Steps Towards OA Prevention

项目总结/摘要 骨关节炎（OA）是导致残疾的主要原因。确定膝关节健康状况不佳的可改变机制 制定疾病预防战略对改善长期健康至关重要。机械异常 负荷理论上是膝关节OA的主要危险因素。大多数研究主要集中在机械 OA发展中关节过度负荷的机制。然而，最近的证据表明， 欠载也可能起作用。通过真实的世界中的日常步数评估低负荷频率的影响 膝关节健康的设置是一个未充分研究的参数异常机械负荷的个人风险 对于OA。前交叉韧带（ACL）损伤患者接受ACL重建（ACLR）手术 是评估低负荷频率对膝关节健康影响的代表性人群，因为 与未受伤者相比，创伤后OA发展的风险较高，并且每日步数较低 个体因此，总体研究目标是确定关节负荷之间的机械联系 频率和综合磁共振成像（MRI）测量膝关节软骨健康， ACLR后的个体。核心假设是，ACLR后每天走得少的人 表现出以胫股软骨成分差为特征的失调、弹性较低的软骨， 更大的软骨应变，代表同样重要，但独立的软骨健康的措施。 此外，在ACLR后的个体中，使用16周的每日步数促进范式增加每日步数， 谁负荷不足（<7000每天的步骤，这是预测的身体不活动）将修复软骨，通过改善 胫股软骨组成和应变。该研究旨在确定：1） 使用一种观察性方法，在ACLR个体（n=56）中， 横断面研究设计，2）16周内增加每日步数对胫股软骨的影响 使用单臂纵向预测试，在每日步数较低的ACLR个体（n=28）中进行成分和应变分析 测试后研究设计。这项拟议的研究是创新的，因为它建立在观察性研究的基础上， 膝关节健康状况不佳，这将是第一项研究，以机械地确定如何改变 加载频率（即，增加每日步数）影响软骨健康的全面体内测量， 有OA风险的人。成功完成拟议的研究将为以下方面提供基础证据： 制定未来的随机对照试验，以确定适应性每日台阶提升的有效性 干预以降低高风险个体中OA发展的风险。K 01职业生涯 发展奖将为研究者提供受保护的时间，以推进分析和解释 MRI测量软骨生物学和力学，并培养临床试验实施技能。的 全面的培训计划对研究者的长期职业发展至关重要， 独立的研究线，开发新的干预措施，预防OA和促进长期生活质量。

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.