Fracture Risk in Patients With Chronic Lung Diseases Treated With Bronchodilator Drugs and Inhaled and Oral Corticosteroids

Abstract

Chronic lung diseases and drugs used to treat patients with chronic lung diseases may be associated with an increased fracture risk. The design was a case-control study of all patients with a fracture (n=124,655) in the year 2000 in Denmark as case subjects. For each case subject, three age- and gender-matched control subjects were randomly drawn from the general population (n=373,962). Chronic lung diseases such as COPD (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.13 to 1.25), emphysema (OR, 1.31; 95% CI, 1.16 to 1.48), and other chronic lung diseases (OR, 1.20; 95% CI, 1.00 to 1.44) were associated with a higher relative risk of any fracture than asthma (OR, 1.06; 95% CI, 1.01 to 1.12). Oral corticosteroids were associated with a dose-dependent increased risk of fractures. Inhaled short-acting beta-agonists were associated with an increase in fracture risk that was not dose dependent and was seen already at low doses. Oral beta-agonists were associated with an increase in fracture risk at low doses but not at higher doses. Other bronchodilators (inhaled long-acting beta-agonists, inhaled beta-agonists plus inhaled corticosteroids, inhaled beta-agonists plus antimuscarinic substances, inhaled antimuscarinic substances, inhaled cromoglycate and cromoglycate-like substances, oral theophylline, and oral leukotriene receptor antagonists), and inhaled corticosteroids were not associated with fracture risk. The increase in fracture risk seen with inhaled short-acting beta-agonists may be linked to the severity of the underlying lung disease rather than with the beta-agonists, per se, as other types of beta-agonists were not associated with fractures.