Vitamin K-dependent proteins regulate blood coagulation as well as bone growth and calcification. Here, we have compared the effects of oral anticoagulants on circulating vitamin K-dependent proteins and on markers for calcium and bone metabolism. Patients with a clinical indication for antithrombotic therapy were randomized into three groups and treated with either aspirin, regular-intensity anticoagulation [target international normalized ratio (INR) values: 2.5–3.5] or low-intensity anticoagulation (target INR values: 1.1–1.6). At the start and after 1 year of treatment, various biochemical markers were assessed. Both the circulating levels and the degree of carboxylation of the various γ-carboxyglutamate (Gla)-containing proteins were affected differently by oral anticoagulant treatment. Circulating osteocalcin was more sensitive to poor vitamin K status than other Gla proteins. From the fact that – except for osteocalcin – neither markers for osteoblast nor osteoclast function were affected by oral anticoagulant treatment, we conclude that bone turnover remained unaltered, which is indicative of an unchanged rate of bone loss. Whether the long-term production of undercarboxylated bone Gla proteins may have a negative effect on the quality of bone (e.g. bone strength) cannot be concluded from this study.