Proton pump inhibitors and risk of hip fracture: a systematic review

Abstract

Objective To explore the effects of using proton pump inhibitors (PPIs) on the outcomes of hip fracture. Methods Searches were conducted through Medline, Embase, Cochrane Library and Chinese Biomedical Literature Database to identify the studies of the association between PPIs exposure and hip fracture. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Pooled odds ratios (ORs) and 95% confidence interval (CIs) were calculated for the risk of hip fracture associated with current exposure of PPIs. And several subgroups were analyzed by dosing duration, dose, osteoporosis and corticosteroid usage to explore potential study heterogeneities. All statistical analyses were performed with STATA software. Results Among 11 publications included for final analysis, there were a total of 1 107 577 subjects with an average age of over 60 years. A positive relationship existed between PPIs exposure and hip fracture with an OR of 1.46 (95%CI: 1.26-1.70, P=0.000) as compared with non-PPI-users, especially those on concurrent corticosteroid and PPIs. A significantly increased risk of hip fracture was found in the group of a short-term duration for under 1 year (OR=1.18, 95%CI: 1.01-1.38, P=0.041), medium-term for 1-3 years (OR=1.23, 95%CI: 1.01-1.49, P=0.038) and longer duration for over 6 years (OR=1.38, 95%CI: 1.27-1.50, P=0.000). Furthermore, concurrent use of PPIs was not associated with an increased risk of hip fracture in a definite dose-response manner. As compared with non-PPI-users, no significantly increased risk of hip fracture was found in PPI-users with osteoporosis (P>0.05). Publication bias was not present. Conclusions Use of PPIs may be somewhat associated with an increased risk of hip fracture. Considering potential adverse effects, clinicians should prescribe cautiously PPIs for high-risk patients, especially elders. Key words: Fractures, bone; Hip; Proton pump inhibitor; Meta-analysis