An Updated Meta-Analysis: The Effect Of Proton Pump Inhibitor On Risk Of Osteoporosis And Fracture

The aim of this study was to evaluate the association between proton pump inhibitor (PPI) use and risk of osteoporosis and fracture by performing an updated meta-analysis. We searched PubMed, EMBASE, and Web of Knowledge from inception to March 2017 for observational studies reporting the risk of osteoporosis and/or fracture with PPIs. Random-effects meta-analysis was used to obtain pooled estimates of effect due to heterogeneity. We identified 27 studies with a total of 1885507 subjects included. According to recent studies, use of PPIs was associated with an elevated risk of osteoporosis (OR 1.39, 95% CI 1.22-1.58). A meta-analysis of 20 observational studies showed that the overall risk of hip fracture was higher among people using PPIs (OR 1.22, 95% CI 1.15-1.30). Similar to hip fracture, high risk of any-site and spine fractures was observed in PPI users (OR 1.19 95% CI 1.12-1.27 and OR 1.53, 95% CI 1.36-1.73, respectively). Subgroup analyses by dose indicated that the high dose and the low dose group were consistent on the strength of the association between PPIs therapy and risk of hip fracture. In addition, no time response relationship was found in subgroup analysis. This meta-analysis demonstrates PPI therapy may be linked to an increased risk of both osteoporosis and fracture, but no evidence of dose-response and duration-response relationship was found in subgroup analysis. Considering the effect of unmeasured confounding, more rigorous experiments are needed to clarify whether PPI therapy or residual confounding lead to the increased risk of osteoporosis and fracture.