Validation of the Pathomechanics and Biology of a Novel Pre-Clinical Rabbit Model for Hip Pre-Osteoarthritis

About This Grant

PROJECT SUMMARY Osteoarthritis (OA) is a worldwide chronic joint disease that causes pain and disability, and limits daily activity. Hip OA is the second most common disease after knee OA. Currently, total hip replacement (THR) is the treatment of choice for advanced hip OA. Given that life expectancy is longer, and we have not found a cure for OA, it is predicted that THR cases in the United States will increase to more than 1.4 million cases per year by 2040 resulting in a tremendous cost for the healthcare system. Hip Femoracetabular Impingement (FAI) is the leading cause of hip osteoarthritis in the young adult hip population. While the number of surgical procedures to treat hip FAI has grown exponentially in the past decade, there is still a 10-25% failure rate following surgical treatment, with progressive deterioration of the joint leading to OA. Surgeries have outpaced the true understanding of the disease resulting in failures rates around 15%, where patients still progress to OA following surgical intervention. Therefore, there is a need to study the mechanisms involved in initiating OA upon FAI and address this scientific gap. Without a validated animal model, our ability to discover the mechanisms of disease progression is limited. With the goal of having a low-cost and easy to reproduce translational animal model, our group has developed a small animal model of femoral head deformity that results in hip OA. Given 1) that FAI and its progression to hip OA stems from a mechanically induced repetitive injury and 2) the mechanical differences between quadrupedal and bipedal species, it is necessary to validate this model to human FAI mechanically and biologically. The goal of this proposal is to confirm that the experimentally induced femoral head hip deformity is a validated model to human FAI, both mechanically and biologically. For this we will: i) Determine differences in the mechanical behavior of the hip joint cartilage 1) before and after experimentally induced femoral head deformity in a rabbit model of hip FAI and 2) compare these changes to those seen in human hip FAI and ii) Investigate expression of proven human key molecular players in the progression of hip OA secondary to FAI in cartilage samples from the established rabbit femoral head deformity model. This project has the potential to tremendously impact the field, as it will allow, for the first time, to have a low cost, small translational animal model of hip FAI and hip OA. This model could be used as a platform to understand in-depth the mechanisms of hip OA, test interventions and translate our discoveries to patient care.