This case-control study was an attempt to characterize fracture risk in children with asthma, but in spite of the high quality of the study design and reporting, it has limited generalizability.
Source: Gray N, Howard A, Zhu J, et al. Association between inhaled corticosteroid use and bone fracture in children with asthma. JAMA Pediatr. 2018;172:57-64. doi:10.1001/jamapediatrics.2017.3579. See AAP Grand Rounds commentary by Dr. Patricia Fechner (subscription required).
Researchers in Ontario, Canada, utilized a number of administrative databases to look at the fracture risk in children 2 - 18 years of age who were diagnosed with asthma over a several year period. They used a nested case-control study design, matching 4 control children with asthma and no fractures to each asthma child who experienced a fracture. They did not find any increased fracture risk for children who had utilized inhaled corticosteroids in the year preceding the fracture, although they did see a correlation between high-dose systemic steroid use and fractures.
The study itself is of high quality, but I'm always interested in how the study results inform patient care. From that perspective, these results have little use outside of a very narrow patient population. Here's why.
I mentioned the researchers used a few different databases to collect information. In order to have a large study population, they queried a prescription drug benefit program for individuals registered in social assistance programs focused on families with low-incomes. An asthma registry database found almost 400,000 children registered over the 12-year study period, of which almost 40,000 had administrative coding for bone fracture. However, over 90% of those asthmatic children with fractures were excluded from the study based on prior diagnosis of cancer, diabetes, or organ transplant, or if they did not have data on age, residence code, or valid health card number, or if they were ineligible for this type of prescription drug coverage. Since I doubt such a large number of children had cancer, diabetes, or organ transplant, I suspect the majority of exclusions were due to lack of eligibility for this coverage. Thus, we are looking at a very small piece of the "asthma pie" here.
Another limitation is that the database used to define asthma diagnosis, while large, does have some inaccuracies. The authors note validation of that database showed a sensitivity of 91.4% and specificity of 82.9%. That could introduce some problems with conclusions, and it would have been ideal for the authors to tell us how the confidence intervals around those figures might affect their conclusions.
This study adds to our understanding of risks of corticosteroid therapy for asthma does not specifically help a primary care provider, or anyone outside of a provider of asthma care for low-income populations in Ontario, reassure families that inhaled corticosteroids carry no increased risk of fractures for these children. One of the frequently forgotten features of medical research is that even high-quality studies seldom have immediate applicability to large patient populations.
