title: Combined Calcium and Vitamin D3 Supplementation in Elderly Women: Confirmation of Reversal of Secondary Hyperparathyroidism and Hip Fracture Risk: The Decalyos II Study Amelioration of osteopenia and hypovitaminosis D by 1α-hydroxyvitamin D3 in elderly patients with Parkinson’s disease Prevention of postmenopausal bone loss by low and conventional doses of calcitriol or conjugated equine estrogen. 1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial. The Effects of Vitamin D Supplementation on Physical Function and Quality of Life in Older Patients With Heart Failure: A Randomized Controlled Trial Falls prevention in residential care homes: a randomised controlled trial. Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients. Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. The necessity and safety of calcium and vitamin D in the elderly. Alfacalcidol reduces accelerated bone turnover in elderly women with osteoporosis Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D. The effect of calcium and vitamin D supplementation on obesity in postmenopausal women: secondary analysis for a large-scale, placebo controlled, double-blind, 4-year longitudinal clinical trial Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Vitamin D supplementation and bone mineral density in early postmenopausal women. Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. Long-term effects of nutrient intervention on markers of bone remodeling and calciotropic hormones in late-postmenopausal women. Single-dose cholecalciferol suppresses the winter increase in parathyroid hormone concentrations in healthy older men and women: a randomized trial. Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation Effect of Supplementation with Vitamin D3 and Calcium on Quantitative Ultrasound of Bone in Elderly Institutionalized Women: A Longitudinal Study
   Annual high-dose vitamin D3 and mental well-being: randomised controlled trial. The Effect of Calcium and Vitamin D3 Supplementation on the Healing of the Proximal Humerus Fracture: A Randomized Placebo-Controlled Study Low-dose calcitriol versus calcium in established postmenopausal osteoporosis. Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with a low creatinine clearance of <65 ml/min Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial Comparison of methods for defining prevalent vertebral deformities: the Study of Osteoporotic Fractures. Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. Efficacy of ipriflavone and 1 alpha vitamin D therapy for the cessation of vertebral bone loss. Vitamin D and Calcitonin Treatment in Patients with Femoral Neck Fracture: A Prospective Controlled Clinical Study Effects of vitamin D supplementation and exercise training on physical performance in Chilean vitamin D deficient elderly subjects Additive impact of alfacalcidol on bone mineral density and bone strength in alendronate treated postmenopausal women with reduced bone mass. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. The efficacy and safety of calcitriol and/or Caltrate D in elderly Chinese women with low bone mass Effects of calcium and vitamin D supplementation on hip bone mineral density and calcium-related analytes in elderly ambulatory Australian women: a five-year randomized controlled trial. Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women. Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study. Calcium, vitamin D and anabolic steroid in treatment of aged bones: double-blind placebo-controlled long-term clinical trial. Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. A randomized controlled study. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Does 24R,25(OH)2-vitamin D3 prevent postmenopausal bone loss? High-dose oral vitamin D3 supplementation in the elderly Consort 2010 statement: extension to cluster randomised trials Calcium Plus Vitamin D Supplementation Has Limited Effects on Femoral Geometric Strength in Older Postmenopausal Women: The Women’s Health Initiative Calcium and vitamin d supplementation in postmenopausal women. Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. Effect of discontinuation of estrogen, calcitriol, and the combination of both on bone density and bone markers. The Association of Radiographically Detected Vertebral Fractures with Back Pain and Function: A Prospective Study Calcitriol treatment is not effective in postmenopausal osteoporosis. 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) Effects of alendronate plus alfacalcidol in osteoporosis patients with a high risk of fracture: the Japanese Osteoporosis Intervention Trial (JOINT) – 02 Effect of low-dose calcitriol and calcium therapy on bone histomorphometry and urinary calcium excretion in osteopenic women. 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 A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: No advantage of loading doses over daily supplementation 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 Vitamin D supplementation improves neuromuscular function in older people who fall. The effect of combined calcium and cholecalciferol supplementation on bone mineral density in elderly women with moderate chronic kidney disease Identification of Early Postmenopausal Women with No Bone Response to HRT: Results of a Five-Year Clinical Trial Effects of 1α-hydroxyvitamin D3 on lumbar bone mineral density and vertebral fractures in patients with postmenopausal osteoporosis Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. Alfacalcidol (alpha D3) and calcium in osteoporosis. A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures TREATMENT OF POST MENOPAUSAL OSTEOPOROSIS. A CONTROLLED THERAPEUTIC TRIAL COMPARING OESTROGEN/GESTAGEN, 1,25‐DIHYDROXY‐VITAMIN D3 AND CALCIUM Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. Calcium- and vitamin D3-fortified milk reduces bone loss at clinically relevant skeletal sites in older men: a 2-year randomized controlled trial. Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: a randomized controlled trial. Do vitamin D supplements improve the physical capabilities of elderly hospital patients? Falls in the elderly: a prospective study of risk factors and risk profiles. Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. The Effect of Season and Vitamin D Supplementation on Bone Mineral Density in Healthy Women: A Double-Masked Crossover Study
   Long-term effect of nandrolone decanoate, 1 alpha-hydroxyvitamin D3 or intermittent calcium infusion therapy on bone mineral content, bone remodeling and fracture rate in symptomatic osteoporosis: a double-blind controlled study. Calcium and vitamin D supplements reduce tooth loss in the elderly. Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis Clinical and laboratory safety of one year's use of a combination calcium + vitamin D tablet in ambulatory elderly women with vitamin D insufficiency: results of a multicenter, randomized, double-blind, placebo-controlled study. Calcium plus vitamin D supplementation and the risk of fractures. Vitamin D-Fortified Liquid Milk: Benefits for the Elderly Community-Based Population Calcium and Vitamin D Supplementation Increases Spinal BMD in Healthy, Postmenopausal Women
   Effects of three-monthly oral 150,000 IU cholecalciferol supplementation on falls, mobility, and muscle strength in older postmenopausal women: a randomized controlled trial. Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial. Clinical, biochemical and histological results of a double-blind trial with 1,25-dihydroxyvitamin D3, estradiol and placebo in post-menopausal osteoporosis. Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Administration of a supplement containing both calcium and vitamin D is more effective than calcium alone to reduce secondary hyperparathyroidism in postmenopausal women with low 25(OH)vitamin D circulating levels Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. Is fall prevention by vitamin D mediated by a change in postural or dynamic balance? Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals 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. Vitamin D Supplementation and Fracture Incidence in Elderly Persons Prevention of femoral and lumbar bone loss with hormone replacement therapy and vitamin D3 in early postmenopausal women: a population-based 5-year randomized trial. Does vitamin D stop inpatients falling? A randomised controlled trial. Distribution and correlates of serum 25-hydroxyvitamin D levels in a sample of patients with hip fracture. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. Long-term effects of calcium-vitamin-D3-fortified milk on bone geometry and strength in older men. Effects of 2 years' treatment of osteoporosis with 1 alpha-hydroxy vitamin D3 on bone mineral density and incidence of fracture: a placebo-controlled, double-blind prospective study. Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients [Treatment of postmenopausal osteoporosis with 1-alpha(OH)D3]. Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecalciferol. Annual injection of vitamin D and fractures of aged bones Reduced occurrence of vertebral crush fractures in senile osteoporosis treated with 1 alpha (OH)-vitamin D3. Histomorphometric effects of calcium or calcium plus 25-hydroxyvitamin D3 therapy in senile osteoporosis. A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy. Knee pain, knee osteoarthritis, and the risk of fracture. The effects of calcitriol on falls and fractures and physical performance tests Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men. A randomized controlled trial of vitamin D3 supplementation in African American 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. Type of dietary fat is associated with the 25-hydroxyvitamin D3 increment in response to vitamin D supplementation. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. The Effect of Calcitriol on Patients with Postmenopausal Osteoporosis with Special Reference to Fracture Frequency A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). Does 1,25(OH)2D3 accelerate spinal bone loss? A controlled therapeutic trial in 70-year-old women. Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. 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. Effect of estrogen/gestagen and 24R,25-dihydroxyvitamin D3 therapy on bone formation in postmenopausal women. The Women's Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. The effects of an open design on trial participant recruitment, compliance and retention – a randomized controlled trial comparison with a blinded, placebo-controlled design Functional improvement with vitamin D replenishment in a cohort of frail, vitamin D-deficient older people. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1 alpha-hydroxyvitamin D3 and calcium supplementation. Role of calcitriol in the treatment of postmenopausal osteoporosis. Calcitriol in the treatment of postmenopausal osteoporosis. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Prophylactic vitamin D in the elderly. Does daily vitamin D 800 IU and calcium 1000 mg supplementation decrease the risk of falling in ambulatory women aged 65-71 years? A 3-year randomized population-based trial (OSTPRE-FPS). Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency. Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. Dose Response to Vitamin D Supplementation in Postmenopausal Women CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials Randomized controlled trial of the effects of calcium with or without vitamin D on bone structure and bone-related chemistry in elderly women with vitamin D insufficiency.
abstract: Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people .  Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures , as proved by Decalyos I. Decalyos II is a 2-year , multicenter , r and omized , double-masked , placebo-controlled confirmatory study . The intention-to-treat population consisted of 583 ambulatory institutionalized women ( mean age 85.2 years , SD = 7.1 ) r and omized to the  calcium – vitamin D3  fixed combination group ( n= 199 ) ; the calcium plus vitamin D3 separate combination group ( n= 190 ) and the placebo group ( n= 194 ) . Fixed and separate combination groups received the same daily amount of calcium ( 1200 mg ) and vitamin D3 ( 800 IU ) , which had similar pharmacodynamic effects . Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent , with levels returning within the normal range after 6 months . In a subgroup of 114 patients  , femoral neck bone mineral density ( BMD ) decreased in the placebo group ( mean = –2.36 % per year , SD = 4.92 ) , while remaining unchanged in women treated with calcium-vitamin D3 ( mean = 0.29 % per year , SD = 8.63 ) . The difference between the two groups was 2.65 % ( 95 % CI = –0.44 , 5.75 % ) with a trend in favor of the active treatment group . No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis . The relative risk ( RR ) of HF in the placebo group compared with the active treatment group was 1.69 ( 95 % CI = 0.96 , 3.0 ) , which is similar to that found in Decalyos I ( RR = 1.7 ; 95 % CI = 1.0 , 2.8 ) . Thus , these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture  in elderly institutionalized women OBJECTIVES A high prevalence of hip and other fractures in elderly patients with Parkinson ’s disease has been linked to reduced bone mass arising from a defect of renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Treatment with 1α-hydroxyvitamin D3 ( 1α(OH)D3 ; an active form of vitamin D ) was evaluated for maintaining bone mass and reducing the incidence of hip and other non-vertebral fractures in patients with Parkinson ’s disease . METHODS In a double blind , r and omised trial , 86 elderly patients with Parkinson ’s disease ( mean Hoehn and Yahr stage , 3 ; mean age 70.6 years ) were r and omised to receive either 1 μg 1α(OH)D3 daily ( treatment group , n=43 ) or a placebo ( n=43 ) for 18 months . Bone mineral densities in the second metacarpals were determined by computed radiographic densitometry . Serum bone turnover indices were measured serially , and incidence of non-vertebral fractures was recorded . RESULTS Bone mineral densities decreased 1.2 % in the treatment group compared with 6.7 % in the placebo group during 18 months ( p<0.0001 ) . At baseline in both groups , the serum concentration of 1 , 25-[OH]2D was reduced . Parathyroid hormone was abnormally increased in 15 patients ( 17 % ) and correlated negatively with serum 25-hydroxyvitamin D , indicating compensatory hyperparathyroidism . Eight patients  sustained fractures ( six at the hip and two at other sites ) in the placebo group , and one hip fracture occurred among treated patients ( odds ratio 9.8 ; p=0.0028 ) . CONCLUSION By increasing serum 1 , 25-[OH]2D concentrations , treatment with 1α(OH)D3 can reduce the risk of hip and other non-vertebral fractures in osteoporotic elderly patients with Parkinson ’s disease by slowing the loss of bone mineral densities OBJECTIVES Estrogen deficiency is the most common cause of postmenopausal osteoporosis and estrogen replacement is well known to retard postmenopausal bone loss . Calcium supplement alone is generally considered to be insufficient for the prevention of bone loss associated with estrogen deficiency while the role of calcitriol is unclear . In the present study we examined the efficacy different doses of estrogen or calcitriol in the prevention of  postmenopausal bone loss in Thais . METHODS The subjects consisted of 146 Thai women no more than 6 years postmenopausal . The subjects were r and omly allocated to receive 750 mg supplemental calcium alone , calcium and conjugated equine estrogen ( CEE ) at 0.3 or 0.625 mg , calcium and calcitriol at 0.25 or 0.5 microg daily . Those receiving CEE also took 5 mg medrogestone for 12 days each month . BMD at L2 - 4 and femoral neck were measured at baseline 1 year and 2 years after treatments . Data were expressed as mean + /- S.E. RESULTS Subjects on supplemental calcium alone had approximately 2.5 % decreases in L2 - 4 ( P < 0.05 ) and femoral BMD ( P < 0.01 ) at 2 years . CEE ( 0.3 mg ) result ed in 3.20 + /- 1.2 % increase in vertebral BMD ( P < 0.05 ) while no significant change in BMD was demonstrated at the femoral neck . Likewise , 0.625 mg of CEE induced 5.4 + /- 1.4 % increase in vertebral BMD at 2 years ( P < 0.001 ) without change in the femoral BMD . In regard to calcitriol , no significant change in vertebral or femoral BMD was demonstrated with either 0.25 or 0.5 microg calcitriol . CONCLUSION We concluded that calcitriol is effective in the prevention of early postmenopausal bone loss in Thais . It represents an option for the prevention of osteoporosis in postmenopausal women who are contraindicated for estrogen replacement An unexplained loss of muscle strength occurs with aging . Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [ 1,25-(OH2)D3 ] to persons with low serum concentrations can improve strength . To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [ 1,25-(OH2)D3 ] , we conducted a r and omized , controlled , double blinded trial in 98 men and women volunteers over 69 yr old . Treatment consisted of 0.25 micrograms 1,25-(OH)2D3 , orally , twice per day or identical placebo for 6 months .  Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer . There was no difference between the two groups at 1 week , 1 month , or 6 months of treatment in any of the measures of muscle strength . We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons . Further research is needed to determine the etiology of the decline in muscle strength associated with aging Background —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels < 50 nmol/L ( 20 ng/mL ) received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P<0.001 ) and maintained this increase at 20 weeks . The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896 OBJECTIVE to determine the effect of risk factor modification and balance exercise on falls rates in residential care homes . DESIGN cluster r and omised controlled trial . PARTICIPANTS 196 residents ( aged 60 years or over ) in 20 residential care homes were enrolled ( 38 % response rate ) . Homes were r and omly allocated to intervention and control arms . A total of 102 residents were consigned to the intervention arm and 94 to the control arm . INTERVENTION a multifactorial falls prevention programme including 3 months gait and balance training , medication review , podiatry and optometry . MAIN OUTCOME MEASURES number of falls/recurrent falls per person , number of medications per person , and change in Tinetti gait and balance measure . RESULTS in the intervention group there was a mean of 2.2 falls per resident per year compared with 4.0 in the control group ; this failed to reach statistical significance ( P = 0.2 ) once the intra-cluster correlation ( ICC , 0.10 ) had been accounted for . Several risk factors were reduced in the intervention arm . CONCLUSIONS falls risk factor reduction is possible in residents of care homes . A modest reduction in falls rates was demonstrated but this failed to reach statistical significance BACKGROUND Different dosing protocol s have been used for vitamin D supplementation , but there has been a lack of comparative data among them . OBJECTIVE Our objective was to determine whether the same cumulative dose of vitamin D3 produces different effects if it is given daily , weekly , or monthly . DESIGN Women , age 81 + /- 8 yr ( + /- sd , n = 48 ) , who had undergone surgery to repair hip fracture were r and omized to vitamin D3-supplementation protocol s at 1,500 IU daily , or 10,500 IU once weekly , or 45,000 IU once every 28 d. The primary outcome measure was the serum 25-hydroxyvitamin D [ 25(OH)D ] concentration attained . RESULTS Initially , serum 25(OH)D concentrations for daily , weekly , and monthly groups were , respectively , 15.13 + /- 6.9 , 15.7 + /- 10.1 , and 16.2 + /- 10.1 ng/ml . By d 7 , these had increased significantly in all the groups ( P < 0.001 ) . On the first day after the monthly dose , both serum 25(OH)D and serum 1,25-dihydroxyvitamin D had increased significantly ( P < 0.012 each ) , whereas these did not change significantly on the day after daily or weekly doses . After 2 months , serum 25(OH)D with daily , weekly , and monthly dosing were , respectively , 33.2 + /- 8.5 , 29.2 + /- 8.9 , and 37.1 + /- 10.3 ng/ml ; there were no significant differences among these values . CONCLUSIONS Supplementation with vitamin D can be achieved equally well with daily , weekly , or monthly dosing frequencies . Therefore , the choice of dose frequency can be based on whichever approach will optimize an individual 's adherence with long-term vitamin D supplementation Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol , are important factors in the pathogenesis of age-related bone loss . The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on  bone loss in elderly women . Four hundred eighty-nine elderly women with normal bone density for their age , aged 65 - 77 yr , were entered into a r and omized double blind , placebo-controlled trial . Women were r and omized to one of four groups : conjugated estrogens ( 0.625 mg , daily ) to women without a uterus ( estrogen replacement therapy ) plus medroxyprogesterone acetate ( 2.5 mg , daily ) to women with a uterus ( hormone replacement therapy ) , calcitriol ( 0.25 microg twice daily ) , a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol , or placebos for 3 yr . The primary outcome was the change in bone mineral density of the femoral neck and spine . In the intent to treat analysis , hormone therapy ( hormone replacement therapy/estrogen replacement therapy ) produced a mean ( + /-1 SD ) increase in bone mineral density of 2.98 % ( + /-5.45 % ) at the femoral neck ( P < 0.0001 ) and 4.36 % ( + /-6.42 % ) at the spine ( P < 0.0001 ) . There were parallel increases in total hip and trochanter bone mineral density . Calcitriol increased bone mineral density 0.10 % ( + /- 4.27 % ) at the femoral neck ( P = 0.57 ) and 1.65 % ( + /- 4.83 % ) at the spine ( P < 0.0124 ) . The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol  increased bone mineral density 3.80 % ( + /-4.95 % ) at the femoral neck ( P < 0.001 ) , 4.91 % ( + /-6.0 % ) at the spine ( P < 0.0001 ) , and parallel changes at the total hip and trochanter . All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck , spine , total hip and trochanter . There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis . In a secondary analysis of the effect in women who were adherent to treatment , calcitriol had a more significant effect on spine ( P = 0.003 ) and total hip ( P = 0.004 ) . The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups . Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter ( P = 0.007 ) and total hip bone mineral density ( P = 0.0017 ) . In summary , hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinical ly relevant sites in a group of elderly women , with normal bone density for their age . Calcitriol was effective in increasing spine bone mineral density . In the adherent women , combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality . Data from r and omized controlled trials are limited . OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3 ) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease ( CVD ) risk . DESIGN We conducted a parallel-group , double-blind , placebo-controlled r and omized controlled trial . R and omization was computer generated . Participants and study investigators were blinded to intervention groupings throughout the trial . SETTING The study was conducted at the Clinical Research Facility , University of Aberdeen , United Kingdom . PARTICIPANTS A total of 305 healthy postmenopausal women aged 60 - 70 yr were recruited for the study . INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3 ) or placebo r and omly allocated . MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [ total , high-density lipoprotein , and low-density lipoprotein cholesterol ; triglycerides ; and apolipoproteins A-1 and B100 ] , insulin resistance ( homeostatic model assessment ) , inflammatory biomarkers ( high-sensitivity C-reactive protein , IL-6 , soluble intracellular adhesion molecule-1 ) , and blood pressure . RESULTS A total of 265 ( 87 % ) participants completed all study visits . Small differences between groups for serum apolipoprotein B100 change [ repeated measures ANOVA , P=0.04 ; mean ( sd ) , -1.0 ( 10.0 ) mg/dl ( 400 IU ) ; -1.0 ( 10.0 ) mg/dl ( 1000 IU ) ; and + 0.02 ( 10.0 ) mg/dl ( placebo ) ] were not considered clinical ly significant . Other systemic markers for CVD risk remained unchanged . There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose ( P<0.001 , linear mixed model ) . Mean ( sd ) reduction in systolic blood pressure from winter to summer was -6.6 ( 10.8 ) mm Hg . CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors . Confounding of seasonality should be recognized and addressed in future studies of vitamin The necessity and safety of an oral calcium ( Ca ) and vitamin D regimen was evaluated in a population of 66 independently living and 73 institutionalized elderly women over an 11-week winter period . The members of both groups were r and omly assigned into trial and control groups . Serum Ca , creatinine , and calcidiol levels were measured before and after the trial . The regimen consisted of 1.558 g of Ca and 45 micrograms ( equal to 1,800 IU ) of vitamin D administered daily in addition to the normal diet . The controls received no treatment . A majority of the elderly subjects living independently had ensured their Ca , and a quarter of them also their vitamin D intake on their own initiative . The mean serum calcidiol concentration before the trial was 24.1 nmol/L in the institutionalized and 38.5 nmol/L in the elderly subjects living independently ( P less than .001 ) . After the trial , serum calcidiol was 10.4 nmol/L in the institutionalized control subjects and had decreased ( P less than .001 ) in both control groups , but increased ( P less than .001 ) in both treatment groups . The safety indicators , serum Ca , creatinine , and calcidiol , did not indicate any group or individual side effect To evaluate the effects of alfacalcidol on bone turnover in elderly women with osteoporosis , an open-label , prospect i ve , calcium-controlled study was conducted . A total of 80 patients with osteoporosis were divided into two groups : the control group , group C ( mean age , 78.0 years ) , in which patients were given calcium , and group D ( mean age , 77.4 years ) , in which the patients were given alfacalcidol 1 µg/day together with calcium for 6 months . Calcium regulation , lumbar bone mineral density ( LBMD ) , and markers for bone turnover were assessed . A significant increase in urinary calcium/creatinine ratio ( 90 % increase from baseline at 3 months ; P = 0.0083 , and 60 % at 6 months ; P = 0.0091 ) and a significant decrease in serum parathyroid hormone ( 30 % decrease from baseline at 6 months ; P < 0.0001 ) was observed in group D compared with the corresponding changes in group C. Significant decreases of bone resorption markers ( deoxypyridinoline and N-telopeptide ) at 6 months ( about 15 % decrease from the baseline values ) were observed in group D compared with the corresponding changes in group C. The changes in bone formation markers ( bone-derived alkaline phosphatase and osteocalcin ) in group D were significantly different at 6 months ( −21.5 % ; P = 0.0047 and −13.4 % ; P = 0.0032 , respectively ) from the values in group C. The magnitudes of the decrease in bone turnover markers were highly correlated with the corresponding baseline values , suggesting that alfacalcidol treatment effectively reduces bone turnover in patients with high bone turnover rates . The LBMD in group D increased by 1.7 % and that in group C decreased by 1.6 % ( P = 0.0384 ) . The changes in calcium metabolism and LBMD were in good agreement with those in previous reports . Although the changes in bone turnover markers in group D were slight , significant reduction in bone turnover with alfacalcidol treatment , together with the change in calcium metabolism , may account for the effects of alfacalcidol on BMD and on fracture prevention reported previously . In conclusion , alfacalcidol reduces bone turnover  in elderly women with high-bone-turnover osteoporosis , and it may have beneficial effects on bone A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side , correlating with the degree of paralysis and vitamin D deficiency due to malnutrition , sunlight deprivation , and immobilization-induced hypercalcemia , and increases the risk of hip fracture . We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [ 1alpha(OH)D3 ; vitamin D3 ] administration on bone mineral density preservation as compared with untreated controls . In a r and omized and prospect i ve study of 103 patients with hemiplegia after stroke ( the mean duration of illness was 4.8 yr ) , 68 ( 34 patients in each group ) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo , whereas the remaining 35 patients received no drug .  Bone mineral density on the hemiplegic side decreased by 1.4 % in the ipriflavone group , 3.8 % in the vitamin D3 group , and 5.4 % in the control group ( P < .0001 , ipriflavone v vitamin D3 and control ) . At baseline , all three groups of patients showed a 25-hydroxyvitamin D insufficiency , increased serum ionized calcium , and low levels of 1 , 25-dihydroxyvitamin D , suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1 , 25-dihydroxyvitamin D. After treatment , the serum 1 , 25-dihydroxyvitamin D level increased by 139.9 % in the ipriflavone group and by 26.9 % in the vitamin D3 group . Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen , and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group , whereas no changes occurred in the other two groups . One patient in the untreated group suffered a hip fracture , compared with none in the ipriflavone and vitamin D3 groups . These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1 , 25-dihydroxyvitamin D concentration Background It is undetermined whether calcium supplementation has an effect on obesity or body composition in postmenopausal women . The purpose of the study is to detect the effect of calcium supplementation on indices of obesity and body composition . Methods This is a secondary analysis of data from a population -based , double-blind , placebo-controlled , r and omized trial design ed to determine the effects of calcium and vitamin D on osteoporotic fractures . The cohort included 1179 postmenopausal women who were r and omly assigned into one of three groups : 1 ) supplemental calcium ( 1400 mg/d or 1500 mg/d ) plus vitamin D placebo ( Ca-only group ) ; 2 ) supplemental calcium ( 1400 mg/d or 1500 mg/d ) plus supplemental vitamin D3 ( 1100 IU/d ) ( Ca + D group ) ; or , 3 ) two placebos ( placebo group ) . After applying the exclusion criteria for this analysis , 870 subjects were included in this study . The primary outcomes for the present study were changes in body mass index , trunk fat , trunk lean , and percentage of trunk fat after calcium supplementation . Results Changes in trunk fat , trunk lean , and percentage of trunk fat were significantly different between the calcium intervention groups ( Ca-only group or Ca + D group ) and the placebo group during the trial ( P < 0.05 ) . The calcium intervention groups gained less trunk fat and maintained more trunk lean when compared to the placebo group . No significant difference was observed for body mass index between groups . Conclusion Calcium supplementation over four years has a beneficial effect on body composition in postmenopausal women BACKGROUND The Food and Nutrition Board of the National Academy of Sciences states that 95 microg vitamin D/d is the lowest observed adverse effect level ( LOAEL ) . OBJECTIVE Our objective was to assess the efficacy and safety of prolonged vitamin D3 intakes of 25 and 100 microg ( 1000 and 4000 IU)/d . Efficacy was based on the lowest serum 25-hydroxyvitamin D [ 25(OH)D ] concentration achieved by subjects taking vitamin D3 ; potential toxicity was monitored by measuring serum calcium concentrations and by calculating urinary calcium-creatinine ratios . DESIGN Healthy men and women ( n = 61 ) aged 41 + /- 9 y ( mean + /- SD ) were r and omly assigned to receive either 25 or 100 microg vitamin D3/d for 2 - 5 mo , starting between January and February . Serum 25(OH)D was measured by radioimmunoassay . RESULTS Baseline serum 25(OH)D was 40.7 + /- 15.4 nmol/L ( mean + /- SD ) . From 3 mo on , serum 25(OH)D plateaued at 68.7 + /- 16.9 nmol/L in the 25-microg/d group and at 96.4 + /- 14.6 nmol/L in the 100-microg/d group . Summertime serum 25(OH)D concentrations in 25 comparable subjects not taking vitamin D3 were 46.7 + /- 17.8 nmol/L. The minimum and maximum plateau serum 25(OH)D concentrations in subjects taking 25 and 100 microg vitamin D3/d were 40 and 100 nmol/L and 69 and 125 nmol/L , respectively . Serum calcium and urinary calcium excretion did not change significantly at either dosage during the study . CONCLUSIONS The 100-microg/d dosage of vitamin D3 effectively increased 25(OH)D to high-normal concentrations in practically all adults and serum 25(OH)D remained within the physiologic range ; therefore , we consider 100 microg vitamin D3/d to be a safe intake BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk  of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P < 0.03 ) . With the use of logistic regression , the unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P < 0.005 ) but did not change significantly for the Ca-only group . In multiple logistic regression models , both treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces  all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170 BACKGROUND Increased vitamin D intake may preserve or increase bone mineral density ( BMD ) in older persons . OBJECTIVE A 2-y double-blind study was undertaken to determine whether weekly administration of 10 000 units of vitamin D(2 ) maintained or increased BMD in younger postmenopausal women more efficiently than did calcium supplements alone . DESIGN One hundred eighty-seven women who were > or= 1 y postmenopausal were r and omly assigned to take either 1000 mg Ca/d after the evening meal or 1000 mg Ca/d plus 10 000 U vitamin D(2)/wk in a double-blind , placebo-controlled format . The BMD of the proximal forearm , lumbar spine , femoral neck , Ward 's triangle , and femoral trochanter was measured at 6-mo intervals by osteodensitometry . RESULTS During the 2-y period , there was no significant difference in the change in BMD at any site between the subjects taking calcium supplements and those taking calcium plus vitamin D(2 ) . Both groups significantly ( P < 0.005 ) gained BMD in Ward 's triangle and the femoral trochanter but significantly ( P < 0.005 ) lost bone in the proximal radius . There was no significant change in the lumbar spine or femoral neck BMD . CONCLUSION In younger postmenopausal women ( age : 56 y ) whose average baseline serum 25-hydroxyvitamin D concentration was well within the normal range , the addition of 10 000 U vitamin D(2)/wk to calcium supplementation at 1000 mg/d did not confer benefits on BMD beyond those achieved with calcium supplementation alone BACKGROUND Supplementation with calcium and vitamin D reduces bone loss and prevents fractures in elderly people , but it is not known whether any lasting benefit remains if the supplements are discontinued . OBJECTIVE The objective was to determine whether gains in bone mineral density ( BMD ) induced by calcium and vitamin D supplementation persist after supplement withdrawal . DESIGN Two-hundred ninety-five healthy , elderly men and women ( aged > /=68 y ) who had completed a 3-y r and omized , placebo-controlled trial of calcium and vitamin D supplementation were followed for an additional 2 y during which no study supplements were given .  BMD was measured by dual-energy X-ray absorptiometry , and biochemical variables related to calcium metabolism and bone turnover were measured . RESULTS In the 128 men , supplement-induced increases in spinal and femoral neck BMD were lost within 2 y of supplement discontinuation , but small benefits in total-body BMD remained . In the 167 women , there were no lasting benefits in total-body BMD or at any bone site . Consistent with the observations on BMD , the bone turnover rates in both men and women ( as measured by serum osteocalcin concentrations ) returned to their original higher concentrations within the same 2-y period . CONCLUSION Discontinued calcium and vitamin D supplementation has limited cumulative effect on bone mass in men and women aged > /=68 BACKGROUND There is currently no consensus on the effect of dietary protein intake on the skeleton , but there is some indication that low calcium intakes adversely influence the effect of dietary protein on fracture risk . OBJECTIVE The objective of the present study was to determine whether supplemental calcium citrate malate and vitamin D influence any associations between  protein intake and change in bone mineral density ( BMD ) . DESIGN Associations between protein intake and change in BMD were examined in 342 healthy men and women ( aged > or = 65 y ) who had completed a 3-y , r and omized , placebo-controlled trial of calcium and vitamin D supplementation . Protein intake was assessed at the midpoint of the study with the use of a food-frequency question naire and  BMD  was assessed every 6 mo by dual-energy X-ray absorptiometry . RESULTS The mean ( + /-SD ) protein intake of all subjects was 79.1 + /- 25.6 g/d and the mean total calcium intakes of the supplemented and placebo groups were 1346 + /- 358 and 871 + /- 413 mg/d , respectively . Higher protein intake was significantly associated with a favorable 3-y change in total-body BMD in the supplemented group ( in a model containing terms for age , sex , weight , total energy intake , and dietary calcium intake ) but not in the placebo group . The pattern of change in femoral neck BMD with increasing protein intake in the supplemented group was similar to that for the total body . CONCLUSION Increasing protein intake may have a favorable effect on change in BMD in elderly subjects supplemented with calcium citrate malate and vitamin BACKGROUND Adequate intakes of calcium and vitamin D reduce bone loss and fracture risk in the elderly . Other nutrients also affect bone health , and adequate intakes may influence bone turnover and balance . OBJECTIVE We compared the long-term effects on bone turnover markers and calciotropic hormones of a multinutrient supplement , a calcium and vitamin D supplement , and dietary instruction aim ed at increasing calcium intake through foods . DESIGN Ninety-nine healthy postmenopausal women participated in a 3-y , r and omized trial , receiving either 1 ) supplemental calcium ( 1450 mg/d ) and vitamin D [ 10 microg ( 400 IU)/d ] , 2 ) calcium , vitamin D , and other nutrients ( multinutrient supplement ) , or 3 ) dietary instruction ( dietary control group ) . Data are from 83 subjects who completed the trial . RESULTS Increases over baseline in calcium intakes and serum 25-hydroxyvitamin D concentrations were sustained over 3 y in all treatment groups . Circulating parathyroid hormone concentrations were reduced at year 1 in all treatment groups but trended toward baseline thereafter . Bone turnover markers followed a similar pattern , and none of the changes in biochemical concentrations differed significantly between groups . CONCLUSIONS All 3 interventions offer long-term feasibility for increasing calcium intake and serum 25-hydroxyvitamin D concentrations . The dietary addition of micronutrients implicated in skeletal physiology confers no obvious bone-sparing effect in healthy postmenopausal women beyond that of calcium and vitamin D alone . The attenuation over time in suppression of parathyroid hormone and bone turnover might help explain why nutrient intervention tends to have less of a bone-sparing effect than do skeletally active medications such as estrogen or bisphosphonates A r and omized double-blind controlled trial of a single oral dose of 2.5 mg ( 100,000 IU ) cholecalciferol ( vitamin D3 ) was conducted in the winter in 189 healthy free-living men and women aged 63 - 76 y. The mean baseline serum concentration for 25-hydroxyvitamin D was 34.5 nmol/L and for parathyroid hormone 3.18 pmol/L. After 5 wk , mean serum 25-hydroxyvitamin D concentrations were 60 % higher in the treated than in the placebo group ( P < 0.001 ) . There was a 12 % difference in parathyroid hormone concentrations in the treated compared with the placebo group ( P < 0.001 ) . No differences in serum calcium were seen . Findings suggest that 25-hydroxyvitamin D has a physiological role in the regulation of parathyroid secretion independent of serum calcium in healthy elderly people .  Parathyroid concentrations rise and 25-hydroxyvitamin D concentrations decline with age . These results may have implication s for the prevention of osteoporotic fractures that occur with increased frequency in winter and in elderly people 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 Abstract : Supplementation of elderly institutionalized women with vitamin D and calcium  decreased hip fractures and increased hip bone mineral density . Quantitative ultrasound ( QUS ) measurements can be performed in nursing homes , and easily repeated for follow-up . However , the effect of the correction of vitamin D deficiency on QUS parameters is not known . Therefore , 248 institutionalized women aged 62–98 years were included in a 2-year open controlled study . They were r and omized into a treated group ( n = 124 ) , receiving 440 IU of vitamin D3 combined with 500 mg calcium ( 1250 mg calcium carbonate , Novartis ) twice daily , and a control group ( n = 124 ) . One hundred and three women ( 42 % ) , aged 84.5 ± 7.5 years , completed the study : 50 in the treated group , 53 in the  controls  . QUS of the calcaneus , which measures BUA ( broadb and ultrasound attenuation ) and SOS ( speed of sound ) , and biochemical analysis were performed before and after 1 and 2 years of treatment . Only the results of the women with a complete follow-up were taken into account . Both groups had low initial mean serum 25-hydroxyvitamin D levels ( 11.9 ± 1.2 and 11.7 ± 1.2 mg/l ; normal range 6.4–40.2 mg/l ) and normal mean serum parathyroid hormone ( PTH ) levels ( 43.1 ± 3.2 and 44.6 ± 3.5 ng/l ; normal range 10–70 ng/l , normal mean 31.8 ± 2.3 ng/l ) . The treatment led to a correction of the metabolic disturbances , with an increase in 25-hydroxyvitamin D by 123 % ( p50.01 ) and a decrease in PTH by 18 % ( p50.05 ) and of alkaline phosphatase by 15 % ( p50.01 ) . In the controls there was a worsening of the hypovitaminosis D , with a decrease of 25-hydroxyvitamin D by 51 % ( p50.01 ) and an increase in PTH by 51 % ( p50.01 ) , while the serum calcium level decreased by only 2 % ( p5 0.01 ) . After 2 years of treatment BUA increased significantly by 1.6 % in the treated group ( p50.05 ) , and decreased by 2.3 % in the controls ( p50.01 ) . Therefore , the difference in BUA between the treated subjects and the controls ( 3.9 % ) was significant after 2 years ( p50.01 ) . However , SOS decreased by the same amount in both groups ( approximately 0.5 % ) . In conclusion , BUA , but not SOS , reflected the positive effect on bone of supplementation with calcium and vitamin D3 in a population of elderly institutionalized women BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women 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 An ongoing r and omized clinical trial of 3 years duration is being undertaken to evaluate the recurrent fracture rate and safety profile associated with low-dose calcitriol versus calcium supplementation in women with at least 3 years postmenopausal osteoporosis who are under the age of 80 years . A total of 856 patients were su bmi tted for possible inclusion in the study by 123 primary care physicians , and 636 met all entry requirements . Each patient was r and omly allocated to receive either 0.25 micrograms of calcitriol twice daily or calcium supplementation of 1,000 mg/d . If significant hypercalcemia developed ( greater than 2.6 mmol/L ) or a deterioration in renal function was observed , the dose of trial medication was to be halved or stopped if laboratory values did not return to normal . Patients were given no specific instructions regarding dietary calcium intake . To date , 528 patient-years experience with calcitriol  and 527 patient-years experience with calcium the calcium supplementation have been accumulated . Thus far , low-dose calcitriol has not been observed to cause hypercalcemia , deterioration in renal function , or nephrocalcinosis . At 1 year , a loss in total anterior height ( P less than .05 ) has been detected in the calcium-treated group compared with the calcitriol-treated group . Thus , calcitriol appears to preserve spinal height . Long-term follow-up of all patients for 2 or 3 years will be continued We previously observed that a creatinine clearance ( CrCl ) of < 65 ml/min is a significant and independent risk factor for the number of fallers and falls in a community-dwelling elderly population and postulated that this increased risk is due to the associated significant lower D-hormone serum levels . To test our hypothesis , we investigated in a post hoc analysis of a double-blind r and omized study whether treatment with alfacalcidol , a synthetic prodrug of the D-hormone , can reduce the high incidence of fallers and the high risk of falls associated with low CrCl . Of 378 Swiss community-dwelling women ( n=191 ) and men ( n=187 ) , aged 70 years and older , 191 received r and omly 1 μg capsules of alfacalcidol ( AlphaD3 : Teva ) , and 187 received one capsule of placebo daily . With the help of question naires we regularly assessed the incidence and frequency of falls . The risk of becoming a faller and the risk of falling were assessed in multivariate-controlled logistic regression models according to treatment groups and according to a CrCl cut-off of 65 ml/min . The presented results are from ITT analyses . In participants with a CrCl of < 65 ml/min , the 36 weeks of treatment with alfacalcidol was , compared with placebo , associated with a significant reduction in the number of fallers ( 14/72 versus 25/70 ; OR 0.26 , 95 % CI 0.08–0.80 , P=0.019 ) , and a significant reduction of the number of falls ( 16/72 versus 28/70 ; OR 0.29 , 95 % CI 0.09–0.88 , P=0.028 ) . No such association was observed in participants with a CrCl of ≥65 ml/min ( for fallers 26/120 versus 21/116 ; OR 0.92 95 % CI 0.34–2.52 , P=0.875 ; for falls 32/120 versus 23/116 ; OR 0.93 95 % CI 0.34–2.54 , P=0.885 ) . In the  placebo group frequency of falls was dependent on CrCl ( P=0.006 ) , whereas in the alfacalcidol  treatment group frequency of falls was independent of CrCl ( P=0.494 ) . No cases of clinical ly relevant hypercalcemia were observed . In a community-dwelling population of elderly men and women with a CrCl of < 65 ml/min , treatment with alfacalcidol can significantly and safely reduce the low CrCl associated increased number of fallers and the high risk of falls The Women 's Health Initiative ( WHI ) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women , including cancer , cardiovascular disease , and osteoporotic fractures . The WHI was initiated in 1992 , with a planned completion date of 2007 . Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial ( CT ) that will include about 64,500 women or an observational study ( OS ) that will include about 100,000 women . The CT is design ed to allow r and omized controlled evaluation of three distinct interventions : a low-fat eating pattern , hypothesized to prevent breast cancer and colorectal cancer and , secondarily , coronary heart disease ; hormone replacement therapy , hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and , secondarily , to reduce the risk of hip and other fractures , with increased breast cancer risk as a possible adverse outcome ; and calcium and vitamin D supplementation , hypothesized to prevent hip fractures and , secondarily , other fractures and colorectal cancer . Overall benefit-versus-risk assessment is a central focus in each of the three CT components . Women are screened for participation in one or both of the components -- dietary modification ( DM ) or hormone replacement therapy (HRT)--of the CT , which will r and omize 48,000 and 27,500 women , respectively . Women who prove to be ineligible for , or who are unwilling to enroll in , these CT components are invited to enroll in the OS . At their 1-year anniversary of r and omization , CT women are invited to be further r and omized into the calcium and vitamin D ( CaD ) trial component , which is projected to include 45,000 women . The average follow-up for women in either CT or OS is approximately 9 years . Concerted efforts are made to enroll women of racial and ethnic minority groups , with a target of 20 % of overall enrollment in both the CT and OS . This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component . Some detail is provided on specific study design choices , including eligibility criteria , recruitment strategy , and sample size , with attention to the partial factorial design of the CT . Some aspects of the CT monitoring approach are also outlined . The scientific and logistic complexity of the WHI implies particular leadership and management challenges . The WHI organization and committee structure employed to respond to these challenges is also briefly described 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 Conflicting data regarding cardiovascular effects of thiazolidinediones ( TZDs ) and extra-skeletal effects of vitamin D supported the need for a definitive trial . The Thiazolidinedione Intervention with vitamin D Evaluation ( TIDE ) trial aim ed to assess the effects of TZDs ( rosiglitazone and pioglitazone ) on cardiovascular outcomes and the effects of vitamin D ( cholecalciferol ) on  cancers and mortality . A large multicentre 3 × 2 factorial double-blind placebo-controlled r and omised trial recruited from outpatient primary care and specialty clinics in 33 countries . From June 2009 to July 2010 , 1,332 people with type 2 diabetes and other cardiovascular risk factors aged ≥50 years whose HbA1c was 6.5–9.5 % ( 48–80 mmol/mol ) when using two or fewer glucose-lowering drugs were r and omised by a central computer system to placebo ( n = 541 ) , rosiglitazone 4–8 mg/day ( n = 399 ) or pioglitazone 30–45 mg/day ( n = 392 ) ; 1,221 participants were r and omised to placebo ( n = 614 ) or vitamin D 1,000 IU/day ( n = 607 ) . Participants and all study personnel were blind to treatment allocation . The primary outcome for the TZD arm was the composite of myocardial infa rct ion , stroke or cardiovascular death , and for the vitamin D arm it was cancer or all-cause death . All r and omised participants were included in the primary analysis . From the study design , 16,000 people were to be followed for approximately 5.5 years . However , the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data . In the TZD arm , the cardiovascular outcome occurred in five participants ( 0.9 % ) in the placebo groups and three participants ( 0.4 % ) in the TZD groups ( two allocated to pioglitazone , one to rosiglitazone ) . In the vitamin D arm , the primary outcome occurred in three participants ( 0.5 % ) in the placebo group and in two participants ( 0.3 % ) receiving vitamin D. Adverse events were comparable in all groups . Uncertainty persists regarding the clinical ly relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial . Clinical Trials.gov NCT00879970 The study was funded by GlaxoSmithKline Women with vertebral deformities caused by osteoporosis have more back pain and disability and are at higher risk for subsequent vertebral deformities than women without deformities . Despite the importance of vertebral deformities , there has been a great deal of controversy about how to identify or define them . In order to compare methods for defining vertebral deformities , we studied  spinal radiographs from women in the Study of Osteoporotic Fractures ( SOF ) , a cohort study of 9704 non-black women over age 65 recruited from population -based listings in four clinical centers . Using radiographs obtained at the baseline exam , we compared five methods for defining vertebral deformities : one based on a semiquantitative reading by a radiologist and four using vertebral morphometry . The semiquantitative method was compared with the other methods in a r and om sample of 503 films , while the morphometric methods were compared with each other in a larger sample of 9575 films . We tested a system of " triage " in which only those films with evidence of deformity were assessed by morphometry . We compared the relationship between deformity , defined by each method , and a variety of clinical criteria including bone mineral density at the lumbar spine , height loss since age 25 , back pain , and incidence of subsequent deformity . Semiquantitative reading and three of the four morphometry-based methods provided similar relationships to clinical criteria . The fourth morphometry method ( based on ratios of each vertebral height to the corresponding height at T4 ) produced significantly weaker relationships for several of the clinical validation criteria . Triage of radiographs rarely result ed in missed deformities and did not reduce the performance of any of the methods . We conclude that use of any of the similar methods , with or without triage , provides a valid approach to defining vertebral deformities 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 OBJECTIVE This study investigated whether a combined regimen of ipriflavone and 1 alpha vitamin D is effective in stopping postmenopausal bone loss . METHODS Ninety-eight postmenopausal women were recruited and r and omly assigned to one of four groups : group 1 , ipriflavone alone ; group 2 , 1 alpha vitamin D alone ; group 3 , combined regimen of ipriflavone and 1 alpha vitamin D ; group 4 , no treatment .  Vertebral bone mineral density , measured by dual energy X-ray absorptiometry , serum alkaline phosphatase , calcitonin , parathyroid hormone , osteocalcin , urinary calcium and hydroxyproline were measured before and at the 6th , 12th and 18th month of the study . All comparisons were made using Student 's t-test of means . RESULT There was a significant reduction in vertebral bone loss in the patients receiving the combined therapy ( mean loss after 18 months 0.33 % in the combination group vs. 2.37 % , 1.15 % and 3.70 % in the ipriflavone alone , 1 alpha vitamin D alone , and control groups , respectively ; P < 0.001 ) . CONCLUSION These findings suggest that the combined regimen could prevent postmenopausal bone loss The effects on general and bone metabolism of femoral neck fracture patients of 0.25 μg α-calcoid given orally twice daily ( n=9 ) and 25 μg calcitonin given subcutaneously 30 times ( n=10 ) in 10 weeks were studied against a  control ( n = ll ) . Bone histology and histomorphometry showed non-age related osteoporosis in 30 % and osteomalacia in 22 % of the patients studied . Impaired serum vitamin D status was found in 47 – 88 % of patients , secondary hyperparathyroidism and increased serum parathyroid hormone in 59 % and decreased serum calcitonin levels in 69 % . On histology , normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3,1,25- and 24,25-dihydroxy vitamin D3 . Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia . Calcitonin improved calcium balance , reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia .  Vitamin  D reduced osteomalacia , slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone . Both treatments gave a similar slight decrease in serum calcitonin concentrations . A mechanism of action for the treatments is suggested The aim was to assess the effects of resistance training and vitamin D supplementation on physical performance of healthy elderly subjects . Ninety-six subjects , aged 70 years or more with 25 OH vitamin D levels of 16 ng/ml or less , were r and omized to a  resistance training or control group . Trained and control groups were further r and omized to receive in a double blind fashion , vitamin D 400 IU plus 800 mg of calcium per day or calcium alone . Subjects were followed for nine months . Serum 25 OH vitamin D increased from 12.4+/-2.2 to 25.8+/-6.5 ng/ml among subjects supplemented with vitamin D. Trained subjects had significant improvements in quadriceps muscle strength , the short physical performance test and timed up and go . The latter improved more in trained subjects supplemented with vitamin D. At the end of the follow up , gait speed was higher among subjects supplemented with vitamin ( whether trained or not ) than in non-supplemented subjects ( 838+/-147 and 768+/-127 m/12 min , respectively , p=0.02 ) . Romberg ratio was lower among supplemented controls than non-supplemented trained subjects ( 128+/-40 % and 144+/-37 % , respectively , p=0.05 ) . In conclusion , vitamin D supplementation improved gait speed and body sway , and training improved muscle strength OBJECTIVES Assessment of additive impact of alfacalcidol 1 μg daily ( Alfa ) on bone mineral density ( BMD ) and on bone strength in postmenopausal women treated with alendronate 70 mg weekly + 500 mg calcium daily . SUBJECTS AND METHODS In a r and omized , double-blind , placebo controlled study , 279 postmenopausal women with osteoporosis or osteopenia participated ( intention to treat analysis [ ITT ] ; aged 73.6∓4.7 years ) and were treated with 70 mg alendronate ( ALN ) weekly and 500 mg calcium daily for 36 months . In addition , these patients received either 1 μg alfacalcidol ( Alfa ) or placebo ( PLC ) daily . BMD was measured with Dual-Energy-X-ray-Absorptiometry ( DXA ) at the lumbar spine and proximal femur and at forearm and tibia with peripheral quantitative computed tomography ( pQCT ) at regular intervals for 36 months . RESULTS DXA-BMD of lumbar spine ( L1 - 4 ) increased after 36 months , by 6.65 % ( p<0.0001 ) in the Alfa/ALN group versus 4.17 % ( p<0.0001 ) in the PLC/ALN group . Group difference was significant after 3 years ( p=0.026 ) . At the end of the study , significant differences were found in favor of the Alfa/ALN group in trabecular density ( tibia ) ( p=0.002 ) , cortical density ( midshaft tibia ) ( p=0.043 ) , and bone strength ( p=0.001 ) . The remaining parameters showed no differences between the treatment arms , apart cortical bone density at midshaft radius . CONCLUSIONS Alfacalcidol significantly increases the efficacy of alendronate treatment in osteopenic/osteoporotic postmenopausal women  on spinal DXA-BMD , cortical and trabecular BMD of the tibia and also bending stiffness of the tibia OBJECTIVES To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents . DESIGN Secondary data analysis of a previously conducted r and omized clinical trial . SETTING Seven hundred twenty-five-bed long-term care facility . PARTICIPANTS One hundred twenty-four nursing home residents ( average age 89 ) . INTERVENTION Participants were r and omly assigned to receive one of four vitamin D supplement doses ( 200 IU , 400 IU , 600 IU , or 800 IU ) or placebo daily for 5 months . MEASUREMENTS Number of fallers and number of falls assessed using facility incident tracking data base . RESULTS Over the 5-month study period , the proportion of participants with falls was 44 % in the placebo group ( 11/25 ) , 58 % ( 15/26 ) in the 200 IU group , 60 % ( 15/25 ) in the 400 IU group , 60 % ( 15/25 ) in the 600 IU group , and 20 % ( 5/23 ) in the 800 IU group . Participants in the 800 IU group had a 72 % lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months ( rate ratio=0.28 ; 95 % confidence interval=0.11 - 0.75 ) . No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups . CONCLUSION Nursing home residents in the highest vitamin D group ( 800 IU ) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses . Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group Abstract Aim : To observe the efficacy and safety of Rocaltrol ( calcitriol ) and /or Caltrate D ( calicum carbonate plus vitamin D ) in elderly Chinese women with osteopenia or osteoporosis . Methods : One hundred fifty Chinese women aged over 65 years with osteopenia or osteoporosis from three centers were r and omly divided into two groups . Seventy-six participants received Caltrate D as one pill daily ; the other 74 participants received 0.25 μg Caltrate D plus Rocaltrol daily . The changes in bone mineral density ( BMD ) served as primary end-points . Height changes , the presence of new vertebral fractures , muscle strength and balance were evaluated . Results : The following are the mean percentage changes ( and SD ) in BMD over 12 months : at L2-L4 , 0.83±3.88 in the Caltrate D group and 2.84±4.04 in the Rocaltrol+Caltrate D group ( P=0.003 , by ANCOVA ) ; at the femoral neck , 0.04±3.94 in the Caltrate D group and 2.01±5.45 in the Rocaltrol+Caltrate D group ( P=0.085 , by ANCOVA ) ; and in the trochanter , 1.59±4.57 in the Caltrate D group and 3.76±6.25 in the Rocaltrol+Caltrate D group ( P=0.053 , by ANCOVA ) . The st and and maximal forward reach test ( SMFRT ) was significantly enhanced in both groups during the 12 months of treatment , but no significant differences were found between these two groups . No severe adverse event related to these medications occurred throughout the study . Conclusion : Treatment with Rocaltrol plus Caltrate D or Caltrate D for 12 months in elderly Chinese postmenopausal women  effectively increased BMD at the lumbar spine . Rocaltrol plus Caltrate D was more effective at the lumbar spine than Caltrate D alone CONTEXT Effects of long-term calcium , with or without vitamin D , on  hip bone mineral density ( BMD ) and bone turnover in sunny climates have not been reported . OBJECTIVE The aim was to evaluate the effect of vitamin D added to calcium supplementation on hip dual-energy x-ray absorptiometry BMD and calcium-related analytes . DESIGN , SETTING , AND PARTICIPANTS The study was a 5-yr r and omized , controlled , double-blind trial of 120 community-dwelling women aged 70 - 80 yr . INTERVENTIONS The interventions were 1200 mg/d calcium with placebo vitamin D ( Ca group ) or with 1000 IU/d vitamin D2 ( CaD group ) , or double placebo ( control ) . MAIN OUTCOME MEASURES Hip BMD , plasma 25-hydroxyvitamin D , biomarkers of bone turnover , PTH , and intestinal calcium absorption were measured . RESULTS Hip BMD was preserved in CaD ( -0.17 % ) and Ca ( 0.19 % ) groups but not controls ( -1.27 % ) at yr 1 and maintained in the CaD group only at yr 3 and 5 . The beneficial effects were mainly in those with baseline 25-hydroxyvitamin D levels below the median ( 68 nmol/liter ) . At yr 1 , compared with controls , the Ca and CaD groups had 6.8 and 11.3 % lower plasma alkaline phosphatase , respectively ( P < or=0.02 ) , and 28.7 and 34.5 % lower urinary deoxypyridinoline to creatinine ratio , respectively ( P < or=0.05 ) . At 5 yr , this suppression was maintained only in the CaD group . CaD reduced PTH at 3 and 5 yr cf . controls ( 27.8 and 31.3 % , P < or=0.005 ) in those with baseline PTH levels above the median ( 3.6 pmol/liter ) . Therapy did not affect intestinal calcium absorption at high carrier loads . CONCLUSIONS Addition of vitamin D to calcium has long-term beneficial effects on bone density in elderly women living in a sunny climate , probably mediated by a long-term reduction in bone turnover rate In a r and omized multicenter , double-blind , double-dummy , parallel group study a comparison of the efficacy and safety of 1 μg alfacalcidol to 880 IU vitamin D plus calcium carbonate ( 1 g calcium ) once daily per os was performed on 148 postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels for 18 months .  Bone mineral density ( BMD ) was measured at baseline , 12 and 18 months . Safety parameters were followed during the entire study period . Sixty-nine ( 90.8 % ) in the alfacalcidol group and 67 ( 93.1 % ) in the vitamin D group were included in the ITT analysis . Lumbar BMD in the alfacalcidol group increased by 0.017 g/cm2 ( 2.33 % ) and 0.021 g/cm2 ( 2.87 % ) from baseline ( P<0.001 ) at 12 and 18 months , respectively , whereas in the vitamin D plus calcium group the increase was 0.005 g/cm2 ( 0.70 % ) from baseline ( N.S. ) at both 12 and 18 months . The higher changes from baseline in the alfacalcidol group , as compared to the changes in the vitamin D plus calcium group at both 12 and 18 months , were found to be statistically significant ( P=0.018 , 0.005 ) . A small increase of mean femoral BMD was achieved in both groups ( N.S. ) . Adverse events were similar in both groups . No significant differences were noted between the groups in serum calcium . In conclusion , alfacalcidol was found to be superior in significantly increasing lumbar BMD as compared to vitamin D plus calcium while safety characteristics were found to be similar in both treatments 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 PURPOSE To assess the comparative effectiveness of several medications on bone mineral density , biochemical bone markers , and the incidence of vertebral fractures in postmenopausal women with osteoporosis . METHODS A total of 396 postmenopausal women , aged 50 to 75 years , were allocated r and omly to six equal-sized groups : hormone replacement therapy , etidronate , eel calcitonin , alfacalcidol , vitamin K ( menatetrenone ) , or control ( no treatment ) .  Thoracic and lumbar spine radiographs , bone mineral density at the distal radius , and markers of bone turnover were assessed at baseline and every 3 months during the 2-year study . RESULTS Compared with baseline , the 2-year mean changes in bone mineral density were 2.0 % for hormone replacement therapy , -0.5 % for etidronate , 1.6 % for calcitonin , -3.6 % for alfacalcidol , -1.9 % for vitamin K , and -3.3 % for control . Seventeen ( 26 % ) of the 66 control patients developed new vertebral fractures . Compared with controls , the relative risks of vertebral fracture were 0.35 ( 95 % confidence interval [ CI ] : 0.14 to 0.83 ) for hormone replacement therapy , 0.40 ( 95 % CI : 0.17 to 0.92 ) for etidronate , 0.41 ( 95 % CI : 0.17 to 0.93 ) for calcitonin , 0.56 ( 95 % CI : 0.26 to 1.12 ) for alfacalcidol , and 0.44 ( 95 % CI : 0.20 to 0.99 ) for vitamin K. CONCLUSION We observed significant reductions in the incidence of vertebral fractures with hormone replacement therapy , etidronate , and calcitonin , and significant improvements in bone mineral density with hormone replacement therapy and calcitonin In a double-blind trial , 327 patients ( 57 men ) over 65 ( mean age 79.5 ) years received all possible combinations of calcium carbonate 3 g , vitamin D3 1000 iu , meth and ienone 2.5 mg and /or placebos daily for 9 months . The higher incidence of bone fractures in the placebo group was not significant . Serum calcium , phosphorus , creatinine , aspartate aminotransferase and alkaline phosphatase were followed : the greatest changes occurred with meth and ienone , which thus reduced osteoporotic activity and increased the muscular mass most effectively ; calcium carbonate had the poorest effect . Surprisingly , coronary mortality was higher among those taking all three active substances . With two treatments the increase was not significant , but when both the groups receiving a combination of any two of the treatments were compared with those taking only one or neither of these two treatments , a significant increase in coronary deaths was seen , most significant ( P less than 0.001 ) in those receiving vitamin D3 and meth and ienone OBJECTIVE To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 ( calcitriol ) in the treatment of osteoporosis . DESIGN Two-year , double-blind , r and omized clinical trial . SETTING University medical center . PATIENTS Fifty postmenopausal women with vertebral fractures recruited by referral . INTERVENTION Calcium intake was adjusted to 25 mmol/d ( 1000 mg/d ) at baseline . Patients were then r and omized to treatment with either calcitriol or placebo . During the study , calcium intake was reduced to 15 mmol/d ( 600 mg/d ) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L ( less than 11.0 mg/dL ) or urine calcium less than 9.96 mmol/d ( less than 400 mg/d ) . MEASUREMENTS AND MAIN RESULTS After 2 years , the mean dose of calcitriol in the treated group was 0.62 micrograms/d . Bone mineral density of the spine increased 1.94 % with calcitriol therapy and decreased 3.92 % with placebo ( P = 0.001 ) . Total body calcium increased 0.21 % with calcitriol therapy and decreased 1.85 % with placebo ( P = 0.004 ) . Patients receiving placebo had significant decreases in spine density ( P = 0.0007 ) and total body calcium ( P = 0.0004 ) . There were no differences in vertebral fracture rates between the groups . Renal function studies were not statistically different between the groups after 2 years . CONCLUSION The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium . No adverse effects on renal function were seen after long-term calcitriol therapy CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867 Summary The effect of oral 24R,25(OH)2-vitamin D3 as a prophylactic for postmenopausal bone loss was examined . Fifty-eight healthy , early postmeno-pausal women entered a double blind therapeutic trial for 2 years . After an initial examination the women were r and omized to treatment with 10 μg 24R,25(OH)2D3 daily or placebo . Participants were thereafter examined every 3 months ( nine examinations in all ) . In both groups the forearm bone mineral ( measured by single photon absorptiometry ) , the lumbar spine mineral , and the total body mineral ( measured by dual photon absorptiometry ) fell significantly and the same magnitude . Further-more , serum calcium , serum alkaline phosphatase concentration , and fasting urinary hydroxyproline were unchanged , as were the 24-hour urinary calcium excretion and the intestinal radiocalcium absorption . Our findings demonstrate that 24R,25(OH)2D3 treatment has no prophylactic effect on postmenopausal bone loss and does not alter calcium metabolic variables Summary Daily dosing with vitamin D often fails to achieve optimal outcomes , and it is uncertain what the target level of 25-hydroxyvitamin D should be . This study found that large loading doses of vitamin D3 rapidly and safely normalize 25OHD levels , and that monthly dosing is similarly effective after 3–5 months . With baseline 25OHD > 50 nmol/L , vitamin D supplementation does not reduce PTH levels . Introduction There is concern that vitamin D supplementation doses are frequently inadequate , and that compliance with daily medication is likely to be suboptimal . Methods This r and omized double-blind trial compares responses to three high-dose vitamin D3 regimens and estimates optimal 25-hydroxyvitamin D ( 25OHD ) levels , from changes in parathyroid hormone ( PTH ) , and procollagen type I amino-terminal propeptide ( P1NP ) in relation to baseline 25OHD . Sixty-three elderly participants were r and omized to three regimens of vitamin D supplementation : a 500,000-IU loading dose ; the loading dose plus 50,000 IU/month ; or 50,000 IU/month . Results The Loading and Loading + Monthly groups showed increases in 25OHD of 58 ± 28 nmol/L from baseline to 1 month . Thereafter , levels gradually declined to plateaus of 69 ± 5 nmol/L and 91 ± 4 nmol/l , respectively . In the Monthly group , 25OHD reached a plateau of ~80 ± 20 nmol/L at 3–5 months . There were no changes in serum calcium concentrations . PTH and P1NP were only suppressed by vitamin D treatment in those with baseline 25OHD levels < 50 and < 30 nmol/L , respectively . Conclusions Large loading doses of vitamin D3 rapidly and safely normalize 25OHD levels in the frail elderly . Monthly dosing is similarly effective and safe , but takes 3–5 months for plateau 25OHD levels to be reached The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the reporting of r and omised controlled trials . It was initially published in 1996 and focused on the reporting of parallel group r and omised controlled trials . The statement was revised in 2001 , with a further up date in 2010 . A separate CONSORT statement for the reporting of abstract s was published in 2008 . In earlier papers we considered the implication s of the 2001 version of the CONSORT statement for the reporting of cluster r and omised trial . In this paper we provide up date d and extended guidance , based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstract s. Calcium plus vitamin D ( CaD ) supplementation has a modest but significant effect on slowing loss of femoral bone mass and reducing risk of hip fractures in adherent postmenopausal women . The goal of this study was to determine if CaD supplementation influences hip structural parameters that are associated with fracture risk . We studied 1,970 postmenopausal women enrolled in the Women ’s Health Initiative r and omized controlled trial of CaD at one of three bone mineral density ( BMD ) clinical centers . Hip structural analysis software measured BMD and strength parameters on DXA scans at three regions : femoral narrow neck , intertrochanter , and shaft . R and om effects models were used to test the average differences in hip BMD and geometry between intervention and placebo . There was greater preservation of hip BMD at the narrow neck with CaD relative to placebo across 6 years of intervention . CaD also altered the underlying cross-sectional geometry at the narrow neck in the direction of greater strength , with small increases in cross-sectional area and section modulus and a decrease in buckling ratio with CaD relative to placebo . While trends at both the intertrochanter and shaft regions were similar to those noted at the narrow neck , no significant intervention effects were evident . There was no significant interaction of  CaD and age or baseline calcium levels for hip structural properties . CaD supplementation is associated with modest beneficial effects on hip structural features at the narrow neck , which may explain some of the benefit of CaD in reducing hip fracture risk CONTEXT Bone health is influenced by the intake of both calcium and vitamin D. OBJECTIVE Our objective was to evaluate the influence of calcium and vitamin D supplementation on PTH and bone turnover . SETTING , PATIENTS , AND DESIGN : At an ambulatory research center , 159 postmenopausal healthy white women participated in this double-blind , placebo-controlled parallel , longitudinal factorial study that was 6 months in duration . INTERVENTIONS Subjects were r and omly allocated to 4 groups : 1 ) double placebo , 2 ) calcium ( 1200 mg daily ) plus placebo , 3 ) vitamin D3 ( 100 μg ) plus placebo , and 4 ) vitamin D3 and calcium . Serum and urine were collected fasting and 2 hours after a calcium load at baseline and at 3 and 6 months . MAIN OUTCOME MEASURES Serum PTH , cross-linked C-telopeptide ( CTX ) , and procollagen type I N-terminal propeptide ( P1NP ) were measured . RESULTS Before study medication , a calcium load result ed in a decline in PTH and CTX and an increase in urinary calcium excretion . Serum CTX and P1NP declined over time with calcium supplementation but did not change with increased vitamin D intake . There was a decline in PTH in the vitamin D groups in the fasting state compared with placebo . Suppression of PTH was greater after a calcium load in the vitamin D groups . A calcium load decreased PTH and CTX and raised urinary calcium . CONCLUSIONS Fasting PTH  declines with vitamin D supplementation . PTH declines after calcium intake . Supplementation of the diet with 1200 mg calcium/d reduces bone turnover markers , whereas supplementation with up to100 μg vitamin D3/d does not CONTEXT Whether ergocalciferol ( D(2 ) ) and cholecalciferol ( D(3 ) ) are equally effective to increase and maintain serum 25-hydroxyvitamin D [ 25(OH)D ] concentration is controversial . OBJECTIVE The aim of the study was to evaluate the effect of daily and once monthly dosing of D(2 ) or D(3 ) on circulating 25(OH)D and serum and urinary calcium . DESIGN , SETTING AND PARTICIPANTS In a university clinical research setting , 64 community dwelling adults age 65 + were r and omly assigned to receive daily ( 1,600 IU ) or once-monthly ( 50,000 IU ) D(2 ) or D(3 ) for 1 yr . MAIN OUTCOME MEASURES Serum 25(OH)D , serum calcium , and 24-h urinary calcium were measured at months 0 , 1 , 2 , 3 , 6 , 9 , and 12 . Serum PTH , bone-specific alkaline phosphatase , and N-telopeptide were measured at months 0 , 3 , 6 , and 12 . RESULTS Serum 25(OH)D was less than 30 ng/ml in 40 % of subjects at baseline ; after 12 months of vitamin D dosing , levels in 19 % of subjects ( n = 12 , seven receiving daily doses and five monthly doses ) remained low , despite compliance of more than 91 % . D(2 ) dosing increased 25(OH)D(2 ) but produced a decline ( P < 0.0001 ) in 25(OH)D(3 ) . Substantial between-individual variation in 25(OH)D response was observed for both D(2 ) and D(3 ) . The highest 25(OH)D observed was 72.5 ng/ml . Vitamin D administration did not alter serum calcium , PTH , bone-specific alkaline phosphatase , N-telopeptide , or 24-h urine calcium . CONCLUSIONS Overall , D(3 ) is slightly , but significantly , more effective than D(2 ) to increase serum 25(OH)D. One year of D(2 ) or D(3 ) dosing ( 1,600 IU daily or 50,000 IU monthly ) does not produce toxicity , and 25(OH)D levels of less than 30 ng/ml persist in approximately 20 % of individuals . Substantial between-individual response to administered vitamin D(2 ) or D(3 ) is observed In a 5-yr r and omized prospect i ve study we examined the treatment effect of estrogen replacement therapy/hormone replacement therapy ( ERT/HRT ) , calcitriol , ERT/HRT and calcitriol , or placebo for 3 yr and the effect of discontinuation of therapy for 2 more yr on bone mineral density ( BMD ) , calciotropic hormones , markers of bone remodeling , and calcium absorption in 489 elderly women . The treatment phase of the study was double-blinded . After discontinuing therapy for 2 yr , there was rapid bone loss in all 3 treatment groups , and most of the decrease in BMD occurred in the first year . In the ERT/HRT group , spine BMD increased 5.5 % in yr 3 , decreased 3.2 % in yr 4 , and decreased 0.7 % in yr 5 ; femoral neck BMD increased 3.7 % in yr 3 , decreased 2.5 % in yr 4 , and decreased 0.4 % in yr 5 ; total body BMD increased 2.1 % in yr 3 , decreased 1.4 % in yr 4 , and decreased 0.6 % in yr 5 . In the combination group , spine BMD increased 7.1 % in yr 3 , decreased 4.3 % in yr 4 , and decreased 0.3 % in yr 5 ; femoral neck BMD increased 4.5 % in yr 3 , decreased 3.0 % in yr 4 , and decreased 0.01 % in yr 5 ; total body BMD increased 2.2 % in yr 3 , decreased 1.5 % in yr 4 , and decreased 0.6 % in yr 5 . In the calcitriol group , spine BMD increased 1.8 % in yr 3 , decreased 1.8 % in yr 4 , and showed no change in yr 5 ; femoral neck BMD increased 0.2 % in yr 3 , decreased 0.2 % in yr 4 , and decreased 0.6 % in yr 5 ; total body BMD decreased 0.4 % in yr 3 , decreased 0.6 % in yr 4 , and decreased 0.4 % in yr 5 . Compared with placebo , all treated groups at yr 5 had significantly higher total body BMD ; only the combination group had significantly higher spine BMD ( 3.4 % ; P < 0.001 ) and total hip BMD ( 2.4 % ; P < 0.01 . ) compared with the placebo group . Compared with baseline , only spine BMD in the combination group was significantly higher ( 2.6 % ; P < 0.001 ) at yr 5 . The increase in calcium absorption and the decrease in serum PTH levels in the calcitriol groups were reversed after discontinuation of treatment , and the decrease in bone markers was reversed in the hormone-treated groups . These results suggest that discontinuation of ERT/HRT and /or calcitriol therapy  in elderly women leads to a decrease in much of the BMD gained on treatment ; however , in the combination group there was a statistically significant residual effect on spine BMD Radiographically detected vertebral fractures ( hereafter referred to as vertebral fractures ) are a hallmark of postmenopausal osteoporosis and an important end point in clinical trials of osteoporosis treatment . Women with vertebral fractures have low bone mass compared with women without these fractures and , independently of bone mass , have an increased risk for additional vertebral and other fractures [ 1 - 4 ] . Vertebral fractures are common : Five percent of 50-year-old white women and 25 % of 80-year-old women have had at least one vertebral fracture [ 5 ] . Surprisingly , however , the manner in which vertebral fractures affect health remains uncertain . Cross-sectional studies in community-derived sample s of older women have demonstrated only a modest association [ 6 - 8 ] or no association [ 9 - 11 ] between prevalent vertebral fractures and back pain or disability . Cross-sectional studies do not distinguish more recent fractures from older vertebral fractures and may fail to capture transient increases in pain or disability [ 12 ] , a limitation that may underestimate the clinical effect of these fractures [ 13 ] . Back pain is common among elderly women [ 14 ] , and frequent causes of back pain , such as degenerative disc disease , facet joint osteoarthritis , spinal stenosis , and scoliosis , may obscure the impact of vertebral fracture . Only about one third of new vertebral fractures come to medical attention [ 15 , 16 ] , suggesting that most vertebral fractures are asymptomatic . However , attitudes toward back pain in older women and access to health care may also play a role in determining whether vertebral fractures come to medical attention . We examined the effect of incident vertebral fractures on back pain and back-related functional limitations in a large community-based sample of elderly women who underwent serial spinal radiography and annual assessment s of back pain and disability over the same period . Methods Participants Study patients were participants in the Study of Osteoporotic Fractures , a cohort recruited from population -based listings in four U.S. metropolitan areas . Details of the design of this study are published elsewhere [ 17 ] .  Lateral spine radiographs were obtained for 9677 white women between the ages of 65 and 99 years ( median age , 70 years ) who underwent baseline examination between 1986 and 1988 . Repeated spinal radiographs suitable for morphometry were obtained for 7223 women ( 75 % of the original cohort ) at a follow-up clinic visit held an average of 3.7 years ( range , 1.3 to 5.1 years ) later . All participants gave informed consent . Vertebral Morphometry Lateral radiographs of the thoracic and lumbar spine were obtained in accordance with current guidelines [ 18 ] . Quantitative vertebral morphometry was performed using six-point digitization as described elsewhere [ 3 , 19 ] to calculate the anterior ( Ha ) , mid- ( Hm ) , and posterior ( Hp ) height for each vertebral body from T4 to L4 . A system of triage of radiographs , described elsewhere [ 3 , 20 ] , was used to reduce the number of radiographs requiring morphometric measurements . Briefly , trained technicians separated sets of radiographs into normal , uncertain , or probably fractured groups on the basis of a limited semiquantitative grading scheme that categorized women by the most abnormal vertebral level [ 20 ] . Uncertain grade s were further categorized by the study radiologist as normal or probably fractured . Morphometry was done on the radiograph pairs that were categorized as probably fractured ( 42 % ) . In a r and om sample of 503 women whose radiographs were triaged and then digitized , triage missed no incident fractures according to the study definition . Definition of Vertebral Fracture A vertebra was classified as having a prevalent fracture on the baseline radiograph if any of the following ratios were more than 3 SDs ( > 4 SDs for severe fractures ) below the normal mean for that vertebral level : ( Ha/Hp ) , ( Hm/Hp ) , or a combination of ( H/H [ ] 1 ) and ( Hai/Hai 1 ) [ 3 , 21 ] . A new ( incident ) fracture was identified if any of the three vertebral heights ( Ha , Hm , or Hp ) on follow-up radiographs decreased by 20 % or more and by at least 4 mm compared with the baseline height . Incident fractures identified by morphometry were review ed by a radiologist to exclude imaging artifacts or such conditions as osteophytosis and Scheuermann disease ; 7 % of vertebrae meeting the morphometric criteria for incident fracture were reclassified as not fractured . Incident Clinical Fractures We used previously described methods [ 22 ] to assess the occurrence of clinical fractures of any bone during follow-up . Women were considered to have a clinical vertebral fracture if they reported a new diagnosis of spinal fracture and a clinical radiology report confirmed that a vertebral fracture was present . Measurements of Pain , Disability , and Limited Activity We evaluated outcome measures by using a previously described question naire [ 7 , 23 ] that asked about back pain and back-related disability in the past 12 months and the number of days of limited activity due to back pain . The question naire was administered at baseline and at three annual follow-up contacts held before assessment of vertebral fractures . The third follow-up contact coincided with follow-up radiography . Back pain was assessed on scales of frequency ( 0 , never or rarely ; 1 , some of the time ; 2 , most of the time ; or 3 , all of the time ) and severity ( 0 , no pain ; 1 , mild pain ; 2 , moderate pain ; or 3 , severe pain ) . The two pain questions had high internal consistency ( Cronbach = 0.81 ) and were summed for a total score that could range from 0 to 6 . We defined clinical ly significant back pain as pain that was experienced most or all of the time or pain that was moderate or severe . Women without significant back pain at baseline were considered to have increased back pain if clinical ly significant pain had developed between any follow-up contacts . For women with clinical ly significant back pain at baseline , increased back pain was defined as an increase in total pain score of at least two points . Both types of increase had a similar association with incident fractures and thus were combined for a single outcome . Back-related disability was assessed with questions about the degree of difficulty ( 0 , no difficulty ; 1 , some difficulty ; 2 , much difficulty ; or 3 , unable to perform activity ) in six activities of daily living that involved the back ( bending down to pick up light-weight objects , lifting a 10-pound object from the floor , reaching for objects just above the head , putting on socks or stockings , getting in and out of an automobile , and st and ing for 2 hours ) . These measures were combined in a back-related disability score ranging from 0 to 18 . As reported elsewhere [ 7 ] , this scale has high internal consistency ( Cronbach = 0.82 ) and is highly correlated ( Spearman r = 0.73 ) with a more extensive instrument used to assess disability caused by low back pain [ 24 ] . We defined clinical ly significant disability as much difficulty or unable in one or more of the six activities . Women without significant disability at baseline were considered to have increased disability if clinical ly significant disability had developed between any follow-up contacts . For women with clinical ly significant disability at baseline , increased disability was defined as an increase in disability score of at least three points . Both types of increase had a similar association with incident fractures and thus were combined for a single outcome . We also asked participants if they had limited their activities because of back pain since the last contact ; if the answer was yes , we asked for the number of days they had stayed in bed and the number of days on which activity was limited ( not including days in bed ) because of back pain . Questions were adapted from previous surveys [ 25 , 26 ] . For all follow-up contacts , we summed the number of days of bed rest and , in a separate measure , the number of days of limited activity ; we then divided these numbers by the total years of follow-up to estimate the average number of affected days per year . Other Measurements The baseline question naire assessed potential confounding factors that may be associated with the risk for incident vertebral fracture and with back pain or disability  , including smoking ( current or past smoker ) ; inactivity , defined as walking less than one block daily ( yes or no ) ; a previous physician diagnosis of osteoporosis or spinal fracture ( yes or no ) ; current use of estrogen ( yes or no ) ; hip pain in the past 12 months ( yes or no ) ; and height at 25 years of age . At the baseline examination , we assessed height and weight and calculated body mass index ( kg/m2 ) . We assessed grip strength by using an isometric dynamometer ( Jamar Hydraulic H and Dynamometer , JA Preston , Jackson , Mississippi ) at baseline and at the follow-up examination and calculated change in grip strength between the two measurements . A r and om sample of 16 % of baseline spine radiographs was assessed for spinal disc degeneration by using previously published methods [ 27 ] . Statistical Analysis Unless otherwise indicated , analyses were done separately in groups stratified by the presence of one or more baseline prevalent vertebral fractures . Descriptive and bivariate associations were assessed by using the t-test for continuous variables and the chi-square test for dichotomous variables . The association between incident vertebral fractures and dichotomous outcomes ( increased back pain and increased back disability ) was analyzed with logistic regression techniques . We analyzed the association of incident vertebral fracture with days of bed rest and days of  limited activity per year by using Poisson regression . The distribution of days of bed rest ( mean SD , 0.44 5.15 ) and limited-activity days ( 16.3 53.7 ) indicate that considerable overdispersion is present . Poisson regression allowing for this overdispersion provides a good estimation and inferential scheme [ STUDY OBJECTIVE To determine if calcitriol is an effective treatment in postmenopausal osteoporosis . DESIGN Double-blind , r and omized clinical trial of 2 years ' duration . SETTING University medical center with patients recruited by media announcements . PATIENTS Eighty-six postmenopausal women with vertebral compression fractures . INTERVENTIONS Patients were treated with calcitriol or placebo . Mean dose was 0.43 micrograms/d . Dietary calcium was 1000 mg/d ( 24.9 mmol/d ) . The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia . MEASUREMENTS AND MAIN RESULTS No significant differences between placebo and control groups were seen in the percent change in total body calcium ( 0.4 % + /- 1.0 compared with 0.0 % + /- 0.9 ) , single photon absorptiometry ( -0.5 % + /- 1.2 compared with -3.1 % + /- 0.9 ) or dual photon absorptiometry ( 0.0 % + /- 1.7 compared with -1.0 % + /- 2.2 ) . New fractures were seen in 16 % of the placebo group and 26 % of the calcitriol groups , so the difference in percent fractures was 10 % ( 95 % CI , -5.7 % to 25.7 % ) . Bone biopsies did not show changes in either group . The calcitriol group had significantly higher serum and urine calcium values , but renal function was not worse than in the placebo group . CONCLUSIONS Calcitriol is not an effective treatment for established postmenopausal osteoporosis 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 Objectives : The authors conducted a r and omized controlled trial to clarify the efficacy and safety of alendronate plus alfacalcidol versus alendronate alone in a clinical setting . Research design and methods : Eligible patients were postmenopausal women with severe osteoporosis who were aged 70 years or older and had several risk factors for incident fractures . The primary endpoint was prevention of incident fractures , and the anti-fracture efficacy was evaluated in relation to the baseline serum 25(OH)D level . Results : A total of 2164 patients were r and omized to alendronate plus alfacalcidol ( combination therapy ) or alendronate alone ( monotherapy ) . Although the overall difference in the incidence of vertebral fracture between the two groups was not significant , the combination therapy group had a significantly reduced risk of vertebral fractures after the first 6 months ( HR , 0.53 ) . In subgroup analyses , the combination therapy group was superior in the strata of number of prevalent vertebral fractures of ≥2 ( HR , 0.51 ) and grade 3 of prevalent vertebral fractures ( HR , 0.55 ) . The rate of non-vertebral weight-bearing bone fractures was significantly lower in the combination therapy group than in the monotherapy group during the follow-up period ( HR , 0.31 ) . A lower baseline 25(OH)D level was associated with a higher incidence of non-vertebral weight-bearing bone fractures ( HR , 3.42 ) despite alendronate use . Although one patient given the combination therapy had mild hypercalcemia , serious hypercalcemia and unknown adverse events were not encountered . Because of the limitations presented in this study , these results may not apply to female patients with longer than 2 years of treatments , and to male osteoporosis patients . Conclusions : The combination therapy was no more effective for overall vertebral fracture prevention . However , subgroup analysis has shown that it was more effective for fracture prevention in patients with severe vertebral deformity , multiple prevalent vertebral fractures , and for non-vertebral weight-bearing bone fracture prevention We evaluated low-dose calcitriol ( 0.25 microgram b.i.d . ) in combination with 1 g of supplemental calcium therapy as treatment for osteopenic women over 60 years of age ( n = 4 ) . Control patients ( n = 6 ) received ergocalciferol ( 50,000 units twice a week ) and 1 g of supplemental calcium .  Bone biopsies and CT-determined bone mineral density were done initially and after 1 year of therapy . Bone mineral density increased from 77 + /- 18 to 88 + /- 9 mg/ml ( NS ) in the calcitriol-treated group and from 87 + /- 13 to 112 + /- 30 mg/ml ( NS ) in the ergocalciferol-treated group . There was also no significant change in bone volume , as determined by bone biopsy in either group . No compression fractures occurred in either treatment group . After 1 year of therapy , urinary calcium excretion was increased significantly above that observed in age-matched untreated women . Creatinine clearance did not change significantly . Hypercalcemia was rare . In summary , we found calcitriol was not superior to ergocalciferol in preventing progressive bone loss and fractures . Both therapies were associated with significant hypercalciuria 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 Background There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients . The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels . Methods In this r and omized controlled study , patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario , Canada . Participants were r and omized to one of three loading dose groups : placebo ; 50,000 IU vitamin D2 ; or 100,000 IU D2 . Following a placebo/loading dose , all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days . Serum 25-hydroxy vitamin D ( 25-OHD ) was measured at baseline , discharge from acute care ( approximately 4-weeks ) , and 3-months . Results Sixty-five patients were enrolled in the study ( 44 % male ) . An immediate rise in 25-OHD occurred in the 100,000 group , however there were no significant differences in 25-OHD between the placebo , 50,000 and 100,000 loading dose groups after 4-weeks ( 69.3 , 84.5 , 75.6 nmol/L , p = 0.15 ) and 3-months ( 86.7 , 84.2 , 73.3 nmol/L , p = 0.09 ) , respectively . At the end of the study , approximately 75 % of the placebo and 50,000 groups had reached the target therapeutic range ( 75 nmol/L ) , and 44 % of the 100,000 group . Conclusions In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture , our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2 . At the end of the study , all three groups were equally effective in attaining improvement in 25-OHD levels . Given that a daily dose of 1,000 IU vitamin D3 ( with or without a loading dose ) result ed in at least 25 % of patients having suboptimal vitamin D status , patients with acute hip fracture may benefit from a higher daily dose of vitamin D.Trial registration Clinical Trials # 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 vitamin D supplementation reduces the incidence of fractures in older adults . This may be partly mediated by effects of vitamin D on neuromuscular function . OBJECTIVE to determine the effects of vitamin D supplementation on aspects of neuromuscular function known to be risk factors for falls and fractures . DESIGN r and omised , double-blind , placebo-controlled study . SETTING falls clinic taking referrals from general practitioners and accident and emergency department . SUBJECTS 139 ambulatory subjects ( > /=65 years ) with a history of falls and 25-hydroxyvitamin D ( 25OHD ) < /=12 microg/l . INTERVENTION patients were r and omised to receive a single intramuscular injection of 600,000 i.u . ergocalciferol or placebo . OUTCOME MEASURES assessment s including biochemistry , postural sway , choice reaction time ( CRT ) , aggregate functional performance time ( AFPT ) , and quadriceps strength were carried out at baseline and 6 months post-intervention . RESULTS baseline characteristics were comparable between both groups . 25OHD in the treatment group increased significantly at 6 months . AFPT deteriorated in the control group and improved in the intervention group , representing a significant difference between groups ( + 6.6 s versus -2.0 s , t = 2.80 , P < 0.05 ) . Similar changes were observed for CRT ( -0.06 s versus + 0.41 s , t = -2.52 , P < 0.01 ) and postural sway ( + 0.0025 versus -0.0138 , t = 2.35 , P < 0.02 ) . There was no significant difference in muscle strength change between groups ( -10 N versus -2 N , t = -1.26 , ns ) . A significant correlation between change in AFPT and change in 25OHD levels was observed ( r = 0.19 , P = 0.03 ) . There was no significant difference in the number of falls ( 0.39 versus 0.24 , t = 1.08 , P = 0.28 ) or fallers ( 14 versus 11 , P = 0.52 ) between two groups . CONCLUSIONS vitamin D supplementation , in fallers with vitamin D insufficiency , has a significant beneficial effect on functional performance , reaction time and balance , but not muscle strength . This suggests that vitamin D supplementation improves neuromuscular or neuroprotective function , which may in part explain the mechanism whereby vitamin D reduces falls and fractures Aims : To examine the effect of combined calcium and vitamin D3 supplementation on bone mineral density ( BMD ) in patients with chronic kidney disease ( CKD ) . Methods : We performed a post-hoc analysis of the DECALYOS II , a 2-year r and omized , double-blind , placebo-controlled  study of 610 women r and omized to : calcium-vitamin D3 fixed combination , calcium plus vitamin D3 separate combination , or placebo . Both active treatment groups received the same daily amount of calcium ( 1,200 mg ) and vitamin D3 ( 800 IU ) . BMD of the distal radius was measured by single X-ray absorptiometry at baseline , 12 and 24 months . Results : At baseline 47.2 % , 36.4 % and 16.4 % of the study population had an eGFR ≥ 60 , 45 – 59 , and < 45 ml/min/1.73 m2 , respectively . Both active regimens vs.  placebo markedly increased serum 25-hydroxyvitamin D levels from baseline in all eGFR groups ( p < 0.0001 ) . Analysis of variance demonstrated an overall treatment effect on distal radius BMD ( p = 0.005 ) , with the active treatment groups showing a lower rate of BMD loss when compared to the placebo group . The effects of the intervention on BMD did not differ significantly according to baseline eGFR ( interaction p > 0.22 for all time points ) . Conclusion : Combined calcium and vitamin D3 supplementation was effective in reducing rate of BMD loss in women with moderate CKD Abstract : Hormone replacement therapy ( HRT ) prevents postmenopausal bone loss and fractures . However , the occurrence of women with no bone response to HRT  has not been widely examined . We identified the densitometric nonresponders to long-term HRT and investigated some characteristics and biochemical variables as possible predictors of densitometric nonresponse in postmenopausal women . The study population was a sub sample of the Kuopio Osteoporosis Study ( n= 14.220 ) . A total of 464 early postmenopausal women were r and omized into four treatment groups : ( 1 ) HRT ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ) ; ( 2 ) vitamin D3 ; ( 3 ) HRT + Vitamin D3 combined ; and ( 4 ) placebo . In this study , the data from HRT and placebo groups were analyzed . Lumbar ( L2–4 ) and femoral neck bone mineral density ( BMD ) were determined by dual-energy X-ray absorptiometry ( DXA ) at baseline and after 5 years of treatment . A densitometric nonresponder was defined as a woman whose 5-year BMD change was similar to the mean BMD change ( + 95 % CI ) of the placebo group or worse . Altogether , 74 women in the HRT group and 104 women in the placebo group complied with the treatment . According to spinal BMD analysis , 11 % of the women were classified as densitometric nonresponders ; the corresponding proportion for femoral BMD analysis was 26 % . Both smoking ( p= 0.003 ) and low body weight ( p= 0.028 ) were significant risk factors for densitometric nonresponse to HRT . After 6 months of treatment the densitometric nonresponders ( hip ) had a significantly higher mean serum follicle stimulating hormone ( FSH ) level ( p= 0.038 ) and lower increases in serum estradiol levels ( p= 0.006 ) than the densitometric responders . The mean changes in serum FSH and alkaline phosphatase levels were significantly lower among the densitometric nonresponders ( spine ) than responders ( p= 0.043 and 0.017 , respectively ) . In conclusion , this prospect i ve study shows that especially current smokers and women with low body weight are at increased risk of poor bone response to HRT .  Repeated serum FSH , estradiol and alkaline phosphatase measurements during the first months of long-term HRT may be helpful in identifying the women with no bone response to HRT The effects of 1α-hydroxyvitamin D3 [ 1α(OH)D3 ] on bone mineral density , fracture incidence , and bone metabolism were evaluated by a double-blind , placebo-controlled study . Eighty postmenopausal osteoporotic Japanese women ( 71.9±7.3 years , mean±SD ) were r and omly assigned to 1 μg of 1α(OH)D3 daily or inactive placebo for 1 year . All patients were given supplemental calcium ( 300 mg of elemental calcium daily ) . Lumbar ( L2–L4 ) bone mineral density ( BMD ) determined by dual energy X-ray absorptiometry increased 0.65 % with 1α(OH)D3 treatment and decreased 1.14 % with placebo ( P=0.037 ) . BMD in both the femoral neck and Ward 's triangle did not yield any significant differences between the two groups , whereas trochanter BMD in the 1α(OH)D3-treated group increased 4.20 % and decreased 2.37 % with placebo ( P=0.055 ) . X-ray analysis demonstrated that new vertebral fractures occurred in two patients with 1α(OH)D3 and in seven patients with placebo . The vertebral fracture rate in the treated group was significantly less ( 75/1000 patient years ) than in the control group ( 277/1000 patient years ; P=0.029 ) . Hypercalcemia ( 12.1 mg/100 ml ) occurred in one patient receiving 1α(OH)D3 ; however , the serum calcium level in this patient promptly decreased to the reference range after cessation of the treatment . There were no significant changes in serum creatinine level in either group . A significant increase in urinary excretion of calcium was found but there was no significant change in urinary excretion of hydroxyproline in the treated group . The serum level of bone-derived alkaline phosphatase activity significantly decreased by−26±26 ( mU/ml ) after the treatment ( P=0.003 ) . These results indicate that 1α(OH)D3 treatment is effective for maintaining trabecular bone mass and prevents further vertebral fractures without any serious adverse effects in postmenopausal osteoporosis BACKGROUND Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospect i ve study . METHODS We assessed potential risk factors , including bone mass , in 9516 white women 65 years of age or older who had had no previous hip fracture . We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture . All reports of hip fractures were vali date d by review of x-ray films . RESULTS During the follow-up period , 192 women had first hip fractures not due to motor vehicle accidents . In multivariable age-adjusted analyses , a maternal history of hip fracture doubled the risk of hip fracture ( relative risk , 2.0 ; 95 percent confidence interval , 1.4 to 2.9 ) , and the increase in risk remained significant after adjustment for bone density . Women who had gained weight since the age of 25 had a lower risk . The risk was higher among women who had previous fractures of any type after the age of 50 , were tall at the age of 25 , rated their own health as fair or poor , had previous hyperthyroidism , had been treated with long-acting benzodiazepines or anticonvulsant drugs , ingested greater amounts of caffeine , or spent four hours a day or less on their feet . Examination findings associated with an increased risk included the inability to rise from a chair without using one 's arms , poor depth perception , poor contrast sensitivity , and tachycardia at rest . Low calcaneal bone density was also an independent risk factor . The incidence of hip fracture ranged from 1.1 ( 95 percent confidence interval , 0.5 to 1.6 ) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 ( 95 percent confidence interval , 20 to 34 ) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age . CONCLUSIONS Women with multiple risk factors and low bone density have an especially high risk of hip fracture . Maintaining body weight , walking for exercise , avoiding long-acting benzodiazepines , minimizing caffeine intake , and treating impaired visual function are among the steps that may decrease the risk In a prospect i ve , r and omized study , 66 osteoporotic postmenopausal women ( mean age , 67 years ) were scheduled to receive either alfacalcidol 0.25 microgram twice daily together with calcium 500 mg twice daily ( treatment group , n = 24 ) or placebo twice daily with calcium 500 mg twice daily ( control group , n = 42 ) for three years . In the treatment group , bone mineral content at the distal radius may have increased by 2 % compared to a significant decrease of 7.8 % in the control group . The difference between the two groups was also significant . Since the dose of alfacalcidol and calcium remained unadjusted , frequent hypercalciuria , as well as occasional mild , transient elevations of serum calcium , were observed in the treatment group . No changes in serum creatinine levels or creatinine clearance throughout the study were observed . The two groups did not differ with respect to the frequency of clinical side effects , which were mainly gastrointestinal and probably related to the calcium supplementation . Alfacalcidol and calcium may prevent further bone loss in women suffering from postmenopausal osteoporosis 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 A controlled therapeutic trial on seventy‐four 70‐year‐old women was carried out with the purpose of finding the optimal treatment for post menopausal osteoporosis .  The bone mineral content ( BMC ) was measured by 125I‐photonabsorptiometry at two sites in the distal part of the forearms , where the trabecular/cortical ratio is 0·25 and 1·5 , respectively . Radiographs were done on the right h and to measure the metacarpal bone mass ( cortical area/total area = CA/TA ) OBJECTIVE Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects . The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-st and ing stroke by vitamin D supplementation . METHODS Ninety-six elderly women with poststroke hemiplegia were followed for two years . Patients were r and omly assigned to one of the two groups , and 48 patients received 1,000 IU ergocalciferol daily , and the remaining 48 received placebo . The number of falls per person and incidence of hip fractures were compared between the two groups . Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study . RESULTS At baseline , serum 25-hydroxyvitamin D levels were in the deficient range ( < 10 ng/ml ) in all patients ; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels .  Vitamin D treatment accounted for a 59 % reduction in falls ( 95 % CI , 28 - 81 % ; p = 0.003 ) . There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group . Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period ( log-rank , p = 0.049 ) . CONCLUSION Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers , which may lead to decreased falls and hip fractures UNLABELLED Dietary supplementation with vitamin K(1 ) , with vitamin D(3 ) and calcium or their combination , was examined in healthy older women during a 2-year , double-blind , placebo-controlled trial . Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius . INTRODUCTION The putative beneficial role of high dietary vitamin K(1 ) ( phylloquinone ) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind , placebo-controlled trial in healthy Scottish women > or = 60 years of age . MATERIAL S AND METHODS Healthy , nonosteoporotic women ( n = 244 ) were r and omized to receive either ( 1 ) placebo , ( 2 ) 200 microg/day vitamin K(1 ) , ( 3 ) 10 microg ( 400 IU ) vitamin D(3 ) plus 1000 mg calcium/day , or ( 4 ) combined vitamins K(1 ) and D(3 ) plus calcium . Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist , markers of bone turnover , and vitamin status . Supplementation effects were tested using multivariate general linear modeling , with full adjustment for baseline and potential confounding variables . RESULTS Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups . However , women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius . Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years , serum vitamin K(1 ) increased by 157 % ( p < 0.001 ) , the percentage of undercarboxylated osteocalcin ( % GluOC ) decreased by 51 % ( p < 0.001 ) , serum 25-hydroxyvitamin D [ 25(OH)D ] increased by 17 % ( p < 0.001 ) , and PTH decreased by 11 % ( p = 0.049 ) . CONCLUSIONS These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1 ) together with supplements of calcium plus moderate vitamin D(3 ) to enhance BMC at the ultradistal radius , a site consisting of principally trabecular bone . The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation UNLABELLED In this 2-year r and omized controlled study of 167 men > 50 years of age , supplementation with calcium-vitamin D3-fortified milk providing an additional 1000 mg of calcium and 800 IU of vitamin D3 per day was effective for suppressing PTH and stopping or slowing bone loss at several clinical ly important skeletal sites at risk for fracture . INTRODUCTION Low dietary calcium and inadequate vitamin D stores have long been implicated in age-related bone loss and osteoporosis . The aim of this study was to assess the effects of calcium and vitamin D3 fortified milk on BMD in community living men > 50 years of age . MATERIAL S AND METHODS This was a 2-year r and omized controlled study in which 167 men ( mean age + /- SD , 61.9 + /- 7.7 years ) were assigned to receive either 400 ml/day of reduced fat ( approximately 1 % ) ultra-high temperature ( UHT ) milk containing 1000 mg of calcium plus 800 IU of vitamin D3 or to a control group receiving no additional milk . Primary endpoints were changes in BMD , serum 25(OH)D , and PTH . RESULTS One hundred forty-nine men completed the study . Baseline characteristics between the groups were not different ; mean dietary calcium and serum 25(OH)D levels were 941 + /- 387 mg/day and 77 + /- 23 nM , respectively . After 2 years , the mean percent change in BMD was 0.9 - 1.6 % less in the milk supplementation compared with control group at the femoral neck , total hip , and ultradistal radius ( range , p < 0.08 to p < 0.001 after adjusting for covariates ) . There was a greater increase in lumbar spine BMD in the milk supplementation group after 12 and 18 months ( 0.8 - 1.0 % , p < or = 0.05 ) , but the between-group difference was not significant after 2 years ( 0.7 % ; 95 % CI , -0.3 , 1.7 ) . Serum 25(OH)D increased and PTH decreased in the milk supplementation relative to control group after the first year ( 31 % and -18 % , respectively ; both p < 0.001 ) , and these differences remained after 2 years . Body weight remained unchanged in both groups at the completion of the study . CONCLUSIONS Supplementing the diet of men > 50 years of age with reduced-fat calcium- and vitamin D3-enriched milk may represent a simple , nutritionally sound and cost-effective strategy to reduce  age-related bone loss  at several skeletal sites at risk for fracture in the elderly UNLABELLED Bone metabolism follows a seasonal pattern with high bone turnover and bone loss during the winter . In a r and omized , open-label 2-year sequential follow-up study of 55 healthy adults , we found that supplementation with oral vitamin D3 and calcium during winter abolished seasonal changes in calciotropic hormones and markers of bone turnover and led to an increase in BMD . Supplementation with oral vitamin D3 and calcium during the winter months seems to counteract the effects of seasonal changes in vitamin D and thus may be beneficial as a primary prevention strategy for age-related bone loss . INTRODUCTION Bone metabolism follows a seasonal pattern characterized by high bone turnover and bone loss during winter . We investigated whether wintertime supplementation with oral vitamin D3 and calcium had beneficial effects on the circannual changes in bone turnover and bone mass . MATERIAL S AND METHODS This prospect i ve study comprised an initial observation period of 12 months ( " year 1 " ) , followed by an intervention during parts of year 2 . Fifty-five healthy subjects living in southwestern Germany ( latitude , 49.5 degrees N ) were r and omized into two groups : 30 subjects were assigned to the treatment group and received oral cholecalciferol ( 500 IU/day ) and calcium ( 500 mg/day ) during the winter months of year 2 ( October-April ) , while 25 subjects assigned to the control group obtained no supplements . Primary endpoints were changes in calciotropic hormones [ serum 25(OH)D , 1,25(OH)2D , and parathyroid hormone ] , markers of bone formation ( serum bone-specific alkaline phosphatase ) and of bone resorption ( urinary pyridinoline and deoxypyridinoline ) , and changes in lumbar spine and femoral neck BMD . RESULTS Forty-three subjects completed the study . During year 1 , calciotropic hormones , markers of bone turnover , and BMD varied by season in both groups . During the winter months of year 1 , bone turnover was significantly accelerated , and lumbar spine and femoral BMD declined by 0.3 - 0.9 % . In year 2 , seasonal changes in calciotropic hormones and markers of bone turnover were either reversed or abolished in the intervention group while unchanged in the control cohort . In the subjects receiving oral vitamin D3 and calcium , lumbar and femoral BMD increased significantly ( lumbar spine : + 0.8 % , p = 0.04 versus year 1 ; femoral neck : + 0.1 % , p = 0.05 versus year 1 ) , whereas controls continued to lose bone ( intervention group versus control group : lumbar spine , p = 0.03 ; femoral neck , p = 0.05 ) . CONCLUSIONS Supplementation with oral vitamin D3 and calcium during winter prevents seasonal changes in bone turnover and bone loss in healthy adults . It seems conceivable that annually recurring cycles of low vitamin D and mild secondary hyperparathyroidism during the winter months contributes , at least in part and over many years , to age-related bone loss . Supplementation with low-dose oral vitamin D3 and calcium during winter may be an efficient and inexpensive strategy for the primary prevention of bone loss in northern latitudes BACKGROUND Care of elderly patients after hip fracture is not well established . METHODS We enrolled 173 patients with acute hip fracture who were 65 years or older ( 79.2 % women ; mean age , 84 years ; 77.4 % living at home ) . Using a factorial design , we r and omly allocated patients to extended physiotherapy ( PT ) ( supervised 60 min/d during acute care plus an unsupervised home program ) vs st and ard PT ( supervised 30 min/d during acute care plus no home program ; single-blinded ) , and to cholecalciferol therapy , 2000 vs 800 IU/d ( double-blinded ) . Primary outcome was rate of falls ; secondary outcome was rate of hospital readmissions during the 12-month follow-up . All analyses included 173 individuals and used multivariate Poisson regression analyses . RESULTS At baseline , 50.9 % of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7 % of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions . Because this was a factorial design trial , all analyses tested the main effect of each treatment while controlling for the other in 173 participants . Extended vs st and ard PT reduced the rate of falls by 25 % ( 95 % confidence interval [ CI ] , -44 % to -1 % ) . Cholecalciferol treatment , 2000 vs 800 IU/d , did not reduce falls ( 28 % ; 95 % CI , -4 % to 68 % ) , but reduced the rate of hospital readmissions by 39 % ( 95 % CI , -62 % to -1 % ) . CONCLUSIONS Extended PT was successful in reducing falls but not hospital readmissions , whereas cholecalciferol treatment , 2000 IU/d , was successful in reducing hospital readmission but not falls . Thus , the 2 strategies may be useful together because they address 2 different and important complications after hip fracture A r and omized double-blind controlled trial of the effect of vitamin D supplementation on the abilities of elderly hospital patients to carry out basic activities of daily life is described . Those patients included in the trial had plasma 25-hydroxyvitamin D concentrations which were low or low normal as judged by the normal range in young adults . After 2 to 9 months on the trial there was no significant difference in the performance of the control and treatment groups 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 Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures . A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites , bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a r and omized , double-blind , placebo-controlled trial . Bone mineral density ( BMD ) was measured by dual x-ray absorptiometry and bone structure by radiographs . Calcium biochemistry and bone turnover markers were measured in blood and urine . The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr . Baseline median calcium intake was 546 mg/day , and median serum 25OH vitamin D3 was 59 nmol/L. On placebo , loss of BMD at total hip was 2 % and femoral medulla expansion was 3 % over 4 yr . Calcium reduced bone loss , secondary hyperparathyroidism , and bone turnover . 25OH vitamin D3 was intermediate between placebo and calcium . Fracture rates and drop-out rates were similar among groups , and there were no serious adverse events with either supplement . A calcium supplement of 750 mg/day prevents loss of BMD , reduces femoral medullary expansion , secondary hyperparathyroidism , and high bone turnover . A supplement of 15 microg/day 25OH vitamin D3 is less effective , and because its effects are seen only at low calcium intakes , suggests that its beneficial effect is to reverse calcium insufficiency Background and aims : Insufficient vitamin D status , commonly found in older people , has been associated with muscle weakness which , in old age , impairs mobility and is a risk factor for falling . In a r and omized , double-blind placebo-controlled trial , we tested the hypothesis that vitamin D + calcium supplementation improves muscle strength and mobility , compared with calcium mono-therapy in vitamin D-insufficient female geriatric patients . Methods : Seventy female geriatric patients > 65 years of age with serum 25-hydroxyvitamin D3 ( 25OHD ) concentrations between 20 and 50 nmol/L , visiting an outpatient geriatric department , were included . Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day ( D/Cal group ) or a placebo + calcium 500 mg/day ( Plac/Cal group ) for 6 months . At baseline and 6 months , muscle strength , power and functional mobility were tested . Results : At baseline , 25OHD was significantly ( p<0.05 ) associated with knee extension strength ( r=0.42 ) , h and grip strength ( r=0.28 ) , leg extension power ( r=0.34 ) , Timed Get Up and Go ( r=−0.31 ) and Modified Cooper test ( r=0.44 ) . At 6 months , a significant difference in 25OHD ( 77.2 vs 41.6 nmol/L , p<0.001 ) and 1,25OHD was found between the two groups . Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups . Conclusions : Daily 400IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients The purpose of the study was to determine the effect of vitamin D supplementation on bone turnover and bone loss in elderly women . Three hundred forty-eight women , ages 70 yr and older , were r and omized to receive 400 IU vitamin D3 per day ( n = 177 ) or placebo ( n = 171 ) , double-blind , for a period of 2 yr . Main outcome measures were bone mineral density of both hips ( femoral neck and trochanter ) and the distal radius , as well as biochemical markers of bone turnover . The effect of vitamin D supplementation was expressed as the difference in mean ( percentage ) change between the placebo group and the vitamin D group . The measurements were repeated in 283 women after 1 yr and in 248 women after 2 yr . Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D ( 250HD ) ( + 35 nmol/L ) and 1,25-dehydroxyvitamin D [ 1,25-(OH)2D ] ( + 7.0 pmol/L ) levels and urinary calcium/creatinine ratios ( + 0.5 % ) and significantly decreased PTH(1 - 84 ) secretion ( -0.74 pmol/L ) after 1 yr . No effect was found for the parameters of bone turnover . The effect on the bone mineral density of the left femoral neck was + 1.8 % in the first yr , + 0.2 % in the second yr , and + 1.9 % during the whole period ( 95 % confidence interval 0.4 , 3.4 % ) . At the right femoral neck the effects were + 1.5 % , + 1.1 % , and + 2.6 % ( confidence interval 1.1 , 4.0 % ) , respectively . No effect was found at the femoral trochanter and the distal radius . Supplementation with 400 IU vitamin D3 daily in elderly women slightly decreases PTH secretion and increases bone mineral density at the femoral neck Abstract : Vitamin D status is known to be an important determinant of bone mineral density ( BMD ) . There is a significant seasonal variation in serum vitamin D , and some studies have reported an associated seasonal variation in BMD . The present study was devised to investigate whether a seasonal variation in BMD could be detected in healthy normal subjects , along with associated variations in serum parathyroid hormone ( PTH ) , intestinal calcium absorption and biochemical markers of bone turnover . A second aim was to investigate whether , if such variations were identified , they could be suppressed by vitamin D supplementation . The subjects were 70 healthy female volunteers ( mean age 47.2 years , range 24–70 years ) recruited into a double-masked crossover study and followed over 2 years . During the first year 35 subjects received a daily oral supplement containing 800 IU ( 20 mg ) cholecalciferol ( group 1 ) and 35 subjects received a placebo preparation ( group 2 ) . During the second year the treatment each group received was reversed . Lumbar spine ( L1–L4 ) , left proximal femur and total body BMD were measured by DXA at 3-month intervals . Serum 25-hydroxyvitamin D ( 25-OHD ) , serum PTH , bone markers ( bone-specific ALP ( BSAP ) and urinary crosslinks ( DYPD/creatinine ) ) and calcium absorption were also measured at each visit . Cholecalciferol treatment increased serum 25-OHD by 25.4 nmol/l ( p < 0.001 ) , while a reciprocal decrease in serum PTH of 6.6 ng/l ( p = 0.011 ) was seen in subjects in the lowest quartile of baseline serum 25-OHD . The treatment had no significant effect on spine , femur or total body BMD , calcium absorption or bone markers . When Fourier analysis was used to analyze the data for seasonal effect ( defined as twice the amplitude of the 1-year period variation ) a highly significant effect for 25-OHD of 18 nmol/l ( p < 0.001 ) was found . However , no effect was found for BMD , PTH , calcium absorption or bone markers . The analysis set a 95 % confidence limit to the seasonal effect of less than 0.6 % for spine , total hip and total body BMD . It was concluded that in the population of healthy women studied there was no evidence of seasonal variation in spine , femur or total body BMD , serum PTH , calcium absorption or bone markers .  Vitamin D supplementation was found to have no effect on BMD A double-blind controlled study was performed in 60 patients with symptomatic osteoporosis with at least one vertebral crush fracture , comparing the effect of n and rolone decanoate , 1 alpha-hydroxyvitamin D3 and intermittent calcium infusions .  Thirty-four out of 60 patients completed the 2 year observation period . N and rolone decanoate statistically significantly increased the bone mineral content at the radius , reduced the endosteal bone loss at the metacarpals and statistically significantly reduced urinary calcium and hydroxyproline excretion . Calcium infusions and 1 alpha-hydroxyvitamin D3 inhibited further loss of bone mineral content , but endosteal bone loss continued . In the second year fracture rate was reduced in the n and rolone decanoate groups compared to the two other groups . We conclude that n and rolone decanoate is an active drug for increasing bone mineral content and reducing endosteal bone loss , while 1 alpha-hydroxyvitamin D3 and calcium infusions only stop further bone mineral loss at the radius but do not inhibit endosteal bone loss as measured at the metacarpals and that single photon absorptiometry and radiography are complementary in interpreting cortical bone mineral changes PURPOSE Oral bone and tooth loss are correlated with bone loss at nonoral sites . Calcium and vitamin D supplementation slow the rate of bone loss from various skeletal sites , but it is not known if intake of these nutrients affects oral bone and , in turn , tooth retention . SUBJECTS AND METHODS Tooth loss was examined in 145 healthy subjects aged 65 years and older who completed a 3-year , r and omized , placebo-controlled trial of the effect of calcium and vitamin D supplementation on bone loss from the hip , as well as a 2-year follow-up study after discontinuation of study supplements . Teeth were counted at 18 months and 5 years . A comprehensive oral examination at 5 years included assessment of caries , oral hygiene , and periodontal disease . The odds ratio ( OR ) and 95 % confidence interval ( CI ) of tooth loss were estimated by stepwise multivariate logistic regression . Initial age ( mean + /- SD ) of subjects was 71 + /- 5 years , and the number of teeth remaining was 22 + /- 7 . RESULTS During the r and omized trial , 11 of the 82 subjects ( 13 % ) taking supplements and 17 of the 63 subjects ( 27 % ) taking placebo  lost one or more teeth ( OR = 0.4 ; 95 % CI : 0.2 to 0.9 ) . During the 2-year follow-up period , 31 of the 77 subjects ( 40 % ) with total calcium intake of at least 1000 mg per day lost one or more teeth compared with 40 of the 68 subjects ( 59 % ) who consumed less ( OR = 0.5 ; 95 % CI : 0.2 to 0.9 ) . CONCLUSION These findings suggest that intake levels of calcium and vitamin D aim ed at preventing osteoporosis have a beneficial effect on tooth retention Abstract The effect of the combined administration of vitamin D3 and vitamin K2 on bone mineral density ( BMD ) of the lumbar spine was examined in postmenopausal women with osteoporosis . Ninety-two osteoporotic women who were more than 5 years after menopause , aged 55–81 years , were r and omly divided into four administration groups : vitamin D3 ( 1α hydroxyvitamin D3 , 0.75 μg/day ) ( D group ; n = 29 ) , vitamin K2 ( menatetrenone , 45 mg/day ) ( K group ; n = 22 ) , vitamin D3 plus vitamin K2 ( DK group , n = 21 ) , and calcium ( calcium lactate , 2 g/day ) ( C group ; n = 20 ) . BMD of the lumbar spine ( L2–L4 ) was measured by dual energy X-ray absorptiometry at 0 , 1 , and 2 years after the treatment started . There were no significant differences in age , body mass index , years since menopause , and initial BMD among the four groups . One-way analysis of variance ( ANOVA ) with repeated measurements showed a significant decrease in BMD in the C group ( P < 0.001 ) . Two-way ANOVA with repeated measurements showed a significant increase in BMD in the D and K groups compared with that in the C group ( P < 0.05 and P < 0.001 , respectively ) , and a significant increase in BMD in the DK group compared with that in the C , D , and K groups ( P < 0.0001 , P < 0.05 and P < 0.01 , respectively ) . These findings indicate that combined administration of vitamin D3 and vitamin K2 , compared with calcium administration , appears to be useful in increasing the BMD of the lumbar spine in postmenopausal women with osteoporosis OBJECTIVE This article presents the results of an evaluation of the clinical and laboratory safety of a 1-year course of treatment with a combination calcium and vitamin D tablet in ambulatory women aged > 65 years with vitamin D insufficiency . METHODS In a multicenter , r and omized , double-blind , placebo-controlled  study conducted in France , women with a 25-hydroxyvitamin D level < or = 12 ng/mL were r and omized to receive either a combination tablet containing calcium carbonate 500 mg and vitamin D3 400 IU taken twice daily or a matching placebo tablet for 1 year . A complete clinical examination was performed at baseline and at 3 , 6 , 9 , and 12 months of treatment ; blood and urine sample s were collected for laboratory analyses at the same time points . Safety was monitored based on adverse events recorded during the treatment period and on the results of laboratory tests , including measurement of creatinine and uric acid levels . RESULTS The study included 192 women ( mean [ SD ] age , 74.6 [ 6.9 ] years ; mean weight , 64.0 [ 12.5 ] kg ) , 95 in the calcium + vitamin D group and 97 in the placebo group . Fifty women ( 21/95 [ 22.1 % ] calcium + vitamin D , 29/96 [ 30.2 % ] placebo ) were prematurely withdrawn from the study for various reasons , with no difference in withdrawals between groups . Treatment-related adverse events were reported in 21 ( 22.1 % ) and 23 ( 24.0 % ) women in the respective treatment groups . These events consisted mainly of metabolic disorders ( 9 [ 9.5 % ] and 10 [ 10.4 % ] , respectively ) , particularly hypercalcemia ( 6 [ 6.3 % ] and 8 [ 8.3 % ] ) and gastrointestinal disorders ( 9 [ 9.5 % ] and 8 [ 8.3 % ] ) . No major complications directly related to calcium and vitamin D supplementation occurred during the course of treatment . Although renal function was not altered , the group who received calcium + vitamin D had significantly elevated concentrations of serum uric acid compared with those who received placebo ( 52.3 % vs 37.2 % ; P = 0.046 ) but not urinary uric acid . CONCLUSIONS In these ambulatory elderly women with vitamin D deficiency , supplementation with calcium + vitamin D appeared to be well tolerated over 1 year of treatment . No significant effects on creatinine clearance were observed . However , the proportion of women with elevated serum uric acid concentrations was significantly greater in those who received calcium + vitamin D compared with those who received placebo 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 . ) 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 Abstract : We undertook a double-masked , r and omized , placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip , spine and forearm . The study was performed in 240 healthy women , 58–67 years of age . Duration of treatment was 2 years . Bone mineral density ( BMD ) was measured at the lumbar spine , hip and forearm . A dietary question naire was administered twice during the study and revealed a fairly good calcium and vitamin D intake ( 919 mg calcium/day ; 3.8 mg vitamin D/day ) . An increase in lumbar spine BMD of 1.6 % was observed in the treatment group after 2 years ( p50.002 ) . In the placebo group no significant changes were observed during the 2 years . Lumbar spine BMD was significantly higher in the treatment group at both 1 ( p50.01 ) and 2 years ( p50.05 ) compared with the placebo group . Though not significant , the same trend was seen at the hip . No significant changes from baseline values were observed at the distal forearm in either the treatment or the placebo group . In conclusion , we found a significant increase in urinary calcium excretion in the treatment group compared with the placebo group . Together with significant changes in serum calcium and serum parathyroid hormone , this indicates that a long-term calcium and vitamin supplement of 1 g elementary calcium ( calcium carbonate ) and 14 mg vitamin D3 increases intestinal calcium absorption . A positive effect on BMD was demonstrated , even in a group of early postmenopausal age , with a fairly good initial calcium and vitamin D status Daily vitamin D in addition to calcium supplementation reduces falls and fractures in older women . However , poor adherence to therapy is a common clinical problem . To examine the effects of supervised oral 3-monthly vitamin D therapy on falls , muscle strength , and mobility , we conducted a 9-month r and omized , double-blind , placebo-controlled trial in 686 community-dwelling ambulant women aged over 70 years . Participants received either oral cholecalciferol 150,000 IU every 3 months ( n = 353 ) or an identical placebo ( n = 333 ) . All participants were advised to increase dietary calcium intake . Falls data were collected 3-monthly . At baseline , 3 , 6 , and 9 months , muscle strength was measured by a h and held dynamometer and mobility by the Timed Up and Go ( TUG ) test . Serum 25 hydroxyvitamin D ( 25OHD ) was measured in a subgroup of 40 subjects . Mean age at baseline was 76.7 ± 4.1 years . The average serum 25OHD value at baseline was 65.8 ± 22.7 nmol/L. By 3 , 6 , and 9 months after supplementation , 25OHD levels of the vitamin D group were approximately 15 nmol/L higher than the placebo group . Calcium intake did not change significantly between baseline ( 864 ± 412 mg/day ) and 9 months ( 855 ± 357 mg/day ) . Faller rates in the two groups did not differ : vitamin D group , 102 of 353 ( 29 % ) ; placebo group , 89 of 333 ( 27 % ) . At 9 months , compared to placebo or baseline , muscle strength , and TUG were not altered by vitamin D. In conclusion , oral cholecalciferol 150,000 IU therapy administered 3-monthly had neither beneficial nor adverse effects on falls or physical function . These data together with previous findings confirm that intermittent large doses of vitamin D are ineffective or have a deleterious effect on falls . Thus despite adherence issues with daily vitamin D replacement , an intermittent , high-dose vitamin D regimen can not be supported as a strategy to reduce falls and fractures OBJECTIVES To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation . DESIGN A r and omised controlled trial of cluster design . SETTING AND SUBJECTS 223 Residential units ( mainly identical 30-bedded units ) , within 118 homes for elderly people throughout Britain , with 3,717 participating residents ( 76 % women , average age 85 years ) . The units provided mainly or entirely residential care ( 35 % of residents ) , nursing care ( 42 % ) or care for elderly mentally infirm ( EMI ) residents ( 23 % ) . METHODS Participants were r and omly allocated by residential unit ( cluster design ) to a treated group offered ergocalciferol 2.5 mg every 3 months ( equivalent to a daily dose of 1,100 IU ) , or to a control group .  Fractures were reported by staff and confirmed in hospital , and routinely collected data on reported falls were obtained . RESULTS After median follow-up of 10 months ( interquartile range 7 - 14 months ) , 64 ( 3.6 % ) of 1,762 vitamin D-treated residents and 51 ( 2.6 % ) of 1,955 controls had one or more non-vertebral fractures , and 24 ( 1.3 % ) and 20 ( 1.0 % ) , respectively , had a hip fracture . The proportion reporting at least one fall was 44 % in vitamin D-treated and 43 % in control residents . The differences between the vitamin D and control groups were not statistically significant . The incidence of all non-vertebral fractures in the care homes ( 3.2 % per year ) and of hip fractures ( 1.1 % per year ) was low , similar to rates in elderly people in sheltered accommodation , and the pre-treatment serum 25-hydroxy vitamin D concentration was high [ median 47 nmol/l , measured in a 1 % ( n = 18 ) sample ] . CONCLUSIONS We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation OBJECTIVES We investigated the incidence of new  non-vertebral fractures  during HRT or low-dose vitamin ( Vit ) D3 supplementation in a 5-year prospect i ve trial . METHODS A total of 464 early postmenopausal women , ( a subgroup of the Kuopio Osteoporosis Study , n = 13100 ) were r and omized to four groups : ( 1 ) HRT , a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ; ( 2 ) Vit D ( 300 IU/day and 100 IU/day during the fifth year ) ; ( 3 ) HRT + Vit D ; and ( 4 ) placebo .  Lumbar ( L2 - 4 ) and femoral neck bone mineral densities ( BMD ) were determined by dual X-ray absorptiometry ( DXA ) at baseline , after 2.5 and 5 years of treatment . All new symptomatic non-vertebral , radiographically defined fractures were recorded . RESULTS Altogether , 368 women ( 79 % ) completed the 5 year treatment . In all , 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up ( HRT 4 , Vit D 10 , HRT + Vit D 8 and placebo 17 ) . The reduction in the incidence of new non-verterbral fractures was significant in women with HRT alone ( P = 0.032 ) when adjusted by baseline BMD and previous fractures ; observed also with the intention-to-treat principle ( P = 0.048 ) . When the HRT groups were pooled , HRT showed a significantly lower incidence of new non-vertebral fractures ( P = 0.042 ) than women receiving placebo and also after adjusting as above ( P = 0.016 ) ; both in valid-case and in the intention-to-treat analysis . In the Vit D group , the fracture incidence was non-significantly decreased ( P = 0.229 ) in comparison with the placebo group . The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 ( 95 % CI , 0.10 - 0.90 ) and with Vit D 0.47 ( 95 % CI , 0.20 - 1.14 ) and with HRT + Vit D 0.44 ( 95 % CI , 0.17 - 1.15 ) , in comparison with the placebo group ( adjusted by femoral BMD and previous fractures ) . CONCLUSIONS This study is the first prospect i ve trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women . The effect of low-dose Vit D remains to be proved Twenty-eight women with postmenopausal osteoporosis were studied in a double-blind trial aim ed to compare the effects of a one-year treatment with 1,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) , estradiol valerate ( E2 ) and placebo . Patients were divided into 4 groups : group 1 was given 1,25(OH)2D3 alone , group 2 was given E2 alone , group 3 was given 1,25(OH)2D3 + E2 , group 4 received a placebo . The evaluation of the effects of the treatments included clinical examination of patients , the measurement of a number of biochemical parameters , such as plasma and urinary calcium and phosphate , urinary hydroxyproline , serum alkaline phosphatase , the measurement of intestinal calcium absorption and bone mineral content ( BMC ) and a histomorphometric study of bone biopsies from the iliac crest . The best clinical results were obtained in the patients who were given 1,25(OH)2D3 alone ; appreciable results were also noticed in the patients who were given E2 alone or in combination with 1,25(OH)2D3 , while patients in the placebo group worsened . BMC decreased in the placebo group and increased , although non significantly , in the patients treated with 1,25(OH)2D3 or E2 or both . The histomorphometric study showed a significant increase in the mean trabecular diameter in patients treated with 1,25(OH)2D3 alone or in combination with E2 . Changes in the volume density of trabecular bone paralleled those in BMC . The results of the trial indicate that 1,25(OH)2D3 is an effective therapeutic agent in postmenopausal osteoporosis OBJECTIVES To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss  and whether rates of change in hard- and soft-tissue mass vary during the year . DESIGN Double-blind , placebo-controlled , 1-year trial in 249 women in which equal numbers of women were r and omized to either placebo or 400 IU of vitamin D daily . All women received 377 mg/d of supplemental calcium largely as calcium citrate malate . PATIENTS Healthy , ambulatory postmenopausal women with usual intakes of vitamin D of 100 IU/d . MEASUREMENTS Duplicate spine and whole-body scans were done by dual energy x-ray absorptiometry at 6-month intervals that were timed to periods when 25-hydroxyvitamin D levels were highest and lowest . Period 1 was June-July to December-January and period 2 was December-January to the next June-July . Serum parathyroid hormone and plasma 25-hydroxyvitamin D levels were measured during periods 1 and 2 . MAIN RESULTS In the placebo group , spinal bone mineral density increased in period 1 , decreased in period 2 , and sustained no net change . Women treated with vitamin D had a similar spinal increase in period 1 ( 1.46 % compared with 1.40 % in placebo ) , less loss in period 2 ( -0.54 % compared with -1.22 % , CI for the difference , 0.05 % to 1.31 % , P = 0.032 ) and a significant overall benefit ( 0.85 % compared with 0.15 % , CI for the difference , 0.03 % to 1.37 % , P = 0.04 ) . In period 2 , 25-hydroxyvitamin D levels were lower and parathyroid hormone levels were higher in the placebo than in the vitamin D group . Whole-body lean and fat tissue and bone mineral density varied during the year but did not change overall . CONCLUSIONS At latitude 42 degrees , healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily . A long-term benefit of preventing vitamin D insufficiency in the winter seems likely although it remains to be shown . Observed changes in bone as well as in fat and lean tissue appear to be related to season Background and aims : Supplementation of postmenopausal women with calcium alone or calcium-vitamin D association  was suggested to have positive effects on bone turnover and bone density , as well as to lower fracture incidence . The beneficial effect appears to be mediated by a reduction in parathyroid hormone secretion . Our aim was to compare the respective efficacy of calcium and calcium-vitamin D supplements in reducing serum parathyroid hormone levels in postmenopausal women with prevalent low 25(OH)vitamin D levels . Methods : One hundred consecutive ambulatory postmenopausal women with serum 25(OH)vitamin D levels below 18 ng/mL were included in a r and omized , prospect i ve , open label study . For a duration of 90 days , the women were r and omly assigned to a daily supplementation of either one tablet of calcium gluconolactate and carbonate ( 500 mg calcium ) , or one powder-pack of an association of calcium carbonate ( 500 mg calcium ) , citric acid ( 2.175 gr ) and cholecalciferol ( 200 IU ) . Changes observed during the 90 days of the study in circulating PTH levels were the primary endpoint , while changes in serum 25(OH)D levels were assessed as secondary endpoint . Results : A significant difference was observed between the calcium-vitamin D ( CaD ) and the calcium ( Ca ) only groups for changes occurring during the 90 days of the study in PTH ( −14.5±40 % and + 2.5±46 % ) ( p=0.009 ) and 25(OH)D ( + 67±77 % and + 18±55 % ) ( p<0.001 ) circulating levels . PTH changes between baseline and day 90 were significant in the CaD group , but not in the Ca group . The odds ratio for a patient in group Ca to experience an absolute ( < 12 ng/mL ) deficiency in circulating 25(OH)vitamin D levels , compared to a group CaD patient was statistically increased ( OR : 3.22 , 95 % CI : 1.33–7.80 ) . Conclusions : Our results support the recommendation of supplementing postmenopausal women with low circulating levels of 25(OH)vitamin D with a combination of calcium and vitamin D , rather than with calcium alone OBJECTIVES To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient . DESIGN R and omized , placebo-controlled double-blind , trial of 2 years ' duration . SETTING Multicenter study in 60 hostels ( assisted living facilities ) and 89 nursing homes across Australia . PARTICIPANTS Six hundred twenty-five residents ( mean age 83.4 ) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L. INTERVENTION Vitamin D supplementation ( ergocalciferol , initially 10,000 IU given once weekly and then 1,000 IU daily ) or placebo for 2 years . All subjects received 600 mg of elemental calcium daily as calcium carbonate . MEASUREMENTS Falls and fractures recorded prospect ively in study diaries by care staff . RESULTS The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , the incident rate ratio for falling was 0.73 ( 95 % confidence interval (CI)=0.57 - 0.95 ) . The odds ratio for ever falling was 0.82 ( 95 % CI=0.59 - 1.12 ) and for ever fracturing was 0.69 ( 95 % CI=0.40 - 1.18 ) . An a priori subgroup analysis of subjects who took at least half the prescribed capsules ( n=540 ) , demonstrated an incident rate ratio for falls of 0.63 ( 95 % CI=0.48 - 0.82 ) , an odds ratio ( OR ) for ever falling of 0.70 ( 95 % CI=0.50 - 0.99 ) , and an OR for ever fracturing of 0.68 ( 95 % CI=0.38 - 1.22 ) . CONCLUSION Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient Introduction The objectives were:(1 ) to vali date a quantitative balance assessment method for fall risk prediction ; ( 2 ) to investigate whether the effect of vitamin D and calcium on the risk of falling is mediated through postural or dynamic balance , as assessed by this method . Material s and methods A secondary analysis of a double blind r and omized controlled trial was employed , which included 64 institutionalized elderly women with complete balance assessment ( age range : 65–97 ; mean 25–hydroxyvitamin D levels : 16.4 ng/ml ( SD ±9.9 ) . Participants received 1,200 mg calcium plus 800 IU cholecalciferol ( n=33 ) or 1,200 mg calcium ( n=31 ) per day over a 3-month treatment period . Using an electronic device attached to the lower back of the participant , balance was assessed as the degree of trunk angular displacement and angular velocity during a postural task ( st and ing on two legs , eyes open , for 20 s ) and a dynamic task ( get up from a st and ard height chair with arm rests , sit down and then st and up again and remain st and ing ) . Results It was found that both postural and dynamic balance independently and significantly predicted the rate of falling within the 3-month follow-up . Vitamin D plus calcium  reduced the rate of falls by 60 % [ relative risk (RR)=0.40 ; 95 % CI : 0.17 , 0.94 ] if compared with calcium alone . Once postural and dynamic balance were added to the regression analysis , they both attenuated the effect of vitamin D plus calcium on the rate of falls . For postural balance , the RR changed by 22 % from 0.40 to 0.62 if angular displacement was added to the model , and by 9 % from 0.40 to 0.49 if angular velocity was added . For dynamic balance , it changed by 1 % from 0.40 to 0.41 if angular displacement was added , and by 14 % from 0.40 to 0.54 if angular velocity was added . Discussion Thus , balance assessment using trunk angular displacement is a valid method for the prediction of falls in older women . Of the observed 60 % reduction in the rate of falls by vitamin D plus calcium supplementation compared with calcium alone , up to 22 % of the treatment effect was explained by a change in postural balance and up to 14 % by dynamic balance OBJECTIVES To study the effect of alfacalcidol ( 1alpha(OH)D3 ) on fall risk in community-dwelling elderly men and women . DESIGN R and omized , double-blind , placebo-controlled intervention trial . SETTING Basel , Switzerl and . PARTICIPANTS Three hundred seventy-eight community-dwelling elderly ( 191 women/187 men ) . INTERVENTION Participants were r and omly assigned to receive 1 microg of alfacalcidol or matched placebo daily for 36 weeks . MEASUREMENTS Serum 25-hydoxyvitamin D3 ( 25(OH ) D,1,25-dihydroxyvitamin D3 ( D-hormone ) , and intact parathormone ( iPTH ) levels were measured using radioimmunoassay at baseline and every 12 weeks . Numbers of fallers and falls were assessed using a question naire during each study site visit . Dietary calcium intake was assessed at baseline using a food frequency question naire . RESULTS At baseline , participants had , on average , normal vitamin D and D-hormone serum levels . Over 36 weeks , alfacalcidol treatment was associated with fewer fallers ( odds ratio (OR)=0.69 , 95 % confidence interval (CI)=0.41 - 1.16 ) than placebo . In a post hoc subgroups analysis by medians of total calcium intake , this reduction reached significance in alfacalcidol-treated subjects with a total calcium intake of more than 512 mg/d ( OR=0.45 , 95 % CI=0.21 - 0.97 , P=.042 ) but not in those who consumed less than 512 mg/d ( OR=1.00 , 95 % CI= 0.47 - 2.11 , P=.998 ) . Alfacalcidol treatment was also , independent of total calcium intake , associated with a significant 37.9 % reduction in iPTH serum levels ( P<.0001 ) . No cases of clinical ly relevant hypercalcemia were observed . CONCLUSION Provided a minimal calcium intake of more than 512 mg/d , alfacalcidol treatment significantly and safely reduces number of fallers in an elderly community dwelling population BACKGROUND A recent meta- analysis found that cholecalciferol ( vitamin D ) should reduce falls by more than 20 % . However , little is known about whether supplemental cholecalciferol plus calcium citrate malate will lower the long-term risk of falling in men , active older individuals , and older individuals with higher 25-hydroxyvitamin D levels . METHODS We studied the effect of 3-year supplementation with cholecalciferol-calcium on the risk of falling  at least once in 199 men and 246 women 65 years or older and living at home . Individuals received 700 IU of cholecalciferol plus 500 mg of calcium citrate malate per day or placebo in a r and omized double-blind manner . Subjects were classified as less physically active if physical activity was below the median level . Low 25-hydroxyvitamin D levels were classified as those below 32 ng/mL ( < 80 nmol/L ) . RESULTS In 3 years , 55 % of women and 45 % of men reported at least 1 fall . Mean + /- SD baseline 25-hydroxyvitamin D levels were 26.6 + /- 12.7 ng/mL ( 66.4 + /- 31.7 nmol/L ) in women and 33.2 + /- 14.2 ng/mL ( 82.9 + /- 34.9 ) in men . Cholecalciferol-calcium significantly reduced the odds of falling in women ( odds ratio [ OR ] , 0.54 ; 95 % confidence interval [ CI ] , 0.30 - 0.97 ) , but not in men ( OR , 0.93 ; 95 % CI , 0.50 - 1.72 ) . Fall reduction was most pronounced in less active women ( OR , 0.35 ; 95 % CI , 0.15 - 0.81 ) . Baseline 25-hydroxyvitamin D level did not modulate the treatment effect . CONCLUSIONS Long-term dietary cholecalciferol-calcium supplementation reduces the odds of falling in ambulatory older women by 46 % , and especially in less active women by 65 % . Supplementation had a neutral effect in men independent of their physical activity level Specific receptors for vitamin D have been identified in human muscle tissue . Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls . We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls . In a double-blind r and omized controlled trial , we studied 122 elderly women ( mean age , 85.3 years ; range , 63 - 99 years ) in long-stay geriatric care . Participants received 1200 mg calcium plus 800 IU cholecalciferol ( Cal+D-group ; n = 62 ) or 1200 mg calcium ( Cal-group ; n = 60 ) per day over a 12-week treatment period . The number of falls per person ( 0 , 1 , 2 - 5 , 6 - 7 , > 7 falls ) was compared between the treatment groups . In an intention to treat analysis , a Poisson regression model was used to compare falls after controlling for age , number of falls in a 6-week pretreatment period , and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations . Among fallers in the treatment period , crude excessive fall rate ( treatment - pretreatment falls ) was compared between treatment groups . Change in musculoskeletal function ( summed score of knee flexor and extensor strength , grip strength , and the timed up&go test ) was measured as a secondary outcome . Among subjects in the Cal+D-group , there were significant increases in median serum 25-hydroxyvitamin D ( + 71 % ) and 1,25-dihydroxyvitamin D ( + 8 % ) . Before treatment , mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group . In the 12-week treatment period , mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group . After adjustment , Cal+D-treatment accounted for a 49 % reduction of falls ( 95 % CI , 14 - 71 % ; p < 0.01 ) based on the fall categories stated above . Among fallers of the treatment period , the crude average number of excessive falls was significantly higher in the Cal-group ( p = 0.045 ) . Musculoskeletal function improved significantly in the Cal+D-group ( p = 0.0094 ) . A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49 % compared with calcium alone . Over this short-term intervention , recurrent fallers seem to benefit most by the treatment . The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function Summary In 242 community-dwelling seniors , supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D result ed in a decrease in the number of subjects with first falls of 27 % at month 12 and 39 % at month 20 . Additionally , parameters of muscle function improved significantly . Introduction The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially . R and omized controlled trials using falls as primary outcome are needed . We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men . Methods Our study population consisted of 242 individuals recruited by advertisements and mailing lists ( mean [ ± SD ] age , 77 ± 4 years ) . All serum 25-hydroxyvitamin D ( 25[OH]D ) levels were below 78 nmol/l . Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months , which was followed by a treatment-free but still blinded observation period of 8 months . Falls were documented using diaries . The study took place in Bad Pyrmont , Germany ( latitude 52 ° ) and Graz , Austria ( latitude 46 ° ) . Results Compared to calcium mono , supplementation with calcium plus vitamin D result ed in a significant decrease in the number of subjects with first falls of 27 % at month 12 ( RR = 0.73 ; CI = 0.54–0.96 ) and 39 % at month 20 ( RR = 0.61 ; CI = 0.34–0.76 ) . Concerning secondary endpoints , we observed significant improvements in quadriceps strength of 8 % , a decrease in body sway of 28 % , and a decrease in time needed to perform the TUG test of 11 % . Discussion Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals 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 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 The long term effects of hormone replacement therapy ( HRT ) and vitamin D3 ( Vit D ) on bone mineral density ( BMD ) were studied . A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study ( n = 13100 ) were r and omized to four groups : 1 ) HRT ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate , 2 ) Vit D3 ( 300 and 100 IU/day during the fifth year ) , 3 ) HRT and Vit D combined , and 4 ) placebo .  Lumbar ( L2-L4 ) and femoral neck BMD were determined by dual x-ray absorptiometry ( DXA ) at baseline and after 2.5 and 5 yr of treatment . Intention to treat analysis ( n = 464 ) showed that after 5 yr , lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [ + 0.2 % ( P = 0.658 ) and + 0.9 % ( P = 0.117 ) , respectively ] , whereas lumbar BMD decreased by 4.6 % in the Vit D group and by 4.5 % in the placebo group ( P < 0.001 in both ) . The loss of femoral neck BMD was less in the HRT ( -1.4 % ; P = 0.005 ) and HRT plus Vit D ( -1.3 % ; P = 0.003 ) groups than in the Vit D and placebo groups ( -4.3 % ; P < 0.001 in both ) . Among those 370 women who complied with the 5-yr treatment , the effect was more pronounced : lumbar BMD had increased by 1.5 % in the HRT ( P = 0.009 ) and by 1.8 % in the HRT plus Vit D group ( P = 0.005 ) , with a plateau after 2.5 yr , whereas lumbar BMD had decreased in both the Vit D and placebo groups ( 4.6 % and 4.7 % ; P < 0.001 , respectively ) . Femoral neck BMD decreased again less in the HRT ( -0.4 % ) and HRT plus Vit D ( -0.6 % ) groups than in the Vit D and placebo groups ( -4.4 % in both ) . This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis . The data suggest that low dose vitamin D3 supplementation does not prevent  bone loss in healthy , nonosteoporotic , early postmenopausal women , and it confers no benefit additional to that of HRT alone BACKGROUND Vitamin D deficiency is common in older people and may increase risk of falls and fracture .  Hospital in patients are at particular risk of falling . Previous studies suggest that vitamin D improves neuromuscular function and reduces falls . OBJECTIVE To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are in patients . DESIGN R and omised , double-blind , controlled study . PARTICIPANTS two hundred and five acute admissions > 65 years to a geriatric medical unit . METHODS Patients were r and omised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg , until discharge or death . RESULTS Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days ( IQR 14.75 - 71.00 ) . In a pre-selected sub-group ( 54/205 participants ) , median admission vitamin D level = 22.00 nmol/l ( IQR 15.00 - 30.50 ) . This did not significantly increase in the treatment versus control group . Median study drug adherence = 88 % , with no significant difference between study groups ( Mann-Whitney : P = 0.711 ) . Although there were fewer fallers in the vitamin D cohort , this did not reach statistical significance ( vitamin D : calcium = 36:45 fallers ; RR 0.82 ( CI 0.59 - 1.16 ) . Neither the mean number of falls  ( vitamin D : calcium = 1.040:1.155 ; Mann-Whitney P = 0.435 ) or time to first fall ( Log-rank test P = 0.377 ) differed between groups . CONCLUSIONS In a population of geriatric hospital in patients , vitamin D did not reduce the number of fallers . Routine supplementation can not be recommended to reduce falls in this group BACKGROUND Vitamin D deficiency is common in older population s , particularly during the winter months due to low levels of ultraviolet light exposure , and in nursing home residents . OBJECTIVE The main objective of the current study was to assess the distribution of serum 25-hydroxyvitamin D and its correlates in a sample of men and women with recent hip fractures who were part of a large clinical trial . METHODS This was a cross-sectional exploratory study of screened and ultimately r and omized patients with hip fractures . They were part of a multinational ( 115 clinical centers in 20 countries ) , r and omized , placebo-controlled , double-blind study testing the efficacy of a yearly IV bisphosphonate ( zoledronic acid ) in the prevention of new clinical fractures in patients with recent hip fracture repair .  Levels of 25-hydroxyvitamin D , calcium , alkaline phosphatase , creatinine clearance , and albumin were measured at a screening visit using blood serum . Demographic variables were assessed by patient self-report . Bone mineral density ( BMD ) was assessed by dual-energy x-ray absorptiometry of the nonfractured hip . RESULTS This report included 1174 screened patients ( 526 with vitamin D measured ) and 655 ( 385 with vitamin D measured ) patients r and omized before the protocol amendment . In screened patients , levels of 25-hydroxyvitamin D were low ( median , 14.7 ng/mL ; interquartilc range , 7.6 , 21.65 ) . Overall , 51 % were at or below the clinical ly meaningful threshold of 15 ng/mL. Among those patients r and omized , the level of 25-hydroxyvitamin D was significantly positively related to male sex ( rho , 0.13 ; P < 0.05 ) , serum calcium ( rho , 0.16 ; P < 0.01 ) , and BMD at the femoral neck ( rho , 0.22 ; P < 0.01 ) in bivariate analyses . Low serum 25-hydroxyvitamin D ( < 15 ng/mL ) was related only to low serum calcium ( odds ratio , 0.16 ; 95 % CI , 0.05 - 0.52 ) in multivariable logistic models controlling for sex , age , race , body mass index , living at home , alkaline phosphatase , and creatinine clearance . CONCLUSIONS We concluded that vitamin D insufficiency was a common problem in this population of elderly patients who had recently suffered a hip fracture . This insufficiency was related only to serum calcium in multivariable controlled models but can not be reliably identified or excluded by measuring serum calcium alone . Physicians should be encouraged to check and monitor patients ' serum levels of 25-hydroxyvitamin OBJECTIVES Low trauma fractures in older people incur enormous physical , social and economic costs . Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group . This strategy requires validation in a population setting . METHODS R and omized , double-blind , placebo-controlled trial of 300,000 IU intramuscular ( i.m . ) vitamin D2 ( ergocalciferol ) injection or matching placebo every autumn over 3 years . 9440 people ( 4354 men and 5086 women ) aged 75 yrs and over were recruited from general practice registers in Wessex , Engl and . Primary outcome measure was all non-vertebral fracture . Secondary outcomes were hip and wrist fractures , and all falls . RESULTS 585 subjects had incident non-spine fractures  ( hip 110 , wrist 116 , ankle 37 ) . Hazard ratios ( HRs ) for fracture in the vitamin D group were : 1.09 [ 95 % confidence interval ( CI ) 0.93 - 1.28 , P = 0.29 ] for any first fracture , 1.49 ( 95 % CI 1.02 - 2.18 , P = 0.04 ) for hip and 1.22 ( 95 % CI 0.85 - 1.76 , P = 0.28 ) for wrist . There was no effect on falls : HR 0.98 ( 0.93 - 1.04 ) . No protective effect was observed in any subgroup when the cohort was stratified by sex , age , previous fracture or mobility . CONCLUSIONS An annual i.m . injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population The long-term effects of calcium and vitamin D supplementation on bone material and structural properties in older men are not known . The aim of this study was to examine the effects of high calcium ( 1000 mg/day)- and vitamin-D(3 ) ( 800 IU/day)-fortified milk on cortical and trabecular volumetric BMD ( vBMD ) and bone geometry at the axial and appendicular skeleton in men aged over 50 years . One hundred and eleven men who were part of a larger 2-year r and omized controlled trial had QCT scans  of the mid-femur and lumbar spine ( L(1)-L(3 ) ) to assess vBMD , bone geometry and indices of bone strength [ polar moment of inertia ( I(polar ) ) ] . After 2 years , there were no significant differences between the milk supplementation and control group for the change in any mid-femur or L(1)-L(3 ) bone parameters for all men aged over 50 years . However , the mid-femur skeletal responses to the fortified milk varied according to age , with a split of < or=62 versus > 62 years being the most significant for discriminating the changes between the two groups . Subsequent analysis revealed that , in the older men ( > 62 years ) , the expansion in mid-femur medullary area was 2.8 % ( P < 0.01 ) less in the milk supplementation compared to control group , which helped to preserve cortical area in the milk supplementation group ( between group difference 1.1 % , P < 0.01 ) . Similarly , for mid-femur cortical vBMD and I(polar ) , the net loss was 2.3 and 2.8 % less in the milk supplementation compared to control group ( P < 0.01 and < 0.001 , respectively ) . In conclusion , calcium-vitamin-D(3)-fortified milk may represent an effective strategy to maintain bone strength by preventing endocortical bone loss and slowing the loss in cortical vBMD in elderly men A two-year double-blind study monitored and evaluated the effects of 1 alpha-hydroxy vitamin D3 ( 1 alpha(OH)D3 ) on the lumbar ( L2 - 4BMD ) and total body bone mineral densities ( TBBMD ) and occurrence of fracture in 113 female osteoporotic patients receiving 0.75 micrograms/day of 1 alpha(OH)D3 ( n = 57 ) or a placebo ( n = 56 ) with calcium supplementation in both groups .  L2 - 4BMD increased 1.81.% and 2.32 % after one and 2 years in the 1 alpha (OH)D3 group , but decreased 1.89 % ( P < 0.05 ) and 0.28 % in the placebo group . A significant difference ( P < 0.01 ) existed between the two groups after one year . TBBMD decreased significantly in the placebo group by 3.34 % ( P < 0.01 ) and 3.52 % after one and 2 years . Six new fractures occurred in the control group , but only two in the 1 alpha(OH)D3 group ( Odd 's ratio = 0.343 , 95 % confidence range ; 0.0648 - 1.815 ) . There were no serious adverse effects of the 1 alpha(OH)D3 treatment . It was concluded that two-year treatment with 1 alpha(OH)D3 increased the lumbar BMD and inhibited the decrease in TBBMD . Although it was not significant , new fracture occurrence in the 1 alpha(OH)D3 group was around 1/3 of that in the control group The efficacy of calcium ( Ca ) in reducing bone loss is debated . In a r and omized placebo-controlled double-masked study , we investigated the effects of oral Ca supplements on femoral shaft ( FS ) , femoral neck ( FN ) and lumbar spine ( LS ) bone mineral density ( BMD ) , and on the incidence of vertebral fracture in vitamin-D-replete elderly . Ninety-three healthy subjects ( 72.1±0.6 years ) were r and omly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months . Sixty-three patients ( 78.4±1.0 years ) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo . FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group ( + 0.6±0.5 % v −1.2±0.7%,p<0.05 ) . There was no difference in effect between the two forms of Ca . The changes of + 0.7±0.8 % v −1.7±1.6 % in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance . In fractured patients , FS , FN and LS BMD changes were −1.3±0.8 , + 0.3±1.6 and + 3.1±1.2 % ( p<0.05 for the last ) . The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group , respectively , and 144.0 in Ca-supplemented fractured patients . Thus , oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly To evaluate the efficacy and safety of 1-alpha(OH ) vitamin D3 in the treatment of postmenopausal osteoporosis , we conducted a six month prospect i ve , double blind study in 20 postmenopausal women . Women were r and omly divided into two groups . One group ( n=12 ) received 1-alpha(OH ) vitamin D3 ( 0.25 mcg twice a day ) , the other ( n=8 ) received placebo . At the same time both groups received one calcium tablet ( 500 mg daily ) . In the group treated with 1-alpha(OH ) vitamin D3 , there was a significant increase in serum calcium ( p<0.01 ) , urinary excretion of calcium ( p<0.05 ) , and serum 1.25(OH)2 vitamin D3 concentracion ( p<0.01 ) , while parathyroid hormone levels showed tendency to fall without statistical significance . In the group treated with placebo and calcium , after treatment there was only a significant increase in serum calcium ( p<0.01 ) . In the placebo group occurrance of one new vertebral fracture was recorded . There were no side effects during treatment in both groups . It was concluded that the administration of 1-alpha(OH ) vitamin D3 is a safe and potentially efficient drug in the treatment of postmenopausal osteoporosis The therapeutic effect of 1,25-dihydroxycholecalciferol ( 1,25(OH)2D3 ) in postmenopausal osteoporosis was tested in a single blind , r and omized prospect i ve study . Thirty-nine women , 50 - 65 years of age , were treated for three years with 0.5 microgram 1,25(OH)2D3 daily . In a control group , 37 women were given 400 IU vitamin D3 daily . There was no significant difference in annual bone loss from the distal or proximal forearm between the groups . New vertebral fractures were evaluated , and in the treatment group , the annual increase in vertebral fractures was 0.18 + /- 0.387 and in the control group 0.13 + /- 0.330 . New long bone fractures were 7 and 5 , respectively . None of the observed differences were statistically significant . In the 1,25(OH)2D3 group , 28 % had to reduce the dose because of slight hypercalcaemia . We conclude that 1,25(OH)2D3 as used in this study is not effective in the treatment of osteoporosis Summary In order to investigate the effect of a supplementation of vitamin D in the prophylaxis of fractures of the bones of aged people , an annual intramuscular injection of ergocalciferol ( 150,000–300,000 IU ) was given to two series of aged subjects : first to 199 ( 45 male ) of 479 subjects ( 110 male ) aged more than 85 years who were living in their own home , and second to 142 ( 29 male ) of 320 ( 58 male ) subjects aged 75–84 and living in a home for aged people . This prospect i ve series was divided into treatment groups according to month of birth . These injections were given annually from September to December in the years 1985–1989 , two to five times to each participant . The fracture rates , laboratory values , vitamin D levels , possible side effects , and mortality were followed until October 1990 . A total of 56  fractures  occurred in the 341 vitamin D recipients ( 16.4 % ) and 100 in 458 controls ( 21.8 % ) ( P=0.034 ) . The fracture rate was about the same in both outpatient and municipal home series . Fractures of the upper limb were fewer in the vitamin D recipients , 10/341=2.9 % ( P=0.025 ) , than in the controls , 28/458=6.1 % , during the follow-up . A similar result was obtained in fractures of ribs , 3/341=0.9 % and 12/458=2.6 % , respectively . Fractures of the lower limbs occurred almost as frequently , 31/341=9.1 % , among the vitamin D recipients as among the controls , 49/458=10.7 % . The fracture rate was higher in females ( 22.2 % ) than in males ( 9.5 % ) . The fractures were fewer in the vitamin D recipients only in females . No significant differences were found in total mortality , or due to any group of diseases , between the two treatment groups . No deleterious effects of the  vitamin D  injections were seen . The authors recommend the supplementation of vitamin D in aged people , at least in northernmost latitudes ( e.g. , as an annual intramuscular injection ) To examine whether the administration of 1 alpha (OH)-vitamin D3 ( 1 alpha (OH)D3 ) could prevent the occurrence of vertebral crush fractures in senile osteoporosis , crush fractures of the thoracic or lumbar spine in senile osteoporosis treated with 1 alpha (OH)D3  , 1.0 microgram/day ( 22 cases ) , 1 alpha (OH)D3 1.0 microgram/day + Ca 1.0 g/day ( 16 cases ) or Ca 1.0 g/day ( 23 cases ) were compared with those in non-treated controls ( 25 cases ) . The average treatment periods were 1.7 + /- 0.7 years in the 1 alpha (OH)D3 group , 2.1 + /- 1.0 years in the 1 alpha (OH)D3 + Ca group and 1.7 + /- 0.9 years in the Ca group . Occurrence of spinal crush fractures per 1000 patient years was significantly less in the 1 alpha (OH)D3 + Ca group ( P less than 0.01 ) than in the non-treated control group . These findings suggest that administration of 1 alpha (OH)D3 is effective in preventing the occurrence of pathological fractures in senile osteoporosis To evaluate the effects of calcium and 25-OHD in the therapy of senile osteoporosis , we studied a group of 39 women aged 69 + /- 7 ( st and ard deviation , SD ) years with severe osteoporosis . The group was characterized histomorphometrically by depressed bone remodeling rates without hyperosteoidosis . No subject had risk factors for osteopenia other than their age and postmenopausal status , and no subject was receiving therapy for bone disease at the onset of the study . Subjects were followed for 2 years after r and omization to receive either 1200 mg/day of calcium ( as calcium carbonate ) and 40 micrograms/day of 25-OHD ( calcium-25-OHD group ) , or 1200 mg/day of calcium plus placebo ( calcium-placebo group ) . Calcium-25-OHD result ed in a clear increase in 25-OHD levels ( p less than 0.001 ) and an increase in calcium absorption as indicated by urinary calcium excretion . Nevertheless , there was no significant change in fasting serum calcium , phosphorus , alkaline phosphatase , PTH , or 1,25-(OH)2D in either group . Radial and phalangeal bone mineral content and trabecular bone volume in the biopsied patients remained stable in both groups over the 2 year period . Unexpectedly , repeat bone biopsies revealed a clear improvement in the rate of mineralization in both groups , presumably as a result of the calcium supplementation alone . In summary , calcium-placebo and calcium-25-OHD treatment were both associated with stable appendicular bone mineral content in women with senile osteopenia . The finding of an effect of calcium supplementation on the rate of mineralization indicates that relative calcium deficiency may impair the mineralization phase of remodeling . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES To investigate the effect of vitamin K2 treatment for a year on spinal bone mineral density ( BMD ) in postmenopausal women , comparing with vitamin D3 hormone replacement therapy and to determine the factors which affect the efficacy of vitamin K2 therapy . SUBJECTS AND METHODS Seventy-two postmenopausal women were r and omized into four groups and treated with respective agents . Before the therapy , 6 and 12 months after the treatment , their lumbar spine BMD were measured by dual energy X-ray absorptiometry . The rates of change in BMD ( delta BMD ) were calculated . Correlations of BMD with age , year since menopause and the initial BMD were determined . RESULTS Vitamin K2 suppressed the decrease in spinal BMD as compared with no treatment group . BMD in women treated with vitamin K2 was inversely correlated with their age ( r = -0.54 ; P < 0.05 ) . CONCLUSIONS Vitamin K2 therapy may be a useful method for preventing postmenopausal spinal bone mineral loss . In addition , the therapy should be started early in postmenopausal period OBJECTIVE Patients with osteoarthritis ( OA ) have increased bone mineral density ; however , the association between knee OA and fracture is controversial . Few data exist on the association between knee pain and fracture . We examined the association of knee OA and knee pain with fracture and falls in elderly men and women . METHODS The study group comprised 6,641 men and women ages > or = 75 years who participated in a 3-year r and omized controlled trial of intramuscular vitamin D therapy .  Patients completed a question naire about knee pain and OA .  Fracture and fall data were collected prospect ively every 6 months . RESULTS Knee pain prevalence and a clinician diagnosis of knee OA were 35.2 % and 6.8 % , respectively . A total of 436 incident nonvertebral fractures were reported , and 3,992 patients sustained a fall . Prevalent knee pain was associated with an increased risk of falls ( hazard ratio [ HR ] 1.26 , 95 % confidence interval [ 95 % CI ] 1.17 - 1.36 ) and hip fracture ( HR 2.0 , 95 % CI 1.18 - 3.37 ) . Increasing severity of knee pain was associated with a greater risk of falls and hip fracture . Clinician diagnosis of knee OA was associated with an increased risk of nonvertebral fractures ( HR 1.61 , 95 % CI 1.09 - 2.36 ) . The increased risk of fracture was not substantially reduced by adjusting for falls , but was attenuated by adjustment for the use of walking aids . CONCLUSION Patients with a clinical diagnosis of knee OA and with knee pain have an increased risk of nonvertebral and hip fracture . This is not explained by the increased risk of falls , but is more likely to be due to the severity of falls sustained . Knee pain and OA should be regarded as independent risk factors for fracture There is an increase in the incidence of falls with aging and about 10 % of falls lead to fractures . Nearly all hip fractures are due to falls and hip fractures are the most severe of the osteoporotic fractures because they lead to a 20 % mortality rate and a loss of independent living in 50 % of cases . Although there are multiple factors associated with falls , our interest is the role that vitamin D metabolism plays in the pathogenesis of falls . Recent clinical trials show that both vitamin D and the metabolite calcitriol reduce the number of falls by 30 - 40 % in elderly subjects . This should also reduce the number of fractures . In European studies , the decrease in falls could be attributed to an improvement in the muscle weakness that often accompanies vitamin D deficiency . However , in the studies using calcitriol there was no vitamin D deficiency , so the mechanism of its efficacy is less clear . It could be due to increased muscle strength , an improvement in the neurological control of balance or both . Underst and ing these mechanisms would allow us to search for analogs of vitamin D that act more selectively on muscle and on the central nervous system OBJECTIVES To study the effects of vitamin D supplementation in healthier population s of men . DESIGN : R and omized , controlled trial . SETTING General clinical research center . PARTICIPANTS Sixty-five healthy , community-dwelling men ( mean age+/-st and ard deviation=76+/-4 , range 65 - 87 ) . INTERVENTION Cholecalciferol ( 1,000 IU/d ) or placebo supplementation for 6 months ; all received 500 mg supplemental calcium . MEASUREMENTS Upper and lower extremity muscle strength and power , physical performance and activity , health perception , calcium and vitamin D intake , and biochemical assessment , including 25-hydroxyvitamin D ( 25OHD ) , parathyroid hormone ( PTH ) , and ionized calcium levels . RESULTS The levels of 25OHD increased and PTH decreased in the cholecalciferol group , whereas there were no significant changes in the control group ( P<.001 ) . Baseline 25OHD levels correlated with baseline single-leg stance time and physical activity score . Baseline PTH levels correlated with baseline 8-foot walk time and physical activity score . No significant difference in strength , power , physical performance , or health perception was found between groups . CONCLUSION The 25OHD or PTH levels correlated with physical activity and physical performance in older , community-dwelling men with normal 25OHD status . Vitamin D supplementation increased 25OHD levels and decreased PTH levels but did not increase muscle strength or improve physical performance or health perception in this group of healthy , older men . Further investigations of the effects of vitamin D supplementation should focus on individuals with low levels of vitamin BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to test the hypothesis that vitamin D(3 ) supplementation would prevent bone loss in calcium-replete , African American postmenopausal women . METHODS Two hundred eight healthy black postmenopausal women , 50 to 75 years of age , were assigned to receive either placebo or 20 microg/d ( 800 IU ) of vitamin D(3 ) . Calcium supplements were provided to ensure a total calcium intake of 1200 to 1500 mg/d . After 2 years , the vitamin D(3 ) dose was increased to 50 microg/d ( 2000 IU ) in the active group , and the study continued for an additional year . Bone mineral density ( BMD ) was measured every 6 months . Markers of bone turnover , vitamin D metabolites , and parathyroid hormone ( PTH ) levels were measured in serum . RESULTS There were no significant differences in BMD between the active and control groups throughout the study . There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss . There was an increase in BMD of the total body , hip , and radius at 1 year in both groups . Over the 3 years , BMD declined at these sites by 0.26 % to 0.55 % per year . The BMD of the lumbar spine increased slightly in the placebo and active groups . There were no persistent changes in serum PTH levels or the markers of bone turnover , although there was a transient decline in PTH in both groups at 3 months . No significant adverse events were attributed to vitamin D supplementation . CONCLUSIONS There was no observed effect of vitamin D(3 ) supplementation on bone loss or bone turnover markers in calcium-replete , postmenopausal African American women . Further studies are needed to determine if these findings are applicable to women of other ethnic groups 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 CONTEXT Mono- and polyunsaturated fats may have opposing effects on vitamin D absorption . OBJECTIVE The purpose of this study was to determine whether intakes of different dietary fats are associated with the increase in serum 25-hydroxyvitamin D ( 25OHD ) after supplementation with vitamin D(3 ) . DESIGN , SETTING , AND PARTICIPANTS This analysis was conducted in the active treatment arm of a r and omized , double-blind , placebo-controlled trial of vitamin D and calcium supplementation to prevent bone loss and fracture . Subjects included 152 healthy men and women age 65 and older who were assigned to 700 IU/d vitamin D(3 ) and 500 mg/d calcium .  Intakes of monounsaturated fatty acids ( MUFA ) , polyunsaturated fatty acids ( PUFA ) , and saturated fatty acids ( SFA ) were estimated by food frequency question naire . MAIN OUTCOME MEASURE The change in plasma 25OHD during 2 yr  vitamin D and calcium supplementation was assessed . RESULTS The change in plasma 25OHD ( nanograms per milliliter ) during vitamin D supplementation was positively associated with MUFA , ( β = 0.94 ; P = 0.016 ) , negatively associated with PUFA , ( β = -0.93 ; P = 0.038 ) , and positively associated with the MUFA/PUFA ratio ( β = 6.46 ; P = 0.014 ) . CONCLUSION The fat composition of the diet may influence the 25OHD response to supplemental vitamin D(3 ) . Diets rich in MUFA may improve and those rich in PUFA may reduce the effectiveness of vitamin D(3 ) supplements in healthy older adults . More studies are needed to confirm these findings BACKGROUND Frequent use of personal , non protocol calcium supplements obscured an adverse effect of coadministered calcium and vitamin D ( CaD ) on cardiovascular risk in the Women 's Health Initiative ( WHI ) . OBJECTIVE We investigated the effects of the use of personal calcium or vitamin D supplements on other outcomes in the WHI CaD Study ( WHI CaD ) by using the WHI limited-access clinical trials data set . DESIGN The WHI CaD was a 7-y , r and omized , placebo-controlled trial of CaD ( 1 g Ca/400 IU vitamin D daily ) in 36,282 community-dwelling , postmenopausal women . The incidence of total cancer ( excluding nonmelanoma skin cancers ) , breast and colorectal cancers , hip and total fracture , and mortality was assessed by using Cox proportional hazards models . RESULTS In the WHI CaD , interactions between the use of either personal calcium or vitamin D supplements and CaD were found for total , breast , and colorectal cancers but not for fracture or mortality .  In 15,646 women ( 43 % ) who were not taking personal calcium or vitamin D supplements at r and omization , CaD significantly decreased the risk of total , breast , and invasive breast cancers by 14 - 20 % and nonsignificantly reduced the risk of colorectal cancer by 17 % . In women taking personal calcium or vitamin D supplements , CaD did not alter cancer risk ( HR : 1.06 - 1.26 ) . CONCLUSIONS For women in the WHI CaD who were not taking personal calcium or vitamin D supplements at r and omization , CaD decreased the risk of total , breast , and colorectal cancers and did not change the risk of fractures or total mortality . The nonskeletal effects of CaD may be more important than the skeletal effects and should be considered when evaluating these supplements . The WHI CaD trial is registered at clinical trials.gov as NCT00000611 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 OBJECTIVES To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge . DESIGN Multicenter , r and omized , controlled trial with a factorial design . SETTING Five hospitals in Auckl and , New Zeal and , and Sydney , Australia . PARTICIPANTS Two hundred forty-three frail older people . INTERVENTIONS Patients were r and omized to receive a single dose of vitamin D ( calciferol , 300,000 IU ) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits . MEASUREMENTS The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months . Physical performance and self-rated function were secondary endpoints . Assessment s took place in the participants ' homes at 3 and 6 months after r and omization and were performed by blinded assessors . RESULTS There was no effect of either intervention on physical health or falls , but patients in the exercise group were at increased risk of musculoskeletal injury ( risk ratio = 3.6 , 95 % confidence interval = 1.5 - 8.0 ) . Vitamin D supplementation did not improve physical performance , even in those who were vitamin D deficient ( < 12 ng/mL ) at baseline . CONCLUSION Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization . There was no effect of vitamin D on physical performance , and the exercises increased the risk of musculoskeletal injury . These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people The progress of spinal bone loss was monitored by measurements of the vertebral body height of T6 to L5 in seventy 70-year-old women who participated in a controlled , double-blind therapeutic trial . They were treated for one year by 1,25(OH)2D3 , 0.50 micrograms a day ( or less if hypercalcemia occurred ) and cyclical estrogen/gestagen , alone or combined , or placebo . Sufficient calcium intake was ensured in all . The vertebral body height decreased significantly , by 1 % , in both of the 1,25(OH)2D3 groups , whereas it remained unchanged in the hormone and the placebo + calcium group . This observation does not encourage the use of 1,25(OH)2D3 for prevention or treatment of postmenopausal bone loss Osteoporosis in men is an emerging public health problem . As calcitriol reduces the rate of vertebral fractures in osteoporotic postmenopausal women , we conducted a prospect i ve study of this treatment in men with primary osteoporosis . Our study was a 2-yr , r and omized , double masked , double placebo-controlled trial of calcitriol ( 0.25 microg twice daily ) or calcium ( 500 mg twice daily ) in 41 men with primary osteoporosis and at least 1 baseline fragility fracture . Thirty-three men ( 85 % ) completed the study . There were no differences in baseline characteristics . Spinal and femoral neck bone mineral densities at 2 yr were unchanged in both groups . Serum osteocalcin decreased in both groups by 30 % ( P < 0.05 ) , whereas urine N-telopeptide cross-links decreased only in the calcium group by 30 % ( P < 0.05 ) . After 2 yr , fractional calcium absorption increased by 34 % ( P < 0.01 ) in the calcitriol group . Nineteen incident fragility fractures occurred ( 14 vertebral and 5 nonvertebral ) in 7 men . Over 2 yr , the number of men with vertebral fractures ( 6 vs. 1 ; P = 0.097 ) was similar in both groups . In conclusion , the efficacy of calcitriol remains unproven as a single agent for the treatment of osteoporosis in men 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 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 The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2-cholecalciferol on bone formation was studied in a r and omized trial with 144 healthy postmenopausal women .  Urinary excretion ( UE ) of 99m-technetium-diphosphonate and serum alkaline phosphatase ( AP ) was determined before and then once a year for 2 years of treatment . Both estimates of bone formation showed highly significant decreases ( p less than .001 ) to normal premenopausal levels in women receiving unopposed 17 beta-estradiol or in a sequential combination with progestagen , whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo . The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass , and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss 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 Background In r and omized trials there may be no overriding reason whether or not to have a placebo control . Purpose We assessed the effects of an open trial design ( no placebo and people know what tablets they are given ) compared with a blinded , placebo-controlled design on recruitment , compliance and retention within a r and omized trial of secondary osteoporotic fracture prevention . Methods We undertook a r and omized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture , recruited in a UK teaching hospital . R and omization was 2 : 1 in favour of the blinded , placebo-controlled trial design . Results From 180 eligible participants r and omized to receive information based on the open trial design , 134 ( 74.4 % ) consented to take part , compared with 233 ( 65.1 % ) of 358 people r and omized to the blinded , placebo-controlled design ( difference 9.4 % , 95 % confidence interval 1.3–17.4 % ) . Reluctance to take a placebo  and the desire to know tablet allocation were reasons given for not taking part in the blinded , placebo-controlled design . There was no significant difference in tablet compliance . Open trial participants were more likely to remain in the trial for one year ( difference 13.9 % , 95 % confidence interval 3.1–24.6 % ) , mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group ( difference 23.6 % , 95 % confidence interval 11.9–35.2 % ) . The odds ratio for reporting an adverse event in the open trial compared to the blinded , placebo-controlled design was 0.64 ( 95 % confidence interval 0.28–1.49 ) , and for reporting a fracture was 0.81 ( 0.36–1.85 ) . Conclusions We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power , but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial OBJECTIVE To evaluate functional improvement in a population of frail , homebound older persons with low vitamin D status as vitamin D stores improve . DESIGN R and omized , controlled intervention study . SETTING Subjects ' homes and a nursing facility in Baltimore , Maryl and . PARTICIPANTS The first 32 subjects ( community-dwelling , homebound older subjects from the Johns Hopkins Elder Housecall Program and nursing home residents from the Johns Hopkins Geriatrics Center ) entered in a longitudinal study of vitamin D replacement . MEASUREMENTS Baseline 25-hydroxyvitamin D levels were measured and repeated at least 1 month after therapy with either placebo or vitamin D ( ergocalciferol ) . Subjects were also administered the Frail Elderly Functional Assessment ( FEFA ) question naire , an instrument demonstrated to be reliable , valid , and sensitive to small increments of functional change in this population . MAIN RESULTS All subjects started with 25-hydroxyvitamin D levels less than 15 ng/mL. Those subjects whose levels improved by at least 3 ng/mL ( > assay coefficient of variation ) also demonstrated improvement in FEFA score . Regression analysis between change in FEFA score compared with change in 25-hydroxyvitamin D was significant ( r = .4 ; P = .02 ) . CONCLUSIONS In this cohort of homebound older people , improvement in vitamin D status was associated with functional improvement as measured by the FEFA question naire BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo .  Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P<0.001 ) . The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures BACKGROUND AND PURPOSE It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients , which might increase their risk of hip fracture . We evaluated the efficacy of 1 alpha-hydroxyvitamin D3 [ 1 alpha (OH)D3 ] and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke . METHODS In a r and omized study , 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 microgram 1 alpha (OH)D3 daily ( treatment group , n = 30 ) or an inactive placebo ( placebo group , n = 34 ) for 6 months and were observed for this duration . Both groups received 300 mg of elemental calcium daily . The bone mineral density ( BMD ) and metacarpal index ( MCI ) in the second metacarpals were determined by computed x-ray densitometry . The incidence of hip fractures in these patients was recorded . RESULTS BMD on the hemiplegic side decreased by 2.4 % in the treatment group and 8.9 % in the placebo group ( P = .0021 ) , while BMD on the intact side increased by 3.5 % and decreased by 6.3 % in the treated and placebo groups , respectively ( P = .0177 ) . In the treatment group , the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before r and omization . This difference increased in the placebo group . We observed a similar improvement in MCI in the treatment group but not in the placebo group . Four patients in the placebo group suffered a hip fracture compared with none in the treatment group ( P = .0362 ) . CONCLUSIONS Treatment with 1 alpha (OH)D3 and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-st and ing stroke . Treatment also may improve these indices on the intact side Treatment with 1,25-(OH)2D3 ( calcitriol ) was compared with placebo in a double-blind , r and omized , parallel clinical trial of 24 months ' duration . Subjects were white women with postmenopausal osteoporosis . The study was completed by 15 patients who received placebo and 12 patients who received calcitriol .  Positive slopes were observed in the active treatment group for total body calcium , bone mineral content of the radius , bone mineral density of the lumbar spine , and radiographic absorptiometry of the middle phalanges . In contrast , negative slopes were observed for the bone mineral measurements in the placebo group . Measurement of urinary hydroxyproline and of serum alkaline phosphatase and osteocalcin suggested that the mechanism of action of 1,25-(OH)2D3 involved reduction of bone resorption . Hypercalciuria occurred regularly and preceded hypercalcemia by about 2 weeks . A decline in creatinine clearance was observed in two patients , one of whom had nephrolithiasis on sonography . Calcitriol is effective in preventing bone loss , but must be used with caution Calcitriol was compared with placebo in the treatment of postmenopausal osteoporosis in a double-blind , r and omized , parallel clinical trial of 24 months ' duration . Adjustment was made in dietary calcium to maximize the dose of calcitriol . The study was completed by 15 patients who received placebo and 12 patients who received calcitriol .  The calcitriol group had positive slopes ( compared with negative slopes for the placebo group ) for total body calcium , bone mineral content of the radius , bone mineral density of the lumbar spine , and radiographic absorptiometry of the middle phalanges . The difference between the two groups was statistically significant for each of these measurements . The fracture rate in the treatment group was 250 per 1,000 patient-years as compared with 333 for the placebo group . The mean dose of calcitriol was 0.8 micrograms per day . Hypercalcemia , hypercalciuria , and perhaps nephrolithiasis were observed as complications of treatment . Calcitriol increased bone mineral density by decreasing bone resorption , but not by increasing bone formation . Future studies should concentrate on treatment with oral calcitriol in lower doses . It would also be of interest to examine parenteral administration of calcitriol . It is possible that bone formation can be increased by achieving higher serum levels of the drug , whereas complications may be avoided by using a non-oral route of administration CONTEXT In humans , few studies have compared the potencies of ergocalciferol and cholecalciferol in improving and maintaining vitamin D status . OBJECTIVE Our objective was to evaluate the effects of a single very large dose of both calciferols on serum changes of 25-hydroxyvitamin D [ 25(OH)D ] , 1,25-dihydroxyvitamin D [ 1,25(OH)(2)D ] , ionized calcium , and parathyroid hormone ( PTH ) at baseline , and at 3 , 7 , 30 , and 60 d. DESIGN This was a prospect i ve r and omized intervention study . SETTING The study was performed in a nursing home residence . PARTICIPANTS A total of 32 elderly female patients ( age range 66 - 97 yr ) , with vitamin D deficiency was included in the study . INTERVENTION Participants were r and omized into four groups of eight to receive a single dose of 300,000 IU ergocalciferol or cholecalciferol by oral ( os ) or i m route . RESULTS 25(OH)D levels sharply increased at d 3 only when vitamins were given os . The 30-d basal difference in serum 25(OH)D was significantly greater after cholecalciferol os administration ( 47.8 + /- 7.3 ng/ml ) compared with other forms ( D(3 ) i m : 15.9 + /- 11.3 ; D(2 ) os : 17.3 + /- 4.7 ; D(2 ) i m : 5 + /- 4.4 ; all P < 0.001 ) . The area under the curve ( AUC ) of the serum 25(OH)D against time ( AUC(60 ) ) was : D(3 ) os , 3193 + /- 759 ng x d/ml vs. D(2 ) os , 1820 + /- 512 , P < 0.001 ; and D(3 ) i m , 1361 + /- 492 vs. D(2 ) i m , 728 + /- 195 , P < 0.01 . 25(OH)D significantly influences PTH levels at 3 ( P < 0.03 ) , 7 ( P < 0.01 ) , 30 ( P < 0.01 ) , and 60 d ( P < 0.05 ) . At 60 d , the form of vitamin ( cholecalciferol ) significantly lowers PTH levels ( P = 0.037 ) . CONCLUSIONS Cholecalciferol is almost twice as potent as ergocalciferol in increasing serum 25(OH)D , when administered either by mouth or i m . 25(OH)D plays a role in modulating serum PTH BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo .  Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people A cross-section of an elderly population was assessed in a double-blind trial for the effects of prophylactic vitamin D. The subjects who completed the trial were assessed clinical ly , by physiotherapy tests of muscle function and by biochemical analysis , before and after a course of vitamin D or placebo . A significant fall in serum phosphate was found in the placebo group but not in the vitamin D group . The fall was maximal between the months of October and March which correspond to maximum and minimum amounts of circulating 25-hydroxy-vitamin D during the year . No difference in muscle function between treated and untreated groups was shown . Two out of 63 individuals on vitamin D  developed hypercalcaemia . It is concluded that , although there appears to be improvement in the phosphate status of treated patients over the short term of this trial , hypercalcaemia after vitamin D administration precludes the continuous prophylactic use of vitamin D at the levels employed in this trial OBJECTIVE The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level . STUDY DESIGN The OSTPRE-FPS was a r and omized population -based open-trial with 3-year follow-up . The supplementation group ( n=1566 ) received daily cholecalciferol 800IU+calcium carbonate 1000 mg , while the  control group ( n=1573 ) received no supplementation or placebo .  A r and omly selected sub sample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements . MAIN OUTCOME MEASURE The occurrence of falls was the primary outcome of the study . The participants in the sub sample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year . RESULTS In the entire trial population ( ETP ) , there were 812 women with 1832 falls in the intervention group and 833 women with 1944 falls in the control group ( risk ratio was 0.98 , 95 % CI 0.92 - 1.05 , P=0.160 ) . The supplementation was not associated with single or multiple falls in the ETP . However , in the sub sample , multiple fall incidence decreased by 30 % ( odds ratio ( OR ) 0.70 , 95 % CI 0.50 - 0.97 , P=0.034 ) in the supplementation group . Further , the supplementation decreased the incidence of multiple falls requiring medical attention ( OR 0.72 , 95 % CI 0.53 - 0.97 , P=0.031 ) in the ETP . The mean compliance in the entire trial population was 78 % and in the sub sample 79 % . DISCUSSION Overall , the primary analysis showed no association between calcium and vitamin D supplementation and risk of falls . However , the results of a post hoc analysis suggested that there was a decreased risk of multiple falls requiring medical attention : this finding requires confirmation OBJECTIVE Calcium and vitamin D deficiency is common in older individuals , particularly those who live in nursing homes , and increases the risk of osteoporosis and fractures . METHODS We conducted a r and omized double-blind placebo-controlled study of combined supplementation with 500 mg of elemental calcium , as carbonate , and 400 IU of vitamin D bid for 12 months in women older than 65 years of age with vitamin D deficiency , defined as serum 25(OH)D concentrations < /=12 ng/ml . RESULTS Mean patient age was 75 + /- 7 years , and median daily dietary intakes of calcium and vitamin D were 697 mg and 66.8 IU in the supplemented group ( n = 95 ) and 671 mg and 61.8 IU in the placebo group ( n = 97 ) . The median serum 25(OH)D level was 7.0 ng/ml in both groups , and the medial intact parathyroid hormone ( PTHi ) levels were 49 and 48 pg/ml in the supplemented and placebo groups , respectively . The median increase in serum 25(OH)D was 22.0 ng/ml in the supplemented group and 4 ng/ml in the placebo group ( P < 0.0001 ) , and the median PTHi decrease was 17 and 5 pg/ml , respectively ( P < 0.0001 ) . The median bone mineral density increase was significantly greater in the supplemented group than in the placebo group : + 2.98 % vs. -0.21 % at L2-L4 ( P = 0.0009 ) , + 1.19 % and -0.83 % at the femoral neck ( P = 0.015 ) , + 0.86 % and -0.56 % at the trochanter ( P = 0.015 ) , and + 0.99 % and + 0.11 % for the whole body ( P = 0.01 ) . Similarly , the median decrease in the main bone markers was significantly greater in the treated group than in the placebo group : -1.35 microg/l vs. + 0.50 microg/l for bone alkaline phosphatase ( P = 0.008 ) , -16.6 nmol/mmol creatinine vs. -2.3 nmol/mmol creatinine for urinary type I amino-terminal telopeptide ( P = 0.001 ) , and -896 pmol/l vs. -201 pmol/l for serum type I carboxy-terminal telopeptide ( P = 0.003 ) . We found no significant differences between the two groups for serum calcium , although urinary calcium excretion changed more in the supplemented group than in the placebo group . In conclusion , bone mass in older women with vitamin D deficiency increases significantly at the lumbar spine , femur , trochanter , and whole body after calcium and vitamin D supplementation for 1 year , and concomitantly bone markers improved as vitamin D levels returned to normal BACKGROUND A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies , but evidence from trials is lacking . OBJECTIVE We determined whether vitamin D supplementation , with or without calcium , improved glucose homeostasis in adults at high risk of diabetes . DESIGN Ninety-two adults were r and omly assigned in a 2-by-2 factorial- design , double-masked , placebo-controlled trial to receive either cholecalciferol ( 2000 IU once daily ) or calcium carbonate ( 400 mg twice daily ) for 16 wk . The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test . Other outcomes were acute insulin response , insulin sensitivity , and measures of glycemia . RESULTS Participants had a mean age of 57 y , a body mass index ( BMI ; in kg/m(2 ) ) of 32 , and glycated hemoglobin ( Hb A(1c ) ) of 5.9 % . There was no significant vitamin D × calcium interaction on any outcomes . The disposition index increased in the vitamin D group and decreased in the no-vitamin D group ( adjusted mean change ± SE : 300 ± 130 compared with -126 ± 127 , respectively ; P = 0.011 ) , which was explained by an improvement in insulin secretion ( 62 ± 39 compared with -36 ± 37 mU · L(-1 ) · min , respectively ; P = 0.046 ) . Hb A(1c ) increased less , but nonsignificantly , in the vitamin D group than in the no-vitamin D group ( 0.06 ± 0.03 % compared with 0.14 ± 0.03 % , respectively ; P = 0.081 ) . There was no significant difference in any outcomes with calcium compared with no calcium . CONCLUSION In adults at risk of type 2 diabetes , short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c ) . This trial was registered at clinical trials.gov as NCT00436475 BACKGROUND Serum 25-hydroxyvitamin D ( 25-[OH]D ) is considered the best biomarker of clinical vitamin D status . OBJECTIVE To determine the effect of increasing oral doses of vitamin D(3 ) on serum 25-(OH)D and serum parathyroid hormone ( PTH ) levels in postmenopausal white women with vitamin D insufficiency ( defined as a 25-[OH]D level ≤50 nmol/L ) in the presence of adequate calcium intake . These results can be used as a guide to estimate the Recommended Dietary Allowance ( RDA ) ( defined as meeting the needs of 97.5 % of the population ) for vitamin D(3 ) . DESIGN R and omized , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00472823 ) SETTING Creighton University Medical Center , Omaha , Nebraska . PARTICIPANTS 163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year . INTERVENTION Participants were r and omly assigned to receive placebo or vitamin D(3 ) , 400 , 800 , 1600 , 2400 , 3200 , 4000 , or 4800 IU once daily . Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg . MEASUREMENTS The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months . RESULTS The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D(3 ) . The RDA of vitamin D(3 ) to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d . A mixed-effects model predicted that 600 IU of vitamin D(3 ) daily could also meet this goal . Compared with participants with a normal body mass index ( < 25 kg/m(2 ) ) , obese women ( ≥30 kg/m(2 ) ) had a 25-(OH)D level that was 17.8 nmol/L lower . Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D(3 ) ( P = 0.012 ) . Depending on the criteria used , hypercalcemia occurred in 2.8 % to 9.0 % and hypercalciuria in 12.0 % to 33.0 % of participants ; events were unrelated to dose . LIMITATION Findings may not be generalizable to other age groups or persons with substantial comorbid conditions . CONCLUSION A vitamin D(3 ) dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5 % of women ; however , a model predicted the same response with a vitamin D(3 ) dosage of 600 IU/d . These results can be used as a guide for the RDA of vitamin D(3 ) , but prospect i ve trials are needed to confirm the clinical significance of these results . PRIMARY FUNDING SOURCE National Institute on Aging The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status . The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone-related chemistry in elderly women with vitamin D insufficiency . Three hundred two elderly women ( age , 77.2 + /- 4.6 yr ) with serum 25(OH)D concentrations < 60 nM participated in a 1-yr r and omized , double-blind , placebo-controlled trial . All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol ( vitamin D(2 ) ) or identical placebo ( control ) . The effects of time and time treatment interactions were evaluated by repeated- measures ANOVA . At baseline , calcium intake was 1100 mg/d , and 25(OH)D was 44.3 + /- 12.9 nM ; this increased in the vitamin D group by 34 % but not the control group after 1 year ( 59.8 + /- 13.8 versus 45.0 + /- 13.3 nM , p < 0.001 ) . Total hip and total body BMD increased significantly , and procollagen type I intact N-terminal propeptide ( PINP ) decreased during the study with no difference between the treatment groups ( hip BMD change :  vitamin D , + 0.5 % ; control , + 0.2 % ; total body BMD change : vitamin D , + 0.4 % ; control , + 0.4 % ; PINP change : vitamin D , -3.9 % ; placebo , -2.8 % ) . Although the fasting plasma and urine calcium increased in both groups equally , there was no detectable change in serum PTH . The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption , which fell equally in both groups ( vitamin D , -17.4 % ; control , -14.8 % ) . In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency , vitamin D(2 ) 1000 IU for 1 year has no extra beneficial effect on bone structure , bone formation markers , or intestinal calcium absorption over an additional 1000 mg of calcium . Vitamin D supplementation adds no extra short-term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency
target: There is high quality evidence that vitamin D plus calcium is associated with a statistically significant reduction in incidence of new non-vertebral fractures .
  Vitamin D alone is unlikely to prevent fractures in the doses and formulations tested so far in older people .
  Supplements of vitamin D and calcium may prevent hip or any type of fracture .
  There was a small but significant increase in gastrointestinal symptoms and renal disease associated with vitamin D and calcium .
  This review found that there was no increased risk of death from taking calcium and vitamin
background: BACKGROUND Vitamin D and related compounds have been used to prevent  osteoporotic fractures in older people .
  This is the third up date of a Cochrane review first published in 1996 .
  OBJECTIVES To determine the effects of vitamin D or related compounds , with or without calcium , for preventing  fractures in post-menopausal women and older men .