Long-term Use of Inhaled Corticosteroids in COPD and the Risk of Fracture

Background: It is uncertain whether long-term use of inhaled corticosteroids (ICSs), widely used to treat COPD, increases the risk of fracture, particularly in women, in view of the postmenopausal risks. We assessed whether long-term ICS use in patients with COPD increases the risk of hip or upper extremity fractures, and examined sex-related differences.

Methods: The Quebec health-care databases were used to form a cohort of patients with COPD over 1990 to 2005, followed until 2007 for the first hip or upper extremity fracture. In a nested case-control analysis, each case of fracture was matched with 20 control subjects on age, sex, and follow-up time. The adjusted rate ratio (RR) of fracture with ICS use, by duration and dose, was estimated using conditional logistic regression, with an interaction term to compare the risk in men and women.

Results: In the cohort of 240,110 subjects, 19,396 sustained a fracture during a mean 5.3 years (rate, 15.2 per 1,000 per year). Any use of ICSs was not associated with an increased rate of fracture (RR, 1.00; 95% CI, 0.97-1.03). The fracture rate was increased with > 4 years of ICS use at daily doses ≥ 1,000 μg in fluticasone equivalents (RR, 1.10; 95% CI, 1.02-1.19). This risk increase did not differ between men and women.

Conclusions: Long-term ICS use at high doses is associated with a modest increase in the risk of hip and upper extremity fractures in patients with COPD. This dose-duration risk increase does not appear to be higher for women.