Biomechanics and osteoarthritis: a novel rat model

Abstract

This thesis has made a number of significant contributions to the evaluation of rodent joint biomechanics, and the relationship between these biomechanics and osteoarthritic pathology. It has presented the first use of static optimization based techniques to evaluate in vivo muscle and joint contact forces in the rat, with model outputs comparing well to experimentally collected kinematics and joint kinetics. The sensitivity of the model to errors in marker placement, muscle geometry and segmental properties was evaluated using elementary effects methods. It was found that errors in marker placement had the largest effect on most model outputs, with the exception of muscle forces, which showed far greater sensitivity to changes in muscle geometry. After validating the model ouputs and their sensitivity to potential sources of experimental error, the effect of inclination and speed on joint kinetics and kinematics was investigated. This was undertaken both to predict the potential of the techniques to differentiate pathologically different gait and to evaluate whether variations in speed and/or inclination could increase medial joint loading to provide a non-invasive method to accelerate osteoarthritic progression in future disease models. It was found that increasing inclination increased the total knee joint contact forces, whereas increasing speed preferentially increased medial side loading. Finally a novel surgical model of malalignment induced osteoarthritis in rats was developed via a high tibial osteotomy (HTO). Biomarkers of cartilage turnover as well as tibial compressive loading in the medial knee compartment measured via musculoskeletal modelling were shown to be significantly higher in HTO operated animals and correlated well with histological grading. This model demonstrates the fact that increasing medial joint loading alone is enough to induce the development of OA and future work will hope to develop the idea of malalignment induced osteoarthritis as a distinct disease phenotype.