title: Amelioration of osteopenia and hypovitaminosis D by 1α-hydroxyvitamin D3 in elderly patients with Parkinson’s disease High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease 1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial. The Effects of Vitamin D Supplementation on Physical Function and Quality of Life in Older Patients With Heart Failure: A Randomized Controlled Trial Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis: A Randomized Clinical Trial. Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D. Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study: A Randomized Clinical Trial Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year randomized clinical trial with 4000 IU vitamin D daily Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Vitamin D supplementation and bone mineral density in early postmenopausal women. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. Vitamin D 20,000 IU per Week for Five Years Does Not Prevent Progression From Prediabetes to Diabetes. The effect of vitamin D supplementation on knee osteoarthritis, the VIDEO study: a randomised controlled trial. 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. Calcium, vitamin D and anabolic steroid in treatment of aged bones: double-blind placebo-controlled long-term clinical trial. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Biochemical parameters after cholecalciferol repletion in hemodialysis: results From the VitaDial randomized trial. Calcitriol treatment is not effective in postmenopausal osteoporosis. 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 Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents Vitamin D, Insulin Secretion, Sensitivity, and Lipids Once-weekly dose of 8400 IU vitamin D(3) compared with placebo: effects on neuromuscular function and tolerability in older adults with vitamin D insufficiency. Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial Do vitamin D supplements improve the physical capabilities of elderly hospital patients? 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. Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. 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. Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily. Effects of vitamin D and calcium supplementation on falls: a randomized controlled 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. Vitamin D and Physical Function in Sedentary Older Men A randomized controlled trial of vitamin D3 supplementation in African American women. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). Effect of monthly high‐dose vitamin D on bone density in community‐dwelling older adults substudy of a randomized controlled trial Effects of large doses of calciferol on patients with rheumatoid arthritis. A double-blind clinical 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. The response of elderly veterans to daily vitamin D3 supplementation of 2,000 IU: a pilot efficacy study. 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. Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1 alpha-hydroxyvitamin D3 and calcium supplementation. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Vitamin D Supplementation and Survival of Patients with Non–small Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas. Cognition and Vitamin D in Older African‐American Women– Physical performance and Osteoporosis prevention with vitamin D in older African Americans Trial and Dementia Exercise and vitamin D in fall prevention among older women: a randomized clinical trial. Correction of vitamin D insufficiency with combined strontium ranelate and vitamin D3 in osteoporotic patients.
abstract: OBJECTIVES A high prevalence of hip and other fractures in elderly patients with Parkinson ’s disease has been linked to reduced bone mass arising from a defect of renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Treatment with 1α-hydroxyvitamin D3 ( 1α(OH)D3 ; an active form of vitamin D ) was evaluated for maintaining bone mass and reducing the incidence of hip and other non-vertebral fractures in patients with Parkinson ’s disease . METHODS In a double blind , r and omised trial , 86 elderly patients with Parkinson ’s disease ( mean Hoehn and Yahr stage , 3 ; mean age 70.6 years ) were r and omised to receive either 1 μg 1α(OH)D3 daily ( treatment group , n=43 ) or a placebo ( n=43 ) for 18 months . Bone mineral densities in the second metacarpals were determined by computed radiographic densitometry . Serum bone turnover indices were measured serially , and incidence of non-vertebral fractures was recorded . RESULTS Bone mineral densities decreased 1.2 % in the treatment group compared with 6.7 % in the placebo group during 18 months ( p<0.0001 ) . At baseline in both groups , the serum concentration of 1 , 25-[OH]2D was reduced . Parathyroid hormone was abnormally increased in 15 patients ( 17 % ) and correlated negatively with serum 25-hydroxyvitamin D , indicating compensatory hyperparathyroidism . Eight patients  sustained fractures ( six at the hip and two at other sites ) in the placebo group , and one hip fracture occurred among treated patients ( odds ratio 9.8 ; p=0.0028 ) . CONCLUSION By increasing serum 1 , 25-[OH]2D concentrations , treatment with 1α(OH)D3 can reduce the risk of hip and other non-vertebral fractures in osteoporotic elderly patients with Parkinson ’s disease by slowing the loss of bone mineral densities BACKGROUND Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P < 0.001 ) . The median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels < 10 ng/mL ) at baseline showed a significant reduction in exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM ) An unexplained loss of muscle strength occurs with aging . Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [ 1,25-(OH2)D3 ] to persons with low serum concentrations can improve strength . To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [ 1,25-(OH2)D3 ] , we conducted a r and omized , controlled , double blinded trial in 98 men and women volunteers over 69 yr old . Treatment consisted of 0.25 micrograms 1,25-(OH)2D3 , orally , twice per day or identical placebo for 6 months .  Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer . There was no difference between the two groups at 1 week , 1 month , or 6 months of treatment in any of the measures of muscle strength . We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons . Further research is needed to determine the etiology of the decline in muscle strength associated with aging 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 Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol , are important factors in the pathogenesis of age-related bone loss . The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on  bone loss in elderly women . Four hundred eighty-nine elderly women with normal bone density for their age , aged 65 - 77 yr , were entered into a r and omized double blind , placebo-controlled trial . Women were r and omized to one of four groups : conjugated estrogens ( 0.625 mg , daily ) to women without a uterus ( estrogen replacement therapy ) plus medroxyprogesterone acetate ( 2.5 mg , daily ) to women with a uterus ( hormone replacement therapy ) , calcitriol ( 0.25 microg twice daily ) , a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol , or placebos for 3 yr . The primary outcome was the change in bone mineral density of the femoral neck and spine . In the intent to treat analysis , hormone therapy ( hormone replacement therapy/estrogen replacement therapy ) produced a mean ( + /-1 SD ) increase in bone mineral density of 2.98 % ( + /-5.45 % ) at the femoral neck ( P < 0.0001 ) and 4.36 % ( + /-6.42 % ) at the spine ( P < 0.0001 ) . There were parallel increases in total hip and trochanter bone mineral density . Calcitriol increased bone mineral density 0.10 % ( + /- 4.27 % ) at the femoral neck ( P = 0.57 ) and 1.65 % ( + /- 4.83 % ) at the spine ( P < 0.0124 ) . The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol  increased bone mineral density 3.80 % ( + /-4.95 % ) at the femoral neck ( P < 0.001 ) , 4.91 % ( + /-6.0 % ) at the spine ( P < 0.0001 ) , and parallel changes at the total hip and trochanter . All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck , spine , total hip and trochanter . There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis . In a secondary analysis of the effect in women who were adherent to treatment , calcitriol had a more significant effect on spine ( P = 0.003 ) and total hip ( P = 0.004 ) . The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups . Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter ( P = 0.007 ) and total hip bone mineral density ( P = 0.0017 ) . In summary , hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinical ly relevant sites in a group of elderly women , with normal bone density for their age . Calcitriol was effective in increasing spine bone mineral density . In the adherent women , combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone 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 A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side , correlating with the degree of paralysis and vitamin D deficiency due to malnutrition , sunlight deprivation , and immobilization-induced hypercalcemia , and increases the risk of hip fracture . We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [ 1alpha(OH)D3 ; vitamin D3 ] administration on bone mineral density preservation as compared with untreated controls . In a r and omized and prospect i ve study of 103 patients with hemiplegia after stroke ( the mean duration of illness was 4.8 yr ) , 68 ( 34 patients in each group ) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo , whereas the remaining 35 patients received no drug .  Bone mineral density on the hemiplegic side decreased by 1.4 % in the ipriflavone group , 3.8 % in the vitamin D3 group , and 5.4 % in the control group ( P < .0001 , ipriflavone v vitamin D3 and control ) . At baseline , all three groups of patients showed a 25-hydroxyvitamin D insufficiency , increased serum ionized calcium , and low levels of 1 , 25-dihydroxyvitamin D , suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1 , 25-dihydroxyvitamin D. After treatment , the serum 1 , 25-dihydroxyvitamin D level increased by 139.9 % in the ipriflavone group and by 26.9 % in the vitamin D3 group . Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen , and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group , whereas no changes occurred in the other two groups . One patient in the untreated group suffered a hip fracture , compared with none in the ipriflavone and vitamin D3 groups . These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1 , 25-dihydroxyvitamin D concentration Importance Cohort studies have reported increased incidence of cardiovascular disease ( CVD ) among individuals with low vitamin D status . To date , r and omized clinical trials of vitamin D supplementation have not found an effect , possibly because of using too low a dose of vitamin D. Objective To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population . Design , Setting , and Participants The Vitamin D Assessment Study is a r and omized , double-blind , placebo-controlled trial that recruited participants mostly from family practice s in Auckl and , New Zeal and , from April 5 , 2011 , through November 6 , 2012 , with follow-up until July 2015 . Participants were community-resident adults aged 50 to 84 years . Of 47 905 adults invited from family practice s and 163 from community groups , 5110 participants were r and omized to receive vitamin D3 ( n = 2558 ) or placebo ( n = 2552 ) . Two participants retracted consent , and all others ( n = 5108 ) were included in the primary analysis . Interventions Oral vitamin D3 in an initial dose of 200 000 IU , followed a month later by monthly doses of 100 000 IU , or placebo for a median of 3.3 years ( range , 2.5 - 4.2 years ) . Main Outcomes and Measures The primary outcome was the number of participants with incident CVD and death , including a prespecified subgroup analysis in participants with vitamin D deficiency ( baseline deseasonalized 25-hydroxyvitamin D [ 25(OH)D ] levels < 20 ng/mL ) . Secondary outcomes were myocardial infa rct ion , angina , heart failure , hypertension , arrhythmias , arteriosclerosis , stroke , and venous thrombosis . Results Of the 5108 participants included in the analysis , the mean ( SD ) age was 65.9 ( 8.3 ) years , 2969 ( 58.1 % ) were male , and 4253 ( 83.3 % ) were of European or other ethnicity , with the remainder being Polynesian or South Asian .  Mean ( SD ) baseline deseasonalized 25(OH)D concentration was 26.5 ( 9.0 ) ng/mL , with 1270 participants ( 24.9 % ) being vitamin D deficient . In a r and om sample of 438 participants , the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group . The primary outcome of CVD occurred in 303 participants ( 11.8 % ) in the vitamin D group and 293 participants ( 11.5 % ) in the placebo group , yielding an adjusted hazard ratio of 1.02 ( 95 % CI , 0.87 - 1.20 ) . Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes . Conclusions and Relevance Monthly high-dose vitamin D supplementation does not prevent CVD . This result does not support the use of monthly vitamin D supplementation for this purpose . The effects of daily or weekly dosing require further study . Trial Registration clinical trials.gov Identifier : Aims Circulating 25-hydroxyvitamin D ( 25OHD ) levels < 75 nmol/L are associated with a nonlinear increase in mortality risk . Such 25OHD levels are common in heart failure ( HF ) . We therefore examined whether oral vitamin D supplementation reduces mortality in patients with advanced HF . Methods and results Four hundred HF patients with 25OHD levels < 75 nmol/L were r and omized to receive 4000 IU vitamin D daily or matching placebo for 3 years . Primary endpoint was all-cause mortality . Key secondary outcome measures included hospitalization , resuscitation , mechanical circulatory support ( MCS ) implant , high urgent listing for heart transplantation , heart transplantation , and hypercalcaemia . Initial 25OHD levels were on average < 40 nmol/L , remained around 40 nmol/L in patients assigned to placebo and plateaued around 100 nmol/L in patients assigned to vitamin D. Mortality was not different in patients receiving vitamin D ( 19.6 % ; n = 39 ) or placebo ( 17.9 % ; n = 36 ) with a hazard ratio ( HR ) of 1.09 [ 95 % confidence interval ( CI ) : 0.69 - 1.71 ; P = 0.726 ] . The need for MCS implant was however greater in patients assigned to vitamin D ( 15.4 % , n = 28 ) vs. placebo [ 9.0 % , n = 15 ; HR : 1.96 ( 95 % CI : 1.04 - 3.66 ) ; P = 0.031 ] . Other secondary clinical endpoints were similar between groups . The incidence of hypercalcaemia was 6.2 % ( n = 10 ) and 3.1 % ( n = 5 ) in patients receiving vitamin D or placebo ( P = 0.192 ) . Conclusion A daily vitamin D dose of 4000 IU did not reduce mortality in patients with advanced HF but was associated with a greater need for MCS implants . Data indicate caution regarding long-term supplementation with moderately high vitamin D doses . Trial Registration Information clinical trials.gov Idenitfier : NCT01326650 BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk  of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P < 0.03 ) . With the use of logistic regression , the unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P < 0.005 ) but did not change significantly for the Ca-only group . In multiple logistic regression models , both treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces  all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170 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 BACKGROUND Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure ( CHF ) . In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines . OBJECTIVE We evaluated the effect of vitamin D supplementation on the survival rate and different biochemical variables in patients with CHF . DESIGN One hundred twenty-three patients r and omly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [ D(+ ) group ] or placebo plus 500 mg Ca/d [ D(- ) group ] for 9 mo . Biochemical variables were assessed at baseline and after 9 mo . The survival rate was calculated for a follow-up period of 15 mo . RESULTS Ninety-three patients completed the study . Significant treatment effects were observed on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D ( P = 0.001 ) , parathyroid hormone ( P = 0.007 ) , tumor necrosis factor alpha ( P = 0.006 ) , and interleukin 10 ( P = 0.042 ) . 25-Hydroxyvitamin D increased by 26.8 ng/mL in the D(+ ) group but increased only by 3.6 ng/mL in the D(- ) group . Compared with baseline , parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+ ) group after 9 mo . The proinflammatory cytokine tumor necrosis factor alpha increased in the D(- ) group but remained constant in the D(+ ) group . The survival rate did not differ significantly between the study groups during the follow-up period . CONCLUSIONS Vitamin D(3 ) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease . Our data provide evidence for the involvement of an impaired vitamin D-parathyroid hormone axis in the progression of CHF 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 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 CONTEXT Vitamin D deficiency is associated with insulin resistance and risk of future diabetes . OBJECTIVE The objective of the study was to test whether supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes mellitus ( T2DM ) . DESIGN This was a r and omized controlled trial performed in 2008 through 2015 . SETTING The study was conducted at the clinical research unit at a teaching hospital . PATIENTS Five hundred eleven subjects ( mean age 62 y , 314 males ) with prediabetes diagnosed with an oral glucose tolerance test as part of the Tromsø Study 2007–2008 were included . A total of 256 were r and omized to vitamin D and 255 to placebo .  Twenty-nine subjects in the vitamin D and 24 in the placebo group withdrew because of adverse events . INTERVENTIONS Interventions included vitamin D ( cholecalciferol ) 20 000 IU/wk vs placebo for 5 years . Annual oral glucose tolerance tests were performed . MAIN OUTCOME MEASURE Progression to T2DM was the main outcome measure . Secondary outcomes were change in glucose levels , insulin resistance , serum lipids , and blood pressure . RESULTS The mean baseline serum 25-hydroxyvitamin D level was 60 nmol/L ( 24 ng/mL ) . One hundred three in the vitamin D and 112 in the placebo group developed T2DM ( hazard risk 0.90 ; 95 % confidence interval 0.69–1.18 , Cox regression , P = .45 , intention to treat analysis ) . No consistent significant effects on the other outcomes were seen . Subgroup analyses in subjects with low baseline 25-hydroxyvitamin D yielded similar results . No serious side effects related to the intervention were recorded . CONCLUSIONS In subjects without vitamin D deficiency , vitamin D supplementation is unlikely to prevent progression from prediabetes to diabetes . Very large studies with inclusion of vitamin D-deficient subjects will probably be needed to show such a putative effect . This study tested if supplementation with  vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes ( T2DM ) OBJECTIVE Epidemiological data suggest low serum 25-hydroxyvitamin D3 ( 25-OH-D3 ) levels are associated with radiological progression of knee osteoarthritis ( OA ) . This study aim ed to assess whether vitamin D supplementation can slow the rate of progression . METHOD A 3-year , double-blind , r and omised , placebo-controlled trial of 474 patients aged over 50 with radiographically evident knee OA comparing  800 IU cholecalciferol daily with placebo . Primary outcome was difference in rate of medial joint space narrowing ( JSN ) . Secondary outcomes included lateral JSN , Kellgren & Lawrence grade , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain , function , stiffness and the Get up and Go test . RESULTS Vitamin D supplementation  increased 25-OH-D3 from an average of 20.7 ( st and ard deviation ( SD ) 8.9 ) μg/L to 30.4 ( SD 7.7 ) μg/L , compared to 20.7 ( SD 8.1 ) μg/L and 20.3 ( SD 8.1 ) μg/L in the placebo group . There was no significant difference in the rate of JSN over 3 years in the medial compartment of the index knee between the treatment group ( average -0.01 mm/year ) and placebo group ( -0.08 mm/year ) , average difference 0.08 mm/year ( 95 % confidence interval ( CI ) [ -0.14 - 0.29 ] , P = 0.49 ) . No significant interaction was found between baseline vitamin D levels and treatment effect . There were no significant differences for any of the secondary outcome measures . CONCLUSION Vitamin D supplementation did not slow the rate of JSN or lead to reduced pain , stiffness or functional loss over a 3-year period . On the basis of these findings we consider that vitamin D supplementation has no role in the management of knee OA 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 In a double-blind trial , 327 patients ( 57 men ) over 65 ( mean age 79.5 ) years received all possible combinations of calcium carbonate 3 g , vitamin D3 1000 iu , meth and ienone 2.5 mg and /or placebos daily for 9 months . The higher incidence of bone fractures in the placebo group was not significant . Serum calcium , phosphorus , creatinine , aspartate aminotransferase and alkaline phosphatase were followed : the greatest changes occurred with meth and ienone , which thus reduced osteoporotic activity and increased the muscular mass most effectively ; calcium carbonate had the poorest effect . Surprisingly , coronary mortality was higher among those taking all three active substances . With two treatments the increase was not significant , but when both the groups receiving a combination of any two of the treatments were compared with those taking only one or neither of these two treatments , a significant increase in coronary deaths was seen , most significant ( P less than 0.001 ) in those receiving vitamin D3 and meth and ienone CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867 BACKGROUND The 2009 KDIGO ( Kidney Disease : Improving Global Outcomes ) chronic kidney disease-mineral and bone disorder clinical practice guideline suggests correcting 25-hydroxyvitamin D3 ( 25[OH]D ) levels<30ng/mL in patients treated with maintenance hemodialysis  , but does not provide a specific treatment protocol . STUDY DESIGN 2-center , double-blind , r and omized , 13-week , controlled trial followed by a 26-week open-label study . SETTING & PARTICIPANTS 55 adult maintenance hemodialysis patients with 25(OH)D levels<30ng/mL were recruited from June 2008 through October 2009 . INTERVENTION Cholecalciferol , 25,000IU , per week orally versus placebo for 13 weeks , then 26 weeks of individualized cholecalciferol prescription based on NKF-KDOQI ( National Kidney Foundation-Kidney Disease Outcomes Quality Initiative ) guidelines . OUTCOMES Primary end point was the percentage of patients with 25(OH)D levels≥30ng/mL at 13 weeks . Secondary outcomes included the percentage of patients with normal calcium , phosphorus , and intact parathyroid hormone ( iPTH ) blood levels . Safety measures included incidence of hypercalcemia and hypervitaminosis D. MEASUREMENTS Blood calcium and phosphate were measured weekly ; iPTH , 25(OH)D , 1,25-dihydroxyvitamin D3 ( 1,25[OH]2D ) , and bone turnover markers , trimonthly ; fetuin A and fibroblast growth factor 23 ( FGF-23 ) serum levels and aortic calcification scores were determined at weeks 0 and 39 . RESULTS The primary end point significantly increased in the treatment group compared with the placebo group ( 61.5 % vs 7.4 % ; P<0.001 ) , as well as 1,25(OH)2D levels ( 22.5 [ IQR , 15 - 26 ] vs 11 [ IQR , 10 - 15]pg/mL ; P<0.001 ) and the proportion of patients achieving the target calcium level ( 76.9 % vs 48.2 % ; P=0.03 ) . Incidence of hypercalcemia and phosphate and iPTH levels were similar between groups . The second 26-week study phase did not significantly modify the prevalence of 25(OH)D level≥30ng/mL in patients issued from the placebo group . LIMITATIONS Small size of the study population . CONCLUSIONS Oral weekly administration of 25,000IU of cholecalciferol for 13 weeks is an effective , safe , inexpensive , and manageable way to increase 25(OH)D and 1,25(OH)2D levels in hemodialysis patients . Further evaluation of clinical end points is suggested STUDY OBJECTIVE To determine if calcitriol is an effective treatment in postmenopausal osteoporosis . DESIGN Double-blind , r and omized clinical trial of 2 years ' duration . SETTING University medical center with patients recruited by media announcements . PATIENTS Eighty-six postmenopausal women with vertebral compression fractures . INTERVENTIONS Patients were treated with calcitriol or placebo . Mean dose was 0.43 micrograms/d . Dietary calcium was 1000 mg/d ( 24.9 mmol/d ) . The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia . MEASUREMENTS AND MAIN RESULTS No significant differences between placebo and control groups were seen in the percent change in total body calcium ( 0.4 % + /- 1.0 compared with 0.0 % + /- 0.9 ) , single photon absorptiometry ( -0.5 % + /- 1.2 compared with -3.1 % + /- 0.9 ) or dual photon absorptiometry ( 0.0 % + /- 1.7 compared with -1.0 % + /- 2.2 ) . New fractures were seen in 16 % of the placebo group and 26 % of the calcitriol groups , so the difference in percent fractures was 10 % ( 95 % CI , -5.7 % to 25.7 % ) . Bone biopsies did not show changes in either group . The calcitriol group had significantly higher serum and urine calcium values , but renal function was not worse than in the placebo group . CONCLUSIONS Calcitriol is not an effective treatment for established postmenopausal osteoporosis 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 Summary The effect of equivalent oral doses of vitamin D3 600 IU/day , 4200 IU/week and 18,000 IU/month on vitamin D status was compared in a r and omized clinical trial in nursing home residents . A daily dose was more effective than a weekly dose , and a monthly dose was the least effective . Introduction It is assumed that equivalent daily , weekly or monthly doses of vitamin D3 equally influence vitamin D status . This was investigated in a r and omized clinical trial in nursing home residents . Methods The study was performed in ten nursing homes including 338 subjects ( 76 male and 262 female ) , with a mean age of 84 ( ± SD 6.3 years ) . They received oral vitamin D3 either 600 IU/day , or 4200 IU/week , or 18,000 IU/month or placebo . After 4 months , calcium was added during 2 weeks , 320 mg/day or 640 mg/day or placebo . Outcome : serum levels of 25-hydroxyvitamin D ( 25(OH)D ) , parathyroid hormone ( PTH ) and bone turnover markers . Statistical approach : linear multilevel analysis . Results At baseline , mean serum 25(OH)D was 25.0 nmol/L ( SD 10.9 ) , and in 98 % , it was lower than 50 nmol/L. After 4 months , mean serum 25(OH)D levels increased to 62.5 nmol/L ( after daily vitamin D3 69.9 nmol/L , weekly 67.2 nmol/L and monthly 53.1 nmol/L , P < 0.001 between groups ) . Median serum PTH levels decreased by 23 % ( p < 0.001 ) . Bone turnover markers did not decrease . Calcium supplementation had no effect on serum PTH and bone turnover . Conclusion Daily vitamin D was more effective than weekly , and monthly administration was the least effective OBJECTIVE Vitamin D deficiency is associated with an unfavorable metabolic profile in observational studies . The intention was to compare insulin sensitivity ( the primary end point ) and secretion and lipids in subjects with low and high serum 25(OH)D ( 25-hydroxyvitamin D ) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels . RESEARCH DESIGN AND METHODS Participants were recruited from a population -based study ( the Tromsø Study ) based on their serum 25(OH)D measurements . A 3-h hyperglycemic clamp was performed , and the participants with low serum 25(OH)D levels were thereafter r and omized to receive capsules of 20,000 IU vitamin D3 or identical-looking placebo twice weekly for 6 months . A final hyperglycemic clamp was then performed . RESULTS The 52 participants with high serum 25(OH)D levels ( 85.6 ± 13.5 nmol/L [ mean ± SD ] ) had significantly higher insulin sensitivity index ( ISI ) and lower HbA1c and triglycerides ( TGs ) than the 108 participants with low serum 25(OH)D ( 40.3 ± 12.8 nmol/L ) , but the differences in ISI and TGs were not significant after adjustments . After supplementation , serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants r and omized to vitamin D and 45 of 53 r and omized to placebo , respectively . At the end of the study , there were no statistically significant differences in the outcome variables between the two groups . CONCLUSIONS Vitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile BACKGROUND Vitamin D insufficiency , which is prevalent in older individuals , is associated with bone and muscle weakness and falls . OBJECTIVE We examined the effects of a weekly dose of 8400 IU vitamin D(3 ) on postural stability , muscle strength , and safety . DESIGN In this double-blind trial , subjects aged > or = 70 y with serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations < or = 20 but > or = 6 ng/mL were r and omly assigned to receive a weekly dose of 8400 IU  vitamin D(3 ) ( n = 114 ) or a placebo ( n = 112 ) . Mediolateral body sway with eyes open ( assessed with the AccuSway(PLUS ) platform ; Advanced Medical Technology Inc , Watertown , MA ) was the primary endpoint . Secondary endpoints included the short physical performance battery ( SPPB ) and serum 25(OH)D concentrations . An analysis of covariance model was used for treatment comparisons . Safety and tolerability were monitored . RESULTS Serum 25(OH)D concentrations rose significantly ( from 13.9 to 26.2 ng/mL , P < 0.001 ) in patients treated with 8400 IU vitamin D(3 ) but not in patients treated with the placebo . After 16 wk , neither mediolateral sway nor SPPB differed significantly between treatment groups . However , in the post hoc analysis of patients subgrouped by baseline sway ( > or = 0.46 compared with < 0.46 cm ) , treatment with 8400 IU vitamin D(3 ) significantly reduced sway compared with treatment with placebo ( P = 0.047 ) in patients with elevated baseline sway but not in patients with normal baseline sway . Adverse experiences and incidences of hypercalcemia , hypercalciuria , and elevated creatinine were similar with both treatments . In patients treated with 8400 IU vitamin D(3 ) , but not in placebo-treated patients , parathyroid hormone decreased significantly . CONCLUSIONS Weekly treatment with 8400 IU vitamin D(3 ) raised 25(OH)D concentrations in elderly , vitamin D-insufficient individuals . Treatment with 8400 IU vitamin D(3 ) did not reduce mediolateral sway significantly compared with treatment with placebo in this population , although in post hoc analysis , treatment with 8400 IU vitamin D(3 ) reduced sway in the subgroup of patients who had elevated sway at baseline . Weekly treatment with 8400 IU vitamin D(3 ) was well tolerated . This trial was registered at clinical trials.gov as NCT00242476 OBJECTIVE Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects . The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-st and ing stroke by vitamin D supplementation . METHODS Ninety-six elderly women with poststroke hemiplegia were followed for two years . Patients were r and omly assigned to one of the two groups , and 48 patients received 1,000 IU ergocalciferol daily , and the remaining 48 received placebo . The number of falls per person and incidence of hip fractures were compared between the two groups . Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study . RESULTS At baseline , serum 25-hydroxyvitamin D levels were in the deficient range ( < 10 ng/ml ) in all patients ; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels .  Vitamin D treatment accounted for a 59 % reduction in falls ( 95 % CI , 28 - 81 % ; p = 0.003 ) . There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group . Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period ( log-rank , p = 0.049 ) . CONCLUSION Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers , which may lead to decreased falls and hip fractures A r and omized double-blind controlled trial of the effect of vitamin D supplementation on the abilities of elderly hospital patients to carry out basic activities of daily life is described . Those patients included in the trial had plasma 25-hydroxyvitamin D concentrations which were low or low normal as judged by the normal range in young adults . After 2 to 9 months on the trial there was no significant difference in the performance of the control and treatment groups 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 BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) often have vitamin D deficiency , which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation . Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking . We therefore investigated whether vitamin D3 ( colecalciferol ) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections . METHODS We did a r and omised , double-blind , placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practice s and four Acute National Health Service Trust clinics in London , UK . Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block r and omisation . Participants and study staff were masked to treatment assignment . Co primary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection . Analysis was by intention to treat . A prespecified subgroup analysis was done to assess whether effects of the intervention on the co primary outcomes were modified by baseline vitamin D status . This trial is registered with Clinical Trials.gov , number NCT00977873 . FINDINGS 240 patients were r and omly allocated to the vitamin D3 group ( n=122 ) and placebo group ( n=118 ) . Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation ( adjusted hazard ratio 0·86 , 95 % CI 0·60 - 1·24 , p=0·42 ) or time to first upper respiratory infection ( 0·95 , 0·69 - 1·31 , p=0·75 ) . Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L ( 0·57 , 0·35 - 0·92 , p=0·021 ) , but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L ( 1·45 , 0·81 - 2·62 , p=0·21 ; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status ) . Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection ( pinteraction=0·41 ) . INTERPRETATION Vitamin D3 supplementation protected against moderate or severe exacerbation , but not upper respiratory infection , in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation . FUNDING UK National Institute for Health Research 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 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 OBJECTIVES To study the effect of alfacalcidol ( 1alpha(OH)D3 ) on fall risk in community-dwelling elderly men and women . DESIGN R and omized , double-blind , placebo-controlled intervention trial . SETTING Basel , Switzerl and . PARTICIPANTS Three hundred seventy-eight community-dwelling elderly ( 191 women/187 men ) . INTERVENTION Participants were r and omly assigned to receive 1 microg of alfacalcidol or matched placebo daily for 36 weeks . MEASUREMENTS Serum 25-hydoxyvitamin D3 ( 25(OH ) D,1,25-dihydroxyvitamin D3 ( D-hormone ) , and intact parathormone ( iPTH ) levels were measured using radioimmunoassay at baseline and every 12 weeks . Numbers of fallers and falls were assessed using a question naire during each study site visit . Dietary calcium intake was assessed at baseline using a food frequency question naire . RESULTS At baseline , participants had , on average , normal vitamin D and D-hormone serum levels . Over 36 weeks , alfacalcidol treatment was associated with fewer fallers ( odds ratio (OR)=0.69 , 95 % confidence interval (CI)=0.41 - 1.16 ) than placebo . In a post hoc subgroups analysis by medians of total calcium intake , this reduction reached significance in alfacalcidol-treated subjects with a total calcium intake of more than 512 mg/d ( OR=0.45 , 95 % CI=0.21 - 0.97 , P=.042 ) but not in those who consumed less than 512 mg/d ( OR=1.00 , 95 % CI= 0.47 - 2.11 , P=.998 ) . Alfacalcidol treatment was also , independent of total calcium intake , associated with a significant 37.9 % reduction in iPTH serum levels ( P<.0001 ) . No cases of clinical ly relevant hypercalcemia were observed . CONCLUSION Provided a minimal calcium intake of more than 512 mg/d , alfacalcidol treatment significantly and safely reduces number of fallers in an elderly community dwelling population 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 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 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 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 CONTEXT Vitamin D or calcium supplementation may have effects on  vascular disease and cancer .  OBJECTIVE Our objective was to investigate whether vitamin D or calcium supplementation affects mortality , vascular disease , and cancer in older people . DESIGN AND SETTING The study included long-term follow-up of participants in a two by two factorial , r and omized controlled trial from 21 orthopedic centers in the United Kingdom . PARTICIPANTS Participants were 5292 people ( 85 % women ) aged at least 70 yr with previous low-trauma fracture . INTERVENTIONS Participants were r and omly allocated to daily vitamin D(3 ) ( 800 IU ) , calcium ( 1000 mg ) , both , or placebo for 24 - 62 months , with a follow-up of 3 yr after intervention . MAIN OUTCOME MEASURES All-cause mortality , vascular disease mortality , cancer mortality , and cancer incidence were evaluated . RESULTS In intention-to-treat analyses , mortality [ hazard ratio ( HR ) = 0.93 ; 95 % confidence interval ( CI ) = 0.85 - 1.02 ] , vascular disease mortality ( HR = 0.91 ; 95 % CI = 0.79 - 1.05 ) , cancer mortality ( HR = 0.85 ; 95 % CI = 0.68 - 1.06 ) , and cancer incidence ( HR = 1.07 ; 95 % CI = 0.92 - 1.25 ) did not differ significantly between participants allocated vitamin D and those not . All-cause mortality ( HR = 1.03 ; 95 % CI = 0.94 - 1.13 ) , vascular disease mortality ( HR = 1.07 ; 95 % CI = 0.92 - 1.24 ) , cancer mortality ( HR = 1.13 ; 95 % CI = 0.91 - 1.40 ) , and cancer incidence ( HR = 1.06 ; 95 % CI = 0.91 - 1.23 ) also did not differ significantly between participants allocated calcium and those not . In a post hoc statistical analysis adjusting for compliance , thus with fewer participants , trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated , although all results remain nonsignificant . CONCLUSIONS Daily vitamin D or calcium supplementation did not affect mortality , vascular disease , cancer mortality , or cancer incidence 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 In a double-blind clinical trial on 49 patients with rheumatoid arthritis , calciferol was given in a dose of 100 000 IU per day for 1 year to 24 patients , while the remaining 25 received placebo .  Objective and subjective improvement was noted in 67 % of the calciferol group and in 36 % of the control group , while objective and subjective deterioration was noted in 4 % of the calciferol group and in 32 % of the control group . The mean values for sedimentation rate and a2-globulin decreased and the mean hemoglobin level increased in the calciferol group . The consumption of analgesics and antiinflammatory medicines  decreased significantly in the calciferol group and after 1 year morning stiffness had eased and h and strength had increased in this group 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 OBJECTIVES To determine the prevalence of hypovitaminosis D ( serum 25-hydroxyvitamin D<32 ng/mL ; HVD ) in a population of elderly veterans and conduct a preliminary assessment of the efficacy of supplementation with cholecalciferol in correcting HVD . DESIGN R and omized , double-blind , placebo-controlled clinical trial . SETTING Geriatric clinic at the Bruce W. Carter Veterans Affairs Medical Center , Miami , Florida . PARTICIPANTS Veterans aged 70 and older . INTERVENTION Oral cholecalciferol 2,000 IU daily or placebo for 6 months . MEASUREMENTS Serum calcium , 25-hydroxyvitamin D , parathyroid hormone , and 24-hour urinary calcium . RESULTS Of the 34 participants who completed the study , 62 % had HVD at baseline . In the treatment group , mean serum 25-hydroxyvitamin D level rose from 28.4±7.9 ng/mL at baseline to 42.7±10.5 ng/mL at the end of the trial , but levels remained less than 32 ng/mL in three of 17 ( 18 % ) of the participants . In the placebo group , the baseline level of 27.7±8.3 ng/mL remained unchanged ( 28.8±8.7 ng/mL ) . Supplementation did not alter serum or urinary calcium levels and did not result in any adverse events . CONCLUSION These initial observations suggest that , in older veterans  , cholecalciferol 2,000 IU daily for 6 months is generally safe and corrects HVD in most but not all individuals 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 AND PURPOSE It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients , which might increase their risk of hip fracture . We evaluated the efficacy of 1 alpha-hydroxyvitamin D3 [ 1 alpha (OH)D3 ] and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke . METHODS In a r and omized study , 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 microgram 1 alpha (OH)D3 daily ( treatment group , n = 30 ) or an inactive placebo ( placebo group , n = 34 ) for 6 months and were observed for this duration . Both groups received 300 mg of elemental calcium daily . The bone mineral density ( BMD ) and metacarpal index ( MCI ) in the second metacarpals were determined by computed x-ray densitometry . The incidence of hip fractures in these patients was recorded . RESULTS BMD on the hemiplegic side decreased by 2.4 % in the treatment group and 8.9 % in the placebo group ( P = .0021 ) , while BMD on the intact side increased by 3.5 % and decreased by 6.3 % in the treated and placebo groups , respectively ( P = .0177 ) . In the treatment group , the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before r and omization . This difference increased in the placebo group . We observed a similar improvement in MCI in the treatment group but not in the placebo group . Four patients in the placebo group suffered a hip fracture compared with none in the treatment group ( P = .0362 ) . CONCLUSIONS Treatment with 1 alpha (OH)D3 and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-st and ing stroke . Treatment also may improve these indices on the intact side Vitamin D recently has been proposed to play an important role in a broad range of organ functions , including cardiovascular ( CV ) health ; however , the CV evidence -base is limited . We prospect ively analyzed a large electronic medical records data base to determine the prevalence of vitamin D deficiency and the relation of vitamin D levels to prevalent and incident CV risk factors and diseases , including mortality . The data base contained 41,504 patient records with at least one measured vitamin D level . The prevalence of vitamin D deficiency ( ≤30 ng/ml ) was 63.6 % , with only minor differences by gender or age . Vitamin D deficiency was associated with highly significant ( p < 0.0001 ) increases in the prevalence of diabetes , hypertension , hyperlipidemia , and peripheral vascular disease . Also , those without risk factors but with severe deficiency had an increased likelihood of developing diabetes , hypertension , and hyperlipidemia . The vitamin D levels were also highly associated with coronary artery disease , myocardial infa rct ion , heart failure , and stroke ( all p < 0.0001 ) , as well as with incident death , heart failure , coronary artery disease/myocardial infa rct ion ( all p < 0.0001 ) , stroke ( p = 0.003 ) , and their composite ( p < 0.0001 ) . In conclusion , we have confirmed a high prevalence of  vitamin D deficiency in the general healthcare population and an association between vitamin D levels and prevalent and incident CV risk factors and outcomes . These observations lend strong support to the hypothesis that vitamin D might play a primary role in CV risk factors and disease . Given the ease of vitamin D measurement and replacement , prospect i ve studies of vitamin D supplementation to prevent and treat CV disease are urgently needed Purpose : Higher serum 25-hydroxyvitamin D ( 25(OH)D ) levels are reportedly associated with better survival in early-stage non – small cell lung cancer ( NSCLC ) . Therefore , whether vitamin D supplementation can improve the prognosis of patients with NSCLC was examined ( UMIN000001869 ) . Patients and Methods : A r and omized , double-blind trial comparing vitamin D supplements ( 1,200 IU/day ) with placebo for 1 year after operation was conducted . The primary and secondary outcomes were relapse-free survival ( RFS ) and overall survival ( OS ) , respectively . Prespecified subgroup analyses were performed with stratification by stage ( early vs. advanced ) , pathology ( adenocarcinoma vs. others ) , and 25(OH)D levels ( low , < 20 ng/mL vs. high , ≥20 ng/mL ) . Polymorphisms of vitamin D receptor ( VDR ) and vitamin D – binding protein ( DBP ) and survival were also examined . Results : Patients with NSCLC ( n = 155 ) were r and omly assigned to receive vitamin D ( n = 77 ) or placebo ( n = 78 ) and followed for a median of 3.3 years . Relapse and death occurred in 40 ( 28 % ) and 24 ( 17 % ) patients , respectively . In the total study population , no significant difference in either RFS or OS was seen with vitamin D compared with the placebo group . However , by restricting the analysis to the subgroup with early-stage adenocarcinoma with low 25(OH)D , the vitamin D group showed significantly better 5-year RFS ( 86 % vs. 50 % , P = 0.04 ) and OS ( 91 % vs. 48 % , P = 0.02 ) than the placebo group . Among the examined polymorphisms , DBP1 ( rs7041 ) TT and CDX2 ( rs11568820 ) AA/AG genotypes were markers of better prognosis , even with multivariate adjustment . Conclusions : In patients with NSCLC  , vitamin D supplementation may improve survival of patients with early-stage lung adenocarcinoma with lower 25(OH)D levels . Clin Cancer Res ; 24(17 ) ; 4089–97 . © 2018 AACR 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 . ) OBJECTIVES To examine the effect of 25-hydroxyvitamin D ( 25(OH)D ) levels recommended by Endocrine Society guidelines ( > 30 ng/mL ) on cognition in healthy older African-American women over 3 years . DESIGN R and omized , double-blind , placebo-controlled clinical trial . SETTING Bone Mineral Research Center at New York University Winthrop Hospital . PARTICIPANTS Healthy postmenopausal African American women aged 65 and older ( N=260 ; mean age 68.2 ± 4.9 ; 46 % college education or higher ) . INTERVENTION Half of the women were r and omized to receive vitamin D ( adjusted to achieve a serum level > 30 ng/mL ) with calcium ( diet and supplement total of 1,200 mg ) , and half were r and omized to receive placebo with calcium ( 1,200 mg ) . MEASUREMENTS Cognitive assessment s every 6 months using the Mini-Mental State Examination ( MMSE ) to detect cognitive decline . Mean MMSE scores were calculated over time for both groups . Those with MMSE scores less than 21 at baseline were excluded . RESULTS The average dose of vitamin D3 was 3,490 ± 1,465 IU per day , and average serum 25(OH)D at 3 years was 46.8 ± 1.2 ng/mL in the active group and 20.7 ± 1.1 ng/mL in the  placebo group . Serum 25(OH)D concentration was maintained at greater than 30 ng/mL in 90 % of the active group . Over the 3-year period , MMSE scores increased in both groups ( p < .001 ) , although change over time was not significantly different between the groups . No adverse events associated with vitamin D were observed . CONCLUSION There was no difference in cognition over time between older African-American women with serum concentrations of 25(OH)D of 30 ng/mL and greater than those taking placebo . There is no evidence to support vitamin D intake greater than the recommended daily allowance in this population for preventing cognitive decline . J Am Geriatr Soc 67:81 - 86 , 2019 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 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
target: In subgroup analyses , all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation ( P for interaction=0.04 ) ; neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality .
  CONCLUSIONS Vitamin D supplementation alone was not associated with  all cause mortality in adults compared with placebo or no treatment .
  Vitamin D supplementation reduced the risk of cancer death by 16 % .
  Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality .
background: OBJECTIVE To investigate whether vitamin D supplementation is associated with lower mortality in adults .