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. 2025 Jun 6:12:1503475.
doi: 10.3389/fmed.2025.1503475. eCollection 2025.

Evaluating inhaled corticosteroids' impact on osteoporosis and fracture risk in COPD patients: a real-world evidence-based systematic review and meta-analysis

Hsiao-Feng Huang #  1 , Chin-Wei Hsu #  2   3   4 , Fei-Ting Hsieh  1 , Kuang-Ming Liao  5   6
Affiliations

Evaluating inhaled corticosteroids' impact on osteoporosis and fracture risk in COPD patients: a real-world evidence-based systematic review and meta-analysis

Hsiao-Feng Huang et al. Front Med (Lausanne). .

Abstract

Background: The impact of current inhaled corticosteroid (ICS) therapies on fracture risk in patients with chronic obstructive pulmonary disease (COPD) remains uncertain.

Objective: This study conducts a systematic review and meta-analysis to assess the risk of fractures associated with ICS use over at least 4 years, synthesizing evidence from observational studies conducted in real-world settings among individuals with COPD.

Methods: We systematically searched PubMed, EMBASE, Scopus, and Web of Science from inception to April 21, 2025. Inclusion criteria encompassed studies conducted in COPD patients, evaluating interventions involving ICS-containing treatments compared to alternatives or no ICS use, using cohort or case-control designs, and reporting outcomes related to osteoporosis or fractures. Pooled odds ratios (OR) and hazard ratios (HR) were calculated using random-effects models. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity.

Results: Nine studies (six case-control, three cohort) were included. The pooled OR from case-control studies was 1.03 (95% CI: 0.99-1.08; I 2 = 50%), and the pooled HR from cohort studies was 0.95 (95% CI: 0.67-1.33; I 2 = 86%). Subgroup analyses indicated a potential increased risk in Asian and European populations but not in North America. Meta-regression revealed that higher oral corticosteroids exposure was significantly associated with increased risk (p = 0.005, R 2 = 100%).

Conclusions: Although ICS did not significantly impact osteoporosis or fracture risk, these are common comorbidities in COPD patients. Methodological differences, such as study design, outcome definitions, and oral corticosteroids use, may influence result interpretation and contribute to heterogeneity, limiting study comparability.

Keywords: chronic obstructive pulmonary disease; fracture; inhaled corticosteroids; meta-analysis; osteoporosis; systematic review.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study selection process of the systematic review and meta-analysis.
Figure 2
Figure 2
Forest plot of case-control studies examining the association between inhaled corticosteroids (ICS) and the risk of fractures or osteoporosis.
Figure 3
Figure 3
Forest plot of cohort studies using Cox proportional hazard regression assessing ICS-related fracture or osteoporosis risk.
Figure 4
Figure 4
Subgroup analysis by outcome definition: osteoporosis, any fracture, hip or upper extremity fracture and non-vertebral fracture.
Figure 5
Figure 5
Subgroup analysis by geographic region of included studies.
Figure 6
Figure 6
Meta-regression analysis examining the association between study-level oral corticosteroid exposure prevalence and ICS-related fracture or osteoporosis risk.
Figure 7
Figure 7
Meta-regression analysis examining the association between study-level bisphosphonate exposure prevalence and ICS-related fracture or osteoporosis risk.
See this image and copyright information in PMC

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References

    1. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. (2007) 356:775–89. 10.1056/NEJMoa063070 - DOI - PubMed
    1. Vestbo J, Anderson JA, Brook RD, Calverley PM, Celli BR, Crim C, et al. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet. (2016) 387:1817–26. 10.1016/S0140-6736(16)30069-1 - DOI - PubMed
    1. Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler vs. long- acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. (2012) 9:CD006829. 10.1002/14651858.CD006829.pub2 - DOI - PMC - PubMed
    1. Nannini LJ, Poole P, Milan SJ, Kesterton A. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler vs. inhaled corticosteroids alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. (2013) 8:CD006826. 10.1002/14651858.CD006826.pub2 - DOI - PMC - PubMed
    1. Calverley PMA, Anderson JA, Brook RD, Crim C, Gallot N, Kilbride S, et al. Fluticasone furoate, vilanterol, and lung function decline in patients with moderate chronic obstructive pulmonary disease and heightened cardiovascular risk. Am J Respir Crit Care Med. (2018) 197:47–55. 10.1164/rccm.201610-2086OC - DOI - PubMed

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