Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. 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) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women. Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation Vitamin D Supplementation and Fracture Incidence in Elderly Persons Effect of vitamin D, calcium and multiple micronutrient supplementation on vitamin D and bone status in Bangladeshi premenopausal garment factory workers with hypovitaminosis D: a double-blinded, randomised, placebo-controlled 1-year intervention. Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. Vitamin D3 and calcium to prevent hip fractures in elderly women. Effect of vitamin D(3) and calcium on fracture risk in 65- to 71-year-old women: a population-based 3-year randomized, controlled trial--the OSTPRE-FPS. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures The Women's Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. Effect of a Nutritional Supplementation on Bone Health in Chilean Elderly Subjects with Femoral Osteoporosis Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency.
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 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 Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community  Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33 OBJECTIVES To investigate the therapeutic effect of combined use of vitamin K(2 ) and D(3 ) on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis . SUBJECTS AND METHODS We enrolled 172 women with vertebral bone mineral density < 0.98 g/cm(2 ) ( osteopenia and osteoporosis ) as measured by dual-energy X-ray absorptiometry . In this study , we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996 . Subjects were r and omized into four groups ( each having 43 subjects in vitamin K(2 ) therapy group , vitamin D(3 ) therapy group , vitamin K(2 ) and D(3 ) combined therapy group , or a control group receiving dietary therapy alone ) and treated with respective agents for 2 years , with bone mineral density was measured prior to therapy and after 6 , 12 , 18 , and 24 months of treatment . The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide ( P1CP ) , serum intact osteocalcin , and urinary pyridinoline . Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time ( APTT ) and analysis of concentrations of antithrombin III ( AT III ) , fibrinogen , and plasminogen . RESULTS Combined therapy with vitamin K(2 ) and D(3 ) for 24 months markedly increased bone mineral density ( 4.92 + /- 7.89 % ) , while vitamin K(2 ) alone increased it only 0.135 + /- 5.44 % . The bone markers measured , revealed stimulation of both bone formation and resorption activity . We observed an increase in coagulation and fibrinolytic activity that was within the normal range , suggesting that balance was maintained in the fibrinolysis-coagulation system . CONCLUSIONS Continuous combination therapy with vitamin K(2 ) and D(3 ) may be useful for increasing vertebral bone mass in postmenopausal women . Furthermore , the increase in coagulation function observed during this therapy was within the physiological range , and no adverse reactions were observed Introduction Osteoporotic fractures in older people are a major and increasing public health problem . We examined the effect of vitamin D supplementation on fracture rate in people living in sheltered accommodation . Methods In a pragmatic double blind r and omised controlled trial of 3 years duration , we examined 3,440 people ( 2,624 women and 816 men ) living in residential or care home . We used four-monthly oral supplementation using 100,000 IU vitamin D2 ( ergocalciferol ) . As a main outcome measure , we used the incidence of first fracture using an intention to treat analysis . This was a multicentre study in 314 care homes or sheltered accommodation complexes in South Wales , UK . Results The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , 205 first fractures occurred in the intervention group during a total of 2,846 person years of follow-up ( 7 fractures per 100 people per year of follow-up ) , with 218 first fractures in the control group over 2,860 person years of follow-up . The hazard ratio of 0.95 ( 95 % confidence interval 0.79–1.15 ) for intervention compared to control was not statistically significant . ConclusionS upplementation with four-monthly 100,000 IU of oral vitamin D2 is not sufficient to affect fracture incidence among older people living in institutional care 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 Due to little outdoor activity and low dietary intake of vitamin D ( VD ) , Bangladeshi low-income women are at risk for osteoporosis at an early age . The present study assessed the effect of VD , Ca and multiple micronutrient supplementation on VD and bone status in Bangladeshi young female garment factory workers . This placebo-controlled 1-year intervention r and omly assigned 200 apparently healthy subjects ( aged 16 - 36 years ) to four groups : VD group , daily 10 microg VD ; VD and Ca ( VD-Ca ) group , daily 10 microg VD+600 mg Ca ; multiple micronutrient and Ca ( MMN-Ca ) group , 10 microg VD and other micronutrients+600 mg Ca ; a placebo group .  Serum 25-hydroxyvitamin D ( S-25OHD ) , intact parathyroid hormone ( S-iPTH ) , Ca , phosphate and alkaline phosphatase were measured . Bone mineral density and bone mineral content were measured by dual-energy X-ray absorptiometry . All measurements were made at baseline and at 12 months . Significantly ( P < 0.001 ) higher S-25OHD concentrations were observed in the supplemented groups than in the placebo group after the intervention . Supplementation had an effect ( P < 0.001 ) on S-iPTH in the VD-Ca and MMN-Ca groups compared with the placebo group . Bone mineral augmentation increased at the femur in the supplemented groups . Supplementation with VD-Ca should be recommended as a strategic option to reduce the risk of osteomalacia and osteoporosis in these subjects . MMN-Ca may have analogous positive health implication s with additional non-skeletal benefits The purpose of the study was to determine the effect of vitamin D supplementation on bone turnover and bone loss in elderly women . Three hundred forty-eight women , ages 70 yr and older , were r and omized to receive 400 IU vitamin D3 per day ( n = 177 ) or placebo ( n = 171 ) , double-blind , for a period of 2 yr . Main outcome measures were bone mineral density of both hips ( femoral neck and trochanter ) and the distal radius , as well as biochemical markers of bone turnover . The effect of vitamin D supplementation was expressed as the difference in mean ( percentage ) change between the placebo group and the vitamin D group . The measurements were repeated in 283 women after 1 yr and in 248 women after 2 yr . Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D ( 250HD ) ( + 35 nmol/L ) and 1,25-dehydroxyvitamin D [ 1,25-(OH)2D ] ( + 7.0 pmol/L ) levels and urinary calcium/creatinine ratios ( + 0.5 % ) and significantly decreased PTH(1 - 84 ) secretion ( -0.74 pmol/L ) after 1 yr . No effect was found for the parameters of bone turnover . The effect on the bone mineral density of the left femoral neck was + 1.8 % in the first yr , + 0.2 % in the second yr , and + 1.9 % during the whole period ( 95 % confidence interval 0.4 , 3.4 % ) . At the right femoral neck the effects were + 1.5 % , + 1.1 % , and + 2.6 % ( confidence interval 1.1 , 4.0 % ) , respectively . No effect was found at the femoral trochanter and the distal radius . Supplementation with 400 IU vitamin D3 daily in elderly women slightly decreases PTH secretion and increases bone mineral density at the femoral neck BACKGROUND Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons .  Calcium and vitamin D supplements reduce this secondary hyperparathyroidism , but whether such supplements reduce the risk of hip fractures among elderly people is not known . METHODS We studied the effects of supplementation with vitamin D3 ( cholecalciferol ) and calcium on the frequency of hip fractures and other nonvertebral fractures , identified radiologically , in 3270 healthy ambulatory women ( mean [ + /- SD ] age , 84 + /- 6 years ) . Each day for 18 months , 1634 women received tricalcium phosphate ( containing 1.2 g of elemental calcium ) and 20 micrograms ( 800 IU ) of vitamin D3 , and 1636 women received a double placebo . We measured serial serum parathyroid hormone and 25-hydroxyvitamin D ( 25(OH)D ) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women . RESULTS Among the women who completed the 18-month study , the number of hip fractures was 43 percent lower ( P = 0.043 ) and the total number of nonvertebral fractures was 32 percent lower ( P = 0.015 ) among the women treated with vitamin D3 and calcium than among those who received placebo . The results of analyses according to active treatment and according to intention to treat were similar . In the vitamin D3-calcium group , the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months ( P < 0.001 ) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value ( P < 0.001 ) . The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group ( P < 0.001 ) . CONCLUSIONS Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women Antifracture efficacy of high-dose vitamin D ( 800 IU ) and calcium ( 1000 mg ) remains controversial . To determine whether daily 800 IU of vitamin D and 1000 mg of calcium supplementation prevents fractures , we r and omized 3432 women of the population -based Osteoporosis Risk Factor and Prevention ( OSTPRE ) Study cohort ( ages 65 to 71 years ) living in the region of northern Savonia , Finl and ( latitude 62 degrees to 64 degrees N ) for 3 years to receive 800 IU of cholecalciferol and 1000 mg of calcium as calcium carbonate or to a control group that did not receive placebo . The main outcome measure was incident fractures . Fracture data were collected in telephone interviews and vali date d. Data on 3195 women , 1586 in the intervention group and 1609 in the control group , were available for analysis . In adjusted Cox proportional hazards models , the risk of any fracture decreased in the vitamin D and calcium group by 17 % [ adjusted hazard ratio ( aHR ) = 0.83 ; 95 % confidence interval ( CI ) 0.61 - 1.12 ] , and the risk of any nonvertebral fracture decreased by 13 % ( aHR = 0.87 ; 95 % CI 0.63 - 1.19 ) . The risk of distal forearm fractures decreased by 30 % ( aHR = 0.70 ; 95 % CI 0.41 - 1.20 ) , and the risk of any upper extremity fractures decreased by 25 % ( aHR = 0.75 ; 95 % CI 0.49 - 1.16 ) , whereas the risk of lower extremity fractures remained essentially equal ( aHR = 1.02 ; 95 % CI 0.58 - 1.80 ) . None of these effects reached statistical significance . In conclusion , this study did not produce statistically significant evidence that vitamin D and calcium supplementation prevents fractures in a 65- to 71-year-old general population of postmenopausal women 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 The effects of higher than recommended vitamin D doses on bone mineral density ( BMD ) and quality are not known . In this study , higher intakes , in postmenopausal women undergoing weight control over 1 year , had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry . Introduction Studies examining how bone responds to a st and ard dose of vitamin D supplementation have been inconsistent . In addition , the effects of higher doses on BMD and quality are not known . Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance . Methods This 1-year-long , r and omized , double-blind controlled study addresses whether vitamin D supplementation , in healthy overweight/obese older women , affects BMD and bone structural parameters . In addition , bone turnover and serum total , free , and bioavailable 25-hydroxyvitamin D ( 25OHD ) responses to one of three daily levels of vitamin D3 ( 600 , 2000 , 4000 IU ) with 1.2 Ca g/day during weight control were examined . Results Fifty-eight women ( age , 58 ± 6 years ; body mass index , 30.2 ± 3.8 kg/m2 , serum 25OHD , 27.3 ± 4.4 ng/mL ) were r and omized to treatment . After 1 year , serum 25OHD concentrations increased to 26.5 ± 4.4 , 35.9 ± 4.5 , and 41.5 ± 6.9 ng/mL , in groups 600 , 2000 , and 4000 IU , respectively , and differed between groups ( p < 0.01 ) . Weight change was similar between groups ( −3.0 ± 4.1 % ) . Cortical ( Ct ) thickness of the tibia changed by −1.5 ± 5.1 % , + 0.6 ± 3.2 % , and + 2.0 ± 4.5 % in groups 600 , 2000 , and 4000 IU , respectively , and each group was significantly different from each other ( p < 0.05 ) . Conclusion The decline in Ct thickness was prevented with higher vitamin D3 supplementation , but there were no other significant changes due to treatment over 1 year . Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies R and omized controlled trials have shown that a combination of vitamin D and calcium can prevent  fragility fractures in the elderly . Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known . We studied if an intervention with 10 microg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded r and omized controlled trial . Residents from 51 nursing homes were allocated r and omly to receive 5 ml of ordinary cod liver oil ( n = 569 ) or 5 ml of cod liver oil where vitamin D was removed ( n = 575 ) . During the study period of 2 years , fractures and deaths were registered , and the principal analysis was performed on the intention-to-treat basis . Biochemical markers were measured at baseline and after 1 year in a sub sample . Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a  hip fracture . The corresponding figures for all nonvertebral fractures were 76 persons ( control group ) and 69 persons ( vitamin D group ) . There was no difference in the incidence of hip fracture ( p = 0.66 , log-rank test ) , or in the incidence of all nonvertebral fractures ( p = 0.60 , log-rank test ) in the vitamin D group compared with the control group . Compared with the control group , persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter ( p = 0.001 ) . In conclusion , we found that an intervention with 10 microg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people Although vitamin D supplementation in the frail elderly improves calcium absorption , suppresses parathyroid hormone , decreases bone loss and reduces the risk of fractures , such treatment may be ineffective in patients with vertebral osteoporosis , because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel . We have therefore performed a r and omized , single masked study comparing the effects of alfacalcidol treatment ( 0.25 µg twice daily ) and vitamin D2 supplementation ( 500 - 1000 units daily ) on calcium absorption and bone turnover in 46 elderly women ( median age 69 years , range 64–79 years ) with radiological evidence of vertebral fractures .  Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D2 ( p<0.001 ) , but was unchanged in the group receiving alfacalcidol  . Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period . Fractional45Ca absorption increased after 3 months of treatment with alfacalcidol ( p<0.05 ) , but was unchanged with vitamin D2 . There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol ( p<0.05 ) which was not seen in the group receiving vitamin D2 . Our study shows that vitamin D2 supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis . By increasing calcium absorption in such patients , alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis Osteoporosis is a major public health issue leading to significant morbidity , loss of independence and excess loss of life . It has been estimated that 13 to 17 million postmenopausal women have low bone mass or osteoporosis ( 1 , 2 ) . This is associated with almost 1.5 million fractures annually , including 300,000 hip fractures ( 2 , 3 ) . A review of the evidence by Cumming in 1990 ( 4 ) and subsequently published r and omized clinical trials have shown that calcium and /or vitamin D supplements may play a role in the prevention and treatment of osteoporosis by slowing the rates of bone loss in postmenopausal and elderly women ( 5–9 ) . However , there are a limited number of calcium and /or vitamin D trials ( 10–13 ) and observational studies [ review of evidence by Cumming and Nevitt ( 14 ) and Kanis ( 15 ) ] , to support a role for calcium and vitamin D supplementation in the reduction of hip and other fractures . It has also been suggested that calcium and vitamin D supplementation may play a role in the reduction of colorectal cancer incidence ( 16–21 ) . To address these major health concerns of postmenopausal women , the Calcium-Vitamin D ( CaD ) trial of the Women ’s Health Initiative ( WHI ) was design ed to test the primary hypothesis that women who are r and omized to receive calcium and vitamin D supplementation will have a lower risk of hip fracture and secondarily , a lower risk of all fractures and colorectal cancer than women receiving corresponding placebo . The objective of this paper is Objective : To study the effects of a special nutritional supplement on bone mineral density and bone turnover markers in Chilean elderly subjects with femoral osteoporosis . Setting : Public primary health care clinics in Chile . Subjects : Free living elderly subjects with femoral osteoporosis . Interventions : Subjects were r and omized to receive the usual nutritional supplement provided by the Chilean Ministry of Health or a special nutritional supplement providing , among other nutrients , 90 mg isoflavones , 800 mg calcium , 400 IU vitamin D , 60 ug vitamin K and 31 g proteins per day . Measures of Outcome : At baseline , and after six and twelve months of supplementation , body composition , bone mineral density , serum 25 OH vitamin D , intact parathyroid hormone ( iPTH ) , osteocalcin , decarboxylated osteocalcin , urinary aminoterminal telopeptide of type I collagen ( NTX ) , deoxypyridoline cross links ( Dpd ) and equol were measured . Every month , urinary daidzein was measured in a morning urine sample . Results : No differences between treatment groups were observed in body composition or bone mineral density changes . The group receiving the special supplement had a significant increase in serum 25 OH vitamin D and a significant decrease in serum iPTH and decarboxylated osteocalcin . No association between daidzein or equol excretion and changes in bone mineralization was observed . Conclusions : A special supplement delivered to elderly subjects with osteoporosis improved serum vitamin D and reduced serum iPTH and undercarboxylated osteocalcin levels but did not affect BMD Significant reduction in bone mineral density ( BMD ) occurs in patients with Parkinson 's disease ( PD ) , correlating with immobilization and with vitamin D deficiency , and increasing the risk of hip fracture , especially in elderly women . As a biological indicator of compromised vitamin K status , an increased serum concentration of undercarboxylated osteocalcin ( Oc ) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women . We evaluated treatment with vitamin K(2 ) ( menatetrenone ; MK-4 ) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD . In a r and om and prospect i ve study of PD patients , 60 received 45 mg of MK-4 daily for 12 months , and the remaining 60 ( untreated group ) did not . At baseline , patients of both groups showed vitamin D and K(1 ) deficiencies , high serum levels of ionized calcium , and glutaminic residue ( Glu ) Oc , and low levels of parathyroid hormone ( PTH ) and 1,25-dihydroxyvitamin D [ 1,25-(OH)(2)D ] , indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion . BMD in the second metacarpals increased by 0.9 % in the treated group and decreased by 4.3 % in the untreated group ( p < 0.0001 ) .  Vitamin K(2 ) level increased by 259.8 % in the treated group . Correspondingly , significant decreases in Glu Oc and calcium were observed in the treated group , in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures ( eight at the hip and two at other sites ) in the untreated group , and one hip fracture occurred among treated patients ( p = 0.0082 ; odds ratio = 11.5 ) . The treatment with MK-4 can increase the BMD of vitamin D- and K-deficient bone by increasing vitamin K concentration , and it can also decrease calcium levels through inhibition of bone resorption , result ing in an increase in 1,25-(OH)(2)D concentration
Two regimens , each represented by one large trial , which showed limited evidence of efficacy in reducing the incidence of hip or other appendicular skeleton fractures were : 1 ) Oral Vitamin D when accompanied by calcium supplementation .
2 ) 1,25 dihydroxy Vitamin D ( calcitriol ) .
This appeared more effective than calcium in a direct comparison .
Hypercalcaemia and gastro-intestinal symptoms , reported in less than 5 % of participants , were slightly more common when Vitamin D analogues were taken .
However , the risk of death was marginally less .
REVIEW ER 'S CONCLUSIONS Uncertainty remains about the efficacy of regimens which include Vitamin D or its analogues in fracture prevention .
Particularly if co-supplementation of calcium is required , significant cost differences are likely to exist between regimens .
BACKGROUND Due to their known effects on bone metabolism , Vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures .
OBJECTIVES To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis .