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Original Investigation
January 23, 2006

Risk of Osteoporotic Fracture in Elderly Patients Taking Warfarin: Results From the National Registry of Atrial Fibrillation 2

Author Affiliations

Author Affiliations: Divisions of General Medical Sciences (Dr Gage and Ms Birman-Deych) and Geriatrics and Nutritional Science (Dr Binder), Washington University School of Medicine, St Louis, Mo; Clinical Quality, NYU Medical Center, New York, NY (Dr Radford); and Centers for Medicare & Medicaid Services, Dallas, Tex (Dr Nilasena).

Arch Intern Med. 2006;166(2):241-246. doi:10.1001/archinte.166.2.241

Background  Vitamin K allows for γ-carboxylation of glutamyl residues, a conversion that activates clotting factors and bone proteins. Vitamin K antagonists such as warfarin inhibit this process. Our goal was to quantify the association between warfarin and osteoporotic fractures in patients with atrial fibrillation.

Methods  This was a retrospective cohort study of Medicare beneficiaries with atrial fibrillation who were hospitalized between March 1998 and April 1999 in all 50 US states. The study outcome was osteoporotic fractures, identified by an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for a fracture of the hip, spine, or wrist.

Results  Compared with 7587 patients who were not prescribed warfarin, the adjusted odds ratio (OR) of fracture was 1.25 (95% confidence interval [CI], 1.06-1.48) in 4461 patients prescribed long-term warfarin therapy (≥1 year). The association between osteoporotic fracture and long-term warfarin use was significant in men (OR, 1.63; 95% CI, 1.26-2.10) but nonsignificant in women (OR, 1.05; 95% CI, 0.88-1.26). In 1833 patients prescribed warfarin for less than a year, the risk of osteoporotic fracture was not increased significantly (OR, 1.03). Odds ratios (95% CIs) of independent predictors of osteoporotic fractures were as follows: increasing age, 1.63 (1.47-1.80) per decade; high fall risk, 1.78 (1.42-2.21); hyperthyroidism, 1.77 (1.16-2.70); neuropsychiatric disease, 1.51 (1.28-1.78); and alcoholism, 1.50 (1.01-2.24). Factors with a reduced OR (95% CI) included African American race, 0.30 (0.18-0.51); male sex, 0.54 (0.46-0.62); and use of β-adrenergic antagonists, 0.84 (0.70-1.00).

Conclusions  Long-term use of warfarin was associated with osteoporotic fractures, at least in men with atrial fibrillation. β-Adrenergic antagonists may protect against osteoporotic fractures.