The Study of Muscle, Mobility and Aging with Knee OA

膝关节 OA 的肌肉、活动度和衰老研究

• 批准号: 10201137
• 负责人: Nancy E Lane
• 金额: $ 61.14万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10201137
• 关键词: Affect; Age; Aging; Assessment tool; Automobile Driving; Autophagocytosis; Biopsy; Blood; Cartilage; Caucasians; Cell physiology; Characteristics; Clinical Research; Communities; Cross-Sectional Studies; Data; Degenerative polyarthritis; Denervation; Deterioration; Development; Diagnostic radiologic examination; Disease; Elderly; Enrollment; Follow-Up Studies; Funding; Gait speed; Gene Expression; Goals; Impairment; Individual; Intervention; Intramuscular; Investigation; Joints; Knee; Knee Osteoarthritis; Knee joint; Lateral; Lead; Lower Extremity; Measurement; Measures; Mediating; Muscle; Muscle Fibers; Muscle function; Musculoskeletal; Obesity; Osteoporosis; Outcome; Pain; Patient Self-Report; Persons; Phenotype; Physical Function; Prevalence; Property; Public Health; Reporting; Research; Research Design; Resources; Risk; Role; Skeletal Muscle; Symptoms; Testing; Thigh structure; Time; Tissues; United States National Institutes of Health; Visit; Walking; Woman; age related; base; clinical outcome measures; clinical phenotype; density; design; disability; ethnic diversity; follow-up; functional outcomes; improved; improved mobility; in vivo; knee pain; knee replacement arthroplasty; men; muscle form; muscle pharmacology; muscle strength; novel; oxidative damage; prevent; quadriceps muscle; reduced muscle mass; walking speed

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.

随着年龄的增长，肌肉骨骼组织的退化导致骨关节炎，活动能力降低， 残疾。骨关节炎（OA）经常影响膝关节，是全球残疾的主要原因。贫困 肌肉特征与膝关节骨性关节炎（KOA）相关， 对照组和KOA受试者在肌肉组成、四头肌肌力和力量方面显示出差异。一 一些小的横断面研究也严格调查了与减少的肌肉质量相关的肌肉质量。 老年人的活动性，独立于KOA，并报告肌肉质量减少，产生能力下降， ATP、去神经支配、氧化损伤和自噬减少。然而，这些临床研究已经被 小，只有横截面，往往不包括个人的风险不动或记录KOA。如何 这些肌肉质量的变化与KOA是未知的，并代表了一个障碍，以了解减少 在KOA中的移动性和残疾增加。NIA/NIH最近资助了一项关于肌肉、流动性和衰老的研究 （SOMMA），刚刚开始招收875名中间功能，种族多样化的妇女和男子年龄 >= 70岁。两个中心。SOMMA研究的目的是：1）了解骨骼肌质量的贡献， 能量学和肌肉组织的关键特性，从活检到主要的不动和残疾;以及2）产生 一个独特的肌肉组织，血液，基因表达数据和临床表型的银行，将用于 科学界。我们建议在首次SOMMA随访访视时获得膝关节X线片，以了解 骨骼肌质量和组成的贡献，导致减少的流动性和残疾的KOA 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 艺术测量来测试肌肉特性（力量，质量，成分，能量学- ATPMax）在KOA受试者中与无KOA个体相比存在差异，并将进行单独分析 对于影像学KOA（不考虑膝关节疼痛）和有症状的KOA， 经常膝盖疼痛。目标1b：我们将使用肌肉特性（强度，质量，成分，能量-ATP最大值） 定义肌肉表型，以检验存在与KOA相关的肌肉表型的假设， KOA和疼痛。目的2：我们将检验一个假设，即有影像学KOA和症状性KOA的人 将有更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）比那些没有KOA的人，这种差异部分是由特定的肌肉介导的 特色我们的目标是确定什么样的肌肉特性组合与功能相关， KOA受试者，并使用这些信息设计新的基于肌肉的治疗方法来帮助KOA受试者。