PPI use associated with a small increased fracture risk in children

Reference

Wang YH, Wintzell V, Ludvigsson JF, Svanstrom H, Pasternak B. Association between proton pump inhibitor use and risk of fracture in children. JAMA Pediatr 2020;174(6):543-551.

Synopsis

These authors used Swedish registries to compare fracture rates in children who had received PPIs with those who had not. For each child with a new prescription for a PPI the researchers age-matched up to 30 children who were PPI-naïve. They then propensity matched the control group to wind up with a net 1:1 match of 115,933 pairs. With a median follow-up of 2.2 years, 5354 children taking PPIs had a fracture (20.2 fractures per 1000 person-years) compared with 4568 children in the control group (18.3 fractures per 1000 person-years). The authors also looked at specific fractures and found that children using PPIs were more likely to have limb fractures and found no association between PPIs and axial fractures. They also looked at duration of PPI use and found progressively increased fracture risk with longer duration treatment, but even less than 30 days was associated with a small increased risk (hazard ratio 1.08; 95% CI 1.03 - 1.13). The authors also looked at individual PPIs, and found that the association was only found with omeprazole. Although it is possible that the fracture risk is highly specific, it is more likely that the association is a reflection of how frequently omeprazole is used compared with the other PPIs or that the entire association is a random finding. Finally, the researchers tried to look at the potential role of histamine receptor antagonists within this cohort but were unable to draw any conclusions, probably because of how they constructed the initial cohort. Since it is possible that children who need chronic acid suppression therapy are more fragile, we need to stay tuned for better studies.