Association Between Inhaled Corticosteroid Use and Bone Fracture in Children With Asthma

Abstract

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, setting, and participants: In this population-based nested case-control study, we used health administrative databases to identify a cohort of children aged 2 to 18 years with a physician diagnosis of asthma between April 1, 2003, and March 31, 2014, who were eligible for public drug coverage through the Ontario Drug Benefit Program (Ontario, Canada). We matched cases of first fracture after asthma diagnosis to fracture-free controls (ratio of 1 to 4) based on date of birth (within 1 year), sex, and age at asthma diagnosis (within 2 years). We used a 1-year lookback period to ascertain history of inhaled corticosteroid use. Multivariable conditional logistic regression was used to obtain an odds ratio (OR) with 95% confidence interval for fracture, comparing no inhaled corticosteroid use vs current, recent, and past use.

Exposures: Inhaled corticosteroid use during the child's 1-year lookback period, measured as current user if the prescription was filled less than 90 days prior to the index date, recent user (91-180 days), past user (181-365 days), or no use.

Main outcomes and measures: First emergency department visit for fracture after asthma diagnosis, identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes.

Results: This study included 19 420 children (61.0% male; largest proportion of children, 31.5%, were aged 6-9 years at their index date). The multivariable regression results did not show a significant association between first fracture after asthma diagnosis and current use (OR, 1.07; 95% CI, 0.97-1.17), recent use (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 with no use, while adjusting for sociodemographic factors and other medication use. However, use of systemic corticosteroids in the 1-year lookback period resulted in greater odds of fracture (OR, 1.17; 95% CI, 1.04-1.33).

Conclusions and relevance: Systemic corticosteroids, but not inhaled corticosteroids, were significantly associated with increased odds of fracture in the pediatric asthma population.

Figure 1.. Adjusted Odds Ratios for Fracture From Conditional Logistic Regression for Boys and Girls

Models were adjusted for rurality, Ontario Marginalization Index, Local Health Integration Networks, and number of systemic corticosteroid prescriptions. Data are shown for boys (n = 11 840) and girls (n = 7580). ICS indicates inhaled corticosteroid.

Figure 2.. Adjusted Odds Ratios for Fracture From Conditional Logistic Regression

Models were adjusted for rurality, Ontario Marginalization Index, Local Health Integration Networks, and number of systemic corticosteroid prescriptions. Data are shown for participants aged 2 to 5 years (n = 5847), 6 to 9 years (n = 6120), 10 to 13 years (n = 5049), and 14 to 18 years (n = 2404) at the index date. ICS indicates inhaled corticosteroid.