Asthma and lower airway disease
Corticosteroid use and bone mineral accretion in children with asthma: Effect modification by vitamin D

https://doi.org/10.1016/j.jaci.2012.04.005Get rights and content

Background

The adverse effects of corticosteroids on bone mineral accretion (BMA) have been well documented. Vitamin D insufficiency, a prevalent condition in the pediatric population, has also been associated with decreased bone mineral density (BMD).

Objective

We sought to determine whether children with asthma who have lower vitamin D levels are more susceptible to the negative effects of corticosteroids on BMD over time.

Methods

Children aged 5 to 12 years with mild-to-moderate asthma who participated in the Childhood Asthma Management Program were followed for a mean of 4.3 years. Total doses of inhaled corticosteroids and oral corticosteroids (OCSs) were recorded, serum 25-hydroxyvitamin D3 levels were measured at the beginning of the trial, and serial dual-energy x-ray absorptiometry scans of the lumbar spine were performed. Annual BMA rates were defined as follows: [(BMD at 4 years’ follow-up − BMD at baseline)/4 years].

Results

BMA was calculated for 780 subjects. In boys baseline vitamin D levels significantly modified the relationship between OCSs and BMA (vitamin D × OCS interaction, P = .023). Stratification by vitamin D levels showed a decrease in BMA with increased use of OCSs in vitamin D–insufficient boys only (P < .001). Compared with vitamin D–sufficient boys, vitamin D–insufficient boys exposed to more than 2 courses of OCSs per year had twice the decrease in BMA rate (relative to boys who were OCS unexposed).

Conclusions

Vitamin D levels significantly modified the effect of OCSs on BMA in boys. Further research is needed to examine whether vitamin D supplementation in children with poorly controlled asthma might confer benefits to bone health.

Section snippets

Study population

The demographics of the subjects enrolled in CAMP and the study design have been described previously.11 Briefly, 1041 children with mild-to-moderate asthma aged 5 to 12 years were randomized to budesonide, nedocromil, or placebo. This was a multicenter trial designed to evaluate the long-term effects of these treatments on lung growth. Follow-up visits occurred at 2 and 4 months after randomization and every 4 months thereafter. The children’s parents or guardians provided informed consent,

Patients’ demographics

From the 7 eligible study centers, a total of 780 subjects had a baseline vitamin D level and BMD measurement at baseline and at 4 years’ follow-up. The subjects lost to follow-up had a lower body mass index (BMI) and higher vitamin D level compared with the study participants, but other demographics did not differ significantly, including the percentage of randomization to budesonide (see Table E1 in this article’s Online Repository at www.jacionline.org). The median vitamin D level was

Discussion

In this evaluation of the combined effects of vitamin D level and corticosteroid use on BMA and BMD in children with asthma, we found a dose-dependent effect of OCS use on BMA in boys that was significantly modified by serum 25(OH)2D levels. Specifically, boys with lower vitamin D levels (≤30 ng/mL) had a doubling of the decrease in BMA after exposure to a moderate-to-high number of OCS treatment courses for asthma exacerbations (Fig 1). This effect was most notable in subjects taking the

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    The Childhood Asthma Management Program is supported by contracts NO1-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052 with the National Heart, Lung, and Blood Institute and General Clinical Research Center grants M01RR00051, M01RR0099718-24, M01RR02719-14, and RR00036 from the National Center for Research Resources. Additional support for this research came from grants P50 HL67664, T32 HL07427, and R21 HL089842 from the National Institutes of Health and the National Heart, Lung, and Blood Institute. This article is subject to the National Institutes of Health’s Public Access Policy (http://publicaccess.nih.gov).

    Disclosure of potential conflict of interest: H. W. Kelly is on the GlaxoSmithKline Steering Committee for FDA-mandated LABA safety study in children and the AstraZeneca, Novartis, and Merck Steering Committees for FDA-mandated LABA safety trials in adults. A. Litonjua has received research support from the National Institutes of Health (NIH) and receives author royalties from UpToDate, Inc. K. Tantisira has received research support from the NIH. The rest of the authors declare that they have no relevant conflicts of interest.

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