Fracture risk in patients with chronic lung diseases treated with bronchodilator drugs and inhaled and oral corticosteroids

Abstract

Background: Chronic lung diseases and drugs used to treat patients with chronic lung diseases may be associated with an increased fracture risk.

Methods: 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).

Results: 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.

Conclusions: 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.