Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2.
BACKGROUND
Vitamin K allows for gamma-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 (> or = 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 beta-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. Beta-adrenergic antagonists may protect against osteoporotic fractures.
Gage
Brian F
BF
Division of General Medical Sciences, Washington University School of Medicine, St Louis, MO 63110, USA. bgage@im.wustl.edu
Birman-Deych
Elena
E
Radford
Martha J
MJ
Nilasena
David S
DS
Binder
Ellen F
EF
D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D016022:Case-Control Studies; D015984:Causality; D016001:Confidence Intervals; D005260:Female; D005598:Fractures, Spontaneous / Q000139:chemically induced* / Q000453:epidemiology*; D015577:Geriatric Assessment; D006801:Humans; D015994:Incidence; D015601:Injury Severity Score; D008297:Male; D016017:Odds Ratio; D010024:Osteoporosis / Q000175:diagnosis* / Q000453:epidemiology; D011379:Prognosis; D012016:Reference Values; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
D014859:Warfarin