Biomarkers & biomechanics associated with injury-mediated osteoarthritis

骨关节炎(OA)的有效干预措施有限，需要创新的研究方法来 推进对这一常见致残性疾病的检测、预防和治疗。损伤介导性骨性关节炎 提供了一种独特的OA模型，在该模型中可以清楚地识别关节新陈代谢变化的开始 (受伤的时间)和进展为骨性关节炎比通过非损伤途径更快的地方。变态人类 运动生物力学和生化标志物水平可能是高危个体的关键标识 对于损伤介导性骨关节炎，谁将从干预措施中受益，如之前的神经肌肉训练计划 受伤后。 我们有极好的机会在现有的大的有前路障碍的队列中研究骨关节炎的进程。 交叉韧带(ACL)损伤。拟议的研究将促进我们对关键标记的理解 (生化和生物力学)与骨性关节炎相关，以及损伤在加速骨性关节炎发病中的作用。 这项建议得益于：1)现有的血清样本和流行病学、损伤和生物力学数据 来自一大群年轻的军校学员，以及2)多产的 流行病学、生物力学、生物标记物和骨关节炎研究人员。 该项目的具体目标是： 1)确定关节代谢的血清生物标志物是否横断面与 无前交叉韧带损伤受试者的运动生物力学； 2)纵向确定事件发生后关节代谢的血清生物标志物是否发生改变 在相同受试者中，前交叉韧带损伤相对于损伤前水平，以及与未损伤的相比 参与者； 3)量化急性前交叉韧带损伤后同侧膝关节骨性关节炎的风险增加； 4)确定与前交叉韧带损伤相关的血清生物标志物的纵向变化是否可以预测 同侧膝关节骨关节炎(在有前交叉韧带损伤的受试者中)。 这项研究是及时的、创新的、具有成本效益的，对于寻求理解 关节损伤后骨性关节炎发生的机制。

Effective interventions for osteoarthritis (OA) are limited, and innovative research approaches are needed to advance the detection, prevention, and treatment of this common and disabling disease. Injury-mediated OA provides a unique model of OA, one in which the onset of joint metabolism changes can be clearly identified (the time of injury) and where progression to OA is faster than via non-injury pathways. Abnormal human movement biomechanics and biochemical marker levels may be critical identifiers of individuals at high risk for injury-mediated OA who would benefit from interventions such as neuromuscular training programs preor post-injury. We have the remarkable opportunity to examine the course of OA among large existing cohort with Anterior Cruciate Ligament (ACL) injury. The proposed study will advance our understanding of key markers (biochemical and biomechanical) associated with OA and ofthe role of injury in accelerafing the onset of OA. This proposal benefits from: 1) existing serum samples and epidemiological, injury, and biomechanical data from a large cohort of young military cadets, and 2) well-established collaborations between prolific epidemiologic, biomechanics, biomarker, and osteoarthritis investigators. Specific Aims of the project are: 1) Determine whether serum biomarkers of joint metabolism are associated cross-sectionally with movement biomechanics in subjects with no ACL injury; 2) Determine longitudinally whether serum biomarkers of joint metabolism are altered following incident ACL injury, relative to pre-injury levels in the same subjects, and in comparison to non-injured participants; 3) Quantify the increase in the risk of radiographic ipsilateral knee OA following incident ACL injury; 4) Determine whether longitudinal changes in serum biomarkers associated with ACL injury predict risk of ipsilateral knee OA (in subjects with incident ACL injury). This study is timely, innovative, cost-efficient, and of great signficance in the quest to understand mechanisms underiying the development of OA in response to joint injury.