Modification of Post-Traumatic Osteoarthritis Progression with Joint Unloading

通过关节卸载来改变创伤后骨关节炎的进展

• 批准号: 10549290
• 负责人: Blaine A. Christiansen
• 金额: $ 44.65万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10549290
• 关键词: Affect; Arthralgia; Articular Range of Motion; Atrophic; Biological Response Modifier Therapy; Biomechanics; Bone Resorption; Bone Spur; Bone structure; Catabolic Process; Cell Death; Clinical; Clinical Research; Consensus; Data; Development; Disease; Exercise; Gait; Goals; Health; Hindlimb Suspension; Hour; Individual; Inflammation; Inflammation Process; Inflammatory; Injury; Intervention; Joint Laxity; Joints; Knee; Life; Mechanics; Modeling; Moderate Activity; Modification; Mus; Muscle; Muscular Atrophy; Operative Surgical Procedures; Outcome; Pain management; Patients; Peptide Hydrolases; Persons; Phase; Population; Process; Recommendation; Replacement Arthroplasty; Research; Rest; Structure; Therapeutic; Time; Traumatic Arthropathy; Walking; anterior cruciate ligament injury; anterior cruciate ligament rupture; articular cartilage; bone; bone preservation; cartilage degradation; clinically relevant; injured; insight; intervention effect; joint destruction; joint injury; joint loading; limb injury; muscle form; muscle strength; preservation; prevent; rehabilitation strategy; repaired; sham surgery; subchondral bone; treatment strategy

Project Summary/Abstract: Post-traumatic osteoarthritis (PTOA) affects at least 50% of people who sustain a traumatic joint injury such as anterior cruciate ligament (ACL) rupture, with symptomatic joint pain typically developing within 1-2 decades following injury. Modulating joint loading (exercise/walking) or unloading (rest/disuse) in the early phase (<7 days) following injury could be used to decrease inflammation and catabolic processes that initiate PTOA. However, there is currently no clinical consensus on recommendations for joint loading or unloading during the early phase, and the effect of post-injury loading/unloading on joint degeneration has never been mechanistically investigated. The overall goal of this research is to determine how biomechanical interventions can be utilized following joint injury to affect the initiation and progression of PTOA. The proposed studies will use a clinically relevant injury model (non-invasive, mechanically-induced ACL rupture in mice) and clinically relevant post-injury conditions (mechanical unloading of the injured limb, intermittent reloading, surgical restabilization of the joint) to determine the effect of biomechanical therapies for slowing PTOA progression after injury. We hypothesize that unloading following injury will reduce inflammation, protease activity, and mechanical damage in the joint during the early post-injury phase, and that mitigation of these early processes will change the trajectory of PTOA progression relative to normally loaded joints. We further hypothesize that muscle and bone atrophy associated with unloading will be ameliorated with intermittent reloading without leading to joint degeneration, and that surgical restabilization of the knee following one week of unloading will further reduce long-term joint degeneration, while restabilization following one week of normal loading will not be as effective for changing the trajectory of PTOA. We will first determine the effect of mechanical unloading during the early phase on inflammatory and catabolic processes and long-term joint degeneration. Next, we will determine the effect of intermittent reloading on muscle mass and strength, subchondral bone structure, and long-term joint degeneration. Finally, we will determine the effect of surgical restabilization of the knee following normal activity or mechanical unloading during the early phase on long-term joint degeneration. These studies will determine if unloading and other biomechanical treatments during the early post-injury phase “pause” PTOA development (i.e., delay but do not prevent long-term joint degeneration), or if they are able to diminish long-term joint degeneration. These studies will allow us to individually evaluate the effects of joint unloading, intermittent reloading, and surgical joint restabilization following injury, and will provide mechanistic insights into biomechanical interventions that will inform subsequent clinical studies, potentially leading to optimization of therapeutic strategies for preserving long-term joint health of patients following injury.

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