Fracture risk in patients treated with amiodarone or digoxin for cardiac arrhythmias: a nation-wide case-control study.
BACKGROUND
Cardiac arrhythmias and osteoporotic fractures are common in the elderly.


OBJECTIVE
We studied whether tachyarrhythmia and/or the drugs used to treat arrhythmias affect risk of fracture.


METHODS
In a population-based nation-wide pharmaco-epidemiological case-control design, we compared 124,655 patients that sustained a fracture during 2000 with 373,962 age- and gender-matched controls. We used computerized registers to assess individual drug use and related these data to individual fracture data and information on confounders.


RESULTS
Risk of any fracture was increased in patients with atrial fibrillation [Odds ratio (OR): 1.14; 95% confidence interval (95%CI): 1.08-1.21] and in patients currently treated with amiodarone (OR: 1.47; 95%CI: 1.21-1.78). Conversely, current use of digoxin decreased fracture risk (OR: 0.75; 95%CI: 0.71-0.79). Subanalysis showed similar effects in men and in women, but drug treatment only affected fracture risk in subjects older than 65 years of age. In current users of digoxin, risk of any fracture and risk of hip and forearm fracture decreased dose-dependently with increased dose. The use of other antiarrhythmics did not affect fracture risk.


CONCLUSIONS
Special attention should be paid to patients on treatment with amiodarone and/or a diagnosis of atrial fibrillation as they may have an increased risk of fracture. Conversely, treatment with digoxin may reduce fracture risk.
Rejnmark
L
L
Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus, Tage Hansens Gade 2, 8000, Aarhus C, Denmark. rejnmark@post6.tele.dk
Vestergaard
P
P
Mosekilde
L
L
D000328:Adult; D000367:Age Factors; D000368:Aged; D000638:Amiodarone / Q000009:adverse effects* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D016022:Case-Control Studies; D004077:Digoxin / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005543:Forearm Injuries / Q000139:chemically induced; D050723:Fractures, Bone / Q000139:chemically induced*; D006620:Hip Fractures / Q000139:chemically induced; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000150:complications*; D012307:Risk Factors; D012737:Sex Factors; D013610:Tachycardia / Q000150:complications / Q000188:drug therapy
D000889:Anti-Arrhythmia Agents; D004077:Digoxin; D000638:Amiodarone