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Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies.
Thorax. 2011 Aug; 66(8):699-708.T

Abstract

BACKGROUND

The effect of inhaled corticosteroids (ICS) on fracture risk in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to evaluate the association between ICS and fractures in COPD.

METHODS

MEDLINE, EMBASE, regulatory documents and company registries were searched up to August 2010. Randomised controlled trials (RCTs) of budesonide or fluticasone versus control treatment for COPD (≥24 weeks duration) and controlled observational studies reporting on fracture risk with ICS exposure vs no exposure in COPD were included. Peto OR meta-analysis was used for fracture risk from RCTs while ORs from observational studies were pooled using the fixed effect inverse variance method. Dose-response analysis was conducted using variance-weighted least squares regression in the observational studies. Heterogeneity was assessed using the I(2) statistic.

RESULTS

Sixteen RCTs (14 fluticasone, 2 budesonide) with 17,513 participants, and seven observational studies (n=69,000 participants) were included in the meta-analysis. ICSs were associated with a significantly increased risk of fractures (Peto OR 1.27; 95% CI 1.01 to 1.58; p=0.04; I(2)=0%) in the RCTs. In the observational studies, ICS exposure was associated with a significantly increased risk of fractures (OR 1.21; 95% CI 1.12 to 1.32; p<0.001; I(2)=37%), with each 500 μg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures, OR 1.09 (95% CI 1.06 to 1.12; p<0.001).

CONCLUSION

Among patients with COPD, long-term exposure to fluticasone and budesonide is consistently associated with a modest but statistically significant increased likelihood of fractures.

Authors+Show Affiliations

School of Medicine, University of East Anglia, Norwich NR4 7TJ, UK. y.loke@uea.ac.ukNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

21602540

Citation

Loke, Yoon K., et al. "Risk of Fractures With Inhaled Corticosteroids in COPD: Systematic Review and Meta-analysis of Randomised Controlled Trials and Observational Studies." Thorax, vol. 66, no. 8, 2011, pp. 699-708.
Loke YK, Cavallazzi R, Singh S. Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies. Thorax. 2011;66(8):699-708.
Loke, Y. K., Cavallazzi, R., & Singh, S. (2011). Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies. Thorax, 66(8), 699-708. https://doi.org/10.1136/thx.2011.160028
Loke YK, Cavallazzi R, Singh S. Risk of Fractures With Inhaled Corticosteroids in COPD: Systematic Review and Meta-analysis of Randomised Controlled Trials and Observational Studies. Thorax. 2011;66(8):699-708. PubMed PMID: 21602540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies. AU - Loke,Yoon K, AU - Cavallazzi,Rodrigo, AU - Singh,Sonal, Y1 - 2011/05/20/ PY - 2011/5/24/entrez PY - 2011/5/24/pubmed PY - 2011/10/4/medline SP - 699 EP - 708 JF - Thorax JO - Thorax VL - 66 IS - 8 N2 - BACKGROUND: The effect of inhaled corticosteroids (ICS) on fracture risk in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to evaluate the association between ICS and fractures in COPD. METHODS: MEDLINE, EMBASE, regulatory documents and company registries were searched up to August 2010. Randomised controlled trials (RCTs) of budesonide or fluticasone versus control treatment for COPD (≥24 weeks duration) and controlled observational studies reporting on fracture risk with ICS exposure vs no exposure in COPD were included. Peto OR meta-analysis was used for fracture risk from RCTs while ORs from observational studies were pooled using the fixed effect inverse variance method. Dose-response analysis was conducted using variance-weighted least squares regression in the observational studies. Heterogeneity was assessed using the I(2) statistic. RESULTS: Sixteen RCTs (14 fluticasone, 2 budesonide) with 17,513 participants, and seven observational studies (n=69,000 participants) were included in the meta-analysis. ICSs were associated with a significantly increased risk of fractures (Peto OR 1.27; 95% CI 1.01 to 1.58; p=0.04; I(2)=0%) in the RCTs. In the observational studies, ICS exposure was associated with a significantly increased risk of fractures (OR 1.21; 95% CI 1.12 to 1.32; p<0.001; I(2)=37%), with each 500 μg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures, OR 1.09 (95% CI 1.06 to 1.12; p<0.001). CONCLUSION: Among patients with COPD, long-term exposure to fluticasone and budesonide is consistently associated with a modest but statistically significant increased likelihood of fractures. SN - 1468-3296 UR - https://www.unboundmedicine.com/medline/citation/21602540/Risk_of_fractures_with_inhaled_corticosteroids_in_COPD:_systematic_review_and_meta_analysis_of_randomised_controlled_trials_and_observational_studies_ L2 - https://thorax.bmj.com/lookup/pmidlookup?view=long&amp;pmid=21602540 DB - PRIME DP - Unbound Medicine ER -