Rejnmark Lars, Vestergaard Peter, Mosekilde Leif
Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Sygehus, Tage Hansens Gade 2, Aarhus C, Denmark.
Int J Cardiol. 2007 Jun 12;118(3):338-44. doi: 10.1016/j.ijcard.2006.07.022. Epub 2006 Oct 18.
Vitamin K antagonists (VKA) are often used as oral anticoagulants in order to prevent thromboembolic diseases. In bone, vitamin K reduces bone resorption and functions as a cofactor in the posttranslational carboxylation of several bone proteins. Discrepant results have been reported on whether VKA affects bone mineral density and fracture risk.
In a nationwide population-based pharmaco-epidemiological case-control study we assessed fracture risk in users of VKA.
We compared 124,655 cases that sustained a fracture during year 2000 with 373,962 age- and gender-matched controls. We used computerized registers to assess individual drug use and related these data to individual fracture data and information on confounders.
VKA was used in 2.2% of the cases and in 1.6% of the controls (crude OR 1.34; 95% CI, 1.28-1.41). After confounder adjustment, current use of VKA was associated with an increased risk of any fracture (OR 1.10; 95%CI, 1.03-1.18). Fracture risk was not increased in former users. Dose-effect analysis showed that only those who had used a relatively low accumulated dose of VKA (less than 100 defined daily dosages) had an increased risk of any fracture (adj. OR 1.49; 95%CI, 1.31-1.69), as well as an increased risk of fractures at the hip (adj. OR 1.43; 95%CI, 1.09-1.87) and forearm (adj. OR 1.42; 95%CI, 1.02-1.97).
Current use of small, accumulated amounts of VKA is associated with an increased fracture risk. This may be due to circumstances related to the disease necessitating therapy as well as due to a pharmacological effect.
维生素K拮抗剂（VKA）常被用作口服抗凝剂以预防血栓栓塞性疾病。在骨骼中，维生素K可减少骨吸收，并在几种骨蛋白的翻译后羧化过程中作为辅助因子发挥作用。关于VKA是否会影响骨矿物质密度和骨折风险，已有不一致的研究结果报道。
在一项基于全国人口的药物流行病学病例对照研究中，我们评估了VKA使用者的骨折风险。
我们将2000年期间发生骨折的124,655例病例与373,962例年龄和性别匹配的对照进行了比较。我们使用计算机化登记系统评估个体药物使用情况，并将这些数据与个体骨折数据及混杂因素信息相关联。
2.2%的病例和1.6%的对照使用了VKA（粗比值比1.34；95%置信区间，1.28 - 1.41）。在对混杂因素进行调整后，当前使用VKA与任何骨折风险增加相关（比值比1.10；95%置信区间，1.03 - 1.18）。既往使用者的骨折风险并未增加。剂量 - 效应分析表明，只有那些使用相对低累积剂量VKA（少于100个限定日剂量）的人有任何骨折风险增加（调整后比值比1.49；95%置信区间，1.31 - 1.69），以及髋部骨折风险增加（调整后比值比1.43；95%置信区间，1.09 - 1.87）和前臂骨折风险增加（调整后比值比1.42；95%置信区间，1.02 - 1.97）。
当前使用少量累积剂量的VKA与骨折风险增加相关。这可能是由于需要治疗的疾病相关情况以及药理作用所致。
