title: Knemometry, urine cortisol excretion, and measures of the insulin-like growth factor axis and collagen turnover in children treated with inhaled glucocorticosteroids.
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.
authors.affiliation: Department of Paediatrics, Kolding Hospital, Denmark.
authors.forename: O D
authors.initials: OD
authors.lastname: Wolthers
authors.forename: M
authors.initials: M
authors.lastname: Hansen
authors.forename: A
authors.initials: A
authors.lastname: Juul
authors.forename: H K
authors.initials: HK
authors.lastname: Nielsen
authors.forename: S
authors.initials: S
authors.lastname: Pedersen
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000730:Androstadienes / Q000009:adverse effects*; D000886:Anthropometry / Q000379:methods; D018927:Anti-Asthmatic Agents / Q000009:adverse effects*; D001507:Beclomethasone / Q000009:adverse effects*; D002648:Child; D003094:Collagen / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D006128:Growth / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D015675:Osteocalcin / Q000097:blood
chemical_list: D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D000068298:Fluticasone; D001507:Beclomethasone; D006854:Hydrocortisone