Vertebral fracture risk reduction with risedronate in post-menopausal women with osteoporosis: a meta-analysis of individual patient data

Background and aims: The effect of risedronate, a potent pyridinyl bisphosphonate, on vertebral fractures in post-menopausal women was evaluated in randomized, placebo-controlled clinical trials. These trials included two large vertebral fracture studies that used time-to-event methods to evaluate the effects of treatment on fracture risk, thereby allowing both the occurrence and the timing of fractures to be considered. Methods: We used individual patient data (IPD) and time-to-event methods to perform a meta-analysis of the anti-fracture efficacy of risedronate (2.5 or 5 mg daily) in osteoporotic women enrolled in five double-blind, placebo-controlled clinical trials. Women were included in the analysis if, at baseline, they had either at least one prevalent vertebral fracture or a femoral neck bone mineral density (BMD) T-score of less than −2.5, were at least 1 year post-menopausal, and had had vertebral fracture assessments (N=3331). Results: Risedronate 5 mg daily reduced the risk of radiographically defined vertebral fracture by 64% (95% CI, 46 to 76%, p<0.001) in the first year of treatment and 45% (95% CI, 31 to 57%, p<0.001) in 3 years. The numbers of patients who needed to be treated with risedronate 5 mg to prevent one new vertebral fracture over 1 and 3 years were 21 and 13, respectively. Comparable findings were observed in sub-populations defined on the basis of either prevalent vertebral fracture without regard to femoral neck BMD, or femoral neck BMD without regard to vertebral fracture status. Risedronate significantly reduced the incidence of clinical (symptomatic) vertebral fractures in the first 6 months of treatment (p<0.001). Conclusions: This meta-analysis, based upon five trials and using IPD and time-to-event statistical methods, provides a more precise estimate of the effect of risedronate in reducing vertebral fracture risk in post-menopausal osteoporotic women than a meta-analysis using summary statistics from the literature.