Bone fracture and the interaction between bisphosphonates and proton pump inhibitors: a meta-analysis

Recent studies suggested an increased risk of fractures with interaction between bisphosphonates (BPs) and proton pump inhibitors (PPIs). We performed a meta-analysis of fractures between patients taking BPs/PPIs and those taking BPs only.

We conducted a PubMed database and Ovid database search, as well as Cochrane Library search (up to July 2014) for studies assessing the association between fractures and BPs or/and PPIs. We performed random effects meta-analysis of odds ratios (OR) according to fracture type and conducted subgroup analyses by race and BP subtypes. Heterogeneity was assessed using Q statistics and I(2) statistic.

After study selection, 4 unique studies (5 comparisons) including 57259 patients were available for this meta-analysis. Pooled analysis of overall fracture risk of BP+PPI group versus BP group showed a significant increase in risk of fractures (OR = 1.52, P = 0.025), with substantial heterogeneity. However, heterogeneity was drastically reduced in subgroup of Asian (I(2) = 24% and P = 0.251), and fracture risk showed a significant increase (OR = 1.75, P = 0.026). In contrast, heterogeneity was little eliminated in subgroup of European, and fracture risk was no statistical difference (OR = 1.42, P = 0.068). Three studies including 4 comparisons reported on spine fracture were included in the pooled analysis demonstrating an increased spine fracture risk associated with BP/PPI interaction (OR = 1.60, 95% CI 1.13-2.26, P = 0.008, I(2) = 58.6%).

This meta-analysis suggests that there is an interaction associated with increased fracture risk (particularly for spine and Asian race) between BP and PPI use. Clinicians should carefully evaluate such risk factors for osteoporosis in patients taking BPs, before routinely prescribing PPIs, and make a careful judgment as to whether PPIs may be safe for patients at high risk of fractures.