Long-term inhaled corticosteroid use in COPD and the risk of fracture in men and women

Abstract

Inhaled corticosteroids (ICS) are widely used to treat chronic obstructive pulmonary disease (COPD), often early in the course of disease and at higher doses. The safety concerns for osteoporosis and fractures with long-term use of ICS could particularly affect post-menopausal women with decreased bone density. To date, the studies have been inconclusive, with none evaluating the differential effect in men and women. Using the Quebec universal health insurance databases, we formed a new-user cohort of COPD patients initiating treatment with ICS or other therapies during 1990-2005, followed through 2007 for a fracture of the hip or of upper extremity. A Cox model with time-dependent ICS exposure was used to estimate the rate ratio of fracture associated with duration and dose of ICS use, adjusted for age, sex, disease severity and co-morbidity, also assessing whether the risk differed between men and women. The cohorts included 139,119 users of ICS and 169,745 non-users, of which 19,396 had a fracture (51% of the hip and 49% of the humerus, radius or ulna) during a mean 4.1 years of follow-up (incidence rate 15.4/1000/year). Any use of ICS was not associated with an increased rate of fracture (rate ratio (RR) 1.00; 95% confidence interval (CI): 0.97-1.03). The rate was elevated with longer than 4 years of ICS use at daily doses of 1000 mcg or more of fluticasone-equivalent (RR 1.10; 95% CI 1.02-1.19). This risk increase did not differ between men and women or among the different ICS agents. In conclusion, long-term use of inhaled corticosteroids in COPD at high doses is associated with a modest increase in the risk of fracture of the hip and upper extremities, similarly so for men and women.