Evaluating the impact of high body mass index on cartilage deformation, cartilage metabolism, and mechanical loading in individuals with anterior cruciate ligament reconstruction

评估高体重指数对前十字韧带重建个体的软骨变形、软骨代谢和机械负荷的影响

• 批准号: 10363622
• 负责人: Steven A. Garcia
• 金额: $ 3.88万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10363622
• 关键词: Biological; Biological Markers; Body mass index; Cartilage; Cartilage Matrix; Chronic; Complex; Degenerative polyarthritis; Development; Diagnosis; Diagnostic; Disease; Evaluation; Exhibits; Fostering; Future; Goals; Health; High Prevalence; Homeostasis; Human; Impairment; Incidence; Individual; Inflammation; Injury; Intervention; Joints; Knee; Knee joint; Knowledge; Link; Measures; Mechanics; Medial; Mission; Motivation; Nature; Obesity; Operative Surgical Procedures; Outcome; Pathogenesis; Pathologic; Pathology; Patients; Physical activity; Physiological; Population; Process; Reaction; Rehabilitation Outcome; Research; Research Personnel; Research Proposals; Response to stimulus physiology; Risk; Risk Factors; Serum; Stimulus; Structure; System; Thick; Time; Tissues; Training; United States National Institutes of Health; Walking; anterior cruciate ligament injury; anterior cruciate ligament reconstruction; articular cartilage; base; career; cartilage degradation; cartilage metabolism; diagnostic tool; disability; experience; health related quality of life; high body mass index; improved; in vivo; in vivo evaluation; innovation; insight; limb injury; mammalian COMP; mechanical load; mechanical stimulus; modifiable risk; prevent; reconstruction; recruit; research study; resilience; response; therapeutic target; treadmill; ultrasound

PROJECT SUMMARY Post-traumatic osteoarthritis (PTOA) is a common and debilitating consequence of anterior cruciate ligament injury and reconstruction (ACLR) as over half of patients develop the disease within two decades impacting their health-related quality of life. Recent research has demonstrated the odds of developing PTOA are nearly 3 times greater in ACLR patients with high body mass index (BMI). Unfortunately, the mechanisms underlying the increased PTOA risk in ACLR patients with high BMI has not been directly evaluated and thus remains poorly understood. The lack of understanding on the potential deleterious impact of high BMI in patients with ACLR serves as the motivation and focus of this proposed research. The investigator’s long-term goal is to identify mechanistic-driven treatment approaches to decrease the incidence and progression of PTOA after ACLR. The objective of this F31 research proposal aims to evaluate the potential deleterious effects of high BMI on multiple components of cartilage health in patients who are between 12 and 24 months post-ACLR. We will accomplish these objectives by leveraging a stimulus-response strategy in which treadmill walking will be used as an in vivo mechanical stimulus to produce a physiological response in system components governing cartilage health, consisting of structural, biological and mechanical processes. This proposal encompasses three specific aims to: 1) determine the negative impact of high BMI on cartilage tissue resiliency (i.e. deformation) to an in vivo walking mechanical stimulus, 2) determine the negative impact of high BMI on biological markers of cartilage breakdown in response to an in vivo walking mechanical stimulus, and 3) evaluate if BMI may moderate the associations between mechanical loading and outcomes from Aims 1 and 2 (i.e. response in cartilage deformation and biological markers of cartilage breakdown). This study is innovative, as the application of a systems-based evaluation of cartilage health, encompassing in vivo assessments of multiple cartilage components, is critical to characterize the negative effects of high BMI after ACLR; an approach imperative given the complex, multifactorial nature of PTOA development. The proposed research is significant because it will improve our understanding of modifiable factors leading to PTOA development after ACLR and provide critical targets for future intervention strategies that may mitigate or prevent onset of PTOA.

项目摘要 创伤后骨关节炎（PTOA）是前交叉韧带的常见后果 伤害和重建（ACLR），因为超过一半的患者在二十年内发展了这种疾病 与健康有关的生活质量。最近的研究表明，开发PTOA的几率几乎是3次 高体重指数（BMI）的ACLR患者中较大。不幸的是，该机制是 ACLR高BMI患者的PTOA风险增加尚未直接评估，因此仍然很差 理解。缺乏对高BMI对ACLR患者的潜在有害影响的了解 作为这项拟议研究的动力和重点。调查人员的长期目标是确定 机械驱动的治疗方法可减少ACLR后PTOA的入射和进展。这 该F31研究建议的目的旨在评估高BMI对多个的潜在有害影响 ACLR 12到24个月的患者的软骨健康成分。我们将完成 这些目标通过利用刺激反应策略，其中跑步机行走将被用作体内 机械刺激以在控制软骨健康的系统组件中产生身体反应， 由结构，生物学和机械过程组成。该建议包括三个特定目标 TO：1）确定高BMI对软骨组织弹性（即变形）对体内的负面影响 步行机械刺激，2）确定高BMI对软骨生物标记的负面影响 响应体内行走机械刺激的崩溃，3）评估BMI是否可能中度 机械载荷与目标1和2的结果之间的关联（即软骨的响应 软骨破裂的变形和生物标记）。这项研究具有创新性，作为应用 软骨健康的基于系统的评估，包括多个软骨的体内评估 组件对于表征ACLR后高BMI的负面影响至关重要。必须给出的方法 PTOA开发的复杂，多因素的性质。拟议的研究很重要，因为它将 提高我们对可修改因素的理解，从而导致ACLR后PTOA开发并提供关键 未来的干预策略的目标，这些策略可能会减轻或阻止PTOA发作。

项目成果

Walking speed differentially affects lower extremity biomechanics in individuals with anterior cruciate ligament reconstruction compared to uninjured controls.

与未受伤的对照组相比，步行速度对前十字韧带重建个体的下肢生物力学有不同的影响。

• DOI: 10.1016/j.clinbiomech.2023.106059
• 发表时间: 2023
• 期刊: Clinical biomechanics (Bristol, Avon)
• 作者: Garcia,StevenA;Kahan,Seth;Gallegos,Jovanna;Balza,Isabella;Krishnan,Chandramouli;Palmieri-Smith,RiannM
• 通讯作者: Palmieri-Smith,RiannM