Comparative Assessment of Bone Mineral Measurements Using Dual X-ray Absorptiometry and Peripheral Quantitative Computed Tomography The Women's Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures Use of Calcium Supplements, Vitamin D Supplements and Specific Osteoporosis Drugs Among French Women Aged 75–85 Years: Patterns of Use and Associated Factors Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. 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 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) Early identification of children predisposed to low peak bone mass and osteoporosis later in life. Prevention of hip fractures by correcting calcium and vitamin D insufficiencies in elderly people. Increase of axial and appendicular trabecular and cortical bone density in established osteoporosis with intermittent nasal salmon calcitonin therapy. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Weekly clodronate treatment prevents bone loss and vertebral fractures in women with subclinical Cushing’s syndrome Long-term effects of calcium-vitamin-D3-fortified milk on bone geometry and strength in older men. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the American College of Physicians Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease [RETRACTED] Alendronate in combination with calcium and vitamin D prevents bone loss after orthotopic liver transplantation: a prospective single-center study. 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Hip fracture prevention with a multifactorial educational program in elderly community-dwelling Finnish women 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. Factors Affecting Bone Loss in Female Endurance Athletes Prevention of osteoporosis as a consequence of aromatase inhibitor therapy in postmenopausal women with early breast cancer: rationale and design of a randomized controlled trial. Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial. Osteoporosis treatment in postmenopausal women after peripheral fractures: impact of information to general practitioners. 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 Chronic Alcohol Ingestion on Bone Mineral Density in Males without Liver Cirrhosis Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group. Effects of protein-rich supplementation and nandrolone on bone tissue after a hip fracture. Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women Impact of the Fracture Risk Assessment on Patient and Physician Behavior in Osteoporosis Prevention Fluoride Salts are no Better at Preventing New Vertebral Fractures than Calcium-Vitamin D in Postmenopausal Osteoporosis: The FAVOStudy Effect of Recombinant Human Parathyroid Hormone (1-84) on Vertebral Fracture and Bone Mineral Density in Postmenopausal Women with Osteoporosis Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study. Fracture incidence and characterization in patients on osteoporosis treatment: the ICARO study. Consumption of vitamin D-and calcium-fortified soft white cheese lowers the biochemical marker of bone resorption TRAP 5b in postmenopausal women at moderate risk of osteoporosis fracture. Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS) Smoking, antioxidant vitamins, and the risk of hip fracture. Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO) Effects of neridronate treatment in elderly women with osteoporosis Safety and efficacy of teriparatide in elderly women with established osteoporosis: bone anabolic therapy from a geriatric perspective.
Abstract : A measurement of bone mass is the single most important determinant of future fracture . However , controversy exists as to which technique ( dual X-ray absorptiometry ( DXA ) or peripheral quanitative computed tomography ( pQCT ) ) , and which site of skeletal measurement ( axial vs appendicular ) provides the best prediction of fracture risk . The aims of this study were : ( 1 ) to determine the ability of pQCT to predict bone mass of the lumbar spine , proximal femur , and distal forearm measured using DXA , and ( 2 ) to compare the ability of DXA and pQCT to discriminate prevalent fractures in women with established osteoporosis . One hundred and sixty-five women were studied , including 47 with established osteoporosis ( vertebral , hip or Colles ' fractures ) as well as 118 who had bone mass measurements to assess osteoporosis risk . Each subject had bone mass measured by DXA at the lumbar spine and femoral neck , and at the distal radius by both DXA and pQCT . In women with fractures , bone mass , when expressed as a st and ardized score , was in general lower using DXA compared with the appendicular skeleton measured using pQCT .  Bone mass determinations at all sites were significantly correlated with each other . The highest correlation coefficients were observed within the axial skeleton . In women with fractures , the highest odds ratios were observed at skeletal regions measured using DXA . Likewise , the areas under the receiver-operating characteristic ( ROC ) curves were comparable at all skeletal regions measured using DXA ; and were significantly greater than the areas under the ROC curves for pQCT measurements . In summary , the strongest discriminators of prevalent fractures were measurements using DXA . Measurements of bone mass at the appendicular skeleton , using either DXA or pQCT , were poorly associated with axial bone mass .  PQCT has the poorer ability to discriminate persons with fractures , and appears to be less sensitive than measurements using DXA Osteoporosis is a major public health issue leading to significant morbidity , loss of independence and excess loss of life . It has been estimated that 13 to 17 million postmenopausal women have low bone mass or osteoporosis ( 1 , 2 ) . This is associated with almost 1.5 million fractures annually , including 300,000 hip fractures ( 2 , 3 ) . A review of the evidence by Cumming in 1990 ( 4 ) and subsequently published r and omized clinical trials have shown that calcium and /or vitamin D supplements may play a role in the prevention and treatment of osteoporosis by slowing the rates of bone loss in postmenopausal and elderly women ( 5–9 ) . However , there are a limited number of calcium and /or vitamin D trials ( 10–13 ) and observational studies [ review of evidence by Cumming and Nevitt ( 14 ) and Kanis ( 15 ) ] , to support a role for calcium and vitamin D supplementation in the reduction of hip and other fractures . It has also been suggested that calcium and vitamin D supplementation may play a role in the reduction of colorectal cancer incidence ( 16–21 ) . To address these major health concerns of postmenopausal women , the Calcium-Vitamin D ( CaD ) trial of the Women ’s Health Initiative ( WHI ) was design ed to test the primary hypothesis that women who are r and omized to receive calcium and vitamin D supplementation will have a lower risk of hip fracture and secondarily , a lower risk of all fractures and colorectal cancer than women receiving corresponding placebo . The objective of this paper is Although vitamin D supplementation in the frail elderly improves calcium absorption , suppresses parathyroid hormone , decreases bone loss and reduces the risk of fractures , such treatment may be ineffective in patients with vertebral osteoporosis , because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel . We have therefore performed a r and omized , single masked study comparing the effects of alfacalcidol treatment ( 0.25 µg twice daily ) and vitamin D2 supplementation ( 500 - 1000 units daily ) on calcium absorption and bone turnover in 46 elderly women ( median age 69 years , range 64–79 years ) with radiological evidence of vertebral fractures .  Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D2 ( p<0.001 ) , but was unchanged in the group receiving alfacalcidol  . Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period . Fractional45Ca absorption increased after 3 months of treatment with alfacalcidol ( p<0.05 ) , but was unchanged with vitamin D2 . There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol ( p<0.05 ) which was not seen in the group receiving vitamin D2 . Our study shows that vitamin D2 supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis . By increasing calcium absorption in such patients , alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis 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 BACKGROUND Supplementation with calcium and vitamin D reduces bone loss and prevents fractures in elderly people , but it is not known whether any lasting benefit remains if the supplements are discontinued . OBJECTIVE The objective was to determine whether gains in bone mineral density ( BMD ) induced by calcium and vitamin D supplementation persist after supplement withdrawal . DESIGN Two-hundred ninety-five healthy , elderly men and women ( aged > /=68 y ) who had completed a 3-y r and omized , placebo-controlled trial of calcium and vitamin D supplementation were followed for an additional 2 y during which no study supplements were given .  BMD was measured by dual-energy X-ray absorptiometry , and biochemical variables related to calcium metabolism and bone turnover were measured . RESULTS In the 128 men , supplement-induced increases in spinal and femoral neck BMD were lost within 2 y of supplement discontinuation , but small benefits in total-body BMD remained . In the 167 women , there were no lasting benefits in total-body BMD or at any bone site . Consistent with the observations on BMD , the bone turnover rates in both men and women ( as measured by serum osteocalcin concentrations ) returned to their original higher concentrations within the same 2-y period . CONCLUSION Discontinued calcium and vitamin D supplementation has limited cumulative effect on bone mass in men and women aged > /=68 Background 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 ) 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 The amount of bone that is gained during adolescence is the main contributor to peak bone mass , which , in turn , is a major determinant of osteoporosis and fracture risk in the elderly . We examined whether computed tomography measurements for the density and the volume of bone in the axial and the appendicular skeletons could be tracked through puberty in 40 healthy white children ( 20 girls and 20 boys ) . Longitudinal measurements of the cross-sectional area and cancellous bone density of the vertebral bodies and the cross-sectional and cortical bone areas of the femurs at the beginning of puberty accounted for 62 - 92 % of the variations seen at sexual maturity ; on average , 3 yr later . When baseline values for these bone traits were divided into quartiles , a linear relation across Tanner stages of sexual development was observed for each quartile in both girls and boys . The regression lines differed among quartiles for each trait , paralleled each other , and did not overlap . Thus , we are now in a position to identify those children who are genetically prone to develop low values for peak bone mass and toward whom osteoporosis prevention trials should be geared 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 The aim of this study was to examine the effect of intranasal administration of salmon calcitonin to a group of 24 postmenopausal women with severe , established osteoporosis ( t score < -2.5 SD ) and more than one vertebral fracture . The patients were treated with 200 IU of nasal salmon calcitonin daily for 2 months with a subsequent pause of 2 months ( 3 cycles ) and 500 mg calcium daily over a total of 12 months in an open r and omized study . The patients were compared with an age matched control group of 18 women of a similar clinical status who were treated with calcium and vitamin D only . In the nasal calcitonin treatment group an increase in the trabecular axial bone density of 2.8 % was achieved , as well as increase in trabecular appendicular ( forearm ) bone density of 1.6 % , together with a cortical bone density increase of 1.8 % axial and 1 % appendicular . Initially , elevated values of urinary deoxypyridinoline were found in 12 women in the nasal calcitonin treatment group ; these levels returned to normal under salmon calcitonin nasal therapy and documented the inhibition of increased osteoclastic activity .  Cyclic intermittent calcitonin nasal therapy led to a general increase in trabecular and cortical axial and appendicular bone density , marked alleviation of the subjective sensation of pain , and a reduction in the daily dose of accompanying nonsteroidal anti-inflammatory drugs by 50 % Description This guideline up date s the 2008 American College of Physicians ( ACP ) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women . This guideline is endorsed by the American Academy of Family Physicians . Methods The ACP Clinical Guidelines Committee based these recommendations on a systematic review of r and omized controlled trials ; systematic review s ; large observational studies ( for adverse events ) ; and case reports ( for rare events ) that were published between 2 January 2005 and 3 June 2011 . The review was up date d to July 2016 by using a machine-learning method , and a limited up date to October 2016 was done . Clinical outcomes evaluated were fractures and adverse events . This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density , including pharmaceutical prescriptions , calcium , vitamin D , and estrogen . Evidence was grade d according to the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) system . Target Audience and Patient Population The target audience for this guideline includes all clinicians . The target patient population includes men and women with low bone density and osteoporosis . Recommendation 1 ACP recommends that clinicians offer pharmacologic treatment with alendronate , risedronate , zoledronic acid , or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis . ( Grade : strong recommendation ; high- quality evidence ) . Recommendation 2 ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 3 ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinical ly recognized osteoporosis . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 4 ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 5 ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women . ( Grade : strong recommendation ; moderate- quality evidence ) . Recommendation 6 ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences , fracture risk profile , and benefits , harms , and costs of medications . ( Grade : weak recommendation ; low- quality evidence ) 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 Introduction : Chronic mild endogenous glucocorticoid excess has been shown to cause bone loss and to increase fracture risk in both post-menopausal and premenopausal women . Currently , it is unclear if patients with sub clinical Cushing ’s syndrome ( SCS ) with osteoporosis or osteopenia may benefit from antiresorptive treatment and the type of therapy to be given . Objective : This pilot r and omized study was aim ed at evaluating the effects of 12-month i m administration of clodronate ( 100 mg every week ) on vertebral and femoral bone mineral density ( BMD ) , bone turnover markers and on subjective pain in premenopausal women with SCS due to adrenal incidentalomas . Methods : Forty-six women ( age , 43.1 ±7.7 yr ) with SCS due to adrenal incidentaloma and osteoporosis/osteopenia were r and omized to receive clodronate plus supplement of Calcium ( 500 mg daily ) and Vitamin D3 ( 800 mg daily ) ( group 1 , no.=23 ) or supplements only ( group 2 , no.=23 ) . Both groups were similar in terms of age , body mass index , cortisol levels , BMD values , and bone turnover markers . All of the women were re-evaluated after 12 months . Results : After 12 months of treatment , in group 1 , a significant increase in lumbar BMD occurred ( p=0.04 ) , while bone turnover markers decreased by about one third ( p<0.05 ) . In group 2 , bone turnover markers did not change and BMD values slightly decreased ( p = ns ) . The differences in bone turnover markers and in lumbar BMD between the two groups were significant ( p<0.05 , all ) . No new vertebral fracture occurred in group 1 , while in group 2 the spine radiographies revealed 2 new fractures and a worsening of two pre-existent fractures . An improvement in subjective back pain , assessed by visual analogue scale pain score was observed in group 1 ( from 4.3±2.7 to 2.9±2.0 ; p<0.05 ) but not in group 2 ( from 4.4±3.1 to 4.2±3.4 ; p = ns ) . No significant changes occurred in cortisol secretion or clinical picture of the SCS during the study . Conclusions : Intramuscular administration of clodronate effectively increased lumbar BMD values , preserved bone mass at the femoral neck , stabilized vertebral fracture index , and decreased subjective back pain in pre-menopausal women with SCS . Since the untreated group continued to lose bone , antiresorptive treatment should be considered in patients with SCS , according to the prevision of surgical treatment , prevalent fractures , BMD values , age , concomitant morbidities , and desire for pregnancy The long-term effects of calcium and vitamin D supplementation on bone material and structural properties in older men are not known . The aim of this study was to examine the effects of high calcium ( 1000 mg/day)- and vitamin-D(3 ) ( 800 IU/day)-fortified milk on cortical and trabecular volumetric BMD ( vBMD ) and bone geometry at the axial and appendicular skeleton in men aged over 50 years . One hundred and eleven men who were part of a larger 2-year r and omized controlled trial had QCT scans  of the mid-femur and lumbar spine ( L(1)-L(3 ) ) to assess vBMD , bone geometry and indices of bone strength [ polar moment of inertia ( I(polar ) ) ] . After 2 years , there were no significant differences between the milk supplementation and control group for the change in any mid-femur or L(1)-L(3 ) bone parameters for all men aged over 50 years . However , the mid-femur skeletal responses to the fortified milk varied according to age , with a split of < or=62 versus > 62 years being the most significant for discriminating the changes between the two groups . Subsequent analysis revealed that , in the older men ( > 62 years ) , the expansion in mid-femur medullary area was 2.8 % ( P < 0.01 ) less in the milk supplementation compared to control group , which helped to preserve cortical area in the milk supplementation group ( between group difference 1.1 % , P < 0.01 ) . Similarly , for mid-femur cortical vBMD and I(polar ) , the net loss was 2.3 and 2.8 % less in the milk supplementation compared to control group ( P < 0.01 and < 0.001 , respectively ) . In conclusion , calcium-vitamin-D(3)-fortified milk may represent an effective strategy to maintain bone strength by preventing endocortical bone loss and slowing the loss in cortical vBMD in elderly men 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 The National Institutes of Health 's consensus conference ( 1 ) defined osteoporosis as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk for fracture . Bone strength reflects the integration of two main features : bone density and bone quality .Bone quality refers to architecture , turnover , damage accumulation ( e.g. , microfractures ) , and mineralization . Although osteoporosis can affect any bone , the hip , spine , and wrist are most likely to be affected . Osteoporosis affects an estimated 44 million Americans or 55 % of people 50 years of age or older . Another 34 million Americans are estimated to have low bone mass , meaning that they are at an increased risk for osteoporosis . Osteoporosis can be diagnosed by the occurrence of fragility fracture . In patients without fragility fracture , osteoporosis is often diagnosed by low bone density .  Dual x-ray absorptiometry ( DXA ) is the current gold st and ard test for diagnosing osteoporosis in people without an osteoporotic fracture .  Dual x-ray absorptiometry results are scored as st and ard deviations ( SDs ) from a young healthy norm ( usually female ) and reported as T-scores . For example , a T-score of 2 indicates a bone mineral density that is 2 SDs below the comparative norm . The international reference st and ard for the description of osteoporosis in postmenopausal women and in men age 50 years or older is a femoral neck bone mineral density of 2.5 SD or more below the young female adult mean ( 2 ) . Low bone density , as measured by DXA , is an imperfect predictor of fracture risk , identifying fewer than half the people who go on to have an osteoporotic fracture . Screening guidelines for women are well established ( 3 ) , and the American College of Physicians ( ACP ) recently published guidelines on screening for men ( 4 ) . This guideline presents the available evidence on various pharmacologic treatments to prevent fractures in men and women with low bone density or osteoporosis . Medications used to treat osteoporosis may affect different parts of the skeletal system differently , and efficacy for vertebral fractures does not necessarily imply efficacy for nonvertebral fractures . The target audience for this guideline is all clinicians and the target patient population is all adult men and women with low bone density or osteoporosis . These recommendations are based on the systematic evidence review by MacLean and colleagues ( 5 ) and the Agency for Healthcare Research and Quality sponsored Southern California Evidence -Based Practice Center evidence report ( 6 ) . The drugs currently approved for prevention of osteoporosis include alendronate , ib and ronate , risedronate , zoledronic acid , estrogen , and raloxifene . The drugs currently approved for treatment of osteoporosis include alendronate , ib and ronate , risedronate , calcitonin , teriparatide , zoledronic acid ( in postmenopausal women ) , and raloxifene . Testosterone , pamidronate , and etidronate are not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Methods The literature search done by MacLean and colleagues for the systematic review ( 5 ) included studies from MEDLINE ( 1966 to December 2006 ) , the ACP Journal Club data base , the Cochrane Central Register of Controlled Trials ( no date limits ) , the Cochrane Data base of Systematic Review s ( no date limits ) , Web sites of the United Kingdom National Institute of Health and Clinical Excellence ( no date limits ) , and the United Kingdom Health Technology Assessment Program ( January 1998 to December 2006 ) . The review ers limited their search to English- language publications and human studies . They derived evidence for comparative benefits of various treatments exclusively from r and omized , controlled trials , whereas they included evidence from other types of studies for short- and long-term harms . Two physicians independently abstract ed data about study population s , interventions , follow-up , and outcome ascertainment by using a structured form . For each group within a r and omized trial , a statistician extracted the sample size and number of persons reporting fractures . Two review ers , under the supervision of the statistician , independently abstract ed information about adverse events . The statistician or the principal investigator resolved disagreements . This guideline is based on an evaluation of 76 r and omized , controlled trials , 4 of which were identified in the up date d search , and 24 meta-analyses that were included in the efficacy analyses . The analyses of adverse events included 491 articles , representing 417 r and omized trials , 25 other controlled clinical trials , 11 open-label trials , 31 large observational studies , and 9 case reports of osteonecrosis among bisphosphonate users . MacLean and colleagues ' background article ( 5 ) includes details about the methods used for the systematic evidence review . The ACP rates the evidence and recommendations by using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) system with minor modifications ( Table 1 ) . In addition , the evidence review ers used predefined criteria to assess the quality of systematic review s and r and omized trials , based on internal and external validity assessment s detailed in the Quality of Reporting of Meta-Analyses ( QUOROM ) statement ( 7 ) . Table 1 . The American College of Physicians ' Guideline Grading System The objective of this guideline is to synthesize the evidence for the following questions : What are the comparative benefits in fracture reduction among and also within the following treatments for low bone density :  bisphosphonates , specifically alendronate , risedronate , etidronate , ib and ronate , pamidronate , and zoledronic acid ; calcitonin ; estrogen for women ; teriparatide ; selective estrogen receptor modulators ( SERMs ) , specifically raloxifene and tamoxifen ; testosterone for men ; vitamins and minerals , specifically vitamin D and calcium ; and the combination of calcium plus vitamin D ? How does fracture reduction result ing from treatments vary among individuals with different risks for fracture as determined by bone mineral density ( borderline , low , or severe ) , previous fractures ( prevention vs. treatment ) , age , sex , glucocorticoid use , and other factors ( such as community-dwelling vs. institutionalized or vitamin Ddeficient vs. not ) ? What are the short- and long-term harms ( adverse effects ) of these therapies , and do these vary by specific sub population s ? Comparative Benefits of Drugs versus Placebo in Fracture Reduction Evidence from 24 meta-analyses ( 830 ) and 35 additional r and omized trials published after the meta-analyses ( 3165 ) described the effect of 9 of the 14 agents ( alendronate , etidronate , risedronate , calcitonin , estrogen , teriparatide , raloxifene , calcium , and vitamin D ) on fracture incidence . For 4 agents ( ib and ronate , pamidronate , zoledronic acid , and tamoxifen ) , the review ers found no meta-analyses and instead gathered the evidence from 14 r and omized trials ( 6679 ) . No studies were found that reported fracture rates for testosterone . Three r and omized trials ( 35 , 80 , 81 ) and 1 meta- analysis ( 82 ) evaluated the combination of calcium plus vitamin D  on fractures .  Bisphosphonates Good- quality evidence showed that alendronate , etidronate , ib and ronate , and risedronate prevent vertebral fractures . In addition , evidence from good- quality studies demonstrated that both alendronate and risedronate prevent nonvertebral and hip fractures . Two large r and omized trials showed that zoledronic acid prevents vertebral and nonvertebral fractures in high-risk population s and reduces the risk for hip fracture ( 67 , 74 ) . Ib and ronate has not been shown to reduce nonvertebral fractures ( 68 ) . Of the 6 fairly small trials that looked at vertebral fractures , 1 demonstrated a statistically significant reduction in fractures with pamidronate relative to placebo ( 0.14 [ 95 % CI , 0.03 to 0.72 ] ) ( 73 ) . However , after these data were pooled , the pooled risk estimate for fractures for pamidronate relative to placebo was not significant ( 0.52 [ CI , 0.21 to 1.24 ] ) ( 6 ) . Calcitonin Fair- quality evidence shows that calcitonin reduces vertebral fractures ( 83 , 84 ) . Good- quality evidence indicates that calcitonin does not reduce nonvertebral fractures ( 13 , 16 ) . Estrogen Good- quality evidence shows that estrogen reduces the incidence of vertebral ( 29 , 85 ) , nonvertebral ( 86 ) , and hip fractures ( 85 ) . Teriparatide Good- quality evidence shows that teriparatide prevents vertebral fractures . The evidence related to teriparatide preventing nonvertebral fractures is mixed ; 1 large r and omized trial showed a reduction in nonvertebral fractures ( 34 ) but 2 small trials did not ( 87 , 88 ) . SERMs Good- quality evidence shows that raloxifene prevents vertebral fractures , but that tamoxifen has no effect on vertebral fractures ( 8991 ) . In addition , both raloxifene and tamoxifen had no effect on hip fractures ( 91 ) . Tamoxifen is not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Testosterone No studies reported fracture rates for testosterone . Calcium and Vitamin D In the studies evaluated by MacLean and colleagues ( 5 ) , the evidence for the effect of calcium alone on reduction of fractures is complex . Most studies of pharmacologic agents for osteoporosis include calcium and vitamin D as part of the treatment regimen . Evidence from 1 meta- analysis ( 27 ) and several r and omized trials ( 35 , 48 , 51 , 92 ) showed no significant difference between calcium and placebo in preventing vertebral , nonvertebral , and hip fractures in postmenopausal women . However , nonadherence to therapy may influence this result , and 1 trial with a prespecified analysis of adherent patients found a reduction in fracture risk ( 48 ) . A recent meta- analysis ( 82 ) concluded that the relative risk ( RR ) for fracture with calcium alone was 0.90 ( CI , 0.80 to 1.00 ) , but it did not include a modestly large trial with negative results ( 35 ) . MacLean and colleagues ( 5 ) BACKGROUND 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 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 Background and aims : Given the high risk of subsequent fracture among elderly persons with fracture , it is important to initiate secondary treatment for osteoporosis . Acute rehabilitation centers may offer a unique opportunity to introduce treatment . Therefore , we evaluated willingness-to-participate and compliance with evidence -based interventions for the secondary prevention of  osteoporotic fracture in a non-r and omized study conducted in the acute rehabilitation setting . We also described differences in baseline characteristics between study participants and non- participants . Methods : All consecutive , community-dwelling admissions to an acute rehabilitation unit ( Boston , MA ) with the diagnosis of fracture were screened for enrollment . Eligible subjects were offered a free , 6-month supply of alendronate/cholecalciferol ( 70 mg/2800 IU weekly ) , calcium and vitamin D supplements , and fall prevention strategies . Six-month compliance ( ≥75 % consumption of medication or supplement ) with the interventions was determined at a home visit . Results : Among 62 eligible subjects , 25 agreed to participate . Non- participants were older than participants ( 86 vs 80 yrs , p<0.01 ) . There was no significant difference between other characteristics of participants and non- participants including sex , weight , type of fracture , cognitive status , and functional status . The most common reason for non-participation was reluctance to take another medication . Among participants , only 52 % were compliant with alendronate and 58 % were compliant with calcium and vitamin D supplementation at 6 months . Conclusions : Willingness-to-participate and compliance with secondary prevention strategies for osteoporosis was low in the acute rehabilitation setting , even when medications were provided free of cost . Educating individuals with fracture and their families on the consequences and treatment of osteoporosis may help to decrease the risk of sustaining a second fracture by accepting secondary preventive measures 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 Excessive intake of vitamin A is postulated to have a detrimental effect on bone by inducing osteoporosis . This may lead to an increased risk of fracture , particularly in persons who are already at risk of osteoporosis . However , few studies have specifically examined the association of vitamin A intake through diet and supplement use , with fractures in a cohort of older , community-dwelling women . We prospect ively followed a cohort of 34,703 postmenopausal women from the Iowa Women ’s Health Study to determine if high levels of vitamin A and retinol intake through food and supplement use were associated with an increased risk of hip or all fractures . A semiquantitative food frequency question naire was used to obtain the participants ’ baseline vitamin A and retinol intake . Participants were followed for a mean duration of 9.5 years for incident self-reported hip and nonhip fractures . After multivariate adjustment , it was revealed that users of supplements containing vitamin A had a 1.18-fold increased risk of incident hip fracture ( n=525 ) compared with nonusers ( 95 % CI , 0.99 to 1.41 ) , but there was no evidence of an increased risk of all fractures ( n=6,502 ) among supplement users . There was also no evidence of a dose-response relationship in hip fracture risk with increasing amounts of vitamin A or retinol from supplements . Furthermore , our results showed no association between vitamin A or retinol intake from food and supplements , or food only , and the risk of hip or all fractures . In conclusion , we found little evidence of an increased risk of hip or all fractures with higher intakes of vitamin A or retinol among a cohort of older , postmenopausal women Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community  Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33 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 UNLABELLED Low vitamin D level may predict rickets , osteomalacia , or osteoporosis . We examined serum 25(OH)D concentration as a predisposing factor for bone stress fracture in 756 military recruits . The average serum 25(OH)D concentration was significantly lower in the group with fracture , suggesting a relationship between vitamin D and fatigue bone stress fracture . INTRODUCTION Low vitamin D level may predict rickets , osteomalacia , or osteoporosis . Fatigue bone stress fracture is one of the most frequently seen types of overuse injuries in athletes and military recruits . An association was recently shown between vitamin D and BMC . A correlation has also been found between low femoral BMD and stress fractures . We measured serum 25(OH)D concentration in a population sample of military recruits to determine if vitamin D is a predisposing factor for fatigue bone stress fracture . MATERIAL S AND METHODS We prospect ively followed 800 r and omly selected , healthy Finnish military recruits with a mean age of 19 years for developing stress fractures in homogenous circumstances . Blood for serum 25(OH)D concentration was drawn at entry into military service , and the weight , height , body mass index ( BMI ) , muscle strength , and 12-minute running were measured for all subjects . Serum 25(OH)D concentrations were measured with enzyme immunoassay . At end of the 90-day follow-up , 756 subjects completed the study . Subjects without fracture constituted controls . RESULTS Twenty-two recruits with stress fracture were identified ( 2.9 % ) , the incidence being 11.6 ( 95 % CI : 6.8 - 16.5 ) per 100 person-years . In the final multivariate analysis , the significant risk factor for stress fracture in conscripts was a below median serum 25(OH)D level ( 75.8 nM ) , OR being 3.6 ( 95 % CI : 1.2 - 11.1 ) . No significant associations between BMI ( p = 0.255 ) , age ( p = 0.216 ) , or smoking ( p = 0.851 ) and bone stress fracture were found in this study population . CONCLUSIONS A lower level of serum 25(OH)D concentration may be a generally predisposing element for bone stress fractures . Considering the obvious need of additional vitamin D in prevention of stress fractures , the effects of vitamin D fortification of foods and supplementation will be subjects of interest for future research BACKGROUND Short trials of calcium supplementation show that it reduces loss of bone density in postmenopausal women ; longer observational studies do not generally find a lower risk of hip fracture with higher-calcium diets . Fewer studies have focused on vitamin D in preventing postmenopausal osteoporosis or fractures . OBJECTIVE We assessed relations between postmenopausal hip fracture risk and calcium , vitamin D , and milk consumption . DESIGN In an 18-y prospect i ve analysis in 72 337 postmenopausal women , dietary intake and nutritional supplement use were assessed at baseline in 1980 and up date d several times during follow-up . We identified 603 incident hip fractures result ing from low or moderate trauma .  Relative risks ( RRs ) from proportional hazards models were controlled for other dietary and nondietary factors . RESULTS Women consuming > or = 12.5 microg vitamin D/d from food plus supplements had a 37 % lower risk of hip fracture ( RR = 0.63 ; 95 % CI : 0.42 , 0.94 ) than did women consuming < 3.5 microg/d . Total calcium intake was not associated with hip fracture risk ( RR = 0.96 ; 95 % CI : 0.68 , 1.34 for > or = 1200 compared with < 600 mg/d ) . Milk consumption was also not associated with a lower risk of hip fracture ( P for trend = 0.21 ) . CONCLUSIONS An adequate vitamin D intake is associated with a lower risk of osteoporotic hip fractures in postmenopausal women . Neither milk nor a high-calcium diet appears to reduce risk . Because women commonly consume less than the recommended intake of vitamin D , supplement use or dark fish consumption may be prudent One of the main focuses of lifestyle modification for the prevention of osteoporosis and osteoporotic fractures  in Japan is improvement in dietary calcium intake . However , virtually no r and omized controlled trial to assess the preventive effects of administration of calcium on the risk of fractures has been conducted in Japan . In this study , we review ed all the scientific papers currently available from medical literature data bases to propose evidence -based recommendations on the preventive procedures for osteoporosis . The result of the present systematic review gives the evidence showing that calcium supplementation or optimal dietary calcium intake increases bone density in childhood and adolescence and reduces the risk of fracture due to osteoporosis in the elderly people regardless of the gender . The evidence also supports the current health policy guiding the elderly to increase their dietary calcium intake in daily life Summary Guidelines suggest identification of women at fracture risk by bone density measurement and subsequently pharmacotherapy . However , most women who sustain a hip fracture do not have osteoporosis in terms of bone density . The present non-pharmacological intervention among elderly women unselected for osteoporosis reduced hip fracture risk by 55 % providing an alternative approach to fracture prevention . Introduction Hip fractures are expensive for society and cause disability for those who sustain them . We studied whether a multifactorial non-pharmacological prevention program reduces hip fracture risk in elderly women . Methods A controlled trial concerning 60- to 70-year-old community-dwelling Finnish women was undertaken . A r and om sample was drawn from the Population Information System and assigned into the intervention group ( IG ) and control group ( CG ) . Of the 2,547 women who were invited to the IG , 1,004 ( 39 % ) and of the 2,120 invited to the CG , 1,174 ( 55 % ) participated . The IG participated in a fracture prevention program for 1 week at a rehabilitation center followed by review days twice . The CG received no intervention . During the 10-year follow-up , both groups participated in survey question naire by mail . Outcome of interest was occurrence of hip fractures and changes in bone – health-related lifestyle . Results During the follow-up , 12 ( 1.2 % ) women in the IG and 29 ( 2.5 % ) in the CG sustained a hip fracture ( P = 0.039 ) . The determinants of hip fractures by stepwise logistic regression were baseline smoking ( odds ratio ( OR ) 4.32 ( 95 % confidence interval [ CI ] 2.14–8.71 ) , age OR 1.15/year ( 95 % CI 1.03–1.28 ) , fall history OR 2.7 ( 95 % CI 1.24–5.9 ) , stroke history OR 2.99 ( 95 % CI 1.19–7.54 ) and participating in this program OR 0.45 ( 95 % CI 0.22–0.93 ) . Starting vitamin D and calcium supplement use was more common in the IG compared with the CG . Conclusions The results suggest that this non-pharmacological fracture prevention program may reduce the risk of hip fractures in elderly Finnish women BACKGROUND 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 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 BACKGROUND Aromatase inhibitors ( AIs ) have improved the prognosis for breast cancer survivors and are now st and ard of care for postmenopausal women with hormone receptor positive early stage breast cancer . One side-effect , however , is a decrease in bone mineral density ( BMD ) and increased fracture risk . Since hormone replacement therapy ( HRT ) is contraindicated in these women , one prevention option is exercise combined with vitamin D and calcium . The effect of this intervention on drug-induced osteoporosis is unknown . METHODS A single-blind r and omized controlled trial will be undertaken to test the hypothesis that exercise combined with vitamin D and calcium can prevent the decrease in BMD associated with the use of AIs . Sixty postmenopausal women prescribed an AI for the treatment of breast cancer will be r and omized into either an exercise or control group . Participants r and omized to the exercise group will undertake a 12-month gym-based exercise program , 3 times per week involving resistance and impact training . Participants in the control group will be advised on the benefits of exercise for preventing osteoporosis , but not prescribed exercise . Both groups will receive vitamin D and calcium supplements . The primary outcome will be total hip bone mineral density measured via dual energy X-ray absorptiometry ( DXA ) . Study outcomes will be compared between groups at baseline , 6months and 12months . SUMMARY This study will investigate the effect of exercise in combination with vitamin D and calcium on prevention of drug-induced osteoporosis in postmenopausal women prescribed AIs for the treatment of breast cancer 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 UNLABELLED A low-impact fracture in a postmenopausal woman should prompt investigations for osteoporosis followed , if needed , by appropriate treatment . OBJECTIVES To evaluate the impact of information alerting general practitioners to the need for osteoporosis treatment in postmenopausal women with a recent history of peripheral fracture . METHODS We conducted a prospect i ve 7-month follow-up study of 78 postmenopausal women , with a mean age of 81.5 years , admitted to the emergency department for peripheral fractures . Three months after the fracture , we sent a letter to the general practitioner of each patient emphasizing the probable contribution of osteoporosis to the fracture and the need for osteoporosis treatment . Six months after the fracture , we interviewed the patients by telephone , and one month later we mailed a question naire to those physicians who had not followed the treatment recommendation . RESULTS At emergency room admission , 9 patients were receiving treatment for osteoporosis  (  hormone replacement therapy in one patient and calcium and vitamin D supplementation in eight patients ) . Admission to a ward was required in 66 ( 85 % ) patients . No treatment for osteoporosis was given at discharge . Six months after discharge , seven patients reported recent initiation of calcium and vitamin D supplementation , and none reported other osteoporosis treatments . The response rate to the physician question naire mailed 7 months after discharge was 54 % ( n=28 ) ; responses showed treatment of 11 additional patients , by calcium and vitamin D supplementation in six cases and by bisphosphonates with or without calcium and vitamin D supplementation in five cases . Treatment initiation rates were similar in patients younger and older than 80 years . CONCLUSIONS Despite information of general practitioners about the need for osteoporosis treatment , such treatment was initiated in only 30.5 % of patients . General practitioners may be reluctant to initiate osteoporosis treatment in patients who are very old or have multiple comorbidities 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 : 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 In postmenopausal women , the use of aromatase inhibitors increases bone turnover and induces bone loss at sites rich in trabecular bone at an average rate of 1 - 3 % per year leading to an increase in fracture incidence compared to that seen during tamoxifen use . The bone loss is much more marked in young women with treatment-induced ovarian suppression followed by aromatase inhibitor therapy ( average 7 - 8 % per annum ) . Pre-treatment with tamoxifen for 2 - 5 years may reduce the clinical significance of the adverse bone effects associated with aromatase inhibitors , particularly if this leads to a shortening in the duration of exposure to an aromatase inhibitor . However , skeletal status should still be assessed at the commencement of aromatase inhibitor therapy . The rate of bone loss in women who experience a premature menopause before the age of 45 or are receiving ovarian suppression therapy is accelerated by the concomitant use of aromatase inhibitors . These patients are considered to be at high risk of clinical ly important bone loss and should have a baseline dual energy X-ray absorptiometry ( DXA ) assessment of bone mineral density ( BMD ) . R and omised clinical trials in postmenopausal women indicate that bisphosphonates prevent the bone loss and accelerated bone turnover associated with aromatase inhibitor therapy and are a promising strategy for the prevention and treatment of osteoporosis in this setting . Treatment initiation recommendations are based on a combination of risk factors for osteoporotic fracture and BMD levels .  Bisphosphonates , along with a healthy lifestyle and adequate intake of calcium and vitamin D are the treatments of choice to prevent bone loss . Due to the rate of bone loss associated with breast cancer treatments , and uncertainties about the interaction between aromatase inhibitor use and BMD for fracture risk , the threshold for intervention has been set at a higher level than that generally recommended for postmenopausal osteoporosis . Management recommendations have been summarised in two algorithms , one for women experiencing a premature menopause and the other for postmenopausal women requiring adjuvant aromatase inhibitor therapy 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 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 Objective : To evaluate the impact of a pharmacist-directed osteoporosis screening program utilizing the  fracture risk assessment ( FRAX ) tool on patient and physician behavior . Methods : Postmenopausal women 45 to 65 years with Achilles T score < −1.0 not receiving bisphosphonate therapy were r and omly assigned to a control or intervention group . All participants received a heel ultrasound and pharmacist education on risks of low bone mass . The intervention group received the FRAX and shared their results with their physician . Three months after screening , a telephonic question naire was administered to all participants . Results : A total of 749 patients were screened , with 87 meeting the enrollment criteria ( 43 control and 44 intervention )  . Physician behavior was not different between the groups with respect to ordering vitamin D levels , prescription medication , or dual-energy x-ray absorptiometry scan . A significant difference in vitamin D supplementation occurred between the 2 groups ( P = .024 ) . At follow-up , 72.2 % of responding participants increased daily calcium intake and 76.4 % started or increased physical activity . Conclusion : Physician behavior was not influenced by FRAX results in the intervention group ; however , positive patient behavior changes occurred in both groups . Primary prevention efforts conducted through heel ultrasound screening and pharmacist consultation led women to follow-up ; however , awareness still needs to be raised of the value of FRAX in osteoporosis prevention Abstract . Although fluoride salts have been shown to be capable of linearly increasing spinal bone mineral density ( BMD ) in postmenopausal osteoporosis , the effects of this gain in density on the vertebral fracture rate remain controversial . We conducted a 2-year multicenter , prospect i ve , r and omized , double-masked clinical trial in 354 osteoporotic women with vertebral fractures ( mean age 65.7 years ) . They received either fluoride ( 208 patients ) , given as sodium fluoride ( 50 mg/day ) or as monofluorophosphate ( 200 mg/day or 150 mg/day ) , or a placebo ( 146 patients ) . All patients received daily supplements of 1 g of calcium ( Ca ) and 800 IU of vitamin D2 ( D ) . A 1-year open follow-up on Ca-D was obtained in 124 patients . After 2 years the fluoride group and the Ca-D group had increased their lumbar BMD by 10.8 % and 2.4 % respectively ( p = 0.0001 ) . However , the rate of patients with at least one new vertebral fracture , defined by semiquantitative assessment and evaluable on an intention-to-treat basis in 89 % of patients , was similar in the fluoride groups and the Ca-D group . No difference between the three fluoride regimens was found . The percentage of patients with nonvertebral fractures was not different in the fluoride and Ca-D groups ( 1.9 % and 1.4 % respectively for hip fractures ) . A lower limb pain syndrome occurred more frequently in the fluoride groups . In the 124 patients followed for 1 year after cessation of fluoride therapy , the percentage of patients with at least one new vertebral fracture after 36 months was identical to the percentages in the previous fluoride group and the Ca-D group . We conclude that flouride-Ca-D regimen was no more effective that Ca-D supplements for the prevention of new vertebral fractures in women with postmenopausal osteoporosis Context Research ers have not previously reported the efficacy and safety of parathyroid hormone ( 1 - 84 ) ( PTH ) for the primary prevention of osteoporotic fractures .  Contributions Among 2532 postmenopausal women with osteoporosis r and omly assigned to receive PTH or placebo , PTH decreased new vertebral fractures . The magnitude of the effect depended on assumptions about fractures in the one third of patients who withdrew from the trial prematurely . Adverse effects included hypercalciuria , hypercalcemia , and nausea . Caution Endogenous PTH and vitamin D levels could affect patients response to the drug but were not assessed in the study . Implication s Parathyroid hormone ( 1 - 84 ) effectively prevented new vertebral fractures but also increased hypercalciuria , hypercalcemia , and nausea . The Editors Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing patients to an increased risk for fracture ( 1 ) . Optimal treatment for osteoporosis should improve the amount , density , and quality of bone , thereby reducing skeletal fragility and fractures .  Antiresorptive agents , such as bisphosphonates , are commonly used for treating postmenopausal osteoporosis . Although these agents preserve bone architecture , they do not stimulate new bone formation or improve bone architecture . Anabolic or bone-forming agents are an alternative approach to the treatment of osteoporosis . Research ers have shown that parathyroid hormone ( PTH ) and certain peptide fragments of PTH increase bone mass and improve bone quality ( 2 , 3 ) . Teriparatide , a fragment of human PTH composed of its N-terminal 34 amino acids , has been approved for the treatment of postmenopausal women with osteoporosis who are at high risk for bone fracture . However , research ers have studied this agent only in women with prevalent vertebral fractures ( 4 ) , and data demonstrating prevention of the first vertebral fracture are lacking . We conducted the Treatment of Osteoporosis with Parathyroid Hormone ( TOP ) Study to examine the efficacy and safety of PTH ( 1 - 84 ) versus placebo for treating postmenopausal women with osteoporosis . We design ed the study to examine the change in incidence of all vertebral fractures between the treatment groups . We also design ed the study to examine the efficacy of this new bone-forming agent in preventing a first vertebral fracture in women without a vertebral fracture . Methods Study Participants We included postmenopausal women 45 to 54 years of age if bone mineral density ( BMD ) was 3.0 SDs or more ( T-score 3.0 ) below the mean peak bone mass of young adult women at the lumbar spine , femoral neck , or total hip with no prevalent vertebral fracture or if BMD T-score was2.5 and they had 1 to 4 vertebral fractures before enrollment . We included postmenopausal women 55 years of age or older if BMD T-score was2.5 and they had no vertebral fractures or if BMD T-score was2.0 and they had 1 to 4 vertebral fractures . We excluded women if baseline serum calcium level was greater than 2.66 mmol/L ( > 10.7 mg/dL ) or if urinary calciumcreatinine ratio was 1.0 or more . We included women with mild hypercalcemia ( serum calcium , 2.55 to 2.66 mmol/L [ 10.2 to 10.7 mg/dL ] ) and mild hypercalciuria ( 24-hour urine calcium7.6 mmol [ 302 mg ] ) at baseline . We did not measure baseline levels of serum PTH and vitamin D. We excluded women if they had taken bisphosphonates for a total of more than 12 months or for more than 90 days in the 12 months before enrollment . We allowed  previous estrogen therapy  if it had been discontinued for at least 4 weeks before the screening visit . We excluded women who had received PTH ( or a peptide fragment or analogue ) , PTH-related protein , fluoride , or strontium and those who had a history of metabolic bone disease ( other than osteoporosis ) , nephrolithiasis , or clinical ly significant hepatic or renal disorders . We also excluded women who were taking medications known to affect bone mineral metabolism . The ethics review committee for each center approved the study . All women provided written informed consent . An independent data and safety monitoring board review ed the progress and safety of the study . Study Design We conducted a r and omized , double-blind , placebo-controlled , parallel-group study in 168 centers in 9 countries . We r and omly assigned the study drug to blocks of 4 patients by using a computer-generated algorithm and shipped it in blocks of 4 to each study site . Women at each site were sequentially assigned the uniquely numbered , r and omly assigned study drug treatment kits by telephone . Women were stabilized for at least 2 weeks with supplemental calcium , 700 mg/d citrate salt , and vitamin D3 , 400 U/d , and then received 100 g of recombinant human PTH or placebo daily by subcutaneous injection for 18 months with continued calcium and vitamin D3 supplementation . Patients were instructed to administer the injection in the morning in the thigh or abdomen by using an injector pen . Study Conduct and Outcome Measures The primary end point was the occurrence of new or worsened vertebral fractures ( in all women and in women with and without a prevalent fracture ) identified by radiography at baseline , month 18 , or the final study visit . Radiologists assessed vertebral fractures in a blinded manner at a central reading organization by using a semiquantitative 4-point grading scale ( 5 ) . An incident vertebral fracture ( new or worsened ) was identified by a change in grade of 1 or more from baseline . Secondary outcomes included changes in BMD at lumbar spine , hip , whole body , and forearm ( distal one-third radius ) that we measured by using dual-energy x-ray absorptiometry with Hologic ( Hologic Inc. , Bedford , Massachusetts ) or Lunar ( GE Medical Systems , Madison , Wisconsin ) densitometers ( reported as percentage change from baseline to st and ardize instrumental differences in determining absolute BMD ) and stadiometric measurements of height . We measured whole body and forearm BMD only in a subset of approximately 300 women from selected sites with appropriate software . We reported nonvertebral clinical fractures and bone loss ( > 7 % at lumbar spine or > 9 % at total hip or femoral neck ) as adverse events . We did not distinguish between traumatic and fragility nonvertebral fractures . We used quantitative computed tomography ( 6 , 7 ) to evaluate the effects of PTH treatment at month 18 on volumetric cortical and trabecular BMD at lumbar vertebra ( L3 ) and the hip in 122 consenting women from a single center at which the technique was available . We assessed bone turnover markers ( serum bone-specific alkaline phosphatase and urinary N-telopeptides of type I collagen ) in the first 600 r and omly assigned women in the study . We measured bone-specific alkaline phosphatase by using the T and em R-Ostase immunoradiometric assay ( interassay coefficient of variation , 8 % ) ( Hybritech , San Diego , California ) . We measured N-telopeptides of type I collagen by using Osteomark enzyme-linked immunoabsorbent assay kits ( interassay coefficient of variation , 4.0 % ) ( Wampole Laboratories , Princeton , New Jersey ) normalized to urine creatinine concentrations . We made safety assessment s at months 1 , 3 , 6 , 9 , 12 , 15 , and 18 that included physical examinations , vital signs , electrocardiography ( months 1 , 12 , and 18 ) , adverse-event monitoring and central clinical laboratory assessment s consisting of chemistry ( including serum total calcium and creatinine ) , hematology , and urinalysis ( including 24-hour urine collection s and fasting , morning urinary calciumcreatinine ratios ) . Adverse events were reported spontaneously by patients , captured in a patients diary , or reported by a patient in response to an open-ended question from clinical study personnel . We used a central laboratory normal range for serum total calcium level of 2.15 to 2.55 mmol/L ( 8.6 to 10.2 mg/dL ) . We performed an analysis for antibodies to PTH with a vali date d electrochemiluminescent immunoassay by using biotinylated recombinant human PTH ( range , 26.3 to 2632.5 pmol/L ; intra-assay coefficient of variation , 8 % to 16 % ) ( Igen International , Inc. , Gaithersburg , Maryl and ) . We obtained iliac crest bone biopsy specimens at month 12 or 18 from a subset of 40 consenting women after tetracycline double-labeling ( 8) that we examined for abnormal bone structure . We anticipated that women might need to discontinue calcium supplementation and reduce the dosing frequency of the study drug to prevent excessive increases in serum calcium level , urinary calcium level , or both . We conservatively predefined hypercalcemia as a single , unconfirmed , predose serum total calcium value greater than 2.66 mmol/L ( > 10.7 mg/dL ) and hypercalciuria as a 24-hour urinary calcium value of 7.6 mmol or more ( 302 mg ) ( increased to > 9.0 mmol [ > 360 mg ] during the study ) or a fasting urinary calciumcreatinine ratio of 1.0 or more . If a woman developed hypercalcemia or hypercalciuria , we discontinued the daily calcium supplementation ; if either condition continued , we reduced the dosing frequency of the study drug . Statistical Analysis We estimated the sample size for our study by assuming that 67 % of the patients would not have a prevalent fracture ; that the 18-month vertebral fracture incidence for patients with and without a prevalent fracture who received placebo would be 10 % and 2.5 % , respectively ; and that 20 % of the patients in each group would discontinue the study early without a new or worsened fracture .  We expected a sample of 2600 patients ( 1300 per treatment group ) to provide at least 90 % power to detect a significant 60 % or greater reduction in vertebral fracture incidence in the PTH treatment group compared with the placebo group ( 2-sided level of 0.05 ) . We analyzed data by using SAS software , version 8.0 ( SAS Institute , Inc. , Cary , North Carolina ) . We used descriptive statistics to summarize demographic and other baseline variables . We assessed comparability of the treatment groups at baseline by using t-tests for continuous 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 UNLABELLED None of the available osteoporosis therapies have been shown to completely abolish the risk of fractures . In clinical practice , the outcome may be even poorer . In 880 patients prescribed with antiresorptives ( alendronate , risedronate , and raloxifene ) for > 1 year , a  fragility fracture  was recorded in 8.9%/year of them . This incidence is considerably higher than that observed in r and omized clinical trials , and it was significantly related to poor compliance and lack of supplementation with calcium and vitamin D. INTRODUCTION Osteoporotic fracture is one of the most important public health concerns among the elderly . Currently available therapies have been shown to significantly decrease the risk of fracture , although none of them completely abolishes this risk . In clinical practice , poor treatment response may also result from a number of other factors . MATERIAL S AND METHODS The Incidence and ChAracterization of inadequate clinical Responders in Osteoporosis ( ICARO ) is a multicenter , observational study carried out in Italy . It aim ed to analyze , in postmenopausal women with established osteoporosis , the risk factors for an " inadequate clinical response " to drug therapy , defined as the occurrence of new vertebral or nonvertebral fragility fractures in patients prescribed , for at least 1 year , alendronate , risedronate , or raloxifene , with a compliance > 50 % . RESULTS In 880 patients treated with antiresorptive agents  for a median of 2.0 years ( 95 % CI : 1.0 - 4.5 ) years , the " inadequate clinical responder ( ICR ) " subjects over the observation period were 220 ( 25 % ) , with an annual incidence of 8.9 % . ICRs , compared with " adequate clinical responders ( ACRs ) , " had more pretreatment fractures and were treated longer ( 2.8 versus 1.8 years ; p < 0.001 ) . After multiple adjustment for these confounding factors , significant determinants of inadequate clinical response were a poorer treatment compliance and a less frequent co-administration of calcium and vitamin D supplements . CONCLUSIONS The incidence of fractures during treatment with antiresorptive agents in a clinical setting is considerably higher than that observed in r and omized clinical trials . Inadequate compliance to treatment and lack of supplementation of calcium and vitamin D are major determinants of this poor response The prevention of increased bone remodeling in postmenopausal women at low 10-y risk of osteoporotic fractures essentially relies on reinforcement of environmental factors known to positively influence bone health , among which nutrition plays an important role . In institutionalized women in their mid-eighties , we previously found that consumption of fortified soft plain cheese increased vitamin D , calcium , and protein intakes , reduced bone resorption biochemical markers , particularly the serum bone specific acid phosphatase tartrate resistant acid phosphatase , isoform 5b ( TRAP 5b ) that reflects osteoclast activity , and stimulated the serum bone anabolic factor insulin-like growth factor-I ( IGF-I ) . Whether these effects occur in much younger women was tested in a prospect i ve control study . Seventy-one healthy postmenopausal women aged 56.6 ± 3.9 y ( mean ± SD ) with low spontaneous supply of both Ca and vitamin D were r and omized to consume daily ( treated , n = 36 ) or not ( controls , n = 35 ) two servings ( 2 × 100 g ) of skimmed-milk , soft plain cheese for 6 wk . The vitamin D and Ca-fortified dairy product provided daily : 661 kJ , 2.5 μg vitamin D , 400 mg calcium , and 13.8 g protein . At the end of the intervention , the decrease in TRAP 5b and the increase in IGF-I were greater in the treated than in the control group ( P < 0.02 ) . The changes in serum carboxy terminal crosslinked telopeptide of type I collagen did not differ significantly between the two groups . In conclusion , like in elderly women , consumption by healthy postmenopausal women of a vitamin D and calcium-fortified dairy product that also increases the protein intake , reduces the serum concentration of the bone resorption biomarker TRAP 5b . This response , combined with the increase in serum IGF-I , is compatible with a nutrition-induced reduction in postmenopausal bone loss rate 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 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 UNLABELLED This study of 9605 community-dwelling residents supports that vitamin D and calcium supplementation may prevent  osteoporotic fractures in elderly in a northern European region known to be deficient in vitamin D , especially during winter periods . INTRODUCTION We evaluated the effect of two programs for the prevention of osteoporotic fractures leading to acute hospital admission in a population of elderly community-dwelling residents . MATERIAL S AND METHODS This was a factorial , cluster-r and omized , pragmatic , intervention study . We included 9605 community-dwelling residents aged 66 + years . We offered a prevention program of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU ( 10 microg ) of vitamin D3 to a total of 4957 participants . Another program with evaluation and suggestions for the improvement of the domestic environment was offered to a total of 5063 participants . Both programs included revision of the resident 's current pharmaceutical treatment . We achieved information on osteoporotic fractures in the study population from the Danish Hospital Registration Data base . We defined osteoporotic fractures as low energy fractures of the proximal humerus , distal forearm , vertebral column , pelvis , cervical femur , and intertrochanteric femur . RESULTS Active participation was 50.3 % in the Calcium and Vitamin D Program and 46.4 % in the Environmental and Health Program . We observed a 16 % reduction in fracture incidence rate ( relative risk [ RR ] , 0.84 ; CI , 0.72 - 0.98 ; p < 0.025 ) among male and female residents offered the Calcium and Vitamin D Program ( intention-to-prevent analysis ) . CONCLUSIONS This study supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in community-dwelling elderly people in a northern European region known to be deficient in vitamin D , especially during winter periods Summary Fall prevention is a key strategy for reducing  osteoporotic fractures . We investigated the association between vitamin D receptor ( VDR ) polymorphisms and reported  falls in postmenopausal women . Bsm1 polymorphisms were associated with falls , balance and muscle power measurements . These results may explain some of the excess fracture risk associated with VDR in some studies . Introduction Fall prevention is a key strategy for reducing osteoporotic fractures . It has been suggested that vitamin D supplementation may reduce the incidence of falls by reducing body sway and increasing muscle power . The vitamin D receptor gene is a well-studied c and i date gene for osteoporosis . We investigated the association between VDR polymorphisms and reported  falls in postmenopausal women . Methods Falls data were collected in two separate population cohorts . Five polymorphisms of the VDR gene were analysed ( Cdx-2 , Fok-1 , BsmI , Taq1 and Apa1 ) in the Aberdeen Prospect i ve Osteoporosis Screening Study ( APOSS ) cohort . Results found in APOSS were then vali date d in an independent cohort — the Osteoporosis and Ultrasound ( OPUS ) study ( Bsm1 and Fok1 only ) , where muscle power and balance were also measured . Results Carriers of the ‘ B ’ allele ( Bsm1 ) showed an increased risk for falls . In APOSS , this was statistically significant for visit 3 multiple falls ( p = 0.047 ) and for recurrent falls ( p = 0.043 ) . Similar results were found in OPUS for visit 1 falls ( p = 0.025 ) and visit 1 multiple falls ( p = 0.015 ) . Bsm1 polymorphisms were also associated with balance and muscle power measurements . Conclusions In conclusion , these results demonstrate an association between the Bsm1 polymorphism and risk of falling that may explain some of the excess fracture risk associated with VDR in some studies Smoking increases the concentrations of free radicals , which have been suggested to be involved in bone resorption . We examined whether the dietary intake of antioxidant vitamins may modify the increased hip fracture risk associated with smoking . We prospect ively studied 66,651 women who were 40 - 76 years of age . Forty-four of the cohort members who sustained a first hip fracture within 2 - 64 months of follow-up ( n = 247 ) and 93 out of 873 age-matched controls were current smokers . Information on diet was obtained by a vali date d food-frequency question naire . The relative risk of hip fracture for current versus never smokers was analyzed in relation to the dietary intake of antioxidant vitamins stratified into two categories ( low/high ) , where median intakes among the controls were used as cut-off points . After adjustment for major osteoporosis risk factors , the odds ratio ( OR ) for hip fracture among current smokers with a low intake of vitamin E was 3.0 ( 95 % confidence interval 1.6 - 5.4 ) and of vitamin C 3.0 ( 1.6 - 5.6 ) . In contrast , the OR decreased to 1.1 ( 0.5 - 2.4 ) and 1.4 ( 0.7 - 3.0 ) with high intakes of vitamin E and C , respectively . This effect was not seen for beta-carotene , selenium , calcium , or vitamin B6 . In current smokers with a low intake of both vitamins E and C , the OR increased to 4.9 ( 2.2 - 11.0 ) . The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers . Our results suggest a role for oxidant stress in the adverse effects on the skeleton of smoking , and that an insufficient dietary intake of vitamin E and C may substantially increase the risk of hip fracture in current smokers , whereas a more adequate intake seems to be protective BACKGROUND There is currently no consensus on the effect of dietary protein intake on the skeleton , but there is some indication that low calcium intakes adversely influence the effect of dietary protein on fracture risk . OBJECTIVE The objective of the present study was to determine whether supplemental calcium citrate malate and vitamin D influence any associations between  protein intake and change in bone mineral density ( BMD ) . DESIGN Associations between protein intake and change in BMD were examined in 342 healthy men and women ( aged > or = 65 y ) who had completed a 3-y , r and omized , placebo-controlled trial of calcium and vitamin D supplementation . Protein intake was assessed at the midpoint of the study with the use of a food-frequency question naire and  BMD  was assessed every 6 mo by dual-energy X-ray absorptiometry . RESULTS The mean ( + /-SD ) protein intake of all subjects was 79.1 + /- 25.6 g/d and the mean total calcium intakes of the supplemented and placebo groups were 1346 + /- 358 and 871 + /- 413 mg/d , respectively . Higher protein intake was significantly associated with a favorable 3-y change in total-body BMD in the supplemented group ( in a model containing terms for age , sex , weight , total energy intake , and dietary calcium intake ) but not in the placebo group . The pattern of change in femoral neck BMD with increasing protein intake in the supplemented group was similar to that for the total body . CONCLUSION Increasing protein intake may have a favorable effect on change in BMD in elderly subjects supplemented with calcium citrate malate and vitamin Low vitamin K status is associated with low BMD and increased fracture risk . Additionally , a specific menaquinone , menatetrenone ( MK4 ) , may reduce fracture risk . However , whether vitamin K plays a role in the skeletal health of North American women remains unclear . Moreover , various K vitamers ( e.g. , phylloquinone and MK4 ) may have differing skeletal effects . The objective of this study was to evaluate the impact of phylloquinone or MK4 treatment on markers of skeletal turnover and BMD in nonosteoporotic , postmenopausal , North American women . In this double-blind , placebo-controlled study , 381 postmenopausal women received phylloquinone  ( 1 mg daily ) , MK4 ( 45 mg daily ) , or placebo for 12 mo . All participants received daily calcium and vitamin D(3 ) supplementation . Serum bone-specific alkaline phosphatase ( BSALP ) and n-telopeptide of type 1 collagen ( NTX ) were measured at baseline and 1 , 3 , 6 , and 12 mo . Lumbar spine and proximal femur BMD and proximal femur geometry were measured by DXA at baseline and 6 and 12 mo . At baseline , the three treatment groups did not differ in demographics or study endpoints . Compliance with calcium , phylloquinone , and MK4  treatment was 93 % , 93 % , and 87 % , respectively . Phylloquinone and MK4 treatment reduced serum undercarboxylated osteocalcin but did not alter BSALP or NTX . No effect of phylloquinone or MK4 on lumbar spine or proximal femur BMD or proximal femur geometric parameters was observed . This study does not support a role for vitamin K supplementation in osteoporosis prevention among healthy , postmenopausal , North American women receiving calcium and vitamin D supplementation Introduction Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures . A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects . Purpose and Methods Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have review ed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases , providing recommendations and guidelines for future studies in this field . Results and conclusions Robust mechanistic evidence is available from in vitro studies and in vivo animal studies , usually employing cholecalciferol , calcidiol or calcitriol in pharmacologic rather than physiologic doses . Although many cross-sectional and prospect i ve association studies in humans have shown that low 25-hydroxyvitamin D levels ( i.e. , < 50 nmol/L ) are consistently associated with chronic diseases , further strengthened by a dose-response relationship , several meta-analyses of clinical trials have shown contradictory results . Overall , large r and omized controlled trials with sufficient doses of vitamin D are missing , and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels  > 50 nmol/L , did not simultaneously assess multiple outcomes , and did not report overall safety ( e.g. , falls ) . Thus , no recommendations can be made to date for the use of vitamin D supplementation in general , parental compounds , or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases . Moreover , attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health can not be recommended based on current evidence , since safety has yet to be confirmed . Finally , the promising findings from mechanistic studies , large cohort studies , and small clinical trials obtained for autoimmune diseases ( including type 1 diabetes , multiple sclerosis , and systemic lupus erythematosus ) , cardiovascular disorders , and overall reduction in mortality require further confirmation Osteoporosis is a common disorder , especially among elderly post-menopausal women . Elderly women are often affected by co-morbidities , impaired gastrointestinal function and reduced mobility ; therefore , the treatment strategy for their osteoporosis can be difficult . In this r and omized pilot study , we have investigated the effects of a 12-month treatment with neridronate on bone mineral density ( BMD ) , bone turnover markers and quality of life ( QoL ) . The study included 40 women ( age , 65–80 yr ; post-menopausal period , > 15yr ) from a single osteoporosis centre . Twenty women received a monthly i m injection of 25 mg of neridronate associated with a daily dose of 500 mg of calcium and 400 U of vitamin D. Twenty women received calcium plus vitamin D supplements alone . Changes in BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry . Serum type I collagen C-telopeptide ( sCTX ) , urinary free-deox-ypyridinoline ( ufDPD ) , bone alkaline phosphatase ( ALP ) and serum osteocalcin levels were determined . For the QoL assessment , the Italian version of the SF-36 test was administrated . Spine and hip BMD rose by 6.6±3 and 4.2±2.3 % , respectively ( p<0.05 ) , after 12 months of neridronate treatment . Markers of skeletal turnover significantly fell already after 3 months of neridronate treatment and decreased progressively thereafter within 12 months . The mean decrease at 12 months ranged from 38±11 % for sCTX to 25.2±15 % for ufDPD ( p<0.001 , all ) . The mean improvement in QoL in the treated group was 45.7 % for bodily pain , 37.5 % for general health perception , 23.1 % for vitality , 18 % for emotional role functioning and 12 % for physical role functioning . The changes observed in BMD , turnover markers and QoL in the untreated group were ns . The intermittent neridronate administration was easily manageable and well tolerated . In conclusion , neridronate currently represents a valid option for the treatment of osteoporosis , since it helps just as much as oral BPs in the improvement of BMD and in particular conditions it can be even more effective OBJECTIVES To assess the safety and efficacy of teriparatide in patients aged 75 and older and compare these findings with those of women younger than 75 using data from the Fracture Prevention Trial ( FPT ) . DESIGN The FPT was a r and omized , multicenter , double-blind , placebo-controlled study . SETTING The FPT multicenter international study . PARTICIPANTS Postmenopausal women aged 42 to 86 were r and omized to placebo ( N=544 ) or teriparatide 20 mug ( N=541 ) by daily self-injection for a median of 19 months . Patients received daily oral supplements of 1,000 mg calcium and 400 to 1,200 IU vitamin D. For this analysis , subgroups were defined according to patient age younger than 75 ( N=841 ) and 75 and older ( N=244 ) . MEASUREMENTS The effects of teriparatide on bone mineral density ( BMD ) of the lumbar spine and femoral neck ; the incidence of new vertebral and new nonvertebral fragility fractures ; bone turnover markers , including bone-specific alkaline phosphatase ; and urinary deoxypyridinoline corrected for creatinine clearance , as well as the safety of teriparatide , were investigated . RESULTS There were no significant treatment-by-age interactions for the bone turnover markers , femoral neck BMD , vertebral fractures , nonvertebral fragility fractures , height loss , hyperuricemia , or hypercalcemia . A significant treatment-by-age interaction for lumbar spine BMD ( P=.08 ) was due to an increase in BMD observed in the placebo group aged 75 and older . There were no treatment-by-age interactions for important treatment-emergent adverse events ( TEAEs ) , including back pain , nausea , leg cramps , and dizziness . The most important TEAEs in women aged 80 and older ( 23 patients from the placebo group and 25 patients from the teriparatide group ) were also review ed ; no unexpected TEAEs were found in the patients treated with teriparatide . These results indicate that the clinical effects of teriparatide were consistent in the older and younger women . CONCLUSION Age does not affect the safety and efficacy of teriparatide in postmenopausal women with osteoporosis
Two regimens , each represented by one large trial , which showed limited evidence of efficacy in reducing the incidence of hip or other appendicular skeleton fractures were : 1 ) Oral Vitamin D when accompanied by calcium supplementation .
2 ) 1,25 dihydroxy Vitamin D ( calcitriol ) .
This appeared more effective than calcium in a direct comparison .
Hypercalcaemia and gastro-intestinal symptoms , reported in less than 5 % of participants , were slightly more common when Vitamin D analogues were taken .
However , the risk of death was marginally less .
REVIEW ER 'S CONCLUSIONS Uncertainty remains about the efficacy of regimens which include Vitamin D or its analogues in fracture prevention .
Particularly if co-supplementation of calcium is required , significant cost differences are likely to exist between regimens .
BACKGROUND Due to their known effects on bone metabolism , Vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures .
OBJECTIVES To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis .