Ibandronate and the risk of non-vertebral and clinical fractures in women with postmenopausal osteoporosis: results of a meta-analysis of phase III studies

ABSTRACT

Objective: The marketed doses of ibandronate, 150?mg once-monthly oral and 3?mg quarterly intravenous (IV) injection, produce greater increases in lumbar spine bone mineral density than treatment with the 2.5?mg oral daily dose. This meta-analysis assessed whether these doses also reduce fracture risk relative to placebo.

Study design and methods: Individual patient data from the intent-to-treat populations of the BONE, IV fracture prevention, MOBILE, and DIVA studies were grouped into three dose levels based on annual cumulative exposure (ACE), defined as the annual dose (mg) × bioavailability (0.6%, oral; 100%, IV) or placebo. Six key non-vertebral fractures (NVFs) (clavicle, humerus, wrist, pelvis, hip, and leg), all NVFs, and all clinical fractures were examined.

Results: This meta-analysis included 8710 patients. Cox proportional-hazards models estimated the adjusted relative risk (RR) for fracture with ibandronate versus placebo, and time to fracture was compared using log-rank tests. The high-dose group (ACE?≥?10.8?mg) showed significant reductions in the adjusted RR of key NVFs (34.4%, p?=?0.032), all NVFs (29.9%, p?=?0.041), and clinical fractures (28.8%, p?=?0.010) relative to placebo. The high-dose group also had significantly longer time to fracture versus placebo for key NVFs (p?=?0.031), all NVFs (p?=?0.025), and clinical fractures (p?=?0.002). Study limitations included: not all studies were placebo-controlled; a limited number of baseline characteristics were available for multivariate analyses.

Conclusion: Ibandronate at dose levels of ACE?≥?10.8?mg, which includes the marketed 150?mg once-monthly oral and 3?mg quarterly IV injection regimens, may provide significant non-vertebral and clinical fracture efficacy.