Fracture Risk with Bisphosphonate Use versus Concurrent Proton Pump Inhibitor and Bisphosphonate Use: A Systematic Review and Meta- Analysis

Abstract

Specific Aims: To determine whether concurrent use of a proton pump inhibitor (PPI) and a bisphosphonate represent an additional fracture risk compared with bisphosphonate use alone and to identify an increased risk of any particular fracture type. Methods: This study was a systematic review and meta-analysis of data collected from PubMed, Cochrane, OVID Medline, Google Scholar, and IPA. The authors utilized the search terms: bisphosphonate, fractures and proton pump inhibitors. Studies which met criteria of being English-language with adults 18 years of age and older were included. Main Results: The studies were cohort studies and primarily evaluated older adults. The summary effect was that use of a PPI with a bisphosphonate showed a slight increase in fracture risk when compared to bisphosphonate-only therapy (odds ratio [OR] 1.12, 95% confidence interval [CI], 1.06-1.18). Systematic review of similar studies showed varied results, making difficult any conclusion regarding fracture risk among the treatments. Conclusion: In this analysis, PPI + bisphosphonate demonstrated a slight increase in fracture rate without inference to an increase in any particular fracture type compared with bisphosphonate only. However, there is minimal data on the association or causal effect of this increase. The few studies available offered contradictory results. Additionally, database studies are subject to the possibility of residual confounding. Further research using randomized control trial (RCT) design evaluating long term use of bisphosphonates with or without PPI and their impact on fractures is needed to determine if there is an additional degree of fracture risk from the concurrent use.