Menon R K, Gill D S, Thomas M, Kernoff P B, Dandona P
J Clin Endocrinol Metab. 1987 Jan;64(1):59-61. doi: 10.1210/jcem-64-1-59.
The total circulating osteocalcin and ratio of inactive (noncarboxylated; GLU) to active (carboxylated; GLA) form of circulating osteocalcin were measured in patients receiving long term warfarin treatment (n = 20), age-matched control patients not receiving warfarin treatment (n = 10), and normal subjects before and after the administration of 30 mg warfarin (n = 7). There was no significant difference in the total osteocalcin concentrations between the control patients and the patients receiving long term warfarin treatment, and it did not significantly change after warfarin ingestion in the normal subjects. The GLU/GLA ratio was significantly increased (P less than 0.002) in the patients receiving long term warfarin treatment compared with that in the control patients. There was a significant increase (P less than 0.01) in the GLU/GLA ratio after warfarin ingestion in the normal subjects. This study demonstrates that osteocalcin carboxylation in humans is a vitamin K-dependent process and that circulating osteocalcin is structurally altered by warfarin administration. This finding has pathophysiological implications for the fetal warfarin embryopathy syndrome, bone disease associated with chronic liver diseases, and possibly for osteoporosis, in which vitamin K deficiency has been implicated.
对接受长期华法林治疗的患者（n = 20）、未接受华法林治疗的年龄匹配对照患者（n = 10）以及服用30 mg华法林前后的正常受试者（n = 7）测定了循环骨钙素总量以及循环骨钙素的无活性（未羧化；GLU）与活性（羧化；GLA）形式的比例。对照患者与接受长期华法林治疗的患者之间的骨钙素总浓度无显著差异，正常受试者服用华法林后骨钙素总浓度也无显著变化。与对照患者相比，接受长期华法林治疗的患者的GLU/GLA比值显著升高（P < 0.002）。正常受试者服用华法林后GLU/GLA比值显著升高（P < 0.01）。本研究表明，人体骨钙素羧化是一个维生素K依赖的过程，华法林给药会使循环骨钙素的结构发生改变。这一发现对胎儿华法林胚胎病综合征、与慢性肝病相关的骨病以及可能与维生素K缺乏有关的骨质疏松症具有病理生理学意义。
