Knemometry, urine cortisol excretion, and measures of the insulin-like growth factor axis and collagen turnover in children treated with inhaled glucocorticosteroids

Pediatr Res. 1997 Jan;41(1):44-50. doi: 10.1203/00006450-199701000-00007.

Abstract

Correlations between knemometric (lower leg length) growth rates and urine free cortisol excretion, respectively, and serum concentrations of IGF-I, IGF binding protein-3, osteocalcin, carboxy terminal propeptide of type I collagen (PICP), carboxy terminal pryridinoline cross-linked telopeptide of type I procollagen (ICTP), and amino terminal propeptide of type III procollagen (PIIINP) were investigated in 17 asthmatic children aged 7-14 y during treatment with fluticasone propionate, 200 micrograms, and beclomethasone dipropionate, 400 and 800 micrograms/d, taken from dry powder inhalers. The study was a double blind, crossover trial with three active treatment periods and two wash-out periods. All periods were 15 d long. Overnight urine free cortisol/ creatinine x 10(6) did not correlate with knemometric growth rates or any of the serum markers. Significant correlations (Pearson's correlation coefficient, P) between knemometric growth rates and IGF-I (0.41; 0.006), IGFBP-3 (0.35; 0.02), PICP (0.44; 0.003), ICTP (0.35; 0.001), and PIIINP (0.46; 0.002) were found. Compared with fluticasone propionate, 200 micrograms, beclomethasone dipropionate, 400 and 800 micrograms, caused significant suppression of lower leg growth rate (F = 12.41; p = 0.002, and F = 23.30; p = 0.0001, respectively) and of urine free cortisol/creatinine x 10(6) (F = 10.52; p = 0.003, and F = 13.74; p = 0.001). Beclomethasone, 800 micrograms, caused suppression of PICP compared with fluticasone propionate, 200 micrograms (F = 8.31; p = 0.008), and beclomethasone, 400 micrograms (F = 7.53; p = 0.01). Both low (F = 6.82; p = 0.02) and high (F = 23.35; p = 0.0001) doses of beclomethasone were associated with reduced concentrations of ICTP, the high dose being the most suppressive (F = 4.42; p = 0.05). Beclomethasone 400 (F = 9.75; p = 0.004) and 800 micrograms (F = 23.61; p = 0.0001) resulted in reduced levels of PIIINP. Reduced short-term knemometric growth rates in children treated with inhaled glucocorticosteroids reflect suppressive effects on type I and type III collagen turnover.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Multicenter Study

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Androstadienes / adverse effects*
  • Anthropometry / methods
  • Anti-Asthmatic Agents / adverse effects*
  • Beclomethasone / adverse effects*
  • Child
  • Collagen / analysis
  • Collagen / drug effects
  • Collagen / metabolism*
  • Double-Blind Method
  • Female
  • Fluticasone
  • Growth / drug effects
  • Humans
  • Hydrocortisone / urine*
  • Insulin-Like Growth Factor I / drug effects
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Osteocalcin / blood

Substances

  • Androstadienes
  • Anti-Asthmatic Agents
  • Osteocalcin
  • Insulin-Like Growth Factor I
  • Collagen
  • Fluticasone
  • Beclomethasone
  • Hydrocortisone