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不足与几种年龄相关疾病有关，包括骨关节炎（OA）。在关节组织中发现了几种维生素K依赖性蛋白，包括基质玻璃蛋白（MGP），其功能是钙化抑制剂。为了使MGP发挥作用，它必须被羧化，这需要维生素K。最近，已经开发了测量人类血浆未羧化MGP（ucMGP）的测定法，并且据报道，动脉钙化患者的血浆ucMGP升高（反映低维生素K状态）。由于MGP存在于血管组织和软骨中，并且动脉钙化和软骨钙化的维生素K依赖性机制相似，因此血浆ucMGP也反映了OA病理学。然而，尚未在OA进展特征良好的人群中测量血浆ucMGP。为了进一步了解维生素K在关节健康中的作用，研究人员建议测量健康、衰老和身体组成（健康ABC）膝关节OA研究存档样本中的循环ucMGP和维生素K1，该研究包括1141名黑人和白色功能良好的社区居民男性和女性，基线年龄为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OA之间的相关性。具体目标2a和2b：确定3年随访期间通过影像学和MRI评估的维生素K状态与老年人膝关节OA进展之间的相关性。 具体目标3：确定维生素K状态与老年人下肢功能之间的横向和纵向关联。Health ABC膝关节OA研究的参与者接受了重复的双侧膝关节X线检查和MRI，并对下肢功能进行了良好的表征，使这项研究成为确定血浆ucMGP、维生素K1和OA之间相关性的理想研究。我们的研究结果将以具有成本效益和有效的方式提供维生素K在OA中作用的机制的创新证据，并将用于制定未来的建议，以进行后续试验，以澄清维生素K在OA进展和相关残疾中的作用。 公共卫生相关性：关节组织中存在几种维生素K依赖性蛋白，越来越多的证据表明维生素K不足与几种慢性疾病有关，包括骨关节炎（OA）。然而，维生素K在OA中的作用尚未完全了解，因为现有的研究仅限于横断面分析，没有一项研究确定了维生素K状态的多种测量与OA进展之间的关联。考虑到OA的公共卫生负担很高，更好地了解维生素K状态与老年人膝关节OA进展之间的纵向关系具有重要的公共卫生意义，因为维生素K不足是可以纠正的。

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.