Skeletal effects of oral anticoagulants

Vitamin K antagonists (VKA) are often used as oral anticoagulants (OA) in order to prevent thromboembolic diseases. In bone, vitamin K reduces bone resorption and functions as a co-factor in the post-translational carboxylation of several bone proteins. Osteocalcin (OC), the most abundant of these bone matrix proteins, is produced by osteoblasts and released in small amounts in blood as a specific marker of bone formation. Carboxylated proteins have a high affinity for calcium and are important in the incorporation of calcium into bone and bone formation. The increased levels of undercarboxylated osteocalcin can bring about an alteration of the bone mineral density and the risk of fracture, even if contradictory results have been observed in several epidemiologic studies. However, some, but not all reports, find that vitamin K deficiency, induced by hydroxycoumarins, may be associated with low bone mass. Additionally, epidemiologic studies have found that the use of OA may be associated with either increased or no change in fracture risk. Such divergent results may imply that human studies are compromised by the physical illnesses for which OA were prescribed. Additional epidemiological or cohort studies are warranted in order to determine whether potential pharmacological effects of VKA on bone metabolism may have clinical consequences.