title: The Effects of Vitamin D Supplementation on Physical Function and Quality of Life in Older Patients With Heart Failure: A Randomized Controlled Trial No significant effect on bone mineral density by high doses of vitamin D3 given to overweight subjects for one year Delivery of a Vitamin D Intervention in Homebound Older Adults Using a Meals-on-Wheels Program: A Pilot Study. Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis: A Randomized Clinical Trial. Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial. Effects of Vitamin D Supplementation on Bone Mineral Density and Bone Markers in HIV-Infected Youth High‐Dose Monthly Vitamin D for Prevention of Acute Respiratory Infection in Older Long‐Term Care Residents: A Randomized Clinical Trial Cholecalciferol Additively Reduces Serum Parathyroid Hormone Levels in Severe Secondary Hyperparathyroidism Treated with Calcitriol and Cinacalcet among Hemodialysis Patients Vitamin D supplementation and bone mineral density in early postmenopausal women. 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 Can vitamin D3 supplementation prevent bone loss in persons with MS? A placebo-controlled trial 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 Effect of High-Dose Vitamin D Supplementation on Calciotropic Hormones and Bone Mineral Density in Obese Subjects with Low Levels of Circulating 25-Hydroxyvitamin D: Results from a Randomized Controlled Study Vitamin D treatment in primary hyperparathyroidism: a randomized placebo controlled trial. Effects of vitamin D supplementation and exercise training on physical performance in Chilean vitamin D deficient elderly subjects Effect of vitamin D, calcium and multiple micronutrient supplementation on vitamin D and bone status in Bangladeshi premenopausal garment factory workers with hypovitaminosis D: a double-blinded, randomised, placebo-controlled 1-year intervention. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. Effects of calcium and vitamin D supplementation on hip bone mineral density and calcium-related analytes in elderly ambulatory Australian women: a five-year randomized controlled trial. Effect of vitamin D supplementation on bone and vitamin D status among Pakistani immigrants in Denmark: a randomised double-blinded placebo-controlled intervention study. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial Vitamin D supplementation after parathyroidectomy: effect on bone mineral density-a randomized double-blind study. Biochemical parameters after cholecalciferol repletion in hemodialysis: results From the VitaDial randomized trial. Randomised controlled trial of vitamin D supplementation in sarcoidosis 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 An initial loading-dose vitamin D versus placebo after hip fracture surgery: randomized trial Vitamin D supplementation improves neuromuscular function in older people who fall. Skeletal Effects of Vitamin D Supplementation in Postmenopausal Black Women Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: a randomized controlled trial. Falls in the elderly: a prospective study of risk factors and risk profiles. The effect of high-dose vitamin D on bone mineral density and bone turnover markers in postmenopausal women with low bone mass—a randomized controlled 1-year trial Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. The Effect of Season and Vitamin D Supplementation on Bone Mineral Density in Healthy Women: A Double-Masked Crossover Study
   Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study The effects of whole-body vibration training and vitamin D supplementation on muscle strength, muscle mass, and bone density in institutionalized elderly women: a 6-month randomized, controlled trial. 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. Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. 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. A Controlled Study of Vitamin D3 to Prevent Bone Loss in Renal-Transplant Patients Receiving Low Doses of Steroids Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial Vitamin D Supplementation and Fracture Incidence in Elderly Persons Prevention of femoral and lumbar bone loss with hormone replacement therapy and vitamin D3 in early postmenopausal women: a population-based 5-year randomized 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. Vitamin D and Physical Function in Sedentary Older Men A parallel group double-blind RCT of vitamin D3 assessing physical function: is the biochemical response to treatment affected by overweight and obesity? A randomized controlled trial of vitamin D3 supplementation in African American women. The effect of high-dose vitamin D3 supplementation on bone mineral density in subjects with prediabetes Effect of isolated vitamin D supplementation on the rate of falls and postural balance in postmenopausal women fallers: a randomized, double-blind, placebo-controlled trial Skeletal and hormonal responses to vitamin D supplementation during sunlight deprivation in Antarctic expeditioners Effect of monthly high‐dose vitamin D on bone density in community‐dwelling older adults substudy of a randomized controlled trial Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). 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 Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas. 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. Effects of Vitamin D3 Supplementation on Lean Mass, Muscle Strength, and Bone Mineral Density During Weight Loss: A Double-Blind Randomized Controlled Trial. Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post-hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial. Correction of vitamin D insufficiency with combined strontium ranelate and vitamin D3 in osteoporotic patients. Randomized controlled trial of the effects of calcium with or without vitamin D on bone structure and bone-related chemistry in elderly women with vitamin D insufficiency.
abstract: 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 In meta-analyses supplementation with vitamin D appears to reduce incidence of fractures , and in cross-sectional studies there is a positive association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and bone mineral density ( BMD ) . However , the effect of supplementation with high doses of vitamin D on BMD is more uncertain and could in theory have both positive and negative effects . Methods The study was a one year , double blind placebo-controlled intervention trial performed at the University Hospital of North Norway . 421 subjects , 21 - 70 years old , were included and 312 completed the study . The subjects were r and omized to vitamin D3 40.000 IU per week ( DD group ) , vitamin D3 20.000 IU per week ( DP group ) , or placebo ( PP group ) . All subjects were given 500 mg calcium daily . Serum 25(OH)D , osteoprotegrin ( OPG ) , receptoractivator of nuclear factor-kappaB lig and ( RANKL ) , and BMD at the lumbar spine and the hip were measured before and at the end of the study . Results At baseline the mean serum 25(OH)D levels were 58 nmol/L ( all subjects ) and increased to 141 and 100 nmol/L in the DD and DP groups , respectively . After one year , no significant differences were found between the three groups regarding change in BMD , serum OPG or RANKL . Conclusions Supplementation with high doses of vitamin D for one year does not appear to have a negative effect on  BMD in healthy subjects . In order to disclose a positive effect , subjects with low BMD and /or low serum 25(OH)D levels need to be studied . Trial registration The trial was registered at Clinical Trials.gov ( NCT00243256 ) OBJECTIVES To assess the feasibility of a vitamin D intervention delivered through a Meals-on-Wheels ( MOW ) program to improve 25-hydroxyvitamin D ( 25(OH)D ) concentrations and reduce falls in homebound older adults . DESIGN Single-blind , cluster r and omized trial . SETTING MOW , Forsyth County , North Carolina . PARTICIPANTS Community-dwelling homebound adults aged 65 to 102 ( N = 68 ) . INTERVENTION MOW clients were r and omized to vitamin D3 ( 100,000 IU/month ; n = 38 ) or active placebo ( 400 IU vitamin E/month ; n = 30 ) according to MOW delivery route . MEASUREMENTS Serum 25(OH)D was assessed at baseline and 5-month follow-up ; proportions of participants in 25(OH)D categories were compared using Fisher exact test . Falls were assessed using monthly fall calendars , and rate of falls was estimated using negative binomial generalized estimating equation models . RESULTS Mean ± st and ard deviation 25(OH)D concentrations were 20.9 ± 11.5 ng/mL at baseline , with 57 % having 25(OH)D concentrations less than 20 ng/mL. Retention and adherence were high ( > 90 % ) . After the 5-month intervention , only one of 34 participants r and omized to vitamin D3 had 25(OH)D concentrations less than 20 ng/mL , compared with 18 of 25 participants r and omized to placebo ( P < .001 ) . In unadjusted analyses , the rate of falls over 5 months was not significantly different according to intervention group ( risk ratio ( RR ) = 0.48 , 95 % confidence interval ( CI ) = 0.19 - 1.19 ) , but after adjustment for sex , race , season of year , baseline 25(OH)D status , and history of falls , participants r and omized to vitamin D3 had a lower rate of falling than those r and omized to placebo ( RR = 0.42 , 95 % CI = 0.21 - 0.87 ) . CONCLUSION A vitamin D intervention delivered through MOW was feasible , result ing in improvements in 25(OH)D concentrations and a lower rate of falls in adjusted analyses . Further research is needed to vali date the reduction in falls from this type of intervention IMPORTANCE Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis , but current trial evidence is contradictory . OBJECTIVE To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels . DESIGN , SETTING , AND PARTICIPANTS A multicenter r and omized , double-blind , placebo-controlled clinical trial in Tasmania and Victoria , Australia . Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D ( 12.5 - 60 nmol/L ) were enrolled from June 2010 to December 2011 . The trial was completed in December 2013 . INTERVENTIONS Participants were r and omly assigned to receive monthly treatment with oral vitamin D3 ( 50,000 IU ; n = 209 ) or an identical placebo ( n = 204 ) for 2 years . MAIN OUTCOMES AND MEASURES Primary outcomes were change in tibial cartilage volume ( assessed using magnetic resonance imaging [ MRI ] ) and change in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) pain score ( 0 [ no pain ] to 500 [ worst pain ] ) from baseline to month 24 . Secondary outcomes were cartilage defects and bone marrow lesions ( assessed using MRI ) . RESULTS Of 413 enrolled participants ( mean age , 63.2 years ; 50 % women ) , 340 ( 82.3 % ) completed the study . The level of 25-hydroxyvitamin D increased more in the vitamin D group ( 40.6 nmol/L ) than in the placebo group ( 6.7 nmol/L ) ( P < .001 ) over 2 years . There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score . There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions . Adverse events ( ≥ 1 per patient ) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group ( P = .04 ) . [ table : see text ] . CONCLUSIONS AND RELEVANCE Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels  , vitamin D supplementation , compared with placebo , did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years . These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01176344 ; anzctr.org.au Identifier : ACTRN12610000495022 IMPORTANCE Vitamin D deficiency has been associated with poor physical performance . OBJECTIVE To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline . DESIGN , SETTING , AND PARTICIPANTS One-year , double-blind , r and omized clinical trial conducted in Zurich , Switzerl and . The screening phase was December 1 , 2009 , to May 31 , 2010 , and the last study visit was in May 2011 . The date s of our analysis were June 15 , 2012 , to October 10 , 2015 . Participants were 200 community-dwelling men and women 70 years and older with a prior fall . INTERVENTIONS Three study groups with monthly treatments , including a low-dose control group receiving 24,000 IU of vitamin D3 ( 24,000 IU group ) , a group receiving 60,000 IU of vitamin D3 ( 60,000 IU group ) , and a group receiving 24,000 IU of vitamin D3 plus 300 μg of calcifediol ( 24,000 IU plus calcifediol group ) . MAIN OUTCOMES AND MEASURES The primary end point was improving lower extremity function ( on the Short Physical Performance Battery ) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months . A secondary end point was monthly reported falls . Analyses were adjusted for age , sex , and body mass index . RESULTS The study cohort comprised 200 participants ( men and women ≥ 70 years with a prior fall ) . Their mean age was 78 years , 67.0 % ( 134 of 200 ) were female , and 58.0 % ( 116 of 200 ) were vitamin D deficient ( < 20 ng/mL ) at baseline . Intent-to-treat analyses showed that , while 60,000 IU and 24,000 IU plus calcifediol were more likely than 24,000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL ( P = .001 ) , they were not more effective in improving lower extremity function , which did not differ among the treatment groups ( P = .26 ) . However , over the 12-month follow-up , the incidence of falls differed significantly among the treatment groups , with higher incidences in the 60,000 IU group ( 66.9 % ; 95 % CI , 54.4 % to 77.5 % ) and the 24,000 IU plus calcifediol group ( 66.1 % ; 95 % CI , 53.5%-76.8 % ) group compared with the 24,000 IU group ( 47.9 % ; 95 % CI , 35.8%-60.3 % ) ( P = .048 ) . Consistent with the incidence of falls , the mean number of falls differed marginally by treatment group . The 60,000 IU group ( mean , 1.47 ) and the 24,000 IU plus calcifediol group ( mean , 1.24 ) had higher mean numbers of falls compared with the 24,000 IU group ( mean , 0.94 ) ( P = .09 ) . CONCLUSIONS AND RELEVANCE Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D , they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24,000 IU . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01017354 Background : Low bone mineral density ( BMD ) is a significant comorbidity in HIV . However , studies evaluating vitamin D supplementation on bone health in this population are limited . This study investigates changes in bone health parameters after 12 months of supplementation in HIV-infected youth with vitamin D insufficiency . Methods : This is a r and omized , active-control , double-blind trial investigating changes in bone parameters with 3 different vitamin D3 doses [ 18,000 ( st and ard/control dose ) , 60,000 ( moderate dose ) , and 120,000 IU/monthly ( high dose ) ] in HIV-infected youth 8–25 years old with baseline serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations < 30 ng/mL.  BMD and bone turnover markers were measured at baseline and 12 months . Results : One hundred two subjects enrolled . Over 12 months , serum 25(OH)D concentrations increased with all doses , but the high dose ( ie , 120,000 IU/monthly ) maintained serum 25(OH)D concentrations in an optimal range ( ≥30 or ≥20 ng/mL ) throughout the study period for more subjects ( 85 % and 93 % , respectively ) compared with either the moderate ( 54 % and 88 % , respectively ) or st and ard dose ( 63 % and 80 % , respectively ) . All dosing groups showed some improvement in BMD ; however , only the high-dose arm showed significant decreases in bone turnover markers for both procollagen type 1 aminoterminal propeptide ( −3.7 ng/mL ; P = 0.001 ) and & Bgr;-CrossLaps ( −0.13 ng/mL ; P = 0.0005 ) . Conclusions : High-dose vitamin D supplementation ( 120,000 IU/mo ) given over 12 months decreases bone turnover markers in HIV-infected youth with vitamin D insufficiency , which may represent an early , beneficial effect on bone health . High vitamin D doses are needed to maintain optimal serum 25(OH)D concentrations 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 We evaluated the improvement of intact parathyroid hormone ( iPTH ) levels and bone parameters by supplementing nutritional vitamin D ( cholecalciferol ) to combined calcimimetic ( cinacalcet ) and active vitamin D analog ( calcitriol ) among severe secondary hyperparathyroidism ( SHPT ) hemodialysis ( HD ) patients . A r and omized , controlled open-label study was undertaken in 60 HD patients with serum iPTH > 1000 pg/mL or persistently high iPTH ≥ 600 pg/mL even after > 3 months of calcitriol ( 3 μg/week ) . The study group received oral cholecalciferol ( 5000 IU/ day ) and the control group received a placebo . All patients received fixed dose cinacalcet ( 30 mg/day , orally ) and calcitriol . Calcitriol was reduced if iPTH ≤ 300 pg/mL and cinacalcet was withdrawn if serum iPTH was persistently low ( iPTH ≤ 300 pg/mL ) for 4 weeks after the reduction of calcitriol . A significantly lower iPTH level was noted from the 20th week in the study group compared to the placebo group , and the target iPTH ≤ 300 pg/mL was achieved at the 24th week in the study group . Most patients achieved serum 25-(OH)D3 ≥ 30 ng/mL in the study group . Nearly 40 % of study patients gained > 10 % improvement in femoral neck ( FN ) bone mineral density ( BMD ) . We conclude that cholecalciferol additively reduced serum iPTH levels , improved 25-(OH)D3 levels and improved FN BMD when used together with cinacalcet/calcitriol in severe SHPT HD patients BACKGROUND Increased vitamin D intake may preserve or increase bone mineral density ( BMD ) in older persons . OBJECTIVE A 2-y double-blind study was undertaken to determine whether weekly administration of 10 000 units of vitamin D(2 ) maintained or increased BMD in younger postmenopausal women more efficiently than did calcium supplements alone . DESIGN One hundred eighty-seven women who were > or= 1 y postmenopausal were r and omly assigned to take either 1000 mg Ca/d after the evening meal or 1000 mg Ca/d plus 10 000 U vitamin D(2)/wk in a double-blind , placebo-controlled format . The BMD of the proximal forearm , lumbar spine , femoral neck , Ward 's triangle , and femoral trochanter was measured at 6-mo intervals by osteodensitometry . RESULTS During the 2-y period , there was no significant difference in the change in BMD at any site between the subjects taking calcium supplements and those taking calcium plus vitamin D(2 ) . Both groups significantly ( P < 0.005 ) gained BMD in Ward 's triangle and the femoral trochanter but significantly ( P < 0.005 ) lost bone in the proximal radius . There was no significant change in the lumbar spine or femoral neck BMD . CONCLUSION In younger postmenopausal women ( age : 56 y ) whose average baseline serum 25-hydroxyvitamin D concentration was well within the normal range , the addition of 10 000 U vitamin D(2)/wk to calcium supplementation at 1000 mg/d did not confer benefits on BMD beyond those achieved with calcium supplementation alone 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 Multiple sclerosis ( MS ) is a possible cause of secondary osteoporosis . In this phase II trial we assessed whether a weekly dose of 20,000 IU vitamin D3 prevents bone loss in ambulatory persons with MS age 18–50 years . Clinical Trials.gov ID NCT00785473 . All patients managed at the University Hospital of North Norway who fulfilled the main inclusion criteria were invited to participate in this double-blinded trial . Participants were r and omised to receive 20,000 IU vitamin D3 or placebo once a week and 500 mg calcium daily for 96 weeks . The primary outcome was the effect of the intervention on percentage change in bone mineral density ( BMD ) at the hip , the spine , and the ultradistal radius over the study period . Of 71 participants r and omised , 68 completed . Mean serum 25-hydroxyvitamin D [ 25(OH)D ] levels in the intervention group increased from 55 nmol/L at baseline to 123 nmol/L at week 96 . After 96 weeks , percentage change in BMD did not differ between groups at any site . BMD decreased at the hip , by 1.4 % in the placebo group ( 95 % CI −2.3 to −0.4 , SD 2.7 , p = 0.006 ) and by 0.7 % in the treatment group ( −1.6 to 0.2 , 2.7 , p = 0.118 ) , difference 0.7 % ( −1.9 to 0.7 , p = 0.332 ) . Findings were not altered by adjustment for sex or serum 25(OH)D. Supplementation with 20,000 IU vitamin D3 a week did not prevent bone loss in this small population . Larger studies are warranted to assess the effect of vitamin D on bone health in persons with MS 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 Low levels of 25-hydroxyvitamin D ( 25OHD ) are associated with increased bone turnover and risk of fractures . Plasma 25OHD is inversely related to body mass index , and vitamin D deficiency is common in obesity . We aim ed to determine whether vitamin D supplementation affects bone turnover and bone mineral density ( BMD ) in obese subjects . Fifty-two healthy obese men and women aged 18–50 years with plasma 25OHD levels below 50 nmol/L were r and omized to 7,000 IU of cholecalciferol daily or placebo for 26 weeks . We measured plasma levels of 25OHD , parathyroid hormone ( PTH ) , and markers of bone turnover , as well as BMD at the hip , spine , forearm , and whole body . Compared with placebo , treatment with cholecalciferol  increased mean plasma 25OHD from 35 to 110 nmol/L ( p < 0.00001 ) and significantly decreased PTH ( p < 0.05 ) . BMD increased significantly at the forearm by 1.6 ± 0.7 % ( p = 0.03 ) . The bone resorption marker C-terminal telopetide of type 1 collagen ( CTX ) decreased borderline significantly in the cholecalciferol group compared with the placebo group ( p = 0.07 ) . Changes in plasma 25OHD correlated inversely with changes in plasma levels of bone-specific alkaline phosphatase ( r = −0.38 , p = 0.01 ) and CTX ( r = −0.33 , p = 0.03 ) . Changes in CTX correlated inversely with changes in spine BMD ( r = −0.45 , p = 0.04 ) . Increasing circulating 25OHD levels by cholecalciferol treatment is of importance to bone health in young obese subjects as increased levels of 25OHD are associated with a decrease in both PTH and bone turnover and with an increase in BMD at the forearm CONTEXT Low 25-hydroxyvitamin D levels are common in patients with primary hyperparathyroidism ( PHPT ) and associated with higher PTH levels and hungry bone syndrome after parathyroidectomy ( PTX ) . However , concerns have been raised about the safety of vitamin D supplementation in PHPT . OBJECTIVE We aim ed to assess safety and effects on calcium homeostasis and bone metabolism of supplementation with high doses of vitamin D in PHPT patients . DESIGN , SETTING This was an investigator-initiated double-blind , r and omized , placebo-controlled , parallel-group trial from a single center . PATIENTS Forty-six PHPT patients were recruited , with a mean age of 58 ( range 29 - 77 ) years , and 35 ( 76 % ) were women . INTERVENTIONS Intervention included daily supplementation with 70 μg ( 2800 IU ) cholecalciferol or identical placebo for 52 weeks . Treatment was administered 26 weeks before PTX and continued for 26 weeks after PTX . MAIN OUTCOME MEASURES PTH , calcium homeostasis , and bone metabolism were evaluated . RESULTS Preoperatively , 25-hydroxyvitamin D increased from 50 to 94 nmol/L in the treatment group and decreased from 57 to 52 nmol/L in the placebo group ( P < .001 ) . Compared with placebo , vitamin D  decreased PTH significantly by 17 % before PTX ( P = .01 ) , increased lumbar spine bone mineral density by 2.5 % ( P = .01 ) , and decreased C-terminal β-CrossLaps by 22 % ( P < .005 ) . The trabecular bone score did not change in response to treatment , but improved after PTX . Postoperatively , PTH remained lower in the cholecalciferol group compared with the placebo group ( P = .04 ) . Plasma creatinine and plasma and urinary calcium did not differ between groups . CONCLUSIONS Daily supplementation with a high vitamin D dose safely improves vitamin D status and decreases PTH in PHPT patients . The vitamin D treatment is accompanied by reduced bone resorption and improved bone mineral density before operation The aim was to assess the effects of resistance training and vitamin D supplementation on physical performance of healthy elderly subjects . Ninety-six subjects , aged 70 years or more with 25 OH vitamin D levels of 16 ng/ml or less , were r and omized to a  resistance training or control group . Trained and control groups were further r and omized to receive in a double blind fashion , vitamin D 400 IU plus 800 mg of calcium per day or calcium alone . Subjects were followed for nine months . Serum 25 OH vitamin D increased from 12.4+/-2.2 to 25.8+/-6.5 ng/ml among subjects supplemented with vitamin D. Trained subjects had significant improvements in quadriceps muscle strength , the short physical performance test and timed up and go . The latter improved more in trained subjects supplemented with vitamin D. At the end of the follow up , gait speed was higher among subjects supplemented with vitamin ( whether trained or not ) than in non-supplemented subjects ( 838+/-147 and 768+/-127 m/12 min , respectively , p=0.02 ) . Romberg ratio was lower among supplemented controls than non-supplemented trained subjects ( 128+/-40 % and 144+/-37 % , respectively , p=0.05 ) . In conclusion , vitamin D supplementation improved gait speed and body sway , and training improved muscle strength Due to little outdoor activity and low dietary intake of vitamin D ( VD ) , Bangladeshi low-income women are at risk for osteoporosis at an early age . The present study assessed the effect of VD , Ca and multiple micronutrient supplementation on VD and bone status in Bangladeshi young female garment factory workers . This placebo-controlled 1-year intervention r and omly assigned 200 apparently healthy subjects ( aged 16 - 36 years ) to four groups : VD group , daily 10 microg VD ; VD and Ca ( VD-Ca ) group , daily 10 microg VD+600 mg Ca ; multiple micronutrient and Ca ( MMN-Ca ) group , 10 microg VD and other micronutrients+600 mg Ca ; a placebo group .  Serum 25-hydroxyvitamin D ( S-25OHD ) , intact parathyroid hormone ( S-iPTH ) , Ca , phosphate and alkaline phosphatase were measured . Bone mineral density and bone mineral content were measured by dual-energy X-ray absorptiometry . All measurements were made at baseline and at 12 months . Significantly ( P < 0.001 ) higher S-25OHD concentrations were observed in the supplemented groups than in the placebo group after the intervention . Supplementation had an effect ( P < 0.001 ) on S-iPTH in the VD-Ca and MMN-Ca groups compared with the placebo group . Bone mineral augmentation increased at the femur in the supplemented groups . Supplementation with VD-Ca should be recommended as a strategic option to reduce the risk of osteomalacia and osteoporosis in these subjects . MMN-Ca may have analogous positive health implication s with additional non-skeletal benefits OBJECTIVES To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents . DESIGN Secondary data analysis of a previously conducted r and omized clinical trial . SETTING Seven hundred twenty-five-bed long-term care facility . PARTICIPANTS One hundred twenty-four nursing home residents ( average age 89 ) . INTERVENTION Participants were r and omly assigned to receive one of four vitamin D supplement doses ( 200 IU , 400 IU , 600 IU , or 800 IU ) or placebo daily for 5 months . MEASUREMENTS Number of fallers and number of falls assessed using facility incident tracking data base . RESULTS Over the 5-month study period , the proportion of participants with falls was 44 % in the placebo group ( 11/25 ) , 58 % ( 15/26 ) in the 200 IU group , 60 % ( 15/25 ) in the 400 IU group , 60 % ( 15/25 ) in the 600 IU group , and 20 % ( 5/23 ) in the 800 IU group . Participants in the 800 IU group had a 72 % lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months ( rate ratio=0.28 ; 95 % confidence interval=0.11 - 0.75 ) . No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups . CONCLUSION Nursing home residents in the highest vitamin D group ( 800 IU ) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses . Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group CONTEXT Effects of long-term calcium , with or without vitamin D , on  hip bone mineral density ( BMD ) and bone turnover in sunny climates have not been reported . OBJECTIVE The aim was to evaluate the effect of vitamin D added to calcium supplementation on hip dual-energy x-ray absorptiometry BMD and calcium-related analytes . DESIGN , SETTING , AND PARTICIPANTS The study was a 5-yr r and omized , controlled , double-blind trial of 120 community-dwelling women aged 70 - 80 yr . INTERVENTIONS The interventions were 1200 mg/d calcium with placebo vitamin D ( Ca group ) or with 1000 IU/d vitamin D2 ( CaD group ) , or double placebo ( control ) . MAIN OUTCOME MEASURES Hip BMD , plasma 25-hydroxyvitamin D , biomarkers of bone turnover , PTH , and intestinal calcium absorption were measured . RESULTS Hip BMD was preserved in CaD ( -0.17 % ) and Ca ( 0.19 % ) groups but not controls ( -1.27 % ) at yr 1 and maintained in the CaD group only at yr 3 and 5 . The beneficial effects were mainly in those with baseline 25-hydroxyvitamin D levels below the median ( 68 nmol/liter ) . At yr 1 , compared with controls , the Ca and CaD groups had 6.8 and 11.3 % lower plasma alkaline phosphatase , respectively ( P < or=0.02 ) , and 28.7 and 34.5 % lower urinary deoxypyridinoline to creatinine ratio , respectively ( P < or=0.05 ) . At 5 yr , this suppression was maintained only in the CaD group . CaD reduced PTH at 3 and 5 yr cf . controls ( 27.8 and 31.3 % , P < or=0.005 ) in those with baseline PTH levels above the median ( 3.6 pmol/liter ) . Therapy did not affect intestinal calcium absorption at high carrier loads . CONCLUSIONS Addition of vitamin D to calcium has long-term beneficial effects on bone density in elderly women living in a sunny climate , probably mediated by a long-term reduction in bone turnover rate Severe vitamin D deficiency is common among Muslim immigrants . The dose necessary to correct the deficiency and its consequence for bone health are not known for immigrants . The aim was to assess the effect of relatively low dosages of supplemental vitamin D on vitamin D and bone status in Pakistani immigrants . This 1-year-long r and omised double-blinded placebo-controlled intervention with vitamin D3 ( 10 and 20 microg/d ) included girls ( 10.1 - 14.7 years ) , women ( 18.1 - 52.7 years ) and men ( 17.9 - 63.5 years ) of Pakistani origin living in Denmark . The main endpoints were serum 25-hydroxyvitamin D ( S-25OHD ) , parathyroid hormone , bone turnover markers and bone mass . The study showed that supplementation with 10 and 20 microg vitamin D3 per d increased S-25OHD concentrations similarly in vitamin D-deficient Pakistani women ( 4-fold ) , and that 10 microg increased S-25OHD concentrations 2-fold and 20 microg 3-fold in Pakistani men . S-25OHD concentrations increased at 6 months and were stable thereafter . Baseline S-25OHD concentrations tended to be lower in girls and women than in men ; females achieved about 46 nmol/l and men 55 nmol/l after supplementation . Serum intact parathyroid hormone concentrations decreased at 6 months , but there was no significant effect of the intervention on bone turnover markers and dual-energy X-ray absorptiometry measurements of the whole body and lumbar spine 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 Summary The effects of higher than recommended vitamin D doses on bone mineral density ( BMD ) and quality are not known . In this study , higher intakes , in postmenopausal women undergoing weight control over 1 year , had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry . Introduction Studies examining how bone responds to a st and ard dose of vitamin D supplementation have been inconsistent . In addition , the effects of higher doses on BMD and quality are not known . Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance . Methods This 1-year-long , r and omized , double-blind controlled study addresses whether vitamin D supplementation , in healthy overweight/obese older women , affects BMD and bone structural parameters . In addition , bone turnover and serum total , free , and bioavailable 25-hydroxyvitamin D ( 25OHD ) responses to one of three daily levels of vitamin D3 ( 600 , 2000 , 4000 IU ) with 1.2 Ca g/day during weight control were examined . Results Fifty-eight women ( age , 58 ± 6 years ; body mass index , 30.2 ± 3.8 kg/m2 , serum 25OHD , 27.3 ± 4.4 ng/mL ) were r and omized to treatment . After 1 year , serum 25OHD concentrations increased to 26.5 ± 4.4 , 35.9 ± 4.5 , and 41.5 ± 6.9 ng/mL , in groups 600 , 2000 , and 4000 IU , respectively , and differed between groups ( p < 0.01 ) . Weight change was similar between groups ( −3.0 ± 4.1 % ) . Cortical ( Ct ) thickness of the tibia changed by −1.5 ± 5.1 % , + 0.6 ± 3.2 % , and + 2.0 ± 4.5 % in groups 600 , 2000 , and 4000 IU , respectively , and each group was significantly different from each other ( p < 0.05 ) . Conclusion The decline in Ct thickness was prevented with higher vitamin D3 supplementation , but there were no other significant changes due to treatment over 1 year . Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies Patients with primary hyperparathyroidism ( PHPT ) have higher bone turnover , lower bone mineral density ( BMD ) , and an increased risk of fractures . They also have a high incidence of low vitamin D levels ( 25-OH-vitamin D < 50 nmol/L ) that could worsen the negative effect on the bone . In this double-blinded clinical trial , 150 patients with PHPT were r and omized , after successful parathyroidectomy ( PTX ) , to 1-year daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg ( D+ ) or calcium carbonate alone ( D- ) . BMD was measured in the lumbar spine , femoral neck , total hip , distal and 33 % radius using dual-energy X-ray absorptiometry ( DXA ) before surgery and after 1 year of study medication . Median age was 60 ( range 30 - 80 ) years and there were 119 ( 79 % ) women and 31 ( 21 % ) men ; 76 % had 25-OH-D < 50 nmol/L before PTX and 50 % had persistent elevated parathyroid hormone ( PTH ) 6 weeks after PTX . A similar increase in BMD in the lumbar spine , femoral neck , and total hip was observed in both groups ( D+ : 3.6 % , 3.2 % , and 2.7 % , p<0.001 , respectively ; and D- : 3.0 % , 2.3 % , and 2.1 % , respectively , p<0.001 ) . Patients with vitamin D supplementation also increased their BMD in distal radius ( median 2.0 % ; interquartile range , -1.7 % to 5.4 % ; p=0.013 ) . The changes in BMD , especially in the hips , were correlated to the baseline concentrations of PTH , ionized calcium , and bone markers ( p<0.001 ) . A benefit from vitamin D substitution was observed among patients with a persistent postoperative PTH elevation , who also improved their BMD at 33 % radius and radius ultradistal ( p<0.05 ) . In conclusion , except for a minor improvement of radius BMD , our data show no beneficial effect on BMD or bone turnover markers of vitamin D supplementation after PTX . Preoperative PTH seems to have the strongest association with improvement in BMD 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 Objectives The role vitamin D intake/production plays in sarcoidosis-associated hypercalcaemia is uncertain . However , authoritative review s have recommended avoiding sunlight exposure and vitamin D supplements , which might lead to adverse skeletal outcomes from vitamin D insufficiency . We investigated the effects of vitamin D supplementation on surrogate measures of skeletal health in patients with sarcoidosis and vitamin D insufficiency . Design R and omised , placebo-controlled trial . Setting Clinical research centre . Participants 27 normocalcaemic patients with sarcoidosis and 25-hydroxyvitamin D ( 25OHD ) < 50 nmol/L. Intervention 50 000 IU weekly cholecalciferol for 4 weeks , then 50 000 IU monthly for 11 months or placebo . Primary and secondary outcome measures The primary endpoint was the change in serum calcium over 12 months , and secondary endpoints included measurements of calcitropic hormones , bone turnover markers and bone mineral density ( BMD ) . Results The mean age of participants was 57 years and 70 % were women . The mean ( SD ) screening 25OHD was 35 ( 12 ) and 38 ( 9 ) nmol/L in the treatment and control groups , respectively . Vitamin D supplementation increased 25OHD to 94 nmol/L after 4 weeks , 84 nmol/L at 6 months and 78 nmol/L at 12 months , while levels remained stable in the control group . 1,25-Dihydroxy vitamin D levels were significantly different between the groups at 4 weeks , but not at 6 or 12 months . There were no between-groups differences in albumin-adjusted serum calcium , 24 h urine calcium , markers of bone turnover , parathyroid hormone or BMD over the trial . One participant developed significant hypercalcaemia after 6 weeks ( total cholecalciferol dose 250 000 IU ) . Conclusions In patients with sarcoidosis and 25OHD < 50 nmol/L  , vitamin D supplements did not alter average serum calcium or urine calcium , but had no benefit on surrogate markers of skeletal health and caused one case of significant hypercalcaemia . Trial registration This trial is registered at the Australian New Zeal and Clinical Trials Registry ( http://www.anzctr.org.au ) . The registration number is ACTRN12607000364471 , date of registration 5/7/2007 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 # 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 ) BACKGROUND vitamin D supplementation reduces the incidence of fractures in older adults . This may be partly mediated by effects of vitamin D on neuromuscular function . OBJECTIVE to determine the effects of vitamin D supplementation on aspects of neuromuscular function known to be risk factors for falls and fractures . DESIGN r and omised , double-blind , placebo-controlled study . SETTING falls clinic taking referrals from general practitioners and accident and emergency department . SUBJECTS 139 ambulatory subjects ( > /=65 years ) with a history of falls and 25-hydroxyvitamin D ( 25OHD ) < /=12 microg/l . INTERVENTION patients were r and omised to receive a single intramuscular injection of 600,000 i.u . ergocalciferol or placebo . OUTCOME MEASURES assessment s including biochemistry , postural sway , choice reaction time ( CRT ) , aggregate functional performance time ( AFPT ) , and quadriceps strength were carried out at baseline and 6 months post-intervention . RESULTS baseline characteristics were comparable between both groups . 25OHD in the treatment group increased significantly at 6 months . AFPT deteriorated in the control group and improved in the intervention group , representing a significant difference between groups ( + 6.6 s versus -2.0 s , t = 2.80 , P < 0.05 ) . Similar changes were observed for CRT ( -0.06 s versus + 0.41 s , t = -2.52 , P < 0.01 ) and postural sway ( + 0.0025 versus -0.0138 , t = 2.35 , P < 0.02 ) . There was no significant difference in muscle strength change between groups ( -10 N versus -2 N , t = -1.26 , ns ) . A significant correlation between change in AFPT and change in 25OHD levels was observed ( r = 0.19 , P = 0.03 ) . There was no significant difference in the number of falls ( 0.39 versus 0.24 , t = 1.08 , P = 0.28 ) or fallers ( 14 versus 11 , P = 0.52 ) between two groups . CONCLUSIONS vitamin D supplementation , in fallers with vitamin D insufficiency , has a significant beneficial effect on functional performance , reaction time and balance , but not muscle strength . This suggests that vitamin D supplementation improves neuromuscular or neuroprotective function , which may in part explain the mechanism whereby vitamin D reduces falls and fractures Black women have lower serum 25-hydroxyvitamin D ( 25[OH]D ) levels and higher parathyroid hormone ( PTH ) levels than white peers but lower bone turnover , suggesting skeletal resistance to PTH . Our objective was to determine if vitamin D supplementation ( 1,000 IU/day ) would prevent bone loss and whether vitamin D receptor ( VDR ) polymorphisms modify the response . We performed a 2-year r and omized , controlled , double-blind study of 1,000 IU vitamin D3 vs. placebo in postmenopausal black women with serum 25(OH)D levels < 20 ng/mL ( n = 103 ) .  Measurements of 25(OH)D , PTH , and bone turnover were evaluated at baseline and 3 , 6 , 12 , 18 , and 24 months . DNA was extracted from peripheral blood leukocytes , and genotyping was conducted using st and ard techniques . Spine and hip bone mineral density ( BMD ) was measured at baseline and every 6 months . Serum 25(OH)D increased 11 ng/mL with vitamin D supplementation ( p < 0.001 ) , with no change in the placebo group . Vitamin D supplementation produced a significant decline in PTH at 3 months only , with no differences in bone turnover between placebo and vitamin D at any time point . Two-year changes in BMD were not significantly different between placebo- and vitamin D-treated black women at any skeletal site . Despite similar elevations in 25(OH)D , femoral neck BMD was only responsive to vitamin D supplementation in FF subjects ( n = 47 ) , not Ff/ff subjects ( n = 31 ) . Vitamin D supplementation does not appear to influence  bone loss in black women . However , in the FF polymorphism of the VDR gene group , vitamin D supplementation may retard the higher rate of bone loss A double-blind placebo-controlled r and omized phase II trial was performed to determine whether High Dose Vitamin D2 supplementation ( HDD ) in women receiving adjuvant anastrozole improves aromatase inhibitor-induced musculoskeletal symptoms ( AIMS S ) and bone loss .  Patients with early breast cancer and AIMS S were stratified according to their baseline 25-hydroxy vitamin D ( 25OHD ) level . Stratum A ( 20–29 ng/ml ) received either HDD 50,000 IU capsules weekly for 8 weeks then monthly for 4 months or placebo . Stratum B ( 10–19 ng/ml ) received either HDD for 16 weeks and then monthly for 2 months , or placebo . AIMS S was assessed by the Brief Pain Inventory-Short Form ( BPI-SF ) , the Fibromyalgia Impact Question naire ( FIQ ) , and the Health Assessment Question naire-Disability Index ( HAQ-DI ) at baseline , 2 , 4 , and 6 months . Bone Mineral Density ( BMD ) was measured at baseline and at 6 months . The primary endpoint of the study was the change-from-baseline musculoskeletal pain . The secondary endpoint was the percent change in BMD at 6 months . Sixty women were enrolled . Baseline characteristics were comparable between the groups . At 2 months , FIQ pain ( P = 0.0045 ) , BPI worst-pain ( P = 0.04 ) , BPI average-pain ( P = 0.0067 ) , BPI pain-severity ( P = 0.04 ) , and BPI interference ( P = 0.034 ) scores were better in the HDD than placebo group . The positive effect of HDD on AIMS S was stronger across all time points in Stratum B than Stratum A ( FIQ pain , P = 0.04 ; BPI average , P = 0.03 ; BPI severity , P = 0.03 ; BPI interference , P = 0.04 ) . BMD at the femoral neck decreased in the placebo and did not change in the HDD group ( P = 0.06 ) . Weekly HDD improves AIMS S and may have a positive effect on bone health . Vitamin D supplementation strategies for breast cancer patients on AI should be further investigated 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 In this prospect i ve study , the authors determined intrinsic risk factors for falls and recurrent falls and constructed a risk profile that indicated the relative contribution of each risk factor and also estimated the probabilities of falls and recurrent falls . In 1992 , over a 28-week period , falls were recorded among 354 elderly subjects aged 70 years or over who were living in homes or apartments for the elderly in Amsterdam and the vicinity . During the study period , 251 falls were reported by 126 subjects ( 36 % ) , and recurrent falls ( > or = 2 falls ) were reported by 57 subjects ( 16 % ) . Associations of falls and recurrent falls with potential risk factors were identified in logistic regression models . Mobility impairment regarding one or more of the tested items ( i.e. , impairment of balance , leg-extension strength , and gait ) was associated with falls ( adjusted odds ratio ( OR ) = 2.6 ) and was strongly associated with recurrent falls ( OR = 5.0 ) . Dizziness upon st and ing was associated with falls ( OR = 2.1 ) and recurrent falls ( OR = 2.1 ) . However , several risk factors were associated with recurrent falls only : history of stroke ( OR = 3.4 ) , poor mental state ( OR = 2.4 ) , and postural hypotension ( OR = 2.0 ) . The authors constructed a risk profile for recurrent falls that included the five risk factors mentioned above . Inclusion of all risk factors in the profile implied an 84 % probability of recurrent falls over a period of 28 weeks , compared with 3 % when no risk factor was present . The probability of recurrent falls ranged only from 11 % to 29 % when predicted by number of falls occurring in the previous year . Physical activity , use of high-risk medication , and the use of vitamin D3 , which was r and omly allocated to the participants , were not strongly related to either falls or recurrent falls . In conclusion , a large range of probabilities of falls , especially of recurrent falls , was estimated by the risk profiles , in which mobility impairment was the major risk factor . Recurrent fallers may therefore be especially amenable to prevention based on mobility improvement Summary Vitamin D is widely used in osteoporosis treatment , although the optimal dose is not known . This 1-year clinical study among 297 women aged 50–80 years old showed that a vitamin D3 dose of 6,500 IU/day was not better than the st and ard dose of 800 IU/day in improving bone mineral density ( BMD ) in the hip and spine . Introduction The purpose of this study was to determine whether a high dose of vitamin D3 was better than the st and ard dose in improving BMD and reducing bone turnover in postmenopausal women with reduced bone mass . Methods The study was a 1-year r and omized double-blind controlled trial comparing high-dose vitamin D3 with the st and ard dose .  Postmenopausal women ( n = 297 ) with a BMD T-score ≤ −2.0 in either lumbar spine ( L2–4 ) or total hip were included and r and omized to 6,500 IU vitamin D3/day ( 20,000 IU twice per week + 800 IU/day ) or 800 IU vitamin D3/day ( placebo twice per week + 800 IU/day ) . Both groups were given 1,000 mg elemental calcium/day . The primary endpoint was a change in BMD in total hip and lumbar spine ( L2–4 ) . Results After 1 year , serum 25-hydroxyvitamin D ( 25(OH)D ) increased [ mean ( SD ) ] from 71 ( 23 ) to 185 ( 34 ) nmol/l and from 71 ( 22 ) to 89 ( 17 ) nmol/l in the high- and st and ard-dose vitamin D groups , respectively . BMD at all measurement sites was unchanged or slightly improved with no significant differences between the groups . Although bone turnover was reduced in both groups , the more pronounced reduction in serum levels of the bone formation marker P1NP in the st and ard-dose group may indicate that this treatment was more efficient . Adverse events did not differ between the groups . Conclusions One year treatment with 6,500 IU vitamin D3/day was not better than 800 IU/day regarding BMD in vitamin D-replete postmenopausal women with reduced bone mass and was less efficient in reducing bone turnover 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 The purpose of the study was to determine the effect of vitamin D supplementation on bone turnover and bone loss in elderly women . Three hundred forty-eight women , ages 70 yr and older , were r and omized to receive 400 IU vitamin D3 per day ( n = 177 ) or placebo ( n = 171 ) , double-blind , for a period of 2 yr . Main outcome measures were bone mineral density of both hips ( femoral neck and trochanter ) and the distal radius , as well as biochemical markers of bone turnover . The effect of vitamin D supplementation was expressed as the difference in mean ( percentage ) change between the placebo group and the vitamin D group . The measurements were repeated in 283 women after 1 yr and in 248 women after 2 yr . Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D ( 250HD ) ( + 35 nmol/L ) and 1,25-dehydroxyvitamin D [ 1,25-(OH)2D ] ( + 7.0 pmol/L ) levels and urinary calcium/creatinine ratios ( + 0.5 % ) and significantly decreased PTH(1 - 84 ) secretion ( -0.74 pmol/L ) after 1 yr . No effect was found for the parameters of bone turnover . The effect on the bone mineral density of the left femoral neck was + 1.8 % in the first yr , + 0.2 % in the second yr , and + 1.9 % during the whole period ( 95 % confidence interval 0.4 , 3.4 % ) . At the right femoral neck the effects were + 1.5 % , + 1.1 % , and + 2.6 % ( confidence interval 1.1 , 4.0 % ) , respectively . No effect was found at the femoral trochanter and the distal radius . Supplementation with 400 IU vitamin D3 daily in elderly women slightly decreases PTH secretion and increases bone mineral density at the femoral neck Abstract : Vitamin D status is known to be an important determinant of bone mineral density ( BMD ) . There is a significant seasonal variation in serum vitamin D , and some studies have reported an associated seasonal variation in BMD . The present study was devised to investigate whether a seasonal variation in BMD could be detected in healthy normal subjects , along with associated variations in serum parathyroid hormone ( PTH ) , intestinal calcium absorption and biochemical markers of bone turnover . A second aim was to investigate whether , if such variations were identified , they could be suppressed by vitamin D supplementation . The subjects were 70 healthy female volunteers ( mean age 47.2 years , range 24–70 years ) recruited into a double-masked crossover study and followed over 2 years . During the first year 35 subjects received a daily oral supplement containing 800 IU ( 20 mg ) cholecalciferol ( group 1 ) and 35 subjects received a placebo preparation ( group 2 ) . During the second year the treatment each group received was reversed . Lumbar spine ( L1–L4 ) , left proximal femur and total body BMD were measured by DXA at 3-month intervals . Serum 25-hydroxyvitamin D ( 25-OHD ) , serum PTH , bone markers ( bone-specific ALP ( BSAP ) and urinary crosslinks ( DYPD/creatinine ) ) and calcium absorption were also measured at each visit . Cholecalciferol treatment increased serum 25-OHD by 25.4 nmol/l ( p < 0.001 ) , while a reciprocal decrease in serum PTH of 6.6 ng/l ( p = 0.011 ) was seen in subjects in the lowest quartile of baseline serum 25-OHD . The treatment had no significant effect on spine , femur or total body BMD , calcium absorption or bone markers . When Fourier analysis was used to analyze the data for seasonal effect ( defined as twice the amplitude of the 1-year period variation ) a highly significant effect for 25-OHD of 18 nmol/l ( p < 0.001 ) was found . However , no effect was found for BMD , PTH , calcium absorption or bone markers . The analysis set a 95 % confidence limit to the seasonal effect of less than 0.6 % for spine , total hip and total body BMD . It was concluded that in the population of healthy women studied there was no evidence of seasonal variation in spine , femur or total body BMD , serum PTH , calcium absorption or bone markers .  Vitamin D supplementation was found to have no effect on BMD Summary In this post hoc analysis of the VITdAL-ICU study , an RCT in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml  , vitamin D3 did not have a significant effect on β-Crosslaps and osteocalcin . Introduction Observational studies have shown accelerated bone loss in ICU survivors . A reversible contributor is vitamin D deficiency . In a post hoc analysis of the VITdAL-ICU study , we evaluated the effect of high-dose vitamin D3 on the bone turnover markers ( BTM ) β-Crosslaps ( CTX ) and osteocalcin ( OC ) . Methods The VITdAL-ICU study was a r and omized , double-blind , placebo-controlled trial in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml who received placebo or high-dose vitamin D3 ( a loading dose of 540,000 IU and starting 1 month after the loading dose five monthly maintenance doses of 90,000 IU ) . In this analysis on 289 survivors ( 209 telephone , 80 personal follow-up visits )  , BTM were analyzed on days 0 , 3 , 7 , 28 , and 180 ; self-reported falls and fractures were assessed . Bone mineral density ( BMD ) was measured after 6 months . Results At baseline , CTX was elevated ; OC was low in both groups — after 6 months , both had returned to normal . There were no differences between groups concerning BTM , BMD , falls , or fractures . In linear mixed effects models , CTX and OC showed a significant change over time ( p < 0.001 , respectively ) , but there was no difference between the vitamin D and placebo group ( p = 0.688 and p = 0.972 , respectively ) . Conclusions Vitamin D supplementation did not have a significant effect on BTM . Further studies should assess the effectiveness of vitamin D  on musculoskeletal outcomes in ICU survivors Sarcopenia and osteoporosis represent a growing public health problem . We studied the potential benefit of whole-body vibration ( WBV ) training given a conventional or a high dose of daily vitamin D supplementation in improving strength , muscle mass , and bone density in postmenopausal women . In a 2 × 2 factorial- design trial , 113 institutionalized elderly females aged over 70 years ( mean age 79.6 years ) were r and omly assigned either to a WBV or a no-training group , receiving either a conventional dose ( 880 IU/day ) or a high dose ( 1600 IU/day ) of vitamin D(3 ) . The primary aim was to determine the effects of 6 months of WBV and /or vitamin D supplementation on isometric and dynamic strength , leg muscle mass , and hip bone mineral density ( BMD ) . Additionally , the increase in 25-hydroxyvitamin D [ 25(OH)D ] levels between conventional and high-dose supplementation was compared . After 6 months of treatment , dynamic muscle strength , hip BMD , and vitamin D serum levels improved significantly in all groups , whereas isometric strength and muscle mass did not change . When compared with no training , the WBV program did not result in additional improvements . When compared with 880 IU , a high dose of 1600 IU of vitamin D did result in higher serum vitamin D levels but did not result in additional improvements . In institutionalized women older than 70 years , the WBV training protocol tested is not more efficient in enhancing muscle mass , strength , and hip BMD compared with vitamin D supplementation . A higher dose of 1600 IU of vitamin D does not provide additional musculoskeletal benefit in this population compared with conventional doses 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 OBJECTIVES To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss  and whether rates of change in hard- and soft-tissue mass vary during the year . DESIGN Double-blind , placebo-controlled , 1-year trial in 249 women in which equal numbers of women were r and omized to either placebo or 400 IU of vitamin D daily . All women received 377 mg/d of supplemental calcium largely as calcium citrate malate . PATIENTS Healthy , ambulatory postmenopausal women with usual intakes of vitamin D of 100 IU/d . MEASUREMENTS Duplicate spine and whole-body scans were done by dual energy x-ray absorptiometry at 6-month intervals that were timed to periods when 25-hydroxyvitamin D levels were highest and lowest . Period 1 was June-July to December-January and period 2 was December-January to the next June-July . Serum parathyroid hormone and plasma 25-hydroxyvitamin D levels were measured during periods 1 and 2 . MAIN RESULTS In the placebo group , spinal bone mineral density increased in period 1 , decreased in period 2 , and sustained no net change . Women treated with vitamin D had a similar spinal increase in period 1 ( 1.46 % compared with 1.40 % in placebo ) , less loss in period 2 ( -0.54 % compared with -1.22 % , CI for the difference , 0.05 % to 1.31 % , P = 0.032 ) and a significant overall benefit ( 0.85 % compared with 0.15 % , CI for the difference , 0.03 % to 1.37 % , P = 0.04 ) . In period 2 , 25-hydroxyvitamin D levels were lower and parathyroid hormone levels were higher in the placebo than in the vitamin D group . Whole-body lean and fat tissue and bone mineral density varied during the year but did not change overall . CONCLUSIONS At latitude 42 degrees , healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily . A long-term benefit of preventing vitamin D insufficiency in the winter seems likely although it remains to be shown . Observed changes in bone as well as in fat and lean tissue appear to be related to season 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 Background . New and potent immunosuppressive regimens allow for reduced doses of corticosteroids after renal transplantation . The aims of our study were to investigate whether the use of low-dose corticosteroids is associated with a reduction in posttransplant bone loss and to assess the ability of cholecalciferol supplementation to further decrease bone loss in this setting . Methods . Ninety patients admitted for renal transplantation and scheduled to be treated per protocol with low doses of prednisolone  were r and omized to receive either 400 mg daily oral calcium ( Ca group , n=44 ) or the same dose of calcium in association with a monthly dose of 25,000 IU of vitamin D3 ( CaVitD group , n=46 ) . Bone mineral density ( BMD ) was measured by dual energy absorptiometry at baseline and at 1 year . Results . The overall population experienced a moderate but significant −2.3±0.9 % loss of lumbar spine BMD ( P<0.01 ) but no bone loss at the femoral neck and shaft during the first posttransplant year . Bone loss tended to be slightly higher in the CaVitD group , but the difference did not reach statistical significance . Patients in the CaVitD group had significantly higher 25(OH ) but not 1,25(OH)2 vitamin D levels . We observed a highly significant negative correlation between 25(OH ) vitamin D and intact parathyroid hormone ( iPTH ) serum levels . Conclusions . Kidney-transplant recipients receiving modern immunosuppressive regimens with low doses of corticosteroids experience only minimal loss of BMD during the first posttransplant year . Cholecalciferol supplementation did not prevent posttransplant bone loss but contributed to the normalization of iPTH levels after renal transplantation 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 Vitamin D deficiency is common in elderly persons , especially those with hip fracture [ 1 , 2 ] . It is caused by low exposure to sunshine , decreased synthesis of vitamin D3 in the aging skin , and a diet low in vitamin D [ 3 , 4 ] . The mean vitamin D intake in elderly persons in the Netherl and s is about 100 IU/d , half that of elderly persons in the United States [ 5 ] . Most of this vitamin D comes from margarine , which is the only vitamin D-supplemented food in the Netherl and s ( 3 IU/g ) . In vitamin D deficiency , the low serum concentration of 25-hydroxyvitamin D [ 25(OH)D ] leads to a low 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] concentration and then to a higher serum parathyroid hormone concentration , especially in the winter [ 6 - 10 ] . Histologically , the increased parathyroid activity is associated with high bone turnover , leading to cortical bone loss and low density bone [ 5 , 11 ] , which may lead to hip fracture . We previously studied the effects of vitamin D supplementation in residents of a home for the elderly and residents of a nursing home [ 10 ] .  Vitamin D3 , 400 IU/d , led to an adequate increase of the serum 25(OH)D concentration , to a small but significant increase of the serum 1,25(OH)2D concentration , and to a decrease of the serum concentration of intact parathyroid hormone . It was recently observed [ 12 , 13 ] that bone mineral density at the hip is positively related to serum 25(OH)D concentration in postmenopausal and elderly women . Therefore , it might be expected that vitamin D supplementation would increase bone mineral density in elderly persons deficient in vitamin D. In line with this expectation , it was shown that vitamin D supplementation prevented bone loss from the spine during the winter in postmenopausal women [ 14 ] . These results suggest that vitamin D supplementation may reduce the incidence of hip fractures , because bone strength shows a strong correlation with bone mineral density [ 15 ] . However , increasing bone mineral density through a therapeutic intervention does not necessarily lead to increased bone strength , as has been shown with sodium fluoride [ 16 ] . Bone structure and bone quality are also determinants of bone strength [ 17 ] , and falls are a risk factor for hip fractures [ 18 ] . Therefore , hip fracture should be the outcome criterion in studies on the effect of vitamin D supplementation . Intervention studies on the prevention of osteoporotic fractures necessitate large numbers of patients , because the outcome has an annual incidence of 0.5 % to 4 % in the elderly population [ 19 ] . We report the results of a large-scale , prospect i ve study on the effect of vitamin D supplementation on the incidence of hip and other osteoporotic fractures . Methods Participants The study included 2578 persons ( 1916 women and 662 men ) 70 years of age and older ( mean age SD , 80 6 years ; range , 70 to 97 years ) . Participants were recruited from general practitioners , from apartment houses for elderly persons , and from homes for elderly persons in Amsterdam and its vicinity . Persons recruited from practitioners were living independently ; those recruited from apartment houses and homes were receiving some care , but less than they would have received in a nursing home . Participants had to be reasonably healthy and able to give informed consent . Persons with a history of hip fracture or total hip arthroplasty , known hypercalcemia , sarcoidosis , or recent urolithiasis ( < 5 years earlier ) were excluded . Patients who had diseases or who used medications that influence bone metabolism ( such as thyroid disease or glucocorticoid medication ) were not excluded . The spontaneous use of vitamin D supplements and multivitamins was discouraged , but the prescription practice s of the general practitioners were not altered . All vitamin use was carefully documented . The study was approved by the Ethical Review Board of the Vrije Universiteit Hospital , and all participants gave informed consent . Study Design After checking the inclusion and exclusion criteria and obtaining informed consent , the participants were r and omly assigned to receive either active treatment with vitamin D3 or placebo . The study was double-blind , and r and omization was done in blocks of 10 per general practice , apartment house , or home . R and omization lists were made using a computerized r and om-number generator . Lists in sealed envelopes were sent to the hospital pharmacy for assignment . Each participant took either one tablet per day that contained vitamin D3 , 400 IU , or one placebo tablet per day that was identical in appearance and taste to the vitamin tablet . After enrollment , the participants received the first container of tablets ( 210 tablets ) . The container was replaced every 6 months with a full container . All participants were also advised in writing to consume at least three servings of dairy products per day ( for example , 1 glass of milk , 1 cup of yogurt , and 1 slice of cheese ) to ensure a calcium intake of at least 800 to 1000 mg/d . The study was started in August 1988 . The last participant was enrolled in December 1990 , and all participants had stopped using study medication by December 1993 . The follow-up period had been planned to last no more than 3 years , but because the number of hip fractures during the study was lower than expected , a 6-month extension was planned . The study participants thus received medication for 3 to 3.5 years ; those who received it for 3.5 years were those who consented to the 6-month extension . Total follow-up was to a maximum of 4 years . Data collected at baseline included an  outdoor activity score  ( 1 equals going outdoors less than once a week ; 2 equals going outdoors 1 or 2 times per week ; and 3 equals going outdoors 3 times per week or more ) and a score for sunshine exposure ( when outside : 1 equals in the shade as much as possible ; 2 equals sometimes in sunshine ; 3 equals much exposure to sunshine ) . These scores show a positive relation with serum 25(OH)D concentration [ 3 ] . Mobility was estimated by a walking score that ranged from 1 ( unable to walk ) to 5 ( walks independently a fair distance on any surface ) [ 20 ] . The dietary calcium intake from dairy products was estimated in a subset of 348 women by using a question naire , as described previously [ 21 ] . The participants were evaluated annually with a question naire on hip fractures , other peripheral fractures , outdoor score , sunshine exposure score , use of vitamin supplements , and walking score . Each general practitioner or caretaker was asked to immediately report change of address , hip fracture , or death . Hip fracture and death were verified by the general practitioner . All participants were followed for the maximal period of 4 years if possible , even if they had stopped using the trial medication , had sustained a fracture , or had moved to another city . To investigate possible selection bias , 267 potential participants in a home for the elderly and its adjunct apartments ( all residents of the institution ) were studied for baseline characteristics , including age , sex , sunshine exposure score , outdoor score , walking score , and reasons for nonparticipation . Compliance was checked when the tablet containers were replaced ( every 6 months ) , by question naire ( every year ) , and by measurement of the serum 25(OH)D concentration . Serum 25(OH)D concentration was measured at baseline and after 1 year in 270 persons who participated in a sub study investigating the effect of vitamin D supplementation on bone mineral density and bone turnover variables . This sub study included a nonr and om sample of participants from several apartment houses and homes for the elderly and is described in detail elsewhere [ 21 ] . In the same sub study , dietary calcium intake from diary products was assessed . Serum 25(OH)D concentration was also estimated during the third year of the study in February and March in a r and om sample of 96 participants drawn from the remaining study population . These participants received a letter giving them an appointment within 10 days ; the blood sample s were drawn at home . Serum 25(OH)D concentration was measured by competitive protein binding assay after being purified by gradient high-pressure liquid chromatography . The intra- and interassay coefficients of variation were 5 % and 6 % , respectively [ 22 ] . Statistical Analysis Baseline data of the vitamin D group and the placebo group were compared using t-tests ( age , calcium intake ) , chi-square tests ( sex , residence ) , and Wilcoxon rank-sum tests ( scores ) . The serum 25(OH)D concentrations of both groups were compared using t-tests . Data on fractures and mortality were analyzed by survival analysis using log-rank tests , Cox proportional-hazards regression , and hazard rate ratios [ 23 ] . Hip fractures are presented using the Kaplan-Meier method . All participants were kept in the study as long as possible . The data were analyzed in two ways . The intention-to-treat analysis included all r and omly assigned participants for either the total follow-up period or until fracture , death , or loss to follow-up . The active treatment analysis included the participants as long as they stated that they were using the trial medication . Thus , the participants were included in the active treatment analysis until they stopped using the trial medication , regardless of whether a fracture occurred after they had stopped . Age , sex , and residence were added in both analyses as covariates to the Cox regression model . Because outdoor score , sunshine score , and walking score were interrelated ( correlation coefficients ranging from 0.21 to 0.59 ) and were likely to indicate general health or mobility , they were averaged over the years and added up to a sum score . For this purpose , the walking score was simplified ( 1 , 2 , or 3 equals 1 ; 4 equals 2 ; 5 equals 3 ) , because the lower walking scores applied to a few participants only . The result ing total score , ranging from 3 to 9 , was entered as a covariate in the model . The level of compliance ( weekly intake as reported on The long term effects of hormone replacement therapy ( HRT ) and vitamin D3 ( Vit D ) on bone mineral density ( BMD ) were studied . A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study ( n = 13100 ) were r and omized to four groups : 1 ) HRT ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate , 2 ) Vit D3 ( 300 and 100 IU/day during the fifth year ) , 3 ) HRT and Vit D combined , and 4 ) placebo .  Lumbar ( L2-L4 ) and femoral neck BMD were determined by dual x-ray absorptiometry ( DXA ) at baseline and after 2.5 and 5 yr of treatment . Intention to treat analysis ( n = 464 ) showed that after 5 yr , lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [ + 0.2 % ( P = 0.658 ) and + 0.9 % ( P = 0.117 ) , respectively ] , whereas lumbar BMD decreased by 4.6 % in the Vit D group and by 4.5 % in the placebo group ( P < 0.001 in both ) . The loss of femoral neck BMD was less in the HRT ( -1.4 % ; P = 0.005 ) and HRT plus Vit D ( -1.3 % ; P = 0.003 ) groups than in the Vit D and placebo groups ( -4.3 % ; P < 0.001 in both ) . Among those 370 women who complied with the 5-yr treatment , the effect was more pronounced : lumbar BMD had increased by 1.5 % in the HRT ( P = 0.009 ) and by 1.8 % in the HRT plus Vit D group ( P = 0.005 ) , with a plateau after 2.5 yr , whereas lumbar BMD had decreased in both the Vit D and placebo groups ( 4.6 % and 4.7 % ; P < 0.001 , respectively ) . Femoral neck BMD decreased again less in the HRT ( -0.4 % ) and HRT plus Vit D ( -0.6 % ) groups than in the Vit D and placebo groups ( -4.4 % in both ) . This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis . The data suggest that low dose vitamin D3 supplementation does not prevent  bone loss in healthy , nonosteoporotic , early postmenopausal women , and it confers no benefit additional to that of HRT alone 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 OBJECTIVES To determine the effectiveness of vitamin D supplementation in preventing decline in physical function in older men . DESIGN R and omized , double-blind , placebo-controlled clinical trial . SETTING Single-center study conducted at a Veterans Affairs Healthcare System . PARTICIPANTS Sedentary men aged 65 to 90 ( mean 72.4 ± 6.8 ) with baseline 25-hydroxyvitamin D ( 25(OH)D levels of less than 30 ng/mL and Short Physical Performance Battery ( SPPB ) test scores of 9 or less ( N = 130 ) . INTERVENTION Daily capsule containing cholecalciferol 4,000 IU daily or placebo for 9 months . MEASUREMENTS Main outcomes were SPPB score and gait speed . RESULTS After the intervention , serum 25(OH)D increased from 23.1 ± 5.0 ng/mL to 46.2 ± 12.7 ng/mL in the cholecalciferol group and from 22.5 ± 5.3 ng/mL to 24.0 ± 7.2 ng/mL in the placebo group . At study end , improvements in SPPB score and gait speed were not significantly greater in men receiving cholecalciferol than in those receiving placebo . No differences were found in adverse events or numbers of falls . CONCLUSION Daily cholecalciferol 4,000 IU for 9 months result ed in significant increases in 25(OH)D concentrations , but achieving these higher levels did not result in improvements in SPPB score or gait speed . These data do not support prescribing vitamin D supplements to older sedentary men to prevent physical function decline Summary Vitamin D may affect skeletal muscle function . In a double-blind , r and omised , placebo-controlled trial , we found that vitamin D3 supplementation ( 400 or 1,000 I.U. vs. placebo daily for 1 year with bimonthly study visits ) does not improve grip strength or reduce falls . Introduction This study aim ed to test the supplementation effects of vitamin D3 on physical function and examine associations between overweight/obesity and the biochemical response to treatment . Methods In a parallel group double-blind RCT , healthy postmenopausal women from North East Scotl and ( latitude—57 ° N ) aged 60–70 years ( body mass index ( BMI ) , 18–45 kg/m2 ) were assigned ( computer r and omisation ) to daily vitamin D3 ( 400 I.U. ( n = 102)/1,000 I.U. ( n = 101 ) ) or matching placebo ( n = 102 ) ( 97 , 96 and 100 participants analysed for outcomes , respectively ) from identical coded containers for 1 year . Grip strength ( primary outcome ) , falls , diet , physical activity and ultraviolet B radiation exposure were measured bimonthly , as were serum 25(OH)D , adjusted calcium ( ACa ) and phosphate . Fat/lean mass ( dual energy X-ray absorptiometry ) , anthropometry , 1,25-dihydroxyvitamin D and parathyroid hormone were measured at baseline and 12 months . Participants and research ers were blinded throughout intervention and analysis . Results Treatment had no effect on grip strength ( mean change (SD)/year = −0.5 ( 2.5 ) , −0.9 ( 2.7 ) and −0.4 ( 3.3 ) kg force for 400/1,000 I.U. vitamin D3 and placebo groups , respectively ( P = .10 , ANOVA ) ) or falls ( P = .65 , chi-squared test ) . Biochemical responses were similar across BMI categories ( < 25.25–29.99 , ≥30 kg/m2 ) with the exception of a small change at 12-months in serum ACa in overweight compared to non-overweight participants ( P = .01 , ANOVA ; 1,000 I.U. group ) . In the  placebo group , 25(OH)D peak concentration change ( winter to summer ) was negatively associated with weight ( r = −.268 ) , BMI ( r = −.198 ) , total ( r = −.278 ) and trunk fat mass ( r = −.251 ) , with total and trunk fat mass predictive of winter to summer 25(OH)D change ( P = .01/.004 respectively , linear regression ) . Conclusion We found no evidence of an improvement in physical function following vitamin D3 supplementation for 1 year BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to test the hypothesis that vitamin D(3 ) supplementation would prevent bone loss in calcium-replete , African American postmenopausal women . METHODS Two hundred eight healthy black postmenopausal women , 50 to 75 years of age , were assigned to receive either placebo or 20 microg/d ( 800 IU ) of vitamin D(3 ) . Calcium supplements were provided to ensure a total calcium intake of 1200 to 1500 mg/d . After 2 years , the vitamin D(3 ) dose was increased to 50 microg/d ( 2000 IU ) in the active group , and the study continued for an additional year . Bone mineral density ( BMD ) was measured every 6 months . Markers of bone turnover , vitamin D metabolites , and parathyroid hormone ( PTH ) levels were measured in serum . RESULTS There were no significant differences in BMD between the active and control groups throughout the study . There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss . There was an increase in BMD of the total body , hip , and radius at 1 year in both groups . Over the 3 years , BMD declined at these sites by 0.26 % to 0.55 % per year . The BMD of the lumbar spine increased slightly in the placebo and active groups . There were no persistent changes in serum PTH levels or the markers of bone turnover , although there was a transient decline in PTH in both groups at 3 months . No significant adverse events were attributed to vitamin D supplementation . CONCLUSIONS There was no observed effect of vitamin D(3 ) supplementation on bone loss or bone turnover markers in calcium-replete , postmenopausal African American women . Further studies are needed to determine if these findings are applicable to women of other ethnic groups 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 Objective : To evaluate the effect of isolated vitamin D supplementation ( VITD ) on the rate of falls and postural balance in postmenopausal women fallers . Methods : In this double-blind , placebo-controlled trial , 160 Brazilian younger postmenopausal women were r and omized into two groups : VITD group , vitamin D3 supplementation 1,000 IU/day/orally ( n = 80 ) and placebo group ( n = 80 ) . Women with amenorrhea at least 12 months , age 50 to 65 years , and a history of falls ( previous 12 months ) were included . Those with neurological or musculoskeletal disorders , vestibulopathies , drugs use that could affect balance and osteoporosis were excluded . The intervention time was 9 months . Postural balance was assessed by stabilometry ( computerized force platform ) and investigation on the occurrence/recurrence of falls was performed by interviews . The plasma concentration of 25-hydroxyvitamin D [ 25(OH)D ] was measured by high-performance liquid chromatography . Statistical analysis was achieved by intention-to-treat , using analysis of variance , Student 's t test , Tukey test , chi-square , and logistic regression . Results : After 9 months , mean values of 25(OH)D increased from 15.0 ± 7.5 ng/mL to 27.5 ± 10.4 ng/mL ( + 45.4 % ) in the VITD group , and decreased from 16.9 ± 6.7 ng/mL to 13.8 ± 6.0 ng/mL ( −18.5 % ) in the placebo group ( P < 0.001 ) . The occurrence of falls was higher in the placebo group ( + 46.3 % ) with an adjusted risk of 1.95 ( 95 % confidence interval [ CI ] 1.23 - 3.08 ) times more likely to fall and 2.80 ( 95 % CI 1.43 - 5.50 ) times higher for recurrent falls compared to the VITD group ( P < 0.001 ) . There was reduction in body sway by stabilometry , with lower amplitude of antero-posterior ( −35.5 % ) and latero-lateral ( −37.0 % ) oscillation , only in the VITD group ( P < 0.001 ) . Conclusions : In Brazilian postmenopausal women fallers  , isolated vitamin D supplementation for 9 months result ed in a lower incidence of falls and improvement in postural balance Summary Sunlight deprivation results in vitamin D deficiency but serum vitamin D levels can be maintained above 50nmol/L when supplemented with 50,000IU at least every alternate month . Introduction Anta rct ic expeditioners are exposed to prolonged sunlight deprivation result ing in vitamin D deficiency . We hypothesised that monthly dosing of 50,000 IU vitamin D ( ~1,600 IU daily ) will increase serum 25-hydroxyvitamin D ( 25(OH)D ) , suppress parathyroid hormone ( PTH ) and improve bone mineral density ( BMD ) , 50,000 IU alternate months ( ~800 IU daily ) will maintain these measures , while a single 50,000 IU dose pre-departure ( ~1,00 IU daily ) will not be protective . Methods This was a r and omised double-blind study involving 110 healthy adults : 91 males , mean age 41 years ( range 24–65 years ) working in Anta rct ica for up to 12 months , who we administered 50,000 IU vitamin D3 monthly , alternate months or a single dose pre-departure  . Serum 25(OH)D , PTH , osteocalcin , CTx and calcium were assessed at baseline , mid- and end of expedition . Proximal femur and lumbar spine BMD were assessed pre- and post-expedition . Results Baseline 25(OH)D was 59 ± 14 nmol/L. By mid-expedition , 25(OH)D increased by 7 nmol/L in those supplemented monthly ( p < 0.05 ) and remained unchanged in those supplemented in alternate months . In those given a single dose pre-departure , 25(OH)D decreased by 8 nmol/L ( p < 0.05 ) and PTH increased by 27 % ( p < 0.09 ) . Serum osteocalcin increased by ~22 % in all groups but BMD remained unchanged . If serum 25(OH)D was > 50 nmol/L at baseline , 25(OH)D was maintained above this level with all regimens . If 25(OH)D was < 50 nmol/L at baseline , monthly or alternate month regimens were needed to achieve levels > 50 nmol/L , the single pre-departure dose was ineffective . Conclusion During sunlight deprivation of up to 12 months , serum 25(OH)D levels can be maintained above 50 nmol/L when expeditioners are provided with 50,000 I U at least every alternate month BACKGROUND Severe vitamin D deficiency causes osteomalacia , yet trials of vitamin D supplementation in the community have not on average demonstrated benefit to bone mineral density ( BMD ) or fracture risk in adults . OBJECTIVE To determine whether monthly high-dose vitamin D supplementation influences BMD in the general population and in those with low 25-hydroxyvitamin D levels . METHODS Two-year sub study of a trial in older community-resident adults . A total of 452 participants were r and omized to receive monthly doses of vitamin D3 100 000 IU , or placebo . The primary end-point was change in lumbar spine BMD . Exploratory analyses to identify thresholds of baseline 25-hydroxyvitamin D for vitamin D effects on BMD were prespecified . RESULTS Intention-to-treat analyses showed no significant treatment effect in the lumbar spine ( between-groups difference 0.0071 g cm-2 , 95%CI : -0.0012 , 0.0154 ) or total body but BMD loss at both hip sites was significantly attenuated by ~1/2 % over 2 years . There was a significant interaction between baseline 25-hydroxyvitamin D and treatment effect ( P = 0.04 ) . With baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 ( n = 46 ) , there were between-groups BMD changes at the spine and femoral sites of ~2 % , significant in the spine and femoral neck , but there was no effect on total body BMD . When baseline 25-hydroxyvitamin D was > 30 nmol L-1 , differences were ~1/2 % and significant only at the total hip . CONCLUSIONS This sub study finds no clinical ly important benefit to BMD  from untargeted vitamin D supplementation of older , community-dwelling adults . Exploratory analyses suggest meaningful benefit in those with baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 . This represents a significant step towards a trial-based definition of vitamin D deficiency for bone health in older adults 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 OBJECTIVES To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge . DESIGN Multicenter , r and omized , controlled trial with a factorial design . SETTING Five hospitals in Auckl and , New Zeal and , and Sydney , Australia . PARTICIPANTS Two hundred forty-three frail older people . INTERVENTIONS Patients were r and omized to receive a single dose of vitamin D ( calciferol , 300,000 IU ) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits . MEASUREMENTS The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months . Physical performance and self-rated function were secondary endpoints . Assessment s took place in the participants ' homes at 3 and 6 months after r and omization and were performed by blinded assessors . RESULTS There was no effect of either intervention on physical health or falls , but patients in the exercise group were at increased risk of musculoskeletal injury ( risk ratio = 3.6 , 95 % confidence interval = 1.5 - 8.0 ) . Vitamin D supplementation did not improve physical performance , even in those who were vitamin D deficient ( < 12 ng/mL ) at baseline . CONCLUSION Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization . There was no effect of vitamin D on physical performance , and the exercises increased the risk of musculoskeletal injury . These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people 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 Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo .  Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people BACKGROUND A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies , but evidence from trials is lacking . OBJECTIVE We determined whether vitamin D supplementation , with or without calcium , improved glucose homeostasis in adults at high risk of diabetes . DESIGN Ninety-two adults were r and omly assigned in a 2-by-2 factorial- design , double-masked , placebo-controlled trial to receive either cholecalciferol ( 2000 IU once daily ) or calcium carbonate ( 400 mg twice daily ) for 16 wk . The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test . Other outcomes were acute insulin response , insulin sensitivity , and measures of glycemia . RESULTS Participants had a mean age of 57 y , a body mass index ( BMI ; in kg/m(2 ) ) of 32 , and glycated hemoglobin ( Hb A(1c ) ) of 5.9 % . There was no significant vitamin D × calcium interaction on any outcomes . The disposition index increased in the vitamin D group and decreased in the no-vitamin D group ( adjusted mean change ± SE : 300 ± 130 compared with -126 ± 127 , respectively ; P = 0.011 ) , which was explained by an improvement in insulin secretion ( 62 ± 39 compared with -36 ± 37 mU · L(-1 ) · min , respectively ; P = 0.046 ) . Hb A(1c ) increased less , but nonsignificantly , in the vitamin D group than in the no-vitamin D group ( 0.06 ± 0.03 % compared with 0.14 ± 0.03 % , respectively ; P = 0.081 ) . There was no significant difference in any outcomes with calcium compared with no calcium . CONCLUSION In adults at risk of type 2 diabetes , short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c ) . This trial was registered at clinical trials.gov as NCT00436475 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 . ) 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 OBJECTIVES To compare the effects of 12 months of vitamin D3 supplementation with that placebo on lean mass , bone mineral density ( BMD ) , and muscle strength in overweight or obese postmenopausal women completing a structured weight-loss program . DESIGN Double-blind , placebo-controlled r and omized clinical trial . SETTING Fred Hutchinson Cancer Research Center , Seattle , Washington . PARTICIPANTS Postmenopausal women aged 50 to 75 with a body mass index ( BMI ) of 25 kg/m(2 ) or greater and a serum 25-hydroxyvitamin D ( 25(OH)D ) concentration between 10.0 and 32.0 ng/mL ( insufficient ) ( N = 218 ) . INTERVENTION Oral vitamin D3 2,000 IU/d or placebo in combination with a lifestyle-based weight loss intervention consisting of a reduction of 500 kcal to 1,000 kcal per day and 225 min/wk of moderate- to vigorous-intensity aerobic exercise .  MEASUREMENTS Serum 25(OH)D , body composition , and muscle strength were measured before r and omization ( baseline ) and at 12 months . Mean changes of the groups were compared ( intention to treat ) using generalized estimating equations . RESULTS Change in 25(OH)D was significantly different between the vitamin D and placebo groups at 12 months ( 13.6 ng/mL vs -1.3 ng/mL , P < .001 ) , but no differences in change in lean mass ( -0.8 kg vs -1.1 kg , P = .53 ) or BMD of the spine ( -0.01 g/cm(2 ) vs 0.0 g/cm(2 ) , P = .82 ) or right femoral neck ( both -0.01 g/cm(2 ) , P = .49 ) were detected between the groups . Leg strength decreased in the vitamin D group but not in the placebo group ( -2.6 pounds vs 1.8 pounds , P = .03 ) . In women r and omized to vitamin D , achieving repletion ( 25(OH)D ≥ 32 ng/mL ) did not alter results . CONCLUSION Vitamin D3 supplementation during weight-loss decreased leg strength but did not alter changes in lean mass or BMD in postmenopausal women with vitamin D insufficiency 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 OBJECTIVE This study aims to investigate the efficacy and safety of oral fixed-dose combination of strontium ranelate 2 g/vitamin D₃ 1000 IU daily vs strontium ranelate 2 g daily for correcting vitamin D insufficiency in osteoporosis . DESIGN A 6-month international , r and omized , double-blind , parallel-group , phase 3 study . METHODS A total of 518 men and postmenopausal women aged ≥50 years with primary osteoporosis ( T-score ≤-2.5 s.d . ) and serum 25-hydroxyvitamin D ( 25(OH)D ) > 22.5 nmol/l were included . Patients were allocated to strontium ranelate 2 g/vitamin D₃ 1000 IU daily ( n=413 ) or strontium ranelate 2 g daily ( n=105 ) . The participants received calcium 1 g daily . The primary endpoint was serum 25(OH)D at last post-baseline evaluation during 3 months . RESULTS Both groups were comparable at baseline . Mean baseline of 25(OH)D was 44.1 ± 14.6 nmol/l . After 3 months , the percentage of patients with 25(OH)D ≥50 nmol/l was higher with strontium ranelate/vitamin D₃ vs strontium ranelate ( 84 vs 44 % , P<0.001 ; adjusted between-group odds ratio=6.7 ; 95 % CI , 4.2 - 10.9 ) . The efficacy of the fixed-dose combination on 25(OH)D was maintained at 6 months ( 86 vs 40 % , P<0.001 ) . Mean 25(OH)D was 65.1 and 49.5 nmol/l , respectively , after 3 months and 66.9 and 45.4 nmol/l after 6 months . Physical performance improved in both groups . Falls were 17 and 20 % in the strontium ranelate/vitamin D₃ and strontium ranelate groups respectively . Parathyroid hormone levels were inversely correlated with 25(OH)D. No clinical ly relevant differences in safety were observed . CONCLUSIONS This study confirms the efficacy and safety of fixed-dose combination of strontium ranelate 2 g/vitamin D₃ 1000 IU for correction of vitamin D insufficiency in osteoporotic patients There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status . The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone-related chemistry in elderly women with vitamin D insufficiency . Three hundred two elderly women ( age , 77.2 + /- 4.6 yr ) with serum 25(OH)D concentrations < 60 nM participated in a 1-yr r and omized , double-blind , placebo-controlled trial . All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol ( vitamin D(2 ) ) or identical placebo ( control ) . The effects of time and time treatment interactions were evaluated by repeated- measures ANOVA . At baseline , calcium intake was 1100 mg/d , and 25(OH)D was 44.3 + /- 12.9 nM ; this increased in the vitamin D group by 34 % but not the control group after 1 year ( 59.8 + /- 13.8 versus 45.0 + /- 13.3 nM , p < 0.001 ) . Total hip and total body BMD increased significantly , and procollagen type I intact N-terminal propeptide ( PINP ) decreased during the study with no difference between the treatment groups ( hip BMD change :  vitamin D , + 0.5 % ; control , + 0.2 % ; total body BMD change : vitamin D , + 0.4 % ; control , + 0.4 % ; PINP change : vitamin D , -3.9 % ; placebo , -2.8 % ) . Although the fasting plasma and urine calcium increased in both groups equally , there was no detectable change in serum PTH . The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption , which fell equally in both groups ( vitamin D , -17.4 % ; control , -14.8 % ) . In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency , vitamin D(2 ) 1000 IU for 1 year has no extra beneficial effect on bone structure , bone formation markers , or intestinal calcium absorption over an additional 1000 mg of calcium . Vitamin D supplementation adds no extra short-term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency
target: For hip fracture , at a 15 % relative risk , the effect estimate lay between the futility boundary and the inferior boundary , meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount , but uncertainty remains as to whether it might increase hip fractures .
  The effect estimate lay within the futility boundary at thresholds of 0·5 % for total hip , forearm , and total body bone mineral density , and 1·0 % for lumbar spine and femoral neck , providing reliable evidence that vitamin D does not alter these outcomes by these amounts .
  INTERPRETATION Our findings suggest that vitamin D supplementation does not prevent fractures or falls , or have clinical ly meaningful effects on bone mineral density .
  There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health .
background: BACKGROUND The effects of vitamin D on fractures , falls , and bone mineral density are uncertain , particularly for high vitamin D doses .
  We aim ed to determine the effect of vitamin D supplementation on fractures , falls , and bone density .