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

• Published in: Current medical research and opinion 2008-01, Vol.24 (1), p.237-245
• Main Authors: Harris, Steven T., Blumentals, William A., Miller, Paul D.
• Format: Article
• Language: English
• Subjects: Aged; Bisphosphonates; Bone and Bones - injuries; Bone Density; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - therapeutic use; Clinical fracture; Clinical Trials, Phase III as Topic; Diphosphonates - administration & dosage; Diphosphonates - therapeutic use; Female; Fractures, Bone - etiology; Fractures, Bone - prevention & control; Humans; Ibandronate; Ibandronic Acid; Meta-analysis; Middle Aged; Non-vertebral fracture; Osteoporosis; Osteoporosis, Postmenopausal - complications; Osteoporosis, Postmenopausal - drug therapy; Risk Factors; Time Factors
• ISSN: 0300-7995; 1473-4877
• DOI: 10.1185/030079908X253717

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.