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

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.