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局，但在前交叉韧带（ACL）非接触性断裂后发生的问题被低估和研究不足。 据估计，大约40-50%的年轻运动员在参加高中体育运动期间遭受ACL损伤后10-20年内有发生进行性骨关节炎（OA）的显著风险。不幸的是，可靠的预测哪些运动员在ACL损伤后发生OA的风险最高并不存在。 我们建议在350名没有受伤的青少年高中运动员的竞争赛季之前、期间和之后，首次建立特定生物标志物的基线血清测量值（目标1）。我们将前瞻性随访该受试者队列4年。同时，我们将研究第二个年龄匹配的年轻高中运动员队列，记录ACL撕裂。将在这些受试者中测量损伤后的生物标志物，直到生物标志物值正常化。 这些受试者将在术后使用患者报告结局（PRO）工具随访2年。我们假设，相对于正常人群，ACL损伤后生物标志物水平会增加。此外，我们假设生物标志物在ACL损伤后骨挫伤更严重的受试者中最高（目标2）。 最后，我们将确定ACL损伤后严重骨挫伤受试者的结局（目标3）。骨挫伤的存在并不是创伤后OA和较低临床结局评分的预测因素，但是，骨挫伤与ACL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、较低的患者报告结局和2年随访时创伤后OA发生的证据之间是否存在任何相关性。我们还将重新检查术前MRI扫描、术前和术后标准化X线检查以及患者报告的随访2年以上的结局（随访率为85%），这是一个前瞻性纵向队列，包括112例无其他合并症的孤立ACL损伤患者。 通常情况下，预计这些患者中有90-100%在ACL损伤后会出现骨挫伤。 预计这些研究的影响将是重大的。生物标志物的鉴定和验证，无论是否支持与ACL断裂相关的骨挫伤程度的相关数据，都将为临床医生提供识别致残性和致残性创伤后骨关节炎高风险青少年的方法，并定制治疗和康复方案，以预防或延迟该弱势人群的早发性骨关节炎。 公共卫生相关性：随着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。前交叉韧带（ACL）损伤伴骨挫伤可能会加速软骨损失，使某些个体易患早发性骨关节炎。这项研究调查了血清生物标志物的能力 和磁共振成像来预测（单独或联合）进行性，持续的软骨损失在高中运动员在ACL损伤时。这项研究的结果可能会显着影响新的，更好的治疗和康复方案在这些年轻运动员的设计和实施。

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.