Oral nitrogen-containing bisphosphonates: a systematic review of randomized clinical trials and vertebral fractures

Background: Vertebral fractures are the most common osteoporotic fracture. They are associated with increased morbidity and mortality, and also predict future vertebral and non-vertebral fracture risk. Bisphosphonates are the current mainstay for the treatment of postmenopausal osteoporosis. Health authority guidelines request that assessment of vertebral fracture risk reduction is part of the evaluation of bisphosphonate efficacy. In this review, we compare the published evidence for the efficacy of the nitrogen-containing oral bisphosphonates in reducing the risk of vertebral fractures. Methods: A review of publications in the treatment of postmenopausal osteoporosis and the most frequently prescribed oral bisphosphonate therapies (alendronate, ibandronate and risedronate) was carried out using the Dialog (Embase and Medline) and Cochrane online scientific citation databases. Eligible publications were those reporting randomized, placebo-controlled trials that included vertebral fracture as the primary or secondary endpoint (any time-point). Results: Of 159 publications identified, six studies assessing alendronate, ibandronate and risedronate met the pre-defined eligibility criteria. In total, 14083 women were included in the studies, with 8182 patients receiving active treatment. Most studies were 3 years in duration. Discontinuation rates varied from 11 to 45%, being highest in those studies that specified one or more vertebral fracture as part of the inclusion criteria. Across these studies, the reduction in the risk of vertebral fractures ranged from 41 to 62% (44-48% for alendronate; 41-49% for risedronate; 62% for ibandronate). Conclusions: Nitrogen-containing oral bisphosphonates effectively reduce the risk of osteoporotic vertebral fracture, with the magnitude of effect ranging from 41 to 62%.