1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial. 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. Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. A randomized controlled trial of vitamin D3 supplementation in African American women. Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Does vitamin D stop inpatients falling? A randomised controlled trial. Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. Randomised controlled trial of prevention of falls in people aged > or =75 with severe visual impairment: the VIP trial. Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. Once-weekly dose of 8400 IU vitamin D(3) compared with placebo: effects on neuromuscular function and tolerability in older adults with vitamin D insufficiency. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. The effects of an open design on trial participant recruitment, compliance and retention--a randomized controlled trial comparison with a blinded, placebo-controlled design. 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. Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1 alpha-hydroxyvitamin D3 and calcium supplementation. Vitamin D supplementation and bone mineral density in early postmenopausal women. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. 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). 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. Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. Calcitriol treatment is not effective in postmenopausal osteoporosis. 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. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Calcium- and vitamin D3-fortified milk reduces bone loss at clinically relevant skeletal sites in older men: a 2-year randomized controlled trial. Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients. 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. Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. Calcium and vitamin D supplementation increases spinal BMD in healthy, postmenopausal women. 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. Vitamin D3 and calcium to prevent hip fractures in the elderly women. Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Effect of supplementation with vitamin D3 and calcium on quantitative ultrasound of bone in elderly institutionalized women: a longitudinal study. Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. 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. Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D. Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. Amelioration of osteopenia and hypovitaminosis D by 1alpha-hydroxyvitamin D3 in elderly patients with Parkinson's disease. Calcium plus vitamin D supplementation and the risk of fractures. The effects of vitamin D supplementation on physical function and quality of life in older patients with heart failure: a randomized controlled trial. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Do vitamin D supplements improve the physical capabilities of elderly hospital patients?
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 randomized, 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. 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 randomized 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. 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, randomized, 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) randomized 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. We conducted a randomized, 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.
                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.
                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.
                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. Bone metabolism follows a seasonal pattern with high bone turnover and bone loss during the winter. In a randomized, 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.
                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.
                This prospective 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 randomized 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.
                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).
                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. 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.
                Multicenter, randomized, controlled trial with a factorial design.
                Five hospitals in Auckland, New Zealand, and Sydney, Australia.
                Two hundred forty-three frail older people.
                Patients were randomized 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.
                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. Assessments took place in the participants' homes at 3 and 6 months after randomization and were performed by blinded assessors.
                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.
                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. To determine whether vitamin D supplementation decreases the incidence of hip fractures and other peripheral bone fractures.
                Prospective, double-blind trial.
                Community setting (Amsterdam and surrounding area).
                2578 persons (1916 women, 662 men) 70 years of age and older (mean age +/- SD, 80 +/- 6 years) living independently, in apartments for elderly persons, or in homes for elderly persons.
                Participants were randomly assigned to receive either vitamin D3, 400 IU in one tablet daily, or placebo for a maximum of 3.5 years.
                Dietary calcium intake and serum 25-hydroxyvitamin D [25(OH)D] were estimated in a subset of participants. During follow-up, attention was concentrated on hip fractures and other peripheral fractures. The maximal follow-up period was 4 years. The results were evaluated by survival analysis.
                Mean dietary calcium intake from dairy products was 868 mg/d. Mean serum 25(OH)D concentration in the third year of the study was 23 nmol/L in the placebo group and 60 nmol/L in the vitamin D group. Median follow-up was 3.5 years, and total follow-up was 8450 patient-years. During follow-up, 306 persons in the placebo group and 282 persons in the vitamin D group died (P = 0.20). Hip fractures occurred in 48 persons in the placebo group and 58 persons in the vitamin D group (P = 0.39, intention-to-treat analysis). Other peripheral fractures occurred in 74 persons in the placebo group and 77 persons in the vitamin D group (P = 0.86).
                Our results do not show a decrease in the incidence of hip fractures and other peripheral fractures in Dutch elderly persons after vitamin D supplementation. Vitamin D deficiency is common in older people and may increase risk of falls and fracture. Hospital inpatients are at particular risk of falling. Previous studies suggest that vitamin D improves neuromuscular function and reduces falls.
                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 inpatients.
                Randomised, double-blind, controlled study. Participants: two hundred and five acute admissions >65 years to a geriatric medical unit.
                Patients were randomised 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.
                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.
                In a population of geriatric hospital inpatients, vitamin D did not reduce the number of fallers. Routine supplementation cannot be recommended to reduce falls in this group. 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.
                In a pragmatic double blind randomised 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 D(2) (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.
                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.
                Supplementation with four-monthly 100,000 IU of oral vitamin D(2) is not sufficient to affect fracture incidence among older people living in institutional care. Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure (CHF). In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines.
                We evaluated the effect of vitamin D supplementation on the survival rate and different biochemical variables in patients with CHF.
                One hundred twenty-three patients randomly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [D(+) group] or placebo plus 500 mg Ca/d [D(-) group] for 9 mo. Biochemical variables were assessed at baseline and after 9 mo. The survival rate was calculated for a follow-up period of 15 mo.
                Ninety-three patients completed the study. Significant treatment effects were observed on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D (P = 0.001), parathyroid hormone (P = 0.007), tumor necrosis factor alpha (P = 0.006), and interleukin 10 (P = 0.042). 25-Hydroxyvitamin D increased by 26.8 ng/mL in the D(+) group but increased only by 3.6 ng/mL in the D(-) group. Compared with baseline, parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+) group after 9 mo. The proinflammatory cytokine tumor necrosis factor alpha increased in the D(-) group but remained constant in the D(+) group. The survival rate did not differ significantly between the study groups during the follow-up period.
                Vitamin D(3) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease. Our data provide evidence for the involvement of an impaired vitamin D-parathyroid hormone axis in the progression of CHF. To study the effect of alfacalcidol (1alpha(OH)D3) on fall risk in community-dwelling elderly men and women.
                Randomized, double-blind, placebo-controlled intervention trial.
                Basel, Switzerland.
                Three hundred seventy-eight community-dwelling elderly (191 women/187 men).
                Participants were randomly assigned to receive 1 microg of alfacalcidol or matched placebo daily for 36 weeks.
                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 questionnaire during each study site visit. Dietary calcium intake was assessed at baseline using a food frequency questionnaire.
                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 clinically relevant hypercalcemia were observed.
                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. To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents.
                Secondary data analysis of a previously conducted randomized clinical trial.
                Seven hundred twenty-five-bed long-term care facility.
                One hundred twenty-four nursing home residents (average age 89).
                Participants were randomly 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.
                Number of fallers and number of falls assessed using facility incident tracking database.
                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.
                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. To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision.
                Randomised controlled trial.
                Dunedin and Auckland, New Zealand.
                391 women and men aged > or =75 with visual acuity of 6/24 or worse who were living in the community; 92% (361 of 391) completed one year of follow-up.
                Participants received a home safety assessment and modification programme delivered by an occupational therapist (n = 100), an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation (n = 97), both interventions (n = 98), or social visits (n = 96).
                Numbers of falls and injuries resulting from falls, costs of implementing the home safety programme.
                Fewer falls occurred in the group randomised to the home safety programme but not in the exercise programme (incidence rate ratios 0.59 (95% confidence interval 0.42 to 0.83) and 1.15 (0.82 to 1.61), respectively). However, within the exercise programme, stricter adherence was associated with fewer falls (P = 0.001). A conservative analysis showed neither intervention was effective in reducing injuries from falls. Delivering the home safety programme cost NZ650 dollars (234 pounds sterling, 344 euros, US432 dollars) (at 2004 prices) per fall prevented.
                The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision. The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group, possibly due to low levels of adherence. Trial registration number ISRCTN15342873. 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.
                A 1-year population-based, double-blind, randomized 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 randomized 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.
                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.
                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. Vitamin D insufficiency, which is prevalent in older individuals, is associated with bone and muscle weakness and falls.
                We examined the effects of a weekly dose of 8400 IU vitamin D(3) on postural stability, muscle strength, and safety.
                In this double-blind trial, subjects aged > or =70 y with serum 25-hydroxyvitamin D [25(OH)D] concentrations < or =20 but > or =6 ng/mL were randomly assigned to receive a weekly dose of 8400 IU vitamin D(3) (n = 114) or a placebo (n = 112). Mediolateral body sway with eyes open (assessed with the AccuSway(PLUS) platform; Advanced Medical Technology Inc, Watertown, MA) was the primary endpoint. Secondary endpoints included the short physical performance battery (SPPB) and serum 25(OH)D concentrations. An analysis of covariance model was used for treatment comparisons. Safety and tolerability were monitored.
                Serum 25(OH)D concentrations rose significantly (from 13.9 to 26.2 ng/mL, P < 0.001) in patients treated with 8400 IU vitamin D(3) but not in patients treated with the placebo. After 16 wk, neither mediolateral sway nor SPPB differed significantly between treatment groups. However, in the post hoc analysis of patients subgrouped by baseline sway (> or = 0.46 compared with <0.46 cm), treatment with 8400 IU vitamin D(3) significantly reduced sway compared with treatment with placebo (P = 0.047) in patients with elevated baseline sway but not in patients with normal baseline sway. Adverse experiences and incidences of hypercalcemia, hypercalciuria, and elevated creatinine were similar with both treatments. In patients treated with 8400 IU vitamin D(3), but not in placebo-treated patients, parathyroid hormone decreased significantly.
                Weekly treatment with 8400 IU vitamin D(3) raised 25(OH)D concentrations in elderly, vitamin D-insufficient individuals. Treatment with 8400 IU vitamin D(3) did not reduce mediolateral sway significantly compared with treatment with placebo in this population, although in post hoc analysis, treatment with 8400 IU vitamin D(3) reduced sway in the subgroup of patients who had elevated sway at baseline. Weekly treatment with 8400 IU vitamin D(3) was well tolerated. This trial was registered at clinicaltrials.gov as NCT00242476. 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.
                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.
                Healthy, nonosteoporotic women (n = 244) were randomized 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.
                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).
                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. In randomized trials there may be no overriding reason whether or not to have a placebo control.
                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 randomized trial of secondary osteoporotic fracture prevention.
                We undertook a randomized 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. Randomization was 2:1 in favour of the blinded, placebo-controlled trial design.
                From 180 eligible participants randomized to receive information based on the open trial design, 134 (74.4%) consented to take part, compared with 233 (65.1%) of 358 people randomized 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).
                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. Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures.
                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 randomly 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.
                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.
                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. 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.
                In a randomized 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.
                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 randomization. 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).
                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-standing stroke. Treatment also may improve these indices on the intact side. Increased vitamin D intake may preserve or increase bone mineral density (BMD) in older persons.
                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.
                One hundred eighty-seven women who were >or= 1 y postmenopausal were randomly 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.
                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.
                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. 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.
                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.
                This was a factorial, cluster-randomized, 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 Database. We defined osteoporotic fractures as low energy fractures of the proximal humerus, distal forearm, vertebral column, pelvis, cervical femur, and intertrochanteric femur.
                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).
                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. 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-standing stroke by vitamin D supplementation.
                Ninety-six elderly women with poststroke hemiplegia were followed for two years. Patients were randomly 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.
                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).
                Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers, which may lead to decreased falls and hip fractures.
                Copyright (c) 2005 S. Karger AG, Basel. 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 randomized double blind, placebo-controlled trial. Women were randomized 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 clinically 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. The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level.Study design: The OSTPRE-FPS was a randomized population-based open-trial with 3-year follow-up. The supplementation group (n=1566) received daily cholecalciferol 800IU+calcium carbonate 1000mg, while the control group (n=1573) received no supplementation or placebo. A randomly selected subsample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements.
                The occurrence of falls was the primary outcome of the study. The participants in the subsample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year.
                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 subsample, 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 subsample 79%.
                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.
                Copyright 2009 Elsevier Ireland Ltd. All rights reserved. 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.
                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.
                randomised controlled trial.
                orthogeriatric rehabilitation ward.
                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.
                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.
                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. 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.
                Randomized, placebo-controlled double-blind, trial of 2 years' duration.
                Multicenter study in 60 hostels (assisted living facilities) and 89 nursing homes across Australia.
                Six hundred twenty-five residents (mean age 83.4) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L.
                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.
                Falls and fractures recorded prospectively in study diaries by care staff.
                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).
                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. To determine if calcitriol is an effective treatment in postmenopausal osteoporosis.
                Double-blind, randomized clinical trial of 2 years' duration.
                University medical center with patients recruited by media announcements.
                Eighty-six postmenopausal women with vertebral compression fractures.
                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.
                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.
                Calcitriol is not an effective treatment for established postmenopausal osteoporosis. 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 randomized 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. Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons.
                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.
                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).
                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. In this 2-year randomized 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 clinically important skeletal sites at risk for fracture.
                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.
                This was a 2-year randomized 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.
                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.
                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. to evaluate the effects of vitamin D supplementation on parathyroid function and bone turnover in aged, chronically immobile patients.
                a randomised double-blind controlled trial.
                two hundred and eighteen long-term inpatients aged over 65 years.
                the patients were randomised into treatment groups of I-III, each receiving 0 IU, 400 IU and 1200 IU cholecalciferol per day, respectively. In case of inadequate consumption of dairy products, patients received a daily calcium substitution of 500 mg.
                plasma concentrations of 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (PTH), amino-terminal propeptide of type I procollagen (PINP), a marker of bone formation, and carboxy-terminal telopeptide of type I collagen (ICTP), a marker of bone resorption, were measured at baseline and after 6 months.
                the patients (age 84.5 years) were chronically bedridden. The baseline 25-OHD was low (23 nmol/l), correlated inversely with PINP, and tended to associate inversely with PTH. The prevalence of vitamin D deficiency (VDD) (25-OHD < 50 nmol/l) was 98% and PTH was elevated in 23% of the patients. Vitamin D supplementation significantly increased 25-OHD concentrations (124% group II, 204% group III) and decreased PTH (-7% group II, -8% group III). PINP tended to decrease, but ICTP tended to increase, and only their ratio decreased significantly. The tendency of ICTP to increase was inconsistent. Changes in 25-OHD correlated inversely with those in PTH and PINP.
                vitamin D supplementation has minor effects on PTH and bone turnover in chronically immobilised aged patients with VDD. Further comparative studies and meta-analyses are warranted to elucidate the confounding effects of different mobility levels on the benefits of vitamin D supplementation in patients with differing baseline PTH levels. 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.
                Randomised double blind controlled trial of 100 000 IU oral vitamin D3 (cholecalciferol) supplementation or matching placebo every four months over five years.
                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.
                Fracture incidence and total mortality by cause.
                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.
                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. 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.
                Pragmatic open randomised controlled trial.
                Practice nurse led clinics in primary care.
                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.
                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).
                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).
                69% of the women who completed the follow-up questionnaire at 24 months were still taking supplements (55% with inclusion of randomised 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.
                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 ISRCTN26118436, controlled trials registry. We undertook a double-masked, randomized, 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 questionnaire was administered twice during the study and revealed a fairly good calcium and vitamin D intake (919 mg calcium/day; 3.8 micrograms vitamin D/day). An increase in lumbar spine BMD of 1.6% was observed in the treatment group after 2 years (p < 0.002). 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 (p < 0.01) and 2 years (p < 0.05) 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 micrograms 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. 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.
                In a multicenter, randomized, double-blind, placebo-controlled study conducted in France, women with a 25-hydroxyvitamin D level < or =12 ng/mL were randomized 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 samples 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.
                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.
                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. Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known.
                We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women.
                Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001).
                Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women. To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation.
                A randomised controlled trial of cluster design.
                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%).
                Participants were randomly 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.
                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].
                We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation. 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 randomized 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 (broadband 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 micrograms/l; normal range 6.4-40.2 micrograms/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% (p < 0.01) and a decrease in PTH by 18% (p < 0.05) and of alkaline phosphatase by 15% (p < 0.01). In the controls there was a worsening of the hypovitaminosis D, with a decrease of 25-hydroxyvitamin D by 51% (p < 0.01) and an increase in PTH by 51% (p < 0.01), while the serum calcium level decreased by only 2% (p < 0.01). After 2 years of treatment BUA increased significantly by 1.6% in the treated group (p < 0.05), and decreased by 2.3% in the controls (p < 0.01). Therefore, the difference in BUA between the treated subjects and the controls (3.9%) was significant after 2 years (p < 0.01). 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. The effect of equivalent oral doses of vitamin D3 600 IU/day, 4200 IU/week and 18,000 IU/month on vitamin D status was compared in a randomized clinical trial in nursing home residents. A daily dose was more effective than a weekly dose, and a monthly dose was the least effective.
                It is assumed that equivalent daily, weekly or monthly doses of vitamin D3 equally influence vitamin D status. This was investigated in a randomized clinical trial in nursing home residents.
                The study was performed in ten nursing homes including 338 subjects (76 male and 262 female), with a mean age of 84 (+/- SD 6.3 years). They received oral vitamin D3 either 600 IU/day, or 4200 IU/week, or 18,000 IU/month or placebo. After 4 months, calcium was added during 2 weeks, 320 mg/day or 640 mg/day or placebo. Outcome: serum levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone turnover markers. Statistical approach: linear multilevel analysis.
                At baseline, mean serum 25(OH)D was 25.0 nmol/L (SD 10.9), and in 98%, it was lower than 50 nmol/L. After 4 months, mean serum 25(OH)D levels increased to 62.5 nmol/L (after daily vitamin D3 69.9 nmol/L, weekly 67.2 nmol/L and monthly 53.1 nmol/L, P < 0.001 between groups). Median serum PTH levels decreased by 23% (p < 0.001). Bone turnover markers did not decrease. Calcium supplementation had no effect on serum PTH and bone turnover.
                Daily vitamin D was more effective than weekly, and monthly administration was the least effective. 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.
                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.
                The study was a 5-yr randomized, controlled, double-blind trial of 120 community-dwelling women aged 70-80 yr.
                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).
                Hip BMD, plasma 25-hydroxyvitamin D, biomarkers of bone turnover, PTH, and intestinal calcium absorption were measured.
                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.
                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. 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 randomized and prospective 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. 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 randomized 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. 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 1alpha-hydroxyvitamin D3 (1alpha(OH)D3; an active form of vitamin D) was evaluated for maintaining bone mass and reducing the incidence of hip and other nonvertebral fractures in patients with Parkinson's disease.
                In a double blind, randomised trial, 86 elderly patients with Parkinson's disease (mean Hoehn and Yahr stage, 3; mean age 70.6 years) were randomised to receive either 1 microg 1alpha(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 nonvertebral fractures was recorded.
                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).
                By increasing serum 1, 25-[OH]2D concentrations, treatment with 1alpha(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. The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal.
                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 randomly 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.
                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 prerandomization serum vitamin D levels.
                Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).
                Copyright 2006 Massachusetts Medical Society 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.
                In a randomized, parallel group, double-blind, placebo-controlled trial, patients with systolic heart failure aged >or=70 years with 25-hydroxyvitamin D levels <50 nmol/L (20 ng/mL) received 100,000 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-alpha. 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).
                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: ISRCTN51372896. 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.
                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.
                This was a 4-y, population-based, double-blind, randomized placebo-controlled trial. The primary outcome was fracture incidence, and the principal secondary outcome was cancer incidence. The subjects were 1179 community-dwelling women randomly 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 randomly assigned to receive 1400-1500 mg supplemental calcium/d alone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca + D), or placebo.
                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.
                Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00352170. 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.
                Randomized, 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, England. Primary outcome measure was all non-vertebral fracture. Secondary outcomes were hip and wrist fractures, and all falls.
                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.
                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. Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.
                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.
                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 randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.
                500,000 IU of cholecalciferol or placebo.
                Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.
                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 substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy 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.
                Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.
                anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867. 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 randomized 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. A randomized 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.
Vitamin D in the form of vitamin D3 seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D2, alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D3 combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.