Effects of Anti-vitamin k oral anticoagulants on bone and cardiovascular health

Vitamin K antagonist oral anticoagulants (VKAs) have been proven over 50 years to be highly effective and acceptably safe in many settings and are still used by millions of people worldwide. The main concern about the safety of VKAs regards the risk of bleeding, but there is accumulation evidence of their potentially negative effects beyond hemostasis. Indeed, VKAs impair the action of several Vitamin-K Dependent Proteins (VKDP), such as Bone Gla protein, Matrix Gla protein, Gas6 Protein, Periostin and Gla-Ric Protein, involved in bone and vascular metabolism, thus exerting a detrimental effect on bone and vascular health. Indeed, although the evidence regarding this issue is not compelling, it has been shown that VKAs use decreases bone mass density, increases the risk of bone fractures and accelerates the process of vascular and valvular calcification. Vascular calcification is a major concern in Chronic Kidney Disease (CKD) patients, also in absence of VKAs, because of mineral metabolism derangement, chronic inflammation and oxidative stress. Direct Oral AntiCoagulants (DOACs) do not affect VKDP involved in vascular and valvular calcification, and do not induce calcific valve degeneration in animal models, being a possible alternative to AVK for CKD patients. However, the efficacy and safety of DOACs in this population, suggested by some recent observations, requires confirmation by dedicated, randomized study. We reviewed here the effects of VKAs in bone and vascular health as compared to DOACs, in order to provide the physicians with some data useful to wisely choose the most suitable anticoagulant for every patient.