Multicenter Investigation of the Mechanical Determinants of Post-Traumatic OA

描述（由申请人提供）：本研究的目的是证明在多中心临床研究中使用创新方法评估关节内骨折的可行性。这些研究的一个关键挑战是，我们还不知道什么机械因素最强烈地影响创伤后骨关节炎的发展。我们的目标是扩大我们开发的用于量化骨折严重程度和术后接触应力挑战（来自残余表面不一致）的客观方法的使用，以提供这些知识，从而为未来关节内骨折患者的临床试验奠定基础。这项工作的长期目标是开发新的干预措施，以预防创伤后骨关节炎的发作。创伤后骨关节炎是一种由关节损伤导致的致残状况。不幸的是，现有治疗方法的不断改进并不能降低创伤后骨关节炎的发生率和严重程度。最近的研究表明，急性冲击关节损伤启动了一系列的生物事件，导致进行性关节变性，导致创伤后骨关节炎。从外植组织和动物研究中出现的大量证据表明，创伤性损伤后不久应用于关节的新的分子干预可以减轻或阻止这些不良事件，从而促进关节愈合。这些研究为关节损伤急性管理的范式转变提供了希望，但迫切需要对照临床试验来实现这一潜力。高能量关节骨折的患者是临床试验的良好候选者，因为损伤是急性识别和治疗的，感兴趣的结果（创伤后骨关节炎）发生相对迅速和频繁，并且关节炎的变化很容易使用标准x线摄影成像。例如，胫骨pilon骨折后，超过50%的踝关节发生创伤后骨关节炎，并在两年内临床表现明显。在拟议的试点和可行性研究中，用这些力学指标评估的患者范围将大大扩大（目的1），并且将确定骨折严重程度和复位后接触应力预测创伤后骨关节炎的程度（目的2）。胫骨pilon骨折患者将通过联邦资助的重大肢体创伤研究联盟（METRC）从更广泛的人群基础中招募，在不同地点使用不同的技术进行治疗。METRC是一个由23个核心民用创伤中心、4个军事治疗设施和38个遍布美国的卫星中心组成的合作项目。拟议的研究和这次合作将为未来预期的生物干预试验提供一个强大的平台，以预防创伤后骨关节炎。

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.