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

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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.