The Study of Muscle, Mobility and Aging with Knee OA

随着年龄的增长，肌肉骨骼组织的退化会导致骨关节炎、活动度降低和增加 残疾。骨关节炎(OA)经常影响膝盖，是世界范围内导致残疾的主要原因。穷 肌肉特征与膝关节骨性关节炎(KOA)和健康人的横断面比较有关 对照组和膝关节骨性关节炎受试者在肌肉成分、股四头肌肌力和力量方面表现出差异。一个 很少有小规模的横断面研究也严格地研究了与肌肉质量下降有关的 独立于膝关节骨性关节炎的老年人的活动能力，据报道肌肉质量减少，产生 三磷酸腺苷、失神经、氧化损伤和自噬减少。然而，这些临床研究一直是 小，只有横断面的，通常不包括有固定活动或有记录的膝骨性关节炎风险的个人。多么 这些肌肉质量随膝关节骨性关节炎的变化尚不清楚，这是理解减少的障碍 KOA中的行动不便和残疾增加。NIA/NIH最近资助了一项关于肌肉、活动能力和衰老的研究 (Somma)，刚刚开始招收875名中等功能、种族多样的年龄段的女性和男性 &gt；=70年。在两个中心。Somma研究的目的是：1)了解骨骼肌质量的贡献， 能量学，以及肌肉组织的关键特性，从活组织检查到严重的静止和残疾；以及2)产生 独一无二的肌肉组织、血液、基因表达数据和临床表型数据库，供 科学界。我们建议在第一次Somma后续访问时获得膝关节X光片，以了解 骨骼肌质量和组成对膝关节骨性关节炎患者活动能力降低和残疾的影响 受试者，如果这与没有KOA的受试者不同。具体目标是：目标1a：我们将使用 ART测量，以测试肌肉特性(力量、质量、成分、能量- ATPMax)在患有膝骨性关节炎的受试者与不患有膝骨性关节炎的个体中有所不同，并将进行单独的分析 对于有放射学膝骨性关节炎的人的放射学膝骨性关节炎(不考虑膝盖疼痛)和症状性膝骨性关节炎 频繁的膝部疼痛。目标1b：我们将使用肌肉特性(力量、质量、成分、能量-ATPmax) 定义肌肉表型以检验肌肉表型与膝关节骨性关节炎和 膝骨性关节炎和疼痛。目的2：我们将检验这样一种假设：患有放射学膝关节骨性关节炎和有症状的膝关节骨性关节炎的人 将具有较差的移动性和功能结果(400米步行速度和移动性评估工具-短 形式，MAT-SF残疾)比没有膝关节骨性关节炎的患者，这种差异部分是由特定的肌肉调节的 特点。我们的目标是确定哪种肌肉特性的组合与功能有关 并利用这些信息设计新的基于肌肉的治疗方法，以帮助患有膝骨性关节炎的患者。

Deterioration of musculoskeletal tissues with age results in osteoarthritis, reduced mobility, and increased disability. Osteoarthritis (OA) frequently affects the knee and is the leading cause of disability worldwide. Poor muscle characteristics are associated with knee OA (KOA) and cross-sectional comparisons of healthy controls and KOA subjects show differences in muscle composition, quadriceps muscle strength and power. A few, small cross-sectional studies have also rigorously investigated muscle qualities associated with reduced mobility in older adults, independent of KOA, and reported reduced muscle mass, decreased ability to generate ATP, denervation, oxidative damage, and decreased autophagy. However, these clinical studies have been small, only cross-sectional, and often did not include individuals at risk for immobility or documented KOA. How these muscle qualities change with KOA is not known and represents a roadblock to understanding reduced mobility and increased disability in KOA. The NIA/NIH recently funded a Study of Muscle, Mobility and Aging (SOMMA), which just began enrolling 875 intermediate functioning, ethnically diverse women and men age >=70yrs. at two centers. The SOMMA study aims to 1) understand the contributions of skeletal muscle mass, energetics, and key properties of muscle tissue from biopsies to major immobility and disability; and 2) produce a unique bank of muscle tissue, blood, gene expression data, and clinical phenotyping to be used by the scientific community. We propose to obtain knee radiographs at the first SOMMA follow-up visit to understand the contributions of skeletal muscle mass and composition that leads to reduced mobility and disability in KOA subjects and if this differs from subjects without KOA. The Specific Aims are: Aim 1a: We will use state of the art measurements to test the hypothesis that muscle properties (strength, mass, composition, energetics- ATPMax) differ in subjects with KOA compared to individuals without KOA, and will perform separate analyses for radiographic KOA (regardless of knee pain) and symptomatic KOA in persons with radiographic OA and frequent knee pain. Aim 1b: We will use muscle properties (strength, mass, composition, energetics-ATPmax) to define muscle phenotypes to test the hypothesis that there are muscle phenotypes associated with KOA and KOA and pain. Aim 2: We will test the hypothesis that persons with radiographic KOA and symptomatic KOA will have worse mobility and functional outcomes (400m walking speed and Mobility Assessment Tool- short form, MAT-sf Disability) than those without KOA and that this difference is mediated in part by specific muscle characteristics. Our goal is to determine what combination of muscle properties are associated with function in KOA subjects and use the information to design novel muscle-based treatments to help subjects with KOA.