Effect of Clodronate Treatment on Risk of Fracture: A Systematic Review and Meta-analysis

Abstract

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.

Network Meta-Analysis of Pharmacological Agents for Osteoporosis Treatment and Fracture Prevention

“…In fact, our findings derived from NMA were consistent with those obtained from previous MA. For instance, Frediani et al compared the relative efficacy COL for preventing new non-fractures in patients with osteoporosis and concluded that patients treated by COL were associated with a significant reduction in the risk of new non-vertebral fractures compared to those received PCB [53]. Another NMA concluded that bazedoxifene was relatively effective for preventing non-vertebral fractures [52].…”

Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis

“…A recent meta-analysis underlined the efficacy of clodronate in reducing the risk of new vertebral, non-vertebral and overall fractures but the majority of the data are from studies with oral clodronate [ 57 ].…”

Transient osteoporosis of the hip after bariatric surgery

“…In addition, there are multiple reports highlighting the fluctuation in bone density with the hormonal and chemical changes during pregnancy [7] , [8] , [9] , which is traditionally associated with TOH. To our knowledge, however, there are no reports describing TOH in patients who underwent bariatric surgery recently, a major cause of metabolic bone disease [10] . The mechanisms of decreased bone density in bariatric surgery patients are not definitively known, but there are a number of hypotheses which include the extreme weight loss and its mechanical effect on the skeletal system, vitamin D deficiency, and postoperative hormonal (ie, ghrelin, glucagon-like peptide-1, leptin) and bile acid metabolic changes [11] .…”