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Long-term warfarin may increase osteoporotic fractures in men but not women. Beta blockers and/or a diet with plenty of vitamin K may offer protection.
Henry I. Bussey, Pharm.D., FCCP, FAHA
Reference: Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF. Risk of Osteoporotic Fracture in Elderly Patients Taking Warfarin; Results From the National Registry of Atrial Fibrillation 2. Arch Intern Med. 2006;166:241-246.
Gage and colleagues conducted a retrospective analysis of over 14,000 patients with atrial fibrillation (7,587 not receiving warfarin, 1,833 receiving warfarin < 1 yr, and 4,461 receiving warfarin for more than 1 year). The use of warfarin for > 1 yr was associated with an increased risk of fracture (odds ratio 1.25), which was significant in men (OR 1.63), but not in women (OR 1.05). Among the men on warfarin > 1 year the fracture rate was 3.6 per 100 patient years vs. 2.6 per 100 patient years in those not taking warfarin. The use of beta blockers was associated with a reduced risk of fracture (OR 0.84). Gage and colleagues point out that the mechanisms by which warfarin use may lead to osteoporosis include alterations in bone matrix protein synthesis and, perhaps, by warfarin users reducing their vitamin K intake. Gage and colleagues present data that low dietary intake of vitamin K leads to a substantial increase in the risk of fracture and that such dietary restrictions also lead to reduced folate intake, which may increase homocysteine, which also has been associated with osteoporosis. This potential value of dietary vitamin K intake is quite interesting in light of other data that increased vitamin K intake also may help stabilize the INR in patients taking warfarin (see Daily Low-dose Vitamin K Supplementation Stabilizes INRs).
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