1. The use of proton pump inhibitors (PPIs) in a large pediatric cohort resulted in a small but statistically significant increase in fracture risk compared to children who were not using PPIs.
Evidence Rating Level: 2 (Good)
Proton pump inhibitors (PPIs) are the primary treatment for gastric acid-related disorders in children, despite this treatment being predominantly rooted in expert opinion rather than empirical data. Little is known related to their safety in pediatric populations yet have been prescribed at an increasing rate over recent years. This Sweden-wide register-based cohort study investigated the association between PPI use and fracture risk in a pediatric population – one known to be at risk for fractures. This study also engaged in a direct comparison of PPI and histamine-2 receptor antagonists (H2RA). PPIs included omeprazole, esomeprazole, pantoprazole, rabeprazole, and lansoprazole. The target population was children under the age of 18 years during the study period of July 1, 2006 to December 31, 2016. Each child undergoing PPI treatment was matched with 30 non-PPI children. The final cohort was based on a 1:1 propensity score match and age groups of two-year bands. Children with organ transplant, cancer, congenital skeletal malformation, trauma-associated fracture in past 10 years, liver failure, and severe fractures were excluded. This resulted in a total of 115,933 child pairs with a mean (SD) follow-up period of 2.2 (1.6) years. During follow-up, more fractures were identified among the PPI group than the non-PPI group (difference 1.9 events per 1,000 person-years, HR 1.08, 95% CI 1.06 to 1.15). While no differences were found between groups for head or spine fractures, PPIs were associated with elevated risk of lower-limb fractures (HR 1.19, 95% CI 1.10 to 1.29), upper-limb fractures (HR 1.08, 95% CI 1.03 to 1.13), and other fractures (HR 1.51, 95% CI 1.16 to 1.97). When focusing on PPI use duration, the categories were ≤30 days (HR 1.08, 95% CI 1.03 to 1.13), 31 to 364 days (HR 1.14, 95% CI 1.09 to 1.20), and ≥365 days (HR 1.34, 95% CI 1.13 to 1.58). High-dimensional propensity score matching resulted in a consistent association (HR 1.10, 95% CI 1.06 to 1.15). Comparisons of PPI and H2RA did not reach statistical significance (HR 1.06, 95% CI 0.97 to 1.15). While relatively small, this study suggests statistically significant differences in fracture risk between children who are exposed to PPI treatment compared to those who are not. This suggests that physicians must carefully weigh the costs and benefits when considering PPI treatment among pediatric populations.
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