Effects of Vitamin K on Lower-extremity Function in Adults with Osteoarthritis: a Randomized Controlled Pilot Trial

项目摘要 膝关节骨关节炎（OA）是成人下肢残疾的主要原因。没有已知的治疗方法，所以 确定有效的策略来减少膝关节OA的后果对于延迟残疾是重要的 并减少相关的成本负担。多条生物学、遗传学和流行病学证据支持 维生素K和维生素K依赖性蛋白（VKDP）在维持关节健康中的关键作用。维生素K 是一种公认的营养不足。临床前模型表明，维生素K不足会对 关节软骨在观察性膝关节OA研究中，循环维生素C浓度低的老年人 K组下肢功能较差。需要维生素K来产生关节中发现的功能性VKDP 有新的证据表明，它通过细胞核调节关节软骨中基因的转录， 受体SXR/PXR。因此，有很强的生理基础来支持保护作用， 维生素K在膝关节OA中的作用然而，尚未进行临床试验。为了解决关键参数 为了设计更大规模的临床试验，我们提议在患有轻度至中度糖尿病的成人中进行一项随机对照初探性研究。 中度膝关节OA和低基线维生素K状态：（1）初步研究程序和评估的可行性 在轻度至中度糖尿病患者中实施更大规模的补充维生素K的确定性临床试验 两个临床站点的膝关节OA和低基线维生素K状态;和（2）确定 低维生素K状态和轻度至中度膝关节炎的成人身体功能的基于性能的测试 骨关节炎这项随机试验研究将产生关键数据，以指导更大规模临床试验的设计 评估维生素K作为缓解成人下肢功能下降的潜在疗法 有症状的膝关节骨性关节炎和维生素K缺乏确定一种耐受性良好的干预措施， 有利地减少膝关节OA进展将代表重要的治疗突破。

PROJECT SUMMARY Knee osteoarthritis (OA) is a leading cause of lower-extremity disability in adults. There is no known cure, so the identification of effective strategies to reduce the consequences of knee OA is important to delay disability and reduce associated cost burden. Multiple lines of biologic, genetic, and epidemiologic evidence support a critical role for vitamin K and vitamin K-dependent proteins (VKDPs) in maintenance of joint health. Vitamin K is an established shortfall nutrient. Preclinical models indicate that vitamin K insufficiency adversely affects articular cartilage. In observational knee OA studies, older adults with low circulating concentrations of vitamin K have poorer lower-extremity function. Vitamin K is required to produce functional VKDPs found in the joint and there is emerging evidence that it regulates transcription of genes in articular cartilage through the nuclear receptor SXR/PXR. Therefore, there are strong physiological underpinnings to support a protective role for vitamin K in knee OA. However, no clinical trials have yet been conducted. To address critical parameters required to design a larger clinical trial, we propose a randomized controlled pilot study in adults with mild to moderate knee OA and low baseline vitamin K status to: (1) Pilot study procedures and assess the feasibility of implementing a larger scale definitive clinical trial of vitamin K supplementation in adults with mild to moderate knee OA and low baseline vitamin K status at two clinical sites; and (2) Determine the responsiveness of performance-based tests of physical function in adults with low vitamin K status and mild to moderate knee osteoarthritis. This randomized pilot study will generate critical data to guide the design of a larger clinical trial to evaluate vitamin K as a potential therapy to mitigate the decline in lower-extremity function among adults with symptomatic knee OA and low vitamin K status. Identifying a single well-tolerated intervention that favorably reduces knee OA progression would represent an important therapeutic breakthrough.