DESCRIPTION: Patellofemoral pain (PFP) is a debilitating condition that peaks in incidence during the middle school years and eventually affects nearly 1 out of 4 school-aged youth. PFP is recognized as one of the most common disorders of the knee with cumulative health care costs estimated to exceed several billion dollars per year. Symptoms of PFP occur 2 to 10 times more often in females and typically restrict adolescents from participation in physical activity. The high recurrence rate of patellofemoral pain and the poor long-term prognosis indicate that prevention strategies would significantly reduce the morbidity associated with PFP developed during youth. Unfortunately, the risk factors that underlie the development of patellofemoral dysfunction and resultant PFP in young females remain unknown. Our long-term goals are to determine the risk factors and mechanisms that underlie the high rate of debilitating knee pain in females in order to develop targeted interventions for prevention. The overall objective of this application is to delineate the specific modifiable and non-modifiable risk factors that contribute to the development of patellofemoral dysfunction and resultant PFP. Our prior findings drive our central hypothesis that predisposing morphologic characteristics associated with growth and maturation, in concert with underdeveloped lower-extremity stabilizing mechanisms, initiate abnormal patellofemoral joint mechanics that lead to the onset of PFP. The expected outcome from the work proposed in Aim 1 will be identification of the onset of specific modifiable risk factors that cluster to differentiate young females at increased risk for the development of PFP. Following determination of modifiable risk factors, we will evaluate if an existing intervention is differentially effective to ameliorate aberrant biomechanics relative to maturational status (Aim 2). The contribution of this application is significant because it is expected to remove focus from unrelated contributors to PFP incidence that would otherwise undermine future definitive clinical investigations that target PFP risk factors. Successful completion of the proposed Aims will strategically position us to develop a competitive R01 application that focuses on the implementation of mechanism-driven PFP risk prediction algorithms and targeted interventions that reduce predisposing deficits to development of PFP in high risk female populations. The implication of a future R01 trial derived from these data is such that up to 25% of the female populous who are at risk to develop PFP will benefit from the resultant findings. The proposed research is innovative because it represents a new and substantive departure from the status quo via prospective identification of predisposing risk factors that will position us to evaluate te effectiveness of mechanism based interventions prior to development of PFP symptoms in a clinical trial. Once these validated strategies are achieved, we will have increased potential to prevent PFP, an important step on the preventative pathway for the reduction of physical inactivity in youth and adults. This proposal aligns with NIH initiatives to reduce physical inactivity in youth, which is the fourth leading cause of global mortality.