title: Does vitamin D supplementation of healthy Danish Caucasian girls affect bone turnover and bone mineralization? Effect of vitamin D supplementation on vitamin D status and bone turnover markers in young adults The necessity and safety of calcium and vitamin D in the elderly. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Effect of Supplementation with Vitamin D3 and Calcium on Quantitative Ultrasound of Bone in Elderly Institutionalized Women: A Longitudinal Study
   Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Calcium and cholecalciferol: effects of small supplements in normal men. Vitamin D supplementation in elderly nursing home residents increases 25(OH)D but not 1,25(OH)2D. Fortification of orange juice with vitamin D(2) or vitamin D(3) is as effective as an oral supplement in maintaining vitamin D status in adults. Estimation of the dietary requirement for vitamin D in healthy adolescent white girls. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. Double Blind Study on the Need for Vitamin D Supplementation in Prepubertal Children Body Size and Serum 25 Hydroxy Vitamin D Response to Oral Supplements in Healthy Older Adults Vitamin D3 and vitamin K1 supplementation of Dutch postmenopausal women with normal and low bone mineral densities: effects on serum 25-hydroxyvitamin D and carboxylated osteocalcin Effect of calcium and vitamin D supplementation on bone mineral density in women aged 65–71 years: a 3-year randomized population-based trial (OSTPRE-FPS) Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents Effects of Vitamin D and Calcium on Proliferation and Differentiation In Normal Colon Mucosa: a Randomized Clinical Trial Supplements of 20 microg/d cholecalciferol optimized serum 25-hydroxyvitamin D concentrations in 80% of premenopausal women in winter. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. The Effect of Season and Vitamin D Supplementation on Bone Mineral Density in Healthy Women: A Double-Masked Crossover Study
   Effects of Postmenopausal Hormone Replacement Therapy With and Without Vitamin D3 on Circulating Levels of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D A randomized, controlled lower leg growth study of vitamin D supplementation to healthy children during the winter season Vitamin D Status and Impact of Vitamin D3 and/or Calcium Supplementation in a Randomized Pilot Study in the Southeastern United States Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Vitamin D Supplementation and Fracture Incidence in Elderly Persons Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men. A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Estimation of the dietary requirement for vitamin D in free-living adults >=64 y of age. Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women. The response of elderly veterans to daily vitamin D3 supplementation of 2,000 IU: a pilot efficacy study. A randomized controlled trial of the effects of vitamin D on muscle strength and mobility in older women with vitamin D insufficiency. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Plasma Vitamin D and 25OHD Responses of Young and Old Men to Supplementation with Vitamin D3 Does daily vitamin D 800 IU and calcium 1000 mg supplementation decrease the risk of falling in ambulatory women aged 65-71 years? A 3-year randomized population-based trial (OSTPRE-FPS). Prediction of bone mass density variation by bone remodeling markers in postmenopausal women with vitamin D insufficiency treated with calcium and vitamin D supplementation. How Much Vitamin D3 Do the Elderly Need? Estimation of the dietary requirement for vitamin D in healthy adults.
abstract: INTRODUCTION A high peak bone mass may be essential for reducing the risk of osteoporosis later in life and a sufficient vitamin D level during puberty may be necessary for optimal bone accretion and obtaining a high peak bone mass . Dietary intake and synthesis during winter of vitamin D might be limited but the effect of vitamin D supplementation in adolescence on bone mass is not well established . OBJECTIVE To investigate the effect of supplementation with 5 and 10 microg/day vitamin D(3 ) for 12 months in 11- to 12-year-old girls on  bone mass and bone turnover as well as the possible influence of VDR and ER genotype on the effect of the supplementation . METHODS The girls ( n=221 ) were r and omized to receive either 5 microg or 10 microg vitamin D(3 ) supplementation per day or placebo for 12 months . Whole body and lumbar spine bone mass measured by DXA and pubertal status were determined at baseline and after 12 months whereas physical activity and dietary intake of calcium and vitamin D were assessed at baseline . Serum ( S ) 25-hydroxyvitamin D ( 25OHD ) , S-osteocalcin , S-parathyroid hormone , S-calcium , S-inorganic phosphate , urinary ( U ) pyridinoline ( Pyr ) and deoxpyridinoline ( Dpyr ) were measured at baseline and after 6 and 12 months . RESULTS The S-25OHD concentration increased ( p<0.001 ) relative to the baseline values in the groups receiving either 5 microg/day ( mean+/-SD ; 11.0+/-10.3 nmol/l , baseline 41.9+/-17.6 nmol/l ) or 10 microg/day ( 13.3+/-11.8 nmol/l , baseline 44.4+/-16.6 nmol/l ) vitamin D(3 ) for 12 months compared to placebo ( -3.1+/-9.8 nmol/l , baseline 43.4+/-17.1 nmol/l ) . There was no effect of vitamin D-supplementation on biomarkers for bone turnover or on whole body or spine bone mineral augmentation . However , vitamin D supplementation increased whole body bone mineral density ( BMD ) ( p=0.007 ) and bone mineral content ( BMC ) ( p=0.048 ) in the FF VDR genotype but not in the Ff or ff VDR genotypes . CONCLUSION Supplementation with vitamin D ( 5 or 10 microg/day ) over 12 months increased the S-25OHD concentration but there was no effect on indices of bone health in the entire group of girls . However , there was an effect on BMD for a subgroup with the FF VDR genotype indicating an influence of genotype Objective : To assess the vitamin D status of healthy young people living in Northern Irel and and the effect of vitamin D supplementation on vitamin D status and bone turnover . Design : Double-blinded r and omised controlled intervention study . Setting : University of Ulster , Coleraine , Northern Irel and .Subjects : In total , 30 apparently healthy students ( 15 male and 15 female subjects ) , aged 18–27 years , were recruited from the university , with 27 completing the intervention . Interventions : Subjects were r and omly assigned , to receive either 15 μg ( 600 IU ) vitamin D3 and 1500 mg calcium/day ( vitamin D group ) , or 1500 mg calcium/day ( control group ) for 8 weeks between January and March . Vitamin D status , bone turnover markers , serum calcium and parathyroid hormone concentrations were measured at baseline and post intervention . Results : At baseline , vitamin D status was low in both the vitamin D group ( 47.9 ( s.d . 16.0 ) ) and the control group ( 55.5 ( s.d . 18.6 ) nmol/l 25(OH)D ) . Post intervention vitamin D status was significantly higher in the vitamin D-treated group ( 86.5 ( s.d . 24.5 ) ) compared to the control group ( 48.3 ( s.d . 16.8 ) nmol/l ) ( P<0.0001 ) . There was no significant effect of supplementation on bone turnover markers or PTH concentrations . Conclusions : This study suggests that young adults in Northern Irel and do not consume an adequate daily dietary intake of vitamin D to maintain plasma vitamin D concentrations in the wintertime . A daily supplement of 15 μg vitamin D3 significantly increased vitamin D status in these individuals to levels of sufficiency . Achievement of an optimum vitamin D status among young adults may have future positive health implication The necessity and safety of an oral calcium ( Ca ) and vitamin D regimen was evaluated in a population of 66 independently living and 73 institutionalized elderly women over an 11-week winter period . The members of both groups were r and omly assigned into trial and control groups . Serum Ca , creatinine , and calcidiol levels were measured before and after the trial . The regimen consisted of 1.558 g of Ca and 45 micrograms ( equal to 1,800 IU ) of vitamin D administered daily in addition to the normal diet . The controls received no treatment . A majority of the elderly subjects living independently had ensured their Ca , and a quarter of them also their vitamin D intake on their own initiative . The mean serum calcidiol concentration before the trial was 24.1 nmol/L in the institutionalized and 38.5 nmol/L in the elderly subjects living independently ( P less than .001 ) . After the trial , serum calcidiol was 10.4 nmol/L in the institutionalized control subjects and had decreased ( P less than .001 ) in both control groups , but increased ( P less than .001 ) in both treatment groups . The safety indicators , serum Ca , creatinine , and calcidiol , did not indicate any group or individual side effect 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 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 BACKGROUND Indirect evidence suggests that optimal vitamin D status is achieved with a serum 25-hydroxyvitamin D [ 25(OH)D ] concentration > 75 nmol/L. OBJECTIVE We aim ed to determine the intake of vitamin D(3 ) needed to raise serum 25(OH)D to > 75 nmol/L. DESIGN The design was a 6-mo , prospect i ve , r and omized , double-blinded , double-dummy , placebo-controlled study of vitamin D(3 ) supplementation .  Serum 25(OH)D was measured by  radioimmunoassay . Vitamin D(3 ) intake was adjusted every 2 mo by use of an algorithm based on serum 25(OH)D concentration . RESULTS A total of 138 subjects entered the study . After 2 dose adjustments , almost all active subjects attained concentrations of 25(OH)D > 75 nmol/L , and no subjects exceeded 220 nmol/L. The mean ( + /-SD ) slope at 9 wk [ defined as 25(OH)D change/baseline dose ] was 0.66 + /- 0.35 (nmol/L)/(microg/d ) and did not differ statistically between blacks and whites . The mean daily dose was 86 microg ( 3440 IU ) . The use of computer simulations to obtain the most participants within the range of 75 - 220 nmol/L predicted an optimal daily dose of 115 microg/d ( 4600 IU ) . No hypercalcemia or hypercalciuria was observed . CONCLUSIONS Determination of the intake required to attain serum 25(OH)D concentrations > 75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations . Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d ( 3800 IU ) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d ( 5000 IU ) for those below that threshold Abstract : Supplementation of elderly institutionalized women with vitamin D and calcium  decreased hip fractures and increased hip bone mineral density . Quantitative ultrasound ( QUS ) measurements can be performed in nursing homes , and easily repeated for follow-up . However , the effect of the correction of vitamin D deficiency on QUS parameters is not known . Therefore , 248 institutionalized women aged 62–98 years were included in a 2-year open controlled study . They were r and omized into a treated group ( n = 124 ) , receiving 440 IU of vitamin D3 combined with 500 mg calcium ( 1250 mg calcium carbonate , Novartis ) twice daily , and a control group ( n = 124 ) . One hundred and three women ( 42 % ) , aged 84.5 ± 7.5 years , completed the study : 50 in the treated group , 53 in the  controls  . QUS of the calcaneus , which measures BUA ( broadb and ultrasound attenuation ) and SOS ( speed of sound ) , and biochemical analysis were performed before and after 1 and 2 years of treatment . Only the results of the women with a complete follow-up were taken into account . Both groups had low initial mean serum 25-hydroxyvitamin D levels ( 11.9 ± 1.2 and 11.7 ± 1.2 mg/l ; normal range 6.4–40.2 mg/l ) and normal mean serum parathyroid hormone ( PTH ) levels ( 43.1 ± 3.2 and 44.6 ± 3.5 ng/l ; normal range 10–70 ng/l , normal mean 31.8 ± 2.3 ng/l ) . The treatment led to a correction of the metabolic disturbances , with an increase in 25-hydroxyvitamin D by 123 % ( p50.01 ) and a decrease in PTH by 18 % ( p50.05 ) and of alkaline phosphatase by 15 % ( p50.01 ) . In the controls there was a worsening of the hypovitaminosis D , with a decrease of 25-hydroxyvitamin D by 51 % ( p50.01 ) and an increase in PTH by 51 % ( p50.01 ) , while the serum calcium level decreased by only 2 % ( p5 0.01 ) . After 2 years of treatment BUA increased significantly by 1.6 % in the treated group ( p50.05 ) , and decreased by 2.3 % in the controls ( p50.01 ) . Therefore , the difference in BUA between the treated subjects and the controls ( 3.9 % ) was significant after 2 years ( p50.01 ) . However , SOS decreased by the same amount in both groups ( approximately 0.5 % ) . In conclusion , BUA , but not SOS , reflected the positive effect on bone of supplementation with calcium and vitamin D3 in a population of elderly institutionalized women BACKGROUND The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known , particularly within ranges comparable to the probable physiologic supply of the vitamin . OBJECTIVES The objectives were to establish the quantitative relation between steady state cholecalciferol input and the result ing serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores . DESIGN Cholecalciferol was administered daily in controlled oral doses labeled at 0 , 25 , 125 , and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha ( 41.2 degrees N latitude ) . The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment . RESULTS From a mean baseline value of 70.3 nmol/L , equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose , with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input . The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study ( ie , in the autumn ) was 12.5 micro g ( 500 IU)/d , whereas the total amount from all sources ( supplement , food , tissue stores ) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g ( approximately 3800 IU)/d . By difference , the tissue stores provided approximately 78 - 82 micro g/d . CONCLUSIONS Healthy men seem to use 3000 - 5000 IU cholecalciferol/d , apparently meeting > 80 % of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months . Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin The effect of small calcium and vitamin D supplements on mineral metabolism in normal persons is unclear . To investigate the biochemical response to these medications , we administered 1000 mg Ca and 25 micrograms cholecalciferol per day or a placebo to 92 normal men for 1 y. The Ca and cholecalciferol were tolerated well . 25-Hydroxycholecalciferol [ 25-(OH)D ] and 24,25-dihydroxycholecalciferol [ 24,25-(OH)2D ] levels rose in treated subjects ; there was no definite change in 1,25-(OH)2D concentrations . The average difference in 25-(OH)D levels between treated and untreated subjects was 30 nmol/L at 1 y. Fasting serum Ca , alkaline phosphatase , creatinine , and parathyroid hormone levels and the fasting urinary excretion of Ca , phosphorus and cAMP , were not affected . However , 24-h urinary Ca excretion was higher in the supplemented group ( 3.5 + /- 1.9 vs 4.7 + /- 1.7 mmol/d , p = 0.006 ) . Serum P concentrations were slightly higher in the supplemented group at 1 y. In normal men  small calcium and cholecalciferol supplements are safe , provide adequate vitamin D nutrition and apparently increase net gastrointestinal Ca absorption Vitamin D metabolism in elderly individuals can be compromised by several mechanisms . We previously described reduced concentrations of 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] in 30 % of elderly nursing home residents . The present study assesses the effect of vitamin D supplementation on 25-hydroxyvitamin D [ 25(OH)D ] and 1,25(OH)2D . We performed a double-blind study in which 30 elderly nursing home residents were r and omly given either 50 micrograms vitamin D or a placebo daily for 6 wk . Vitamin D metabolites , immunometrically assayed parathyroid hormone ( IRMA-PTH ) , ionized calcium , and bone Gla hormone ( BGP ) were measured in serum at baseline and biweekly for 6 wk . Serum 25(OH)D concentrations increased significantly ( P less than 0.0001 ) over the 6 wk in the treatment group but were unchanged in the placebo group . Serum 1,25(OH)2D , ionized calcium , BGP , and PTH were not significantly altered by the supplement . We conclude that vitamin D supplementation results in an increase in circulating 25(OH)D but not 1,25(OH)2D ; however , the long-term effect on bone mineral metabolism remains unclear BACKGROUND Vitamin D has been added to calcium-fortified orange juice . It is unknown whether vitamin D is as bioavailable from orange juice as it is from supplements . OBJECTIVES The objective was to compare the bioavailability of vitamin D(2 ) and vitamin D(3 ) from orange juice with that from vitamin D(2 ) and vitamin D(3 ) supplements . A secondary aim was to determine which form of vitamin D is more bioavailable in orange juice . DESIGN A r and omized , placebo-controlled , double-blind study was conducted in healthy adults aged 18 - 84 y ( 15 - 20/group ) who received 1000 IU vitamin D(3 ) , 1000 IU vitamin D(2 ) , or placebo in orange juice or capsule for 11 wk at the end of winter . RESULTS A total of 64 % of subjects began the study deficient in vitamin D ( ie , 25-hydroxyvitamin D [ 25(OH)D ] ) concentrations < 20 ng/mL ) . Analysis of the area under the curve showed no significant difference in serum 25(OH)D between subjects who consumed vitamin D-fortified orange juice and those who consumed vitamin D supplements ( P = 0.084 ) . No significant difference in serum 25(OH)D(3 ) was observed between subjects who consumed vitamin D(3)-fortified orange juice and vitamin D(3 ) capsules ( P > 0.1 ) . Similarly , no significant difference in serum 25(OH)D(2 ) was observed between subjects who consumed vitamin D(2)-fortified orange juice and vitamin D(2 ) capsules ( P > 0.1 ) . No significant overall difference in parathyroid hormone concentrations was observed between the groups ( P = 0.82 ) . CONCLUSION Vitamin D(2 ) and vitamin D(3 ) are equally bioavailable in orange juice and capsules BACKGROUND Knowledge gaps have contributed to considerable variation ( between 0 and 15 μg/d ) in international dietary recommendations for  vitamin D in adolescents . OBJECTIVE We aim ed to establish the distribution of dietary vitamin D required to maintain serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations above several proposed cutoffs ( 25 , 37.5 , 40 , and 50 nmol/L ) during wintertime in adolescent white girls . DESIGN Data ( baseline and 6 mo ) from 2 r and omized ,  placebo-controlled  , double-blind , 12-mo intervention studies in Danish ( 55 ° N ) and Finnish ( 60 ° N ) girls ( n = 144 ; mean age : 11.3 y ; mean vitamin D intake : 3.7 μg/d ) at vitamin D(3 ) supplementation amounts of 0 , 5 , and 10 μg/d were used . Serum 25(OH)D was measured with an HPLC assay in a central ized laboratory . RESULTS Clear dose-related increments ( P < 0.0001 ) in serum 25(OH)D with increasing supplemental vitamin D(3 ) were observed . The slope of the relation between vitamin D intake and serum 25(OH)D at the end of winter was 2.43 nmol ⋅ L(-1 ) ⋅ μg intake(-1 ) , and no difference in the slopes between Finnish and Danish girls was observed . The vitamin D intakes that maintained serum 25(OH)D concentrations at > 25 , > 37.5 , and > 50 nmol/L in 97.5 % of the sample were 8.3 , 13.5 , and 18.6 μg/d , respectively , whereas an intake of 6.3 μg/d maintained a serum 25(OH)D concentration > 40 nmol/L in 50 % of the sample . CONCLUSION The vitamin D intakes required to ensure that adequate vitamin D status [ defined variably as serum 25(OH)D > 25 and > 50 nmol/L ] is maintained during winter in the vast majority ( > 97.5 % ) of adolescent girls ( mean age : 11.3 y ) at northern latitudes ( > 55 ° N ) are 8.3 and 18.6 μg/d , respectively . This trial was registered at clinical trials.gov as NCT00267540 UNLABELLED This study of 9605 community-dwelling residents supports that vitamin D and calcium supplementation may prevent  osteoporotic fractures in elderly in a northern European region known to be deficient in vitamin D , especially during winter periods . INTRODUCTION We evaluated the effect of two programs for the prevention of osteoporotic fractures leading to acute hospital admission in a population of elderly community-dwelling residents . MATERIAL S AND METHODS This was a factorial , cluster-r and omized , pragmatic , intervention study . We included 9605 community-dwelling residents aged 66 + years . We offered a prevention program of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU ( 10 microg ) of vitamin D3 to a total of 4957 participants . Another program with evaluation and suggestions for the improvement of the domestic environment was offered to a total of 5063 participants . Both programs included revision of the resident 's current pharmaceutical treatment . We achieved information on osteoporotic fractures in the study population from the Danish Hospital Registration Data base . We defined osteoporotic fractures as low energy fractures of the proximal humerus , distal forearm , vertebral column , pelvis , cervical femur , and intertrochanteric femur . RESULTS Active participation was 50.3 % in the Calcium and Vitamin D Program and 46.4 % in the Environmental and Health Program . We observed a 16 % reduction in fracture incidence rate ( relative risk [ RR ] , 0.84 ; CI , 0.72 - 0.98 ; p < 0.025 ) among male and female residents offered the Calcium and Vitamin D Program ( intention-to-prevent analysis ) . CONCLUSIONS This study supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in community-dwelling elderly people in a northern European region known to be deficient in vitamin D , especially during winter periods ABSTRACT . Fifty‐one healthy prepubertal schoolchildren were followed for 13 months in a double blind study . Twenty‐four of them were supplemented with 400 IU of vitamin D2 5–7 times weekly , while 27 received a placebo . The children were examined in winter both at the beginning and at the end of the study , and in the middle of the study in autumn . Mean 25‐hydroxyvitamin D levels in the supplemented group were significantly higher than those in the placebo group both in autumn and in winter , when the study ended . The vitamin D supplementation did not , however , affect other vitamin D metabolites , serum calcium , albumin , inorganic phosphorus , parathyroid hormone concentrations or alkaline phosphatase activity . Moreover , the supplementation caused no alterations in the weight or height gain or bone mineral content of the distal radius of the children , and thus sub clinical rickets could not be shown Background : Vitamin D insufficiency is prevalent in the northeast United States . Since vitamin D insufficiency is readily amenable to supplementation , it is important to underst and what factors are associated with serum 25 hydroxy vitamin D ( 25(OH)D ) response to vitamin D supplementation . Objective : In this study we examined the association of serum 25(OH)D response to vitamin D supplementation with body size in a population of elderly subjects . Methods : 257 healthy , ambulatory men and women 65 years of age or older were r and omly assigned to treatment with either 700 IU/day ( 17.5 μg/d ) of supplemental vitamin D3 and 500 mg/day ( 12.5 mmol/d ) of supplemental calcium , or to placebo . Results : In multivariate regression analyses , after adjusting for baseline 25(OH)D , season , and sex , we found change in 25(OH)D to be inversely associated with baseline BMI ( p = 0.01 ) in subjects treated with supplements for one year . Change in 25(OH)D was also negatively associated with other baseline anthropometric measurements in these subjects . Conclusion : Our study implies that body size should be taken into account when estimating the amount of vitamin D intake needed to raise 25(OH)D to the desired level Objective : Improvement of vitamin D and K status of about 60 -y-old postmenopausal Dutch women . Design : In a r and omized study postmenopausal women with normal ( T-score > −1 ; n=96 ) and low ( T-score≤−1 ; n=45 ) bone mineral density ( BMD ) of the lumbar spine , were supplemented with 350–400 IU vitamin D3 , 80 μg vitamins K1 , vitamins K1+D3 , or placebo for 1 y. Serum 25-hydroxyvitamin D [ 25(OH)D ] and percentage carboxylated osteocalcin ( % carbOC ) were measured at baseline and after 3 , 6 and 12 months . Results : Baseline % carbOC of the entire study population was positively correlated with BMD of the lumbar spine and femoral neck . Correspondingly , women with low BMD had lower % carbOC at baseline than women with normal BMD but this difference disappeared after 1 y of supplementation with vitamin K1 ( ( mean±s.d . ) 68±11 % ( 95 % CI , 64.5–71.2 % ) vs 72±6 % ( 95 % CI , 70.1–72.9 % ) , respectively ) . One year of supplementation with vitamin D3 showed maximum increases in 25(OH)D of 33±29 % ( 95 % CI , 24.8–41.8 % ) and 68±58 % ( 95 % CI , 50.1–84.6 % ) in women with normal and low BMD , respectively . During winter , however , a 29 % decline in maximum 25(OH)D levels was not prevented in women with low BMD . Conclusion : Daily supplementation of Dutch postmenopausal women with > 400 IU vitamin D3 is indicated to prevent a winter decline in 25(OH)D and to control serum parathyroid hormone levels . Daily supplementation with 80 μg vitamin K1 seems to be necessary to reach premenopausal % carbOC levels . A stimulatory effect of calcium and /or vitamin D on % carbOC can not be excluded . European Journal of Clinical Nutrition ( 2000 ) 54 , 626–631 Summary The Osteoporosis Risk Factor and Prevention-Fracture Prevention Study ( OSTPRE-FPS ) was a r and omized population -based open trial ( n = 593 ) . The supplementation group ( n = 287 ) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group ( n = 306 ) received neither supplementation nor placebo . Daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women . Introduction Vitamin D deficiency is common in the elderly , and vitamin D levels are associated with low bone mineral density ( BMD ) . The working hypothesis was that vitamin D and calcium supplementation could prevent bone loss in ambulatory postmenopausal women . Methods The OSTPRE-FPS was a r and omized population -based open trial with a 3-year follow-up in 3,432 women ( aged 66 to 71 years ) . A r and omly selected sub sample of 593 subjects underwent BMD measurements . The supplementation group ( n = 287 ) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group ( n = 306 ) received neither supplementation nor placebo . Results In the intention-to-treat analysis , total body BMD ( n = 362 ) increased significantly more in the intervention group than in the control group ( 0.84 % vs. 0.19 % , p = 0.011 ) . The BMD change differences at the lumbar spine ( p = 0.372 ) , femoral neck ( p = 0.188 ) , trochanter ( p = 0.085 ) , and total proximal femur ( p = 0.070 ) were statistically nonsignificant . Analyses in compliant women ( ≥80 % of use ) result ed in stronger and statistically significant effects at the total body and femoral regions . Conclusion Daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women with adequate nutritional calcium intake 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 To investigate the potential efficacy of calcium and vitamin D in reducing risk for colorectal neoplasms and to develop “ treatable ” phenotypic biomarkers of risk for colorectal neoplasms , we conducted a pilot , r and omized , double-blind , placebo-controlled , 2 × 2 factorial clinical trial to test the effects of these agents on cell cycle markers in the normal colorectal mucosa . Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with 2 g/day calcium and /or 800 IU/day vitamin D3 versus placebo over 6 months . Overall expression and distributions of p21waf1/cip1 ( marker of differentiation ) , MIB-1 ( marker of short-term proliferation ) , and hTERT ( marker of long-term proliferation ) in colorectal crypts in the normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis . In the calcium , vitamin D , and calcium plus vitamin D groups relative to the placebo , p21 expression increased by 201 % ( P = 0.03 ) , 242 % ( P = 0.005 ) , and 25 % ( P = 0.47 ) , respectively , along the full lengths of colorectal crypts after 6 months of treatment . There were no statistically significant changes in the expression of either MIB-1 or hTERT in the crypts overall ; however , the proportion of hTERT , but not MIB-1 , expression that extended into the upper 40 % of the crypts was reduced by 15 % ( P = 0.02 ) in the vitamin D plus calcium group relative to the placebo . These results indicate that calcium and vitamin D promote colorectal epithelial cell differentiation and may “ normalize ” the colorectal crypt proliferative zone in sporadic adenoma patients , and support further investigation of calcium and vitamin D as chemopreventive agents against colorectal neoplasms . ( Cancer Epidemiol Biomarkers Prev 2009;18(11):2933–41 The serum 25-hydroxyvitamin D [ 25(OH)D ] response to daily supplementation with 20 microg cholecalciferol ( D3 ) during winter in predominantly white premenopausal women living in Maine was measured and the effects of body composition and hormonal contraceptive use on baseline serum 25(OH)D concentrations and the response to supplementation were examined . A total of 112 women ( 22.2 + /- 3.7 y old ) received placebo from March 2005 until September 2005 when they were r and omized to receive either placebo or 20 microg/d D3 through February 2006 . Eighty-six women completed the study .  Actual mean D3 content of the supplements was 22 microg per capsule . In February 2005 the serum 25(OH)D concentration was 62.0 + /- 23.4 nmol/L ( mean + /- SD ) . Serum 25(OH)D concentrations increased by 35.3 + /- 23.2 nmol/L from February 2005 to February 2006 in the treatment group , significantly more than the 10.9 + /- 16.9 nmol/L increase in the placebo group . Treatment group , magnitude of summer increase in 25(OH)D , estrogen dose , and baseline serum 25(OH)D concentrations , but not body fat , were significant predictors of the 1-y change in 25(OH)D concentrations used to assess the magnitude of the response to supplementation . Daily supplementation with 20 microg D3 during winter achieved optimal 25(OH)D concentrations ( > or = 75 nmol/L ) in 80 % of participants , indicating that this dose is adequate to optimize vitamin D status in most young women in Maine UNLABELLED Dietary supplementation with vitamin K(1 ) , with vitamin D(3 ) and calcium or their combination , was examined in healthy older women during a 2-year , double-blind , placebo-controlled trial . Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius . INTRODUCTION The putative beneficial role of high dietary vitamin K(1 ) ( phylloquinone ) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind , placebo-controlled trial in healthy Scottish women > or = 60 years of age . MATERIAL S AND METHODS Healthy , nonosteoporotic women ( n = 244 ) were r and omized to receive either ( 1 ) placebo , ( 2 ) 200 microg/day vitamin K(1 ) , ( 3 ) 10 microg ( 400 IU ) vitamin D(3 ) plus 1000 mg calcium/day , or ( 4 ) combined vitamins K(1 ) and D(3 ) plus calcium . Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist , markers of bone turnover , and vitamin status . Supplementation effects were tested using multivariate general linear modeling , with full adjustment for baseline and potential confounding variables . RESULTS Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups . However , women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius . Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years , serum vitamin K(1 ) increased by 157 % ( p < 0.001 ) , the percentage of undercarboxylated osteocalcin ( % GluOC ) decreased by 51 % ( p < 0.001 ) , serum 25-hydroxyvitamin D [ 25(OH)D ] increased by 17 % ( p < 0.001 ) , and PTH decreased by 11 % ( p = 0.049 ) . CONCLUSIONS These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1 ) together with supplements of calcium plus moderate vitamin D(3 ) to enhance BMC at the ultradistal radius , a site consisting of principally trabecular bone . The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation UNLABELLED Bone metabolism follows a seasonal pattern with high bone turnover and bone loss during the winter . In a r and omized , open-label 2-year sequential follow-up study of 55 healthy adults , we found that supplementation with oral vitamin D3 and calcium during winter abolished seasonal changes in calciotropic hormones and markers of bone turnover and led to an increase in BMD . Supplementation with oral vitamin D3 and calcium during the winter months seems to counteract the effects of seasonal changes in vitamin D and thus may be beneficial as a primary prevention strategy for age-related bone loss . INTRODUCTION Bone metabolism follows a seasonal pattern characterized by high bone turnover and bone loss during winter . We investigated whether wintertime supplementation with oral vitamin D3 and calcium had beneficial effects on the circannual changes in bone turnover and bone mass . MATERIAL S AND METHODS This prospect i ve study comprised an initial observation period of 12 months ( " year 1 " ) , followed by an intervention during parts of year 2 . Fifty-five healthy subjects living in southwestern Germany ( latitude , 49.5 degrees N ) were r and omized into two groups : 30 subjects were assigned to the treatment group and received oral cholecalciferol ( 500 IU/day ) and calcium ( 500 mg/day ) during the winter months of year 2 ( October-April ) , while 25 subjects assigned to the control group obtained no supplements . Primary endpoints were changes in calciotropic hormones [ serum 25(OH)D , 1,25(OH)2D , and parathyroid hormone ] , markers of bone formation ( serum bone-specific alkaline phosphatase ) and of bone resorption ( urinary pyridinoline and deoxypyridinoline ) , and changes in lumbar spine and femoral neck BMD . RESULTS Forty-three subjects completed the study . During year 1 , calciotropic hormones , markers of bone turnover , and BMD varied by season in both groups . During the winter months of year 1 , bone turnover was significantly accelerated , and lumbar spine and femoral BMD declined by 0.3 - 0.9 % . In year 2 , seasonal changes in calciotropic hormones and markers of bone turnover were either reversed or abolished in the intervention group while unchanged in the control cohort . In the subjects receiving oral vitamin D3 and calcium , lumbar and femoral BMD increased significantly ( lumbar spine : + 0.8 % , p = 0.04 versus year 1 ; femoral neck : + 0.1 % , p = 0.05 versus year 1 ) , whereas controls continued to lose bone ( intervention group versus control group : lumbar spine , p = 0.03 ; femoral neck , p = 0.05 ) . CONCLUSIONS Supplementation with oral vitamin D3 and calcium during winter prevents seasonal changes in bone turnover and bone loss in healthy adults . It seems conceivable that annually recurring cycles of low vitamin D and mild secondary hyperparathyroidism during the winter months contributes , at least in part and over many years , to age-related bone loss . Supplementation with low-dose oral vitamin D3 and calcium during winter may be an efficient and inexpensive strategy for the primary prevention of bone loss in northern latitudes Abstract : Vitamin D status is known to be an important determinant of bone mineral density ( BMD ) . There is a significant seasonal variation in serum vitamin D , and some studies have reported an associated seasonal variation in BMD . The present study was devised to investigate whether a seasonal variation in BMD could be detected in healthy normal subjects , along with associated variations in serum parathyroid hormone ( PTH ) , intestinal calcium absorption and biochemical markers of bone turnover . A second aim was to investigate whether , if such variations were identified , they could be suppressed by vitamin D supplementation . The subjects were 70 healthy female volunteers ( mean age 47.2 years , range 24–70 years ) recruited into a double-masked crossover study and followed over 2 years . During the first year 35 subjects received a daily oral supplement containing 800 IU ( 20 mg ) cholecalciferol ( group 1 ) and 35 subjects received a placebo preparation ( group 2 ) . During the second year the treatment each group received was reversed . Lumbar spine ( L1–L4 ) , left proximal femur and total body BMD were measured by DXA at 3-month intervals . Serum 25-hydroxyvitamin D ( 25-OHD ) , serum PTH , bone markers ( bone-specific ALP ( BSAP ) and urinary crosslinks ( DYPD/creatinine ) ) and calcium absorption were also measured at each visit . Cholecalciferol treatment increased serum 25-OHD by 25.4 nmol/l ( p < 0.001 ) , while a reciprocal decrease in serum PTH of 6.6 ng/l ( p = 0.011 ) was seen in subjects in the lowest quartile of baseline serum 25-OHD . The treatment had no significant effect on spine , femur or total body BMD , calcium absorption or bone markers . When Fourier analysis was used to analyze the data for seasonal effect ( defined as twice the amplitude of the 1-year period variation ) a highly significant effect for 25-OHD of 18 nmol/l ( p < 0.001 ) was found . However , no effect was found for BMD , PTH , calcium absorption or bone markers . The analysis set a 95 % confidence limit to the seasonal effect of less than 0.6 % for spine , total hip and total body BMD . It was concluded that in the population of healthy women studied there was no evidence of seasonal variation in spine , femur or total body BMD , serum PTH , calcium absorption or bone markers .  Vitamin D supplementation was found to have no effect on BMD Abstract . The effects of  postmenopausal hormone replacement therapy ( HRT ) and vitamin D3 on vitamin D metabolites ( 25OHD and 1,25(OH)2D ) were studied in a population -based prospect i ve 1-year study . The serum concentrations of intact parathyroid hormone ( PTH ) , calcium , and phosphate were also studied . A total of 72 women were r and omized into four treatment groups : HRT group ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ) , Vit D3 group ( vitamin D3 300 IU/day + calcium lactate 500 mg/day ) , HRT + Vit D3 group ( both above ) and placebo group ( calcium lactate 500 mg/day ) . Serum sample s were taken in March – April , when vitamin D formation from sunlight in Finl and is minimal after the dark winter . Serum concentrations of 25OHD increased in the Vit D3 group ( 33.5 % , P < 0.001 ) and in the HRT + Vit D3 group ( 38.2 % , P < 0.001 ) but had not changed significantly in the HRT and placebo groups at the 1-year follow-up examination . Serum concentrations of calcitriol ( 1,25(OH)2D ) increased , however , only in the HRT group ( 23.7 % , P < 0.05 ) , and remained unchanged in other groups . Serum concentrations of PTH decreased by 23.2 % ( P < 0.05 ) in the placebo group , but did not change significantly in the other three groups . The concentrations of serum calcium increased in the nonhormone groups ( P < 0.001 ) , whereas serum phosphate concentrations decreased in the hormone groups ( P < 0.05 and 0.001 ) . Our results confirm the positive effect of 1 year of HRT on serum calcitriol .  Vitamin D3 supplementation increased 25OHD concentrations , but did not affect calcitriol concentrations even though the initial levels were low . Interestingly , the combination of HRT and vitamin D3 did not increase serum calcitriol concentrations as much as HRT alone Background : The deceleration of longitudinal growth in children during winter occurs simultaneously with a decrease in the number of daylight hours and a reduction in vitamin D status . Due to worries about deleterious effects on bone of a relative insufficiency , vitamin D supplementation to healthy children has been suggested . Aim : To see whether supplementation of vitamin D to healthy children during winter affects seasonal growth . Subjects and methods : Twelve girls and eight boys aged 6.2 - 13.7 ( mean 9.8 ) years , all healthy , were enrolled in a double-blind , r and omized , placebo-controlled cross-over study with two 4-week treatment periods and 2-week run-in and wash-out periods . Vitamin D 3 600 IU was given in one tablet ABCDin ® daily .  Knemometry  of the right lower leg was performed on the first and last day of each period . Results : Lower leg growth rates ( mean - SEM ) during placebo and vitamin D 3 administration were identical : 0.28 - 0.04 mm per week ( p = 0.94 , t = 0.1 , 95 % CI : m 0.12 - 0.13 mm per week ) . Conclusion : Supplementation with vitamin D 3 600 IU day m 1 to healthy children during winter may not improve seasonal growth . Therefore , supplementation may not be recommended on the grounds of concerns about growth ; however firm conclusions await r and omized long-term studies Objective : Vitamin D supplementation may be required for certain subgroups in the United States in whom status and intake are inadequate , but the impact of various doses , and whether calcium administration jointly or independently influences vitamin D metabolite levels , is unclear . Methods : In a pilot chemoprevention trial of biomarkers of risk for colorectal adenoma , we measured the impact of vitamin D supplementation and /or calcium supplementation on plasma vitamin D metabolite concentrations . Ninety-two adult men and women living in the southeastern United States were r and omized to 800 IU vitamin D3 , 2000 mg elemental calcium , both , or placebo daily for 6 months . We examined vitamin D status at baseline and postintervention and compared the change in plasma 25-hydroxyvitamin D ( 25(OH)D ) and 1,25(OH)2D levels by intervention group using general linear models . Results : Eighty-two percent of the study population had insufficient plasma 25(OH)D concentrations ( < 75 nmol/L ) at baseline , with the lowest levels observed among African American participants . Vitamin D supplements , with or without calcium supplementation , raised plasma 25(OH)D concentrations , on average , by 25 to 26 nmol/L. Half of the study participants were classified as having sufficient 25(OH)D status after 6 months of 800 IU of vitamin D3 daily . Calcium alone did not influence 25(OH)D concentrations . Conclusion : In this southeastern U.S. population , half of the study participants receiving 800 IU vitamin D3 daily had blood 25(OH)D concentrations of ≤75 nmol/L after a 6-month intervention period , supporting higher vitamin D dose requirements estimated by some groups . More research is needed to identify the optimal vitamin D dose to improve 25(OH)D status in various at-risk population OBJECTIVES To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss  and whether rates of change in hard- and soft-tissue mass vary during the year . DESIGN Double-blind , placebo-controlled , 1-year trial in 249 women in which equal numbers of women were r and omized to either placebo or 400 IU of vitamin D daily . All women received 377 mg/d of supplemental calcium largely as calcium citrate malate . PATIENTS Healthy , ambulatory postmenopausal women with usual intakes of vitamin D of 100 IU/d . MEASUREMENTS Duplicate spine and whole-body scans were done by dual energy x-ray absorptiometry at 6-month intervals that were timed to periods when 25-hydroxyvitamin D levels were highest and lowest . Period 1 was June-July to December-January and period 2 was December-January to the next June-July . Serum parathyroid hormone and plasma 25-hydroxyvitamin D levels were measured during periods 1 and 2 . MAIN RESULTS In the placebo group , spinal bone mineral density increased in period 1 , decreased in period 2 , and sustained no net change . Women treated with vitamin D had a similar spinal increase in period 1 ( 1.46 % compared with 1.40 % in placebo ) , less loss in period 2 ( -0.54 % compared with -1.22 % , CI for the difference , 0.05 % to 1.31 % , P = 0.032 ) and a significant overall benefit ( 0.85 % compared with 0.15 % , CI for the difference , 0.03 % to 1.37 % , P = 0.04 ) . In period 2 , 25-hydroxyvitamin D levels were lower and parathyroid hormone levels were higher in the placebo than in the vitamin D group . Whole-body lean and fat tissue and bone mineral density varied during the year but did not change overall . CONCLUSIONS At latitude 42 degrees , healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily . A long-term benefit of preventing vitamin D insufficiency in the winter seems likely although it remains to be shown . Observed changes in bone as well as in fat and lean tissue appear to be related to season Calcium supplementation is effective in reducing blood pressure in various states of hypertension , including pregnancy-induced hypertension and preeclampsia . In addition , calcitropic hormones are associated with blood pressure . The hypothesis is that short-term therapy with calcium and vitamin D(3 ) may improve blood pressure as well as secondary hyperparathyroidism more effectively than calcium monotherapy . The effects of 8 weeks of supplementation with vitamin D(3 ) ( cholecalciferol ) and calcium on blood pressure and biochemical measures of bone metabolism were studied . The sample consisted of 148 women ( mean + /- SD age , 74 + /- 1 yr ) with a 25-hydroxycholecalciferol ( 25OHD(3 ) ) level below 50 nmol/L. They received either 1200 mg calcium plus 800 IU vitamin D(3 ) or 1200 mg calcium/day . We measured intact PTH , 25OHD(3 ) , 1,25-dihydroxyvitamin D(3 ) , blood pressure , and heart rate before and after treatment . Compared with calcium , supplementation with vitamin D(3 ) and calcium result ed in an increase in serum 25OHD(3 ) of 72 % ( P < 0.01 ) , a decrease in serum PTH of 17 % ( P = 0.04 ) , a decrease in systolic blood pressure ( SBP ) of 9.3 % ( P = 0.02 ) , and a decrease in heart rate of 5.4 % ( P = 0.02 ) . Sixty subjects ( 81 % ) in the  vitamin D(3 ) and calcium group compared with 35 ( 47 % ) subjects in the calcium group showed a decrease in SBP of 5 mm Hg or more ( P = 0.04 ) . No statistically significant difference was observed in the diastolic blood pressures of the calcium-treated and calcium- plus vitamin D(3)-treated groups ( P = 0.10 ) . Pearson coefficients of correlation between the change in PTH and the change in SBP were 0.49 ( P < 0.01 ) for the vitamin D(3 ) plus calcium group and 0.23 ( P < 0.01 ) for the calcium group . A short-term supplementation with vitamin D(3 ) and calcium is more effective in reducing SBP than calcium alone . Inadequate vitamin D(3 ) and calcium intake could play a contributory role in the pathogenesis and progression of hypertension and cardiovascular disease in elderly women UNLABELLED The effect of vitamin D supplementation on bone mineral augmentation in 212 adolescent girls with adequate calcium intake was studied in a r and omized placebo-controlled setting . Bone mineral augmentation determined by DXA increased with supplementation both in the femur and the lumbar vertebrae in a dose-responsive manner . Supplementation decreased the urinary excretion of resorption markers , but had no impact on formation markers . INTRODUCTION Adequate vitamin D intake protects the elderly against osteoporosis , but there exists no indisputable evidence that vitamin D supplementation would benefit bone mineral augmentation . The aim of this 1-year study was to determine in a r and omized double-blinded trial the effect of 5 and 10 microg vitamin D3 supplementation on bone mineral augmentation in adolescent girls with adequate dietary calcium intake . MATERIAL S AND METHODS Altogether , 228 girls ( mean age , 11.4 + /- 0.4 years ) participated . Their BMC was measured by DXA from the femur and lumbar spine . Serum 25-hydroxyvitamin D [ S-25(OH)D ] , intact PTH ( S-iPTH ) , osteocalcin ( S-OC ) , and urinary pyridinoline ( U-Pyr ) and deoxypyridinoline ( U-Dpyr ) were measured . Statistical analysis was performed both with the intention-to-treat ( IT ) and compliance-based ( CB ) method . RESULTS In the CB analysis , vitamin D supplementation increased femoral BMC augmentation by 14.3 % with 5 microg and by 17.2 % with 10 microg compared with the placebo group ( ANCOVA , p = 0.012 ) . A dose-response effect was observed in the vertebrae ( ANCOVA , p = 0.039 ) , although only with the highest dose . The mean concentration of S-25(OH)D increased ( p < 0.001 ) in the 5-microg group by 5.7 + /- 15.7 nM and in the 10-microg group by 12.4 + /- 13.7 nM , whereas it decreased by 6.7 + /- 11.3 nM in the placebo group . Supplementation had no effect on S-iPTH or S-OC , but it decreased U-DPyr ( p = 0.042 ) . CONCLUSIONS Bone mineral augmentation in the femur was 14.3 % and 17.2 % higher in the groups receiving 5 and 10 microg of vitamin D , respectively , compared with the placebo group , but only 10 mug increased lumbar spine BMC augmentation significantly . Vitamin D supplementation decreased the concentration of bone resorption markers , but had no impact on bone formation markers , thus explaining increased bone mineral augmentation . However , the positive effects were noted with the CB method but not with IT 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 Vitamin D deficiency is common in elderly persons , especially those with hip fracture [ 1 , 2 ] . It is caused by low exposure to sunshine , decreased synthesis of vitamin D3 in the aging skin , and a diet low in vitamin D [ 3 , 4 ] . The mean vitamin D intake in elderly persons in the Netherl and s is about 100 IU/d , half that of elderly persons in the United States [ 5 ] . Most of this vitamin D comes from margarine , which is the only vitamin D-supplemented food in the Netherl and s ( 3 IU/g ) . In vitamin D deficiency , the low serum concentration of 25-hydroxyvitamin D [ 25(OH)D ] leads to a low 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] concentration and then to a higher serum parathyroid hormone concentration , especially in the winter [ 6 - 10 ] . Histologically , the increased parathyroid activity is associated with high bone turnover , leading to cortical bone loss and low density bone [ 5 , 11 ] , which may lead to hip fracture . We previously studied the effects of vitamin D supplementation in residents of a home for the elderly and residents of a nursing home [ 10 ] .  Vitamin D3 , 400 IU/d , led to an adequate increase of the serum 25(OH)D concentration , to a small but significant increase of the serum 1,25(OH)2D concentration , and to a decrease of the serum concentration of intact parathyroid hormone . It was recently observed [ 12 , 13 ] that bone mineral density at the hip is positively related to serum 25(OH)D concentration in postmenopausal and elderly women . Therefore , it might be expected that vitamin D supplementation would increase bone mineral density in elderly persons deficient in vitamin D. In line with this expectation , it was shown that vitamin D supplementation prevented bone loss from the spine during the winter in postmenopausal women [ 14 ] . These results suggest that vitamin D supplementation may reduce the incidence of hip fractures , because bone strength shows a strong correlation with bone mineral density [ 15 ] . However , increasing bone mineral density through a therapeutic intervention does not necessarily lead to increased bone strength , as has been shown with sodium fluoride [ 16 ] . Bone structure and bone quality are also determinants of bone strength [ 17 ] , and falls are a risk factor for hip fractures [ 18 ] . Therefore , hip fracture should be the outcome criterion in studies on the effect of vitamin D supplementation . Intervention studies on the prevention of osteoporotic fractures necessitate large numbers of patients , because the outcome has an annual incidence of 0.5 % to 4 % in the elderly population [ 19 ] . We report the results of a large-scale , prospect i ve study on the effect of vitamin D supplementation on the incidence of hip and other osteoporotic fractures . Methods Participants The study included 2578 persons ( 1916 women and 662 men ) 70 years of age and older ( mean age SD , 80 6 years ; range , 70 to 97 years ) . Participants were recruited from general practitioners , from apartment houses for elderly persons , and from homes for elderly persons in Amsterdam and its vicinity . Persons recruited from practitioners were living independently ; those recruited from apartment houses and homes were receiving some care , but less than they would have received in a nursing home . Participants had to be reasonably healthy and able to give informed consent . Persons with a history of hip fracture or total hip arthroplasty , known hypercalcemia , sarcoidosis , or recent urolithiasis ( < 5 years earlier ) were excluded . Patients who had diseases or who used medications that influence bone metabolism ( such as thyroid disease or glucocorticoid medication ) were not excluded . The spontaneous use of vitamin D supplements and multivitamins was discouraged , but the prescription practice s of the general practitioners were not altered . All vitamin use was carefully documented . The study was approved by the Ethical Review Board of the Vrije Universiteit Hospital , and all participants gave informed consent . Study Design After checking the inclusion and exclusion criteria and obtaining informed consent , the participants were r and omly assigned to receive either active treatment with vitamin D3 or placebo . The study was double-blind , and r and omization was done in blocks of 10 per general practice , apartment house , or home . R and omization lists were made using a computerized r and om-number generator . Lists in sealed envelopes were sent to the hospital pharmacy for assignment . Each participant took either one tablet per day that contained vitamin D3 , 400 IU , or one placebo tablet per day that was identical in appearance and taste to the vitamin tablet . After enrollment , the participants received the first container of tablets ( 210 tablets ) . The container was replaced every 6 months with a full container . All participants were also advised in writing to consume at least three servings of dairy products per day ( for example , 1 glass of milk , 1 cup of yogurt , and 1 slice of cheese ) to ensure a calcium intake of at least 800 to 1000 mg/d . The study was started in August 1988 . The last participant was enrolled in December 1990 , and all participants had stopped using study medication by December 1993 . The follow-up period had been planned to last no more than 3 years , but because the number of hip fractures during the study was lower than expected , a 6-month extension was planned . The study participants thus received medication for 3 to 3.5 years ; those who received it for 3.5 years were those who consented to the 6-month extension . Total follow-up was to a maximum of 4 years . Data collected at baseline included an  outdoor activity score  ( 1 equals going outdoors less than once a week ; 2 equals going outdoors 1 or 2 times per week ; and 3 equals going outdoors 3 times per week or more ) and a score for sunshine exposure ( when outside : 1 equals in the shade as much as possible ; 2 equals sometimes in sunshine ; 3 equals much exposure to sunshine ) . These scores show a positive relation with serum 25(OH)D concentration [ 3 ] . Mobility was estimated by a walking score that ranged from 1 ( unable to walk ) to 5 ( walks independently a fair distance on any surface ) [ 20 ] . The dietary calcium intake from dairy products was estimated in a subset of 348 women by using a question naire , as described previously [ 21 ] . The participants were evaluated annually with a question naire on hip fractures , other peripheral fractures , outdoor score , sunshine exposure score , use of vitamin supplements , and walking score . Each general practitioner or caretaker was asked to immediately report change of address , hip fracture , or death . Hip fracture and death were verified by the general practitioner . All participants were followed for the maximal period of 4 years if possible , even if they had stopped using the trial medication , had sustained a fracture , or had moved to another city . To investigate possible selection bias , 267 potential participants in a home for the elderly and its adjunct apartments ( all residents of the institution ) were studied for baseline characteristics , including age , sex , sunshine exposure score , outdoor score , walking score , and reasons for nonparticipation . Compliance was checked when the tablet containers were replaced ( every 6 months ) , by question naire ( every year ) , and by measurement of the serum 25(OH)D concentration . Serum 25(OH)D concentration was measured at baseline and after 1 year in 270 persons who participated in a sub study investigating the effect of vitamin D supplementation on bone mineral density and bone turnover variables . This sub study included a nonr and om sample of participants from several apartment houses and homes for the elderly and is described in detail elsewhere [ 21 ] . In the same sub study , dietary calcium intake from diary products was assessed . Serum 25(OH)D concentration was also estimated during the third year of the study in February and March in a r and om sample of 96 participants drawn from the remaining study population . These participants received a letter giving them an appointment within 10 days ; the blood sample s were drawn at home . Serum 25(OH)D concentration was measured by competitive protein binding assay after being purified by gradient high-pressure liquid chromatography . The intra- and interassay coefficients of variation were 5 % and 6 % , respectively [ 22 ] . Statistical Analysis Baseline data of the vitamin D group and the placebo group were compared using t-tests ( age , calcium intake ) , chi-square tests ( sex , residence ) , and Wilcoxon rank-sum tests ( scores ) . The serum 25(OH)D concentrations of both groups were compared using t-tests . Data on fractures and mortality were analyzed by survival analysis using log-rank tests , Cox proportional-hazards regression , and hazard rate ratios [ 23 ] . Hip fractures are presented using the Kaplan-Meier method . All participants were kept in the study as long as possible . The data were analyzed in two ways . The intention-to-treat analysis included all r and omly assigned participants for either the total follow-up period or until fracture , death , or loss to follow-up . The active treatment analysis included the participants as long as they stated that they were using the trial medication . Thus , the participants were included in the active treatment analysis until they stopped using the trial medication , regardless of whether a fracture occurred after they had stopped . Age , sex , and residence were added in both analyses as covariates to the Cox regression model . Because outdoor score , sunshine score , and walking score were interrelated ( correlation coefficients ranging from 0.21 to 0.59 ) and were likely to indicate general health or mobility , they were averaged over the years and added up to a sum score . For this purpose , the walking score was simplified ( 1 , 2 , or 3 equals 1 ; 4 equals 2 ; 5 equals 3 ) , because the lower walking scores applied to a few participants only . The result ing total score , ranging from 3 to 9 , was entered as a covariate in the model . The level of compliance ( weekly intake as reported on OBJECTIVES To study the effects of vitamin D supplementation in healthier population s of men . DESIGN : R and omized , controlled trial . SETTING General clinical research center . PARTICIPANTS Sixty-five healthy , community-dwelling men ( mean age+/-st and ard deviation=76+/-4 , range 65 - 87 ) . INTERVENTION Cholecalciferol ( 1,000 IU/d ) or placebo supplementation for 6 months ; all received 500 mg supplemental calcium . MEASUREMENTS Upper and lower extremity muscle strength and power , physical performance and activity , health perception , calcium and vitamin D intake , and biochemical assessment , including 25-hydroxyvitamin D ( 25OHD ) , parathyroid hormone ( PTH ) , and ionized calcium levels . RESULTS The levels of 25OHD increased and PTH decreased in the cholecalciferol group , whereas there were no significant changes in the control group ( P<.001 ) . Baseline 25OHD levels correlated with baseline single-leg stance time and physical activity score . Baseline PTH levels correlated with baseline 8-foot walk time and physical activity score . No significant difference in strength , power , physical performance , or health perception was found between groups . CONCLUSION The 25OHD or PTH levels correlated with physical activity and physical performance in older , community-dwelling men with normal 25OHD status . Vitamin D supplementation increased 25OHD levels and decreased PTH levels but did not increase muscle strength or improve physical performance or health perception in this group of healthy , older men . Further investigations of the effects of vitamin D supplementation should focus on individuals with low levels of vitamin Vitamin D has been shown to be an important immune system regulator . Vitamin D insufficiency during winter may cause increased susceptibility to upper respiratory tract infections ( URIs ) . To determine whether vitamin D supplementation during the winter season prevents or decreases URI symptoms , 162 adults were r and omized to receive 50 microg vitamin D3 ( 2000 IU ) daily or matching placebo for 12 weeks . A bi-weekly question naire was used to record the incidence and severity of URI symptoms . There was no difference in the incidence of URIs between the vitamin D and placebo groups ( 48 URIs vs. 50 URIs , respectively , P=0.57 ) . There was no difference in the duration or severity of URI symptoms between the vitamin D and placebo groups [ 5.4+/-4.8 days vs. 5.3+/-3.1 days , respectively , P=0.86 ( 95 % CI for the difference in duration -1.8 to 2.1 ) ] . The mean 25-hydroxyvitamin D level at baseline was similar in both groups ( 64.3+/-25.4 nmol/l in the vitamin D group ; 63.0+/-25.8 nmol/l in the placebo group ; n.s . ) . After 12 weeks , 25-hydroxyvitamin D levels increased significantly to 88.5+/-23.2 nmol/l in the vitamin D group , whereas there was no change in vitamin D levels in the placebo group . There was no benefit of vitamin D3 supplementation in decreasing the incidence or severity of symptomatic URIs during winter . Further studies are needed to determine the role of vitamin D in infection BACKGROUND Older adults may be more prone to developing vitamin D deficiency than younger adults . Dietary requirements for vitamin D in older adults are based on limited evidence . OBJECTIVE The objective was to establish the dietary intake of vitamin D required to maintain serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations above various cutoffs between 25 and 80 nmol/L during wintertime , which accounted for the effect of summer sunshine exposure and diet . DESIGN A r and omized , placebo-controlled , double-blind , 22-wk intervention was conducted in men and women aged > /=64 y ( n = 225 ) at supplemental levels of 0 , 5 , 10 , and 15 microg vitamin D(3)/d from October 2007 to March 2008 . RESULTS Clear dose-related increments ( P < 0.0001 ) in serum 25(OH)D were observed with increasing supplemental vitamin D(3 ) intakes . The slope of the relation between total vitamin D intake and serum 25(OH)D was 1.97 nmol . L(-1 ) . microg intake(-1 ) . The vitamin D intake that maintained serum 25(OH)D concentrations > 25 nmol/L in 97.5 % of the sample was 8.6 microg/d . Intakes were 7.9 and 11.4 microg/d in those who reported a minimum of 15 min daily summer sunshine exposure or less , respectively . The intakes required to maintain serum 25(OH)D concentrations of > 37.5 , > 50 , and > 80 nmol/L in 97.5 % of the sample were 17.2 , 24.7 , and 38.7 microg/d , respectively . CONCLUSION To ensure that the vitamin D requirement is met by the vast majority ( > 97.5 % ) of adults aged > /=64 y during winter , between 7.9 and 42.8 microg vitamin D/d is required , depending on summer sun exposure and the threshold of adequacy of 25(OH)D. This trial was registered at http://www.controlled-trials.com/IS RCT N20236112 as IS RCT N registration no. IS RCT N20236112 To examine the relation of the vitamin D status and the remaining estrogen activity with bone turnover and bone mineral density ( BMD ) in elderly women , BMD was measured at both hips using dual-energy X-ray absorptiometry and at the distal radius using single photon absorptiometry , in 330 healthy women aged 70 and over .  Vitamin D metabolites , sex hormone binding globulin ( SHBG ) , PTH(1 - 84 ) , osteocalcin , alkaline phosphatase , and hydroxyproline and calcium excretion in 2 h fasting urine were measured . Multiple linear regression was used to adjust for potential confounders . In 65 % of the women , serum 25(OH)D was below 30 nmol/l . Only values below a threshold for 25(OH)D were negatively related to serum PTH(1 - 84 ) ( p = 0.02 , threshold at 25 nmol/l ) and to osteocalcin levels ( p = 0.04 , threshold at 30 nmol/l ) . BMD of the femoral neck and trochanter was positively related to serum 25(OH)D ( left neck p = 0.001 ) with thresholds at 30 nmol/l whereas the distal radius was not ( p = 0.32 ) . Serum PTH was negatively related to BMD at all measurement sites ( all p < 0.001 ) . Serum SHBG , an inverse measure of estrogen activity , was positively related to osteocalcin levels ( p = 0.004 ) and the urinary hydroxyproline/creatinine ratio ( p = 0.002 ) and negatively related to the BMD of the trochanter ( left trochanter p = 0.02 ) and the distal radius ( p = 0.001 ) . We conclude that in elderly women , serum 25(OH)D levels below 30 nmol/l are associated with secondary hyperparathyroidism and increased bone turnover . SHBG is positively related to bone turnover . ( ABSTRACT TRUNCATED AT 250 WORDS 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 OBJECTIVES To evaluate the effects of vitamin D treatment on muscle strength and mobility in older women with vitamin D insufficiency . DESIGN One-year population -based , double-blind , r and omized , controlled trial . SETTING Perth , Australia ( latitude 32 ° S ) . PARTICIPANTS Three hundred two community-dwelling ambulant elderly women aged 70 to 90 with a serum 25-hydroxyvitamin D ( 25(OH)D ) concentration less than 24 ng/mL. INTERVENTION Vitamin D(2 ) 1,000 IU/d or identical placebo ; calcium citrate ( 1 g calcium/d ) in both groups . MEASUREMENTS Lower limb muscle strength and mobility as assessed using the Timed Up and Go Test ( TUAG ) . RESULTS At baseline , mean ± st and ard deviation serum 25(OH)D was 17.7 ± 4.2 ng/mL ; this increased to 24.0 ± 5.6 ng/mL in the vitamin D group after 1 year but remained the same in the placebo group . For hip extensor and adductor strength and TUAG , but not for other muscle groups , a significant interaction between treatment group and baseline values was noted . In those with baseline values in the lowest tertile , vitamin D  improved muscle strength and TUAG more than calcium alone ( mean ( st and ard error ) : hip extensors 22.6 % ( 9.5 % ) ; hip adductors 13.5 % ( 6.7 % ) , TUAG 17.5 % ( 7.6 % ) , P < .05 ) . Baseline 25(OH)D levels did not influence patient response to supplementation . CONCLUSION Vitamin D therapy was observed to increase muscle function in those who were the weakest and slowest at baseline . Vitamin D should be given to people with insufficiency or deficiency to improve muscle strength and mobility BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo .  Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P<0.001 ) . The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo .  Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people Objectives : This study was conducted to determine whether there are age differences in the plasma parent vitamin D and 25-hydroxyvitamin D ( 25OHD ) responses to eight weeks of supplementation with 20 μg/day of vitamin D3 . Methods : Twenty-five healthy young men ( age 18–35 ) and 25 healthy older men ( 62–79 ) were r and omly assigned to supplementation with 20 μg/day of vitamin D3 or to no intervention and followed for eight weeks . Plasma vitamin D3 was measured by high performance liquid chromatography and 25OHD was measured by competitive protein binding . Results : Both young and old men in the supplemented group had pronounced , rapid and similar increases in plasma vitamin D3 , whereas vitamin D3 concentrations were stable in the control group . By the end of the eight-week adaptation period , plasma vitamin D3 of young and old men had increased by 4.3 and 6.2 nmol/L respectively . In the supplemented group , mean 25OHD concentrations of both the young and old men increased during the study , and the magnitude of the change after eight weeks was nearly identical in the two age groups ( 22.5 and 22.1 nmol/L in the young and the old men , respectively ) . In the control group there was a modest decrease in 25OHD of both the young and old men . Conclusions : There appears to be no age-related impairment among men in the absorption or metabolism of 20 μg/day of vitamin D3 taken orally for at least eight weeks OBJECTIVE The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level . STUDY DESIGN The OSTPRE-FPS was a r and omized population -based open-trial with 3-year follow-up . The supplementation group ( n=1566 ) received daily cholecalciferol 800IU+calcium carbonate 1000 mg , while the  control group ( n=1573 ) received no supplementation or placebo .  A r and omly selected sub sample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements . MAIN OUTCOME MEASURE The occurrence of falls was the primary outcome of the study . The participants in the sub sample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year . RESULTS In the entire trial population ( ETP ) , there were 812 women with 1832 falls in the intervention group and 833 women with 1944 falls in the control group ( risk ratio was 0.98 , 95 % CI 0.92 - 1.05 , P=0.160 ) . The supplementation was not associated with single or multiple falls in the ETP . However , in the sub sample , multiple fall incidence decreased by 30 % ( odds ratio ( OR ) 0.70 , 95 % CI 0.50 - 0.97 , P=0.034 ) in the supplementation group . Further , the supplementation decreased the incidence of multiple falls requiring medical attention ( OR 0.72 , 95 % CI 0.53 - 0.97 , P=0.031 ) in the ETP . The mean compliance in the entire trial population was 78 % and in the sub sample 79 % . DISCUSSION Overall , the primary analysis showed no association between calcium and vitamin D supplementation and risk of falls . However , the results of a post hoc analysis suggested that there was a decreased risk of multiple falls requiring medical attention : this finding requires confirmation The aim of this study was to determine whether early changes in bone markers could predict long-term response in bone mineral density ( BMD ) after calcium ( 500 mg ) and vitamin D ( 400 IU ) supplementation twice daily in ambulatory elderly women with vitamin D insufficiency ( 25-hydroxyvitamin D , < 12 ng/ml ) . One hundred and ninety-two women ( mean age , 75 + /- 7 yr ) were r and omized to receive either the supplementation ( n = 95 ) or a placebo ( n = 97 ) in a double-blind , controlled clinical trial for 1 yr . In comparison with the placebo group , supplementation significantly increased BMD , normalized 25-hydroxyvitamin D and significantly decreased intact PTH and bone remodeling markers . The initial values of telopeptide cross-links were correlated with improvement in total body BMD [ urinary N-telopeptides ( NTX ) , r = 0.38 ; C-telopeptides ( CTX ) , r = 0.32 ; serum CTX , r = 0.28 ] , and the 3-month changes in the same markers were correlated with improvement in total body ( urinary N-telopeptides , r = -0.29 ; serum CTX , r = -0.26 ) and vertebral BMD ( CTX , r = -0.26 ; all P < 0.05 ) . We concluded that short-term changes in bone resorption markers can predict long-term variations in BMD in elderly women with vitamin D insufficiency receiving calcium  and vitamin D supplementation Background : Vitamin D insufficiency poses a problem in many parts of the world , the elderly being an especially vulnerable group . This insufficiency results from an inadequate amount of sunshine and a low dietary intake of vitamin D. Typically , insufficiency is accompanied with high intact parathyroid hormone , ( S-iPTH ) concentrations . Aims of the Study : We studied how serum 25-hydroxy vitamin D ( S-25-OHD ) concentrations respond to different doses of vitamin D3 supplementation . Secondly to determine the smallest efficient dose to maintain serum 25-OHD concentration above the insufficiency level . We also studied which dose would be efficient in decreasing S-iPTH concentration in these subjects . Subjects and Methods : Forty-nine 65- to 85-year-old women participated . The women were r and omly assigned into one of four groups receiving 0 ( placebo ) , 5 , 10 or 20 μg of vitamin D3 daily for 12 weeks . Fasting morning blood was drawn at the beginning of the study , and thereafter every second week . Calciotropic variables were assessed from serum and urine sample s. Results : The S-25-OHD concentration increased significantly ( p < 0.001 ) in all supplemented groups [ 5 μg : by 10.9 ( 8.5 ) nmol/L , 10 μg : by 14.4 ( 6.9 ) nmol/L , 20 μg : by 23.7 ( 11.9 ) nmol/L ] , whereas it decreased in the placebo group by 8.3 ( 13.2 ) nmol/L. Equilibrium in S-25-OHD concentration was reached in all groups after 6 weeks of supplementation at 57.7 ( 8.9 ) nmol/L , 59.9 ( 8.9 ) nmol/L and 70.9 ( 8.9 ) nmol/L in the groups with increasing vitamin D supplementation . The dose-response to supplementation decreased with increasing vitamin D status at baseline , r = −0.513 , p = 0.002 . S-iPTH tended to decrease in those with highest dose response to supplementation . Conclusions : A clear dose response was noted in S-25-OHD to different doses of vitamin D3 . The recommended dietary intake of 15 μg is adequate to maintain the S-25-OHD concentration around 40–55 nmol/L during winter , but if the optimal S-25-OHD is higher than that even higher vitamin D intakes are needed . Interestingly , subjects with lower vitamin D status at baseline responded more efficiently to supplementation than those with more adequate status BACKGROUND Knowledge gaps have contributed to considerable variation among international dietary recommendations for vitamin D. OBJECTIVE We aim ed to establish the distribution of dietary vitamin D required to maintain serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations above several proposed cutoffs ( ie , 25 , 37.5 , 50 , and 80 nmol/L ) during wintertime after adjustment for the effect of summer sunshine exposure and diet . DESIGN A r and omized , placebo-controlled , double-blind 22-wk intervention study was conducted in men and women aged 20 - 40 y ( n = 238 ) by using different supplemental doses ( 0 , 5 , 10 , and 15 microg/d ) of vitamin D(3 ) throughout the winter .  Serum 25(OH)D concentrations were measured by using enzyme-linked immunoassay at baseline ( October 2006 ) and endpoint ( March 2007 ) . RESULTS There were clear dose-related increments ( P < 0.0001 ) in serum 25(OH)D with increasing supplemental vitamin D(3 ) . The slope of the relation between  vitamin D intake and serum 25(OH)D was 1.96 nmol x L(-1 ) x microg(-1 ) intake . The vitamin D intake that maintained serum 25(OH)D concentrations of > 25 nmol/L in 97.5 % of the sample was 8.7 microg/d . This intake ranged from 7.2 microg/d in those who enjoyed sunshine exposure , 8.8 microg/d in those who sometimes had sun exposure , and 12.3 microg/d in those who avoided sunshine . Vitamin D intakes required to maintain serum 25(OH)D concentrations of > 37.5 , > 50 , and > 80 nmol/L in 97.5 % of the sample were 19.9 , 28.0 , and 41.1 microg/d , respectively . CONCLUSION The range of vitamin D intakes required to ensure maintenance of wintertime vitamin D status [ as defined by incremental cutoffs of serum 25(OH)D ] in the vast majority ( > 97.5 % ) of 20 - 40-y-old adults , considering a variety of sun exposure preferences , is between 7.2 and 41.1 microg/d
target: Inclusion of 95 % range in the model to account for inter-individual variability increased the predicted intake of vitamin D needed to maintain serum 25(OH)D ≥ 50 nmol/l to 930 IU/d .
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