The development of post-traumatic and idiopathic osteoarthritis of the knee [electronic resource]

Osteoarthritis (OA) of the knee is a prevalent and painful disease, yet there is no cure or robust treatment to slow disease progression. Improving solutions for patients with knee OA requires a better understanding of the disease mechanisms. While joint injuries are a significant risk factor in OA development (post-traumatic OA, PTOA), in many cases, the initial disease causation is unknown (idiopathic OA, IOA). Literature suggests that structural, mechanical, and biological factors on many scales are involved and interact in both PTOA and IOA development. Therefore, the overall goal of this thesis project was to test for differences in and interactions between structural, mechanical, and biological factors in populations at risk of developing PTOA and IOA. The first study in this dissertation tested a cohort of subjects at risk of developing PTOA due to partial medial meniscectomy. In this population, limb differences in both transverse and sagittal plane gait mechanics differed between walking and stair traversing activities. This study may provide novel information for post-operative care as the results indicate the need to sufficiently challenge the knee joint both in dynamic load and range of motion to elicit differences in clinically meaningful kinematic measures after meniscectomy. To test the whether these measured kinematic limb differences persist longer-term after medial meniscectomy, a sub-cohort of the post-meniscectomy population was tested again at 33 months post-operation. The results indicate that dynamic flexion angle ranges of motion (ROM) became more like that of a control population with time past surgery. Furthermore, these kinematic changes were correlated with between-time point changes in flexion and extension moments, suggesting that the observed kinematic changes may be attributable to increased thigh strength and/or activation at the time of follow-up. The first two studies presented in this thesis provide important insights into structural and mechanical factors involved in PTOA development after meniscectomy. The final two studies presented in this thesis focus on the development of idiopathic OA by utilizing a unique cohort of individuals who were asymptomatic with no prior knee or lower limb injury, but had magnetic resonance imaging (MRI) evidence of cartilage loss ("Pre-OA"). Here, the Pre-OA subjects were less extended near terminal stance and had decreased maximum extension moment in terminal stance than control subjects. The Pre-OA group also had greater systemic levels of inflammation (greater serum tumor necrosis factor-alpha concentrations, TNFα) compared to the control subjects. The fact that the observed gait alterations and elevated inflammatory markers in this population were consistent with differences seen in patients with medial compartment OA suggests a general response to the early stages of joint degeneration that is consistent with a continuum of structural, mechanical, and biological changes throughout the OA disease process beginning long before clinical diagnosis. The final study tested the interactions between gait mechanics, serum inflammation level, and cartilage structure (average cartilage thickness) in the aforementioned Pre-OA cohort. It was found that both systemic inflammation and coronal plane gait kinetics were positively correlated with femur and tibia regional average cartilage thickness values. In general, the results support a multi-factor, multi-scale model of OA pathogenesis. Furthermore, these results suggest measures for early disease detection and potential pre-OA disease modification. Together, this thesis presents four studies probing the pathogenesis of OA by testing for structural, mechanical, and biological differences in subjects at increased risk of developing post-traumatic and idiopathic OA.

Keywords: Mechanical Engineering.
Advisor: Andriacchi Th. P. (Thomas P.) primary advisor. Thesis advisor
Kuhl Ellen
Levenston Marc Elliot advisor. Thesis advisor