Steps Towards OA Prevention

项目摘要/摘要 骨关节炎(OA)是导致残疾的主要原因。确定膝关节健康不良的可修改机制 制定疾病预防战略对于改善长期健康至关重要。异常机械 负重已被认为是膝骨性关节炎的主要危险因素。大多数研究主要集中在机械方面 关节负荷过大在骨性关节炎发生中的作用机制。然而，最近的证据表明，联合 超载也可能起到一定作用。在现实世界中通过日常步骤评估低负荷频率的效果 膝关节健康的设置是危险个体异常机械负荷的一个未被充分研究的参数 对于办公自动化来说。接受前十字韧带重建(ACLR)手术的前交叉韧带(ACL)损伤患者 是评估低负荷频率对膝关节健康影响的代表性人群，因为他们 创伤后发生骨性关节炎的风险较高，与未受伤的人相比，每天的步数较少 个人。因此，研究的总体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综合磁共振成像测量 ACLR后的个人。中心假设是，ACLR后每天步行较少的人将 表现为松弛的、弹性较差的软骨，其特征是胫股软骨成分差和 更大的软骨应变代表着同样重要但独立的软骨健康衡量标准。 此外，在ACLR后的个人中，使用16周的每日步数提升范例来增加每日步数 世界卫生组织负荷不足(每天7000步，这预示着身体缺乏活动)将通过改善 胫股软骨的组成和应变。这项拟议的研究旨在确定：1) 应用观察性研究ACLR患者(n=56)的胫股软骨组成和应变的每日步数 横断面研究设计，2)连续16周增加每日步数对胫股软骨的影响 采用单臂纵向预试的低日步数ACLR患者(n=28)的成分和应变 后测研究设计。这项拟议的研究具有创新性，因为它建立在观察性研究的基础上 负荷不足，膝关节健康状况不佳，这将是第一个从机械上确定如何改变 加载频率(即增加每天的步数)影响体内软骨健康的全面测量 有骨性关节炎风险的个体。拟议研究的成功完成将为 未来一项随机对照试验的发展，以确定适应性每日阶梯推进的疗效 采取干预措施降低高危人群发生骨性关节炎的风险。建议的K01职业生涯 发展奖将为调查人员提供受保护的时间，以推进分析和解释 MRI测量软骨生物和力学指标，以及在临床试验实施中发展技能。这个 全面的培训计划对侦查人员的长期职业发展至关重要 独立研究路线，以开发预防骨性关节炎的新干预措施，并提高长期生活质量。

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.