Joram S. Seggev, MD, FAAAAI, FACAAI, FACP
In patients with chronic obstructive pulmonary disease (COPD), is long-term use of inhaled corticosteroids (ICSs) associated with increased risk for fractures?
Included studies were randomized controlled trials (RCTs) that compared fluticasone (FLU) or budesonide (BUD) with control, or an ICS and a long-acting β2-agonist (LABA) with LABA alone, in patients with COPD, and reported fractures. Observational studies that compared any ICS exposure with no ICS exposure in patients with COPD and reported odds ratios or data that enabled calculation of odds ratios for fractures were also included. Studies that assessed ICS use in acute exacerbations of COPD, those that included patients with other diseases but did not separately report outcomes for patients with COPD, and those with follow-up < 24 weeks were excluded.
MEDLINE and EMBASE/Excerpta Medica (to Aug 2010), Web sites of the US Food and Drug Administration, European regulatory authorities, manufacturers' clinical trials register of FLU and BUD, and bibliographies of included studies and Cochrane systematic reviews were searched for parallel-group RCTs or controlled observational studies. 16 RCTs (n = 17 513, mean age 52 to 66 y, 51% to 99% men) with a mean duration of 90 weeks and 7 observational studies (n = 69 000), including 5 nested case–control studies and 2 cross-sectional studies, met the selection criteria.
Meta-analysis of RCTs showed that overall ICSs increased risk for fractures; this difference was not significant when ICSs plus LABAs were compared with LABAs alone or when ICSs alone were compared with placebo (Table). Meta-analysis of observational studies showed an increase in fractures in patients who were current (odds ratio [OR] 1.3, 95% CI 1.1 to 1.4), recent (OR 1.2, CI 1.1 to 1.4), or current/ever (OR 1.2, CI 1.1 to 1.3) users of ICSs.
In patients with chronic obstructive pulmonary disease, long-term use of inhaled corticosteroids increases risk for fractures.
*LABA = long-acting β2-agonist; other abbreviations defined in Glossary. Weighted intervention event rates, RRI, NNH, and CI calculated from data in article using a fixed-effect model.
Joram S. Seggev. Review: Long-term use of inhaled corticosteroids increases fracture risk in COPD. Ann Intern Med. 2012;156:JC3–7. doi: 10.7326/0003-4819-156-6-201202210-02007
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Published: Ann Intern Med. 2012;156(6):JC3-7.
Chronic Obstructive Airway Disease, Pulmonary/Critical Care.
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