Abstract
Growth suppression is usually most evident during the first year of inhaled steroid therapy. Steroid-induced changes in bone metabolism may contribute to this growth suppression. The aim of the present study was to evaluate the changes in biochemical markers of bone metabolism in relation to adrenal and growth suppression during the initiation phase of inhaled steroid therapy. Seventy-five school-aged children with new asthma were enrolled into budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromone (CROM, n = 15) treatment groups. BUD dose was 800 μg/d during the first two months and 400 μg/d thereafter. The respective FP doses were 500 and 200 μg/d. Biochemical markers of bone metabolism were measured before treatment and after 2 and 4 mo of therapy. In the control (CROM) group, the mean concentrations of serum osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP) (formation markers) and type I collagen carboxyterminal telopeptide (ICTP) (degradation marker) tended to increase. In the BUD group, OC and PICP decreased during the 4 mo by a mean of 23% (p < 0.001) and 15% (p < 0.05), respectively, while ICTP did not change significantly. In the FP group, OC and ICTP decreased during the first 2 mo by a mean of 19% (p < 0.01) and 21% (p < 0.01), respectively, returning to the pretreatment level at 4 mo, while PICP tended to increase during the 4 mo (14%, p = 0.12). In the steroid treated children whose height SD score decreased during the first 12 mo of therapy, both OC and PICP decreased during the first 4 mo by a mean of 20% (p < 0.01) and 21% (p < 0.001), respectively. In those children who had no growth suppression, the changes were not significant: −4% in OC and +13% in PICP. Furthermore, in children who developed evidence of adrenocortical suppression (on the basis of a low-dose ACTH test), OC decreased more (23%, p < 0.01) than in those with normal adrenocortical function (10%, p = 0.06). In conclusion, both inhaled BUD and FP caused dose-dependent effects on biochemical markers of bone metabolism. The children who developed growth or adrenocortical suppression were likely to have changes also in bone metabolism.
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
- BUD:
-
Budesonide
- CROM:
-
Cromones (cromoglycate and nedocromil)
- FEV1:
-
Forced expiratory volume in one second
- FP:
-
Fluticasone propionate
- ICTP:
-
Type I collagen carboxyterminal telopeptide
- OC:
-
Osteocalcin
- PICP:
-
Carboxypropeptide of type I procollagen
References
Agertoft L, Pedersen S 2000 Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 343: 1064–1069
Nicolaizik WH, Marchant JL, Preece MA, Warner JO 1994 Endocrine lung function in asthmatic children on inhaled corticosteroids. Am J Respir Crit Care Med 150: 624–628
Kannisto S, Korppi M, Remes K, Voutilainen R 2000 Adrenal suppression, evaluated by a low-dose ACTH-test, growth in asthmatic children treated with inhaled steroids. J Clin Endocrinol Metab 85: 652–657
Wolthers OD, Pedersen S 1991 Growth of asthmatic children during treatment with budesonide: a double blind trial. BMJ 303: 163–165
Douill IJM, Freezer NJ, Holgate ST 1995 Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate. Am J Respir Crit Care Med 151: 1715–1719
Sorva R, Turpeinen M, Juntunen-Backman K, Karonen S-L, Sorva A 1992 Effect of inhaled budesonide on serum markers of bone metabolism in children with asthma. J Allergy Clin Immunol 90: 808–815
Crowley S, Trivedi P, Risteli L, Risteli J, Hindmarsh PC, Brook CG 1998 Collagen metabolism growth in prepubertal children with asthma treated with inhaled steroids. J Pediatr 132: 409–413
Hahn TJ, Halstead LR, Baran DT 1981 Effects of short term glucocorticoid administration on intestinal calcium absorption circulating vitamin D metabolite concentrations in man. J Clin Endocrinol Metab 52: 111–115
Suzuki Y, Ichikawa Y, Saito E, Homma M 1983 Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy. Metabolism 32: 151–156
Hanania NA, Chapman KR, Sturtridge WC, Szalai JP, Kesten S 1995 Dose-related decrease in bone density among asthmatic patients treated with inhaled corticosteroids. J Allergy Clin Immunol 96: 571–579
Laatikainen AK, Kröger HPJ, Tukiainen HO, Honkanen RJ, Saarikoski SV 1999 Bone mineral density in perimenopausal women with asthma. Am J Respir Crit Care Med 159: 1179–1185
Wong CA, Walsh LJ, Smith CJP, Wisniewski AF, Lewis SA, Hubbard R, Cawte S, Green DJ, Pringle M, Tattersfield AE 2000 Inhaled corticosteroid use bone-mineral density in patients with asthma. Lancet 355: 1399–1403
Holt S, Suder A, Weatherall M, Cheng S, Shirtcliffe P, Beasley R 2001 Dose-response relation of inhaled fluticasone propionate in adolescents adults with asthma: meta-analysis. BMJ 323: 253–256
Lipworth BJ 1999 Systemic adverse effects of inhaled corticosteroid therapy: a systematic review meta-analysis. Arch Intern Med 159: 941–955
Brown JP, Malaval L, Chapuy MC, Delmas PD, Edouard C, Meunier PJ 1984 Serum bone GLA-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet 1: 1091–1093
Delmas PD 1990 Biochemical markers of bone turnover for the clinical assessment of metabolic bone disease. Endocrinol Metab Clin North Am 19: 1–18
Parfitt AM, Simon LS, Villaneuva AR, Krane SM 1987 Procollagen type I carboxy-terminal extension peptide in serum as a marker of collagen biosynthesis in bone: correlation with iliac bone formation rates comparison with total alkaline phosphatase. J Bone Miner Res 2: 427–436
Risteli L, Risteli J 1993 Biochemical markers of bone metabolism. Ann Med 25: 385–393
Sorva R, Tähtelä R, Turpeinen M, Juntunen-Backman K, Haahtela T, Risteli L, Risteli J, Sorva A 1996 Changes in bone markers in children with asthma during inhaled budesonide nedocromil treatments. Acta Paediatr 85: 1176–1180
Risteli J, Elomaa I, Niemi S, Novamo A, Risteli L 1993 Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. Clin Chem 39: 635–640
Högger P, Rohdewald P 1988 Glucocorticoid receptors fluticasone propionate. Rev Contemp Pharmacother 9: 501–522
Ferguson AC, Spier S, Manjra A, Versteegh GA, Mark S, Zhang P 1999 Efficacy safety of high-dose inhaled steroids in children with asthma: a comparison of fluticasone propionate with budesonide. J Pediatr 134: 422–427
Sorva R, Perheentupa J, Tolppanen EM 1984 A novel format for a growth chart. Acta Paediatr Scand 73: 527–529
Crofton PM, Wade JC, Taylor MRH, Holland CV 1997 Serum concentrations of carboxyl-terminal propeptide of type I procollagen, amino-terminal propeptide of type III procollagen, cross-linked carboxyl-terminal telopeptide of type I collagen, their interrelationships in schoolchildren. Clin Chem 43: 1577–1581
Eriksen EF, Brixen K, Charles P 1995 New markers of bone metabolism: clinical use in metabolic bone disease. Eur J Endocrinol 132: 251–263
Birkebaek NH, Esberg G, Andersen K, Wolthers O, Hassager C 1995 Bone collagen turnover during treatment with inhaled dry powder budesonide beclomethasone dipropionate. Arch Dis Child 73: 524–527
Hedlin G, Svedmyr J, Ryden A-C 1999 Systemic effects of a short course of betamethasone compared with high-dose inhaled budesonide in early childhood asthma. Acta Paediatr 88: 48–51
Reilly SM, Hambleton G, Adams JE, Mughal MZ 2001 Bone density in asthmatic children treated with inhaled steroids. Arch Dis Child 84: 183–184
Johansen JS, Giwercman A, Hartwell D, Nielsen CT, Price PA, Christiansen C, Skakkebaek NE 1988 Serum bone Gla-protein as a marker of bone growth in children adolescents: correlation with age, height, serum insulin-like growth factor I, serum testosterone. J Clin Endocrinol Metab 67: 273–278
Trivedi P, Risteli J, Risteli L, Hindmarsh PC, Brook CGD, Mowat AP 1991 Serum concentration of the type I III procollagen propeptides as biochemical markers of growth velocity in healthy infants children in children with growth disorders. Pediatr Res 30: 276–280
Calvo MS, Eyre DR, Gundberg CM 1996 Molecular basis clinical application of biological markers of bone turnover. Endocr Rev 17: 333–368
Hoekx JCM, Hedlin G, Pedersen W, Sorva R, Hollingworth K, Efthimiou J 1996 Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 μg/day. Eur Respir J 9: 2263–2272
König P, Hillman L, Cervantes C, Levine C, Maloney C, Douglass B, Johnson L, Allen S 1993 Bone metabolism in children with asthma treated with inhaled beclomethasone dipropionate. J Pediatr 122: 219–226
Martinati LC, Bertoldo F, Gasperi E, Micelli S, Boner AL 1996 Effect on cortical trabecular bone mass of different anti-inflammatory treatments in preadolescent children with chronic asthma. Am J Respir Crit Care Med 153: 232–236
Martinati LC, Bertoldo F, Gasperi E, Fortunati P, Lo Cascio V, Boner AL 1998 Longitudinal evaluation of bone mass in asthmatic children treated with inhaled beclomethasone dipropionate or cromolyn sodium. Allergy 53: 705–708
Rao R, Gregson RK, Jones AC, Miles EA, Campbell MJ, Warner JO 1999 Systemic effects of inhaled corticosteroids on growth bone turnover in childhood asthma: comparison of fluticasone with beclomethasone. Eur Respir J 13: 87–94
Allen HDW, Thong IG, Clifton-Bligh P, Holmes S, Nery L, Wilson KB 2000 Effects of high-dose inhaled corticosteroids on bone metabolism in prepubertal children with asthma. Pediatr Pulmonol 29: 188–193
Saggese G, Baroncelli GI, Bertelloni S, Cinquanta L, DiNero G 1993 Effects of long-term treatment with growth hormone on bone mineral metabolism in children with growth hormone deficiency. J Pediatr 122: 37–45
Saha MT, Laippala P, Lenko HL 1997 Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids. Acta Paediatr 86: 138–142
Acknowledgements
The study was supported by the Finnish Foundation of Pediatric Research, Academy of Finland, Sigrid Juselius Foundation and Kuopio University Hospital.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kannisto, S., Korppi, M., Arikoski, P. et al. Biochemical Markers of Bone Metabolism in Relation to Adrenocortical and Growth Suppression During the Initiation Phase of Inhaled Steroid Therapy. Pediatr Res 52, 258–262 (2002). https://doi.org/10.1203/00006450-200208000-00019
Issue date:
DOI: https://doi.org/10.1203/00006450-200208000-00019


