Journal of Clinical Endocrinology & Metabolism, Vol 72, 530-540, Copyright © 1991 by Endocrine Society

ARTICLES

Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin

AB Hodsman, JH Toogood, B Jennings, LJ Fraher and JC Baskerville
Lawson Research Institute, St. Joseph's Health Centre, London, Ontario, Canada.

Inhaled glucocorticosteroids have been developed for the treatment of asthma in an attempt to minimize the suppression of endogenous adrenal function that complicates oral or injected steroid usage, but it is unclear whether this strategy leads to reduced systemic complications in other areas, such as the skeleton. In this study we evaluated serum osteocalcin levels as a marker of skeletal metabolism in healthy volunteers treated with oral and inhaled steroids alone and in response to an oral calcitriol stimulation test. Forty subjects, aged 33 +/- 9 (mean +/- SD) yr were randomized to receive either high or low dose oral prednisolone (40 vs. 10 mg/day) or inhaled budesonide (3.2 vs. 0.8 mg/day). Each dose of budesonide is known to have a greater antiasthmatic potency than the dose of prednisolone with which it was compared. In addition 10 control subjects received placebos containing no active steroid drugs. During the second week of treatment, half of the subjects in each of the 4 steroid-treated groups and all subjects in the control group received oral calcitriol (2.0 micrograms/day). There was a marked dose-dependent reduction in serum cortisol levels, but this reduction was significantly less pronounced during budesonide treatment, such that low dose budesonide was without effect. During the first week of steroid therapy there were significant dose-dependent reductions in serum osteocalcin (P = 0.003), but this reduction was not significantly different between budesonide and prednisolone treatments. In response to calcitriol, serum osteocalcin increased by 35% in the control group (P = 0.06). Osteocalcin levels increased by 56% and 50% in the low dose budesonide and prednisolone groups and by 106% in the high dose budesonide group, but did not change in the high dose prednisolone group. The osteocalcin response to calcitriol was significantly higher in the budesonide groups (P = 0.03, by analysis of variance). High dose prednisolone caused increases in serum 1,25- dihydroxyvitamin D3 (P less than 0.02), urinary calcium excretion (P = 0.07), and urinary hydroxyproline (P less than 0.01). None of these changes was seen during budesonide therapy. There are as yet no data for these variables after long term use of inhaled budesonide in asthmatic patients, but our acute studies suggest that this potent topical glucocorticoid may have considerably less impact on the skeleton than oral prednisolone, even if used at doses high enough to suppress endogenous adrenal function.

This article has been cited by other articles:

				K. E. Scholz-Ahrens, G. Delling, B. Stampa, A. Helfenstein, H.-J. Hahne, Y. Acil, W. Timm, R. Barkmann, J. Hassenpflug, J. Schrezenmeir, et al. Glucocorticosteroid-induced osteoporosis in adult primiparous Gottingen miniature pigs: effects on bone mineral and mineral metabolism Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E385 - E395. [Abstract] [Full Text] [PDF]

				Y. Kikuchi, T. Imakiire, M. Yamada, T. Saigusa, T. Hyodo, T. Kushiyama, K. Higashi, N. Hyodo, K. Yamamoto, S. Suzuki, et al. Effect of risedronate on high-dose corticosteroid-induced bone loss in patients with glomerular disease Nephrol. Dial. Transplant., June 1, 2007; 22(6): 1593 - 1600. [Abstract] [Full Text] [PDF]

				A.A. Ionescu and E. Schoon Osteoporosis in chronic obstructive pulmonary disease Eur. Respir. J., November 2, 2003; 22(46_suppl): 64s - 75s. [Abstract] [Full Text] [PDF]

				D. M. Biskobing COPD and Osteoporosis Chest, February 1, 2002; 121(2): 609 - 620. [Abstract] [Full Text] [PDF]

				T W Harrison, A Wisniewski, J Honour, and A E Tattersfield Comparison of the systemic effects of fluticasone propionate and budesonide given by dry powder inhaler in healthy and asthmatic subjects Thorax, March 1, 2001; 56(3): 186 - 191. [Abstract] [Full Text]

				T C Medici, E Grebski, M Häcki, P Rüegsegger, C Maden, and J Efthimiou Effect of one year treatment with inhaled fluticasone propionate or beclomethasone dipropionate on bone density and bone metabolism: a randomised parallel group study in adult asthmatic subjects Thorax, May 1, 2000; 55(5): 375 - 382. [Abstract] [Full Text]

				M. F. Goldstein, J. J. Fallon Jr, and R. Harning Chronic Glucocorticoid Therapy-Induced Osteoporosis in Patients With Obstructive Lung Disease* Chest, December 1, 1999; 116(6): 1733 - 1749. [Abstract] [Full Text] [PDF]

				B. J. Lipworth Systemic Adverse Effects of Inhaled Corticosteroid Therapy: A Systematic Review and Meta-analysis Arch Intern Med, May 10, 1999; 159(9): 941 - 955. [Abstract] [Full Text] [PDF]

				J A Hughes, B G Conry, S M Male, and R Eastell One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density Thorax, March 1, 1999; 54(3): 223 - 229. [Abstract] [Full Text]