Twenty RCTs (n=44,878 women, sample size range 327 to 9,331 women) and 11 retrospective observational studies (n=331,256 women, sample size range 2,613 to 101,038 women) were included in the review. The median proportion of women completing the studies was 79% in the RCTs (interquartile range 66 to 88%).The authors stated that the included studies were uniformly well designed.
All fractures: There were statistically significant benefits associated with bisphosphonate treatment observed in seven RCTs that evaluated the occurrence of fractures (OR 0.762, 95% CI 0.680 to 0.855; n=23,769 women). Pooled data from the six observational studies also showed significant benefits of bisphosphonate treatment on fracture occurrence (OR 0.797, 95% CI 0.748 to 0.850; n=113,459 women). Across all 13 studies, a statistically significant 22% reduction in the occurrence of all fractures was observed (OR 0.776, 95% CI 0.729 to 0.826). Results of the sensitivity analyses showed similar significant treatment effects for different bisphosphonate types, study periods (one to two years or three to five years), effect size measures (OR or HR), and geographic regions (USA or other and multiple sites).
Single fracture types: There were significantly lower risks observed in the RCTs with bisphosphonate treatment of non-vertebral fractures (OR 0.796, 95% CI 0.739 to 0.858; 17 RCTs; n=37,460 women), vertebral fractures (OR 0.413, 95% CI 0.279 to 0.612; four RCTs; n=14,865 women), hip fractures (OR 0.711, 95% CI 0.616 to 0.820; 10 RCTs; n=34,415 women). There were no differences in the occurrence of wrist fractures for both RCTs and observational studies.
The was no evidence of statistical heterogeneity or publication bias for the results for all fracture types across the RCTs.