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， 推进对这种常见致残疾病的检测、预防和治疗。损伤介导的OA 提供了一个独特的OA模型，其中关节代谢变化的发作可以清楚地识别 (the损伤时间），并且其中进展为OA比通过非损伤途径更快。人体异常 运动生物力学和生化标志物水平可能是高风险个体的关键标识符 对于损伤介导的OA患者， 受伤后。 我们有一个难得的机会来检查现有的大型前节段骨性关节炎队列的病程。 交叉韧带（ACL）损伤。这项拟议中的研究将促进我们对关键标志物的理解 （生物化学和生物力学）以及损伤在加速OA发病中的作用。 该建议受益于：1）现有的血清样本和流行病学，损伤和生物力学数据 从一大批年轻的军事学员，和2）之间建立良好的合作，多产 流行病学、生物力学、生物标志物和骨关节炎研究者。 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与关节炎相关。 无ACL损伤受试者的运动生物力学; 2)纵向确定关节代谢的血清生物标志物是否在事件发生后改变 ACL损伤，相对于相同受试者的损伤前水平，并与未受伤的受试者进行比较 参与者; 3)量化ACL损伤后影像学同侧膝关节OA风险的增加; 4)确定与ACL损伤相关的血清生物标志物的纵向变化是否可预测 同侧膝关节OA（发生ACL损伤的受试者）。 本研究是及时的，创新的，成本效益高的，并在寻求理解的重要意义 关节损伤后OA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.