Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Physical Therapy

Collaborative Specialization

Musculoskeletal Health Research

Supervisor

Birmingham, Trevor B

2nd Supervisor

Beier, Frank

Co-Supervisor

Abstract

Knee osteoarthritis (OA) is now considered a “whole joint disease”, with substantial evidence that low-grade inflammation plays a critical role in OA pathogenesis. It is important to understand how changes in joint mechanics are related to inflammatory processes in OA, which may help identify ways to increase joint resilience. Therefore, the overall purpose of this thesis was to explore the effects of altering load on joint inflammation in patients with knee OA, using high tibial osteotomy (HTO) as a model.

Chapter 2 was a validation study of the new semi-quantitative Knee Inflammation Magnetic Resonance Imaging (MRI) Scoring System (KIMRISS). KIMRISS bone marrow lesion (BML) scores are moderately associated with manual segmentations. Additionally, changes following surgery varied significantly, where some participants had large increases in BMLs, and others had large decreases. This study suggested that KIMRISS can reliably detect small changes in BML scores after HTO and can be learned by a novice reader.

Chapter 3 explored the changes in synovial fluid biomarkers after HTO, and the associations of these changes with changes in MRI measures of effusion-synovitis and cartilage composition. This study suggested that decreasing medial compartment load on the knee is associated with an overall improvement in biological and MRI measures of joint health.

Chapter 4 explored the differences in gait biomechanics (i.e., surrogate measures of load) between participants who had a biological “response” to HTO vs those who did not. The results of this study suggested that those participants whose biological profile responded to HTO had greater changes in knee joint moments than participants who did not.

Overall, this thesis provides evidence that inflammation in OA is complex, and therefore multiple measures of inflammation should be used to gain a more comprehensive picture of joint physiology. Additionally, this thesis provides further evidence that mechanoinflammation is an active pathway in knee OA, and can be changed by altering load, furthering our understanding of the pathophysiological mechanisms behind OA and suggesting avenues towards novel therapeutic approaches.

Summary for Lay Audience

Knee osteoarthritis (OA) is one of the leading causes of pain and disability worldwide, and effects the entire joint. It is important to understand how changes in joint loading are related to inflammatory processes in knee OA, to help give us a better understanding of the mechanisms that drive the disease.

Chapter 2 used a new magnetic resonance imaging (MRI) scoring system to measure inflammation in knee OA. This new scoring system is easy to learn by novice readers and can reliably score inflammation in knee OA after surgical realignment.

Chapter 3 explored the relationship between the changes in biological markers of inflammation found in the joint, and MRI measures of inflammation one year after limb realignment surgery. The results of this study suggested that decreasing load on the joint is associated with an overall improvement in joint inflammation.

Chapter 4 evaluated the changes in knee load during walking in those who had a biological inflammatory “response” (i.e., improvement) versus those who did not after surgical realignment. The results demonstrated that those who responded had greater changes in knee load than those who did not.

All these findings demonstrate that inflammation in plays a major role in OA is and very complex, therefore multiple different techniques should be used to measure inflammation. Additionally, joint load is a major contributor to inflammation in OA, but by changing load we can change inflammation and improve overall joint health.

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