In their recently published large population-based case control study, Rejnmark and coworkers have demonstrated that current use of small, accumulated amounts of vitamin K antagonists (VKA) was associated with increased fracture risk. However, they found that risk of fracture was not increased in patients who had used a large accumulated dose. They proposed that risk of fracture was increased due to circumstances related to initiation therapy rather than due to a direct pharmacological effect of VKA [1]. As far as every clinician knows, warfarin decreases the tendency of blood to clot by inhibiting the vitamin Kdependent gamma-carboxylation of clotting factors, namely II, VII, IX and X [2]. Interestingly, warfarin inhibits the gamma-carboyxlation of osteocalcin; non-carboxylated osteocalcin cannot bind calcium effectively [3]. Moreover, vitamin K might directly reduce bone resorption by the mechanisms of decreased prostaglandin E2 synthesis and osteoclast-like cell formation [4,5]. Those data have led the clinicians to suspect that warfarin may adversely affect bone metabolism. Some important clinical findings have supported this hypothesis. First, mean serum vitamin K concentrations in patients with fractures have been found to be lower than in normals [6,7]. Second, it was shown that the percentage of non-carboyxlated osteocalcin in elderly women was higher than in young women [8]. Third, another study clearly demonstrated that the risk of hip fracture in women with high serum levels of non-carboyxlated osteocalcin were higher than in women with low levels [9]. Lastly, vitamin K therapy has been shown to reduce urinary excretions of hydroxyproline which is a marker of bone