LONG-TERM ORAL ANTICOAGULATION REDUCES BONE MASS IN PATIENTS WITH PREVIOUS HEMISPHERIC INFARCTION AND NONRHEUMATIC ATRIAL-FIBRILLATION

Background and Purpose Vitamin K is an essential factor for synthesis of plasma clotting proteins and for site-specific carboxylation of bon e Gla protein and other bone matrix proteins. Low vitamin It 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 eval uated vitamin ii and bone mineral density in nonrheumatic atrial fibri llation patients who had long-term warfarin therapy after an ischemic stroke. Methods Sera were collected from 61 patients with nonrheumatic atrial fibrillation and ischemic stroke who had been treated with war farin, 63 stroke patients without warfarin, and 39 control subjects. A ll stroke patients in both groups had hemiplegia. Sera were assayed fo r vitamins K-1 and K-2 bone Gla protein, and 25-hydroxyvitamin D. Bone mineral density was determined in both second metacarpals. Results Se rum vitamin K-1 concentrations (ng/mL) were lower in treated patients (.234 +/- .177 ng/mL) than in untreated patients (.329 +/- .284) or co ntrols (.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 patie nts than in untreated patients (P < .0001). Vitamin K-1, and bone Gla protein were significantly related to bone mineral density bilaterally in treated but not in untreated patients. Conclusions Bone mineral de nsity was significantly lower in stroke patients with long-term warfar in treatment than in untreated patients, Both warfarin-induced reducti on in vitamin K function and lowered vitamin K-1 concentration are pro bable causes of this osteopenia.