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


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) x 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 > or = 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.


CONCLUSIONS
Ibandronate at dose levels of ACE > or = 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.
Harris
Steven T
ST
University of California, San Francisco, CA 94155-3044, USA. steve.harris@ucsf.edu
Blumentals
William A
WA
Miller
Paul D
PD
D000368:Aged; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001842:Bone and Bones / Q000293:injuries; D017326:Clinical Trials, Phase III as Topic; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D000077557:Ibandronic Acid; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy*; D012307:Risk Factors; D013997:Time Factors
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077557:Ibandronic Acid