title: Combined Calcium and Vitamin D3 Supplementation in Elderly Women: Confirmation of Reversal of Secondary Hyperparathyroidism and Hip Fracture Risk: The Decalyos II Study The Effects of Vitamin D Supplementation on Physical Function and Quality of Life in Older Patients With Heart Failure: A Randomized Controlled Trial Low serum levels of 25-hydroxyvitamin D predict hip fracture in the elderly: a NOREPOS study. High‐Dose Monthly Vitamin D for Prevention of Acute Respiratory Infection in Older Long‐Term Care Residents: A Randomized Clinical Trial Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation 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. Relationship between the effect of eldecalcitol and serum 25(OH)D level Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials 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. Hip Fractures and Bone Mineral Density in the Elderly—Importance of Serum 25-Hydroxyvitamin D Association between plasma 25-hydroxyvitamin D levels and fracture risk: the EPIC-Oxford study. Biochemical parameters after cholecalciferol repletion in hemodialysis: results From the VitaDial randomized trial. Multivitamin and mineral supplementation is associated with the reduction of fracture risk and hospitalization rate in Chinese adult males: a randomized controlled study Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: No advantage of loading doses over daily supplementation Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care An initial loading-dose vitamin D versus placebo after hip fracture surgery: randomized trial Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: a randomized controlled trial. Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation 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 the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Calciotropic hormones and the risk of hip and nonspine fractures in older adults: the Health ABC Study. The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer. Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial Does vitamin D stop inpatients falling? A randomised controlled trial. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial. Annual injection of vitamin D and fractures of aged bones Vitamin D3 and calcium to prevent hip fractures 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. The effect of high-dose vitamin D3 supplementation on bone mineral density in subjects with prediabetes Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial. 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). Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. 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. Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: the Women's Health Initiative (WHI). 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. Effects of Enhanced Exercise and Combined Vitamin D and Calcium Supplementation on Muscle Strength and Fracture Risk in Postmenopausal Chinese Women. Baseline Characteristics of the Vitamin D and Type 2 Diabetes (D2d) Study: A Contemporary Prediabetes Cohort That Will Inform Diabetes Prevention Efforts A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas. The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct Exercise and vitamin D in fall prevention among older women: a randomized clinical trial. Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: a 1-year double-blind RCT in postmenopausal women. 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: Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people .  Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures , as proved by Decalyos I. Decalyos II is a 2-year , multicenter , r and omized , double-masked , placebo-controlled confirmatory study . The intention-to-treat population consisted of 583 ambulatory institutionalized women ( mean age 85.2 years , SD = 7.1 ) r and omized to the  calcium – vitamin D3  fixed combination group ( n= 199 ) ; the calcium plus vitamin D3 separate combination group ( n= 190 ) and the placebo group ( n= 194 ) . Fixed and separate combination groups received the same daily amount of calcium ( 1200 mg ) and vitamin D3 ( 800 IU ) , which had similar pharmacodynamic effects . Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent , with levels returning within the normal range after 6 months . In a subgroup of 114 patients  , femoral neck bone mineral density ( BMD ) decreased in the placebo group ( mean = –2.36 % per year , SD = 4.92 ) , while remaining unchanged in women treated with calcium-vitamin D3 ( mean = 0.29 % per year , SD = 8.63 ) . The difference between the two groups was 2.65 % ( 95 % CI = –0.44 , 5.75 % ) with a trend in favor of the active treatment group . No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis . The relative risk ( RR ) of HF in the placebo group compared with the active treatment group was 1.69 ( 95 % CI = 0.96 , 3.0 ) , which is similar to that found in Decalyos I ( RR = 1.7 ; 95 % CI = 1.0 , 2.8 ) . Thus , these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture  in elderly institutionalized women Background —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels < 50 nmol/L ( 20 ng/mL ) received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P<0.001 ) and maintained this increase at 20 weeks . The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896 BACKGROUND Despite considerable interest , the relationship between circulating 25-hydroxyvitamin D and the risk of hip fracture is not fully established . OBJECTIVE The objective of the study was to study the association between serum 25-hydroxyvitamin D concentrations [ s-25(OH)D ] and the  risk of hip fracture in Norway , a high-latitude country that has some of the highest hip fracture rates worldwide . METHODS A total of 21 774 men and women aged 65 - 79 years attended 4 community-based health studies during 1994 - 2001 . Information on subsequent hip fractures was retrieved from electronic hospital discharge registers , with a maximum follow-up of 10.7 years . Using a stratified case-cohort design , s-25(OH)D was determined by HPLC-atmospheric pressure chemical ionization-mass spectrometry in stored serum sample s in hip fracture cases ( n = 1175 ; 307 men , 868 women ) and in gender-stratified r and om sample s ( n = 1438 ) . Cox proportional hazards regression adapted for the case-cohort design was performed . RESULTS We observed an inverse association between s-25(OH)D and hip fracture ; those with s-25(OH)D in the lowest quartile ( < 42.2 nmol/L ) had a 38 % [ 95 % confidence interval ( CI ) 9 - 74 % ] increased risk of hip fracture compared with the highest quartile ( ≥67.9 nmol/L ) in a model accounting for age , gender , study center , and body mass index . The association was stronger in men than in women : hazard ratio 1.65 ( 95 % CI 1.04 - 2.61 ) vs hazard ratio 1.25 ( 95 % CI 0.95 - 1.65 ) . CONCLUSION In this prospect i ve case-cohort study of hip fractures , the largest ever reported , we found an increased risk of hip fracture in subjects in the lowest compared with the highest quartile of serum 25-hydroxyvitamin D. In accordance with the findings of previous community-based studies , low vitamin D status was a modest risk factor for hip fracture OBJECTIVES To determine the efficacy and safety of high-dose vitamin D supplementation for prevention of acute respiratory infection ( ARI ) in older long-term care residents . DESIGN R and omized controlled trial investigating high-dose vs st and ard-dose vitamin D from 2010 to 2014 . SETTING Colorado long-term care facilities . PARTICIPANTS Long-term care residents aged 60 and older ( n = 107 ) . INTERVENTION The high-dose group received monthly supplement of vitamin D3 100,000 IU , the st and ard-dose group received a monthly placebo ( for participants taking 400 - 1,000 IU/d as part of usual care ) or a monthly supplement of 12,000 IU of vitamin D3 ( for participants taking < 400 IU/d as part of usual care ) . MEASUREMENTS The primary outcome was incidence of ARI during the 12-month intervention . Secondary outcomes were falls and fractures , 25-hydroxyvitamin D levels , hypercalcemia , and kidney stones . RESULTS Participants ( 55 high dose , 52 st and ard dose ) were r and omized and included in the final analysis . The high-dose group had 0.67 ARIs per person-year and the st and ard-dose group had 1.11 ( incidence rate ratio ( IRR ) = 0.60 , 95 % confidence interval ( CI ) = 0.38 - 0.94 , P = .02 ) . Falls were more common in the high-dose group ( 1.47 per person-year vs 0.63 in st and ard-dose group ; IRR = 2.33 , 95 % CI = 1.49 - 3.63 , P < .001 ) . Fractures were uncommon and similar in both groups ( high dose 0.10 vs st and ard dose 0.19 per person-year ; P = .31 ) . Mean trough 25-hydroxyvitamin D levels during the trial were 32 . ng/mL in the high-dose group and 25.1 ng/mL in the st and ard-dose group . There was no hypercalcemia or kidney stones in either group . CONCLUSION Monthly high-dose vitamin D3 supplementation reduced the incidence of ARI in older long-term care residents but was associated with a higher rate of falls without an increase in fractures Introduction Osteoporotic fractures in older people are a major and increasing public health problem . We examined the effect of vitamin D supplementation on fracture rate in people living in sheltered accommodation . Methods In a pragmatic double blind r and omised controlled trial of 3 years duration , we examined 3,440 people ( 2,624 women and 816 men ) living in residential or care home . We used four-monthly oral supplementation using 100,000 IU vitamin D2 ( ergocalciferol ) . As a main outcome measure , we used the incidence of first fracture using an intention to treat analysis . This was a multicentre study in 314 care homes or sheltered accommodation complexes in South Wales , UK . Results The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , 205 first fractures occurred in the intervention group during a total of 2,846 person years of follow-up ( 7 fractures per 100 people per year of follow-up ) , with 218 first fractures in the control group over 2,860 person years of follow-up . The hazard ratio of 0.95 ( 95 % confidence interval 0.79–1.15 ) for intervention compared to control was not statistically significant . ConclusionS upplementation with four-monthly 100,000 IU of oral vitamin D2 is not sufficient to affect fracture incidence among older people living in institutional care 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 In previous studies , we demonstrated that 12-month treatment with 0.75μg/day eldecalcitol increased bone mineral density in osteoporotic patients regardless of serum 25-hydroxyvitamin D ( 25(OH)D ) level , and in a 3-year r and omized double-blind clinical trial , eldecalcitol significantly reduced the incidences of vertebral and wrist fractures compared to alfacalcidol . However , it remains unclear whether the fracture risk reduction by eldecalcitol is affected by serum 25(OH)D. In the fracture prevention trial , patients with low 25(OH)D level at baseline were supplemented with 400IU/day native vitamin D3 . In the current study , patients from that trial were divided according to the tertiles of serum 25(OH)D level at 6 months after treatment initiation . The increases in lumbar and hip BMD by eldecalcitol were significantly higher in all tertiles than those by alfacalcidol .  The incidences of vertebral and osteoporotic fractures tended to be lower in each tertile of the eldecalcitol-treated group than in the corresponding tertile of the alfacalcidol-treated group , with the exception of vertebral fractures in the low tertile . We also investigated whether eldecalcitol treatment affected levels of serum 25(OH)D , serum 1,25(OH)2D , and parathyroid hormone in patients without vitamin D supplementation .  With eldecalcitol treatment , serum 1,25(OH)2D concentration was reduced by approximately 50 % , whereas serum levels of parathyroid hormone and 25(OH)D were not affected . The major findings of the present study were that eldecalcitol did not affect serum 25(OH)D levels , and that it reduced the incidence of osteoporotic fractures and increased BMD in comparison with alfacalcidol regardless of serum 25(OH)D level within the range of serum 25(OH)D concentrations at or higher than 20ng/mL. Whether eldecalcitol is similarly effective at vitamin D deficient serum 25(OH)D levels remains to be clarified . This article is part of a Special Issue entitled ' Vitamin D Workshop ' 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 Ergocalciferol ( vitamin D(2 ) ) supplementation plays a role in fall prevention , but the effect in patients living in the community in sunny climates remains uncertain . We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling . METHODS A 1-year population -based , double-blind , r and omized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth , Australia ( latitude , 32 degrees S ) , with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year . Participants were r and omized to receive ergocalciferol , 1000 IU/d , or identical placebo ( hereinafter , ergocalciferol and control groups , respectively ) . Both groups received calcium citrate , 1000 mg/d . Fall data were collected every 6 weeks . RESULTS Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height , which was significantly different between the 2 groups ( ergocalciferol group , 53.0 % ; control group , 62.9 % ; odds ratio [ OR ] , 0.61 ; 95 % confidence interval [ CI ] , 0.37 - 0.99 ) . When those who fell were grouped by the season of first fall or the number of falls they had , ergocalciferol treatment reduced the risk of having the first fall in winter and spring ( ergocalciferol group , 25.2 % ; control group , 35.8 % ; OR , 0.55 ; 95 % CI , 0.32 - 0.96 ) but not in summer and autumn , and reduced the risk of having 1 fall ( ergocalciferol group , 21.2 % ; control group , 33.8 % ; OR , 0.50 ; 95 % CI , 0.28 - 0.88 ) but not multiple falls . CONCLUSION Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium , which is associated with a 19 % reduction in the relative risk of falling , mostly in winter Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more 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 significance of serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations for hip fracture risk of the elderly is still uncertain . Difficulties reaching both frail and healthy elderly people in r and omized controlled trials or large cohort studies may in part explain discordant findings . We determined hazard ratios for  hip fractures of elderly men and women related to serum 25(OH)D , including both the frail and the healthy segment of the elderly population . Methods The AGES-Reykjavik Study is a prospect i ve study of 5764 men and women , age 66–96 years , based on a representative sample of the population of Reykjavik , Icel and . Participation was 71.8 % .  Hazard ratios of incident hip fractures and baseline bone mineral density were determined according to serum concentrations of 25(OH)D at baseline . Results Mean follow-up was 5.4 years . Compared with referent values ( 50–75 nmol/L ) , hazard ratios for hip fractures were 2.24 ( 95 % CI 1.63 , 3.09 ) for serum 25(OH)D < 30 nmol/L , adjusting for age , sex , body mass index , height , smoking , alcohol intake and season , and 2.08 ( 95 % CI 1.51 , 2.87 ) , adjusting additionally for physical activity . No difference in risk was associated with 30–50 nmol/L or ≥75 nmol/L in either model compared with referent . Analyzing the sexes separately , hazard ratios were 2.61 ( 95 % CI 1.47 , 4.64 ) in men and 1.93 ( 95 % CI 1.31 , 2.84 ) in women . Values < 30 nmol/L were associated with significantly lower bone mineral density of femoral neck compared with referent , z-scores -0.14 ( 95 % CI −0.27 , −0.00 ) in men and −0.11 ( 95 % CI −0.22 , −0.01 ) in women . Conclusions Our results lend support to the overarching importance of maintaining serum 25(OH)D above 30 nmol/L for bone health of elderly people while potential benefits of having much higher levels could not be detected The importance of vitamin D for bone health is well established , but few data exist on the relation between plasma levels of 25-hydroxyvitamin D and risk of fracture . The authors examined this association within the EPIC-Oxford ( European Prospect i ve Investigation into Cancer and Nutrition-Oxford cohort ) study of men and women in the United Kingdom ( 1993 - 1999 ) . Five years after recruitment , participants completed a follow-up question naire where fracture incidence was self-reported . Plasma 25-hydroxyvitamin D concentration was measured in 730 incident fracture cases and 1,445 matched controls . There was a clear association between plasma 25-hydroxyvitamin D concentration and month of blood draw , the highest values being during the summer months . Among women , there were significant relations between 25-hydroxyvitamin D levels and age , body mass index , marital status , use of hormone therapy , physical activity , diet group , dietary intake of vitamin D , and alcohol . Similar relations were seen among men , although often they were nonsignificant because of smaller numbers . There was no evidence of an association between plasma 25-hydroxyvitamin D and fracture risk for men or women ; the relative risks associated with a doubling of plasma 25-hydroxyvitamin D were 1.15 ( 95 % confidence interval : 0.82 , 1.61 ) and 0.95 ( 95 % confidence interval : 0.80 , 1.13 ) , respectively . These results were not affected by adjustment for potential confounders and were consistent across a number of subgroups 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 Controversy exists in the literature regarding the efficacy of bone health-related nutrients , especially calcium and vitamin D , in preventing fractures . The aim of our present study was to determine the effect of multivitamin and mineral supplementation on fracture incidence among 3,318 participants from a nutritional intervention trial in Linxian , China . A total of 1,461 men and 1,857 women were enrolled and r and omized to daily supplementation with 26 vitamins and minerals tablet or placebo pills for 6 years , followed by a 16-year post-interventional follow-up . The date s , sites , and causes of the fractures were collected retrospectively via a st and ardized question naire . Cox proportional hazard model was used to estimate hazard ratios and 95 % confidence intervals of fracture incidence in the intervention versus the placebo group . A total of 221 fractures ( 57 in men and 164 in women ) occurred during the entire study period of 21 years and 9 months . In men , the supplement reduced the risk of fracture by 63 % during the trial period , and this protective effect was sustained and statistically significant when analysis included both the trial period and 5- or 10-year post-intervention follow-up ( years 0–11 , P = 0.04 ; years 0–16 , P = 0.02 , respectively ) . The protection against fracture was not apparent > 10 years after cessation of the intervention . In women , no significant effect of supplementation on fracture incidence was seen in any of the study periods . These results demonstrate that a 6-year multivitamin and mineral intervention was associated with significant reduction of fracture risk and fracture-related hospitalization in men , but not in women 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 There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients . The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels . Methods In this r and omized controlled study , patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario , Canada . Participants were r and omized to one of three loading dose groups : placebo ; 50,000 IU vitamin D2 ; or 100,000 IU D2 . Following a placebo/loading dose , all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days . Serum 25-hydroxy vitamin D ( 25-OHD ) was measured at baseline , discharge from acute care ( approximately 4-weeks ) , and 3-months . Results Sixty-five patients were enrolled in the study ( 44 % male ) . An immediate rise in 25-OHD occurred in the 100,000 group , however there were no significant differences in 25-OHD between the placebo , 50,000 and 100,000 loading dose groups after 4-weeks ( 69.3 , 84.5 , 75.6 nmol/L , p = 0.15 ) and 3-months ( 86.7 , 84.2 , 73.3 nmol/L , p = 0.09 ) , respectively . At the end of the study , approximately 75 % of the placebo and 50,000 groups had reached the target therapeutic range ( 75 nmol/L ) , and 44 % of the 100,000 group . Conclusions In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture , our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2 . At the end of the study , all three groups were equally effective in attaining improvement in 25-OHD levels . Given that a daily dose of 1,000 IU vitamin D3 ( with or without a loading dose ) result ed in at least 25 % of patients having suboptimal vitamin D status , patients with acute hip fracture may benefit from a higher daily dose of vitamin D.Trial registration Clinical Trials # 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 Background Improving vitamin D ( 25-OHD ) status may be an important modifiable factor that could reduce disability severity , fall-rates and mortality associated after hip fracture surgery . Providing a loading-dose post-surgery may overcome limitations in adherence to daily supplementation . Method In this r and omized , double-blind , placebo-controlled trial , 218 adults , aged 65-years or older , requiring hip fracture surgery were assigned to receive a single loading-dose of cholecalciferol ( 250,000 IU vitamin-D3 , the REVITAHIP - Replenishment of Vitamin D in Hip Fracture strategy ) or placebo , both receiving daily vitamin-D(800 IU ) and calcium ( 500 mg ) for 26-weeks . Outcome measures were 2.4 m gait-velocity , falls , fractures , death ( Week-4 ) , 25-OHD levels , quality -of-life measure ( EuroQoL ) and mortality at weeks-2 , 4 and 26 . Results Mean age of 218 participants was 83.9(7.2 ) years and 77.1 % were women .  Baseline mean 25-OHD was 52.7(23.5)nmol/L , with higher levels at Week-2 ( 73 vs 66 nmol/L ; p = .019 ) and Week-4 ( 83 vs 75 nmol/L ; p = .030 ) in the Active-group , but not at Week-26 . At week-4 , there were no differences in 2.4 m gait-velocity ( 0.42 m/s vs 0.39 m/s , p = .490 ) , fractures ( 2.7 % vs 2.8 % , p = .964 ) but Active participants reported less falls ( 6.3 % vs 21.1 % , χ2 = 4.327 ; p = 0.024 ) , with no significant reduction in deaths at week-4 ( 1 vs 3 , p = 0.295 ) , higher percentage reporting ‘ no pain or discomfort ’ ( 96.4 % vs 88.8 % , p = 0.037 ) , and trended for higher EuroQoL-scores ( p = 0.092 ) at week-26 . One case of hypercalcemia at week-2 normalised by week-4 . Conclusion Among older people after hip fracture surgery , the REVITAHIP strategy is a safe and low cost method of improving vitamin-D levels , reducing falls and pain levels . Trial registration The protocol for this study is registered with the Australian New Zeal and Clinical Trials Registry ANZCTRN ACTRN12610000392066 ( Date of registration : 14/05/2010 ) 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 Importance Evidence suggests that low vitamin D status may increase the risk of cancer . Objective To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of  cancer among older women . Design , Setting , and Participants A 4-year , double-blind , placebo-controlled , population -based r and omized clinical trial in 31 rural counties ( June 24 , 2009 , to August 26 , 2015—the final date of follow-up ) . A total of 2303 healthy postmenopausal women 55 years or older were r and omized , 1156 to the treatment group and 1147 to the placebo group . Duration of treatment was 4 years . Interventions The treatment group ( vitamin D3 + calcium group ) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium ; the placebo group received identical placebos . Main Outcomes and Measures The primary outcome was the incidence of all-type cancer ( excluding nonmelanoma skin cancers ) , which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling . Results Among 2303 r and omized women ( mean age , 65.2 years [ SD , 7.0 ] ; mean baseline serum 25-hydroxyvitamin D level , 32.8 ng/mL [ SD , 10.5 ] ) , 2064 ( 90 % ) completed the study . At year 1 , serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group . A new diagnosis of cancer was confirmed in 109 participants , 45 ( 3.89 % ) in the vitamin D3 + calcium group and 64 ( 5.58 % ) in the placebo group ( difference , 1.69 % [ 95 % CI , −0.06 % to 3.46 % ] ; P = .06 ) . Kaplan-Meier incidence over 4 years was 0.042 ( 95 % CI , 0.032 to 0.056 ) in the vitamin D3 + calcium group and 0.060 ( 95 % CI , 0.048 to 0.076 ) in the placebo group ; P = .06 . In unadjusted Cox proportional hazards regression , the hazard ratio was 0.70 ( 95 % CI , 0.47 to 1.02 ) . Adverse events potentially related to the study included renal calculi ( 16 participants in the vitamin D3 + calcium group and 10 in the placebo group ) , and elevated serum calcium levels ( 6 in the vitamin D3 + calcium group and 2 in the placebo group ) . Conclusions and Relevance Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL , supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years . Further research is necessary to assess the possible role of vitamin D in cancer prevention . Trial Registration clinical trials.gov Identifier : BACKGROUND Care of elderly patients after hip fracture is not well established . METHODS We enrolled 173 patients with acute hip fracture who were 65 years or older ( 79.2 % women ; mean age , 84 years ; 77.4 % living at home ) . Using a factorial design , we r and omly allocated patients to extended physiotherapy ( PT ) ( supervised 60 min/d during acute care plus an unsupervised home program ) vs st and ard PT ( supervised 30 min/d during acute care plus no home program ; single-blinded ) , and to cholecalciferol therapy , 2000 vs 800 IU/d ( double-blinded ) . Primary outcome was rate of falls ; secondary outcome was rate of hospital readmissions during the 12-month follow-up . All analyses included 173 individuals and used multivariate Poisson regression analyses . RESULTS At baseline , 50.9 % of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7 % of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions . Because this was a factorial design trial , all analyses tested the main effect of each treatment while controlling for the other in 173 participants . Extended vs st and ard PT reduced the rate of falls by 25 % ( 95 % confidence interval [ CI ] , -44 % to -1 % ) . Cholecalciferol treatment , 2000 vs 800 IU/d , did not reduce falls ( 28 % ; 95 % CI , -4 % to 68 % ) , but reduced the rate of hospital readmissions by 39 % ( 95 % CI , -62 % to -1 % ) . CONCLUSIONS Extended PT was successful in reducing falls but not hospital readmissions , whereas cholecalciferol treatment , 2000 IU/d , was successful in reducing hospital readmission but not falls . Thus , the 2 strategies may be useful together because they address 2 different and important complications after hip fracture 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 and aims : Insufficient vitamin D status , commonly found in older people , has been associated with muscle weakness which , in old age , impairs mobility and is a risk factor for falling . In a r and omized , double-blind placebo-controlled trial , we tested the hypothesis that vitamin D + calcium supplementation improves muscle strength and mobility , compared with calcium mono-therapy in vitamin D-insufficient female geriatric patients . Methods : Seventy female geriatric patients > 65 years of age with serum 25-hydroxyvitamin D3 ( 25OHD ) concentrations between 20 and 50 nmol/L , visiting an outpatient geriatric department , were included . Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day ( D/Cal group ) or a placebo + calcium 500 mg/day ( Plac/Cal group ) for 6 months . At baseline and 6 months , muscle strength , power and functional mobility were tested . Results : At baseline , 25OHD was significantly ( p<0.05 ) associated with knee extension strength ( r=0.42 ) , h and grip strength ( r=0.28 ) , leg extension power ( r=0.34 ) , Timed Get Up and Go ( r=−0.31 ) and Modified Cooper test ( r=0.44 ) . At 6 months , a significant difference in 25OHD ( 77.2 vs 41.6 nmol/L , p<0.001 ) and 1,25OHD was found between the two groups . Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups . Conclusions : Daily 400IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients 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 OBJECTIVES To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation . DESIGN A r and omised controlled trial of cluster design . SETTING AND SUBJECTS 223 Residential units ( mainly identical 30-bedded units ) , within 118 homes for elderly people throughout Britain , with 3,717 participating residents ( 76 % women , average age 85 years ) . The units provided mainly or entirely residential care ( 35 % of residents ) , nursing care ( 42 % ) or care for elderly mentally infirm ( EMI ) residents ( 23 % ) . METHODS Participants were r and omly allocated by residential unit ( cluster design ) to a treated group offered ergocalciferol 2.5 mg every 3 months ( equivalent to a daily dose of 1,100 IU ) , or to a control group .  Fractures were reported by staff and confirmed in hospital , and routinely collected data on reported falls were obtained . RESULTS After median follow-up of 10 months ( interquartile range 7 - 14 months ) , 64 ( 3.6 % ) of 1,762 vitamin D-treated residents and 51 ( 2.6 % ) of 1,955 controls had one or more non-vertebral fractures , and 24 ( 1.3 % ) and 20 ( 1.0 % ) , respectively , had a hip fracture . The proportion reporting at least one fall was 44 % in vitamin D-treated and 43 % in control residents . The differences between the vitamin D and control groups were not statistically significant . The incidence of all non-vertebral fractures in the care homes ( 3.2 % per year ) and of hip fractures ( 1.1 % per year ) was low , similar to rates in elderly people in sheltered accommodation , and the pre-treatment serum 25-hydroxy vitamin D concentration was high [ median 47 nmol/l , measured in a 1 % ( n = 18 ) sample ] . CONCLUSIONS We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation The effects of vitamin D and parathyroid hormone ( PTH ) levels on incident fracture remain uncertain . To test the hypothesis that increasing serum 25-hydroxyvitamin D [ 25(OH)D ] and decreasing PTH levels are associated with decreased risk of hip and any nonspine fracture , we conducted a prospect i ve cohort study among 2614 community-dwelling white and black participants , aged ≥70 years , from the Health , Aging and Body Composition ( Health ABC ) Study . Serum and plasma sample s were drawn at year 2 , which formed the baseline for this analysis . Serum 25(OH)D and intact PTH ( 1 - 84 ) were measured using radioimmunoassay with DiaSorin reagents and EDTA plasma with a two-site immunoradiometric assay kit , respectively . Incident fractures ( hip and any nonspine ) were assessed after year 2 , every 6 months , by self-report and vali date d by radiology reports . The median ( interquartile range ) follow-up times for hip and any nonspine fractures were 6.4 ( 6.1 - 6.5 ) and 6.4 ( 5.5 - 6.5 ) years , respectively . Cox proportional hazards regression was used to estimate the hazard ratios ( HR ) with 95 % confidence intervals ( CI ) for fracture . There were 84 hip and 247 nonspine fractures that occurred over the follow-up period . The multivariable adjusted HRs ( 95 % CIs ) of hip fracture for participants in the lowest ( ≤17.78 ng/mL ) , second ( 17.79 to 24.36 ng/mL ) , and third quartiles ( 24.37 to 31.94 ng/mL ) of 25(OH)D were 1.92 ( 0.97 to 3.83 ) , 0.75 ( 0.32 to 1.72 ) and 1.86 ( 1.00 to 3.45 ) , respectively , compared with participants in the highest 25(OH)D quartile ( > 31.94 ng/mL ) ( p trend = 0.217 ) . Additional adjustment for IL-6 ( p = 0.107 ) , PTH ( p = 0.124 ) , and hip areal bone mineral density ( p = 0.137 ) attenuated HRs of hip fracture in the lowest quartile by 16.3 % , 17.4 % , and 26.1 % , respectively . There was no evidence of an association between 25(OH)D and any nonspine fractures , or between PTH and hip or any nonspine fractures . We found limited evidence to support an association between calciotropic hormones and hip and nonspine fractures in older men and women BACKGROUND Vitamin D , specifically serum 25(OH)D has been associated with mortality , cancer and multiple other health endpoints in observational studies , but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population -wide supplementation . We have therefore launched the D-Health Trial , a r and omized trial of vitamin D supplementation for prevention of mortality and cancer . Here we report the methods and describe the trial cohort . METHODS The D-Health Trial is a r and omized placebo-controlled trial , with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers . Participants aged 65 - 84years were recruited from the general population of Australia . The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo . The primary outcome is all-cause mortality . Secondary outcomes are total cancer incidence and colorectal cancer incidence . RESULTS We recruited 21,315 participants to the trial between February 2014 and May 2015 . The participants in the two arms of the trial were well-balanced at baseline . Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health , to be current smokers or to have diabetes than the Australian population . However , the proportion overweight or with health conditions such as arthritis and angina was similar . CONCLUSIONS Observational data can not be considered sufficient to support interventions delivered at a population level . Large-scale r and omized trials such as the D-Health Trial are needed to inform public health policy and practice OBJECTIVES To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient . DESIGN R and omized , placebo-controlled double-blind , trial of 2 years ' duration . SETTING Multicenter study in 60 hostels ( assisted living facilities ) and 89 nursing homes across Australia . PARTICIPANTS Six hundred twenty-five residents ( mean age 83.4 ) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L. INTERVENTION Vitamin D supplementation ( ergocalciferol , initially 10,000 IU given once weekly and then 1,000 IU daily ) or placebo for 2 years . All subjects received 600 mg of elemental calcium daily as calcium carbonate . MEASUREMENTS Falls and fractures recorded prospect ively in study diaries by care staff . RESULTS The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , the incident rate ratio for falling was 0.73 ( 95 % confidence interval (CI)=0.57 - 0.95 ) . The odds ratio for ever falling was 0.82 ( 95 % CI=0.59 - 1.12 ) and for ever fracturing was 0.69 ( 95 % CI=0.40 - 1.18 ) . An a priori subgroup analysis of subjects who took at least half the prescribed capsules ( n=540 ) , demonstrated an incident rate ratio for falls of 0.63 ( 95 % CI=0.48 - 0.82 ) , an odds ratio ( OR ) for ever falling of 0.70 ( 95 % CI=0.50 - 0.99 ) , and an OR for ever fracturing of 0.68 ( 95 % CI=0.38 - 1.22 ) . CONCLUSION Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient Specific receptors for vitamin D have been identified in human muscle tissue . Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls . We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls . In a double-blind r and omized controlled trial , we studied 122 elderly women ( mean age , 85.3 years ; range , 63 - 99 years ) in long-stay geriatric care . Participants received 1200 mg calcium plus 800 IU cholecalciferol ( Cal+D-group ; n = 62 ) or 1200 mg calcium ( Cal-group ; n = 60 ) per day over a 12-week treatment period . The number of falls per person ( 0 , 1 , 2 - 5 , 6 - 7 , > 7 falls ) was compared between the treatment groups . In an intention to treat analysis , a Poisson regression model was used to compare falls after controlling for age , number of falls in a 6-week pretreatment period , and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations . Among fallers in the treatment period , crude excessive fall rate ( treatment - pretreatment falls ) was compared between treatment groups . Change in musculoskeletal function ( summed score of knee flexor and extensor strength , grip strength , and the timed up&go test ) was measured as a secondary outcome . Among subjects in the Cal+D-group , there were significant increases in median serum 25-hydroxyvitamin D ( + 71 % ) and 1,25-dihydroxyvitamin D ( + 8 % ) . Before treatment , mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group . In the 12-week treatment period , mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group . After adjustment , Cal+D-treatment accounted for a 49 % reduction of falls ( 95 % CI , 14 - 71 % ; p < 0.01 ) based on the fall categories stated above . Among fallers of the treatment period , the crude average number of excessive falls was significantly higher in the Cal-group ( p = 0.045 ) . Musculoskeletal function improved significantly in the Cal+D-group ( p = 0.0094 ) . A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49 % compared with calcium alone . Over this short-term intervention , recurrent fallers seem to benefit most by the treatment . The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function Summary In 242 community-dwelling seniors , supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D result ed in a decrease in the number of subjects with first falls of 27 % at month 12 and 39 % at month 20 . Additionally , parameters of muscle function improved significantly . Introduction The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially . R and omized controlled trials using falls as primary outcome are needed . We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men . Methods Our study population consisted of 242 individuals recruited by advertisements and mailing lists ( mean [ ± SD ] age , 77 ± 4 years ) . All serum 25-hydroxyvitamin D ( 25[OH]D ) levels were below 78 nmol/l . Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months , which was followed by a treatment-free but still blinded observation period of 8 months . Falls were documented using diaries . The study took place in Bad Pyrmont , Germany ( latitude 52 ° ) and Graz , Austria ( latitude 46 ° ) . Results Compared to calcium mono , supplementation with calcium plus vitamin D result ed in a significant decrease in the number of subjects with first falls of 27 % at month 12 ( RR = 0.73 ; CI = 0.54–0.96 ) and 39 % at month 20 ( RR = 0.61 ; CI = 0.34–0.76 ) . Concerning secondary endpoints , we observed significant improvements in quadriceps strength of 8 % , a decrease in body sway of 28 % , and a decrease in time needed to perform the TUG test of 11 % . Discussion Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals Falls are a serious health problem in the aging population . Because low levels of vitamin D have been associated with increased fall rates , many trials have been performed with vitamin D ; two meta-analyses showed either a small effect or no effect of vitamin D on falls . We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D ( 25OHD ) and data on falls was collected as a secondary outcome . In a 12-month double blind r and omized placebo trial , elderly women , mean age 66 years , were r and omized to one of seven daily oral doses of vitamin D or placebo . The main inclusion criterion for study was a baseline serum 25OHD<20ng/ml ( 50nmol/L ) . A history of falls was collected at baseline and fall events were collected every 3 months . Results showed that the effect of vitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels . There was no decrease in falls on low vitamin D doses 400 , 800 IU , a significant decrease on medium doses 1600 , 2400,3200 IU ( p=0.020 ) and no decrease on high doses 4000 , 4800 IU compared to placebo ( p=0.55 ) . When compared to 12-month serum 25OHD quintiles , the faller rate was 60 % in the lowest quintile < 25ng/ml ( < 50nmol/L ) , 21 % in the low middle quintile 32 - 38ng/ml ( 80 - 95nmo/L ) , 72 % in the high middle quintile 38 - 46ng/ml ( 95 - 115nmo/L ) and 45 % in the highest quintile 46 - 66ng/ml ( 115 - 165nmol/L ) . In the subgroup with a fall history , fall rates were 68 % on low dose , 27 % on medium doses and 100 % on higher doses . Fall rates on high doses were increased compared to medium doses ( Odds Ratio 5.6.95 % CI : 2.1 - 14.8 ) . In summary , the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32 - 38ng/ml ( 80 - 95nmol/L ) and faller rates increase as serum 25OHD exceed 40 - 45ng/ml ( 100 - 112.5nmol/L ) . The Tolerable upper limit ( TUL ) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history BACKGROUND Vitamin D deficiency is common in older people and may increase risk of falls and fracture .  Hospital in patients are at particular risk of falling . Previous studies suggest that vitamin D improves neuromuscular function and reduces falls . OBJECTIVE To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are in patients . DESIGN R and omised , double-blind , controlled study . PARTICIPANTS two hundred and five acute admissions > 65 years to a geriatric medical unit . METHODS Patients were r and omised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg , until discharge or death . RESULTS Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days ( IQR 14.75 - 71.00 ) . In a pre-selected sub-group ( 54/205 participants ) , median admission vitamin D level = 22.00 nmol/l ( IQR 15.00 - 30.50 ) . This did not significantly increase in the treatment versus control group . Median study drug adherence = 88 % , with no significant difference between study groups ( Mann-Whitney : P = 0.711 ) . Although there were fewer fallers in the vitamin D cohort , this did not reach statistical significance ( vitamin D : calcium = 36:45 fallers ; RR 0.82 ( CI 0.59 - 1.16 ) . Neither the mean number of falls  ( vitamin D : calcium = 1.040:1.155 ; Mann-Whitney P = 0.435 ) or time to first fall ( Log-rank test P = 0.377 ) differed between groups . CONCLUSIONS In a population of geriatric hospital in patients , vitamin D did not reduce the number of fallers . Routine supplementation can not be recommended to reduce falls in this group OBJECTIVES Low trauma fractures in older people incur enormous physical , social and economic costs . Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group . This strategy requires validation in a population setting . METHODS R and omized , double-blind , placebo-controlled trial of 300,000 IU intramuscular ( i.m . ) vitamin D2 ( ergocalciferol ) injection or matching placebo every autumn over 3 years . 9440 people ( 4354 men and 5086 women ) aged 75 yrs and over were recruited from general practice registers in Wessex , Engl and . Primary outcome measure was all non-vertebral fracture . Secondary outcomes were hip and wrist fractures , and all falls . RESULTS 585 subjects had incident non-spine fractures  ( hip 110 , wrist 116 , ankle 37 ) . Hazard ratios ( HRs ) for fracture in the vitamin D group were : 1.09 [ 95 % confidence interval ( CI ) 0.93 - 1.28 , P = 0.29 ] for any first fracture , 1.49 ( 95 % CI 1.02 - 2.18 , P = 0.04 ) for hip and 1.22 ( 95 % CI 0.85 - 1.76 , P = 0.28 ) for wrist . There was no effect on falls : HR 0.98 ( 0.93 - 1.04 ) . No protective effect was observed in any subgroup when the cohort was stratified by sex , age , previous fracture or mobility . CONCLUSIONS An annual i.m . injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population OBJECTIVES We investigated the incidence of new non-vertebral fractures  during HRT or low-dose vitamin ( Vit ) D3 supplementation in a 5-year prospect i ve trial . METHODS A total of 464 early postmenopausal women , ( a subgroup of the Kuopio Osteoporosis Study , n = 13,100 ) were r and omized to four groups : ( 1 ) HRT , a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ; ( 2 ) Vit D ( 300 IU/day and 100 IU/day during the fifth years ) ; ( 3 ) HRT + Vit D ; and ( 4 ) placebo .  Lumbar ( L2 - 4 ) and femoral neck bone mineral densities ( BMD ) were determined by dual X-ray absorptiometry ( DXA ) at baseline , after 2.5 and 5 years of treatment . All new symptomatic non-vertebral , radiographically defined fractures were recorded . RESULTS Altogether , 368 women ( 79 % ) completed the 5 year treatment . In all , 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up ( HRT 4 , Vit D 10 , HRT + Vit D 8 and placebo 17 ) . The reduction in the incidence of new non-vertebral fractures was significant in women with HRT alone ( P = 0.032 ) when adjusted by baseline BMD and previous fractures ; observed also with the intention-to-treat principle ( P = 0.048 ) . When the HRT groups were pooled , HRT showed a significantly lower incidence of new non-vertebral fractures ( P = 0.042 ) than women receiving placebo and also after adjusting as above ( P = 0.016 ) ; both in valid-case and in the intention-to-treat analysis . In the Vit D group , the fracture incidence was non-significantly decreased ( P = 0.229 ) in comparison with the placebo group . The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 ( 95 % CI , 0.10 - 0.90 ) and with Vit D 0.47 ( 95 % CI , 0.20 - 1.14 ) and with HRT + Vit D 0.44 ( 95 % CI , 0.17 - 1.15 ) , in comparison with the placebo group ( adjusted by femoral BMD and previous fractures ) . CONCLUSIONS This study is the first prospect i ve trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women . The effect of low-dose Vit D remains to be proved Summary In order to investigate the effect of a supplementation of vitamin D in the prophylaxis of fractures of the bones of aged people , an annual intramuscular injection of ergocalciferol ( 150,000–300,000 IU ) was given to two series of aged subjects : first to 199 ( 45 male ) of 479 subjects ( 110 male ) aged more than 85 years who were living in their own home , and second to 142 ( 29 male ) of 320 ( 58 male ) subjects aged 75–84 and living in a home for aged people . This prospect i ve series was divided into treatment groups according to month of birth . These injections were given annually from September to December in the years 1985–1989 , two to five times to each participant . The fracture rates , laboratory values , vitamin D levels , possible side effects , and mortality were followed until October 1990 . A total of 56  fractures  occurred in the 341 vitamin D recipients ( 16.4 % ) and 100 in 458 controls ( 21.8 % ) ( P=0.034 ) . The fracture rate was about the same in both outpatient and municipal home series . Fractures of the upper limb were fewer in the vitamin D recipients , 10/341=2.9 % ( P=0.025 ) , than in the controls , 28/458=6.1 % , during the follow-up . A similar result was obtained in fractures of ribs , 3/341=0.9 % and 12/458=2.6 % , respectively . Fractures of the lower limbs occurred almost as frequently , 31/341=9.1 % , among the vitamin D recipients as among the controls , 49/458=10.7 % . The fracture rate was higher in females ( 22.2 % ) than in males ( 9.5 % ) . The fractures were fewer in the vitamin D recipients only in females . No significant differences were found in total mortality , or due to any group of diseases , between the two treatment groups . No deleterious effects of the  vitamin D  injections were seen . The authors recommend the supplementation of vitamin D in aged people , at least in northernmost latitudes ( e.g. , as an annual intramuscular injection ) 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 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 Summary The rationale of this study was to determine the effect of high-dose vitamin D3 supplementation on bone mineral density ( BMD ) .  Prediabetic males given vitamin D had significantly less reduction in BMD at the femoral neck compared to the controls . The clinical implication s of our findings require further investigation . Introduction Type 2 diabetes mellitus is associated with increased fracture risk , and recent studies show crosstalk between bone and glucose metabolism . Few studies have investigated the effect of vitamin D supplementation on the bone without additional calcium . In the present study , we aim ed to determine whether a high dose of vitamin D3 could improve bone mass density ( BMD ) in prediabetic subjects . Methods The current study was conducted as a secondary research on a previously performed trial , in which 511 subjects with prediabetes were r and omized to vitamin D3 ( 20,000 IU per week ) versus placebo for 5 years  . BMD was measured using dual-energy X-ray absorptiometry ( DEXA ) . Results Two hundred and fifty-six subjects were r and omized to vitamin D and 255 to placebo . Mean baseline serum 25-hydroxyvitamin D ( 25(OH)D ) level was 60 nmol/L. Two hundred and two and 214 in the vitamin D and placebo groups , respectively , completed BMD measurements , whereas one in each group was excluded due to use of bisphosphonates . Males given vitamin D had significantly less reduction in BMD at the femoral neck measurement site compared to the controls ( 0.000 versus − 0.010 g/cm2 , p = 0.008 ) . No significant differences between intervention groups were seen at the total hip measurement site , regarding both males and females . Conclusions Vitamin D3 supplementation alone may be beneficial in males with prediabetes , but confirmatory studies are needed Context Vitamin D supplementation may help prevent fractures , but the relationship between blood vitamin D concentrations and fracture risk is unclear . Contribution These authors observed an increased risk for hip fracture among women with lower serum 25-hydroxyvitamin D [ 25(OH ) vitamin D ] concentrations that was independent of measures of frailty , body mass index , physical function , and falls . Caution The authors did not measure bone mineral density ( BMD ) , so they could not determine whether 25(OH ) vitamin D concentrations give different information about fracture risk than that offered by BMD . Implication Low serum 25(OH ) vitamin D concentrations seem to be associated with a higher hip fracture risk . The Editors Vitamin  D deficiency is common in older adults , especially during the winter ( 1 ) and in homebound population s ( 2 ) , general medical in patients ( 3 ) , and community-dwelling women admitted to the hospital with acute hip fracture ( 4 ) . A recently published evidence -based report on vitamin D and bone health ( 5 ) found the level of evidence for an association between serum 25-hydroxyvitamin D [ 25(OH ) vitamin D ] concentrations and fracture risk to be inconsistent ( 5 ) . Since publication of that review , 1 prospect i ve study ( 6 ) reported no relationship between serum 25(OH ) vitamin D concentrations and fractures , whereas another ( 7 ) reported a significantly lower risk for hip fracture with 25(OH ) vitamin D concentrations greater than 60 nmol/L. Vitamin D concentration could be associated with fractures in several ways . It could influence muscle strength and balance , both of which contribute to falls and disability ( 810 ) . The association between 25(OH ) vitamin D concentrations and fracture may also be influenced by renal function , because renal insufficiency has been linked to fracture ( 11 ) and to vitamin D deficiency ( 12 ) . Several interactions between vitamin D and estrogen receptors have been described ( 13 ) ; hormone therapy has been shown to reverse abnormalities in vitamin D metabolism ( 14 ) , and low vitamin D concentrations have also been linked to higher bone turnover ( 15 , 16 ) . Thus , sex-steroid hormones and bone turnover could contribute to the association between 25(OH ) vitamin D concentration and fractures . We conducted a nested casecontrol study within the WHI-OS ( Women 's Health Initiative Observational Study ) among 400 case- patients with adjudicated incident hip fracture and 400 control participants . We tested whether low serum 25(OH ) vitamin D concentrations are associated with a higher risk for hip fractures in community-dwelling women and whether this relationship may be mediated by poor physical functioning , frailty , falls , sex-steroid hormones , renal function , or bone turnover . Methods Study Population Our study population came from the WHI-OS , a prospect i ve cohort study that enrolled 93676 women between 1994 and 1998 at 40 U.S. clinical centers ( age range , 50 to 79 years ) . Study methods are described in detail elsewhere ( 17 ) . In brief , women were eligible if they were postmenopausal , were unlikely to move or die within 3 years , were not enrolled in the WHI clinical trials , and were not currently participating in any other clinical trial . The human subjects review committees from each participating institution approved the study . Follow-up and Outcome Ascertainment We sent women question naires annually to report any hospitalization and other outcomes , including fractures . As of August 2004 , median follow-up duration was 7.1 years ( range , 0.7 to 9.3 years ) . At that time , 3.7 % of participants had withdrawn or were lost to follow-up and 5.3 % had died . We review ed medical records to verify cases of hip fracture , and blinded central adjudicators confirmed the cases ( 18 ) . We excluded patients with pathologic hip fractures . Nested CaseControl Study Design The present study is a casecontrol study nested within the prospect i ve design of WHI-OS . We excluded women who had a history of hip fracture ; were receiving hormone therapy up to 1 year before enrollment ; or were currently receiving and rogens , selective estrogen receptor modulators , antiestrogens , or other osteoporosis treatments ( bisphosphonates , calcitonin , or parathyroid hormone ) . We also excluded women with insufficient serum stored or of unknown ethnicity , leaving 39793 eligible participants . Of these , 404 women had a hip fracture . We r and omly selected 400 of these women to form the incident hip fracture group . For each case-patient , we selected 1 control participant who was within 1 year of the case-patient 's age at screening , was of matching race or ethnicity , and had their blood drawn within 120 days of the case-patient 's blood draw date ; 99 % of case- patients and control participants were matched within 30 days . Baseline Clinical Variables We divided clinical centers into 3 geographic regions on the basis of latitude : northern ( > 40 N ) , middle ( 35 to 40 N ) , and southern ( < 35 N ) . We ascertained all covariates at baseline . Clinic interviewers recorded current use of prescription medications by direct inspection of medicine containers . We entered prescription names into the WHI data base and assigned drug codes by using Medispan software ( First Data Bank , San Bruno , California ) . Average amounts of elemental calcium and vitamin D preparations were entered directly from supplement containers . Dietary intakes of calcium and vitamin D were assessed by using a semiquantitative food-frequency question naire ( 19 ) . Total calcium and vitamin D intake was defined as the sum of diet and supplements . We used question naires to ascertain date of birth , race or ethnicity , age at menopause , history of any fracture after age 55 years , smoking , parental history of hip fracture , self-rated health status , and alcohol consumption . We classfied physical activity on the basis of frequency and duration of walking and mild , moderate , and strenuous activities in the previous week . We calculated kilocalories of energy expended in 1 week as the metabolic equivalent ( kcal hours/week per kg ) ( 20 ) . We measured physical function by using the R AND Short Form-36 physical function scale , which comprises 10 items measuring whether health now limits physical function in moderate or vigorous activity ( 2 items ) ; strength to lift , carry , stoop , bend , or stair climb ( 4 items ) ; ability to walk various distances without difficulty ( 3 items ) ; and self-care ( 1 item ) ( 21 ) . The scale is scored from 0 to 100 , with higher scores indicating better physical function . We compared women with a score greater than 90 versus those with a score less than or equal to 90 , a cutoff value corresponding to the median score . We computed a frailty score , which included self-reported muscle weakness and impaired walking speed ( R AND Short Form-36 physical function scale score < 75 ) , exhaustion ( R AND Short Form-36 vitality scale score < 55 ) , low physical activity ( lowest quartile of physical activity ) , and unintended weight loss between baseline and 3 years of follow-up ( 22 ) . A woman was considered frail if she reported 3 or more of these indicators . Weight was measured on a balance-beam scale with the participant dressed in indoor clothing without shoes . Height was measured by using a wall-mounted stadiometer . Body mass index was calculated as weight ( in kg ) divided by height ( in m2 ) . Laboratory Procedures Laboratory personnel blinded to casecontrol status obtained a 12-hour fasting blood sample at the baseline visit , which was processed and stored at 80C according to strict quality control procedures ( 23 ) . Serum 25(OH ) vitamin D concentrations and sex-steroid hormone levels were measured at the Reproductive Endocrine Research Laboratory at the University of Southern California .  25-Hydroxyvitamin vitamin D was measured by using a radioimmunoassay with DiaSorin reagents ( DiaSorin , Stillwater , Minnesota ) . The sensitivity of the assay was 3.75 nmol/L. The interassay coefficients of variation were 11.7 % , 10.5 % , 8.6 % , and 12.5 % at 14.0 , 56.8 , 82.5 , and 122.5 nmol/L , respectively . Estradiol and testosterone concentrations were quantified by using sensitive and specific radioimmunoassays after organic solvent extraction and celite column partition chromatography ( 2427 ) . The intra- and interassay coefficients of variation were 7.9 % and 8 % to 12 % , respectively , for estradiol and 6 % and 10 % to 12 % , respectively , for testosterone . We calculated bioavailable hormone concentrations by using mass action equations ( 2830 ) . We measured sex hormonebinding globulin by using a solid-phase , 2-site chemiluminescent immunoassay . The intra- and interassay coefficients of variation were 4.1 % to 7.7 % and 5.8 % to 13 % , respectively . Serum cystatin C , a marker of renal function that is independent of age and weight , was measured at Medical Research Laboratories International , Highl and Heights , Kentucky , by using the Dade Behring BN-II nephelometer and Dade Behring reagents ( Dade Behring , Ramsey , Minnesota ) in a particle-enhanced immunonepholometric assay . Serum C-terminal telopeptide of type I collagen and aminoterminal procollagen extensions propeptide were measured by immunoassay ( Synarc , Lyon , France ) . Statistical Analysis We used chi-square and t tests to compare baseline characteristics between case- patients with hip fracture and matched control participants . We assigned 25(OH ) vitamin D concentrations to quartile categories defined on the basis of the distribution in the control participants . To further assess confounding , we compared baseline characteristics across quartiles of 25(OH ) vitamin D concentrations in case- patients and control participants combined . We calculated the P values for trend by using logistic regression and coding the variable of interest as a continuous variable . We assessed the association between serum 25(OH ) vitamin D concentrations and incident hip fracture in conditional logistic regression models that retained the matched casecontrol design . We first examined the unadjusted associations and then adjusted for age , IMPORTANCE Experts debate optimal 25-hydroxyvitamin D ( 25[OH]D ) levels for musculoskeletal health . OBJECTIVE To compare the effects of placebo , low-dose cholecalciferol , and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption , bone mineral density , Timed Up and Go and five sit-to-st and tests , and muscle mass in postmenopausal women with vitamin D insufficiency . DESIGN , SETTING , AND PARTICIPANTS This r and omized , double-blind , placebo-controlled clinical trial was conducted at a single center in Madison , Wisconsin , from May 1 , 2010 , through July 31 , 2013 , and the final visit was completed on August 8 , 2014 . A total of 230 postmenopausal women 75 years or younger with baseline 25(OH)D levels of 14 through 27 ng/mL and no osteoporosis were studied . INTERVENTIONS Three arms included daily white and twice monthly yellow placebo ( n=76 ) , daily 800 IU vitamin D3 and twice monthly yellow placebo ( n=75 ) , and daily white placebo and twice monthly 50,000 IU vitamin D3 ( n=79 ) . The high-dose vitamin D regimen achieved and maintained 25(OH)D levels≥30 ng/mL. MAIN OUTCOMES AND MEASURES Outcome measures were 1-year change in total fractional calcium absorption using 2 stable isotopes , bone mineral density and muscle mass using dual energy x-ray absorptiometry , Timed Up and Go and five sit-to-st and tests , functional status ( Health Assessment Question naire ) , and physical activity ( Physical Activity Scale for the Elderly ) , with Benjamini-Hochberg correction of P values to control for the false discovery rate . RESULTS After baseline absorption was controlled for , calcium absorption increased 1 % ( 10 mg/d ) in the high-dose arm but decreased 2 % in the low-dose arm ( P = .005 vs high-dose arm ) and 1.3 % in the placebo arm ( P = .03 vs high-dose arm ) . We found no between-arm changes in spine , mean total-hip , mean femoral neck , or total-body bone mineral density , trabecular bone score , muscle mass , and Timed Up and Go or five sit-to-st and test scores . Likewise , we found no between-arm differences for numbers of falls , number of fallers , physical activity , or functional status . CONCLUSIONS AND RELEVANCE High-dose cholecalciferol therapy increased calcium absorption , but the effect was small and did not translate into beneficial effects on bone mineral density , muscle function , muscle mass , or falls . We found no data to support experts ' recommendations to maintain serum 25(OH)D levels of 30 ng/mL or higher in postmenopausal women . Instead , we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/mL. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00933244 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 R and omized controlled trials have shown that a combination of vitamin D and calcium can prevent  fragility fractures in the elderly . Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known . We studied if an intervention with 10 microg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded r and omized controlled trial . Residents from 51 nursing homes were allocated r and omly to receive 5 ml of ordinary cod liver oil ( n = 569 ) or 5 ml of cod liver oil where vitamin D was removed ( n = 575 ) . During the study period of 2 years , fractures and deaths were registered , and the principal analysis was performed on the intention-to-treat basis . Biochemical markers were measured at baseline and after 1 year in a sub sample . Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a  hip fracture . The corresponding figures for all nonvertebral fractures were 76 persons ( control group ) and 69 persons ( vitamin D group ) . There was no difference in the incidence of hip fracture ( p = 0.66 , log-rank test ) , or in the incidence of all nonvertebral fractures ( p = 0.60 , log-rank test ) in the vitamin D group compared with the control group . Compared with the control group , persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter ( p = 0.001 ) . In conclusion , we found that an intervention with 10 microg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people 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 Low 25-hydroxyvitamin D [ 25(OH)D ] levels have been linked to hip fracture in white women . To study the association of 25(OH)D with risk of fracture in multiethnic women , we performed a nested case-control study within the prospect i ve Women 's Health Initiative ( WHI ) Observational Study . Incident fractures were identified in 381 black , 192 Hispanic , 113 Asian , and 46 Native American women over an average of 8.6 years . A r and om sample of 400 white women who fractured was chosen . One control individual was selected per case and matched on age , race/ethnicity , and blood draw date .  25(OH)D , parathyroid hormone , and vitamin D-binding protein ( DBP )  were measured in fasting baseline serum . Conditional logistic regression models were used to calculate the odds ratio ( OR ) and 95 % CI . In multivariable models , higher 25(OH)D levels compared with levels less than 20 ng/mL were associated with a lower risk of fracture in white women ( 20 to < 30 ng/mL : OR = 0.82 , 95 % CI 0.58 - 1.16 ; ≤30.0 ng/mL : OR = 0.56 , 95 % CI 0.35 - 0.90 ; p trend = 0.02 ) . In contrast , higher 25(OH)D ( ≥20 ng/mL ) compared with levels less than 20 ng/mL were associated with a higher risk of fracture in black women ( OR = 1.45 , 95 % CI 1.06 - 1.98 ; p trend = 0.043 ) . Higher 25(OH)D ( ≥30.0 ng/mL ) was associated with higher fracture risk in Asian women after adjusting for DBP ( OR = 2.78 , 95 % CI 0.99 - 7.80 ; p trend = 0.04 ) . There was no association between 25(OH)D and fracture in Hispanic or Native American women . Our results suggest divergent associations between 25(OH)D and fracture by race/ethnicity . The optimal level of 25(OH)D for skeletal health may differ in white and black women 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 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 OBJECTIVE To describe baseline characteristics of the Vitamin D and Type 2 Diabetes ( D2d ) study , the first large U.S. diabetes prevention clinical trial to apply current American Diabetes Association ( ADA ) criteria for prediabetes . RESEARCH DESIGN AND METHODS This is a multicenter ( n = 22 sites ) , r and omized , double-blind , placebo-controlled , primary prevention clinical trial testing effects of oral daily 4,000 IU cholecalciferol ( D3 ) compared with placebo on incident diabetes in U.S. adults at risk for diabetes . Eligible participants were at risk for diabetes , defined as not meeting criteria for diabetes but meeting at least two 2010 ADA glycemic criteria for prediabetes : fasting plasma glucose ( FPG ) 100–125 mg/dL , 2-h postload glucose ( 2hPG ) after a 75-g oral glucose load 140–199 mg/dL , and /or a hemoglobin A1c ( HbA1c ) 5.7–6.4 % ( 39–46 mmol/mol ) . RESULTS A total of 2,423 participants ( 45 % of whom were women and 33 % nonwhite ) were r and omized to cholecalciferol or placebo . Mean ( SD ) age was 60 ( 9.9 ) years and BMI 32.1 ( 4.5 ) kg/m2 . Thirty-five percent met all three prediabetes criteria , 49 % met the FPG/HbA1c criteria only , 9.5 % met the 2hPG/FPG criteria only , and 6.3 % met the 2hPG/HbA1c criteria only . Black participants had the highest mean HbA1c and lowest FPG concentration compared with white , Asian , and other races ( P < 0.01 ) ; 2hPG concentration did not differ among racial groups . When compared with previous prediabetes cohorts , the D2d cohort had lower mean 2hPG concentration but similar HbA1c and FPG concentrations . CONCLUSIONS D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria BACKGROUND Epidemiologic and pre clinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia . To further study the chemopreventive potential of these nutrients , we conducted a r and omized , double-blind , placebo-controlled trial of supplementation with vitamin D , calcium , or both for the prevention of colorectal adenomas . METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy . We r and omly assigned 2259 participants to receive daily vitamin D3 ( 1000 IU ) , calcium as carbonate ( 1200 mg ) , both , or neither in a partial 2 × 2 factorial design . Women could elect to receive calcium plus r and om assignment to vitamin D or placebo . Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations , according to the endoscopist 's recommendation . The primary end point was adenomas diagnosed in the interval from r and omization through the anticipated surveillance colonoscopy . RESULTS Participants who were r and omly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter , relative to participants given placebo . Overall , 43 % of participants had one or more adenomas diagnosed during follow-up . The adjusted risk ratios for recurrent adenomas were 0.99 ( 95 % confidence interval [ CI ] , 0.89 to 1.09 ) with vitamin D versus no vitamin D , 0.95 ( 95 % CI , 0.85 to 1.06 ) with calcium versus no calcium , and 0.93 ( 95 % CI , 0.80 to 1.08 ) with both agents versus neither agent . The findings for advanced adenomas were similar . There were few serious adverse events . CONCLUSIONS Daily supplementation with vitamin D3 ( 1000 IU ) , calcium ( 1200 mg ) , or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00153816 . ) Background It is hypothesized that in individuals without clinical cardiovascular disease ( CVD ) , but at increased CVD risk , a 50 % to 60 % reduction in CVD risk could be achieved using fixed dose combination ( FDC ) therapy ( usually comprised of multiple blood‐pressure agents and a statin [ with or without aspirin ] ) in a single “ polypill ” . However , the impact of a polypill in preventing clinical CV events has not been evaluated in a large r and omized controlled trial . Methods TIPS‐3 is a 2x2x2 factorial r and omized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population . This study aims to determine whether the Polycap ( comprised of atenolol , ramipril , hydrochlorothiazide , and a statin )  reduces CV events in persons without a history of CVD , but who are at least at intermediate CVD risk . Additional interventions in the factorial design of the study will compare the effect of ( 1 ) aspirin versus placebo on CV events ( and cancer ) , ( 2 ) vitamin D versus placebo on the risk of fractures , and ( 3 ) the combined effect of aspirin and the Polycap on CV events . Results The study has r and omized 5713 participants across 9 countries . Mean age of the study population is 63.9 years , and 53 % are female . Mean INTERHEART risk score is 16.8 , which is consistent with a study population at intermediate CVD risk . Conclusion Results of the TIP‐3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD 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 Few year-long vitamin D supplementation trials exist that match seasonal changes . The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density ( BMD ) change in postmenopausal women in a 1-year double-blind placebo controlled trial in Scotl and . White women aged 60 to 70 years ( n = 305 ) were r and omized to one of two doses of vitamin D or placebo . All participants started simultaneously in January/February 2009 , attending visits at bimonthly intervals with 265 ( 87 % ) women attending the final visit and an additional visit 1 month after treatment cessation . BMD ( Lunar iDXA ) and 1,25-dihydroxyvitamin D[1,25(OH)2 D ] , N-terminal propeptide of type 1 collagen [ P1NP ] , C-terminal telopeptide of type I collagen [ CTX ] , and fibroblast growth factor-23 [ FGF23 ] were measured by immunoassay at the start and end of treatment . Circulating PTH , serum Ca , and total 25-hydroxyvitamin D [ 25(OH)D ] ( latter by t and em mass spectrometry ) were measured at each visit . Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group ( 0.05 % ± 1.46 % ) compared with the 400 IU vitamin D or placebo groups ( 0.57 % ± 1.33 % and 0.60 % ± 1.67 % , respectively ) ( p < 0.05 ) . Mean ( ± SD ) baseline 25(OH)D was 33.8 ± 14.6 nmol/L ; comparative 25(OH)D change for the placebo , 400 IU , and 1000 IU vitamin D groups was -4.1 ± 11.5 nmol/L , + 31.6 ± 19.8 nmol/L , and + 42.6 ± 18.9 nmol/L , respectively . Treatment did not change markers of bone metabolism , except for a small reduction in PTH and an increase in serum calcium ( latter with 1000 IU dose only ) . The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome , nor how much vitamin D is being stored 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: Conclusions and Relevance In this systematic review and meta- analysis , neither intermittent nor daily dosing with st and ard doses of vitamin D alone was associated with reduced risk of fracture , but daily supplementation with both vitamin D and calcium was a more promising strategy
background: Importance Vitamin D and calcium supplements are recommended for the prevention of fracture , but previous r and omized clinical trials ( RCTs ) have reported conflicting results , with uncertainty about optimal doses and regimens for supplementation and their overall effectiveness .
  Objective To assess the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D ( 25[OH]D ) in observational studies and the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs .