Evidence of sustained vertebral and nonvertebral antifracture efficacy with ibandronate therapy: a systematic review

Background: The antifracture efficacy of ibandronate at vertebral and nonvertebral sites was assessed. Methods: A literature review of randomized phase III clinical trials, meta-analyses or observational studies that reported fracture endpoints or surrogate markers, and compared ibandronate with placebo or an active comparator. Results: In a phase III study, 2.5 mg daily oral ibandronate reduced the incidence of new vertebral fractures versus placebo and the relative risk reduction (RRR) was sustained over 3 years (62%; p = 0.0001). In two bridging studies, oral ibandronate 150 mg once monthly and 3mg quarterly intravenous (i.v.) were superior to oral 2.5 mg daily in producing bone mineral density (BMD) increases at all sites over 2 years (p < 0.05). These improvements were sustained over 5 years. In meta-analyses of pivotal ibandronate studies, doses equivalent to annual cumulative exposure (ACE) >= 10.8 mg (including 150 mg once monthly and 3 mg quarterly i.v.) significantly reduced the incidence of nonvertebral fractures versus placebo or ACE 5.5 mg (2.5 mg daily) (RRR 29.9% and 38%, respectively; p< 0.05). Therefore, prevention of nonvertebral fractures was found in all patients with the commercially available highest doses, and not only in high-risk patients as observed in randomized clinical trials with lower doses. Finally, a 12-month, observational study of claims databases reported comparable rates of nonvertebral fractures and a statistically significantly lower rate of vertebral fractures (p< 0.01) with ibandronate versus weekly bisphosphonates. Conclusion: A large body of evidence suggests that ibandronate has sustained vertebral and nonvertebral antifracture efficacy in women with postmenopausal osteoporosis.