A pooled analysis of vitamin D dose requirements for fracture prevention.

BACKGROUND: The results of meta-analyses examining the relationship between vitamin D supplementation and fracture reduction have been inconsistent. METHODS: We pooled participant-level data from 11 double-blind, randomized, controlled trials of oral vitamin D supplementation (daily, weekly, or every 4 months), with or without calcium, as compared with placebo or calcium alone in persons 65 years of age or older. Primary end points were the incidence of hip and any nonvertebral fractures according to Cox regression analyses, with adjustment for age group, sex, type of dwelling, and study. Our primary aim was to compare data from quartiles of actual intake of vitamin D (including each individual participant's adherence to the treatment and supplement use outside the study protocol) in the treatment groups of all trials with data from the control groups. RESULTS: We included 31,022 persons (mean age, 76 years; 91% women) with 1111 incident hip fractures and 3770 nonvertebral fractures. Participants who were randomly assigned to receive vitamin D, as compared with those assigned to control groups, had a nonsignificant 10% reduction in the risk of hip fracture (hazard ratio, 0.90; 95% confidence interval [CI], 0.80 to 1.01) and a 7% reduction in the risk of nonvertebral fracture (hazard ratio, 0.93; 95% CI, 0.87 to 0.99). By quartiles of actual intake, reduction in the risk of fracture was shown only at the highest intake level (median, 800 IU daily; range, 792 to 2000), with a 30% reduction in the risk of hip fracture (hazard ratio, 0.70; 95% CI, 0.58 to 0.86) and a 14% reduction in the risk of any nonvertebral fracture (hazard ratio, 0.86; 95% CI, 0.76 to 0.96). Benefits at the highest level of vitamin D intake were fairly consistent across subgroups defined by age group, type of dwelling, baseline 25-hydroxyvitamin D level, and additional calcium intake. CONCLUSIONS: High-dose vitamin D supplementation (≥800 IU daily) was somewhat favorable in the prevention of hip fracture and any nonvertebral fracture in persons 65 years of age or older. (Funded by the Swiss National Foundations and others.).

Influence of estrogen therapy at conventional and high doses on the degree of mineralization of iliac bone tissue: a quantitative microradiographic analysis in postmenopausal women.

The beneficial skeletal effects of menopausal estrogen replacement therapy (HRT) are well documented. The role of secondary mineralization of bone as a determinant of bone quality is now well established in postmenopausal women treated with bisphosphonates or SERMs. The aim of present study was to investigate the effect of conventional and high doses of estrogen on the main parameters reflecting the degree of mineralization of bone (DMB). Bone biopsies were obtained from 20 women with osteopenia or osteoporosis before and after 24 months (18 to 38 months) of conventional HRT, and from 19 women who had received high doses of estradiol (implant 100 mg every 3-6 months for 1.5-20 years). DMB parameters (mean DMB, DMB Freq. Max. and Heterogeneity Index of the individual distributions of DMB) were measured using quantitative microradiography in cortical, cancellous, and total bone and expressed as g mineral/cm(3) bone. Values obtained in women before HRT were lower than those reported in pre- and postmenopausal control women. After conventional HRT, there was an increase in mean DMB (total bone) of 4.4 +/- 1.9% (mean +/- SEM) versus pre-treatment values (4.1 +/- 2.1% in cortical bone, 4.5 +/- 2.3% in cancellous bone); these differences did not reach statistical significance (P = 0.055). Results were similar for DMB Freq. Max. but Heterogeneity Index was not significantly changed. After high dose estradiol therapy, mean DMB (total bone) was 6.9 +/- 1.9% higher than in untreated women (8.6 +/- 2.1% in cortical bone, 6.5 +/- 2.1% in cancellous bone); this difference was statistically significant (P

Consumption of a high calcium mineral water lowers biochemical indices of bone remodeling in postmenopausal women with low calcium intake.

Many postmenopausal women have a calcium intake far below the recommended amount and, in addition to attempting to improve their diet, need a calcium supplement. The aim of the study was to assess the effects of the consumption of a high calcium mineral water (HCaMW) on biochemical indices of bone remodeling in postmenopausal women with low Ca intake. A 6-month randomized double-blind placebo-controlled trial was designed to assess the effects of a daily consumption of 1 liter of a HCaMW (596 mg Ca/l) on serum parathyroid hormone (PTH) and biochemical markers of bone remodeling in postmenopausal women with a dietary Ca intake lower than 700 mg/day. The placebo group drank 1 liter of a mineral water with a low calcium content (10 mg/l). One hundred eighty healthy women were recruited (mean age: 70.1+/-4.0 years); 152 completed the 6-month trial. The changes from baseline of biochemical indices after 6 months consisted of a significant 14.1% decrease of serum PTH, osteocalcin (-8.6%), bone alkaline phosphatase (-11.5%), serum (-16.3%) and urine (-13.0%) type-1 collagen C-telopeptide in the HCaMW group compared to the placebo group, where all biochemical indices increased after 6 months. The additive effect of a small vitamin D supplement (400 iu/day) was also evaluated. In women receiving vitamin D in addition to HCaMW, the decrease in bone indices was not found to be greater than in women drinking only the HCaMW. A daily supplement of 596 mg of Ca through the consumption of 1 l of HCaMW was able to lower serum PTH and the indices of bone turnover in postmenopausal women with a low Ca intake. This could contribute to the repair of calcium deficiency and to the reduction of age-related bone loss in this population.

The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis.

BACKGROUND: Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. METHODS: To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. RESULTS: New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. CONCLUSIONS: Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.

Calcium-vitamin D3 supplementation is cost-effective in hip fractures prevention.

OBJECTIVE: To assess the cost implications for a preventive treatment strategy for institutionalised elderly women with a combined 1200 mg/day calcium and 800 IU/day vitamin D(3) supplementation in seven European countries. DESIGN: Retrospective cost effectiveness analysis based on a prospective placebo-controlled randomised clinical trial. DATA SOURCES: Recently published cost studies in seven European countries. Clinical results from Decalyos, a 3-year placebo-controlled study in elderly institutionalised women. TRIALS: Decalyos study, with 36 months follow-up of 3270 mobile elderly women living in 180 nursing homes, allocated to two groups. One group received 1200 mg/day elemental calcium in the form of tricalcium phosphate together with 800 IU/day (20 microg) of cholecalciferol (vitamin D(3)), the other placebo. RESULTS: In the 36 months analysis of the Decalyos study, 138 hip fractures occurred in the group of 1176 women, receiving supplementation and 184 hip fractures in the placebo group of 1127 women. The mean duration of treatment was 625.4 days. Adjusted to 1000 women, 46 hip fractures were avoided by the calcium and vitamin D(3) supplementation. For all countries, the total costs in the placebo group were higher than in the group receiving supplementation, resulting in a net benefit of 79000-711000 per 1000 women. CONCLUSION: This analysis suggests that the supplementation strategy is cost saving. The results may underestimate the net benefits, as this treatment has also shown to be effective in decreasing the incidence of other non-vertebral fractures in elderly institutionalised women.