Preventing bone loss in renal transplant recipients with vitamin D. Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis. Vitamin D3 and calcium to prevent hip fractures in the elderly women. Effect of supplementation with vitamin D3 and calcium on quantitative ultrasound of bone in elderly institutionalized women: a longitudinal study. Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. 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 trial of intermittent versus continuous oral alfacalcidol treatment of hyperparathyroidism in end-stage renal disease.
Very rapid bone loss, osteopenia, and osteoporosis have been documented in the first 6 to 12 mo after renal transplantation. Investigated was the effect of treatment with active vitamin D on the prevention of posttransplantation bone loss. Forty adult men who were recent renal transplant recipients were enrolled onto the study. Patients were randomized into two groups: group 1 received daily alfacalcidol 0.5 micro g by mouth, and group 2 (control) received placebo. Every patient in both groups received daily 500-mg calcium carbonate supplements. Parameters of bone metabolism and bone mineral density measured at three sites were assessed before and after the study period. Bone mineral density was increased by 2.1%, 1.8%, and 3.2% at lumbar spine, femoral neck, and forearm, respectively, in group 1, whereas it decreased by 3.2%, 3.8%, and 1.8% at the same sites in the control group (P < 0.05). Serum intact parathyroid hormone level decreased significantly in group 1 compared with the control group (P = 0.003). Early bone loss that occurs during the first 1 yr after renal transplantation could be prevented by alfacalcidol. Use of alfacalcidol early after transplantation is safe and well tolerated. 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 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. In a randomized multicenter, double-blind, double-dummy, parallel group study a comparison of the efficacy and safety of 1 microg alfacalcidol to 880 IU vitamin D plus calcium carbonate (1 g calcium) once daily per os was performed on 148 postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels for 18 months. Bone mineral density (BMD) was measured at baseline, 12 and 18 months. Safety parameters were followed during the entire study period. Sixty-nine (90.8%) in the alfacalcidol group and 67 (93.1%) in the vitamin D group were included in the ITT analysis. Lumbar BMD in the alfacalcidol group increased by 0.017 g/cm2 (2.33%) and 0.021 g/cm2 (2.87%) from baseline (P<0.001) at 12 and 18 months, respectively, whereas in the vitamin D plus calcium group the increase was 0.005 g/cm2 (0.70%) from baseline (N.S.) at both 12 and 18 months. The higher changes from baseline in the alfacalcidol group, as compared to the changes in the vitamin D plus calcium group at both 12 and 18 months, were found to be statistically significant (P=0.018, 0.005). A small increase of mean femoral BMD was achieved in both groups (N.S.). Adverse events were similar in both groups. No significant differences were noted between the groups in serum calcium. In conclusion, alfacalcidol was found to be superior in significantly increasing lumbar BMD as compared to vitamin D plus calcium while safety characteristics were found to be similar in both treatments. 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. 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. Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women. 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. Secondary hyperparathyroidism, a major clinical problem in patients with chronic renal failure, develops in response to phosphate retention and impaired calcitriol [1,25-dihydroxyvitamin D3] synthesis. Vitamin D therapy, particularly alfacalcidol [1 alpha-hydroxyvitamin D3], has been shown to be effective in the treatment of secondary hyperparathyroidism. The aim of this study was to compare the effect of a 12-week course of continuous versus intermittent oral alfacalcidol therapy on parathyroid hormone suppression.
                34 patients were selected and randomly divided into 2 groups to receive either intermittent or continuous oral alfacalcidol. Baseline data were obtained on serum calcium, phosphorus, alkaline phosphatase and PTH. All but the PTH were monitored monthly. PTH levels were measured again until the end of the protocol. The intervention was 2 microg of alfacalcidol given after each dialysis session (intermittent group) or 1 microg given 6 days/week (continuous group).
                Serum calcium and phosphorus showed a tendency to increase from baseline levels in both groups. Mean PTH levels for both groups showed a progressive reduction over time during the study period. This decrement showed no significant difference with regard to the schedule of alfacalcidol administration when comparing the 2 groups. There also was no difference in the incidence of side effects--hypercalcemia and hyperphosphatemia--between the intermittent and continuous intervention.
                Feedback regulation of PTH with oral alfacalcidol therapy is efficient in the treatment of hyperparathyroidism. However, intermittent and continuous oral administration are equally effective in suppressing an elevated PTH level in hemodialysis patients, with similar safety margins.
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.