Introduction: Proton pump inhibitors (PPIs) are the most commonly used drug for the treatment of gastric upset. Epidemiological studies presented inconsistent findings concerning the proton pump inhibitor use and the risk of hip fracture. So, this systematic review and meta-analysis was performed with the aim to quantify the risk of hip fractures associated with PPI use.
Materials & methods: We included observational studies assessing the association between PPI use and hip fracture. Relevant studies were identified by searching the suitable MeSH term in PubMed database from inception to 9th July 2017. Search was limited to English language. We extracted the following information from each eligible study: first author, study design, study period, age, number of participants in each group and relative risk (adjusted and unadjusted). Newcastle-Ottawa scale was used to judge the quality of the study. In order to assess the heterogeneity, subgroup and sensitivity analysis was also performed. Meta-analysis was done by generic inverse variance method using RevMan v5.3.
Results: Sixteen studies meet the eligibility criteria for inclusion in the meta-analysis with a total of 1013916 control and 243278 cases. One-third of the studies were found to be of high quality. Pooled analysis showed statistically significant high risk of hip fracture among PPI user in an adjusted analysis [RR 1.26 (95% CI: 1.17 to 1.37), I2 = 70%, p<0.00001)], While higher risk of hip fracture was noticed in an unadjusted analysis RR 1.55 (95% CI: 1.36 to 1.76), I2 = 87%, p<0.000001). Studies in medium quality subgroup have higher risk as compared to studies in lower quality [RR 1.28 (95% CI: 1.17 to 1.39) vs RR 1.20 (95% CI: 1.01 to 1.43)]. Risk was almost similar after stratification according to sex, geographical region and study design.
Discussions: PPI use was associated with increased risk of fracture including hip, spine and other sites as revealed by several studies [1-2]. The exact mechanism of PPI induced hip fracture is still not clear but it is assumed that PPI reduces bone mineral density by altering intestinal calcium absorption. PPI use is also responsible for hypomagnesemia which is a well-known risk factor for fracture [3].
Conclusion: This meta-analysis suggests that PPI user have 26% higher risk of hip fracture. Physicians should take caution in prescribing PPI to patients who are at higher risk of fracture.
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