Multicenter Investigation of the Mechanical Determinants of Post-Traumatic OA

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DESCRIPTION (provided by applicant): The objective of the proposed research is to demonstrate the feasibility of utilizing innovative methods for the assessment of intra-articular fractures in multi-center clinical studies. A key challenge in these studies is that we do not yet know what mechanical factors most strongly influence post-traumatic osteoarthritis development. We aim to scale up the use of objective methods that we have developed for quantifying fracture severity and post-operative contact stress challenge (from residual surface incongruity) to provide this knowledge, thereby laying the foundation for future clinical trials in patients with intra-articular fractures. The long-term goal of this work is to develop new interventions that forestall the onset of post-traumatic osteoarthritis. Post-traumatic osteoarthritis is a disabling condition resulting from joint injury. Unfortunately, continued refinement of existing treatment methods has failed to decrease the substantial incidence and severity of post- traumatic osteoarthritis. Recent research indicates that acute-impact joint injuries initiate a sequence of biologic events that cause the progressive joint degeneration that leads to post-traumatic osteoarthritis. There is considerable evidence emerging from explant tissue and animal studies that new molecular interventions applied to the joint soon after traumatic injury can mitigate or arrest these adverse events and thus, promote joint healing. These studies offer hope for a paradigm shift in the acute management of articular joint injury, but controlled clinical trials are desperately needed to realize this potential. Patients who sustain high-energy articular fractures are good candidates for a clinical trial because the injury is identified and treated acutely, the outcome of interest (post-traumatic osteoarthritis) occurs relatively quickly and frequently, and the arthritic changes are readily imaged using standard radiography. For instance, after tibial pilon fractures, post-traumatic osteoarthritis occurs in over fifty percent of affected ankles and is clinically evident within two years. In the proposed pilot and feasibility study the scope of patients evaluated with these mechanical metrics will be expanded considerably (Aim 1), and the extent to which fracture severity and post-reduction contact stress predict post-traumatic osteoarthritis will be determined (Aim 2). Tibial pilon fracture patients will be enrolled from a wider population base, treated with different techniques at different locations, through the federally funded Major Extremity Trauma Research Consortium (METRC). METRC is a collaboration of 23 core civilian trauma centers, 4 military treatment facilities, and 38 satellite centers throughout the United States. The proposed study and this collaboration will provide a strong platform for future contemplated trials of biologic intervention to prevent post-traumatic osteoarthritis. PUBLIC HEALTH RELEVANCE: Post-traumatic osteoarthritis is a disabling condition that results from joint injury, most predictably after fractures of joints such as the ankle, knee, or hip. Continued refinement of existing treatment methods has failed to decrease the substantial incidence and severity of post-traumatic osteoarthritis. Recent research offers hope for a paradigm shift in the acute management of articular joint injury, but clinical trials with appropriate control of confounding variables are desperately needed to realize this potential. This study and the collaboration between the federally funded Major Extremity Trauma Research Consortium and the University Of Iowa Center Of Research Translation provide a platform for future contemplated trials of biologic intervention to prevent this crippling disorder.