Prevention and treatment of glucocorticoid-induced osteoporosis with active vitamin D3 analogues:: a review with meta-analysis of randomized controlled trials including organ transplantation studies

The aim of this review with meta-analysis was to determine if there is a rationale to use activated forms of vitamin D-3 to treat or prevent glucocorticoid-induced osteoporosis, and to compare the effect of active vitamin D-3 metabolites with that of other anti-osteoporosis therapies. We performed a systemic search using MEDLINE/PubMed (1966-2003). Animal studies and clinical trials involving humans with data on therapy to treat or prevent glucocorticoid-induced osteoporosis with active vitamin D-3 analogues were included. Animal studies and basic research studies with active vitamin D-3 were reviewed (qualitative review). Meta-analysis (quantitative review) on clinical trials (including organ transplantation studies) was performed with percent change in lumbar spine bone mineral density or bone mineral content as the primary outcome measure; the secondary outcome measure was incidence of vertebral fractures. Fifty-four articles were found. Animal and basic research studies showed that active vitamin D-3 analogues can inhibit bone loss during treatment with glucocorticoids. Concerning the effect on bone mineral density, the pooled effect size of active vitamin D-3 analogues compared with no treatment, placebo, plain vitamin D-3 and/or calcium was 0.35 (95% confidence interval (CI) 0.18, 0.52). Compared with bisphosphonates, the pooled effect size was -1.03 (95% CI -1.71, -0.36). The pooled estimate of the relative risk for vertebral fractures of active vitamin D-3 analogues compared with no treatment, placebo, plain vitamin D-3 and/or calcium was 0.56 (95% CI 0.34, 0.92) and compared with bisphosphonates it was 1.20 (95% CI 0.32, 4.55). Active vitamin D-3 analogues not only preserve bone during glucocorticoid therapy more effectively than no treatment, placebo, plain vitamin D-3 and/or calcium, but are also more effective in decreasing the risk of vertebral fractures. Bisphosphonates, however, are more effective in preserving bone and decreasing the risk of vertebral fractures than active vitamin D-3 analogues.