Evidence of Sustained Vertebral and Nonvertebral Antifracture Efficacy with Ibandronate Therapy: A Systematic Review

Abstract

The antifracture efficacy of ibandronate at vertebral and nonvertebral sites was assessed. 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. 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 3 mg 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. A large body of evidence suggests that ibandronate has sustained vertebral and nonvertebral antifracture efficacy in women with postmenopausal osteoporosis.