Osteoarthritis After ACL Injury: Establishing Cumulative Joint Loading as a Preventative Target

项目摘要 在美国，每年有25万人的前十字韧带严重受伤， (ACL)，一半的人将在十年内出现膝关节骨关节炎（OA）的放射学体征。不幸的是， 预防创伤后膝关节OA的循证干预措施尚不存在。关节结构变化 ACL损伤后，与膝关节放射学OA相关的功能改变会迅速发生，特别是1） 两个月内定量磁共振成像（MRI）显示关节软骨基质组织 ACL重建后，2）ACL损伤后早期和ACL重建后6个月， 重建，和3）ACL重建前自我报告膝关节功能差。身体活动不足 水平在老年人的OA中发挥作用，但其对创伤后OA进展的影响尚不清楚， 特别是结合关节载荷。了解这些早期的变化和 身体活动水平和运动模式与后期关节结果（关节软骨破坏，膝关节 功能）对于未来开发干预措施以阻止OA进展至关重要。这样做的目的 这项研究的目的是确定预测ACL损伤后关节预后不良的最早迹象的标志物。我们将 通过加速度计（步数）和生物力学功能（膝关节峰值）测量日常身体活动 在步态的负荷阶段期间的时刻）在ACL损伤的一个月内以及在2，4， 前交叉韧带重建术后6个月。参与者将在基线和六个月时完成MRI测试 在ACL重建后测定关节软骨微结构的变化（通过T2测量 弛豫时间）。将通过膝关节损伤和骨关节炎结局评分（KOOS）测量膝关节功能 ACL重建术后6个月。在目标1中，我们将确定身体活动水平和 ACL重建前后的生物力学功能与6个月时T2弛豫时间的变化有关 ACL重建后。累积关节负荷（每日平均步数与膝关节屈曲力矩的乘积） 将根据个人身体活动和生物力学因素进行测试，以确定最坚固的关节 T2弛豫时间的加载决定因素。在目标2中，我们将确定日常身体活动的水平， KOOS上的术后膝关节功能较差。这项工作将定义运动生物标志物， ACL损伤后软骨微观结构（目的1）和术后膝关节功能（目的2）的变化。 成功完成本研究将导致识别健康膝关节的初始目标或范围 ACL损伤后的负荷水平。我们的研究结果将为检验不同方案的疗效提供基础 旨在优化关节负荷，以减少ACL损伤后关节软骨的退行性变化。我们 预测这些治疗将延迟ACL断裂或其他创伤性关节损伤后OA的发作。

Project Abstract Each year in the United States, a quarter million individuals will severely injure their anterior cruciate ligament (ACL), and half will develop radiographic signs of knee osteoarthritis (OA) within ten years. Unfortunately, evidence-based interventions to prevent post-traumatic knee OA do not yet exist. Changes in joint structure and function that are linked to radiographic knee OA occur quickly after ACL injury, particularly 1) alterations in articular cartilage matrix organization on quantitative magnetic resonance imaging (MRI) within two months after ACL reconstruction, 2) abnormal joint unloading early after ACL injury and six months after ACL reconstruction, and 3) self-reported poor knee function before ACL reconstruction. Insufficient physical activity levels play a role in OA in older adults, but their influence in progression to post-traumatic OA is unknown, particularly in combination with joint loading. Understanding these early changes and relationships between physical activity levels and movement patterns with later joint outcomes (articular cartilage breakdown, knee function) is critical for future development of interventions to hinder progression to OA. The purpose of this study is to identify markers that predict the earliest signs of poor joint outcomes after ACL injury. We will measure daily physical activity through accelerometry (step counts) and biomechanical function (peak knee moments during loading phase of gait) in participants within one month of ACL injury and again at two, four, and six months after ACL reconstruction. Participants will complete MRI testing at baseline and six months after ACL reconstruction to determine changes in the articular cartilage microstructure (measured by T2 relaxation time). Knee function will be measured by the Knee injury and Osteoarthritis Outcome Score (KOOS) at six months after ACL reconstruction. In Aim 1, we will determine how physical activity levels and biomechanical function before and after ACL reconstruction relate to changes in T2 relaxation time at 6 months after ACL reconstruction. Cumulative joint loading (product of mean steps per day and knee flexion moment) will be tested against individual physical activity and biomechanical factors to determine the strongest joint loading determinant of T2 relaxation time. In Aim 2, we will identify levels of daily physical activity that predict poor post-operative knee function on the KOOS. This work will define movement biomarkers that predict early changes in cartilage microstructure (Aim 1) and post-operative knee joint function (Aim 2) after ACL injury. Successful completion of this study will result in identification of an initial target or range of healthy knee joint loading levels after ACL injury. Our findings will provide a foundation to test the efficacy of different regimens aimed at optimizing joint loading to reduce degenerative changes in articular cartilage following ACL injury. We predict that these treatments will delay onset of OA following ACL rupture or other traumatic joint injury.