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.