Steps Towards OA Prevention

预防 OA 的步骤

• 批准号: 10642327
• 负责人: Caroline M Lisee
• 金额: $ 12.09万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642327
• 关键词: Affect; Animal Model; Biology; Biomechanics; Cartilage; Clinical Research; Clinical Trials; Collagen; Cross-Sectional Studies; Data; Degenerative polyarthritis; Development; Frequencies; Funding; Future; Goals; Health; Individual; Intervention; Joints; K-Series Research Career Programs; Knee Osteoarthritis; Knee joint; Knowledge; Laboratories; Limb structure; Link; Magnetic Resonance Imaging; Measures; Mechanics; Medial; Mentors; Mission; Observational Study; Participant; Persons; Physical activity; Pilot Projects; Population; Pre-Post Tests; Prevention; Prevention Research; Prevention strategy; Principal Investigator; Productivity; Proteoglycan; Public Health; Quality of life; Randomized, Controlled Trials; Recommendation; Reconstructive Surgical Procedures; Relaxation; Research; Research Design; Research Personnel; Rest; Risk; Risk Factors; Risk Reduction; Series; Sports Medicine; Standardization; Surrogate Endpoint; Testing; Thick; Time; Training; Traumatic Arthropathy; United States; United States National Institutes of Health; Walking; anterior cruciate ligament injury; anterior cruciate ligament reconstruction; arm; career; career development; clinical trial implementation; density; disability; disorder prevention; efficacy evaluation; health assessment; high risk; high risk population; human subject; improved; in vivo; innovation; joint loading; mechanical load; novel; physical inactivity; pilot test; preventive intervention; reconstruction; resilience; response; risk mitigation; skill acquisition; skills; theories

PROJECT SUMMARY/ABSTRACT Osteoarthritis (OA) is a leading cause of disability. Identifying modifiable mechanisms of poor knee joint health development for disease prevention strategies are critical to improving long-term health. Aberrant mechanical loading has been theorized as a primary risk factor for knee OA. Most studies primarily focus on mechanical mechanisms of excessive joint loading in OA development. However, recent evidence suggests that joint underloading may also play a role. The effects of low loading frequency assessed via daily steps in real world settings on knee joint health is an understudied parameter of aberrant mechanical loading in individuals at risk for OA. Individuals with anterior cruciate ligament (ACL) injury who undergo ACL reconstruction (ACLR) surgery are a representative population to assess the effects of low loading frequency on knee joint health because they are at elevated risk for posttraumatic OA development and demonstrate low daily steps compared to uninjured individuals. Therefore, the overall study objective is to determine the mechanistic links between joint loading frequency and comprehensive magnetic resonance imaging (MRI) measures of knee joint cartilage health in individuals post-ACLR. The central hypothesis is that individuals post-ACLR who take low daily steps will demonstrate deconditioned, less resilient cartilage characterized by poor tibiofemoral cartilage composition and greater cartilage strain which represent equally important, but independent measures of cartilage health. Furthermore, increasing daily steps using a 16-week daily step promotion paradigm in individuals post-ACLR who underload (<7000 daily steps which is predictive of physical inactivity) will recondition cartilage by improving tibiofemoral cartilage composition and strain. The proposed study aims to determine: 1) associations between daily steps with tibiofemoral cartilage composition and strain in ACLR individuals (n=56) using an observational cross-sectional study design, and 2) the effects of increasing daily steps over 16-weeks on tibiofemoral cartilage composition and strain in ACLR individuals with low daily steps (n=28) using a single arm, longitudinal pre-test post-test study design. The proposed study is innovative because it builds on observational studies linking underloading with poor knee joint health and will be the first study to mechanistically determine how altering loading frequency (i.e., increasing daily steps) affects comprehensive in vivo measures of cartilage health in individuals at risk for OA. Successful completion of the proposed study will provide foundational evidence for the development of a future randomized controlled trial to determine the efficacy of an adaptive daily step promotion intervention to reduce the risk of OA development in high-risk individuals. The proposed K01 Career Development Award will provide the investigator with protected time to advance analysis and interpretation of MRI measures of cartilage biology and mechanics as well as develop skills in clinical trial implementation. The comprehensive training plan is vital to the investigator’s long-term career development in establishing an independent research line to develop novel interventions for OA prevention and promote long-term quality of life.

项目摘要/摘要 骨关节炎（OA）是残疾的主要原因。识别可修改的膝盖关节健康状况不佳的机制 疾病预防策略的发展对于改善长期健康至关重要。异常机械 从理论上讲，负载是膝盖OA的主要危险因素。大多数研究主要关注机械 OA开发中过量关节负载的机制。但是，最近的证据表明联合 下载也可能起作用。通过现实世界中每日步骤评估低负载频率的影响 在膝关节健康上的设置是有风险的个体异常机械负载的参数 对于OA。接受ACL重建（ACLR）手术的前交叉韧带（ACL）损伤的个体 是评估低负荷频率对膝关节健康的影响的代表人群，因为 与未受伤相比 个人。因此，总体研究目标是确定关节载荷之间的机械联系 膝关节软骨健康的频率和全面的磁共振成像（MRI）测量 ACLR后的个人。中心假设是，在每日较低步骤的ACLR之后的个人将会 表现为脱节，耐药性软骨，其特征是胫骨软骨组成和 更大的软骨菌株代表同样重要的软骨健康。 此外，使用16周的每日步骤促销范式在-ACLR后增加每日步骤 谁负荷（可预测身体不活动的每日步骤<7000个步骤）将通过改善修复软骨 胫骨软骨组成和应变。拟议的研究旨在确定：1） 使用检查的ACLR个体中胫骨软骨组成和应变的每日步骤（n = 56）使用检查 横断面研究设计，以及2）在16周上增加每日步骤对胫骨软骨的影响 使用单臂，纵向预测试的ACLR较低步骤（n = 28）的ACLR个体组成和应变 测试后研究设计。拟议的研究具有创新性，因为它以连接的观察性研究为基础 膝关节健康不良的负荷下载，将是第一项机械确定改变的研究 加载频率（即增加日期步骤）会影响软骨健康的全面体内测量 有OA风险的人。拟议研究的成功完成将为 开发未来的随机对照试验，以确定自适应每日促进的效率 干预措施以降低高风险个体OA发展的风险。拟议的K01职业 开发奖将为调查员提供受保护的时间，以提高分析和解释 软骨生物学和力学的MRI测量以及临床试验实施方面的技能。这 全面的培训计划对于调查员的长期职业发展至关重要 独立的研究系列，以开发预防OA的新干预措施并促进长期生活质量。