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(Stroke. 1997;28:2390-2394.)
© 1997 American Heart Association, Inc.

Articles

Long-term Oral Anticoagulation Reduces Bone Mass in Patients with Previous Hemispheric Infarction and Nonrheumatic Atrial Fibrillation

Yoshihiro Sato, MD; Yoshiaki Honda, MD; Haruko Kunoh, MD; Kotaro Oizumi, MD

From the Department of Neurology, Futase Social Insurance Hospital, Iizuka (Y.S., Y.H., H.K.), and First Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan (K.O.).

Correspondence to Dr. Yoshihiro Sato, Department of Neurology, Kurume University Medical Center, 155-1, Kokubumachi, Kurume 839, Japan. E-mail y-sato{at}ktarn.or.jp.

Background and Purpose Vitamin K is an essential factor for synthesis of plasma clotting proteins and for site-specific carboxylation of bone Gla protein and other bone matrix proteins. Low vitamin K has been associated with reduced bone mineral density. Warfarin therapy, which inhibits vitamin K–dependent blood-clotting, has been demonstrated to reduce the risk of stroke in nonrheumatic atrial fibrillation. We evaluated vitamin K and bone mineral density in nonrheumatic atrial fibrillation patients who had long-term warfarin therapy after an ischemic stroke.

Methods Sera were collected from 64 patients with nonrheumatic atrial fibrillation and ischemic stroke who had been treated with warfarin, 63 stroke patients without warfarin, and 39 control subjects. All stroke patients in both groups had hemiplegia. Sera were assayed for vitamins K₁ and K₂, bone Gla protein, and 25-hydroxyvitamin D. Bone mineral density was determined in both second metacarpals.

Results Serum vitamin K₁ concentrations (ng/mL) were lower in treated patients (.234±.177 ng/mL) than in untreated patients (.329±.284) or controls (.553±.164). Bone Gla protein was lower in treated patients' sera (1.241±.799 ng/mL) than in untreated patients (4.476±3.226). Concentrations of 25-hydroxyvitamin D were lower in both patient groups. Bone mineral density was lower on both sides in treated patients than in untreated patients (P<.0001). Vitamin K₁ and bone Gla protein were significantly related to bone mineral density bilaterally in treated but not in untreated patients.

Conclusions Bone mineral density was significantly lower in stroke patients with long-term warfarin treatment than in untreated patients. Both warfarin-induced reduction in vitamin K function and lowered vitamin K₁ concentration are probable causes of this osteopenia.

Key Words: atrial fibrillation • bone • osteoporosis • vitamin K • warfarin

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