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 μg, and beclomethasone dipropionate, 400 and 800 μg/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 × 106 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 μg, beclomethasone dipropionate, 400 and 800 μg, 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 × 106(F = 10.52; p = 0.003, and F = 13.74;p = 0.001). Beclomethasone, 800 μg, caused suppression of PICP compared with fluticasone propionate, 200 μg (F = 8.31;p = 0.008), and beclomethasone, 400 μg (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 μg (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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- IGFBP-3:
-
IGF binding protein-3
- PICP:
-
carboxy terminal propeptide of type I procollagen
- ICTP:
-
carboxy terminal pyridinoline cross-linked telopeptide of type I procollagen
- PIIINP:
-
amino terminal propeptide of type III procollagen
References
Priftis K, Milner AD, Conway E, Honour JW 1990 Adrenal function in asthma. Arch Dis Child 65: 838–840.
Law CM, Marchant JL, Honour JW, Preece MA, Warner JO 1986 Nocturnal adrenal suppression in asthmatic children taking inhaled beclomethasone dipropionate. Lancet 1: 942:94944
Wolthers OD 1996 Long, intermediate and short term growth studies in asthmatic children treated with inhaled glucocorticosteroids. Eur Respir J 9: 821–827.
Wolthers OD, Pedersen S 1990 Short term linear growth in asthmatic children during treatment with prednisolone. BMJ 301: 145–148.
Wolthers OD, Pedersen S 1991 Growth of asthmatic children during treatment with budesonide: a double blind trial. BMJ 303: 163–165.
Wolthers OD, Pedersen S 1992 Controlled study of linear growth in asthmatic children during treatment with inhaled glucocorticosteroids. Pediatrics 89: 839–842.
Wolthers OD, Riis BJ, Pedersen S 1993 Bone turnover in asthmatic children treated with oral prednisolone or inhaled budesonide. Pediatr Pulmonol 16: 341–346.
Wolthers OD, Juul A, Hansen M, Müller J, Pedersen S 1994 The insulin-like growth factor axis and collagen turnover during prednisolone treatment. Arch Dis Child 71: 409–413.
Wolthers OD, Juul A, Hansen M, Müller J, Pedersen S 1995 The insulin-like growth factor axis and collagen turnover in asthmatic children treated with ihaled budesonide. Acta Paediatr 84: 393–397.
Birkebæk NH, Esberg G, Andersen K, Wolthers OD, Hassager C 1995 Bone and collagen turnover during treatment with inhaled dry powder budesonide and beclomethasone dipropionate. Arch Dis Child 73: 524–527.
Wolthers OD, Heuck C, Ternowitz T, Heickendorff L, Nielsen HK, Frystyk F 1996 The insulin-like growth factor axis and bone and collagen turnover in children with atopic dermatitis treated with topical glucocorticosteroids. Dermatology 192: 337–342.
Hyams JS, Moore RE, Leichtner AM, Carey DE, Goldberg BD 1988 Relationship of type I procollagen to corticosteroid therapy in children with inflammatory bowel disease. J Pediatr 112: 893–898.
Allen DB, Goldberg BD 1992 Stimulation of collagen synthesis and linear growth by growth hormone in glucocorticoid-treated children. Pediatrics 89: 416–421.
Sorva R, Turpeinen M, Juntunen-Backman K, Karonen SL, Sorva A 1992 Effects of inhaled budesonide on serum markers of bone metabolism in children with asthma. J Allergy Clin Immunol 90: 808–815.
Wolthers OD, Pedersen S 1995 Measures of systemic activity of inhaled glucocorticosteroids: a comparison of urine cortisol excretion and knemometry. Respir Med 89: 347–349.
Wolthers OD, Pedersen S 1993 Short term growth during treatment with inhaled fluticasone propionate and beclomethasone dipropionate. Arch Dis Child 68: 673–676.
Tanner JM 1962 Growth at Adolescence. Blackwell, Oxford
Lantto O, Lindbäk B, Damkjaer Nielsen M, Pomöll UM, Björkhem I 1983 Assay of cortisol with a radioimmunoassay method calibrated by isotope dilution-mass spectrometry: a Nordic collaborative study. Scand J Clin Lab Invest 43: 433–437.
Hsu TH, Bledsoe T 1970 Measurements of urinary free corticoids by competitive protein-binding radioassay in hypoadrenal states. J Clin Endocrinol Metab 30: 443–448.
Bang P, Eriksson U, Sara V, Wivall IL, Hall K 1991 Comparison of acid ethanol extraction and acid gel filtration prior to IGF-I and IGF-II radioimmunoassays: Improvement of determinations in acid ethanol extracts by the use of truncated IGF-I as radioligand. Acta Endocrinol 124: 620–629.
Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jørgensen K, Müller Hall K 1994 Serum insulin-like growth factor-I in 1030 healthy children, adolescents and adults, in relation to age, sex, stage of puberty, testicular size and body mass index. J Clin Endocrinol Metab 78: 744–752.
Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeisel HJ, Bierich JR 1990 A specific radioimmunoassay for the growth hormone(GH)-dependent somatomedinbinding protein: its use for diagnosis of GH deficiency. J Clin Endocrinol Metab 90: 1292–1298.
Juul A, Dalgaard P, Blum WF, Bang P, Hall K, Michaelsen KF, Müller J, Skakkebæk NE 1995 Serum levels of insulin-like growth factor (IGF)- binding protein-3 (IGFBP-3) in healthy infants, children and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex body mass index, and pubertal maturation. J Clin Endocrinol Metab 80: 2534–2542.
Nielsen HK, Charles P, Mosekilde L 1988 The effects of single oral doses of prednisone on the circadian rhythm of serum osteocalcin in normal subjects. J Clin Endocrinol Metab 67: 1025–1030.
Melkko J, Niemi S, Risteli L, Risteli J 1990 Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen. Clin Chem 36: 1328–1332.
Risteli J, Eloma I, Niemi S, Novamo A, Risteli L 1993 Radioimmunoassay for the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. Clin Chem 39: 635–640.
Risteli J, Niemi S, Trivedi P, Mäentausta O, Mowat AP, Risteli L 1988 Rapid equilibrium immunoassay for the amino-terminal propeptide of human type III procollagen. Clin Chem 34: 715–718.
Hertel NT, Stoltenberg M, Juul A, Main KM, Muller J, Nielsen CT, Lorenzen I, Skakkebaek NE Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate. J Clin Endocrinol Metab 76: 924–927.
Snedecor GW, Cochran WG 1989 Statistical Methods, 8 Ed. Iowa State University Press, Ames
Leblanc P, Mink S, Keistinen T, Saareleinen PA, Ringdal N, Payne SL 1994 A comparison of fluticasone propionate 200 μg/day with beclomethasone dipropionate 400 μg/day in adult asthma. Allergy 49: 380–385.
Dahl R, Lundbäck B, Malo J-L, Mazza JA, Nieminen MM, Saareleinen P, Barnacle H 1993 A dose-ranging study of fluticasone propionate in adult patients with moderate asthma. Chest 104: 1352–1358.
Bisgaard H, Nielsen MD, Andersen B, Andersen P, Foged N, Fuglsang G, Høst A, Leth C, Pedersen M, Pelck I, Stafanger G, Osterballe O 1988 Adrenal function in children with bronchial asthma treated with beclomethasone dipropionate or budesonide. J Allergy Clin Immunol 81: 1088–1095.
Pedersen S, Fuglsang G 1988 Urine cortisol excretion in children treated with high doses of inhaled corticosteroids: a comparison of budesonide and beclomethasone. Eur Respir J 1: 433–435.
Teelucksingh S, Padfield PL, Tibi L, Gough KJ, Holt PR 1991 Inhaled corticosteroids, bone formation, and osteocalcin. Lancet 338: 60–61.
Masters PW, Jones RG, Purves DA, Cooper EH, Cooney JM 1994 Commercial assays for serum osteocalcin give clinically discordant results. Clin Chem 40: 358–363.
Kucharz EJ 1991 The Collagens: Biochemistry and Pathophysiology. Springer Verlag, Berlin
Eriksen EF, Charles P, Melsen F, Mosekilde L, Risteli L, Risteli J 1993 Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry. J Bone Miner Res 8: 127–132.
Hørslev-Petersen K 1990 Circulating extracellular matrix components as markers for connective tissue response to inflammation. Dissertation, Laegeforeningens Forlag, Copenhagen
Oikarinen A, Autio P, Vuori J, Väänänen K, Risteli K, Kiistala U, Risteli J 1992 Systemic glucocorticoid treatment decreases serum concentrations of carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type III procollagen. Br J Dermatol 126: 172–178.
Wolthers OD, Heuck C, Hansen M, Kollerup G 1995 Bone and collagen turnover in asthmatic adolescents treated with inhaled glucocorticosteroids. Eur Respir J 8: suppl 19 P2316.
Melkko J, Hellevik T, Risteli L, Risteli J, Smedsrod B 1994 Clearance of NH2-terminal propeptides of types I and III procollagen is a physiological function of the scavenger receptor in liver endothelial cells. J Exp Med 179: 405–412.
Smedsrod B, Melkko J, Risteli L, Risteli J 1990 Circulating C-terminal propeptide of type I procollagen is cleared mainly via the mannose receptor in liver endothelial cells. Biochemistry 271: 345–350.
Hansen M, Stoltenberg M, Høst NB, Boesby S, Lorenzen I, Bentsen KD 1995 Glucocorticoids inhibit the synthesis rate of type III collagen, but do not affect the hepatic clearance of its aminoterminal propeptide (PIIINP). Scand J Clin Lab Invest 55: 543–548.
Wolthers OD, Konstantin-Hansen K, Pedersen S, Petersen KE 1992 Knemometry in the assessment of short-term linear growth in a population of healthy school children. Horm Res 37: 156–159.
Acknowledgements
The knemometry data are reproduced by permission from Archives of Disease in Childhood.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wolthers, O., Hansen, M., Juul, A. et al. Knemometry, Urine Cortisol Excretion, and Measures of the Insulin-Like Growth Factor Axis and Collagen Turnover in Children Treated with Inhaled Glucocorticosteroids. Pediatr Res 41, 44–50 (1997). https://doi.org/10.1203/00006450-199701000-00007
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199701000-00007
This article is cited by
-
A Pilot Study of the Normative Range of Overnight Urinary Free Cortisol Corrected for Creatinine in Children
Clinical Drug Investigation (2018)
-
A Review on the Safety and Efficacy of Inhaled Corticosteroids in the Management of Asthma
Pulmonary Therapy (2017)
-
Effects of inhaled corticosteroids on growth in asthmatic children
Current Allergy and Asthma Reports (2001)
