FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 345:941-947 September 27, 2001 Number 13 Next

	Full Text PDF Editorial by Dawson-Hughes, B. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article by Kerwin, E. PubMed Citation

ABSTRACT

Background Inhaled glucocorticoids are the most commonly used medications for the long-term treatment of patients with asthma. Whether long-term therapy with inhaled glucocorticoids reduces bone mass, as oral glucocorticoid therapy does, is controversial. In a three-year prospective study, we examined the relation between the dose of inhaled glucocorticoids and the rate of bone loss in premenopausal women with asthma.

Methods We studied 109 premenopausal women, 18 to 45 years of age, who had asthma and no known conditions that cause bone loss and who were treated with inhaled triamcinolone acetonide (100 µg per puff). We measured bone density by dual-photon absorptiometry at base line, at six months, and at one, two, and three years. Serum osteocalcin and parathyroid hormone and urinary N-telopeptide, cortisol, and calcium excretion were measured serially. We measured inhaled glucocorticoid use by means of monthly diaries, supported by the use of an automated actuator-monitoring device.

Results Inhaled glucocorticoid therapy was associated with a dose-related decline in bone density at both the total hip and the trochanter of 0.00044 g per square centimeter per puff per year of treatment (P=0.01 and P=0.005, respectively). No dose-related effect was noted at the femoral neck or the spine. Even after the exclusion of all women who received oral or parenteral glucocorticoids at any time during the study, there was still an association between the decline in bone density and the number of puffs per year of use. Serum and urinary markers of bone turnover or adrenal function did not predict the degree of bone loss.

Conclusions Inhaled glucocorticoids lead to a dose-related loss of bone at the hip in premenopausal women.

Source Information

From the Department of Medicine, Division of Pulmonary and Critical Care Medicine (E.I., T.R.B.), and the Skeletal Health and Osteoporosis Program, Division of Endocrinology–Hypertension (M.S.L.), Brigham and Women's Hospital and Harvard Medical School; the Departments of Biostatistics (G.M.F.) and Environmental Health (T.V.K.), Harvard School of Public Health; and the Department of Internal Medicine, Harvard Pilgrim Health Care (K.L.) — all in Boston.

Address reprint requests to Dr. Israel at the Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, or at eisrael{at}partners.org.

Full Text of this Article

This article has been cited by other articles:

• Fanta, C. H. (2009). Asthma. NEJM 360: 1002-1014 [Full Text]  
• Kelly, H. W., Van Natta, M. L., Covar, R. A., Tonascia, J., Green, R. P., Strunk, R. C., for the CAMP Research Group, (2008). Effect of Long-term Corticosteroid Use on Bone Mineral Density in Children: A Prospective Longitudinal Assessment in the Childhood Asthma Management Program (CAMP) Study. Pediatrics 122: e53-e61 [Abstract] [Full Text]  
• Kearns, A. E., Khosla, S., Kostenuik, P. J. (2008). Receptor Activator of Nuclear Factor {kappa}B Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease. Endocr. Rev. 29: 155-192 [Abstract] [Full Text]  
• Pujades-Rodriguez, M., Smith, C.J.P., Hubbard, R.B. (2007). Inhaled corticosteroids and the risk of fracture in chronic obstructive pulmonary disease. QJM 100: 509-517 [Abstract] [Full Text]  
• (2007). Treatment of Mild Persistent Asthma. NEJM 356: 2096-2100 [Full Text]  
• Hubbard, R., Tattersfield, A., Smith, C., West, J., Smeeth, L., Fletcher, A. (2006). Use of inhaled corticosteroids and the risk of fracture.. Chest 130: 1082-1088 [Abstract] [Full Text]  
• Swanson, C., Lorentzon, M., Conaway, H. H., Lerner, U. H. (2006). Glucocorticoid Regulation of Osteoclast Differentiation and Expression of Receptor Activator of Nuclear Factor-{kappa}B (NF-{kappa}B) Ligand, Osteoprotegerin, and Receptor Activator of NF-{kappa}B in Mouse Calvarial Bones. Endocrinology 147: 3613-3622 [Abstract] [Full Text]  
• Rideout, C. A., Linden, W., Barr, S. I. (2006). High cognitive dietary restraint is associated with increased cortisol excretion in postmenopausal women.. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 61: 628-633 [Abstract] [Full Text]  
• Gartlehner, G., Hansen, R. A., Carson, S. S., Lohr, K. N. (2006). Efficacy and Safety of Inhaled Corticosteroids in Patients With COPD: A Systematic Review and Meta-Analysis of Health Outcomes. Ann Fam Med 4: 253-262 [Abstract] [Full Text]  
• Adcock, I. M., Ito, K. (2005). Glucocorticoid Pathways in Chronic Obstructive Pulmonary Disease Therapy. Proc Am Thorac Soc 2: 313-319 [Abstract] [Full Text]  
• Chu, E. K., Drazen, J. M. (2005). Asthma: One Hundred Years of Treatment and Onward. Am. J. Respir. Crit. Care Med. 171: 1202-1208 [Abstract] [Full Text]  
• Johannes, C. B., Schneider, G. A., Dube, T. J., Alfredson, T. D., Davis, K. J., Walker, A. M. (2005). The Risk of Nonvertebral Fracture Related to Inhaled Corticosteroid Exposure Among Adults With Chronic Respiratory Disease. Chest 127: 89-97 [Abstract] [Full Text]  
• Scanlon, P. D., Connett, J. E., Wise, R. A., Tashkin, D. P., Madhok, T., Skeans, M., Carpenter, P. C., Bailey, W. C., Buist, A. S., Eichenhorn, M., Kanner, R. E., Weinmann, G., the Lung Health Study Research Group, (2004). Loss of Bone Density with Inhaled Triamcinolone in Lung Health Study II. Am. J. Respir. Crit. Care Med. 170: 1302-1309 [Abstract] [Full Text]  
• Wermers, R. A., Hurley, D. L., Kearns, A. E. (2004). Osteoporosis Associated With Megestrol Acetate. Mayo Clin Proc. 79: 1557-1561 [Abstract]  
• Tattersfield, A. E., Harrison, T. W., Hubbard, R. B., Mortimer, K. (2004). Safety of Inhaled Corticosteroids. Proc Am Thorac Soc 1: 171-175 [Abstract] [Full Text]  
• Visser, M.J., van der Veer, E., Postma, D.S., Arends, L.R., de Vries, T.W., Brand, P.L.P., Duiverman, E.J. (2004). Side-effects of fluticasone in asthmatic children: no effects after dose reduction. Eur Respir J 24: 420-425 [Abstract] [Full Text]  
• Campbell, I A, Douglas, J G, Francis, R M, Prescott, R J, Reid, D M (2004). Five year study of etidronate and/or calcium as prevention and treatment for osteoporosis and fractures in patients with asthma receiving long term oral and/or inhaled glucocorticoids. Thorax 59: 761-768 [Abstract] [Full Text]  
• Sin, D. D., Man, J., Sharpe, H., Gan, W. Q., Man, S. F. P. (2004). Pharmacological Management to Reduce Exacerbations in Adults With Asthma: A Systematic Review and Meta-analysis. JAMA 292: 367-376 [Abstract] [Full Text]  
• Gluck, O., Colice, G. (2004). Recognizing and Treating Glucocorticoid-Induced Osteoporosis in Patients With Pulmonary Diseases. Chest 125: 1859-1876 [Abstract] [Full Text]  
• Lee, T. A., Weiss, K. B. (2004). Fracture Risk Associated with Inhaled Corticosteroid Use in Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 169: 855-859 [Abstract] [Full Text]  
• Kemp, J. P., Osur, S., Shrewsbury, S. B., Herje, N. E., Duke, S. P., Harding, S. M., Faulkner, K., Crim, C. C. (2004). Potential Effects of Fluticasone Propionate on Bone Mineral Density in Patients With Asthma: A 2-Year Randomized, Double-Blind, Placebo-Controlled Trial. Mayo Clin Proc. 79: 458-466 [Abstract]  
• Gourlay, M. L., Brown, S. A. (2004). Clinical Considerations in Premenopausal Osteoporosis. Arch Intern Med 164: 603-614 [Abstract] [Full Text]  
• Purucker, M. E., Rosebraugh, C. J., Zhou, F., Meyer, R. J. (2003). Inhaled Fluticasone Propionate by Diskus in the Treatment of Asthma: A Comparison of the Efficacy of the Same Nominal Dose Given Either Once or Twice a Day. Chest 124: 1584-1593 [Abstract] [Full Text]  
• van Staa, T. P., Leufkens, H. G. M., Cooper, C., Hubbard, R. B., Harrison, T. W., Tattersfield, A. E., Smeeth, L. (2003). Inhaled corticosteroids and hip fracture: Disease or drugs?. Am. J. Respir. Crit. Care Med. 168: 128-129 [Full Text]  
• Adler, R. A., Funkhouser, H. L., Petkov, V. I., Elmore, B. L., Via, P. S., McMurtry, C. T., Adera, T. (2003). Osteoporosis in Pulmonary Clinic Patients: Does Point-of-Care Screening Predict Central Dual-Energy X-ray Absorptiometry?. Chest 123: 2012-2018 [Abstract] [Full Text]  
• Roux, C., Kolta, S., Desfougeres, J.-L., Minini, P., Bidat, E. (2003). Long-Term Safety of Fluticasone Propionate and Nedocromil Sodium on Bone in Children With Asthma. Pediatrics 111: e706-713 [Abstract] [Full Text]  
• Jehle, P. M. (2003). Steroid-induced osteoporosis: how can it be avoided?. Nephrol Dial Transplant 18: 861-864 [Full Text]  
• Price, D B, Hernandez, D, Magyar, P, Fiterman, J, Beeh, K M, James, I G, Konstantopoulos, S, Rojas, R, van Noord, J A, Pons, M, Gilles, L, Leff, J A (2003). Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax 58: 211-216 [Abstract] [Full Text]  
• Sharma, P. K., Malhotra, S., Pandhi, P., Kumar, N. (2003). Effect of Inhaled Steroids on Bone Mineral Density: A Meta-Analysis. J Clin Pharmacol 43: 193-197 [Abstract] [Full Text]  
• Freund, K. M., Dolan, N. C., Nelson, H. D. (2003). Update in Women's Health. ANN INTERN MED 138: 119-127 [Full Text]  
• Hubbard, R. B., Smith, C. J. P., Smeeth, L., Harrison, T. W., Tattersfield, A. E. (2002). Inhaled Corticosteroids and Hip Fracture: A Population-based Case-Control Study. Am. J. Respir. Crit. Care Med. 166: 1563-1566 [Abstract] [Full Text]  
• Buhl, R., Hanf, G., Soler, M., Bensch, G., Wolfe, J., Everhard, F., Champain, K., Fox, H., Thirlwell, J. (2002). The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma. Eur Respir J 20: 1088-1094 [Abstract] [Full Text]  
• Rubin, M. R., Bilezikian, J. P. (2002). The Role of Parathyroid Hormone in the Pathogenesis of Glucocorticoid-Induced Osteoporosis: A Re-Examination of the Evidence. J. Clin. Endocrinol. Metab. 87: 4033-4041 [Full Text]  
• Fitzpatrick, L. A. (2002). Secondary Causes of Osteoporosis. Mayo Clin Proc. 77: 453-468 [Abstract]  
• Kerwin, E., van Staa, T.-P., Leufkens, B., Cooper, C., Glazer, J. L., Israel, E., Fitzmaurice, G. M., LeBoff, M. S. (2002). Bone Loss and Inhaled Glucocorticoids. NEJM 346: 533-535 [Full Text]  
• (2002). Robin Goodfellow. Rheumatology (Oxford) 41: 118-118 [Full Text]  
• (2001). Inhaled Glucocorticoids Reduce BMD in Reproductive-Age Women. JWatch Women's Health 2001: 2-2 [Full Text]  
• Dawson-Hughes, B. (2001). Bone Loss Accompanying Medical Therapies. NEJM 345: 989-991 [Full Text]