Long-term use of inhaled glucocorticoids in patients with stable chronic obstructive pulmonary disease and risk of bone fractures: a narrative review of the literature

Abstract

Patients with chronic obstructive pulmonary disease (COPD) demonstrate a greater osteoporosis prevalence than the general population. This osteoporosis risk may be enhanced by treatment with inhaled corticosteroids (ICSs), which are recommended for COPD management when combined with long-acting bronchodilators, but may also be associated with reduced bone mineral density (BMD). We conducted a narrative literature review reporting results of randomized controlled trials (RCTs) of an ICS versus placebo over a treatment period of at least 12 months, with the aim of providing further insight into the link between bone fractures and ICS therapy. As of 16 October 2017, we identified 17 RCTs for inclusion. The ICSs studied were budesonide (six studies), fluticasone propionate (five studies), mometasone furoate (three studies), beclomethasone dipropionate, triamcinolone acetonide, and fluticasone furoate (one each). We found no difference in the number of bone fractures among patients receiving ICSs versus placebo across the six identified RCTs reporting fracture data. BMD data were available for subsets of patients in few studies, and baseline BMD data were rare; where these data were given, they were reported for treatment groups without stratification for factors known to affect BMD. Risk factors for reduced BMD and fractures, such as smoking and physical activity, were also often not reported. Furthermore, a standardized definition of the term “fracture” was not employed across these studies. The exact relationship between long-term ICS use and bone fracture incidence in patients with stable COPD remains unclear in light of our review. We have, however, identified several limiting factors in existing studies that may form the basis of future RCTs designed specifically to explore this relationship.

Keywords:

• COPD
• inhaled corticosteroids
• osteoporosis
• fracture risk

Abbreviation list

BMD, bone mineral density; CI, confidence interval; COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; IL, interleukin; LABA, long-acting β2-adrenergic agonist; LAMA, long-acting muscarinic antagonist; RCT, randomized controlled trial; TNF, tumor necrosis factor.

Acknowledgments

Writing assistance for this manuscript was provided by Matthew Hallam, MSc(Res), of Gardiner-Caldwell Communications, an Ashfield Healthcare Communications company, part of UDG Healthcare plc, which was funded by GlaxoSmithKline plc (GSK) in compliance with Good Publication Practice 3 ethical guidelines (Battisti et al Ann Intern Med 2015; 163:461–4). The authors would like to thank Maria Sandra Magnoni for her contributions to documenting the methodology followed in conducting this review, and both Fabio Arpinelli and Maria Sandra Magnoni for their identification of studies for inclusion. The paper was prepared using published data. The authors have not received any fee.

Author contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

FA is an employee of GSK and owns stock in GSK. LS was an employee of GSK at the time of preparation of the manuscript. GC reports grants, personal fees, and non-financial support from Astra Zeneca, Boehringer Ingelheim, GSK, and Menarini Group, and grants from AlfaSigma, outside the submitted work. The authors report no other conflicts of interest in this work.