title: The effects of a 30-month dietary intervention on bone mineral density: the Postmenopausal Health Study. Treatment of Vitamin D Deficiency Increases Lower Limb Muscle Strength in Institutionalized Older People Independently of Regular Physical Activity: A Randomized Double-Blind Controlled Trial The Effect of Calcium and Vitamin D3 Supplementation on the Healing of the Proximal Humerus Fracture: A Randomized Placebo-Controlled Study Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. Trials and tribulations of recruiting 2,000 older women onto a clinical trial investigating falls and fractures: Vital D study Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women. Falls in the elderly: a prospective study of risk factors and risk profiles. Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation Vitamin D-Fortified Liquid Milk: Benefits for the Elderly Community-Based Population Skeletal site-dependent response of bone mineral density and quantitative ultrasound parameters following a 12-month dietary intervention using dairy products fortified with calcium and vitamin D: the Postmenopausal Health Study. The Effect of Calcitriol on Patients with Postmenopausal Osteoporosis with Special Reference to Fracture Frequency Calcium-vitamin D3 supplementation is cost-effective in hip fractures prevention. Sun, vitamin D, and cardiovascular disease.
abstract: Low dietary Ca intake and vitamin D insufficiency have been implicated as part of the aetiology leading to osteoporosis . The aim of the present study was to examine the effects of a 30-month dietary intervention that combined supplementation of dairy products fortified with Ca and vitamin D3 and lifestyle and nutrition counselling sessions on  bone mineral density ( BMD )  of postmenopausal women . Sixty-six postmenopausal women ( aged 55 - 65 years ) were r and omised into a dietary group ( DG ; n 35 ) , receiving daily and for the first 12 months 1200 mg Ca and 7.5 microg vitamin D3 , while for the next 18 months of intervention 1200 mg Ca and 22.5 microg vitamin D3 through fortified dairy products , and a control group ( CG ; n 31 ) receiving neither counselling nor dairy products . The DG was found to have more favourable changes in arms ( P < 0.001 ) , total spine ( P = 0.001 ) and total body BMD ( P < 0.001 ) compared with the CG . Furthermore , a significant increase was observed for the DG in lumbar spine BMD ( 0.056 ; 95 % CI 0.009 , 0.103 ) , which was not found to differentiate significantly compared with the change observed in the CG ( P = 0.075 ) . In conclusion , the present study showed that intakes of vitamin D of about 22.5 microg/d and of Ca close to the recommended level of 1200 mg from fortified dairy foods for 30 months , with compliance ensured by lifestyle and nutrition counselling sessions , can induce favourable changes in arms , total spine and total body BMD of postmenopausal women Aims : To investigate the effects of a 6-month supplementation with calcium and cholecalciferol on biochemical parameters and muscle strength of institutionalized elderly . Methods : This prospect i ve , double-blind , placebo-controlled , r and omized trial included Brazilian institutionalized people ≥60 years of age receiving a 6-month supplementation ( December to May ) of daily calcium plus monthly placebo ( calcium/placebo group ) or daily calcium plus oral cholecalciferol ( 150,000 IU once a month during the first 2 months , followed by 90,000 IU once a month for the last 4 months ; calcium/vitamin D group ) . Fasting blood sample s for 25(OH)D , PTH and calcium determination were collected ( n = 56 ) and muscle tests were performed ( n = 46 ) to measure the strength of hip flexors ( SHF ) and knee extensors ( SKE ) before ( baseline ) and after the 6-month intervention ( 6 months ) . Results : Due to seasonal variations , serum 25(OH)D significantly enhanced in both groups after treatment , but the calcium/vitamin D group had significantly higher 25 (OH)D levels than the calcium/placebo group ( 84 vs. 33 % , respectively ; p < 0.0001 ) . No cases of hypercalcemia were observed . While the calcium/placebo group showed no improvement in SHF and SKE at 6 months ( p = 0.93 and p = 0.61 , respectively ) , SHF was increased in the calcium/vitamin D group by 16.4 % ( p = 0.0001 ) and SKE by 24.6 % ( p = 0.0007 ) . Conclusions : The suggested cholecalciferol supplementation was safe and efficient in enhancing 25(OH)D levels and lower limb muscle strength in the elderly , in the absence of any regular physical exercise practice The purpose of this study was to ( 1 ) quantify the healing process of the human osteoporotic proximal humerus fracture ( PHF ) expressed in terms of callus formation over the fracture region using BMD scanning , and ( 2 ) quantify the impact of medical intervention with vitamin D3 and calcium on the healing process of the human osteoporotic fracture . The conservatively treated PHF was chosen in order to follow the genuine fracture healing without influence of osteosynthetic material s or casts . Thirty women ( mean age = 78 years ; range = 58–88 ) with a PHF , osteoporosis or osteopenia ( based on a hip scan , WHO criteria ) , and not taking any drugs related to bone formation , including calcium or vitamin D supplementation  , were r and omly assigned to either oral 800 IU vitamin D3 plus 1 g calcium or placebo , in a double-blind prospect i ve study . We measured biochemical , radiographic , and bone mineral density effect parameters to evaluate the impact on the healing process . Scanning procedures of the fractured shoulder included use of a fixation device to obtain the highest possible precision . Double scans of the fractured shoulder revealed a coefficient of variation ( CV ) on BMD measurements that improved from 2.8 % immediately after fracture occurrence to 1.7 % at 12 weeks ( P = 0.003 ) approaching the 1.2 % levels observed over the healthy shoulder . BMD was similar in the two groups at baseline ( active 0.534 g/cm2 vs. placebo 0.518 g/cm2 ) , and both increased over the 12-week observation period , with peak levels in week 6 . By week 6 BMD levels were higher in the active group ( 0.623 g/cm2 ) compared with the placebo group ( 0.570 g/cm2 , P = 0.006 ) . Thirty seven percent of the patients presented with vitamin D levels below 30 nmol/l , indicative of mild vitamin D insufficiency . In conclusion , we have demonstrated that it is possible to quantify callus formation of the PHF with sufficiently high precision to demonstrate the positive influence of vitamin D3 and calcium over the first 6 weeks after fracture . Whether this results in more stable fractures , extends to other fracture types , or applies to other osteogenic bone agents such as bisphosphonates remains to be examined BACKGROUND Ergocalciferol ( vitamin D(2 ) ) supplementation plays a role in fall prevention , but the effect in patients living in the community in sunny climates remains uncertain . We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling . METHODS A 1-year population -based , double-blind , r and omized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth , Australia ( latitude , 32 degrees S ) , with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year . Participants were r and omized to receive ergocalciferol , 1000 IU/d , or identical placebo ( hereinafter , ergocalciferol and control groups , respectively ) . Both groups received calcium citrate , 1000 mg/d . Fall data were collected every 6 weeks . RESULTS Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height , which was significantly different between the 2 groups ( ergocalciferol group , 53.0 % ; control group , 62.9 % ; odds ratio [ OR ] , 0.61 ; 95 % confidence interval [ CI ] , 0.37 - 0.99 ) . When those who fell were grouped by the season of first fall or the number of falls they had , ergocalciferol treatment reduced the risk of having the first fall in winter and spring ( ergocalciferol group , 25.2 % ; control group , 35.8 % ; OR , 0.55 ; 95 % CI , 0.32 - 0.96 ) but not in summer and autumn , and reduced the risk of having 1 fall ( ergocalciferol group , 21.2 % ; control group , 33.8 % ; OR , 0.50 ; 95 % CI , 0.28 - 0.88 ) but not multiple falls . CONCLUSION Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium , which is associated with a 19 % reduction in the relative risk of falling , mostly in winter Background R and omised , placebo-controlled trials are needed to provide evidence demonstrating safe , effective interventions that reduce falls and fractures in the elderly . The quality of a clinical trial is dependent on successful recruitment of the target participant group . This paper documents the successes and failures of recruiting over 2,000 women aged at least 70 years and at higher risk of falls or fractures onto a placebo-controlled trial of six years duration . The characteristics of study participants at baseline are also described for this study . Methods The Vital D Study recruited older women identified at high risk of fracture through the use of an eligibility algorithm , adapted from identified risk factors for hip fracture . Participants were r and omised to orally receive either 500,000 IU vitamin D3 ( cholecalciferol ) or placebo every autumn for five consecutive years . A variety of recruitment strategies were employed to attract potential participants . Results Of the 2,317 participants r and omised onto the study , 74 % ( n = 1716/2317 ) were consented onto the study in the last five months of recruiting . This was largely due to the success of a targeted mail-out . Prior to this only 541 women were consented in the 18 months of recruiting . A total of 70 % of all participants were recruited as a result of targeted mail-out . The response rate from the letters increased from 2 to 7 % following revision of the material by a public relations company . Participant demographic or risk factor profile did not differ between those recruited by targeted mail-outs compared with other methods . Conclusion The most successful recruitment strategy was the targeted mail-out and the response rate was no higher in the local region where the study had extensive exposure through other recruiting strategies . The strategies that were labour-intensive and did not result in successful recruitment include the activities directed towards the GP medical centres . Comprehensive recruitment programs employ overlapping strategies simultaneously with ongoing assessment of recruitment rates . In our experience , and others direct mail-outs work best although rights to privacy must be respected . Trial registration IS RCT N83409867 and ACTR12605000658617 Abstract Objective To assess whether supplementation with calcium and cholecaliferol ( vitamin D3 ) reduces the risk of fracture in women with one or more risk factors for fracture of the hip . Design Pragmatic open r and omised controlled trial . Setting Practice nurse led clinics in primary care . Participants 3314 women aged 70 and over with one or more risk factors for hip fracture : any previous fracture , low body weight ( < 58 kg ) , smoker , family history of hip fracture , or fair or poor self reported health . Intervention Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls , or leaflet only ( control group ) . Main outcome measures Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment , falls , and quality of life ( measured with the SF-12 ) . Results 69 % of the women who completed the follow-up question naire at 24 months were still taking supplements ( 55 % with inclusion of r and omised participants known to be alive ) . After a median follow-up of 25 months ( range 18 to 42 months ) , clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures ( odds ratio for fracture in supplemented group 1.01 , 95 % confidence interval 0.71 to 1.43 ) . The odds ratio for hip fracture was 0.75 ( 0.31 to 1.78 ) . The odds of a woman having a fall at six and 12 months was 0.99 and 0.98 , respectively . Quality of life did not significantly differ between the groups . Conclusion We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture . Registration IS RCT N26118436 , controlled trials registry BACKGROUND Seasonal Affective Disorder ( SAD ) is a sub-type of depression that only occurs during the winter months . A reduction in vitamin D may be linked to SAD . Since vitamin D deficiency has been reported to be common in older people , vitamin D supplementation may be expected to reduce seasonal mood disturbance in this group . OBJECTIVE To assess the effect of vitamin D supplementation on the mental health of older women . SETTING Primary care in three areas of the UK ( Herts , Newcastle , York ) . SUBJECTS Women aged 70 years or more recruited to the trial in the months May-October . INTERVENTION Eligible women were r and omised to receive calcium and vitamin D supplementation or no supplementation . OUTCOME MEASURE At baseline and the six monthly assessment the mental component score ( MCS ) , calculated from the SF-12 question naire was used to assess participants ' subjective psychological well-being . RESULTS A total of 2117 women recruited to the trial had their baseline measures taken between the months of May-October ( 1205 woman in the control group and 912 women in the intervention group ) . Of these women , 1621 had a  MCS score at baseline and six months . Comparison of the six month mean MCS scores , adjusting for baseline MCS score and age , showed there was no significant difference between the two scores ( p = 0.262 ) . CONCLUSIONS Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores In this prospect i ve study , the authors determined intrinsic risk factors for falls and recurrent falls and constructed a risk profile that indicated the relative contribution of each risk factor and also estimated the probabilities of falls and recurrent falls . In 1992 , over a 28-week period , falls were recorded among 354 elderly subjects aged 70 years or over who were living in homes or apartments for the elderly in Amsterdam and the vicinity . During the study period , 251 falls were reported by 126 subjects ( 36 % ) , and recurrent falls ( > or = 2 falls ) were reported by 57 subjects ( 16 % ) . Associations of falls and recurrent falls with potential risk factors were identified in logistic regression models . Mobility impairment regarding one or more of the tested items ( i.e. , impairment of balance , leg-extension strength , and gait ) was associated with falls ( adjusted odds ratio ( OR ) = 2.6 ) and was strongly associated with recurrent falls ( OR = 5.0 ) . Dizziness upon st and ing was associated with falls ( OR = 2.1 ) and recurrent falls ( OR = 2.1 ) . However , several risk factors were associated with recurrent falls only : history of stroke ( OR = 3.4 ) , poor mental state ( OR = 2.4 ) , and postural hypotension ( OR = 2.0 ) . The authors constructed a risk profile for recurrent falls that included the five risk factors mentioned above . Inclusion of all risk factors in the profile implied an 84 % probability of recurrent falls over a period of 28 weeks , compared with 3 % when no risk factor was present . The probability of recurrent falls ranged only from 11 % to 29 % when predicted by number of falls occurring in the previous year . Physical activity , use of high-risk medication , and the use of vitamin D3 , which was r and omly allocated to the participants , were not strongly related to either falls or recurrent falls . In conclusion , a large range of probabilities of falls , especially of recurrent falls , was estimated by the risk profiles , in which mobility impairment was the major risk factor . Recurrent fallers may therefore be especially amenable to prevention based on mobility improvement Background and aims : Insufficient vitamin D status , commonly found in older people , has been associated with muscle weakness which , in old age , impairs mobility and is a risk factor for falling . In a r and omized , double-blind placebo-controlled trial , we tested the hypothesis that vitamin D + calcium supplementation improves muscle strength and mobility , compared with calcium mono-therapy in vitamin D-insufficient female geriatric patients . Methods : Seventy female geriatric patients > 65 years of age with serum 25-hydroxyvitamin D3 ( 25OHD ) concentrations between 20 and 50 nmol/L , visiting an outpatient geriatric department , were included . Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day ( D/Cal group ) or a placebo + calcium 500 mg/day ( Plac/Cal group ) for 6 months . At baseline and 6 months , muscle strength , power and functional mobility were tested . Results : At baseline , 25OHD was significantly ( p<0.05 ) associated with knee extension strength ( r=0.42 ) , h and grip strength ( r=0.28 ) , leg extension power ( r=0.34 ) , Timed Get Up and Go ( r=−0.31 ) and Modified Cooper test ( r=0.44 ) . At 6 months , a significant difference in 25OHD ( 77.2 vs 41.6 nmol/L , p<0.001 ) and 1,25OHD was found between the two groups . Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups . Conclusions : Daily 400IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients Abstract . To assess the efficacy and acceptability of vitamin D-fortified liquid milk in the management of hypovitaminosis D we carried out a double-blind , r and omized , controlled trial on 51 community-based , elderly subjects with serum 25 hydroxyvitamin D ( 25OHD ) levels of less than 12.9 ng/ml ( normal range 10–80 ng/ml ) . Each subject had a dietary assessment , mental test score , outdoor score , serum 25 hydroxyvitamin D level , and a general biochemical screening at baseline in April 1993 which was repeated in September 1993 , April 1994 , and September 1994 . All subjects received 500 ml of milk per day , delivered to their homes in specially manufactured , blank , tetrapak cartons , from June 1993 to June 1994 : 23 subjects received unfortified milk ( control group ) and 28 subjects received fortified milk ( active group ) . Our results showed a baseline mean 25OHD level in the active group of 9.6 ( range < 5.5–12.7 ) ng/ml and in the control group of 10.0 ( range < 5.5–12.9 ) ng/ml ( P < 0.4 ) . One year later the mean 25OHD level in the active group had risen significantly from its baseline to 18.5 ( range 9.6–26.7 ) ng/ml ( P < 0.001 ) and was significantly different from the control group with a 1-year mean of 12.7 ( range < 4–24.1 ) ng/ml ( P < 0.001 ) . Serum calcium levels in the active group also showed a significant rise over the 1-year period ( P < 0.001 ) whereas those in the control group did not . We conclude that vitamin D-fortified liquid milk is a safe , effective , and acceptable method of administering vitamin D to the elderly , community-based population The aim of the current study was to examine whether calcium supplementation could prevent bone loss in postmenopausal women or more favourable outcomes could be obtained via the consumption of dairy products fortified with calcium and vitamin D3 . For this purpose changes in bone mineral density ( BMD ) at different skeletal sites , assessed by dual-energy X-ray absorptiometry , as well as in quantitative ultrasound ( QUS ) parameters of the calcaneus over 12 months were estimated . A population of 101 postmenopausal women ( 55 - 65 years old ) was r and omized into a dairy group ( DG : n 39 ) , receiving approximately 1200 mg calcium/d and 7.5 microg vitamin D3/d through fortified dairy products ; a calcium-supplemented group ( CaG : n 26 ) provided with a calcium supplement of 600 mg/d ; and a control group ( CG : n 36 ) . Over the intervention period the DG was found to have more favourable changes in pelvis ( P=0.040 ) , total spine ( P<0.001 ) and total body BMD ( P<0.001 ) than the other groups . A significant increase was also observed for DG in lumbar spine BMD ( 2.0 % ; 95 % CI 0.5 , 3.5 ) although it did not differentiate significantly compared to the other groups . No significant differences were observed with respect to the changes in QUS parameters . The current study revealed that recommended intakes of vitamin D3 and calcium via fortified dairy products for 12 months can induce favourable changes in pelvis , total spine and total body BMD in postmenopausal women but not in QUS parameters . No such favourable changes were observed via supplementation of calcium alone Malabsorption of calcium is a common finding in patients with postmenopausal osteoporosis ( 1 , 2 ) . In a number of studies serum 1,25 dihydroxyvitamin D levels were found to be significantly lower in osteoporotic patients , which could account for the calcium absorptive defect ( 3–6 ) . Based on these findings , we studied the effects of synthetic calcitriol ( Rocaltrol ) in women with osteoporosis . We showed that calcitriol , 0.25 μg twice daily , improved and normalized the absorption of calcium in all patients and improved calcium balance ( 7 ) . Urine hydroxyproline , which is a measure of bone resorption , decreased significantly after 2 years of treatment with Rocaltrol . Because of these preliminary findings , further clinical studies were carried out at two centers using a variable dose of Rocaltrol . In these studies we focused on the effectiveness of Rocaltrol in preventing vertebral fractures in patients with spinal osteoporosis . Methods The results from two centers have been analyzed both as separate groups and as one combined group . One study was performed at the Mayo Clinic ( Protocol 861 ) and the other at Creighton University ( Protocol 860 ) . In both centers the studies performed were double blind and r and omized , and compared the effect of placebo against Rocaltrol for a period of 1 year . At the end of 1 year all patients on placebo were crossed over to treatment with Rocaltrol and followed for 2 more years . Patients initially treated with Rocaltrol were followed for an additional 2 years , thus yielding treatment data extending to 3 years in a number of patients . In the study design , patients were given Rocaltrol at a starting dose of 0.25 μg twice daily , if hypercalcemia and hypercalciuria did not occur the dose then was increased to 0.75 μg or 1.0 μg daily at the discretion of the investigator OBJECTIVE To assess the cost implication s for a preventive treatment strategy for institutionalised elderly women with a combined 1200 mg/day calcium and 800 IU/day vitamin D(3 ) supplementation in seven European countries . DESIGN Retrospective cost effectiveness analysis based on a prospect i ve placebo-controlled r and omised clinical trial . DATA SOURCES Recently published cost studies in seven European countries . Clinical results from Decalyos , a 3-year placebo-controlled study in elderly institutionalised women . TRIALS Decalyos study , with 36 months follow-up of 3270 mobile elderly women living in 180 nursing homes , allocated to two groups . One group received 1200 mg/day elemental calcium in the form of tricalcium phosphate together with 800 IU/day ( 20 microg ) of cholecalciferol ( vitamin D(3 ) ) , the other placebo . RESULTS In the 36 months analysis of the Decalyos study , 138 hip fractures occurred in the group of 1176 women , receiving supplementation  and 184 hip fractures in the placebo group of 1127 women . The mean duration of treatment was 625.4 days . Adjusted to 1000 women , 46 hip fractures were avoided by the calcium and vitamin D(3 ) supplementation . For all countries , the total costs in the placebo group were higher than in the group receiving supplementation , result ing in a net benefit of 79000 - 711000 per 1000 women . CONCLUSION This analysis suggests that the supplementation strategy is cost saving . The results may underestimate the net benefits , as this treatment has also shown to be effective in decreasing the incidence of other non-vertebral fractures in elderly institutionalised women Globally , cardiovascular disease ( CVD ) is the number one cause of death , being responsible for approximately 30 % of deaths worldwide . Urbanization and a westernized lifestyle are thought to play a major role in the development of CVD . There is accumulating evidence that vitamin D is a nonclassical risk factor for CVD . The active vitamin D metabolite , 1,25-dihydroxyvitamin D , which is synthesized from its precursor 25-hydroxyvitamin D ( 25[OH]D ) , down-regulates several negative and up-regulates various protective pathways in the heart and vasculature . First r and omized trials demonstrate that vitamin D supplementation leads to vasodilatation and suppresses cardiovascular risk markers such as triglycerides and the inflammation marker tumor necrosis factor-α . Solar UV-B radiation is the major source of vitamin D for humans . Consequently , the vitamin D status is largely influenced by season , geographic latitude , daily outdoor activities , and the percentage of body surface exposed to solar UV-B. A significant proportion of individuals in Europe and North America have  vitamin D concentrations in the deficiency range ( 25[OH]D<25 nmol/l ) . Available data indicate that low solar UV-B exposure and /or low 25(OH)D concentrations are associated with an increased risk of CVD . Large nonr and omized studies indicate that CVD mortality is more than twice as high in older individuals with deficient 25(OH)D concentrations compared with those individuals who have adequate 25(OH)D concentrations ( > 75 nmol/l ) . Together , experimental and epidemiological evidence does support a plausible role for improving vitamin D status in CVD prevention in the population at large . Nevertheless , future r and omised clinical trials are needed to evaluate whether vitamin D is effective with respect to primary , secondary , and /or tertiary prevention of CVD
target: Vitamin D in the form of vitamin D(3 ) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care .
  Vitamin D(2 ) , alfacalcidol , and calcitriol had no statistically significant effect on mortality .
  Vitamin D(3 ) combined with calcium significantly increased nephrolithiasis .
  Both alfacalcidol and calcitriol significantly increased hypercalcaemia
background: BACKGROUND The available evidence on vitamin D and mortality is inconclusive .
  OBJECTIVES To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults .