Differential fracture risk among proton pump inhibitors in older adults: evidence network and pharmacovigilance validation
Abstract
Background: Proton pump inhibitors (PPIs) are the first-line therapy for acid-related disorders, with particularly high rates of chronic use in adults aged ≥65 years. Nearly all existing studies treat PPIs as a uniform drug class, overlooking potential heterogeneity in fracture risk across individual agents. This study aimed to evaluate the relative fracture risk of individual PPIs in elderly adults, using a complementary dual-method approach of network meta-analysis (NMA) and disproportionality analysis.
Methods: First, we performed a NMA to compare the relative risk of any-site fracture associated with individual PPIs. Second, we performed a complementary disproportionality analysis using data from the US FDA Adverse Event Reporting System (FAERS) database, with additional analysis of osteoporosis/osteopenia events defined by the Standardised Medical Dictionary for Regulatory Activities (MedDRA) Standardised Query (SMQ).
Results: The NMA included 9 eligible studies, enrolling a total of 257,445 participants. Compared with non-PPI users, omeprazole (OR 1.51, 95%CI 1.36-1.67), rabeprazole (OR 1.47, 95%CI 1.22-1.78), pantoprazole (OR 1.44, 95%CI 1.28-1.62), and lansoprazole (OR 1.32, 95%CI 1.14-1.53) were associated with a significantly increased risk of any-site fracture. In contrast, esomeprazole showed no significant association with overall fracture risk (OR 1.16, 95%CI 0.97-1.38). Pairwise comparisons from the NMA showed that esomeprazole had a lower relative fracture…
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