Multicenter Investigation of the Mechanical Determinants of Post-Traumatic OA

创伤后 OA 机械决定因素的多中心研究

• 批准号: 8192655
• 负责人: Donald D Anderson
• 金额: $ 25.77万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8192655
• 关键词: Accounting; Acute; Adverse event; Affect; Aftercare; Ankle; Arthritis; Clinical Trials; Collaborations; Community Health Centers; Confounding Factors (Epidemiology); Congestive; Controlled Clinical Trials; Data; Degenerative polyarthritis; Development; Diagnostic radiologic examination; Disease; End stage renal failure; Enrollment; Event; Feasibility Studies; Foundations; Fracture; Funding; Future; Goals; Healed; Heart; Hip region structure; Image; Impairment; Incidence; Influentials; Injury; Intervention; Investigation; Iowa; Joints; Knee; Knowledge; Limb structure; Location; Measures; Mechanics; Methods; Metric; Military Personnel; Molecular; Multi-Institutional Clinical Trial; Operative Surgical Procedures; Outcome; Pathogenesis; Patients; Pilot Projects; Postoperative Period; Randomized; Randomized Clinical Trials; Research; Residual state; Risk; Severities; Stress; Surface; Techniques; Translational Research; Trauma Research; United States; Universities; Work; animal tissue; clinical research site; comparative; healing; innovation; interest; joint injury; novel; population based; prevent; prospective; scale up; trauma centers

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.

描述（由申请人提供）：拟议的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。这些研究中的一个主要挑战是，我们尚不知道哪些机械因素最强烈影响创伤后骨关节炎的发育。我们旨在扩大我们开发的客观方法的使用，以量化骨折严重程度和术后接触应力挑战（来自残留表面不一致）以提供此知识，从而为未来的关节内骨折患者的临床试验奠定了基础。这项工作的长期目标是制定新的干预措施，以阻止创伤后骨关节炎的发作。 创伤后骨关节炎是因关节损伤引起的残疾疾病。不幸的是，现有治疗方法的持续细化未能降低后创伤性骨关节炎的大量发生率和严重程度。最近的研究表明，急性影响关节损伤引发了一系列生物事件，导致渐进性关节变性，导致创伤后骨关节炎。来自外植体组织和动物研究的证据表明，创伤性损伤后不久对关节应用的新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。这些研究为关节关节损伤的急性管理范式转移提供了希望，但是迫切需要进行对照临床试验来实现这一潜力。维持高能关节骨折的患者是临床试验的良好候选者，因为损伤是被识别和治疗的，感兴趣的结果（创伤后骨关节炎）相对较快，经常发生，并且使用标准射线照相对关节炎的变化进行了相对较快的速度。例如，在胫骨pil骨骨折后，创伤后骨关节炎发生在50％的受影响脚踝，并且在两年内在临床上很明显。 在拟议的试点和可行性研究中，将大大扩展使用这些机械指标评估的患者的范围​​（AIM 1），并且确定骨折后的骨折严重程度和还原后接触应力预测将确定创伤后骨关节炎后（AIM 2）。胫骨pilon骨折患者将从更广泛的人口基础中招募，并通过联邦资助的主要肢体创伤联盟（METRC）在不同位置接受不同技术的治疗。 METRC是23个核心创伤中心，4个军事治疗设施和38个卫星中心的合作。拟议的研究和这项合作将为未来的生物学干预试验提供一个强大的平台，以防止创伤后骨关节炎。 公共卫生相关性：创伤后的骨关节炎是一种致命的疾病，是由于关节损伤引起的，最可预见的是，在关节骨折（如脚踝，膝盖或臀部）之后。现有治疗方法的持续细化未能降低创伤后骨关节炎的大量发生率和严重性。最近的研究为关节关节损伤的急性管理范式转移提供了希望，但是迫切需要对混杂变量进行适当控制的临床试验来实现这一潜力。这项研究以及联邦政府资助的主要肢体创伤研究联盟与爱荷华大学研究中心翻译中心之间的合作为将来的生物学干预试验提供了一个平台，以防止这种残酷的疾病。