A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study. The effect of high-dose vitamin D3 supplementation on bone mineral density in subjects with prediabetes Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study No significant effect on bone mineral density by high doses of vitamin D3 given to overweight subjects for one year Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence Factors Affecting Bone Loss in Female Endurance Athletes Vitamin D Supplementation and Fracture Incidence in Elderly Persons Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women Exercise and vitamin D in fall prevention among older women: a randomized clinical trial. Prevention of hip fractures by correcting calcium and vitamin D insufficiencies in elderly people. Estimation of the optimum dose of vitamin D for disease prevention in older people: Rationale, design and baseline characteristics of the BEST-D trial Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease [RETRACTED] Vitamin D3 and calcium to prevent hip fractures in elderly women. The Effect of High-Dose Vitamin D Supplementation on Calciotropic Hormones and Bone Mineral Density in Obese Subjects with Low Levels of Circulating 25-Hydroxyvitamin D: Results from a Randomized Controlled Study Calcium plus vitamin D supplementation and the risk of fractures. Positive effects of anabolic steroids, vitamin D and calcium on muscle mass, bone mineral density and clinical function after a hip fracture. A randomised study of 63 women. Vitamin D receptor gene polymorphisms are associated with the risk of fractures in postmenopausal women, independently of bone mineral density. Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women Investigation of Bone Health Subsequent to Vitamin D Supplementation in Children Following Burn Injury. An open-label trial comparing alendronate and alphacalcidol in reducing falls and hip fractures in disabled stroke patients. Hypovitaminosis D and 'functional hypoparathyroidism'-the NoNoF (Nottingham Neck of Femur) study.
BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year Summary The rationale of this study was to determine the effect of high-dose vitamin D3 supplementation on bone mineral density ( BMD ) .  Prediabetic males given vitamin D had significantly less reduction in BMD at the femoral neck compared to the controls . The clinical implication s of our findings require further investigation . Introduction Type 2 diabetes mellitus is associated with increased fracture risk , and recent studies show crosstalk between bone and glucose metabolism . Few studies have investigated the effect of vitamin D supplementation on the bone without additional calcium . In the present study , we aim ed to determine whether a high dose of vitamin D3 could improve bone mass density ( BMD ) in prediabetic subjects . Methods The current study was conducted as a secondary research on a previously performed trial , in which 511 subjects with prediabetes were r and omized to vitamin D3 ( 20,000 IU per week ) versus placebo for 5 years  . BMD was measured using dual-energy X-ray absorptiometry ( DEXA ) . Results Two hundred and fifty-six subjects were r and omized to vitamin D and 255 to placebo . Mean baseline serum 25-hydroxyvitamin D ( 25(OH)D ) level was 60 nmol/L. Two hundred and two and 214 in the vitamin D and placebo groups , respectively , completed BMD measurements , whereas one in each group was excluded due to use of bisphosphonates . Males given vitamin D had significantly less reduction in BMD at the femoral neck measurement site compared to the controls ( 0.000 versus − 0.010 g/cm2 , p = 0.008 ) . No significant differences between intervention groups were seen at the total hip measurement site , regarding both males and females . Conclusions Vitamin D3 supplementation alone may be beneficial in males with prediabetes , but confirmatory studies are needed 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 Summary In this post hoc analysis of the VITdAL-ICU study , an RCT in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml  , vitamin D3 did not have a significant effect on β-Crosslaps and osteocalcin . Introduction Observational studies have shown accelerated bone loss in ICU survivors . A reversible contributor is vitamin D deficiency . In a post hoc analysis of the VITdAL-ICU study , we evaluated the effect of high-dose vitamin D3 on the bone turnover markers ( BTM ) β-Crosslaps ( CTX ) and osteocalcin ( OC ) . Methods The VITdAL-ICU study was a r and omized , double-blind , placebo-controlled trial in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml who received placebo or high-dose vitamin D3 ( a loading dose of 540,000 IU and starting 1 month after the loading dose five monthly maintenance doses of 90,000 IU ) . In this analysis on 289 survivors ( 209 telephone , 80 personal follow-up visits )  , BTM were analyzed on days 0 , 3 , 7 , 28 , and 180 ; self-reported falls and fractures were assessed . Bone mineral density ( BMD ) was measured after 6 months . Results At baseline , CTX was elevated ; OC was low in both groups — after 6 months , both had returned to normal . There were no differences between groups concerning BTM , BMD , falls , or fractures . In linear mixed effects models , CTX and OC showed a significant change over time ( p < 0.001 , respectively ) , but there was no difference between the vitamin D and placebo group ( p = 0.688 and p = 0.972 , respectively ) . Conclusions Vitamin D supplementation did not have a significant effect on BTM . Further studies should assess the effectiveness of vitamin D  on musculoskeletal outcomes in ICU survivors Background In meta-analyses supplementation with vitamin D appears to reduce incidence of fractures , and in cross-sectional studies there is a positive association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and bone mineral density ( BMD ) . However , the effect of supplementation with high doses of vitamin D on BMD is more uncertain and could in theory have both positive and negative effects . Methods The study was a one year , double blind placebo-controlled intervention trial performed at the University Hospital of North Norway . 421 subjects , 21 - 70 years old , were included and 312 completed the study . The subjects were r and omized to vitamin D3 40.000 IU per week ( DD group ) , vitamin D3 20.000 IU per week ( DP group ) , or placebo ( PP group ) . All subjects were given 500 mg calcium daily . Serum 25(OH)D , osteoprotegrin ( OPG ) , receptoractivator of nuclear factor-kappaB lig and ( RANKL ) , and BMD at the lumbar spine and the hip were measured before and at the end of the study . Results At baseline the mean serum 25(OH)D levels were 58 nmol/L ( all subjects ) and increased to 141 and 100 nmol/L in the DD and DP groups , respectively . After one year , no significant differences were found between the three groups regarding change in BMD , serum OPG or RANKL . Conclusions Supplementation with high doses of vitamin D for one year does not appear to have a negative effect on  BMD in healthy subjects . In order to disclose a positive effect , subjects with low BMD and /or low serum 25(OH)D levels need to be studied . Trial registration The trial was registered at Clinical Trials.gov ( NCT00243256 ) INTRODUCTION Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D(3 ) have yielded conflicting results . The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D ( 25-OH D ) , bone turnover markers , bone mineral density ( BMD ) , radius bone loss and incidence of fracture in postmenopausal women . METHODS 669 postmenopausal women ( mean age : 62.2 years ) belonging to a population -based cohort were followed prospect ively for a median of 11.2 years . At baseline , 25-OH D levels , BMD , bone turnover markers and clinical risk factors of osteoporosis were assessed . BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs . RESULTS 73 % and 35 % of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention . 11 % of women had levels below 30 nmol/l . Serum 25-OH D correlated modestly with intact PTH ( r(2)=0.023 , p<0.0001 ) , but not with bone turnover markers or BMD at the hip and radius after adjustment for age . When levels of 25-OH D were considered as a continuous variable , there was no significant association between 25-OH D levels and radius BMD loss or fracture risk . After adjustment for age , there was no significant difference in incidence of fracture , BMD , radius BMD loss , bone turnover markers , grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75 , 50 or 30 nmol/l . CONCLUSIONS In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency , vitamin D status may not be an important determinant of bone health Background Osteoporosis is a major health problem , and the economic burden is expected to rise due to an increase in life expectancy throughout the world . Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk . As vitamin B12 and folate intake and status play a large role in homocysteine metabolism , it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration . Methods / Design The B-PROOF ( B-Vitamins for the PRevention Of Osteoporotic Fractures ) study is a r and omized double-blind placebo-controlled trial . The intervention comprises a period of two years , and includes 2919 subjects , aged 65 years and older , independently living or institutionalized , with an elevated homocysteine concentration ( ≥ 12 μmol/L ) . One group receives daily a tablet with 500 μg vitamin B12 and 400 μg folic acid and the other group receives a placebo tablet . In both tablets 15 μg ( 600 IU ) vitamin D is included . The primary outcome of the study is osteoporotic fractures . Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers , physical performance and physical activity including falls , nutritional intake and status , cognitive function , depression , genetics and quality of life . This large multi-center project is carried out by a consortium from the Erasmus MC ( Rotterdam , the Netherl and s ) , VUmc ( Amsterdam , the Netherl and s ) and Wageningen University , ( Wageningen , the Netherl and s ) , the latter acting as coordinator . Discussion To our best knowledge , the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population . We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013 . The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures . Trial Registration The B-PROOF study is registered with the Netherl and s Trial ( NTR NTR1333 ) and with Clinical Trials.gov ( NCT00696514 ) Background : Low bone mass leading to stress fractures is a well-known and yet unsolved problem among female athletes . Purpose : To quantify the rate of bone loss in healthy female athletes and investigate the effects of estrogen and vitamin K supplementation on bone loss . Study Design : Prospect i ve cohort study . Methods : We classified 115 female endurance athletes into amenorrheic , eumenorrheic , or estrogen-supplemented groups and r and omized them to receive either placebo or vitamin K1 . The bone mineral densities of the subjects ' femoral neck and lumbar spine were measured at baseline and after 2 years . Results : Bone mineral density in the lumbar spine remained constant , but bone density in the femoral neck had decreased significantly after 2 years in all three subgroups . The decrease was higher in amenorrheic ( —6.5 % ± 4.0 % ) than in eumenorrheic ( —3.2 % ± 4.1 % ) and estrogen-supplemented athletes ( —3.9 % ± 3.1 % ) . Supplementation with vitamin K did not affect the rate of bone loss . Conclusions : The rate of bone loss in all three subgroups of female athletes was unexpectedly high ; neither estrogen nor vitamin K supplementation prevented bone loss . Clinical Relevance : High-intensity training maintained over several years must be regarded in women as a risk factor for osteoporosis , and protocol s for optimal treatment should be developed 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 It has been reported that vitamin K supplementation effectively prevents fractures and sustains bone mineral density in osteoporosis . However , there are only limited reported data concerning the association between vitamin K nutritional status and bone mineral density ( BMD ) or fractures in Japan . The objectives were to evaluate the association between plasma phylloquinone ( K1 ) or menaquinone ( MK-4 and MK-7 ) concentration and BMD or fracture in Japanese women prospect ively . A total of 379 healthy women aged 30–88 years ( mean age , 63.0 years ) were consecutively enrolled .  Plasma K1 , MK-4 , MK-7 , and serum undercarboxylated osteocalcin ( ucOC ) concentrations , BMD , and incidence of vertebral fractures were evaluated . In stepwise multiple linear regression analyses , L2–4 BMD and a bone turnover marker , log K1 , concentrations were independently correlated with vertebral fracture incidence . When subjects were divided into low and high K1 groups by plasma K1 concentration , the incidence of vertebral fracture in the low K1 group ( 14.4 % ) was significantly higher than that in the high K1 group ( 4.2 % ) , and its age-adjusted RR was 3.58 ( 95 % CI , 3.26–3.93 ) . L2–4 BMD was not different between the two groups . These results suggest that subjects with  vitamin K1 insufficiency in bone have increased susceptibility for vertebral fracture independently from BMD IMPORTANCE While vitamin D supplementation and exercise are recommended for prevention of falls for older people , results regarding these 2 factors are contradictory . OBJECTIVE To determine the effectiveness of targeted exercise training and vitamin D supplementation in reducing falls and injurious falls among older women . DESIGN , SETTING , AND PARTICIPANTS A 2-year r and omized , double-blind , placebo-controlled vitamin D and open exercise trial conducted between April 2010 and March 2013 in Tampere , Finl and . Participants were 409 home-dwelling women 70 to 80 years old . The main inclusion criteria were at least 1 fall during the previous year , no use of vitamin D supplements , and no contraindication to exercise . INTERVENTIONS Four study groups , including placebo without exercise , vitamin D ( 800 IU/d ) without exercise , placebo and exercise , and vitamin D ( 800 IU/d ) and exercise . MAIN OUTCOMES AND MEASURES The primary outcome was monthly reported falls . Injurious falls and the number of fallers and injured fallers were reported as secondary outcomes . In addition , bone density , physical functioning ( muscle strength , balance , and mobility ) , and vitamin D metabolism were assessed . RESULTS Intent-to-treat analyses showed that neither vitamin D nor exercise reduced falls . Fall rates per 100 person-years were 118.2 , 132.1 , 120.7 , and 113.1 in the placebo without exercise , vitamin D without exercise , placebo and exercise , and vitamin D and exercise study groups , respectively ; however , injurious fall rates were 13.2 , 12.9 , 6.5 , and 5.0 , respectively . Hazard ratios for injured fallers were significantly lower among exercisers with vitamin D ( 0.38 ; 95 % CI , 0.17 - 0.83 ) and without vitamin D ( 0.47 ; 95 % CI , 0.23 - 0.99 ) . Vitamin D maintained femoral neck bone mineral density and increased tibial trabecular density slightly . However , only exercise improved muscle strength and balance .  Vitamin D did not enhance exercise effects on physical functioning . CONCLUSIONS AND RELEVANCE The rate of injurious falls and injured fallers more than halved with strength and balance training in home-dwelling older women , while neither exercise nor vitamin D affected the rate of falls . Exercise improved physical functioning . Future research is needed to determine the role of vitamin D in the enhancement of strength , balance , and mobility . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00986466 For a 50-year old caucasian woman today , the risk of a hip fracture over her remaining lifetime is about 17 % . Tomorrow the situation will clearly be worse because the continual increase in life expectancy will cause a 3-fold rise in worldwide fracture incidence over the next 60 years , particularly in women , but also in men . In addition , a secular increase in the incidence of hip fractures in individuals of the same age has been noted in both sexes by several investigators , and the cost of hip fractures is expected to dramatically increase in the next decades . Consequently , preventive strategies are urgently required . A great deal has been learned in recent years about the risk factors for hip fracture , the pathophysiology of this fracture , and the prediction of fracture risk , particularly through bone mass measurements on the hip and biochemical evaluations of parathyroid and vitamin D status . The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility . A substantial femoral bone loss continues throughout the old age , with a continuous and exponential increase in the risk of hip fracture , and any reduction or arrest of this loss will induce an important reduction in the incidence of hip fractures . A preventive effect on the risk of hip fracture may be partly achieved by using long term estrogen replacement therapy after menopause , but also by using vitamin D and calcium supplements for a late prevention in elderly people .  Vitamin D insufficiency and deficit in calcium intake are very common in elderly people living either in institutions or at home , particularly in Europe where dairy products are not fortified with vitamin D. The cumulative response to this deficit in calcium intake and low vitamin D status is a negative calcium balance which stimulates parathyroid hormone secretion . In 300 residents of nursing homes , we recently found a significant negative correlation between serum 25 OHD and log serum PTH after age-adjustment . In addition , in 446 elderly women living at home in 5 French cities and selected from the voting lists , we also found an age-adjusted relationship between serum 25 OHD and PTH concentrations . This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements . We have shown in a 3-year controlled prospect i ve study that the daily use of these supplements ( 1.2 g of calcium and 800 IU of vitamin D3 ) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced of 23 % ( intention-to-treat analysis ) the number of hip fractures and other non vertebral fractures . In parallel , serum perathyroid hormone concentration was reduced of 28 % and low serum 25-hydroxyvitamin D concentration returned to normal values . After 18 months of treatment the bone density of the total proximal femoral region had increased 2.7 % the vitamin D3-calcium group and decreased 4.6 % in the placebo group ( p < 0.001 ) . This prevention is safe and can be recommended in people living in institutions . It could be also useful in other elderly subjects particularly at risk because of a low calcium intake , an absence of solar exposure and a previous history of falls . From the data of our study we assessed the economic consequences in terms of medical cost of this prevention . In case of treatment of all women living in nursing homes in France , this would saved FF 150000000 per year , the economic balance of prevention becoming positive as soon as the age of the beginning of the prevention reaches 73.5 years . It is now possible to partly stop bone loss in elderly people and it is never too late to prevent hip fractures with calcium and vitamin D supplements Highlights • The BEST-D ( Biochemical Efficacy and Safety Trial of vitamin D ) trial will compare the biochemical and other effects of daily dietary supplementation with 100 μg or 50 μg vitamin D3 or placebo , when administered for 12 months , in 305 ambulant community-dwelling older people living in Oxfordshire , Engl and .• The primary analyses will compare 12-month mean plasma concentrations of 25(OH)D as well as the proportion of participants with a 12-month concentration > 90 nmol/L between participants allocated 100 μg and participants allocated 50 μg daily . Secondary analyses will compare the two active doses ( both separately and when combined ) with placebo.• Additional end-points include biochemical assessment s of safety , blood pressure , arterial stiffness , falls , fractures , heel and wrist bone density , grip strength and physical performance and echocardiographic assessment s of cardiac function in a r and om sample of participants .• The results of this trial will help determine the optimum dose of vitamin D to test in a larger trial investigating whether vitamin D supplementation can reduce the risk of fractures , cardiovascular disease or cancer BACKGROUND There is a high incidence of hip fractures in patients with Parkinson disease ( PD ) .  Bone mineral density ( BMD ) is decreased in patients with PD , correlating with the immobilization-induced bone resorption and hypovitaminosis D with compensatory hyperparathyroidism . OBJECTIVE To evaluate the effectiveness of risedronate , an inhibitor of bone resorption , on osteoporosis and the risk of hip fractures in elderly men with PD . METHODS This was a 2-year , r and omized , double-blind , placebo-controlled trial . In a prospect i ve study of patients with PD , 121 patients received a daily dose of 2.5 mg risedronate and vitamin D2 1,000 IU for 2 years , and the remaining 121 received placebo and vitamin D2  1,000 IU . Incidence of hip fractures was compared between the two groups . RESULTS Nine patients sustained hip fractures in the placebo group , and three hip fractures occurred in the risedronate group . The relative risk of a hip fracture in the risedronate group vs the placebo group was 0.33 ( 95 % CI , 0.09 to 1.20 ) . BMD increased by 2.2 % in the risedronate group and decreased by 2.9 % in the placebo group ( p < 0.0001 ) . Urinary deoxypyridinoline , a bone resorption marker , decreased by 46.7 % in the risedronate group and by 33.0 % in the placebo group . CONCLUSION Treatment with risedronate and vitamin D2 increases bone mineral density in elderly men with Parkinson disease and reduces the risk of hip fractures BACKGROUND Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons .  Calcium and vitamin D supplements reduce this secondary hyperparathyroidism , but whether such supplements reduce the risk of hip fractures among elderly people is not known . METHODS We studied the effects of supplementation with vitamin D3 ( cholecalciferol ) and calcium on the frequency of hip fractures and other nonvertebral fractures , identified radiologically , in 3270 healthy ambulatory women ( mean [ + /- SD ] age , 84 + /- 6 years ) . Each day for 18 months , 1634 women received tricalcium phosphate ( containing 1.2 g of elemental calcium ) and 20 micrograms ( 800 IU ) of vitamin D3 , and 1636 women received a double placebo . We measured serial serum parathyroid hormone and 25-hydroxyvitamin D ( 25(OH)D ) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women . RESULTS Among the women who completed the 18-month study , the number of hip fractures was 43 percent lower ( P = 0.043 ) and the total number of nonvertebral fractures was 32 percent lower ( P = 0.015 ) among the women treated with vitamin D3 and calcium than among those who received placebo . The results of analyses according to active treatment and according to intention to treat were similar . In the vitamin D3-calcium group , the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months ( P < 0.001 ) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value ( P < 0.001 ) . The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group ( P < 0.001 ) . CONCLUSIONS Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women Low levels of 25-hydroxyvitamin D ( 25OHD ) are associated with increased bone turnover and risk of fractures . Plasma 25OHD is inversely related to body mass index , and vitamin D deficiency is common in obesity . We aim ed to determine whether vitamin D supplementation affects bone turnover and bone mineral density ( BMD ) in obese subjects . Fifty-two healthy obese men and women aged 18–50 years with plasma 25OHD levels below 50 nmol/L were r and omized to 7,000 IU of cholecalciferol daily or placebo for 26 weeks . We measured plasma levels of 25OHD , parathyroid hormone ( PTH ) , and markers of bone turnover , as well as BMD at the hip , spine , forearm , and whole body . Compared with placebo , treatment with cholecalciferol  increased mean plasma 25OHD from 35 to 110 nmol/L ( p < 0.00001 ) and significantly decreased PTH ( p < 0.05 ) . BMD increased significantly at the forearm by 1.6 ± 0.7 % ( p = 0.03 ) . The bone resorption marker C-terminal telopetide of type 1 collagen ( CTX ) decreased borderline significantly in the cholecalciferol group compared with the placebo group ( p = 0.07 ) . Changes in plasma 25OHD correlated inversely with changes in plasma levels of bone-specific alkaline phosphatase ( r = −0.38 , p = 0.01 ) and CTX ( r = −0.33 , p = 0.03 ) . Changes in CTX correlated inversely with changes in spine BMD ( r = −0.45 , p = 0.04 ) . Increasing circulating 25OHD levels by cholecalciferol treatment is of importance to bone health in young obese subjects as increased levels of 25OHD are associated with a decrease in both PTH and bone turnover and with an increase in BMD at the forearm BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo .  Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P<0.01 ) . Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . ) A total of 63 women who had an operation for a fracture of the hip was r and omly allocated to one year of treatment either with anabolic steroids , vitamin D and calcium ( anabolic group ) or with calcium only ( control group ) . The thigh muscle volume was measured by quantitative CT . The bone mineral density of the hip , femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound . Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did ( p<0.01 ) . There was less bone loss in the proximal tibia in the anabolic group than in the control group . The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months . Anabolic steroids , even in this moderate dose , given in combination with vitamin D and calcium had a beneficial effect on muscle volume , bone mineral density and clinical function in this group of elderly women CONTEXT Osteoporosis is a systemic disease with a strong genetic component . Vitamin D receptor ( VDR ) gene polymorphisms explain only a small part of the genetic influence on the level of bone mineral density ( BMD ) , whereas their effect on fracture remains uncertain . OBJECTIVE The objective of this study was to investigate the relationships between VDR genotypes  and fracture risk . DESIGN A prospect i ve population -based cohort was studied . SUBJECTS A total of 589 postmenopausal women ( mean age , 62 yr ) were followed prospect ively during a median ( interquartile ) of 11 ( 1.1 ) yr . MAIN OUTCOME MEASURE The study measured incidents of vertebral and nonvertebral fractures . RESULTS VDR allele B was significantly and dose dependently overrepresented in women who fractured , including 34 and 86 women with first incident vertebral and nonvertebral fragility fractures , respectively . This corresponded to an odds ratio of 1.5 ( 95 % confidence interval , 0.95 - 2.40 ) for heterozygous carriers ( bB , n = 286 ) and 2.10 ( 95 % confidence interval , 1.16 - 3.79 ) for homozygous carriers ( BB , n = 90 ) of the B allele , compared with women with the bb genotype ( n = 213 ) . VDR genotype groups did not differ for demographics , physical activity , grip strength , personal and maternal history of fracture , and calcium intake . The association was independent of BMD of the spine , hip , and radius , and of the BMD loss at the radius . The relationship between VDR polymorphisms and fracture risk was not altered after adjustment for baseline circulating levels of bone turnover markers , estradiol , dehydroepi and rosterone sulfate , SHBG , IGF-I , intact PTH , and 25 hydroxyvitamin D. CONCLUSION VDR genotypes are associated with the risk of fracture  in postmenopausal women independently of BMD , rate of postmenopausal forearm BMD loss , bone turnover , and endogenous hormones . The mechanisms by which VDR genotypes influence bone strength remain to be determined Alendronate decreases the risk of femoral neck fracture by suppressing bone turnover , and also decreases the serum total osteocalcin level . A low serum carboxylated osteocalcin level or high undercarboxylated osteocalcin level could be risk factors for femoral neck fracture . Vitamin K mediates the carboxylation of osteocalcin , but the effect of alendronate therapy with or without vitamin K2 supplementation remains unknown . Forty-eight postmenopausal women were enrolled in a 1-year prospect i ve r and omized trial and assigned to alendronate monotherapy ( 5 mg/day ) ( group A , n = 26 ) or vitamin K2 ( 45 mg/day ) plus alendronate ( 5 mg/day ) ( group AK , n = 22 ) . Bone mineral density was measured by dual-energy X-ray absorptiometry at 0 and 12 months ; bone turnover parameters were measured at 0 , 3 , and 12 months . Four patients discontinued alendronate therapy , and we analyzed the remaining 44 patients ( 23 in group A and 21 in group AK ) who completed 1 year of treatment . Alendronate decreased undercarboxylated osteocalcin ; carboxylated osteocalcin was not affected . Addition of vitamin K2 enhanced the decrease of undercarboxylated osteocalcin levels and led to a greater increase of femoral neck bone mineral density .  Alendronate monotherapy does not decrease carboxylation of osteocalcin , and combination of vitamin K2 and alendronate brings further benefits on both osteocalcin carboxylation and BMD of femoral neck in postmenopausal women with osteoporosis BACKGROUND The effect of supplemental vitamin D on fracture occurrence following burn injuries is unclear . The objective of this study was to evaluate postintervention incidence of fractures in children during the rehabilitative phase postburn ( PB ) following participation in a r and omized clinical trial of vitamin D supplementation . MATERIAL S AND METHODS Follow-up for fracture evaluation was obtained in 39 of 50 patients r and omized to daily enteral vitamin D2 , D3 , or placebo throughout the acute burn course .  Serum 25-hydroxyvitamin D , 1,25-dihydroxyvitamin D , D2 , D3 , calcitonin , and bone alkaline phosphatase ( BAP ) measurements were obtained PB day 7 , midpoint , discharge , and 1-year PB . Urinary calcium was obtained PB day 7 and midpoint . Dual-energy x-ray absorptiometry ( DXA ) was performed at discharge and 1-year PB . RESULTS Fractures were reported in 6 of 39 respondents . Four fractures occurred in the placebo group , 2 in the D2 group , and none in the D3 group . Serum vitamin D , calcitonin , BAP , and urinary calcium were similar between fracture groups . The group with fracture morbidity had larger burn size ( 83.8 % ± 4.9 % vs 53.0 % ± 2.9 % , P < .0001 ) , greater full-thickness burn ( 69.7 % ± 9.4 % vs 39.4 % ± 4.1 % , P = .02 ) , and increased incidence of inhalation injury ( 33 % vs 6 % , P = .04 ) . Decreased bone mineral density z score was noted at discharge in the placebo fracture compared with no-fracture group ( P < .05 ) . CONCLUSION This preliminary report suggests there may be benefit of vitamin D3 in reducing postdischarge fracture risk . Results reaffirm the importance of monitoring bone health in pediatric patients postburn Although vitamin D supplementation has been suggested to reduce the risk of falling in ambulatory or institutionalized elderly persons , no study has examined whether it reduces the frequency of falling in immobilized stroke patients who have immobilization-induced hypercalcemia reflecting increased bone resorption leading to inhibited renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Bisphosphonate is known to reduce immobilization-induced hypercalcemia by inhibiting bone resorption of calcium . This study compared the efficacy of 2 drugs in reducing the risk of falling in patients with long-st and ing stroke . Eighty-two elderly patients with poststroke hemiparesis were followed for 1 year . The patients were r and omly assigned to one of 2 groups ; 41 patients received alendronate 35 mg once weekly , and 41 patients received alphacalcidiol 1 μg daily . The number of falls per person and incidence of hip fracture in the 2 groups were compared . At baseline , all patients had a low serum 1 , 25-[OH]2D level  . Alphacalcidol therapy enhanced immobilization-induced hypercalcemia by increasing intestinal calcium absorption , leading to a reduction of serum 1 , 25-[OH]2D level , while alendronate therapy enhanced 1 , 25-[OH]2D production by decreasing hypercalcemia  . Alendronate treatment accounted for a 55 % reduction in falls ( 95 % confidence interval [CI]=25 - 72 % ; P=.0021 ) . During the 1-year study period , hip fracture occurred in 1 of 41 subjects in the alphacalcidol group and in no subjects in the alendronate  group . Bone mineral density was increased by 3.2 % in the alendronate group and decreased by 0.1 % in the alphacalcidol group ( P<.0001 ) . Alendronate therapy increased serum 1 , 25-[OH]2D levels by improving immobilization-induced hypercalcemia , which may lead to decreased falling and subsequent hip fractures BACKGROUND calcium and vitamin D deficiency are common in elderly people and lead to increased bone loss , with an enhanced risk of osteoporotic fractures . Although hip fractures are a serious consequence , few therapeutic measures are given for primary or secondary prevention . A combination of calcium and vitamin D may not be the most effective treatment for all patients . OBJECTIVE to investigate the effects of hypovitaminosis D on the calcium-parathyroid hormone endocrine axis , bone mineral density and fracture type , and the optimal role of combination calcium and vitamin D therapy after hip fracture in elderly patients . DESIGN a population -based , prospect i ve cohort study . METHODS 150 elderly subjects were recruited from the fast-track orthogeriatric rehabilitation ward within 7 days of surgery for hip fracture . This ward accepts people who live at home and are independent in activities of daily living . All subjects had a baseline medical examination , biochemical tests ( parathyroid hormone ,  25-hydroxyvitamin D  and  1,25-dihydroxyvitamin D ) and were referred for bone densitometry . RESULTS at 68 % , the prevalence of hypovitaminosis D ( 25-hydroxyvitamin D<30 nmol/l ) was high . However , only half the patients had evidence of secondary hyperparathyroidism , the rest having a low to normal level of parathyroid hormone ( ' functional hypoparathyroidism ' ) . Patients with secondary hyperparathyroidism and hypovitaminosis D had a higher mean corrected calcium , higher 1,25-dihydroxyvitamin D , lower hip bone mineral density and an excess of extracapsular over intracapsular fractures than the ' functional hypoparathyroid ' group ( P<0.01 ) . CONCLUSION there is a high prevalence of hypovitaminosis D in active , elderly people living at home who present with a hip fracture . However , secondary hyperparathyroidism occurs in only half of these patients . This subgroup attempts to maintain calcium homeostasis but does so at the expense of increased bone turnover , leading to amplified hip bone loss and an excess of extracapsular over intracapsular fractures .  Combination calcium and vitamin D treatment may be effective in preventing a second hip fracture in these patients , but its role in patients with hypovitaminosis D without secondary hyperparathyroidism and ' vitamin D-replete ' subjects needs further evaluation
For hip fracture , at a 15 % relative risk , the effect estimate lay between the futility boundary and the inferior boundary , meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount , but uncertainty remains as to whether it might increase hip fractures .
The effect estimate lay within the futility boundary at thresholds of 0·5 % for total hip , forearm , and total body bone mineral density , and 1·0 % for lumbar spine and femoral neck , providing reliable evidence that vitamin D does not alter these outcomes by these amounts .
INTERPRETATION Our findings suggest that vitamin D supplementation does not prevent fractures or falls , or have clinical ly meaningful effects on bone mineral density .
There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health .
BACKGROUND The effects of vitamin D on fractures , falls , and bone mineral density are uncertain , particularly for high vitamin D doses .
We aim ed to determine the effect of vitamin D supplementation on fractures , falls , and bone density .