Clinical and Biochemical Predictors of Outcome after Knee Injury in Young Patient

描述(由申请人提供)：创伤后骨关节炎是接触性运动损伤的公认结果，但在前十字韧带(ACL)非接触性断裂后出现的问题被低估和研究不足。据估计，大约40%-50%的年轻运动员在高中参加体育活动期间遭受前交叉韧带损伤10-20年后，有发生进行性骨关节炎(OA)的显著风险。不幸的是，哪些运动员在前交叉韧带损伤后发生骨性关节炎的风险最高，目前尚不存在可靠的预测指标。我们首次提出在350名没有受伤的青少年高中运动员的竞赛赛季之前、期间和之后建立特定生物标记物的基线血清测量方法(目标1)。我们将前瞻性地跟踪这组受试者4年。同时，我们将研究第二组年龄匹配的年轻高中运动员，他们有记录在案的前交叉韧带撕裂。生物标记物将在这些受试者受伤后进行测量，直到生物标记物的值正常化。这些受试者将在术后使用患者报告结果(PRO)工具进行为期两年的跟踪调查。我们假设，相对于正常人群，前交叉韧带损伤后的生物标记物水平将会升高。此外，我们假设生物标记物在前交叉韧带损伤后有更严重骨挫伤的受试者中最高(目标2)。最后，我们将确定前交叉韧带损伤后严重骨挫伤受试者的预后(目标3)。骨挫伤的存在并不是创伤后骨性关节炎和较低的临床结果评分的预测指标，然而，骨挫伤与前交叉韧带损伤后骨关节炎的进展有关。我们将检查骨挫伤的大小、分布或严重程度、较低的患者报告结果和创伤后2年随访的骨性关节炎开始的证据之间是否存在相关性。我们还将重新检查手术前MRI扫描、手术前和手术后标准化X光，以及患者报告的超过2年的结果(随访率为85%)，对112名无其他合并症的孤立前交叉韧带损伤患者进行前瞻性纵向队列研究。通常，这些患者中90%-100%可能会在前交叉韧带损伤后出现骨挫伤。预计这些研究的影响将是巨大的。生物标志物的识别和验证，以及与前交叉韧带断裂相关的骨挫伤程度的相关数据的支持，将为临床医生提供手段，以识别青少年患致残和致残创伤后骨关节炎的高风险，并为这一脆弱群体提供量身定制的治疗和康复方案，以预防或推迟早期发病的骨关节炎。 公共卫生相关性：随着参加高中体育活动的增加，年轻人膝盖的非接触性损伤正以惊人的速度流行。前十字韧带(ACL)损伤伴骨挫伤可能会加速软骨丢失，使一些人易患早期骨性关节炎。这项研究调查了一种血清生物标记物的能力 和磁共振成像，以(单独或联合)预测高中运动员在前交叉韧带损伤时进行性、持续性的软骨丢失。这项研究的结果可能会对这些年轻运动员设计和实施新的、更好的治疗和康复方案产生重大影响。

DESCRIPTION (provided by applicant): Posttraumatic osteoarthritis is an acknowledged outcome of contact-related sports injuries but is an underestimated and understudied problem occurring after non-contact rupture of the anterior cruciate ligament (ACL). It is estimated that approximately 40-50% of young athletes are at significant risk for developing progressive osteoarthritis (OA) 10-20 years after ACL injury suffered during high school sports participation. Unfortunately, reliable predictors of which athletes are at highest risk for developing OA after ACL injury do not exist. We propose to establish, for the first time, baseline serum measures of specific biomarkers in 350 injury- free adolescent high school athletes before, during, and after their competitive season (Aim 1). We will follow this cohort of subjects prospectively for 4 years. Simultaneously, we will study a second age- matched cohort of young high school athletes with documented ACL tears. Biomarkers will be measured in these subjects post-injury, until biomarker values normalize. These subjects will be followed for two years post-operatively using patient reported outcome (PRO) instruments. We hypothesize that biomarker levels will increase after ACL injury relative to a normative population. In addition, we hypothesize that biomarkers will be highest in subjects with more severe bone bruising after ACL injury (Aim 2). Finally, we will determine outcomes of subjects with severe bone bruises following ACL injury (Aim 3). The presence of bone bruise is not known to be a predictor of posttraumatic OA and lower clinical outcomes scores, however, bone bruises have been implicated in the progression of osteoarthritis after ACL injury. We will examine if any correlation exists between the magnitude, distribution, or severity of bone bruise, lower patient reported outcomes, and evidence of posttraumatic OA initiation at 2 year follow-up. We will also re-examine pre-operative MRI scans, pre and post-operative standardized x-ray, and patient reported outcomes followed over 2 years (with a follow-up rate of 85%) in a prospective longitudinal cohort of 112 isolated ACL injured patients with no additional comorbidities. Typically, 90-100% of these patients may be expected to have a bone bruise after ACL injury. The impact of these studies is expected to be significant. The identification and validation of biomarkers, with and without supporting correlating data from the extent of bone bruise associated with ACL rupture, will provide clinicians with the means to identify adolescents at high risk for the development of disabling and crippling posttraumatic osteoarthritis and tailor treatment and rehabilitation protocols that may prevent or delay early onset osteoarthritis in this vulnerable population. PUBLIC HEALTH RELEVANCE: Non-contact injuries to the knee in the young are becoming prevalent at an alarming rate as participation in high school sports increases. Anterior cruciate ligament (ACL) injuries with bone bruises may hasten cartilage loss, predisposing some individuals to early onset osteoarthritis. This study investigates the ability of a serum biomarker and magnetic resonance imaging to predict (separately or in combination) progressive, unremitting cartilage loss in high school athletes at the time of ACL injury. The result of this study may significantly impact the design and implementation of new, better treatment and rehabilitation protocols in these young athletes.