Skip to main content
Thorax logoLink to Thorax
. 1997 Oct;52(10):853–860. doi: 10.1136/thx.52.10.853

Cross sectional investigation of the effects of inhaled corticosteroids on bone density and bone metabolism in patients with asthma

A F Wisniewski, S A Lewis, D J Green, W Maslanka, H Burrell, A E Tattersfield
PMCID: PMC1758420  PMID: 9404371

Abstract

BACKGROUND: Bone mineral density has been reduced in patients with asthma taking inhaled corticosteroids in some cross sectional studies and this could be important if treatment is continued for several decades. The possibility of confounding by age, menopausal status, physical activity and, especially, past oral steroid use has not been excluded in most studies. The present study was designed to assess the magnitude of any reduction in bone mineral density in relation to inhaled steroid use after adjusting for these factors. METHODS: Bone mineral density (BMD), vertebral fractures, and markers of bone metabolism (serum osteocalcin, procollagen peptide I, bone-specific alkaline phosphatase, and urinary deoxypyridinoline cross links) were measured in 81 patients with asthma age 20-40 years; 34 patients (19 men) who had never had inhaled or systemic steroids and 47 (19 men) who had taken inhaled steroids for at least five years with limited exposure to systemic steroids in the past. Data relating to past medication use, physical activity, smoking, and other confounding factors were collected by questionnaire. The relation between inhaled steroid dose and duration and BMD was assessed by linear regression analysis, accounting for potential confounders including weight, exercise, and oral steroid use. RESULTS: The 47 patients taking an inhaled steroid had a mean current dose of 620 micrograms/day (range 100-3000 micrograms), a mean duration of use of 7.8 years, and had had a mean of 0.85 courses of prednisolone in the past. There was no significant difference in mean BMD values between those who were and those who were not on inhaled steroids in men or women. However, on multivariate analysis, cumulative inhaled steroid dose was associated with a reduction in posterior-anterior (P-A) and lateral lumbar spine bone mineral density in women, equivalent to a 0.11 standard deviation reduction in bone density per 1000 micrograms/day inhaled steroid per year after adjustment for potential confounding factors (95% CI for P-A spine 0.01 to 0.22; for lateral spine 0.02 to 0.21). Previous oral steroid use was not an important confounding factor in these patients. Inhaled steroid use was not related to BMD at the wrist or hip in women or at any skeletal site in men. Women taking an inhaled steroid had lower levels of serum osteocalcin than those not taking them, although this was not dose related. Inhaled steroid use was not associated with differences in other markers of bone metabolism in men or women or with the presence of vertebral fractures. CONCLUSIONS: Although an effect of confounding factors cannot be excluded entirely in a cross sectional study, our findings are in keeping with an effect of inhaled steroid therapy in reducing bone density in the spine in women and provide an estimate of the magnitude of this effect. 




Full Text

The Full Text of this article is available as a PDF (162.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balfour-Lynn L. Growth and childhood asthma. Arch Dis Child. 1986 Nov;61(11):1049–1055. doi: 10.1136/adc.61.11.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Boulet L. P., Giguère M. C., Milot J., Brown J. Effects of long-term use of high-dose inhaled steroids on bone density and calcium metabolism. J Allergy Clin Immunol. 1994 Nov;94(5):796–803. doi: 10.1016/0091-6749(94)90145-7. [DOI] [PubMed] [Google Scholar]
  4. Carter D. R., Orr T. E. Skeletal development and bone functional adaptation. J Bone Miner Res. 1992 Dec;7 (Suppl 2):S389–S395. doi: 10.1002/jbmr.5650071405. [DOI] [PubMed] [Google Scholar]
  5. Dalsky G. P. Exercise: its effect on bone mineral content. Clin Obstet Gynecol. 1987 Dec;30(4):820–832. doi: 10.1097/00003081-198712000-00006. [DOI] [PubMed] [Google Scholar]
  6. Eastell R., Cedel S. L., Wahner H. W., Riggs B. L., Melton L. J., 3rd Classification of vertebral fractures. J Bone Miner Res. 1991 Mar;6(3):207–215. doi: 10.1002/jbmr.5650060302. [DOI] [PubMed] [Google Scholar]
  7. Gibson P. G., Henry R. L., Vimpani G. V., Halliday J. Asthma knowledge, attitudes, and quality of life in adolescents. Arch Dis Child. 1995 Oct;73(4):321–326. doi: 10.1136/adc.73.4.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hanania N. A., Chapman K. R., Sturtridge W. C., Szalai J. P., Kesten S. Dose-related decrease in bone density among asthmatic patients treated with inhaled corticosteroids. J Allergy Clin Immunol. 1995 Nov;96(5 Pt 1):571–579. doi: 10.1016/s0091-6749(95)70254-7. [DOI] [PubMed] [Google Scholar]
  9. Ip M., Lam K., Yam L., Kung A., Ng M. Decreased bone mineral density in premenopausal asthma patients receiving long-term inhaled steroids. Chest. 1994 Jun;105(6):1722–1727. doi: 10.1378/chest.105.6.1722. [DOI] [PubMed] [Google Scholar]
  10. James V. H., Munro D. D., Feiwel M. Pituitary-adrenal function after occlusive topical therapy with betamethasone-17-valerate. Lancet. 1967 Nov 18;2(7525):1059–1061. doi: 10.1016/s0140-6736(67)90336-4. [DOI] [PubMed] [Google Scholar]
  11. Jennings B. H., Andersson K. E., Johansson S. A. Assessment of systemic effects of inhaled glucocorticosteroids: comparison of the effects of inhaled budesonide and oral prednisolone on adrenal function and markers of bone turnover. Eur J Clin Pharmacol. 1991;40(1):77–82. doi: 10.1007/BF00315143. [DOI] [PubMed] [Google Scholar]
  12. Kerstjens H. A., Postma D. S., van Doormaal J. J., van Zanten A. K., Brand P. L., Dekhuijzen P. N., Koëter G. H. Effects of short-term and long-term treatment with inhaled corticosteroids on bone metabolism in patients with airways obstruction. Dutch CNSLD Study Group. Thorax. 1994 Jul;49(7):652–656. doi: 10.1136/thx.49.7.652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kinberg K. A., Hopp R. J., Biven R. E., Gallagher J. C. Bone mineral density in normal and asthmatic children. J Allergy Clin Immunol. 1994 Sep;94(3 Pt 1):490–497. doi: 10.1016/0091-6749(94)90205-4. [DOI] [PubMed] [Google Scholar]
  14. König P., Hillman L., Cervantes C., Levine C., Maloney C., Douglass B., Johnson L., Allen S. Bone metabolism in children with asthma treated with inhaled beclomethasone dipropionate. J Pediatr. 1993 Feb;122(2):219–226. doi: 10.1016/s0022-3476(06)80116-2. [DOI] [PubMed] [Google Scholar]
  15. Leech J. A., Hodder R. V., Ooi D. S., Gay J. Effects of short-term inhaled budesonide and beclomethasone dipropionate on serum osteocalcin in premenopausal women. Am Rev Respir Dis. 1993 Jul;148(1):113–115. doi: 10.1164/ajrccm/148.1.113. [DOI] [PubMed] [Google Scholar]
  16. Marshall D. H., Crilly R., Nordin B. E. The relation between plasma androstenedione and oestrone levels in untreated and corticosteroid-treated post-menopausal women. Clin Endocrinol (Oxf) 1978 Nov;9(5):407–412. doi: 10.1111/j.1365-2265.1978.tb03580.x. [DOI] [PubMed] [Google Scholar]
  17. Martinati L. C., Bertoldo F., Gasperi E., Micelli S., Boner A. L. Effect on cortical and trabecular bone mass of different anti-inflammatory treatments in preadolescent children with chronic asthma. Am J Respir Crit Care Med. 1996 Jan;153(1):232–236. doi: 10.1164/ajrccm.153.1.8542121. [DOI] [PubMed] [Google Scholar]
  18. Meeran K., Hattersley A., Burrin J., Shiner R., Ibbertson K. Oral and inhaled corticosteroids reduce bone formation as shown by plasma osteocalcin levels. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):333–336. doi: 10.1164/ajrccm.151.2.7842187. [DOI] [PubMed] [Google Scholar]
  19. Packe G. E., Douglas J. G., McDonald A. F., Robins S. P., Reid D. M. Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids. Thorax. 1992 Jun;47(6):414–417. doi: 10.1136/thx.47.6.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pocock N. A., Eisman J. A., Dunstan C. R., Evans R. A., Thomas D. H., Huq N. L. Recovery from steroid-induced osteoporosis. Ann Intern Med. 1987 Sep;107(3):319–323. doi: 10.7326/0003-4819-107-2-319. [DOI] [PubMed] [Google Scholar]
  21. Pouw E. M., Prummel M. F., Oosting H., Roos C. M., Endert E. Beclomethasone inhalation decreases serum osteocalcin concentrations. BMJ. 1991 Mar 16;302(6777):627–628. doi: 10.1136/bmj.302.6777.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Power M. J., Fottrell P. F. Osteocalcin: diagnostic methods and clinical applications. Crit Rev Clin Lab Sci. 1991;28(4):287–335. doi: 10.3109/10408369109106867. [DOI] [PubMed] [Google Scholar]
  23. Reid D. M., Nicoll J. J., Smith M. A., Higgins B., Tothill P., Nuki G. Corticosteroids and bone mass in asthma: comparisons with rheumatoid arthritis and polymyalgia rheumatica. Br Med J (Clin Res Ed) 1986 Dec 6;293(6560):1463–1466. doi: 10.1136/bmj.293.6560.1463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rizzato G., Montemurro L. Reversibility of exogenous corticosteroid-induced bone loss. Eur Respir J. 1993 Jan;6(1):116–119. [PubMed] [Google Scholar]
  25. Rosenthal D. I., Mayo-Smith W., Hayes C. W., Khurana J. S., Biller B. M., Neer R. M., Klibanski A. Age and bone mass in premenopausal women. J Bone Miner Res. 1989 Aug;4(4):533–538. doi: 10.1002/jbmr.5650040412. [DOI] [PubMed] [Google Scholar]
  26. Rüegsegger P., Medici T. C., Anliker M. Corticosteroid-induced bone loss. A longitudinal study of alternate day therapy in patients with bronchial asthma using quantitative computed tomography. Eur J Clin Pharmacol. 1983;25(5):615–620. doi: 10.1007/BF00542348. [DOI] [PubMed] [Google Scholar]
  27. Sowers M. R., Clark M. K., Hollis B., Wallace R. B., Jannausch M. Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss. J Bone Miner Res. 1992 Jun;7(6):647–657. doi: 10.1002/jbmr.5650070609. [DOI] [PubMed] [Google Scholar]
  28. Sowers M. R., Galuska D. A. Epidemiology of bone mass in premenopausal women. Epidemiol Rev. 1993;15(2):374–398. doi: 10.1093/oxfordjournals.epirev.a036126. [DOI] [PubMed] [Google Scholar]
  29. Toogood J. H., Baskerville J. C., Markov A. E., Hodsman A. B., Fraher L. J., Jennings B., Haddad R. G., Drost D. Bone mineral density and the risk of fracture in patients receiving long-term inhaled steroid therapy for asthma. J Allergy Clin Immunol. 1995 Aug;96(2):157–166. doi: 10.1016/s0091-6749(95)70003-x. [DOI] [PubMed] [Google Scholar]
  30. Wolff A. H., Adelsberg B., Aloia J., Zitt M. Effect of inhaled corticosteroid on bone density in asthmatic patients: a pilot study. Ann Allergy. 1991 Aug;67(2 Pt 1):117–121. [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES