title: Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial Treatment of Osteoporosis in Australian Residential Aged Care Facilities: Update on Consensus Recommendations for Fracture Prevention. The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized placebo-controlled study. Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group. The Effect of the Modified Eighth Section of Eight-Section Brocade on Osteoporosis in Postmenopausal Women Calcium, vitamin D and anabolic steroid in treatment of aged bones: double-blind placebo-controlled long-term clinical trial. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Biochemical parameters after cholecalciferol repletion in hemodialysis: results From the VitaDial randomized trial. Calcium and vitamin d supplementation in postmenopausal women. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. Correcting calcium nutritional deficiency prevents spine fractures in elderly women. Calcium plus vitamin D supplementation and the risk of fractures. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial. Effects of three-monthly oral 150,000 IU cholecalciferol supplementation on falls, mobility, and muscle strength in older postmenopausal women: a randomized controlled trial. Vitamin D Supplementation and Fracture Incidence in Elderly Persons Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. Effect of calcium supplementation on bone loss in postmenopausal women. Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women. Effect of vitamin D(3) and calcium on fracture risk in 65- to 71-year-old women: a population-based 3-year randomized, controlled trial--the OSTPRE-FPS. Women’s Health Initiative clinical trials: interaction of calcium and vitamin D with hormone therapy The effect of fluoride and calcium on spinal bone mineral content: A controlled, prospective (3 years) study Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly 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. The effects of an open design on trial participant recruitment, compliance and retention – a randomized controlled trial comparison with a blinded, placebo-controlled design Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. Randomized controlled trial of calcium in healthy older women. Effects of Enhanced Exercise and Combined Vitamin D and Calcium Supplementation on Muscle Strength and Fracture Risk in Postmenopausal Chinese Women. Exercise and vitamin D in fall prevention among older women: a randomized clinical trial. Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post-hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial.
abstract: Summary This trial compared the effects of daily treatment with vitamin D or placebo for 1 year on blood tests of vitamin D status . The results demonstrated that daily 4000 IU vitamin D3 is required to achieve blood levels associated with lowest disease risks , and this dose should be tested in future trials for fracture prevention . Introduction The aim of this trial was to assess the effects of daily supplementation with vitamin D3 4000 IU ( 100 μg ) , 2000 IU ( 50 μg ) or placebo for 1 year on biochemical markers of vitamin D status in preparation for a large trial for prevention of fractures and other outcomes . Methods This is a r and omized placebo-controlled trial in 305 community-dwelling people aged 65 years or older in Oxfordshire , UK . Outcomes included biochemical markers of vitamin D status ( plasma 25-hydroxy-vitamin D [ 25[OH]D ] , parathyroid hormone [ PTH ] , calcium and alkaline phosphatase ) , cardiovascular risk factors and tests of physical function . Results Mean ( SD ) plasma 25(OH)D levels were 50 ( 18 ) nmol/L at baseline and increased to 137 ( 39 ) , 102 ( 25 ) and 53 ( 16 ) nmol/L after 12 months in those allocated 4000 IU , 2000 IU or placebo , respectively ( with 88 % , 70 % and 1 % of these groups achieving the pre-specified level of > 90 nmol/L ) . Neither dose of vitamin D3 was associated with significant deviation outside the normal range of PTH or albumin-corrected calcium . The additional effect on 25(OH)D levels of 4000 versus 2000 IU was similar in all subgroups except for body mass index , for which the further increase was smaller in overweight and obese participants compared with normal-weight participants . Supplementation with vitamin D had no significant effects on cardiovascular risk factors or on measures of physical function . Conclusions After accounting for average 70 % compliance in long-term trials , doses of 4000 IU vitamin D3 daily may be required to achieve plasma 25(OH)D levels associated with lowest disease risk in observational studies 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 Conflicting data regarding cardiovascular effects of thiazolidinediones ( TZDs ) and extra-skeletal effects of vitamin D supported the need for a definitive trial . The Thiazolidinedione Intervention with vitamin D Evaluation ( TIDE ) trial aim ed to assess the effects of TZDs ( rosiglitazone and pioglitazone ) on cardiovascular outcomes and the effects of vitamin D ( cholecalciferol ) on  cancers and mortality . A large multicentre 3 × 2 factorial double-blind placebo-controlled r and omised trial recruited from outpatient primary care and specialty clinics in 33 countries . From June 2009 to July 2010 , 1,332 people with type 2 diabetes and other cardiovascular risk factors aged ≥50 years whose HbA1c was 6.5–9.5 % ( 48–80 mmol/mol ) when using two or fewer glucose-lowering drugs were r and omised by a central computer system to placebo ( n = 541 ) , rosiglitazone 4–8 mg/day ( n = 399 ) or pioglitazone 30–45 mg/day ( n = 392 ) ; 1,221 participants were r and omised to placebo ( n = 614 ) or vitamin D 1,000 IU/day ( n = 607 ) . Participants and all study personnel were blind to treatment allocation . The primary outcome for the TZD arm was the composite of myocardial infa rct ion , stroke or cardiovascular death , and for the vitamin D arm it was cancer or all-cause death . All r and omised participants were included in the primary analysis . From the study design , 16,000 people were to be followed for approximately 5.5 years . However , the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data . In the TZD arm , the cardiovascular outcome occurred in five participants ( 0.9 % ) in the placebo groups and three participants ( 0.4 % ) in the TZD groups ( two allocated to pioglitazone , one to rosiglitazone ) . In the vitamin D arm , the primary outcome occurred in three participants ( 0.5 % ) in the placebo group and in two participants ( 0.3 % ) receiving vitamin D. Adverse events were comparable in all groups . Uncertainty persists regarding the clinical ly relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial . Clinical Trials.gov NCT00879970 The study was funded by GlaxoSmithKline BACKGROUND Older people living in residential aged care facilities ( RACFs ) are at a higher risk of suffering fractures than the community-dwelling older population . The first Consensus Conference on Treatment of Osteoporosis in RACFs in Australia , held in Sydney in July 2009 , aim ed to address some of the issues relating to the treatment of older residents with osteoporosis in RACFs . Considering that the field of osteoporosis diagnosis and management has significantly advanced in the last 5 years and that new evidence has been generated from studies performed within RACFs , a Second Consensus Conference was held in Sydney in November 2014 . METHODS An expert panel met in November 2014 in Penrith , NSW , Australia in an attempt to reach a consensus on diverse issues related to the treatment of osteoporosis at RACFs . Participants were selected by the scientific committee on the basis of their practice in an RACF and /or major published articles . The co-chairs distributed topics r and omly to all participants , who then had to propose a statement on each topic for approval by the conference after a short , evidence -based presentation , when possible . RESULTS This article provides an up date on the most relevant evidence on osteoporosis  in older people living in RACFs grade d according to its level , quality , and relevance . CONCLUSION As with the first consensus , it is hoped that this statement will constitute an important guide to aid physicians in their decision making while practicing at RACFs This placebo-controlled r and omized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women , 57 of whom were early postmenopausal ( five years after menopause ) and six of whom were mid-postmenopausal ( five to ten years after menopause ) .  Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years . The two groups were similar in baseline age , years postmenopause ( 3.3 in the calcium citrate group vs 2.7 in the placebo group ) , height , weight , calcium intake , and L2-L4 bone density . L2-L4 bone density did not change during calcium citrate treatment ( + 1.03 % after two years ) , whereas it declined significantly by -2.38 % after two years on placebo ( P < .001 ) . Femoral neck bone density did not change in either group . Radial shaft bone density did not change in the calcium citrate group ( -0.02 % after two years ) , but it declined significantly in the placebo group ( -1.79 % after one year and -3.03 % after two years , P < .01 ) . The difference in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups . An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause , but a protective effect after three years . Although serum PTH did not change , serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group , indicative of parathyroid suppression . Serum bone-specific alkaline phosphatase and osteocalcin , and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods , indicative of a reduction in bone turnover . Thus , calcium citrate supplementation ( 400 mg of calcium twice daily ) averted bone loss and stabilized bone density in the spine , femoral neck , and radial shaft in women relatively soon after menopause . This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression BACKGROUND AND METHODS Laboratory , clinical , and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas . We conducted a r and omized , double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas . We r and omly assigned 930 subjects ( mean age , 61 years ; 72 percent men ) with a recent history of colorectal adenomas to receive either calcium carbonate ( 3 g [ 1200 mg of elemental calcium ] daily ) or placebo , with follow-up colonoscopies one and four years after the qualifying examination . The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to ( and including ) the second follow-up examination . Risk ratios for the recurrence of adenomas were adjusted for age , sex , lifetime number of adenomas before the study , clinical center , and length of the surveillance period . RESULTS The subjects in the calcium group had a lower risk of recurrent adenomas . Among the 913 subjects who underwent at least one study colonoscopy , the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 ( 95 percent confidence interval , 0.74 to 0.98 ; P=0.03 ) . The main analysis was based on the 832 subjects ( 409 in the calcium group and 423 in the placebo group ) who completed both follow-up examinations . At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group ( 31 percent ) and 159 subjects in the placebo group ( 38 percent ) ; the adjusted risk ratio was 0.81 ( 95 percent confidence interval , 0.67 to 0.99 ; P=0.04 ) . The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 ( 95 percent confidence interval , 0.60 to 0.96 ; P=0.02 ) . The effect of calcium was independent of initial dietary fat and calcium intake . CONCLUSIONS Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas Abstract Osteoporosis and related fragility fractures represent a serious and global public health problem . To evaluate whether the modified eighth section of Eight-section Brocade ( MESE ) exercise could improve the symptom and indexes associated with osteoporosis in postmenopausal women . Guangzhou and Liuzhou hospital of traditional Chinese medicine in China . Women ( n = 198 ) aged 50 to 75 years were r and omized into Control , Ca , MESE , and MESE + Ca . Subjects in Ca and MESE groups were separately asked to consume thrice daily Calcium Carbonate Chewable D3 tablet and to perform thrice daily MESE exercise by 7 repetitions per time for 12 months . Subjects in MESE + Ca group performed such the combined treatment project for 12 months . Body height and Hospital for Special Surgery ( HSS ) scores of both knees , chronic back pain visual analogue scale scores ( VAS ) , bone mineral density ( BMD ) at L2 to L4 and the left femoral neck , 3-feet Up and Go Test ( 3′ ) and one-leg Stance ( OLS ) . In our study , the improvement in chronic back pain of the patients in Ca , MESE , and MESE + Ca group was better than that in control group . There was 1.9 % and 1.7 % , 2.3 % , and 2.1 % net profit in left femoral neck and lumbar BMD after the treatment for 12 months in MESE and MESE + Ca groups . For the balance capacity , the subjects in MESE and MESE + Ca groups secured much better performance than those in Ca and control group after the treatment for 12 months ( P < 0.001 , P < 0.001 ) . The treatment of MESE exercise is the most effective for the improvement of the symptom and indexes in postmenopausal women . Importantly , the low attrition and the high exercise compliance indicate that MESE exercise is safe , feasible , and well tolerated by postmenopausal women In a double-blind trial , 327 patients ( 57 men ) over 65 ( mean age 79.5 ) years received all possible combinations of calcium carbonate 3 g , vitamin D3 1000 iu , meth and ienone 2.5 mg and /or placebos daily for 9 months . The higher incidence of bone fractures in the placebo group was not significant . Serum calcium , phosphorus , creatinine , aspartate aminotransferase and alkaline phosphatase were followed : the greatest changes occurred with meth and ienone , which thus reduced osteoporotic activity and increased the muscular mass most effectively ; calcium carbonate had the poorest effect . Surprisingly , coronary mortality was higher among those taking all three active substances . With two treatments the increase was not significant , but when both the groups receiving a combination of any two of the treatments were compared with those taking only one or neither of these two treatments , a significant increase in coronary deaths was seen , most significant ( P less than 0.001 ) in those receiving vitamin D3 and meth and ienone CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867 BACKGROUND The 2009 KDIGO ( Kidney Disease : Improving Global Outcomes ) chronic kidney disease-mineral and bone disorder clinical practice guideline suggests correcting 25-hydroxyvitamin D3 ( 25[OH]D ) levels<30ng/mL in patients treated with maintenance hemodialysis  , but does not provide a specific treatment protocol . STUDY DESIGN 2-center , double-blind , r and omized , 13-week , controlled trial followed by a 26-week open-label study . SETTING & PARTICIPANTS 55 adult maintenance hemodialysis patients with 25(OH)D levels<30ng/mL were recruited from June 2008 through October 2009 . INTERVENTION Cholecalciferol , 25,000IU , per week orally versus placebo for 13 weeks , then 26 weeks of individualized cholecalciferol prescription based on NKF-KDOQI ( National Kidney Foundation-Kidney Disease Outcomes Quality Initiative ) guidelines . OUTCOMES Primary end point was the percentage of patients with 25(OH)D levels≥30ng/mL at 13 weeks . Secondary outcomes included the percentage of patients with normal calcium , phosphorus , and intact parathyroid hormone ( iPTH ) blood levels . Safety measures included incidence of hypercalcemia and hypervitaminosis D. MEASUREMENTS Blood calcium and phosphate were measured weekly ; iPTH , 25(OH)D , 1,25-dihydroxyvitamin D3 ( 1,25[OH]2D ) , and bone turnover markers , trimonthly ; fetuin A and fibroblast growth factor 23 ( FGF-23 ) serum levels and aortic calcification scores were determined at weeks 0 and 39 . RESULTS The primary end point significantly increased in the treatment group compared with the placebo group ( 61.5 % vs 7.4 % ; P<0.001 ) , as well as 1,25(OH)2D levels ( 22.5 [ IQR , 15 - 26 ] vs 11 [ IQR , 10 - 15]pg/mL ; P<0.001 ) and the proportion of patients achieving the target calcium level ( 76.9 % vs 48.2 % ; P=0.03 ) . Incidence of hypercalcemia and phosphate and iPTH levels were similar between groups . The second 26-week study phase did not significantly modify the prevalence of 25(OH)D level≥30ng/mL in patients issued from the placebo group . LIMITATIONS Small size of the study population . CONCLUSIONS Oral weekly administration of 25,000IU of cholecalciferol for 13 weeks is an effective , safe , inexpensive , and manageable way to increase 25(OH)D and 1,25(OH)2D levels in hemodialysis patients . Further evaluation of clinical end points is suggested CONTEXT Bone health is influenced by the intake of both calcium and vitamin D. OBJECTIVE Our objective was to evaluate the influence of calcium and vitamin D supplementation on PTH and bone turnover . SETTING , PATIENTS , AND DESIGN : At an ambulatory research center , 159 postmenopausal healthy white women participated in this double-blind , placebo-controlled parallel , longitudinal factorial study that was 6 months in duration . INTERVENTIONS Subjects were r and omly allocated to 4 groups : 1 ) double placebo , 2 ) calcium ( 1200 mg daily ) plus placebo , 3 ) vitamin D3 ( 100 μg ) plus placebo , and 4 ) vitamin D3 and calcium . Serum and urine were collected fasting and 2 hours after a calcium load at baseline and at 3 and 6 months . MAIN OUTCOME MEASURES Serum PTH , cross-linked C-telopeptide ( CTX ) , and procollagen type I N-terminal propeptide ( P1NP ) were measured . RESULTS Before study medication , a calcium load result ed in a decline in PTH and CTX and an increase in urinary calcium excretion . Serum CTX and P1NP declined over time with calcium supplementation but did not change with increased vitamin D intake . There was a decline in PTH in the vitamin D groups in the fasting state compared with placebo . Suppression of PTH was greater after a calcium load in the vitamin D groups . A calcium load decreased PTH and CTX and raised urinary calcium . CONCLUSIONS Fasting PTH  declines with vitamin D supplementation . PTH declines after calcium intake . Supplementation of the diet with 1200 mg calcium/d reduces bone turnover markers , whereas supplementation with up to100 μg vitamin D3/d does not 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 Abstract Objective To assess whether supplementation with calcium and cholecaliferol ( vitamin D3 ) reduces the risk of fracture in women with one or more risk factors for fracture of the hip . Design Pragmatic open r and omised controlled trial . Setting Practice nurse led clinics in primary care . Participants 3314 women aged 70 and over with one or more risk factors for hip fracture : any previous fracture , low body weight ( < 58 kg ) , smoker , family history of hip fracture , or fair or poor self reported health . Intervention Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls , or leaflet only ( control group ) . Main outcome measures Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment , falls , and quality of life ( measured with the SF-12 ) . Results 69 % of the women who completed the follow-up question naire at 24 months were still taking supplements ( 55 % with inclusion of r and omised participants known to be alive ) . After a median follow-up of 25 months ( range 18 to 42 months ) , clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures ( odds ratio for fracture in supplemented group 1.01 , 95 % confidence interval 0.71 to 1.43 ) . The odds ratio for hip fracture was 0.75 ( 0.31 to 1.78 ) . The odds of a woman having a fall at six and 12 months was 0.99 and 0.98 , respectively . Quality of life did not significantly differ between the groups . Conclusion We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture . Registration IS RCT N26118436 , controlled trials registry UNLABELLED Dietary supplementation with vitamin K(1 ) , with vitamin D(3 ) and calcium or their combination , was examined in healthy older women during a 2-year , double-blind , placebo-controlled trial . Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius . INTRODUCTION The putative beneficial role of high dietary vitamin K(1 ) ( phylloquinone ) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind , placebo-controlled trial in healthy Scottish women > or = 60 years of age . MATERIAL S AND METHODS Healthy , nonosteoporotic women ( n = 244 ) were r and omized to receive either ( 1 ) placebo , ( 2 ) 200 microg/day vitamin K(1 ) , ( 3 ) 10 microg ( 400 IU ) vitamin D(3 ) plus 1000 mg calcium/day , or ( 4 ) combined vitamins K(1 ) and D(3 ) plus calcium . Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist , markers of bone turnover , and vitamin status . Supplementation effects were tested using multivariate general linear modeling , with full adjustment for baseline and potential confounding variables . RESULTS Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups . However , women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius . Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years , serum vitamin K(1 ) increased by 157 % ( p < 0.001 ) , the percentage of undercarboxylated osteocalcin ( % GluOC ) decreased by 51 % ( p < 0.001 ) , serum 25-hydroxyvitamin D [ 25(OH)D ] increased by 17 % ( p < 0.001 ) , and PTH decreased by 11 % ( p = 0.049 ) . CONCLUSIONS These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1 ) together with supplements of calcium plus moderate vitamin D(3 ) to enhance BMC at the ultradistal radius , a site consisting of principally trabecular bone . The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation 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 We tested the spine antifracture and bone sparing efficacy of 1.2 g/day of oral calcium as carbonate in two groups of elderly women , one with prevalent fractures ( PF , n = 94 ) on entry and the other without ( NPF , n = 103 ) . It was a prospect i ve r and omized , double-blind , placebo-controlled trial in mostly rural communities in women over age 60 who were living independently and were consuming < 1 g/day of calcium .  We obtained annual lateral spine radiographs  and semiannual forearm bone density  over 4.3 + /- 1.1 years and determined vertebral fractures by radiographic morphometry augmented by physician assessment . In the PF group , 15 of 53 subjects on calcium had incident fractures , compared with 21 of 41 on placebo ( p = 0.023 , chi2 ) . Calcium did not reduce the rate of incident fractures in the NPF group . Those with a prevalent fracture on entry and not treated with calcium were 2.8 times more likely to experience an incident fracture than all others . Change in the forearm bone mass on placebo in the PF group was -1.24 + /- 2.41%/year compared with + 0.31 + /- 1.80%/year on calcium ( p < 0.001 ) . In the NPF group , the difference was less : -0.39 + /- 2.08%/year versus 0.00 + /- 1.64%/year ( p = 0.2 ) . We conclude that in elderly postmenopausal women with spine fractures and selfselected calcium intakes of < 1 g/day , a calcium supplement of 1.2 g/day reduces the incidence of spine fractures and halts measurable bone loss BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo .  Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P<0.01 ) . Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . ) IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension . No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension , the most common pattern of hypertension in older people . OBJECTIVE To test whether high-dose , intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension . DESIGN Parallel group , double-blind , placebo-controlled  r and omized trial . SETTING Primary care clinics and hospital clinics . PARTICIPANTS Patients 70 years and older with isolated systolic hypertension ( supine systolic blood pressure > 140 mm Hg and supine diastolic blood pressure < 90 mm Hg ) and baseline 25-hydroxyvitamin D levels less than 30 ng/mL were r and omized into the trial from June 1 , 2009 , through May 31 , 2011 . INTERVENTIONS A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year . MAIN OUTCOMES AND MEASURES Difference in office blood pressure , 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , insulin resistance , and b-type natriuretic peptide level during 12 months . RESULTS A total of 159 participants were r and omized ( mean age , 77 years ) .  Mean baseline office systolic blood pressure was 163/78 mm Hg . Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group ( + 8 ng/mL at 1 year , P < .001 ) . No significant treatment effect was seen for mean ( 95 % CI ) office blood pressure ( −1 [ −6 to 4]/−2 [ −4 to 1 ] mm Hg at 3 months and 1 [ −2 to 4]/0 [ −2 to 2 ] mm Hg overall treatment effect ) . No significant treatment effect was evident for any of the secondary outcomes ( 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , glucose level , and walking distance ) . There was no excess of adverse events in the treatment group , and the total number of falls was nonsignificantly lower in the group receiving vitamin D ( 36 vs 46 , P = .24 ) . CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N92186858 Daily vitamin D in addition to calcium supplementation reduces falls and fractures in older women . However , poor adherence to therapy is a common clinical problem . To examine the effects of supervised oral 3-monthly vitamin D therapy on falls , muscle strength , and mobility , we conducted a 9-month r and omized , double-blind , placebo-controlled trial in 686 community-dwelling ambulant women aged over 70 years . Participants received either oral cholecalciferol 150,000 IU every 3 months ( n = 353 ) or an identical placebo ( n = 333 ) . All participants were advised to increase dietary calcium intake . Falls data were collected 3-monthly . At baseline , 3 , 6 , and 9 months , muscle strength was measured by a h and held dynamometer and mobility by the Timed Up and Go ( TUG ) test . Serum 25 hydroxyvitamin D ( 25OHD ) was measured in a subgroup of 40 subjects . Mean age at baseline was 76.7 ± 4.1 years . The average serum 25OHD value at baseline was 65.8 ± 22.7 nmol/L. By 3 , 6 , and 9 months after supplementation , 25OHD levels of the vitamin D group were approximately 15 nmol/L higher than the placebo group . Calcium intake did not change significantly between baseline ( 864 ± 412 mg/day ) and 9 months ( 855 ± 357 mg/day ) . Faller rates in the two groups did not differ : vitamin D group , 102 of 353 ( 29 % ) ; placebo group , 89 of 333 ( 27 % ) . At 9 months , compared to placebo or baseline , muscle strength , and TUG were not altered by vitamin D. In conclusion , oral cholecalciferol 150,000 IU therapy administered 3-monthly had neither beneficial nor adverse effects on falls or physical function . These data together with previous findings confirm that intermittent large doses of vitamin D are ineffective or have a deleterious effect on falls . Thus despite adherence issues with daily vitamin D replacement , an intermittent , high-dose vitamin D regimen can not be supported as a strategy to reduce falls and fractures Vitamin D deficiency is common in elderly persons , especially those with hip fracture [ 1 , 2 ] . It is caused by low exposure to sunshine , decreased synthesis of vitamin D3 in the aging skin , and a diet low in vitamin D [ 3 , 4 ] . The mean vitamin D intake in elderly persons in the Netherl and s is about 100 IU/d , half that of elderly persons in the United States [ 5 ] . Most of this vitamin D comes from margarine , which is the only vitamin D-supplemented food in the Netherl and s ( 3 IU/g ) . In vitamin D deficiency , the low serum concentration of 25-hydroxyvitamin D [ 25(OH)D ] leads to a low 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] concentration and then to a higher serum parathyroid hormone concentration , especially in the winter [ 6 - 10 ] . Histologically , the increased parathyroid activity is associated with high bone turnover , leading to cortical bone loss and low density bone [ 5 , 11 ] , which may lead to hip fracture . We previously studied the effects of vitamin D supplementation in residents of a home for the elderly and residents of a nursing home [ 10 ] .  Vitamin D3 , 400 IU/d , led to an adequate increase of the serum 25(OH)D concentration , to a small but significant increase of the serum 1,25(OH)2D concentration , and to a decrease of the serum concentration of intact parathyroid hormone . It was recently observed [ 12 , 13 ] that bone mineral density at the hip is positively related to serum 25(OH)D concentration in postmenopausal and elderly women . Therefore , it might be expected that vitamin D supplementation would increase bone mineral density in elderly persons deficient in vitamin D. In line with this expectation , it was shown that vitamin D supplementation prevented bone loss from the spine during the winter in postmenopausal women [ 14 ] . These results suggest that vitamin D supplementation may reduce the incidence of hip fractures , because bone strength shows a strong correlation with bone mineral density [ 15 ] . However , increasing bone mineral density through a therapeutic intervention does not necessarily lead to increased bone strength , as has been shown with sodium fluoride [ 16 ] . Bone structure and bone quality are also determinants of bone strength [ 17 ] , and falls are a risk factor for hip fractures [ 18 ] . Therefore , hip fracture should be the outcome criterion in studies on the effect of vitamin D supplementation . Intervention studies on the prevention of osteoporotic fractures necessitate large numbers of patients , because the outcome has an annual incidence of 0.5 % to 4 % in the elderly population [ 19 ] . We report the results of a large-scale , prospect i ve study on the effect of vitamin D supplementation on the incidence of hip and other osteoporotic fractures . Methods Participants The study included 2578 persons ( 1916 women and 662 men ) 70 years of age and older ( mean age SD , 80 6 years ; range , 70 to 97 years ) . Participants were recruited from general practitioners , from apartment houses for elderly persons , and from homes for elderly persons in Amsterdam and its vicinity . Persons recruited from practitioners were living independently ; those recruited from apartment houses and homes were receiving some care , but less than they would have received in a nursing home . Participants had to be reasonably healthy and able to give informed consent . Persons with a history of hip fracture or total hip arthroplasty , known hypercalcemia , sarcoidosis , or recent urolithiasis ( < 5 years earlier ) were excluded . Patients who had diseases or who used medications that influence bone metabolism ( such as thyroid disease or glucocorticoid medication ) were not excluded . The spontaneous use of vitamin D supplements and multivitamins was discouraged , but the prescription practice s of the general practitioners were not altered . All vitamin use was carefully documented . The study was approved by the Ethical Review Board of the Vrije Universiteit Hospital , and all participants gave informed consent . Study Design After checking the inclusion and exclusion criteria and obtaining informed consent , the participants were r and omly assigned to receive either active treatment with vitamin D3 or placebo . The study was double-blind , and r and omization was done in blocks of 10 per general practice , apartment house , or home . R and omization lists were made using a computerized r and om-number generator . Lists in sealed envelopes were sent to the hospital pharmacy for assignment . Each participant took either one tablet per day that contained vitamin D3 , 400 IU , or one placebo tablet per day that was identical in appearance and taste to the vitamin tablet . After enrollment , the participants received the first container of tablets ( 210 tablets ) . The container was replaced every 6 months with a full container . All participants were also advised in writing to consume at least three servings of dairy products per day ( for example , 1 glass of milk , 1 cup of yogurt , and 1 slice of cheese ) to ensure a calcium intake of at least 800 to 1000 mg/d . The study was started in August 1988 . The last participant was enrolled in December 1990 , and all participants had stopped using study medication by December 1993 . The follow-up period had been planned to last no more than 3 years , but because the number of hip fractures during the study was lower than expected , a 6-month extension was planned . The study participants thus received medication for 3 to 3.5 years ; those who received it for 3.5 years were those who consented to the 6-month extension . Total follow-up was to a maximum of 4 years . Data collected at baseline included an  outdoor activity score  ( 1 equals going outdoors less than once a week ; 2 equals going outdoors 1 or 2 times per week ; and 3 equals going outdoors 3 times per week or more ) and a score for sunshine exposure ( when outside : 1 equals in the shade as much as possible ; 2 equals sometimes in sunshine ; 3 equals much exposure to sunshine ) . These scores show a positive relation with serum 25(OH)D concentration [ 3 ] . Mobility was estimated by a walking score that ranged from 1 ( unable to walk ) to 5 ( walks independently a fair distance on any surface ) [ 20 ] . The dietary calcium intake from dairy products was estimated in a subset of 348 women by using a question naire , as described previously [ 21 ] . The participants were evaluated annually with a question naire on hip fractures , other peripheral fractures , outdoor score , sunshine exposure score , use of vitamin supplements , and walking score . Each general practitioner or caretaker was asked to immediately report change of address , hip fracture , or death . Hip fracture and death were verified by the general practitioner . All participants were followed for the maximal period of 4 years if possible , even if they had stopped using the trial medication , had sustained a fracture , or had moved to another city . To investigate possible selection bias , 267 potential participants in a home for the elderly and its adjunct apartments ( all residents of the institution ) were studied for baseline characteristics , including age , sex , sunshine exposure score , outdoor score , walking score , and reasons for nonparticipation . Compliance was checked when the tablet containers were replaced ( every 6 months ) , by question naire ( every year ) , and by measurement of the serum 25(OH)D concentration . Serum 25(OH)D concentration was measured at baseline and after 1 year in 270 persons who participated in a sub study investigating the effect of vitamin D supplementation on bone mineral density and bone turnover variables . This sub study included a nonr and om sample of participants from several apartment houses and homes for the elderly and is described in detail elsewhere [ 21 ] . In the same sub study , dietary calcium intake from diary products was assessed . Serum 25(OH)D concentration was also estimated during the third year of the study in February and March in a r and om sample of 96 participants drawn from the remaining study population . These participants received a letter giving them an appointment within 10 days ; the blood sample s were drawn at home . Serum 25(OH)D concentration was measured by competitive protein binding assay after being purified by gradient high-pressure liquid chromatography . The intra- and interassay coefficients of variation were 5 % and 6 % , respectively [ 22 ] . Statistical Analysis Baseline data of the vitamin D group and the placebo group were compared using t-tests ( age , calcium intake ) , chi-square tests ( sex , residence ) , and Wilcoxon rank-sum tests ( scores ) . The serum 25(OH)D concentrations of both groups were compared using t-tests . Data on fractures and mortality were analyzed by survival analysis using log-rank tests , Cox proportional-hazards regression , and hazard rate ratios [ 23 ] . Hip fractures are presented using the Kaplan-Meier method . All participants were kept in the study as long as possible . The data were analyzed in two ways . The intention-to-treat analysis included all r and omly assigned participants for either the total follow-up period or until fracture , death , or loss to follow-up . The active treatment analysis included the participants as long as they stated that they were using the trial medication . Thus , the participants were included in the active treatment analysis until they stopped using the trial medication , regardless of whether a fracture occurred after they had stopped . Age , sex , and residence were added in both analyses as covariates to the Cox regression model . Because outdoor score , sunshine score , and walking score were interrelated ( correlation coefficients ranging from 0.21 to 0.59 ) and were likely to indicate general health or mobility , they were averaged over the years and added up to a sum score . For this purpose , the walking score was simplified ( 1 , 2 , or 3 equals 1 ; 4 equals 2 ; 5 equals 3 ) , because the lower walking scores applied to a few participants only . The result ing total score , ranging from 3 to 9 , was entered as a covariate in the model . The level of compliance ( weekly intake as reported on OBJECTIVES Low trauma fractures in older people incur enormous physical , social and economic costs . Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group . This strategy requires validation in a population setting . METHODS R and omized , double-blind , placebo-controlled trial of 300,000 IU intramuscular ( i.m . ) vitamin D2 ( ergocalciferol ) injection or matching placebo every autumn over 3 years . 9440 people ( 4354 men and 5086 women ) aged 75 yrs and over were recruited from general practice registers in Wessex , Engl and . Primary outcome measure was all non-vertebral fracture . Secondary outcomes were hip and wrist fractures , and all falls . RESULTS 585 subjects had incident non-spine fractures  ( hip 110 , wrist 116 , ankle 37 ) . Hazard ratios ( HRs ) for fracture in the vitamin D group were : 1.09 [ 95 % confidence interval ( CI ) 0.93 - 1.28 , P = 0.29 ] for any first fracture , 1.49 ( 95 % CI 1.02 - 2.18 , P = 0.04 ) for hip and 1.22 ( 95 % CI 0.85 - 1.76 , P = 0.28 ) for wrist . There was no effect on falls : HR 0.98 ( 0.93 - 1.04 ) . No protective effect was observed in any subgroup when the cohort was stratified by sex , age , previous fracture or mobility . CONCLUSIONS An annual i.m . injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population BACKGROUND The use of calcium supplements slows bone loss in the forearm and has a beneficial effect on the axial bone density of women in late menopause whose calcium intake is less than 400 mg per day . However , the effect of a calcium supplement of 1000 mg per day on the axial bone density of postmenopausal women with higher calcium intakes is not known . METHODS We studied 122 normal women at least three years after they had reached menopause who had a mean dietary calcium intake of 750 mg per day . The women were r and omly assigned to treatment with either calcium ( 1000 mg per day ) or placebo for two years . The bone mineral density of the total body , lumbar spine , and proximal femur was measured every six months by dual-energy x-ray absorptiometry .  Serum and urine indexes of calcium metabolism were measured at base line and after 3 , 12 , and 24 months . RESULTS The mean ( + /- SE ) rate of loss of total-body bone mineral density was reduced by 43 percent in the calcium group ( -0.0055 + /- 0.0010 g per square centimeter per year ) as compared with the placebo group ( -0.0097 + /- 0.0010 g per square centimeter per year , P = 0.005 ) . The rate of loss of bone mineral density was reduced by 35 percent in the legs ( P = 0.02 ) , and loss was eliminated in the trunk ( P = 0.04 ) . Calcium use was of significant benefit in the lumbar spine ( P = 0.04 ) , and in Ward 's triangle the rate of loss was reduced by 67 percent ( P = 0.04 ) . Calcium supplementation had a similar effect whether dietary calcium intake was above or below the mean value for the group . Serum parathyroid hormone concentrations tended to be lower in the calcium group , as were urinary hydroxyproline excretion and serum alkaline phosphatase concentrations . CONCLUSIONS Calcium supplementation significantly slowed axial and appendicular bone loss in normal post-menopausal women BACKGROUND Increased dietary calcium intake has been proposed as a population -based public health intervention to prevent osteoporotic fractures . We have examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action . METHODS Five-year , double-blind , placebo-controlled study of 1460 women recruited from the population and older than 70 years ( mean age , 75 years ) who were r and omized to receive calcium carbonate , 600 mg twice per day , or identical placebo .  The primary end points included clinical incident osteoporotic fractures , vertebral deformity , and adverse events ascertained in 5 years . Bone structure was also measured using dual x-ray absorptiometry of the hip and whole body , quantitative ultrasonography of the heel , and peripheral quantitative computed tomography of the distal radius . RESULTS Among our patients , 16.1 % sustained 1 or more clinical osteoporotic fractures . In the intention-to-treat analysis , calcium supplementation did not significantly reduce fracture risk ( hazard ratio , 0.87 ; 95 % confidence interval , 0.67 - 1.12 ) . However , 830 patients ( 56.8 % ) who took 80 % or more of their tablets ( calcium or placebo ) per year had reduced fracture incidence in the calcium compared with the placebo groups ( 10.2 % vs 15.4 % ; hazard ratio , 0.66 ; 95 % confidence interval , 0.45 - 0.97 ) . Calcium-treated patients had improved quantitative ultrasonography findings of the heel , femoral neck and whole-body dual x-ray absorptiometry data , and bone strength compared with placebo-treated patients . Of the 92 000 adverse events recorded , constipation was the only event increased by the treatment ( calcium group , 13.4 % ; placebo group , 9.1 % ) . CONCLUSION Supplementation with calcium carbonate tablets supplying 1200 mg/d is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance , but it is effective in those patients who are compliant Antifracture efficacy of high-dose vitamin D ( 800 IU ) and calcium ( 1000 mg ) remains controversial . To determine whether daily 800 IU of vitamin D and 1000 mg of calcium supplementation prevents fractures , we r and omized 3432 women of the population -based Osteoporosis Risk Factor and Prevention ( OSTPRE ) Study cohort ( ages 65 to 71 years ) living in the region of northern Savonia , Finl and ( latitude 62 degrees to 64 degrees N ) for 3 years to receive 800 IU of cholecalciferol and 1000 mg of calcium as calcium carbonate or to a control group that did not receive placebo . The main outcome measure was incident fractures . Fracture data were collected in telephone interviews and vali date d. Data on 3195 women , 1586 in the intervention group and 1609 in the control group , were available for analysis . In adjusted Cox proportional hazards models , the risk of any fracture decreased in the vitamin D and calcium group by 17 % [ adjusted hazard ratio ( aHR ) = 0.83 ; 95 % confidence interval ( CI ) 0.61 - 1.12 ] , and the risk of any nonvertebral fracture decreased by 13 % ( aHR = 0.87 ; 95 % CI 0.63 - 1.19 ) . The risk of distal forearm fractures decreased by 30 % ( aHR = 0.70 ; 95 % CI 0.41 - 1.20 ) , and the risk of any upper extremity fractures decreased by 25 % ( aHR = 0.75 ; 95 % CI 0.49 - 1.16 ) , whereas the risk of lower extremity fractures remained essentially equal ( aHR = 1.02 ; 95 % CI 0.58 - 1.80 ) . None of these effects reached statistical significance . In conclusion , this study did not produce statistically significant evidence that vitamin D and calcium supplementation prevents fractures in a 65- to 71-year-old general population of postmenopausal women Objective This study aims to test the added value of calcium and vitamin D ( CaD ) in fracture prevention among women taking postmenopausal hormone therapy ( HT ) . Methods This is a prospect i ve , partial-factorial , r and omized , controlled , double-blind trial among Women ’s Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years . A total of 27,347 women were r and omized to HT ( 0.625 mg of conjugated estrogens alone , or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily ) , and 36,282 women were r and omized to 1,000 mg of elemental calcium ( carbonate ) plus 400 IU of vitamin D3 daily , each compared with placebo .  A total of 16,089 women participated in both arms . The predefined outcomes were adjudicated hip fractures and measured bone mineral density . Results Interaction between HT and CaD on hip fracture ( P interaction = 0.01 ) was shown . The effect of CaD  was stronger among women assigned to HT ( hazard ratio [ HR ] , 0.59 ; 95 % CI , 0.38 - 0.93 ) than among women assigned to placebo ( HR , 1.20 ; 95 % CI , 0.85 - 1.69 ) . The effect of HT on hip fracture was stronger among women assigned to active CaD ( HR , 0.43 ; 95 % CI , 0.28 - 0.66 ) than among women assigned to placebo ( HR , 0.87 ; 95 % CI , 0.60 - 1.26 ) . CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake . There was no interaction between HT and  CaD  on change in hip or spine bone mineral density .  Conclusions Postmenopausal women at normal risk for hip fracture who are on CaD supplementation  experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake Summary Daily treatment with 30 mg of sodium fluoride ( NaF ) and 1 g of calcium over a 3-year period increased the bone mineral content ( BMC ) in the spines of women ( n=25 ) with osteoporosis . Determination of the BMC was followed with dual photon absorptiometry ( 137Cs-241Am ) in the third lumbar vertebra . No increase in BMC was found with only 10 mg sodium fluoride in combination with calcium ( n=25 ) , with calcium alone ( n=25 ) , or with placebo ( n=25 ) . No serious side effects were registered . There was , however , minor gastrointestinal distress in one-fifth of the patients taking 30 mg NaF daily We report a 4-year r and omized , double-blind , placebo-controlled clinical trial in 236 normal postmenopausal women ( mean age + /- SE , 66.3+/-0.2 years ) who were r and omized to a calcium ( 1600 mg/day as the citrate ) or placebo group .  The women were seen every 6 months ; 177 completed the trial . Net percentage changes in each group are given relative to baseline . The differences in net percentage changes ( calcium group minus placebo group ) in medians were : for lumbar spine bone density , 2.0 % ( p < 0.001 ) at year 1 and 0.3 % ( not significant ) at year 4 ; for proximal femur bone density , 1.3 % ( p = 0.003 ) at year 1 and 1.3 % ( p = 0.015 ) at year 4 ; and for total body bone mineral , 0.4 % ( p = 0.002 ) at year 1 and 0.9 % ( p = 0.017 ) at year 4 . Similar differences at year 4 were : -18.9 % ( p = 0.002 ) for parathyroid hormone ( PTH ) , -11.9 % ( p = 0.026 ) for serum osteocalcin , and -32.2 % ( p = 0.003 ) for urine free pyridinoline . We conclude that long-term administration of calcium supplements  to elderly women partially reverses age-related increases in serum PTH level and bone resorption and decreases bone loss . However , the effects on bone loss were weaker than those reported for estrogen , bisphosphonates , or calcitonin therapy , indicating that calcium supplements alone can not substitute for these in treating established osteoporosis . Nonetheless , because of their safety , high tolerance , and low expense , calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year Background In r and omized trials there may be no overriding reason whether or not to have a placebo control . Purpose We assessed the effects of an open trial design ( no placebo and people know what tablets they are given ) compared with a blinded , placebo-controlled design on recruitment , compliance and retention within a r and omized trial of secondary osteoporotic fracture prevention . Methods We undertook a r and omized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture , recruited in a UK teaching hospital . R and omization was 2 : 1 in favour of the blinded , placebo-controlled trial design . Results From 180 eligible participants r and omized to receive information based on the open trial design , 134 ( 74.4 % ) consented to take part , compared with 233 ( 65.1 % ) of 358 people r and omized to the blinded , placebo-controlled design ( difference 9.4 % , 95 % confidence interval 1.3–17.4 % ) . Reluctance to take a placebo  and the desire to know tablet allocation were reasons given for not taking part in the blinded , placebo-controlled design . There was no significant difference in tablet compliance . Open trial participants were more likely to remain in the trial for one year ( difference 13.9 % , 95 % confidence interval 3.1–24.6 % ) , mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group ( difference 23.6 % , 95 % confidence interval 11.9–35.2 % ) . The odds ratio for reporting an adverse event in the open trial compared to the blinded , placebo-controlled design was 0.64 ( 95 % confidence interval 0.28–1.49 ) , and for reporting a fracture was 0.81 ( 0.36–1.85 ) . Conclusions We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power , but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo .  Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P<0.001 ) . The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo .  Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people BACKGROUND A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies , but evidence from trials is lacking . OBJECTIVE We determined whether vitamin D supplementation , with or without calcium , improved glucose homeostasis in adults at high risk of diabetes . DESIGN Ninety-two adults were r and omly assigned in a 2-by-2 factorial- design , double-masked , placebo-controlled trial to receive either cholecalciferol ( 2000 IU once daily ) or calcium carbonate ( 400 mg twice daily ) for 16 wk . The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test . Other outcomes were acute insulin response , insulin sensitivity , and measures of glycemia . RESULTS Participants had a mean age of 57 y , a body mass index ( BMI ; in kg/m(2 ) ) of 32 , and glycated hemoglobin ( Hb A(1c ) ) of 5.9 % . There was no significant vitamin D × calcium interaction on any outcomes . The disposition index increased in the vitamin D group and decreased in the no-vitamin D group ( adjusted mean change ± SE : 300 ± 130 compared with -126 ± 127 , respectively ; P = 0.011 ) , which was explained by an improvement in insulin secretion ( 62 ± 39 compared with -36 ± 37 mU · L(-1 ) · min , respectively ; P = 0.046 ) . Hb A(1c ) increased less , but nonsignificantly , in the vitamin D group than in the no-vitamin D group ( 0.06 ± 0.03 % compared with 0.14 ± 0.03 % , respectively ; P = 0.081 ) . There was no significant difference in any outcomes with calcium compared with no calcium . CONCLUSION In adults at risk of type 2 diabetes , short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c ) . This trial was registered at clinical trials.gov as NCT00436475 PURPOSE Calcium has been shown to have positive effects on bone mineral density in postmenopausal women . However , these effects are small , it is unknown whether they are sustained with long-term use , they have not been shown with intention-to-treat analyses , and the evidence for fracture prevention with calcium monotherapy is inconsistent . METHODS A r and omized controlled trial of calcium ( 1 g/day as the citrate ) in 1471 healthy postmenopausal women ( aged 74+/-4 years ) was performed to assess the effects on  bone density and fracture incidence over 5 years . RESULTS Follow-up was complete in 90 % of subjects , and average medication compliance was 55 % to 58 % . Calcium had a significant beneficial effect on bone density ( intention-to-treat analysis ) , with between-groups differences at 5 years of 1.8 % ( spine ) , 1.6 % ( total hip ) , and 1.2 % ( total body ) . Effects were greater in a per- protocol analysis ( 5-year differences of 2.3 % , 2.8 % , and 1.8 % , respectively ) . A total of 425 fractures occurred in 281 women .  Hazard ratios , based on time to first fracture , were 0.90 ( 95 % confidence interval [ CI ] , 0.71 - 1.16 ) for any symptomatic fracture , 0.72 ( 95 % CI , 0.44 - 1.18 ) for vertebral , 3.55 ( 95 % CI , 1.31 - 9.63 ) for hip , and 0.65 ( 95 % CI , 0.41 - 1.04 ) for forearm fracture . Per- protocol analysis found respective hazard ratios of 0.86 ( 95 % CI , 0.64 - 1.17 ) , 0.62 ( 95 % CI , 0.33 - 1.16 ) , 3.24 ( 95 % CI , 0.65 - 16.1 ) , and 0.45 ( 95 % CI , 0.24 - 0.87 ) . Height loss was reduced by calcium in the per- protocol population ( P=.03 ) . Serum alkaline phosphatase and procollagen type-I N-terminal propeptide were lower in the calcium group at 5 years , but constipation was more common . CONCLUSIONS Calcium results in a sustained reduction in bone loss and turnover , but its effect on fracture remains uncertain . Poor long-term compliance limits its effectiveness Objective To observe the effects of enhanced exercise and combined vitamin D and calcium supplementation on muscular strength and fracture occurrence in postmenopausal women with a high risk of osteoporosis . Methods Totally 614 postmenopausal women at high risk factors of osteoporosis were enrolled in Dongcheng district of Beijing and r and omized into four groups : group A(control group , n=173),group B(regular Tai Chi exercise , n=171),group C(calcium 600 mg/d+VitD3 800 U/d , n=139 ) , and group D[calcium 600 mg/d+25 hydroxyl vitamin D(25OHD ) 0.25 μg/d , n=131].Muscular strength was measured at baseline and one and two years after intervention . Bone turnover markers were measured at baseline and during the two-year follow-up . Falls and fractures were recorded . Results The incidence of 25OHD<50 nmol/L was approximately 92.6%.During the follow-up , the left grip strength decreased significantly two years after intervention(t=-3.252,P=0.001)in group A.Right grip strength decreased significantly in group B(t=2.460,P=0.015)while left grip strength improved significantly in group C(t=-2.051,P=0.043)one year after intervention . In group D , muscular strength in both 12-month and 24-month did not change compared with baseline(both P>0.05).Furthermore , serum procollagen type I N-terminal propeptide elevated significantly in group A(t=-2.962,P=0.004),group B(t=-2.888,P=0.005 ) , and group C(t=-2.441,P=0.016),whereas β-C-terminal telopeptide of type I collagen decreased significantly in group B(t=2.285,P=0.024 ) and group D(t=2.596,P=0.011)two years after intervention . Conclusion Enhanced exercise and combined calcium vitamin D supplementation may help sustain muscle strength in postmenopausal women , while calcium and vitamin D supplementation may improve muscular strength within a short period of time IMPORTANCE While vitamin D supplementation and exercise are recommended for prevention of falls for older people , results regarding these 2 factors are contradictory . OBJECTIVE To determine the effectiveness of targeted exercise training and vitamin D supplementation in reducing falls and injurious falls among older women . DESIGN , SETTING , AND PARTICIPANTS A 2-year r and omized , double-blind , placebo-controlled vitamin D and open exercise trial conducted between April 2010 and March 2013 in Tampere , Finl and . Participants were 409 home-dwelling women 70 to 80 years old . The main inclusion criteria were at least 1 fall during the previous year , no use of vitamin D supplements , and no contraindication to exercise . INTERVENTIONS Four study groups , including placebo without exercise , vitamin D ( 800 IU/d ) without exercise , placebo and exercise , and vitamin D ( 800 IU/d ) and exercise . MAIN OUTCOMES AND MEASURES The primary outcome was monthly reported falls . Injurious falls and the number of fallers and injured fallers were reported as secondary outcomes . In addition , bone density , physical functioning ( muscle strength , balance , and mobility ) , and vitamin D metabolism were assessed . RESULTS Intent-to-treat analyses showed that neither vitamin D nor exercise reduced falls . Fall rates per 100 person-years were 118.2 , 132.1 , 120.7 , and 113.1 in the placebo without exercise , vitamin D without exercise , placebo and exercise , and vitamin D and exercise study groups , respectively ; however , injurious fall rates were 13.2 , 12.9 , 6.5 , and 5.0 , respectively . Hazard ratios for injured fallers were significantly lower among exercisers with vitamin D ( 0.38 ; 95 % CI , 0.17 - 0.83 ) and without vitamin D ( 0.47 ; 95 % CI , 0.23 - 0.99 ) . Vitamin D maintained femoral neck bone mineral density and increased tibial trabecular density slightly . However , only exercise improved muscle strength and balance .  Vitamin D did not enhance exercise effects on physical functioning . CONCLUSIONS AND RELEVANCE The rate of injurious falls and injured fallers more than halved with strength and balance training in home-dwelling older women , while neither exercise nor vitamin D affected the rate of falls . Exercise improved physical functioning . Future research is needed to determine the role of vitamin D in the enhancement of strength , balance , and mobility . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00986466 BACKGROUND Adults with low concentrations of 25-hydroxyvitamin D ( 25[OH]D ) in blood have an increased risk of falls and fractures , but r and omised trials of vitamin D supplementation have had inconsistent results . We aim ed to assess the effect of high-dose vitamin D supplementation on fractures and falls . METHODS The Vitamin D Assessment ( ViDA ) Study was a r and omised , double-blind , placebo-controlled trial of healthy volunteers aged 50 - 84 years conducted at one centre in Auckl and , New Zeal and . Participants were r and omly assigned to receive either an initial oral dose of 200 000 IU ( 5·0 mg ) colecalciferol ( vitamin D3 ) followed by monthly 100 000 IU ( 2·5 mg ) colecalciferol or equivalent placebo dosing . The prespecified primary outcome was cardiovascular disease and secondary outcomes were respiratory illness and fractures . Here , we report secondary outcome data for fractures and post-hoc outcome data for falls . Cox proportional hazards models were used to estimate hazard ratios ( HRs ) for time to first fracture or time to first fall in individuals allocated vitamin D compared with placebo . The analysis of fractures included all participants who gave consent and was by intention-to-treat ; the analysis of falls included all individuals who returned one or more question naires . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12611000402943 . FINDINGS Between April 5 , 2011 , and Nov 6 , 2012 , 5110 participants were recruited and r and omly assigned either colecalciferol ( n=2558 ) or placebo ( n=2552 ) . Two participants allocated placebo withdrew consent after r and omisation ; thus , a total of 5108 individuals were included in the analysis of fractures . The mean age of participants was 65·9 years ( SD 8·3 ) and 2971 ( 58 % ) were men . The mean concentration of 25(OH)D in blood was 63 nmol/L ( SD 24 ) at baseline , with 1534 ( 30 % ) having 25(OH)D concentrations lower than 50 nmol/L. Follow-up was until July 31 , 2015 , with a mean treatment duration of 3·4 years ( SD 0·4 , range 2·5 - 4·2 ) . During follow-up , 2638 participants reported having a fall , 1312 ( 52 % ) of 2539 in the vitamin D group compared with 1326 ( 53 % ) of 2517 in the placebo group . The HR for falls-adjusted for age , sex , ethnic origin , history of recent fall , physical activity , and baseline 25(OH)D-was 0·99 ( 95 % CI 0·92 - 1·07 ; p=0·82 ) for vitamin D compared with placebo . Non-vertebral fractures were reported in 292 individuals , 156 ( 6 % ) of 2558 in the vitamin D group and 136 ( 5 % ) of 2550 in the placebo group . The adjusted HR for fractures was 1·19 ( 95 % CI 0·94 - 1·50 ; p=0·15 ) for vitamin D compared with placebo . 123 ( 2 % ) people died  during the trial , 65 assigned vitamin D and 58 allocated placebo ; the difference between treatment groups was not significant . INTERPRETATION High-dose bolus vitamin D supplementation of 100 000 IU colecalciferol monthly over 2·5 - 4·2 years did not prevent falls or fractures in this healthy , ambulatory , adult population . Further research is needed to ascertain the effects of daily vitamin D dosing , with or without calcium . FUNDING Health Research Council of New Zeal and and Accident Compensation Corporation of New Zeal and
target: Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose , sex , fracture history , dietary calcium intake , and baseline serum 25-hydroxyvitamin D concentration .
  Conclusions and Relevance In this meta- analysis of r and omized clinical trials , the use of supplements that included calcium , vitamin D , or both compared with placebo or no treatment was not associated with a lower risk of fractures  among community-dwelling older adults .
background: Importance The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal .
  Previous studies have reached mixed conclusions regarding the association between calcium , vitamin D , or combined calcium and vitamin D supplements and fracture incidence in older adults .
  Objective To investigate whether calcium , vitamin D , or combined calcium and vitamin D supplements are associated with a lower fracture incidence in community-dwelling older adults .