Osteoarthritis (OA) is the most common type of joint disorder in the world and a major cause of disability in the adult population. Globally, it is one of the fastest-growing health conditions and OA prevalence is expected to continue rising due to an aging global population. The knee is the most affected joint in OA, accounting for approximately 80% of the global OA burden, making it an important joint to consider in the context of OA. Knee OA is characterized by bone and joint structural changes, such as changes in the apparent bone mineral density, thickening of the subchondral bone plate and joint space narrowing. Detection of these changes has traditionally been considered the reserve of X-ray radiography, which is challenged by inherent anatomical overlap of a 2D imaging modality. Weight bearing computed tomography (WBCT) has recently been utilized to image and investigate OA-related structural changes in the knee, as it provides a 3D visualization of the joint whilst in a functionally relevant loaded stance. In this thesis, the utility of WBCT in measuring bone mineral density (BMD) was investigated. Next, methods to measure joint space width (JSW) subchondral bone plate thickness (SBP.Th) were implemented and tested on end-stage knee OA cohort with age- and sex- matched healthy controls. The first study showed that BMD measurement accuracy is influenced by the apparent BMD at the measurement site, with greater accuracy in trabecular bone regions. The second study demonstrated that the JSW and SBP.Th measurement methods implemented in this thesis were comparable to existing methods and able to distinguish between healthy and OA knees. A narrower JSW and thicker lateral SBP.Th in the load-bearing region of the femur was found in OA knees compared to control knees. These results show that WBCT and the implemented analysis methods may be used to measure OA-related bone and joint changes in vivo at the knee.