Abstract
BACKGROUND—Inhaled corticosteroids are clearly beneficial for patients with asthma of moderate severity, but the risks and benefits of using them in patients with milder asthma are less clear. We have compared the change in bone mineral density over 2 years in adults with mild asthma randomised to receive an inhaled corticosteroid or non-corticosteroid treatment. METHODS—Subjects with mild asthma (mean forced expiratory volume in one second (FEV1) 86% predicted, mean age 35 years, taking β agonists only) were randomised to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for 2 years in a prospective randomised open study in 19 centres in France, New Zealand, Spain, and the UK. The corticosteroid dose was adjusted according to a written self-management plan. The main outcome measure—change in bone mineral density after 6, 12, and 24 months—was measured "blind". Secondary outcomes included lung function, the relation between change in bone density and inhaled steroid dose and change in biochemical markers of bone metabolism. RESULTS—Of 374 subjects randomised, 239 (64%) completed the study and were included in the analysis. The median daily doses of inhaled budesonide (n=87) and beclomethasone (n=74) were 389 µg and 499 µg, respectively. Subjects treated with an inhaled corticosteroid had better asthma control than those in the reference group (n=78). Change in bone mineral density did not differ between the three groups over the 2 years, nor did it correlate with changes in markers of bone metabolism. The mean change in bone mineral density over 2 years in the budesonide, beclomethasone dipropionate, and reference groups was 0.1%, -0.4%, and 0.4% for the lumbar spine and -0.9%, -0.9%, and -0.4% for neck of the femur. Mean daily dose of inhaled steroid was related to reduction in bone mineral density at the lumbar spine but not at the femoral neck. CONCLUSION—In subjects with mild asthma an inhaled corticosteroid provided better asthma control than alternative non-corticosteroid treatment with no difference in change in bone mineral density over 2 years. The relation between dose of inhaled corticosteroid and change in bone density at the lumbar spine may be due to a direct effect of inhaled corticosteroids on bone. Since inhaled steroid dose is also related inversely to lung function, an effect of asthma severity on bone density was also possible.
Full Text
The Full Text of this article is available as a PDF (178.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baraldi E., Bollini M. C., De Marchi A., Zacchello F. Effect of beclomethasone dipropionate on bone mineral content assessed by X-ray densitometry in asthmatic children: a longitudinal evaluation. Eur Respir J. 1994 Apr;7(4):710–714. doi: 10.1183/09031936.94.07040710. [DOI] [PubMed] [Google Scholar]
- Barnes P. J., Pedersen S. Efficacy and safety of inhaled corticosteroids in asthma. Report of a workshop held in Eze, France, October 1992. Am Rev Respir Dis. 1993 Oct;148(4 Pt 2):S1–26. doi: 10.1164/ajrccm/148.4_Pt_2.S1. [DOI] [PubMed] [Google Scholar]
- Boulet L. P., Milot J., Gagnon L., Poubelle P. E., Brown J. Long-term influence of inhaled corticosteroids on bone metabolism and density. Are biological markers predictors of bone loss? Am J Respir Crit Care Med. 1999 Mar;159(3):838–844. doi: 10.1164/ajrccm.159.3.9802096. [DOI] [PubMed] [Google Scholar]
- Efthimiou J., Barnes P. J. Effect of inhaled corticosteroids on bones and growth. Eur Respir J. 1998 May;11(5):1167–1177. doi: 10.1183/09031936.98.11051167. [DOI] [PubMed] [Google Scholar]
- Egan J. J., Maden C., Kalra S., Adams J. E., Eastell R., Woodcock A. A. A randomized, double-blind study comparing the effects of beclomethasone and fluticasone on bone density over two years. Eur Respir J. 1999 Jun;13(6):1267–1275. [PubMed] [Google Scholar]
- Geddes D. M. Inhaled corticosteroids: benefits and risks. Thorax. 1992 Jun;47(6):404–407. doi: 10.1136/thx.47.6.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Genant H. K., Grampp S., Glüer C. C., Faulkner K. G., Jergas M., Engelke K., Hagiwara S., Van Kuijk C. Universal standardization for dual x-ray absorptiometry: patient and phantom cross-calibration results. J Bone Miner Res. 1994 Oct;9(10):1503–1514. doi: 10.1002/jbmr.5650091002. [DOI] [PubMed] [Google Scholar]
- Haahtela T., Järvinen M., Kava T., Kiviranta K., Koskinen S., Lehtonen K., Nikander K., Persson T., Reinikainen K., Selroos O. Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. N Engl J Med. 1991 Aug 8;325(6):388–392. doi: 10.1056/NEJM199108083250603. [DOI] [PubMed] [Google Scholar]
- Hughes J. A., Conry B. G., Male S. M., Eastell R. 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. 1999 Mar;54(3):223–229. doi: 10.1136/thx.54.3.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Juniper E. F., Svensson K., O'Byrne P. M., Barnes P. J., Bauer C. A., Löfdahl C. G., Postma D. S., Pauwels R. A., Tattersfield A. E., Ullman A. Asthma quality of life during 1 year of treatment with budesonide with or without formoterol. Eur Respir J. 1999 Nov;14(5):1038–1043. doi: 10.1183/09031936.99.14510389. [DOI] [PubMed] [Google Scholar]
- Malo J. L., Cartier A., Ghezzo H., Mark S., Brown J., Laviolette M., Boulet L. P. Skin bruising, adrenal function and markers of bone metabolism in asthmatics using inhaled beclomethasone and fluticasone. Eur Respir J. 1999 May;13(5):993–998. doi: 10.1034/j.1399-3003.1999.13e11.x. [DOI] [PubMed] [Google Scholar]
- Pauwels R. A., Löfdahl C. G., Laitinen L. A., Schouten J. P., Postma D. S., Pride N. B., Ohlsson S. V. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med. 1999 Jun 24;340(25):1948–1953. doi: 10.1056/NEJM199906243402503. [DOI] [PubMed] [Google Scholar]
- Pauwels R. A., Löfdahl C. G., Postma D. S., Tattersfield A. E., O'Byrne P., Barnes P. J., Ullman A. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med. 1997 Nov 13;337(20):1405–1411. doi: 10.1056/NEJM199711133372001. [DOI] [PubMed] [Google Scholar]
- Quanjer P. H., Tammeling G. J., Cotes J. E., Pedersen O. F., Peslin R., Yernault J. C. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5–40. [PubMed] [Google Scholar]
- Smith R. Corticosteroids and osteoporosis. Thorax. 1990 Aug;45(8):573–578. doi: 10.1136/thx.45.8.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Toogood J. H., Hodsman A. B., Fraher L. J., Markov A. E., Baskerville J. C. Serum osteocalcin and procollagen as markers for the risk of osteoporotic fracture in corticosteroid-treated asthmatic adults. J Allergy Clin Immunol. 1999 Oct;104(4 Pt 1):769–774. doi: 10.1016/s0091-6749(99)70286-1. [DOI] [PubMed] [Google Scholar]
- Wong C. A., Walsh L. J., Smith C. J., Wisniewski A. F., Lewis S. A., Hubbard R., Cawte S., Green D. J., Pringle M., Tattersfield A. E. Inhaled corticosteroid use and bone-mineral density in patients with asthma. Lancet. 2000 Apr 22;355(9213):1399–1403. doi: 10.1016/S0140-6736(00)02138-3. [DOI] [PubMed] [Google Scholar]