Effect of clodronate treatment on risk of fracture: a systematic review and meta-analysis

A systematic review and a meta-analysis of data of literature were performed to evaluate the efficacy of clodronate in the reduction of risk of fractures in patients with osteoporosis or tumour diseases. A systematic review was conducted to identify original articles, reviews, and any other literature report suitable for the purposes of the meta-analysis, limited to prospective randomized trials that included a placebo or an untreated control arm. The search has identified 18 trials, 13 of which in patients with cancer diseases (breast cancer and multiple myeloma were prevalent), 4 in patients with osteoporosis/low BMD, and 1 in elderly women living in community. A placebo control arm was used in 13 trials. Treatment and follow-up duration ranged from 3 months to 5 years. The meta-analysis showed that treatment with clodronate was associated with a reduction of the probability of new fractures compared with controls (OR = 0.572, 95% CI 0.465-0.704 for new vertebral fractures; OR = 0.668, 95% CI 0.494-0.905 for new non-vertebral fractures; and OR = 0.744, 95% CI 0.635-0.873 for new overall fractures in those articles where vertebral and non-vertebral new fractures were not considered separately). Similar findings were observed in the separate analysis in patients with cancer forms or osteoporosis. The results of the meta-analysis have demonstrated that clodronate is effective in reducing the risk of vertebral, non-vertebral, and overall fractures in patients with skeletal fragility.