Association between inhaled corticosteroid use and bone fracture in children with asthma

Importance — Daily use of inhaled corticosteroids is a widely recommended treatment for mild persistent asthma in children. There is concern that, similar to systemic corticosteroids, inhaled corticosteroids may have adverse effects on bone health.

Objective — To determine whether there is an increased risk of bone fracture associated with inhaled corticosteroid use in children with asthma.

Design — In this nested case-control study, we utilized health administrative databases from 2003–2014 to identify a cohort of children with physician-diagnosed asthma. We matched cases of first fracture after asthma diagnosis to fracture-free controls (1:4) based on date of birth (within 1 year), sex and age at asthma diagnosis (within 2 years). We used a one-year lookback period to ascertain history of inhaled corticosteroid use. Multivariable conditional logistic regression was used to obtain an odds ratio with 95% confidence interval for fracture, comparing no inhaled corticosteroid use to current, recent and past use.

Setting — Population-based study in Ontario, Canada.

Participants — Children aged 2-18 years with a physician diagnosis of asthma between 2003 and 2014 eligible for public drug coverage through the Ontario Drug Benefit program.

Main Exposure — Inhaled corticosteroid use during the child’s one-year lookback period, measured as current use if prescription was filled <90 days prior to index date, recent user (91-180 days), past user (181-365 days), or no use.

Main Outcome and Measurements — First emergency department visit for fracture after asthma diagnosis, identified using ICD-10 codes.

Results — In the 19,420 children included, the multivariable regression results did not show a significant association between first fracture after asthma diagnosis and current (OR: 1.07, 95% CI: 0.97-1.17), recent (OR: 0.96, 95% CI: 0.86-1.07), or past use (OR: 1.00, 95% CI: 0.91-1.11) of inhaled corticosteroids, compared to no use, while adjusting for sociodemographic factors and other medication use. However, use of systemic corticosteroids in the year lookback period resulted in a significantly greater odds of fracture (OR: 1.17, 95% CI: 1.04-1.33).

Conclusion and Relevance — Systemic corticosteroids, but not inhaled corticosteroids, were significantly associated with an increased odds of fracture in the pediatric asthma population.