Effect of proton pump inhibitors on bone mineral density: A systematic review and meta-analysis of observational studies

Despite the fact that proton pump inhibitors (PPIs) are one of the most prescribed medications, several epidemiological studies have reported many adverse effects related to their long-term usage. Nevertheless, there were inconsistent findings in the literature with regard to PPI use and bone mineral density (BMD) change. The aim of this systematic review and meta-analysis is to evaluate the association between the use of PPIs and change in BMD. The PubMed/MEDLINE, EMBASE, Cochrane and CINAHL databases were searched up to March 2019. Ten studies fulfilled the eligibility criteria (4761 cases and 30,809 controls), from which the mean difference and mean annualized percent change in BMD were pooled using RevMan 5.3.5 The results showed no statistically significant association between PPI users and non-users in mean annualized percent change in BMD (0.06; 95% CI −0.07, 0.18) with moderate heterogeneity (I2: 63%). There was a statistically significant reduction in the mean BMD difference among PPI users (−0.03; 95% CI −0.04, −0.01) with no substantial heterogeneity (I2: 26%). This meta-analysis reported inconsistent results regarding the use of PPIs and BMD loss. Thus, the effect of PPIs on BMD needs to be elucidated by other studies, and healthcare providers should prescribe PPIs with caution considering their unfavorable consequences on bone health.