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


OBJECTIVE
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 >or=1600 microg 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.


CONCLUSIONS
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.
de Vries
Frank
F
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Pouwels
Sander
S
Bracke
Madelon
M
Leufkens
Hubert G M
HG
Cooper
Cyrus
C
Lammers
Jan-Willem J
JW
van Staa
Tjeerd-Pieter
TP
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000009:adverse effects*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000368:Aged; D016723:Bone Remodeling / Q000187:drug effects; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005264:Femoral Fractures / Q000139:chemically induced*; D006620:Hip Fractures / Q000139:chemically induced*; D006801:Humans; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D012307:Risk Factors
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists