A multicenter cohort analysis of fractures in histamine-2-receptor antagonist treated pediatric patients

Histamine 2 receptor antagonists (H2RA) are amongst the most entrenched antacid therapies available including over-the-counter. They have an excellent safety profile including no known teratogenic risk. Fracture risk is generally recognized with chronic proton pump inhibitor (PPI) therapy in adults and children although the related mechanism is poorly understood. The analogous risk in H2RAs, including in children, is unclear. We studied the fracture risk and characteristics among hospitalized pediatric patients exposed to H2RA compared to an untreated cohort.The Pediatric Health Information System (PHIS) multicenter database was queried for hospital encounters of children aged 6 months - 15.5 years and between 7/2016 and 8/2017. Patients with comorbidities and medications including PPI that predispose for fractures were excluded from the cohort and a propensity-matched control was identified. The subjects and controls were followed for 2 years for hospitalization with fracture diagnoses.Our cohort included 3526 patients with exposure to H2RA and matched controls. Fractures were reported in 1% of patients (67) with no statistical difference between the groups. Upper, then lower extremity fractures were the most common in both groups. Axial skeleton fractures were the least frequently encountered fractures among both groups.H2RA exposure is not associated with an increased risk of fracture in hospitalized children exposed to H2RA when compared with a matched untreated cohort, further studies are needed to determine if long-term exposure to H2RA may be associated with fracture risk in both those with and without comorbidities or on fracture predisposing medication.PLAIN LANGUAGE SUMMARYWhat is knownHistamine-2-receptor antagonists (H2RA) are amongst the most widely used acid suppression therapy in children.H2RA therapy is regarded as safe in children including infants.Fracture risk associated with proton pump inhibitor (PPI) therapy in children has not been adequately studied in children.What is newThe incidence of fractures in children aged 6 months through 15.5 years followed for 2 years after H2RA therapy was not increased when compared to a matched controlUse of H2RA therapy is safer than PPI therapy with respect to fracture risk in children with no other risk factors.Further studies are needed to assess the association of long-term exposure to H2RA with fracture risk in children without predisposing risk for fracture.