DECREASED AXIAL AND PERIPHERAL BONE-DENSITY IN PATIENTS TAKING LONG-TERM WARFARIN

Impaired vitamin K metabolism is associated with under-carboxylation o f the non-collagenous bone-matrix protein osteocalcin, which is requir ed in its fully carboxylated state for normal bone formation. Post-men opausal women have under-carboxylation of osteocalcin which increases with age and is marked in the elderly. A similarly marked degree of im paired carboxylation occurs during coumarin therapy, and a key questio n is whether this may lead to accelerated loss of bone mass which is c linically important. We measured axial and peripheral bone mineral den sity (BMD) in 40 male patients on warfarin and 40 controls individuall y matched for age, disease and other drug therapy. A consistent trend for reduced BMD at all sites was observed in the warfarin-treated pati ents. This was particularly marked in the cancellous bone at the dista l radius (9% reduction, p = 0.023) and at the cancellous rich lumbar s pine site (10.4% reduction, p < 0.004). No significant relationship wa s observed between warfarin dose, International Normalized Ratio (INR) or duration of therapy and bone density. Because of the biochemical s imilarity, this study provides a new lead on post-menopausal osteoporo sis, and supports tbe hypothesis that impaired carboxylation of osteoc alcin plays a role in the pathogenesis of bone loss in the elderly thr ough deficiency in vitamin K metabolism.