Risk of fractures with inhaled corticosteroids in COPD

Systematic review and meta-analysis of randomised controlled trials and observational studies

Yoon K. Loke, Rodrigo Cavallazzi, Sonal Singh

Research output: Contribution to journalArticle

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 I2 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; p2=37%), with each 500 mg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures, OR 1.09 (95% CI 1.06 to 1.12; p

Original languageEnglish (US)
Pages (from-to)699-708
Number of pages10
JournalThorax
Volume66
Issue number8
DOIs
StatePublished - Aug 2011

Fingerprint

Chronic Obstructive Pulmonary Disease
Observational Studies
Meta-Analysis
Adrenal Cortex Hormones
Randomized Controlled Trials
Budesonide
Beclomethasone
Least-Squares Analysis
MEDLINE
Registries
Fluticasone

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Risk of fractures with inhaled corticosteroids in COPD : Systematic review and meta-analysis of randomised controlled trials and observational studies. / Loke, Yoon K.; Cavallazzi, Rodrigo; Singh, Sonal.

In: Thorax, Vol. 66, No. 8, 08.2011, p. 699-708.

Research output: Contribution to journalArticle

@article{a6002176c3f3471883d2e83e44af8519,
title = "Risk of fractures with inhaled corticosteroids in COPD: Systematic review and meta-analysis of randomised controlled trials and observational studies",
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 I2 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; p2=37{\%}), with each 500 mg increase in beclomethasone dose equivalents associated with a 9{\%} increased risk of fractures, OR 1.09 (95{\%} CI 1.06 to 1.12; p",
author = "Loke, {Yoon K.} and Rodrigo Cavallazzi and Sonal Singh",
year = "2011",
month = "8",
doi = "10.1136/thx.2011.160028",
language = "English (US)",
volume = "66",
pages = "699--708",
journal = "Thorax",
issn = "0040-6376",
publisher = "BMJ Publishing Group",
number = "8",

}

TY - JOUR

T1 - Risk of fractures with inhaled corticosteroids in COPD

T2 - Systematic review and meta-analysis of randomised controlled trials and observational studies

AU - Loke, Yoon K.

AU - Cavallazzi, Rodrigo

AU - Singh, Sonal

PY - 2011/8

Y1 - 2011/8

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 I2 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; p2=37%), with each 500 mg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures, OR 1.09 (95% CI 1.06 to 1.12; p

AB - 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 I2 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; p2=37%), with each 500 mg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures, OR 1.09 (95% CI 1.06 to 1.12; p

UR - http://www.scopus.com/inward/record.url?scp=79960568619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960568619&partnerID=8YFLogxK

U2 - 10.1136/thx.2011.160028

DO - 10.1136/thx.2011.160028

M3 - Article

VL - 66

SP - 699

EP - 708

JO - Thorax

JF - Thorax

SN - 0040-6376

IS - 8

ER -