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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要创伤后骨关节炎 (PTOA) 是前十字韧带常见且令人衰弱的后果损伤和重建（ACLR），因为超过一半的患者在二十年内患上这种疾病，影响他们的生活最近的研究表明，患 PTOA 的几率几乎是与健康相关的生活质量的 3 倍。不幸的是，ACLR 患者的体重指数 (BMI) 较高，其潜在机制尚不清楚。高 BMI 的 ACLR 患者的 PTOA 风险增加尚未得到直接评估，因此仍然很差人们对高 BMI 对 ACLR 患者的潜在有害影响缺乏了解。作为这项拟议研究的动机和重点，研究者的长期目标是确定。机械驱动的治疗方法可减少 ACLR 后 PTOA 的发生率和进展。该 F31 研究计划的目的旨在评估高 BMI 对多种疾病的潜在有害影响我们将完成 ACLR 术后 12 至 24 个月患者软骨健康的各个组成部分。通过利用刺激响应策略来实现这些目标，其中跑步机行走将被用作体内机械刺激在控制软骨健康的系统组件中产生生理反应，该提案包含三个具体目标。 1) 确定高 BMI 对体内软骨组织弹性（即变形）的负面影响行走机械刺激，2) 确定高 BMI 对软骨生物标志物的负面影响对体内行走机械刺激的分解，以及 3) 评估 BMI 是否可以调节机械负荷与目标 1 和 2 的结果之间的关联（即软骨反应）这项研究是创新的，作为一种应用。基于系统的软骨健康评估，包括多软骨的体内评估鉴于 ACLR 方法势在必行，因此对于描述高 BMI 的负面影响至关重要； PTOA 发展的复杂性、多因素性质使得这项研究意义重大，因为它将提高我们对 ACLR 后导致 PTOA 发展的可改变因素的理解，并提供关键的未来可能减轻或预防 PTOA 发生的干预策略的目标。