Systemic effects of inhaled corticosteroids on growth and bone turnover in childhood asthma: a comparison of fluticasone with beclomethasone

Abstract

Inhaled steroids are frequently used in childhood asthma, but concerns based on limited objective evidence remain, regarding long-term side-effects. In this study the systemic effects of standard doses of inhaled steroids in childhood asthma were assessed, comparing beclomethasone dipropionate (BDP) with fluticasone propionate (FP). The study was prospective, randomized and double-blind. Twenty-three steroid-naive children with moderately severe asthma, aged 5-10 yrs, were allocated either BDP (400 microg x day(-1) or FP (200 microg x day(-1)) using a metered-dose inhaler with a spacer. Asthma control was assessed at regular intervals over 20 months. Fasting morning blood and overnight urine samples were collected for estimation of serum cortisol, serum 1-carboxyterminal telopeptide (ICTP), serum osteocalcin and urine deoxypyridinoline (DPD). Bone mineral density (BMD) was measured at each visit. None of the markers of bone turnover showed any change during the study period. BMD increased at normal rates with age. Serum cortisol significantly decreased on BDP, but not on FP. A significant difference in growth rates was found between the groups, with a slower rate of growth towards the end of the observation period in the BDP group. In conclusion when taken in a relatively modest dose over a period of time, beclomethasone dipropionate had significant effects on the hypothalamic-pituitary-adrenal axis and statural growth in childhood asthma. These systemic effects were not seen with an equipotent dose of fluticasone propionate.

Endocrine Effects of Inhaled Corticosteroids in Children

“…60 Several studies [60][61][62][63] have looked at younger children to minimize the confounder of puberty. Three studies [60][61][62] found no deleterious effects of standard doses of beclomethasone or fluticasone on BMD in children 12 years and younger. However, a study 63 daily) for a mean (SD) of 2.9 (1.6) years revealed that lumbar BMD was more than 1 SD below the mean in 35% of treated patients compared with controls (P = .001).…”

Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in children under the age of 12 years

“…All patients in Rao and colleagues' study 202 completed the initial 10 weeks and were well matched (except for immunoglobulin E levels, which were significantly higher in the BDP group).…”

“…Only Gustafsson and colleagues 201 reported a power calculation (the outcome used was PEF) and neither of the trials stated that they used an ITT analysis. In the study by Rao and colleagues, 202 the three arms ran for 10 weeks. After this period, the placebo arm merged with the FP arm as it was considered unethical to continue the placebo for longer, thus breaking randomisation.…”

“…Rao and colleagues 202 were predominantly interested in comparing the effect of FP with BDP on growth and bone turnover.…”

“…The duration of the trials ranged from 6 weeks 201 to 20 months. 202 The six-week study by Gustafsson and colleagues 201 was a large multi-centre trial (32 centres in 11 countries) with 398 children aged from 4 to 19 years, who were inadequately controlled on current treatment. The other trial was smaller and the number of centres was not reported.…”