Skip to main content
Top
Published in: Drug Safety 5/2008

01-05-2008 | Original Research Article

Inhaled Corticosteroids and the Risk of Fractures in Older Adults

A Systematic Review and Meta-Analysis

Authors: Dr Mahyar Etminan, Mohsen Sadatsafavi, Saeedreza Ganjizadeh Zavareh, Bahi Takkouche, J. Mark FitzGerald

Published in: Drug Safety | Issue 5/2008

Login to get access

Abstract

Background: Inhaled corticosteroids (ICS) are commonly prescribed medications for the management of asthma and chronic obstructive pulmonary disease. It is well established that long-term use of these drugs may lower bone mineral density. However, whether ICS increase the risk of fractures remains unknown. Recent studies that have attempted to explore this risk have had conflicting results. We sought to explore the risk of ICS and fractures among older adults by conducting a systematic review and meta-analysis of the literature.
Methods: We systematically searched several databases, including MEDLINE, EMBASE and the Cochrane Library, to identify pertinent studies.Those studies that potentially met our inclusion criteria were identified by two reviewers. Relative risks (RRs) were pooled using the random effects model. We also explored dose-response by stratifying the analysis on high and low doses of ICS. Heterogeneity was assessed using the Q statistic and publication bias was assessed using the funnel plot.
Results: Thirteen studies, including four randomized controlled trials, were included in the review. The pooled RRs for hip fractures and any fractures were 0.91 (95% CI 0.87, 0.96) and 1.02 (95% CI 0.96, 1.08), respectively. When we restricted the analysis to users of high-dose ICS, the pooled RRs for any fractures and hip fractures were 1.30 (95% CI 1.07, 1.58) and 1.32 (95% CI 0.90, 1.92), respectively. The funnel plot did not show evidence of publication bias.
Conclusion: We found no association between the use of ICS and fractures in older adults. A slight increase in risk was seen in those using high-dose ICS. The significance of this association should be investigated further.
Literature
1.
go back to reference Viegi G, Scognamiglio S, Baldacci F, et al. Epidemiology of chronic obstructive pulmonary disease (COPD). Respiration 2001; 68: 4–19PubMedCrossRef Viegi G, Scognamiglio S, Baldacci F, et al. Epidemiology of chronic obstructive pulmonary disease (COPD). Respiration 2001; 68: 4–19PubMedCrossRef
2.
go back to reference Buckley NS, Salopeter SR. Systematic review of clinical outcomes in chronic obstructive pulmonary disease: beta-agonist use compared with anticholinergics and inhaled corticosteroids. Clin Rev Allergy Immunol 2006; 31: 210–30 Buckley NS, Salopeter SR. Systematic review of clinical outcomes in chronic obstructive pulmonary disease: beta-agonist use compared with anticholinergics and inhaled corticosteroids. Clin Rev Allergy Immunol 2006; 31: 210–30
3.
go back to reference Motimer KJ, Harrison TW, Tattersfield AE. Effects of inhaled corticosteroids on bone. Ann Allergy Asthma Immunol 2005; 94: 15–21CrossRef Motimer KJ, Harrison TW, Tattersfield AE. Effects of inhaled corticosteroids on bone. Ann Allergy Asthma Immunol 2005; 94: 15–21CrossRef
4.
go back to reference Johnell O, Pauwels R, Lofdahl CG, et al. Bone mineral density in patients with chronic obstructive pulmonary disease treated with budesonide Turbuhaler. Eur Respir J 2002; 19: 1058–63PubMedCrossRef Johnell O, Pauwels R, Lofdahl CG, et al. Bone mineral density in patients with chronic obstructive pulmonary disease treated with budesonide Turbuhaler. Eur Respir J 2002; 19: 1058–63PubMedCrossRef
5.
go back to reference Hubbard RB, Smith CJ, Smeeth L, et al. Inhaled corticosteroids and hip fracture: a population-based case-control study. Am J Respir Crit Care Med 2002; 166: 1563–6PubMedCrossRef Hubbard RB, Smith CJ, Smeeth L, et al. Inhaled corticosteroids and hip fracture: a population-based case-control study. Am J Respir Crit Care Med 2002; 166: 1563–6PubMedCrossRef
6.
go back to reference Lee TA, Weiss KB. Fracture risk associated with inhaled corti-costeroid use in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004; 169: 855–9PubMedCrossRef Lee TA, Weiss KB. Fracture risk associated with inhaled corti-costeroid use in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004; 169: 855–9PubMedCrossRef
7.
go back to reference Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007; 356: 775–89PubMedCrossRef Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007; 356: 775–89PubMedCrossRef
8.
go back to reference Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000 19; 283(15): 2008–12PubMedCrossRef Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000 19; 283(15): 2008–12PubMedCrossRef
9.
go back to reference Moher D, Cook DJ, Eastwood S, et al. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 1999; 354(9193): 1896–900PubMedCrossRef Moher D, Cook DJ, Eastwood S, et al. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 1999; 354(9193): 1896–900PubMedCrossRef
10.
go back to reference Scanlon PD, Connett JE, Wise RA, et al. Lung Health Study Research Group. Loss of bone density with inhaled triamcinolone in Lung Health Study II. Am J Respir Crit Care Med 2004; 170: 1302–9PubMedCrossRef Scanlon PD, Connett JE, Wise RA, et al. Lung Health Study Research Group. Loss of bone density with inhaled triamcinolone in Lung Health Study II. Am J Respir Crit Care Med 2004; 170: 1302–9PubMedCrossRef
11.
go back to reference Pauwels RA, Lofdahl CG, Laitinen LA, et al. 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; 340: 1948–53PubMedCrossRef Pauwels RA, Lofdahl CG, Laitinen LA, et al. 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; 340: 1948–53PubMedCrossRef
12.
go back to reference Suissa S, Baltzan M, Kremer R, et al. Inhaled and nasal corticosteroid use and the risk of fracture. Am J Respir Crit Care Med 2004; 169: 83–8PubMedCrossRef Suissa S, Baltzan M, Kremer R, et al. Inhaled and nasal corticosteroid use and the risk of fracture. Am J Respir Crit Care Med 2004; 169: 83–8PubMedCrossRef
13.
go back to reference Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with systemic and topical corticosteroids. J Intern Med 2005; 257: 374–84PubMedCrossRef Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with systemic and topical corticosteroids. J Intern Med 2005; 257: 374–84PubMedCrossRef
14.
go back to reference Johannes CB, Schneider GA, Dube TJ, et al. The risk of nonvertebral fracture related to inhaled corticosteroid exposure among adults with chronic respiratory disease. Chest 2005; 127: 89–97PubMedCrossRef Johannes CB, Schneider GA, Dube TJ, et al. The risk of nonvertebral fracture related to inhaled corticosteroid exposure among adults with chronic respiratory disease. Chest 2005; 127: 89–97PubMedCrossRef
15.
go back to reference de Vries F, Pouwels S, Lammers JW, et al. Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study. J Intern Med 2007; 261: 170–7PubMed de Vries F, Pouwels S, Lammers JW, et al. Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study. J Intern Med 2007; 261: 170–7PubMed
16.
go back to reference de Vries F, van Staa TP, Bracke MS, et al. Severity of obstructive airway disease and risk of osteoporotic fracture. Eur Respir J 2005; 25: 879–84PubMedCrossRef de Vries F, van Staa TP, Bracke MS, et al. Severity of obstructive airway disease and risk of osteoporotic fracture. Eur Respir J 2005; 25: 879–84PubMedCrossRef
17.
go back to reference Baltzan MA, Suissa S, Bauer DC, et al. Hip fractures attributable to corticosteroid use. Study of Osteoporotic Fractures Group. Lancet 1999; 353: 1327PubMedCrossRef Baltzan MA, Suissa S, Bauer DC, et al. Hip fractures attributable to corticosteroid use. Study of Osteoporotic Fractures Group. Lancet 1999; 353: 1327PubMedCrossRef
18.
go back to reference Lau E, Mamdani M, Tu K. Inhaled or systemic corticosteroids and the risk of hospitalization for hip fracture among elderly women. Am J Med 2003; 114: 142–5PubMedCrossRef Lau E, Mamdani M, Tu K. Inhaled or systemic corticosteroids and the risk of hospitalization for hip fracture among elderly women. Am J Med 2003; 114: 142–5PubMedCrossRef
19.
go back to reference Hubbard R, Tattersfield A, Smith C, et al. Use of inhaled corticosteroids and the risk of fracture. Chest 2006; 130: 1082–8PubMedCrossRef Hubbard R, Tattersfield A, Smith C, et al. Use of inhaled corticosteroids and the risk of fracture. Chest 2006; 130: 1082–8PubMedCrossRef
20.
go back to reference Costa-Bouzas J, Takkouche B, Cadarso-Suarez C, et al. HEpiMA: software for the identification of heterogeneity in meta-analysis. Comput Methods Programs Biomed 2001; 64: 101–7PubMedCrossRef Costa-Bouzas J, Takkouche B, Cadarso-Suarez C, et al. HEpiMA: software for the identification of heterogeneity in meta-analysis. Comput Methods Programs Biomed 2001; 64: 101–7PubMedCrossRef
21.
go back to reference van Staa TP, Leufkens HG, Cooper C. Use of inhaled corticosteroids and risk of fractures. J Bone Miner Res 2001; 16: 581–8PubMedCrossRef van Staa TP, Leufkens HG, Cooper C. Use of inhaled corticosteroids and risk of fractures. J Bone Miner Res 2001; 16: 581–8PubMedCrossRef
22.
go back to reference Fletcher AE, Jones DJ, Bulpitt CJ, et al. The MRC trial of assessment and management of older people in the community: objectives, design and interventions. BMC Health Services Res 2002; 2(1): 1–10CrossRef Fletcher AE, Jones DJ, Bulpitt CJ, et al. The MRC trial of assessment and management of older people in the community: objectives, design and interventions. BMC Health Services Res 2002; 2(1): 1–10CrossRef
23.
go back to reference Tomlinson JE, McMashon AD, Chaudhuri R, et al. Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma. Thorax 2005; 60: 282–7PubMedCrossRef Tomlinson JE, McMashon AD, Chaudhuri R, et al. Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma. Thorax 2005; 60: 282–7PubMedCrossRef
24.
go back to reference Van Staa TP, Leufkens B, Cooper C. Bone loss and inhaled gluccorticoids [letter]. New Engl J Med 2002; 346: 533PubMedCrossRef Van Staa TP, Leufkens B, Cooper C. Bone loss and inhaled gluccorticoids [letter]. New Engl J Med 2002; 346: 533PubMedCrossRef
Metadata
Title
Inhaled Corticosteroids and the Risk of Fractures in Older Adults
A Systematic Review and Meta-Analysis
Authors
Dr Mahyar Etminan
Mohsen Sadatsafavi
Saeedreza Ganjizadeh Zavareh
Bahi Takkouche
J. Mark FitzGerald
Publication date
01-05-2008
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 5/2008
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.2165/00002018-200831050-00005

Other articles of this Issue 5/2008

Drug Safety 5/2008 Go to the issue

Conference Paper

Phytotherapic Compounds