The adaptive response of skeletal muscle, bone, and cartilage to severe knee trauma involving ACL disruption with and without concomitant injury to the meniscus

骨骼肌、骨骼和软骨对严重膝关节创伤（涉及 ACL 破坏，伴有或不伴有半月板损伤）的适应性反应

• 批准号: 10428378
• 负责人: Bruce Beynnon
• 金额: $ 40.41万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10428378
• 关键词: Address; Affect; Ancillary Study; Anterior Cruciate Ligament; Architecture; Body mass index; Bone structure; Cartilage; Cartilage Matrix; Clinical Treatment; Clinical Trials; Contralateral; Data; Databases; Degenerative polyarthritis; Disease; Evolution; Future; Geometry; Individual; Injury; Intervention; Investigation; Joints; Knee; Knee joint; Knowledge; Limb structure; Mediating; Meniscus structure of joint; Muscle; Operative Surgical Procedures; Parents; Pathology; Patients; Persons; Population; Predisposition; Prevention; Process; Prospective Studies; Quality of life; Rehabilitation therapy; Research; Retrospective Studies; Risk; Seminal; Severities; Skeletal Muscle; Structure; Thick; Time; Tissues; Trauma; Trauma patient; anterior cruciate ligament injury; anterior cruciate ligament rupture; articular cartilage; base; bone; cost; early onset; joint injury; knowledge base; limb injury; meniscus injury; muscular structure; prospective; reconstruction; response; sex; symptom treatment; trauma surgery

Project Summary: Post-traumatic osteoarthritis (PTOA) is debilitating due to its early onset, predisposition to affect younger, active individuals and the need for earlier surgical and rehabilitative interventions, all of which decrease quality of life. More broadly, 12% of OA cases are due to joint trauma (12.7 million people), costing $3 billion/yr. Injuries of the anterior cruciate ligament (ACL) and meniscus are the most common concerns that place individuals at increased risk of developing PTOA about the knee. However, a dilemma exists in the treatment of PTOA because we do not understand how the severity of the injury affects the adaptive responses of the limb (muscle, bone, and articular cartilage), nor how these adaptations are modified by concomitant meniscus injury, the subject's sex, BMI and joint geometry. Moreover, it is unknown how these adaptive responses are associated with changes in early markers of the PTOA disease process. These knowledge gaps represent critical barriers to developing more effective, early PTOA treatment paradigms that are informed by an understanding of adaptions in skeletal muscle, bone and articular cartilage. To date, no study has prospectively characterized subjects prior to ACL injury and then evaluated the adaptive response of the limb to ACL rupture and surgical reconstruction. Our current knowledge base is built entirely on retrospective studies, and consequently we propose a prospective study that will evaluate two aims. Aim 1: Characterize the adaptive changes in skeletal muscle size and function, bone architecture, and articular cartilage matrix components that occur in response to severe knee trauma; and determine how these changes differ depending on the type of trauma (ACL disruption with and without concomitant injury to the menisci), the patient's sex, BMI, and joint geometry. Aim 2: Assess the effects of severe knee trauma on change in thickness of the articular cartilage (an early marker of PTOA) and determine if these effects are modified by structures involved in the trauma (ACL disruption with and without concomitant meniscus injury), the patient's sex, BMI, and joint geometry; and mediated by adaptive changes in skeletal muscle size and function, bone architecture, and articular cartilage matrix components. The study will provide data on the integrative, adaptive response of multiple tissues of the injured limb to knee trauma and surgery and builds logically upon the parent investigation. The study will provide a mechanistic understanding of the evolution of knee joint pathology that leads to PTOA, and the modifying effects of sex, BMI and joint geometry. Knowledge from this study will address critical barriers to progress in PTOA treatment by determining how the severity of the trauma affects cartilage structure at a time when interventions will be effective for prevention of incident or worsening PTOA: the barrier to trials focused on treatment of PTOA.

项目概要： 创伤后骨关节炎（PTOA）由于其早期发病，易影响年轻人， 积极的个人和需要早期手术和康复干预，所有这些都降低了质量 生命更广泛地说，12%的OA病例是由于关节创伤（1270万人）造成的，每年损失30亿美元。 前交叉韧带（ACL）和半月板损伤是最常见的问题， 膝关节周围发生PTOA风险增加的个体。然而，在治疗中存在着一个困境 因为我们不了解损伤的严重程度如何影响患者的适应性反应， 肢体（肌肉、骨和关节软骨），也不知道这些适应性如何被伴随的半月板改变 损伤、受试者的性别、BMI和关节几何形状。此外，还不知道这些适应性反应是如何产生的。 与PTOA疾病过程的早期标志物的变化相关。这些知识差距代表了 开发更有效的早期PTOA治疗模式的关键障碍， 了解骨骼肌、骨和关节软骨的适应性。到目前为止，没有任何研究 在ACL损伤前前瞻性地描述受试者的特征，然后评估肢体的适应性反应 前交叉韧带断裂和手术重建我们目前的知识库完全建立在回顾性的基础上 因此，我们提出了一项前瞻性研究，将评估两个目标。 目的1：描述骨骼肌大小和功能、骨结构和骨密度的适应性变化， 关节软骨基质成分发生在严重的膝关节创伤;并确定如何 这些变化取决于创伤的类型（ACL断裂伴或不伴损伤， 患者的性别、BMI和关节几何形状。 目的2：评估严重膝关节创伤对关节软骨厚度变化的影响（早期评估）。 PTOA的标志物），并确定这些影响是否被创伤中涉及的结构（ACL）所改变 破裂伴或不伴半月板损伤）、患者性别、BMI和关节几何形状;以及 由骨骼肌大小和功能、骨结构和关节软骨的适应性变化介导 基质成分 该研究将提供有关受伤肢体多个组织对膝关节的综合适应性反应的数据 创伤和手术，逻辑上建立在父母的调查。这项研究将提供一个机制， 了解导致PTOA的膝关节病理学演变，以及性别的改变作用， BMI和关节几何结构。本研究的知识将解决PTOA治疗进展的关键障碍 通过确定创伤的严重程度如何影响软骨结构， 有效预防PTOA事件或恶化：针对PTOA治疗的试验的障碍。