No Excess Bone Risk With Inhaled Steroids in Kids

Veronica Hackethal, MD

November 15, 2017

Children who use daily inhaled corticosteroids (ICSs) for moderate persistent asthma do not have significantly increased risk for bone fractures compared with children with asthma who are not taking steroids, a new study showed.

"Clinicians using ICSs to optimize the control of childhood asthma should be reassured by the lack of association with fractures; fear of fracture is not a reason to limit the therapeutic use of ICSs," write Natasha Gray, MPH, from The Hospital for Sick Children, Toronto, Ontario, Canada, and colleagues in an article published online on November 13 in JAMA Pediatrics.

However, the study also found that systemic steroids were associated with significantly increased fracture risk.

Noting that concerns over the safety of ICSs may result in failure to take daily asthma controller medication, leading to inadequate asthma control and the need for systemic steroids, the authors added: "[A]sthma control with ICSs might decrease the likelihood of asthma exacerbations requiring systemic corticosteroid use, so wider appropriate use of ICSs may potentially lead to a reduced fracture risk."

Daily ICSs are the gold standard for long-term therapy in children with mild persistent asthma. However, research in adults has shown that systemic steroids can predispose to osteoporosis and increase the risk for fracture. That finding had raised concerns about whether ICSs had a similar effect on bone health during childhood, a critical period for bone development. Yet studies on ICS safety in children are few and have yielded inconsistent results.

To investigate the issue, researchers conducted a population-based case-control study in Ottawa, Ontario, Canada. Using administrative databases, they identified 19,420 children aged 2 to 18 years (61% male) who had been diagnosed with asthma between April 2003 and March 2014.

The researchers matched children in a 1:4 ratio based on birth date, sex, and age at asthma diagnosis. Cases included 3884 children who had experienced a first fracture after an asthma diagnosis. Controls included 15,536 children free of fractures after an asthma diagnosis. Then researchers evaluated ICS use going back 1 year before fractures occurred. The analysis controlled for sociodemographic factors, as well as systemic steroid and other medication use.

Results showed no significant link between first fracture after an asthma diagnosis and current ICS use (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.97 - 1.17; P = .20), recent ICS use (OR, 0.96; 95% CI, 0.86 - 1.07; P = .53), or past ICS use (OR, 1.00; 95% CI, 0.91 - 1.11; P = .86) compared with no ICS use.

Use of systemic steroids 1 year before a fracture occurred was associated with a 17% increased odds of fracture (OR, 1.17; 95% CI, 1.04 - 1.33; P = .01) compared with no  use of systemic steroids.

The authors note that having severe asthma could account for some of the association between fracture risk and systemic corticosteroids because children with severe asthma may have lower activity levels, which could have a detrimental effect on bone strength.

They conclude, "Future research should investigate how severity of asthma may play a role in the risk of fracture, as some of the increased risk associated with systemic corticosteroids may be due to the underlying illness itself."

The authors mentioned several study limitations, including the use of administrative data, which precluded evaluation for nutrition, disease severity, and vitamin D and calcium levels. Also, to be included children had to be eligible for public drug coverage via the Ontario Drug Benefit Program. Thus, most patients came from low-income families, and the results may not generalize more widely to moderate- and high-income populations.

The study was funded by the Institute for Clinical Evaluative Sciences, which is supported by the Ontario Ministry of Health and Long-Term Care, and the SickKids Research Institute. The authors have disclosed no relevant financial relationships.

JAMA Pediatr. Published online November 13, 2017.  Abstract

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