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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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 SUMMARY

What is known

• Histamine-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 new

• The 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 control

• Use 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.

Keywords:

• Adverse effects
• acid-suppression
• peptic ulcer disease therapy

MESH terms:

• Histamine H2 Antagonists/therapeutic use
• Fractures
• Bone/epidemiology
• Retrospective Studies United States/epidemiology
• Gastroesophageal Reflux/drug therapy

Transparency

Declaration of funding

This paper was not funded.

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

TMA, NRF; inception, study design, NRF, TR; search algorithm, code selection, TR: data analysis, statistical computations, TMA, critical review and write up.

Acknowledgements

None.