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

项目摘要 在美国，每年有25万人会严重损伤他们的前交叉韧带 其中一半人将在十年内出现膝骨性关节炎(OA)的放射征象。不幸的是， 目前尚不存在预防创伤后膝骨性关节炎的循证干预措施。关节结构的变化 在前交叉韧带损伤后，与X线片显示的膝关节骨性关节炎相关的功能迅速发生，特别是1) 两个月内定量磁共振成像的关节软骨基质组织 前交叉韧带重建后2)前交叉韧带损伤后早期及术后6个月关节卸荷异常 重建，以及3)重建前自报膝关节功能差。体力活动不足 水平在老年人的骨性关节炎中发挥作用，但它们对创伤后骨性关节炎进展的影响尚不清楚。 特别是与联合加载相结合时。了解这些早期的变化以及它们之间的关系 体力活动水平和运动模式与后来的关节结果(关节软骨破裂，膝关节 功能)对于今后制定干预措施以阻止向骨质疏松症的进展至关重要。这样做的目的是 这项研究是为了找出预测前交叉韧带损伤后关节预后不良的最早迹象的标志物。我们会 通过加速计步法(步数)和生物力学功能(最佳膝关节)测量日常体力活动 步态负荷阶段的瞬间)，在前交叉韧带损伤后1个月内，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内完成MRI测试 重建前交叉韧带后确定关节软骨微结构的变化(T2测量 放松时间)。膝关节功能将通过膝关节损伤和骨关节炎结果评分(KOOS)来衡量 在前交叉韧带重建后6个月。在目标1中，我们将确定体力活动水平和 前交叉韧带重建前后生物力学功能与术后6个月T2松弛时间变化的关系 在重建ACL之后。累计关节载荷(日均步数与膝关节屈曲力矩的乘积) 将根据个人的身体活动和生物力学因素进行测试，以确定最强的关节 T2松弛时间的载荷行列式。在目标2中，我们将确定预测每日体力活动水平 古氏家族术后膝关节功能不佳。这项工作将定义预测早期运动的生物标记物 前交叉韧带损伤后软骨微结构(AIM 1)和术后膝关节功能(AIM 2)的变化。 这项研究的成功完成将导致确定健康膝关节的初始目标或范围 前交叉韧带损伤后的负荷水平。我们的发现将为测试不同方案的疗效提供基础。 旨在优化关节负荷，减少前交叉韧带损伤后关节软骨的退行性改变。我们 预测这些治疗将延缓前交叉韧带断裂或其他创伤性关节损伤后骨性关节炎的发病。

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.