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

项目总结 膝骨性关节炎(OA)是导致成人肢体残疾的主要原因。目前还没有已知的治疗方法，所以 确定有效的策略以减少膝骨性关节炎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依赖蛋白(VKDPs)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缺乏会对 关节软骨。在观察性膝骨性关节炎研究中，循环维生素浓度较低的老年人 K组患者的下肢功能较差。在关节中发现的VKDP需要维生素K来产生功能性VKDP 有新的证据表明，它通过核调节关节软骨中基因的转录。 受体SXR/PXR。因此，有强大的生理基础来支持保护作用。 膝盖骨关节炎中的维生素K。然而，目前还没有进行临床试验。解决关键参数的问题 需要设计一项更大规模的临床试验，我们建议对患有轻度到中度以下疾病的成年人进行随机对照试验研究。 中度膝关节骨关节炎和低基线维生素K状况：(1)先导研究程序和评估的可行性 对轻度至中度的成人实施更大规模的维生素K补充的最终临床试验 两个临床站点的膝骨性关节炎和低基线维生素K状况；以及(2)确定 低维生素K状态和轻中度膝关节成年人的运动功能测试 骨性关节炎。这项随机先导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作为一种潜在的治疗方法来缓解成人下肢功能的下降 有症状的膝骨性关节炎和低维生素K状态。确定单一的耐受性良好的干预措施 有利地减少膝骨性关节炎的进展将代表着一项重要的治疗突破。

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.