Vitamin K, Knee Osteoarthritis, and Physical Function in Older Adults

描述(由申请人提供)：越来越多的证据表明，维生素K缺乏与几种年龄相关的疾病有关，包括骨关节炎(OA)。在关节组织中发现了几种依赖维生素K的蛋白质，包括起钙化抑制作用的基质玻璃蛋白(MGP)。为了使MGP发挥作用，它必须被羧化，这需要维生素K。最近，人们已经开发出检测人类血浆未羧化MGP(UcMGP)的方法，据报道，动脉钙化患者的血浆ucMGP升高(反映低维生素K状态)。由于MGP同时存在于血管组织和软骨中，而且动脉钙化和软骨钙化的维生素K依赖机制是相似的，因此，血浆ucMGP也反映了OA的病理。然而，血浆ucMGP还没有在有明确的骨关节炎进展特征的人群中被测量到。为了促进我们对维生素Ks在关节健康中作用的了解，研究人员建议测量健康、老龄化和身体成分(Health ABC)膝盖骨关节炎研究(Health，Aging and Body Component(Health ABC)Knee OA Study)存档样本中循环中的ucMGP和维生素K1，该研究由1141名居住在社区、年龄在70-79岁之间的黑人和白人组成的队列组成。将讨论以下具体目标：具体目标1a：确定老年人低维生素K状态(通过血浆ucMGP和维生素K1测量)与症状性膝骨性关节炎之间的联系。具体目标2a和2b：对3年以上的老年人进行放射学和核磁共振检查，以确定维生素K状况和膝骨性关节炎进展之间的关系。具体目标3：确定老年人维生素K状况与下肢功能之间的横向和纵向关联。Health ABC膝关节骨性关节炎研究的参与者接受了反复的双侧膝关节X光检查和核磁共振成像，并具有良好的下肢功能特征，这使得这项研究成为确定血浆ucMGP、维生素K1和骨性关节炎之间关系的理想研究。我们的结果将以经济有效的方式为维生素K在骨性关节炎中的潜在作用机制提供创新的证据，并将被用于制定未来的建议，以开展后续试验，以阐明维生素K在骨性关节炎进展和相关残疾中的作用。

DESCRIPTION (provided by applicant): A growing body of evidence suggests that vitamin K insufficiency is associated with several age-related diseases, including osteoarthritis (OA). Several vitamin K-dependent proteins are found in joint tissue, including matrix gla protein (MGP), which functions as a calcification inhibitor. In order for MGP to function it must be carboxylated, which requires vitamin K. Recently assays that measure plasma uncarboxylated MGP (ucMGP) in humans have been developed, and plasma ucMGP is reported to be elevated (reflective of low vitamin K status) in patients with arterial calcification. Since MGP is present n both vascular tissue and cartilage and the vitamin K-dependent mechanisms underlying arterial calcification and cartilage calcification are similar, it is plausible that plasma ucMGP also reflets OA pathology. However, plasma ucMGP has not been measured in persons well-characterized for OA progression. To advance our understanding of vitamin Ks role in joint health, the investigators propose to measure circulating ucMGP and vitamin K1 in archived samples from the Health, Aging and Body Composition (Health ABC) Knee OA Study, a cohort of 1141 black and white well-functioning community-dwelling men and women aged 70-79 yrs at baseline. The following specific aims will be addressed: Specific aim 1a: To determine the association between low vitamin K status (measured by plasma ucMGP and vitamin K1) and symptomatic knee OA in older adults. Specific aims 2a and 2b: To determine the association between vitamin K status and knee OA progression assessed radiographically and by MRI in older adults over 3 years of follow-up. Specific aim 3: To determine the cross-sectional and longitudinal association between vitamin K status and lower extremity function in older adults. Participants in the Health ABC Knee OA study underwent repeated bilateral knee x-rays and MRIs and are well characterized for lower-extremity function, making this study an ideal study to determine the associations between plasma ucMGP, vitamin K1 and OA. Our results will provide innovative evidence of the mechanisms underlying vitamin Ks role in OA in a cost-effective and efficient manner, and will be used to develop future proposals to carry out follow-up trials to clarify the vitamin Ks role in OA progression and related disability.