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

^* From the Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, Aarhus, Denmark.

Correspondence to: Peter Vestergaard, MD, PhD, DrMedSc, The Osteoporosis Clinic, Aarhus Amtssygehus, Tage Hansens Gade 2, DK-8000 Aarhus C, Denmark; e-mail: p-vest{at}post4.tele.dk

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 ß-agonists were associated with an increase in fracture risk that was not dose dependent and was seen already at low doses. Oral ß-agonists were associated with an increase in fracture risk at low doses but not at higher doses. Other bronchodilators (inhaled long-acting ß-agonists, inhaled ß-agonists plus inhaled corticosteroids, inhaled ß-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 ß-agonists may be linked to the severity of the underlying lung disease rather than with the ß-agonists, per se, as other types of ß-agonists were not associated with fractures.

Key Words: asthma • ß-agonist • COPD • corticosteroid • cromoglycate • emphysema • fracture • leukotriene receptor antagonists • theophylline