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不足与几种与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维生素k依赖蛋白，包括作为钙化抑制剂的基质玻璃蛋白（MGP）。为了使MGP发挥作用，它必须羧化，这需要维生素K。最近，研究人员开发了一种测定人类血浆未羧化MGP （ucMGP）的方法，据报道，动脉钙化患者血浆ucMGP升高（反映维生素K水平低）。由于MGP存在于血管组织和软骨中，并且动脉钙化和软骨钙化背后的维生素k依赖机制是相似的，因此血浆ucMGP也可能反映OA病理。然而，血浆ucMGP尚未在OA进展明显的患者中测量。为了增进我们对维生素k在关节健康中的作用的理解，研究人员建议在健康、衰老和身体组成（health ABC）膝关节OA研究的档案样本中测量循环ucMGP和维生素K1，该研究包括1141名功能良好的社区生活男性和女性，年龄在70-79岁。具体目标1a：确定低维生素K状态（通过血浆ucMGP和维生素K1测量）与老年人症状性膝关节炎之间的关系。具体目的2a和2b：确定维生素K状态与膝关节OA进展之间的关系，通过影像学和MRI对老年人进行为期3年的随访。具体目的3：确定维生素K状态与老年人下肢功能之间的横断面和纵向关联。健康ABC膝关节OA研究的参与者反复接受双侧膝关节x光片和mri检查，下肢功能特征良好，使该研究成为确定血浆ucMGP、维生素K1和OA之间关系的理想研究。我们的研究结果将以经济有效的方式为维生素k在OA中的作用机制提供创新证据，并将用于制定未来的后续试验建议，以阐明维生素k在OA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. PUBLIC HEALTH RELEVANCE: Several vitamin K-dependent proteins are present in joint tissue, and a growing body of evidence suggests that vitamin K insufficiency is associated with several chronic diseases, including osteoarthritis (OA). However, vitamin Ks role in OA is not completely understood because available studies are limited to cross-sectional analyses and none have determined the association between multiple measures of vitamin K status and OA progression. Considering the public health burden of OA is high, a better understanding of the longitudinal relationship between vitamin K status and knee OA progression in older adults is of significant public health importance, since vitamin K insufficiency is correctable.