Ibandronate for the prevention of nonvertebral fractures: a pooled analysis of individual patient data.

SUMMARY: This analysis was conducted to assess the effect of high versus lower doses of ibandronate on nonvertebral fractures. The results were adjusted for clinical fracture, age, and bone density. The treatment effect was dose-dependent. Higher doses of ibandronate significantly reduced the risk of nonvertebral fractures more effectively compared with lower doses. INTRODUCTION: The objective of this study was to assess the efficacy of different doses of ibandronate on nonvertebral fractures in a pooled analysis. METHODS: Eight randomized trials of ibandronate were reviewed for inclusion. Alternative definitions of high versus low doses based on annual cumulative exposure (ACE) were explored. A time-to-event analysis was conducted using Kaplan-Meier methodology. Hazard ratios (HR) were derived using Cox regression and adjusted for covariates. RESULTS: Combining higher ACE doses of > or = 10.8 mg (150 mg once monthly, 3 mg i.v. quarterly, and 2 mg i.v. every 2 months) versus ACE doses of 5.5 mg, from two trials, resulted in an HR 0.62 (95% CI 0.396-0.974, p = 0.038). There was a dose-response trend with increasing ACE doses (7.2-12 mg) versus ACE of 5.5 mg. CONCLUSIONS: A dose-response effect on nonvertebral fractures was observed when comparing high with low ACE doses. A significant reduction in nonvertebral fractures was noted when pooling data from trials using ACE doses of > or = 10.8 mg versus ACE < or = 7.2 mg; and with ACE > or = 10.8 mg versus ACE of 5.5 mg (38% reduction). Higher ibandronate dose levels (150 mg monthly or 3 mg i.v. quarterly) significantly reduced nonvertebral fracture risk in postmenopausal women.