin D intake in all groups . The change in hip BMD correlated with weight loss ( r = 0.84 , P < 0.0001 ) and changes in lean mass ( r = 0.74 , P < 0.0001 ) and leptin ( r = 0.53 , P < 0.0001 ) . Peripheral fractures were self-reported in RYGB ( 4/18 patients ) , SG ( 2/19 patients ) , and IMT ( 4/16 patients ) . CONCLUSIONS Surgically induced weight loss is associated with modest reductions in lean mass , bone mineral content , and BMD , despite calcium and vitamin D supplementation in patients with T2DM . Awareness for bone loss is indicated for patients undergoing bariatric procedures CONTEXT Low 25-hydroxyvitamin D levels are common in patients with primary hyperparathyroidism ( PHPT ) and associated with higher PTH levels and hungry bone syndrome after parathyroidectomy ( PTX ) . However , concerns have been raised about the safety of vitamin D supplementation in PHPT . OBJECTIVE We aim ed to assess safety and effects on calcium homeostasis and bone metabolism of supplementation with high doses of vitamin D in PHPT patients . DESIGN , SETTING This was an investigator-initiated double-blind , r and omized , placebo-controlled , parallel-group trial from a single center . PATIENTS Forty-six PHPT patients were recruited , with a mean age of 58 ( range 29 - 77 ) years , and 35 ( 76 % ) were women . INTERVENTIONS Intervention included daily supplementation with 70 μg ( 2800 IU ) cholecalciferol or identical placebo for 52 weeks . Treatment was administered 26 weeks before PTX and continued for 26 weeks after PTX . MAIN OUTCOME MEASURES PTH , calcium homeostasis , and bone metabolism were evaluated . RESULTS Preoperatively , 25-hydroxyvitamin D increased from 50 to 94 nmol/L in the treatment group and decreased from 57 to 52 nmol/L in the placebo group ( P < .001 ) . Compared with placebo , vitamin D  decreased PTH significantly by 17 % before PTX ( P = .01 ) , increased lumbar spine bone mineral density by 2.5 % ( P = .01 ) , and decreased C-terminal β-CrossLaps by 22 % ( P < .005 ) . The trabecular bone score did not change in response to treatment , but improved after PTX . Postoperatively , PTH remained lower in the cholecalciferol group compared with the placebo group ( P = .04 ) . Plasma creatinine and plasma and urinary calcium did not differ between groups . CONCLUSIONS Daily supplementation with a high vitamin D dose safely improves vitamin D status and decreases PTH in PHPT patients . The vitamin D treatment is accompanied by reduced bone resorption and improved bone mineral density before operation 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 Sarcopenia and osteoporosis represent a growing public health problem . We studied the potential benefit of whole-body vibration ( WBV ) training given a conventional or a high dose of daily vitamin D supplementation in improving strength , muscle mass , and bone density in postmenopausal women . In a 2 × 2 factorial- design trial , 113 institutionalized elderly females aged over 70 years ( mean age 79.6 years ) were r and omly assigned either to a WBV or a no-training group , receiving either a conventional dose ( 880 IU/day ) or a high dose ( 1600 IU/day ) of vitamin D(3 ) . The primary aim was to determine the effects of 6 months of WBV and /or vitamin D supplementation on isometric and dynamic strength , leg muscle mass , and hip bone mineral density ( BMD ) . Additionally , the increase in 25-hydroxyvitamin D [ 25(OH)D ] levels between conventional and high-dose supplementation was compared . After 6 months of treatment , dynamic muscle strength , hip BMD , and vitamin D serum levels improved significantly in all groups , whereas isometric strength and muscle mass did not change . When compared with no training , the WBV program did not result in additional improvements . When compared with 880 IU , a high dose of 1600 IU of vitamin D did result in higher serum vitamin D levels but did not result in additional improvements . In institutionalized women older than 70 years , the WBV training protocol tested is not more efficient in enhancing muscle mass , strength , and hip BMD compared with vitamin D supplementation . A higher dose of 1600 IU of vitamin D does not provide additional musculoskeletal benefit in this population compared with conventional doses Summary The effects of higher than recommended vitamin D doses on bone mineral density ( BMD ) and quality are not known . In this study , higher intakes , in postmenopausal women undergoing weight control over 1 year , had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry . Introduction Studies examining how bone responds to a st and ard dose of vitamin D supplementation have been inconsistent . In addition , the effects of higher doses on BMD and quality are not known . Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance . Methods This 1-year-long , r and omized , double-blind controlled study addresses whether vitamin D supplementation , in healthy overweight/obese older women , affects BMD and bone structural parameters . In addition , bone turnover and serum total , free , and bioavailable 25-hydroxyvitamin D ( 25OHD ) responses to one of three daily levels of vitamin D3 ( 600 , 2000 , 4000 IU ) with 1.2 Ca g/day during weight control were examined . Results Fifty-eight women ( age , 58 ± 6 years ; body mass index , 30.2 ± 3.8 kg/m2 , serum 25OHD , 27.3 ± 4.4 ng/mL ) were r and omized to treatment . After 1 year , serum 25OHD concentrations increased to 26.5 ± 4.4 , 35.9 ± 4.5 , and 41.5 ± 6.9 ng/mL , in groups 600 , 2000 , and 4000 IU , respectively , and differed between groups ( p < 0.01 ) . Weight change was similar between groups ( −3.0 ± 4.1 % ) . Cortical ( Ct ) thickness of the tibia changed by −1.5 ± 5.1 % , + 0.6 ± 3.2 % , and + 2.0 ± 4.5 % in groups 600 , 2000 , and 4000 IU , respectively , and each group was significantly different from each other ( p < 0.05 ) . Conclusion The decline in Ct thickness was prevented with higher vitamin D3 supplementation , but there were no other significant changes due to treatment over 1 year . Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies Calcium and vitamin D are essential nutrients for bone health . Periods of activity with repetitive mechanical loading , such as military training , may result in increases in parathyroid hormone ( PTH ) , a key regulator of Ca metabolism , and may be linked to the development of stress fractures . Previous studies indicate that consumption of a Ca and vitamin D supplement may reduce stress fracture risk in female military personnel during initial military training , but circulating markers of Ca and bone metabolism and measures of bone density and strength have not been determined . This r and omized , double-blind , placebo-controlled trial sought to determine the effects of providing supplemental Ca and vitamin D ( Ca+Vit D , 2000 mg and 1000IU/d , respectively ) , delivered as 2 snack bars per day throughout 9weeks of Army initial military training ( or basic combat training , BCT ) on PTH , vitamin D status , and measures of bone density and strength in personnel undergoing BCT , as well as independent effects of BCT on bone parameters . A total of 156 men and 87 women enrolled in Army BCT ( Fort Sill , OK ; 34.7 ° N latitude ) volunteered for this study . Anthropometric , biochemical , and dietary intake data were collected pre- and post-BCT . In addition , peripheral quantitative computed tomography was utilized to assess tibia bone density and strength in a subset of volunteers ( n=46 ) . Consumption of supplemental Ca+Vit D  increased circulating ionized Ca ( group-by-time , P=0.022 ) , maintained PTH ( group-by-time , P=0.032 ) , and increased the osteoprotegerin : RANKL ratio ( group-by-time , P=0.006 ) . Consistent with the biochemical markers , Ca+Vit D  improved vBMD ( group-by-time , P=0.024 ) at the 4 % site and cortical BMC ( group-by-time , P=0.028 ) and thickness ( group-by-time , P=0.013 ) at the 14 % site compared to placebo . These data demonstrate the benefit of supplemental Ca and vitamin D for maintaining bone health during periods of elevated bone turnover , such as initial military training . This trial was registered with ClincialTrials.gov , NCT01617109 OBJECTIVE Patients with osteoarthritis ( OA ) have increased bone mineral density ; however , the association between knee OA and fracture is controversial . Few data exist on the association between knee pain and fracture . We examined the association of knee OA and knee pain with fracture and falls in elderly men and women . METHODS The study group comprised 6,641 men and women ages > or = 75 years who participated in a 3-year r and omized controlled trial of intramuscular vitamin D therapy .  Patients completed a question naire about knee pain and OA .  Fracture and fall data were collected prospect ively every 6 months . RESULTS Knee pain prevalence and a clinician diagnosis of knee OA were 35.2 % and 6.8 % , respectively . A total of 436 incident nonvertebral fractures were reported , and 3,992 patients sustained a fall . Prevalent knee pain was associated with an increased risk of falls ( hazard ratio [ HR ] 1.26 , 95 % confidence interval [ 95 % CI ] 1.17 - 1.36 ) and hip fracture ( HR 2.0 , 95 % CI 1.18 - 3.37 ) . Increasing severity of knee pain was associated with a greater risk of falls and hip fracture . Clinician diagnosis of knee OA was associated with an increased risk of nonvertebral fractures ( HR 1.61 , 95 % CI 1.09 - 2.36 ) . The increased risk of fracture was not substantially reduced by adjusting for falls , but was attenuated by adjustment for the use of walking aids . CONCLUSION Patients with a clinical diagnosis of knee OA and with knee pain have an increased risk of nonvertebral and hip fracture . This is not explained by the increased risk of falls , but is more likely to be due to the severity of falls sustained . Knee pain and OA should be regarded as independent risk factors for fracture BACKGROUND Kidney transplantation is associated with an increased risk of bone fracture and rapid loss of bone mineral density after kidney transplantation . STUDY DESIGN R and omized controlled trial . SETTING & PARTICIPANTS Patients were r and omly assigned to treatment ( n = 46 ) or control ( no treatment ; n = 47 ) groups . Patients were stratified according to parathyroid hormone level and sex . Those with parathyroid hormone level less than 150 pg/mL were excluded . INTERVENTION The treatment and control groups received pamidronate , 1 mg/kg , perioperatively and then at 1 , 4 , 8 , and 12 months or no treatment , respectively . All received calcium ( 500 mg ) and vitamin D ( 400 units ) daily . Immunosuppression was cyclosporine and prednisolone , with no difference in dosing between the 2 groups . OUTCOMES & MEASUREMENTS Bone mineral density was evaluated by means of dual-energy x-ray absorptiometry of the lumbar spine and hip at baseline and 3 , 6 , 12 , and 24 months , with the primary end point at 1 year of percentage of change in bone mineral density from baseline . Clinical fractures were recorded and also evaluated by means of spinal radiographs at baseline and 1 and 2 years . RESULTS Pamidronate protected bone mineral density at the lumbar spine ; bone mineral density increased by 2.1 % in the treatment group and decreased by 5.7 % in the control group at 12 months ( P = 0.001 ) . Protection was also seen in Ward 's area of the hip ( P = 0.002 ) and the total hip ( P = 0.004 ) . There was no difference in femoral neck bone mineral density loss between the 2 groups . Fracture rates in the treatment and control groups were 3.3 % and 6.4 % per annum , respectively . LIMITATIONS This study was not powered to detect differences in fracture rates . CONCLUSION Pamidronate protects against posttransplantation bone loss at the lumbar spine and Ward 's area of the hip Background : Low bone mineral density ( BMD ) is a significant comorbidity in HIV . However , studies evaluating vitamin D supplementation on bone health in this population are limited . This study investigates changes in bone health parameters after 12 months of supplementation in HIV-infected youth with vitamin D insufficiency . Methods : This is a r and omized , active-control , double-blind trial investigating changes in bone parameters with 3 different vitamin D3 doses [ 18,000 ( st and ard/control dose ) , 60,000 ( moderate dose ) , and 120,000 IU/monthly ( high dose ) ] in HIV-infected youth 8–25 years old with baseline serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations < 30 ng/mL.  BMD and bone turnover markers were measured at baseline and 12 months . Results : One hundred two subjects enrolled . Over 12 months , serum 25(OH)D concentrations increased with all doses , but the high dose ( ie , 120,000 IU/monthly ) maintained serum 25(OH)D concentrations in an optimal range ( ≥30 or ≥20 ng/mL ) throughout the study period for more subjects ( 85 % and 93 % , respectively ) compared with either the moderate ( 54 % and 88 % , respectively ) or st and ard dose ( 63 % and 80 % , respectively ) . All dosing groups showed some improvement in BMD ; however , only the high-dose arm showed significant decreases in bone turnover markers for both procollagen type 1 aminoterminal propeptide ( −3.7 ng/mL ; P = 0.001 ) and & Bgr;-CrossLaps ( −0.13 ng/mL ; P = 0.0005 ) . Conclusions : High-dose vitamin D supplementation ( 120,000 IU/mo ) given over 12 months decreases bone turnover markers in HIV-infected youth with vitamin D insufficiency , which may represent an early , beneficial effect on bone health . High vitamin D doses are needed to maintain optimal serum 25(OH)D concentrations Daily bisphosphonate is effective in preventing and treating corticosteroid-induced osteoporosis in renal transplant recipients , although it frequently has gastrointestinal side effects . The aim was to assess efficacy and side effect profile of weekly oral risedronate .  Eighty-four renal transplant patients , receiving either cyclosporin A or tacrolimus and steroids were prospect ively included . The study group ( 39 patients ) received 35 mg risedronate weekly , vitamin D and calcium , while control group ( 45 patients ) only vitamin D and calcium . At baseline , 6 and 12 months , creatinine , calcium , phosphorus , alkaline phosphatase and iPTH were determined . Fractures and bone mineral densities were assessed by X-rays and dual-energy X-ray absorptiometry , respectively . Pain was assessed by clinical interview . Mineral bone density score increased significantly in risedronate group after 1 year . There were no differences in the incidence of fractures , although , anamnestic pain assessment revealed that 3 % of treatment group reported to have bone pain compared with 18 % in nontreatment group ( P < 0.05 ) . Follow-up calcium , phosphorus , alkaline phosphatases , and iPTH levels showed no differences from basal measures . Risedronate was well tolerated with no major side effects . Weekly oral risedronate in renal transplanted patients reduces bone mineral loss and bone pain and has an excellent side effect profile Osteoporosis is characterized by low bone mass and architectural changes in bone that render the skeleton brittle and susceptible to fracture [ 1 ] . As the elderly population grows , the worldwide annual incidence of hip fractures is projected to increase from 1.7 million in 1990 to 6.3 million by 2050 , placing great economic strain on health care systems [ 2 ] . Currently , a 50-year-old woman is estimated to have a risk as high as 40 % for sustaining a fracture related to osteoporosis at some point in the future [ 3 ] . The age-adjusted risk for fracture seems to be increasing , and this risk may be an underestimate for the future [ 4 ] . Bone loss after menopause , which results in low bone density , is an important determinant of risk for fracture , although other factors ( such as advanced age , hip geometry , and falls and injuries ) also contribute [ 5 , 6 ] . Bone loss is most rapid during the first few years after menopause , but evidence suggests that the rate of loss also becomes accelerated in advanced old age [ 7 , 8 ] . One strategy to reduce the number of fractures in postmenopausal women is to begin treatment for osteoporosis only in patients who are at high risk for fracture , including those with osteoporosis or previous fragility fractures .  Pharmacologic therapy in women with osteoporosis with or without fractures reduces the incidence of fracture by about 50 % [ 9 , 10 ] . However , half of women who would have sustained fractures without treatment still do so with treatment . Thus , preventing rather than treating osteoporosis is a more appealing clinical objective because it can avoid the increased risk for fracture . There may also be an advantage in terms of preserving the normal microarchitecture of bone . Preventing bone loss associated with menopause and aging and maintaining normal microarchitecture provide important opportunities for the prevention of osteoporosis and fractures . Estrogen is effective in preventing bone loss in early and late postmenopausal women , but it must be taken over the long term to decrease the incidence of vertebral and hip fractures [ 11 ] . Estrogen also relieves menopausal symptoms and , in epidemiologic cohort studies , seemed to protect against cardiovascular disease . However , most women who begin estrogen therapy do not continue it for more than a year , in part because of such side effects as breast tenderness , headache , fluid retention , and withdrawal bleeding [ 12 , 13 ] . Although the benefits of estrogen therapy outweigh the risks in most women , concern about risk for breast cancer is sufficiently great that many women avoid estrogen therapy [ 14 , 15 ] . Alendronate sodium ( monosodium 4-amino , 1-hydroxybutylidene-1 , 1-bisphosphonate ) is a potent and selective inhibitor of osteoclast-mediated bone resorption . Studies in animals with low bone mineral density have shown that alendronate therapy is associated with increased bone mass of normal quality and increased bone strength [ 16 ] . Alendronate treatment of osteoporosis in postmenopausal women induces progressive increases in bone density and a reduction in the incidence of new fractures of the vertebrae , hip , and forearm in osteoporotic women [ 9 , 10 ] . We performed a 3-year r and omized , double-blind , placebo-controlled , dose-ranging study to evaluate the efficacy of alendronate therapy in preventing bone loss in healthy women who had recently experienced menopause . Methods Study Participants Healthy women aged 40 to 59 years who had experienced menopause 6 to 36 months before enrollment were eligible to participate in this study . Women were excluded if their spine bone mineral density was more than 2 SDs above or below normal peak bone mineral density or if they had a history of nontraumatic spine or hip fracture . Women with disorders of bone and mineral metabolism were also excluded , as were those with recent ( within 1 year of study entry ) major upper gastrointestinal diseases ( such as peptic ulcer , esophageal disease , and malabsorption ) . Other exclusion criteria were previous treatment with bisphosphonates or fluoride ( > 1 mg/d ) or treatment within the 12 months before enrollment with estrogen , progestin , calcitonin , glucocorticoids , anticonvulsant agents , phosphate-binding antacids , or excessive vitamin A or vitamin D. Women who regularly used ( > four times per week ) any medication that had the potential to cause gastrointestinal irritation ( such as aspirin ) , who smoked more than 20 cigarettes per day , or who drank three or more alcoholic beverages per day were also excluded . Four hundred forty-seven women met the inclusion criteria and were enrolled at 15 centers throughout the world . The target sample size of 250 women completing the study was selected to detect a difference in bone density of 2.4 % between an individual alendronate dosage and placebo at a P value of 0.05 or less , with 95 % power using an SD of 3.3 % that was obtained from 1-year bone density data in placebo recipients [ 17 ] . All centers conducted the study with appropriate approval from the institutional review boards , and all participants gave informed consent . Treatment Participants were r and omly assigned ( in allocation blocks of five ) to one of five regimens : placebo for 3 years ; alendronate at 1 , 5 , or 10 mg/d for 3 years ; or alendronate at 20 mg/d for 2 years followed by placebo for 1 year ( 20/0 mg/d ) . In all groups , double-blinding was maintained for all 3 years . Alendronate and placebo tablets were identical in size , shape , and color . The women were instructed to take the study drug daily at least 1 hour before breakfast or , as a less desirable alternative , at least 2 hours after a meal and 1 hour before the next meal . All participants also received a daily supplement of calcium carbonate ( Os-Cal 500 , Smith-Kline Beecham Consumer Br and s , LP , Pittsburgh , Pennsylvania , or the equivalent ) unless dietary calcium intake exceeded 1000 mg/d . This supplement was usually taken with the evening meal . After beginning therapy , each participant was seen at months 1 and 3 and every 3 months thereafter . Eight participants ( four in the placebo group and four in the 1-mg/d group ) lost more than 6 % of their spine bone density at 24 months relative to their baseline measurements and were therefore design ated fast bone losers . Seven of these participants completed the study ; from month 24 to the end of the study , they received 5 mg of open-label alendronate per day . The other patient discontinued therapy at month 24 . Bone Mineral Density Bone mineral density of the spine , proximal femur , total body , and forearm was measured every 6 months by dual-energy x-ray absorptiometry with a Hologic QDR-1000 , 1000/W , or 2000 densitometer ( Waltham , Massachusetts ) or a Lunar DPX-L densitometer ( Madison , Wisconsin ) . One bone density quality assurance center ( Oregon Osteoporosis Center ) that remained blinded to treatment allocation was responsible for the quality control of all participant and phantom calibration scans [ 18 ] . Factors to correct for machine calibration drift were applied as necessary . The primary end point was bone mineral density of the lumbar spine ; the other most important end points were bone mineral density of the femoral neck , trochanter , and total body . Bone mineral density of the total body , total hip , and forearm was measured at the centers that had densitometers capable of performing these measurements ( 11 centers measured bone mineral density of the total body ; 10 centers measured bone mineral density of the total hip and forearm ) . Biochemical Markers and Indices of Mineral Metabolism Fasting serum and urine sample s ( second morning void ) were obtained at all clinic visits except those in months 27 and 33 . The resorption markers included urine deoxypyridinoline , measured by high-pressure liquid chromatography , and ( in a subgroup of 268 participants ) urine N-telopeptide cross-links of type I collagen ( Ostex , Seattle , Washington ) . Each of these markers was expressed as a ratio to urine creatinine . Serum osteocalcin levels , measured by radioimmunoassay ( INCSTAR , Stillwater , Nebraska ) , and serum bone-specific alkaline phosphatase levels were used to assess the rate of bone formation . Levels of serum calcium , phosphorus , intact parathyroid hormone ( measured by immunoradiometric assay ) , and 1,25 dihydroxyvitamin D ( measured by competitive binding assay ) were also determined to assess the effects of treatment on mineral metabolism .  N-telopeptide  levels were measured by Medical Research Laboratories ( Highl and Heights , Kentucky ) . All other assays were done at Corning-Nichols Institute ( San Juan Capistrano , California ) . Safety Evaluations At each visit , vital signs were measured and any new or worsening symptoms were recorded . Physical examinations were performed at the baseline , month 3 , and yearly visits . St and ard laboratory safety evaluations ( including evaluations of hematologic , renal , and liver function ) were performed at every visit . Investigators reported any unfavorable or unintended clinical or laboratory events as adverse experiences . After 3 years of therapy , biopsy specimens of transiliac bone were obtained for histologic and histomorphometric assessment from 55 women who provided specific informed consent for this procedure . These analyses were performed , as previously described , by a single investigator who was blinded to treatment groups [ 19 ] . Statistical Analysis The Tukey trend test [ 20 ] was used to assess the trend in response with increasing alendronate dosages . The 20/0-mg/d group was excluded from this test because of the change in dosage . This test uses the minimum P value , adjusted for multiplicity [ 21 ] , that was obtained from tests of the regression sloped on three dosage scalings . The test is done in a stepwise manner , with the highest dosage eliminated , until the minimum P value exceeds 0.05 . Dose-response relations were examined for the responses of the percentage change in bone density variables , natural logarithm ( fraction of the baseline value ) for biochemical Patients with primary hyperparathyroidism ( PHPT ) have higher bone turnover , lower bone mineral density ( BMD ) , and an increased risk of fractures . They also have a high incidence of low vitamin D levels ( 25-OH-vitamin D < 50 nmol/L ) that could worsen the negative effect on the bone . In this double-blinded clinical trial , 150 patients with PHPT were r and omized , after successful parathyroidectomy ( PTX ) , to 1-year daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg ( D+ ) or calcium carbonate alone ( D- ) . BMD was measured in the lumbar spine , femoral neck , total hip , distal and 33 % radius using dual-energy X-ray absorptiometry ( DXA ) before surgery and after 1 year of study medication . Median age was 60 ( range 30 - 80 ) years and there were 119 ( 79 % ) women and 31 ( 21 % ) men ; 76 % had 25-OH-D < 50 nmol/L before PTX and 50 % had persistent elevated parathyroid hormone ( PTH ) 6 weeks after PTX . A similar increase in BMD in the lumbar spine , femoral neck , and total hip was observed in both groups ( D+ : 3.6 % , 3.2 % , and 2.7 % , p<0.001 , respectively ; and D- : 3.0 % , 2.3 % , and 2.1 % , respectively , p<0.001 ) . Patients with vitamin D supplementation also increased their BMD in distal radius ( median 2.0 % ; interquartile range , -1.7 % to 5.4 % ; p=0.013 ) . The changes in BMD , especially in the hips , were correlated to the baseline concentrations of PTH , ionized calcium , and bone markers ( p<0.001 ) . A benefit from vitamin D substitution was observed among patients with a persistent postoperative PTH elevation , who also improved their BMD at 33 % radius and radius ultradistal ( p<0.05 ) . In conclusion , except for a minor improvement of radius BMD , our data show no beneficial effect on BMD or bone turnover markers of vitamin D supplementation after PTX . Preoperative PTH seems to have the strongest association with improvement in BMD The aim of this placebo-controlled study was to determine whether once-weekly clodronate could prevent  osteoporosis in patients with arthritis at the start of corticosteroid therapy . One hundred sixty-three patients , 18 to 90 years of age , with rheumatoid or psoriatic arthritis , were r and omly assigned to receive either clodronate ( 100 mg im/week ) plus calcium and vitamin D ( 1000 mg and 800 UI , respectively ) or calcium and vitamin D alone .  Patients had started therapy with prednisone or its equivalent within the previous 100 days and had bone mineral density < 2.5 SD below mean young normal values at the lumbar spine or femoral neck . The primary outcome was the difference between the two treatment groups at months 12 , 24 , 36 , and 48 in the mean percentage change from baseline in the bone mineral density of the lumbar spine , femur ( neck and total ) , and total body . Secondary measurements included changes in the stiffness index evaluated by ultrasound measurements and the rate of new vertebral fractures . The bone density and stiffness did not change significantly in the clodronate plus calcium and vitamin D group , whereas it declined significantly in the calcium plus vitamin D group . The difference between treatment groups at 48 months in the mean change from baseline was 8.78 + /- 1.4 % for the lumbar spine ( P < 0.01 ) , 7.31 + /- 1.12 % for the femoral neck ( P < 0.01 ) , 7.92 + /- 1.93 % for the trochanter ( P < 0.01 ) , 8.39 + /- 1.80 % for total femur ( P < 0.01 ) , 6.94 + /- 1.09 % for total body ( P < 0.01 ) , and 9.38 + /- 2.21 % for stiffness of os calcis ( P < 0.01 ) . Depending on the skeletal regions evaluated , 85 to 98 % of patients treated with clodronate had a densitometric change lower than the lowest significant densitometric difference . One hundred percent of patients treated with calcium plus vitamin D had a densitometric decrease greater than the lowest significant difference . The relative risk of vertebral fractures and multiple vertebral fractures in the clodronate group compared to the calcium plus vitamin D group was 0.63 ( 0.35 - 0.98 , 95 % CI ) and 0.25 ( 0.15 - 0.91 , 95 % CI ) , respectively . We concluded that pulsatory administration of i m clodronate once weekly is a safe therapy for preventing corticosteroid induced osteoporosis in patients with arthritis Summary The Osteoporosis Risk Factor and Prevention-Fracture Prevention Study ( OSTPRE-FPS ) was a r and omized population -based open trial ( n = 593 ) . The supplementation group ( n = 287 ) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group ( n = 306 ) received neither supplementation nor placebo . Daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women . Introduction Vitamin D deficiency is common in the elderly , and vitamin D levels are associated with low bone mineral density ( BMD ) . The working hypothesis was that vitamin D and calcium supplementation could prevent bone loss in ambulatory postmenopausal women . Methods The OSTPRE-FPS was a r and omized population -based open trial with a 3-year follow-up in 3,432 women ( aged 66 to 71 years ) . A r and omly selected sub sample of 593 subjects underwent BMD measurements . The supplementation group ( n = 287 ) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group ( n = 306 ) received neither supplementation nor placebo . Results In the intention-to-treat analysis , total body BMD ( n = 362 ) increased significantly more in the intervention group than in the control group ( 0.84 % vs. 0.19 % , p = 0.011 ) . The BMD change differences at the lumbar spine ( p = 0.372 ) , femoral neck ( p = 0.188 ) , trochanter ( p = 0.085 ) , and total proximal femur ( p = 0.070 ) were statistically nonsignificant . Analyses in compliant women ( ≥80 % of use ) result ed in stronger and statistically significant effects at the total body and femoral regions . Conclusion Daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women with adequate nutritional calcium intake BACKGROUND & AIMS Osteoporosis is a major health problem worldwide . Low weight is a major risk factor for low bone mass and fractures . The aim of this study was to investigate the effects on bone tissue of protein-rich supplementation alone or in combination with n and rolone decanoate in lean elderly women after a hip fracture . METHODS Sixty elderly women with BMI < 24 kg/m(2 ) admitted to hospital due to a femoral neck fracture were r and omised to a  control group  , to receive a protein-rich formula or to receive the same formula with an addition of n and rolone decanoate for 6 months . All patients received additional calcium and vitamin D. The effects after 6 and 12 months were measured by means of bone mineral density ( BMD ) using dual-energy X-ray absorptiometry ( DXA ) , and with biochemical bone markers . Osteocalcin and C-terminal telopeptide of collagen-1 ( CTX ) were used to estimate bone formation and bone resorption , respectively . RESULTS The analyses showed an increase in total body BMD at 6 and 12 months in patients who received protein-rich supplementation . N and rolone decanoate did not appear to have any additional effect on BMD . Osteocalcin increased in all groups while no significant changes were found for CTX . CONCLUSION The overall results of the study indicated that protein-rich supplementation given to lean elderly female hip fracture patients increased the total body BMD Summary Vitamin K mediates the synthesis of proteins regulating bone metabolism . We have tested whether high vitamin K2 intake promotes bone mineral density and bone strength . Results showed that K2 improved BMC and femoral neck width , but not DXA-BMD . Hence high vitamin K2 intake may contribute to preventing postmenopausal bone loss . Introduction Vitamin K is involved in the synthesis of several proteins in bone . The importance of K vitamins for optimal bone health has been suggested by population -based studies , but intervention studies with DXA-BMD as a clinical endpoint have shown contradicting results . Unlike BMC , DXA-BMD does not take into account the geometry ( size , thickness ) of bone , which has an independent contribution to bone strength and fracture risk . Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake . Methods A r and omized clinical intervention study among 325 postmenopausal women receiving either placebo or 45 mg/day of vitamin K2 ( MK-4 , menatetrenone ) during three years .  BMC and hip geometry were assessed by DXA . Bone strength indices were calculated from DXA-BMD , femoral neck width ( FNW ) and hip axis length ( HAL ) . Results K2 did not affect the DXA-BMD , but BMC and the FNW had increased relative to placebo . In the K2-treated group hip bone strength remained unchanged during the 3-year intervention period , whereas in the placebo group bone strength decreased significantly . Conclusions Vitamin K2 helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW , whereas it has little effect on DXA-BMD OBJECTIVE To determine the relative importance of fall characteristics , body habitus , and femoral bone mineral density ( BMD ) in predicting hip fracture in community-dwelling elderly . DESIGN Prospect i ve case-control study . SETTING Community-based academic hospital . PARTICIPANTS A total of 149 ambulatory , community-dwelling fallers ( 126 women , 23 men ) aged 65 years and older , including 72 case patients ( fallers with hip fracture ) and 77 control fallers ( fallers with no hip fracture ) . MAIN OUTCOME MEASURES Fall characteristics , body habitus , femoral BMD . RESULTS Significant and independent risk factors for hip fracture in both sexes were direction of the fall ( adjusted odds ratio [ OR ] , 5.7 ; 95 % confidence interval [ CI ] , 2.3 to 14.0 ; P < .001 ) ; femoral neck BMD ( a decrease of 1 SD ; adjusted OR , 2.7 ; 95 % CI , 1.6 to 4.6 ; P < .001 ) ; potential energy of the fall ( an increase of 1 SD ; adjusted OR , 2.8 ; 95 % CI , 1.5 to 5.2 ; P < .001 ) ; and body mass index ( a decrease of 1 SD ; adjusted OR , 2.2 ; 95 % CI , 1.2 to 3.8 ; P < .01 ) . Importantly , the OR for the fall direction was unaffected by the addition or removal of BMD from the model . CONCLUSIONS We conclude that among elderly fallers -- in most of whom hip BMD is already less than the fracture threshold -- fall characteristics and body habitus are important risk factors for hip fracture and touch on a domain entirely missed by knowledge of BMD . These data suggest new targets for preventive therapy . In addition to the maintenance of bone density , reductions in fall severity ( eg , by use of trochanteric padding or enhancement of muscle strength ) may provide additional strategies for prevention of hip fracture in this age group 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 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 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 Long-term administration of low doses of corticosteroids is common in the treatment of autoimmune diseases , chronic obstructive lung disease , asthma , and allergic conditions . Although treatment with high doses of corticosteroids causes osteoporosis ( especially in trabecular bone , such as that found in the lumbar spine [ 1 ] ) , use of corticosteroids in low doses ( < 10 mg/d ) was thought to be associated with few substantial side effects [ 2 ] . However , recent research suggests that use of low doses of corticosteroids is also associated with loss of bone mineral density in the lumbar spine [ 3 - 6 ] and that patients receiving continuous therapy with low-dose corticosteroids  have a higher rate of vertebral fracture [ 7 - 9 ] . Corticosteroids cause osteoporosis by several mechanisms , such as decreasing levels of sex steroids [ 10 , 11 ] and direct effects on osteoblast [ 12 ] and osteoclast function [ 13 ] . Use of corticosteroids also decreases absorption of intestinal calcium [ 14 - 17 ] , thereby causing secondary hyperparathyroidism [ 18 ] . Some studies [ 19 , 20 ] have shown that vitamin D3 and its more potent analogues can improve calcium absorption in patients receiving corticosteroids .  Treatment with 1,25-dihydroxyvitamin D3 ( calcitriol ) and calcium stabilized bone mineral density in the lumbar spine in patients receiving moderate to high doses of corticosteroids [ 21 ] . However , calcitriol is a potent vitamin D analogue that can cause hypercalcemia and hypercalciuria [ 22 ] . The associated toxicity and expense make it impractical for widespread use for prevention of bone loss in all patients receiving long-term treatment with low-dose corticosteroids . Vitamin D3 , the parent compound , is generally well tolerated and rarely causes side effects when used in the recommended dosage ( 400 to 800 IU/d ) . It has been suggested that vitamin D3 and calcium should be given to all patients receiving long-term corticosteroid therapy [ 23 ] . However , few data support this approach . Early studies [ 24 ] suggested that calcium and pharmacologic dosages of vitamin D3 ( 50 000 IU three times a week ) increased bone mineral density in patients taking long-term corticosteroids  , but bone mineral density was measured only in the radius . Adachi and colleagues [ 25 ] recently reported that treatment with calcium ( 1000 mg/d ) and vitamin D3 ( 50 000 IU/wk ) did not prevent bone loss associated with moderate- to high-dose treatment with corticosteroids , but Healy and colleagues [ 26 ] found that calcium and vitamin D3 prevented substantial loss of bone mineral density in a similar group of patients starting corticosteroid treatment . No r and omized , controlled , clinical trials have shown the effectiveness of calcium and vitamin D3 supplementation for prevention of bone loss secondary to long-term low-dose corticosteroid treatment . Therefore , we studied the effects of calcium ( 1000 mg/d ) and vitamin D3 ( 500 IU/d ) supplementation on the bone mineral density of patients with rheumatoid arthritis and contrasted the efficacy of this supplementation in patients who were and those who were not receiving corticosteroids . Methods Patients Patients with rheumatoid arthritis who were followed at the University of Vermont , College of Medicine ( n = 354 ) were identified through a computer listing by diagnostic code . All identified patients were contacted by mail and asked whether they were interested in participating in a study of the effects of rheumatoid arthritis and medication on bone mineral density . Patients were eligible if they were between 18 and 65 years of age and had a diagnosis of rheumatoid arthritis as defined by the revised American College of Rheumatology criteria [ 27 ] , serum creatinine level less than 176.8 mol/L , and normal liver function . Patients were excluded if they were receiving an anticonvulsant medication , hydrochlorothiazide , bisphosphonates , fluoride , calcitonin , or calcitriol or if they had a history of malabsorption , hyperparathyroidism , immobilization , metabolic bone disease , or thyroid disease with an abnormal thyroid-stimulating hormone . One hundred thirty patients met these criteria , agreed to participate , and entered the study between January 1991 and January 1992 . Study Design The study was approved by the Committee on Human Research of the University of Vermont , and informed consent was obtained as patients entered the study . Patients were stratified by sex , menopausal status ( premenopausal , postmenopausal without estrogen replacement , or postmenopausal with estrogen replacement ) , and current dosage of prednisone ( < 10 mg/d or 10 mg/d ) . Patients were r and omly assigned in blocks of four to a treatment group using a r and om-number table . Group assignment was kept in sealed envelopes to ensure blinding . Patients received either calcium carbonate ( 1000 mg/d ) and vitamin D3 ( 500 IU/d ) ( two tablets twice a day of Os-Cal 250 + D , SmithKline Beecham Healthcare , Pittsburgh , Pennsylvania ) or an identical placebo . Study medication was taken with breakfast and dinner . Measurement Demographic information and information about risk factors for osteoporosis , such as smoking history , use of alcohol , menstrual history , parity , fracture history , and use of medications ( including thyroid medication and estrogen replacement therapy ) were obtained from question naires given at the beginning of the study and annually thereafter . Calcium intake was assessed using the Food Frequency Question naire [ 28 ] and 3-day dietary history . Disease-related information included activity level , measured by the Framingham Activity Index [ 29 ] ; disease severity , measured by the Health Assessment Question naire [ 30 ] ; and a severity score , based on radiologic findings [ 31 ] . Information about disease duration and use of prednisone or disease-modifying antirheumatic drugs was ascertained by chart review . Bone mineral densities of the femur ( femoral neck , Ward triangle , and trochanter ) and lumbar spine were measured in all patients by  dual-energy x-ray absorptiometry  ( Lunar Corp. , Madison , Wisconsin ) at the beginning of the study and at yearly follow-up visits . All studies were done using the same machine . Stability of measurement was assured with daily quality -assurance calibration by the manufacturer , weekly Lunar aluminum phantom in water bath , and Hologic spine phantom three times weekly . The coefficient of variation ( calculated using 11 patients and three measurements ) was 1.2 % for the anteroposterior spine and 2.2 % for the femoral neck . At the start of the study , the lateral scan of the spine was thought to be the most sensitive measurement for detecting changes induced by cortico-steroids [ 32 ] . However , we and others [ 33 ] have found the reproducibility of this view with the available technology to be suboptimal , especially in patients with arthritis , because correct positioning is difficult . We subsequently obtained anteroposterior scans of the spine . For patients from whom only the lateral view of the spine was available at baseline ( n = 48 [ 20 patients in the treatment group and 28 in the placebo group ] ) , we determined the anteroposterior value by adding the difference between the anteroposterior and lateral scans obtained after the first year of the study to the lateral scan obtained at baseline . This provided adequate measurement because the differences between anteroposterior and lateral views for each patient remained relatively constant ( within 0.10 0.07 g/cm2 for 87 % of patients ) . Patients were seen by the study coordinator at 6-month intervals to assess compliance . At these visits , pills were counted and patients were question ed about side effects of medication . Statistical Analysis Because loss of bone mineral density over time is presumed to be proportional to the amount of bone mineral density remaining , the yearly rate of change ( ) was estimated using data from the three time points ( baseline , year 1 , and year 2 ) in the following equation : Equation 1 Differences in rates for the two treatment groups were assessed by using the t-test . The effect of treatment after adjustment for group differences in disease severity and duration was examined by linear regression analysis . Patients who received prednisone during the study and those who did not were analyzed separately and in combination . Clinical characteristics of the two treatment groups were compared using t-tests and chi-square tests . Potential interactions between treatment effects and patient characteristics were examined by analysis of variance . All analyses were done using SPS statistical software ( SPS , Inc. , Chicago , Illinois ) . Results Baseline characteristics of the patients completing both years of the study are listed in Table 1 . The patients studied were primarily middle-aged white women . Although study groups were similar for most characteristics , the patients receiving calcium and vitamin D3 tended to have disease of greater severity ( by radiologic stage ) and longer duration than did those receiving placebo . Among patients who were receiving corticosteroids , the mean dosage of prednisone at the initial visit was 5.9 mg/d for the calcium and vitamin D3 group and 5.0 mg/d for the placebo group . During the first year of study , 68 % of patients were taking prednisone ( mean dosage , 5.5 mg/d ; range , 1 to 20 mg/d ) ; during the second year , 65 % were taking prednisone ( mean dosage , 5.6 mg/d ; range , 0.5 to 20 mg/d ) . Table 1 . Baseline Characteristics of Patients Who Had Bone Mineral Density Measurements Available for All Time Points * During the 2-year study period , 29 of the original 130 patients ( 22 % ) dropped out of the study . Fifteen of the patients who dropped out had been in the calcium and vitamin D3 group and 14 had been in the placebo group . Fourteen patients withdrew for personal reasons , 1 patient died , and 3 patients developed serious illness ( inflammatory bowel disease , cancer , and amyotrophic lateral sclerosis ) . Eleven patients ( 7 in the calcium and vitamin D3 group and 4 in the placebo group ) dropped out of the study 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 ) Objective This study aims to test the added value of calcium and vitamin D ( CaD ) in fracture prevention among women taking postmenopausal hormone therapy ( HT ) . Methods This is a prospect i ve , partial-factorial , r and omized , controlled , double-blind trial among Women ’s Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years . A total of 27,347 women were r and omized to HT ( 0.625 mg of conjugated estrogens alone , or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily ) , and 36,282 women were r and omized to 1,000 mg of elemental calcium ( carbonate ) plus 400 IU of vitamin D3 daily , each compared with placebo .  A total of 16,089 women participated in both arms . The predefined outcomes were adjudicated hip fractures and measured bone mineral density . Results Interaction between HT and CaD on hip fracture ( P interaction = 0.01 ) was shown . The effect of CaD  was stronger among women assigned to HT ( hazard ratio [ HR ] , 0.59 ; 95 % CI , 0.38 - 0.93 ) than among women assigned to placebo ( HR , 1.20 ; 95 % CI , 0.85 - 1.69 ) . The effect of HT on hip fracture was stronger among women assigned to active CaD ( HR , 0.43 ; 95 % CI , 0.28 - 0.66 ) than among women assigned to placebo ( HR , 0.87 ; 95 % CI , 0.60 - 1.26 ) . CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake . There was no interaction between HT and  CaD  on change in hip or spine bone mineral density .  Conclusions Postmenopausal women at normal risk for hip fracture who are on CaD supplementation  experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake Bone loss is a common complication in patients before and after liver transplantation ( LT ) . The aim of this study was to investigate the efficacy of prophylactic treatment with bisphosphonates after LT in preventing progressive bone loss in LT patients . We included 136 patients with end-stage liver diseases awaiting LT .  Bone mineral density ( BMD ) ( by dual X-ray absorptiometry ) and markers of bone metabolism were determined before , and 4 , 12 , 24 , 36 , and 48 months after LT . All patients received vitamin D and calcium supplementation before and after LT , those with osteopenia or osteoporosis prior to LT were additionally treated with alendronate following LT . Decreased BMD was seen in a high percentage of patients undergoing LT ( osteopenia 48.5 % , osteoporosis 23.5 % ) . Reduced BMD before LT was not related to gender , underlying liver disease , or Child-Turcotte-Pugh classification . Body mass index ( BMI ) prior to LT , however , correlated significantly with the fracture risk . Alendronate prevented the ubiquitously observed bone loss after LT in patients with osteoporosis and osteopenia and , in addition , led to an increase in BMD in patients with osteoporosis within 24 months after LT . In conclusion , our study suggests that alendronate is efficacious in preventing the natural course of bone loss associated with LT 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 Fracture of the proximal femur is the most dramatic clinical sequela of osteoporosis [ 1 , 2 ] . It is associated with a high mortality rate , need for long-term medical care , and prolonged disability [ 3 - 5 ] . Protein malnutrition is often seen in elderly persons and is more severe in patients with hip fracture [ 6 - 11 ] . Protein deficiency may contribute to the occurrence of hip fracture by reducing muscle strength , impairing movement coordination , and diminishing the protective layer of soft tissue padding [ 9 , 10 , 12 - 14 ] It may also be associated with lower bone mineral density at the proximal femur [ 15 ] . Furthermore , malnutrition in general and protein deficiency in particular at admission and during recovery may adversely influence clinical outcome after hip fracture [ 7 , 9 , 10 , 16 - 18 ] . Protein restriction has been shown to reduce plasma levels of insulin-like growth factor-I ( IGF-I ) by inducing resistance to the action of growth hormone in the liver and increasing the metabolic clearance rate of the growth factor [ 19 - 23 ] . Furthermore , evidence shows that protein depletion may blunt the effect of IGF-I on target organs [ 20 ] . Thus , low protein intake in elderly persons may be detrimental to skeletal integrity , muscle strength , and immune response [ 11 , 24 - 27 ] because of decreased production and action of IGF-I , which favorably influences these systems [ 28 - 33 ] . Previous studies [ 16 , 17 ] have shown that a 5-week course of protein supplements can reduce the medical complication rate and duration of hospital stay in patients with recent hip fracture . These findings were independent of energy , calcium , and vitamin D intake [ 17 ] . Whether these observations were related to the restoration of decreased IGF-I levels and whether bone may benefit from long-term protein supplementation are not known . We investigated whether protein supplements in vitamin D-replete patients with a recent hip fracture who were receiving calcium supplements could increase circulating IGF-I levels and favorably influence bone mineral density . Methods Patients Patients were recruited in the orthopedic ward of Geneva University Hospital , the referral center that receives 94.6 % of all patients with hip fracture from an area with a population of approximately 400 000 persons [ 5 ] . The protocol was approved by the ethical committee of the Geneva University Hospital Department of Surgery . Inclusion criteria were age greater than 60 years ; recent hip fracture ( within 2 weeks ) attributable to osteoporosis ( that is , a fracture after a minor trauma , such as a fall from st and ing height ) ; and the ability to give written , informed consent . Exclusion criteria were pathologic fracture ; fracture caused by severe trauma ; history of contralateral hip fracture ; severe mental impairment ; active metabolic bone disease ; renal failure ( plasma creatinine concentration 200 mol/L ) ; acute illness that could interfere with the study protocol ; severe malnutrition ( serum albumin level < 15 g/L ) ; consumption of drugs known to alter bone metabolism , such as calcitonin , fluoride , sex hormones , corticosteroids , or bisphosphonates ; and life expectancy of less than 1 year . Using a r and om number table , we assigned patients to receive an oral protein supplement composed of 90 % milk proteins or a placebo made isocaloric by the addition of maltodextrins . Patients took the assigned intervention 5 days a week for 6 months in addition to their regular diet . All patients received one oral dose of vitamin D3 , 200 000 IU ( vitamine D3B.O.N. , Doms-Adrian , Courbevoie , France ) , to correct any possible vitamin D deficiency [ 34 ] . The daily protein supplement ( Meritene , S and oz Nutrition Ltd. , Berne , Switzerl and ) provided 1050 kJ ( 250 kcal ) of energy in the form of 20 g of proteins , 3.1 g of lipids , and 35.7 g of carbohydrates ( 54.4 g in placebo ) . The other constituents of the 65 g powder supplement were vitamin A ( 1000 IU ) , vitamin K1 ( 30 g ) , vitamin C ( 20 mg ) , calcium ( 550 mg ) , magnesium ( 91 mg ) , phosphorus ( 429 mg ) , and sodium ( 228 mg ) . The supplement is design ed to normalize but not overcompensate for the insufficient dietary intake of protein of elderly persons with a recent fracture of the proximal femur [ 16 ] . Compliance was verified by weekly phone calls and by counting the remaining nutritional supplement bags , which were forwarded monthly by mail . Clinical Data Medical history , clinical characteristics , anthropometric data , and performance status according to an Activities of Daily Living score [ 35 ] were evaluated . Dietary intakes were recorded by using a food-frequency question naire [ 36 ] about the week before the fracture . Food intakes were analyzed by using a nutrient software system ( Fruitdor , Astra-Calve , Paris , France ) . Dietary intake of calcium , phosphorus , and protein was calculated from intake of dairy products , meat , fish , and vegetables . Because many patients were unable to st and a few days after hip fracture , their height was determined with a fathom measure while they were recumbent . Body weight was determined with a scale that correlated highly with that provided by measurement of whole body bone , fat , and lean mass as assessed by dual x-ray absorptiometry [ 37 ] . Mid-arm circumference was measured with a tape measure ( coefficient of variation , 2 % ) . Isometric muscle strength of the biceps of the dominant arm was evaluated with a dynamometer ( Lido , Lidoactive Isokinetic System , Loredan Biomedical Inc. , West Sacramento , California ) , which measures the peak torque ( coefficient of variation < 5 % ) . The grip strength of the same arm was measured with a dynamometer ( Vigorimeter , Martin Medizin-Technik , Tuttlingen , Germany ) [ 38 ] . The mean of three measurements was used for calculation . Biochemical Data Within 120 hours after surgery , we used st and ard methods to analyze venous blood sample s for protein-corrected plasma levels of calcium , phosphate , creatinine , total proteins , albumin , and prealbumin . We also measured levels of IGF-I ( Nichols Institute , San Juan Capistrano , California ) after acid-ethanol extraction and cryoprecipitation [ 39 ] , intact parathyroid hormone ( Immulite , Diagnostic Products , Los Angeles , California ) , calcitriol , calcidiol ( Incstar , Stillwater , Minnesota ) , and osteocalcin ( CIS-BIO International , Gif-sur-Yvette , France ) . Biochemical measurements were repeated 6 and 12 months after the fracture . Serum IGF-I binding proteins were measured by Western lig and blot analysis [ 40 ] . Briefly , 3 L of serum was boiled and separated onto 15 % sodium dodecylsulfate polyacrilamide gel electrophoresis under nonreducing conditions . Proteins were electrically blotted onto a nitrocellulose membrane , and IGF-I binding proteins were detected after incubating the membranes with radioiodinated IGF-I at 4C for 24 hours . Insulin-like growth factor binding proteins were quantified by phosphorimaging ( Molecular Dynamics , Sunnyvale , California ) . The intensity of the b and s corresponding to the appropriate molecular weights [ 40 ] was expressed as the percentage of total bound radioactive IGF-I. Measurements of calcium , phosphate , and creatinine were obtained from the second fasting morning urine . The ratio of hydroxyproline to creatinine in the same sample was taken as a reflection of bone resorption . Markers of bone resorption ( pyridinoline and deoxypyridinoline ) in the first morning spot urine were measured by detecting fluorescence emission after acid hydrolysis and separation with isocratic reverse-phase high-performance liquid chromatography ( BioRad System , Munich , Germany ) , and the values were adjusted to the creatinine concentration . Immunologic Data Concentrations of IgA , IgG , IgM , and isohemagglutinins were measured by using st and ard methods . Cell-mediated immunity was assessed by using a skin-test antigens for cellular hypersensitivity system ( STACH , Institut Merieux , Lyon , France ) , which evaluates the size of the skin reaction to various antigens injected intradermally [ 41 ] . Bone Mass Assessment We measured areal bone mineral density at the lumbar spine ( anteroposterior and lateral views ) , the contralateral proximal femur ( femoral neck and trochanter ) , and the contralateral mid-femoral shaft . We also measured whole-body bone mineral content , fat , and lean mass by using dual x-ray absorptiometry ( Hologic QDR-2000 , Waltham , Massachusetts ) . The coefficients of variation of these measurements are reported elsewhere [ 37 , 42 ] . Vertebral Deformity Two series of lateral radiography of the thoracic and lumbar spine were taken at the start of the study and at 12 months . The films were examined by a single investigator ( who was unaware of treatment group assignment ) according to a 6-point analysis procedure for each vertebral body from T4 to L4 [ 43 , 44 ] ( intra-observer coefficient of variation , 1.8 % to 3.1 % ) . At baseline , fracture was defined by a decrease of 20 % in the ratio of anterior or middle height to posterior height . Patients were considered to have a new vertebral deformity if the anterior , middle , or posterior height decreased by more than 20 % between the two examinations . Statistical Analysis All values are given as the mean SD for baseline measurement and the mean SE for comparisons of outcome results . All analyses were performed by using the SAS procedure ( Cary , North Carolina ) . One-way analysis of variance was used . A two-tailed P value less than 0.05 was considered significant . Role of the Funding Sources This study was supported by grants from S and oz Nutrition Ltd. , Berne , Switzerl and , and the Swiss National Research Science Foundation . The skin-test antigens for cellular hypersensitivity system was supplied by Rhone-Poulenc , Thalwil , Switzerl and . No organization influenced the design , conduct , or reporting of the study . Results Of 842 patients evaluated from April 1992 to February 1994 , 82 were recruited into the r and omized , double-blind , placebo-controlled trial . This low enrollment rate was due to patients ' poor medical or cognitive conditions and reluctance to give informed consent . OBJECTIVES A high prevalence of hip and other fractures in elderly patients with Parkinson ’s disease has been linked to reduced bone mass arising from a defect of renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Treatment with 1α-hydroxyvitamin D3 ( 1α(OH)D3 ; an active form of vitamin D ) was evaluated for maintaining bone mass and reducing the incidence of hip and other non-vertebral fractures in patients with Parkinson ’s disease . METHODS In a double blind , r and omised trial , 86 elderly patients with Parkinson ’s disease ( mean Hoehn and Yahr stage , 3 ; mean age 70.6 years ) were r and omised to receive either 1 μg 1α(OH)D3 daily ( treatment group , n=43 ) or a placebo ( n=43 ) for 18 months . Bone mineral densities in the second metacarpals were determined by computed radiographic densitometry . Serum bone turnover indices were measured serially , and incidence of non-vertebral fractures was recorded . RESULTS Bone mineral densities decreased 1.2 % in the treatment group compared with 6.7 % in the placebo group during 18 months ( p<0.0001 ) . At baseline in both groups , the serum concentration of 1 , 25-[OH]2D was reduced . Parathyroid hormone was abnormally increased in 15 patients ( 17 % ) and correlated negatively with serum 25-hydroxyvitamin D , indicating compensatory hyperparathyroidism . Eight patients  sustained fractures ( six at the hip and two at other sites ) in the placebo group , and one hip fracture occurred among treated patients ( odds ratio 9.8 ; p=0.0028 ) . CONCLUSION By increasing serum 1 , 25-[OH]2D concentrations , treatment with 1α(OH)D3 can reduce the risk of hip and other non-vertebral fractures in osteoporotic elderly patients with Parkinson ’s disease by slowing the loss of bone mineral densities 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 Background : Osteoporosis in men is an important public health problem . Because of the tendency of the numbers of the elderly population to increase , and age-specific incidence of fractures , it is inevitable that the health burden due to fractures will increase . Chronic alcoholism is associated with other risk factors , such as poor nutrition , leanness , liver disease , malabsorption , vitamin D deficiency , hypogonadism , hemosiderosis , parathyroid dysfunction and tobacco use , and these may contribute to the pathogenesis of bone disease related to alcoholism . Chronic alcohol intake may reduce bone density , but can also increase bone density . It is well established that liver disease also induces bone density changes , thus it is difficult to distinguish the role of liver disease from that of alcohol itself in the bone alterations occurring in patients with chronic alcohol consumption . Chronic male alcoholics , not having liver cirrhosis were studied to assess the effect of chronic alcohol consumption on their bone mineral density . Methods : The study subjects comprised of 18 chronic heavy drinkers of more than 40 g of alcohol per day for at least 3 years and 18 age-matched controls who drank less than 20 g of alcohol per day .  The serum and urinary parameters of bone and mineral metabolism were determined . The bone mineral density ( BMD ) was measured by dual-energy X-ray absorptiometry at four axial sites ( lumbar spine , femoral neck , Ward ’s triangle and trochanter ) . Results : The alcoholic and control patients drank an average of 97.6 g and 7.2 g of alcohol per day . Osteocalcin , a marker of bone formation , was slightly decreased in alcoholic patients , and deoxypyridinoline , a marker of bone resorption , was slightly increased , but the difference was not statistically significant ( p>0.05 ) . There were no differences between the two groups in the levels of free testosterone , estradiol , 25(OH ) vitamin D and parathyroid hormone . The Ward ’s triangle and trochanter BMDs of the femur were significantly lower in the alcoholics than the controls , and lumbar spine BMD was decreased in proportion to the total alcohol intake in the alcoholics ( r=−0.625 , p=0.01 ) . Conclusion : We suggest that chronic alcohol consumption induces low bone density in the femur Ward ’s triangle and trochanter . There was also a significant inverse correlation between the lumbar spine BMD and the total amount of alcohol consumed . Large scaled r and omized and prospect i ve studies are needed to clarify the pathogenesis of alcohol-induced osteoporosis
For hip fracture , at a 15 % relative risk , the effect estimate lay between the futility boundary and the inferior boundary , meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount , but uncertainty remains as to whether it might increase hip fractures .
The effect estimate lay within the futility boundary at thresholds of 0·5 % for total hip , forearm , and total body bone mineral density , and 1·0 % for lumbar spine and femoral neck , providing reliable evidence that vitamin D does not alter these outcomes by these amounts .
INTERPRETATION Our findings suggest that vitamin D supplementation does not prevent fractures or falls , or have clinical ly meaningful effects on bone mineral density .
There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health .
BACKGROUND The effects of vitamin D on fractures , falls , and bone mineral density are uncertain , particularly for high vitamin D doses .
We aim ed to determine the effect of vitamin D supplementation on fractures , falls , and bone density .