Use of beta‐2 agonists and risk of hip/femur fracture: a population‐based case‐control study

Administration of beta‐2 agonists decreased bone mineral density in rats. But the association between bronchodilators and fracture risk has not been studied in humans. Objectives To examine the association between use of beta‐2 agonists and risk of hip/femur fracture. Methods We conducted a population‐based case‐control study (6763 cases) in the Dutch PHARMO database. Current beta‐2 agonist use was compared to never use. We adjusted for severity of the underlying respiratory disease and disease and drug history. Results A hospitalisation for asthma/COPD in the year before index date increased risk of hip/femur fracture: crude OR 2.17 (95% CI, 1.41–3.34). Patients using higher doses of beta‐2 agonists had increased risk of hip/femur fracture: crude OR 1.94 (95% CI, 1.41–2.66) for daily dosages of ≥1600 µg albuterol equivalent. The excess fracture risk reduced after adjustment for disease severity (1.46; 95% CI, 1.02–2.08) and after exclusion of oral glucocorticoid users (1.31; 95% CI, 0.80–2.15). Risk of hip/femur fracture was similar between users of beta‐2 agonists, inhaled glucocorticoids and anticholinergics. Conclusion We found increases in the risk of hip/femur fracture in patients using higher doses of beta‐2 agonists. However, the excess risk of hip/femur fracture substantially reduced after exclusion of oral glucocorticoid users and after adjustment for the underlying disease. Risk of hip/femur fracture was similar between users of beta‐2 agonists, inhaled glucocorticoids and anticholinergics. The severity of the underlying disease, rather than the use of beta‐2 agonists, may play an important role in the aetiology of hip/femur fractures in patients using beta‐2 agonists. Copyright © 2006 John Wiley & Sons, Ltd.