Factors affecting the knee joint in health and disease : towards an improved understanding of knee osteoarthritis

Osteoarthritis (OA) is a significant public health problem. It is the most common single cause of pain and disability in the elderly. OA is a complex disease that affects the whole joint. The knee is one of the joints most commonly affected by OA. The understanding of knee OA has been hampered by the lack of a sensitive tool to non-invasively assess disease severity. The ideal imaging modality for the assessment of OA would provide data pertaining to all joint structures, including a direct measure of both cartilage and bone, as well as other intra and extra-articular structures in three dimensions. Magnetic Resonance Imaging (MRI) promises to fulfil many of these criteria. There is no known treatment for OA that stops the progression of the disease so current strategies are aimed only at relieving symptoms. There is evidence to suggest that the incidence and progression of knee OA may involve different mechanisms. The goal for researchers is to identify and understand the mechanisms of modifiable risk factors for OA in order to develop preventative strategies. The aim of this thesis was to address this by examining risk factors for structural changes in the knee that are associated with either the development or the progression of disease in both healthy/asymptomatic populations as well as in a population with knee OA. This provided the opportunity to examine these across the spectrum of disease from the normal joint through to one with OA. Paper 1 presented within this thesis describes the natural history of cartilage defects and factors associated with the progression in those with knee OA. In this study, cartilage defects tended to progress over 2 years in people with symptomatic knee OA. Factors associated with progression of cartilage defects were increasing age and baseline tibial bone area. Papers 2 and 3 describe the prevalence and significance of meniscal tears and also the relationship between gait parameters and meniscal tears in a cohort of asymptomatic post-menopausal women. Meniscal tears were found to be common and became more common with increasing age. Tears were also associated with greater tibial plateau bone area, and prevalence of meniscal tears at baseline was weakly associated with decreased lateral cartilage volume and an increased progression of tibiofemoral cartilage defects over 2 years. In addition, gait parameters that isolate medial tibiofemoral joint loads were associated with medial meniscal pathology. The presence and severity of medial meniscal tears was positively associated with the peak external knee adduction moment during early stance, and tended toward a similar association during late stance. Moreover, the presence of medial meniscal lesions was also positively associated with the degree of internal foot rotation when the external knee adduction moment peaked during late stance, independent of the magnitude of the adduction moment. Papers 4 and 5 explore local biomechanical factors affecting the tibiofemoral and patellofemoral compartments. In people with knee OA, a change in knee alignment from genu varum toward genu valgum over 2 years was associated with a reduction in the annual rate of medial tibial cartilage volume loss in the subsequent 2.5 years. Change in alignment did not affect the rate of change in lateral tibial cartilage volume. In addition within the patellofemoral compartment, a shallower femoral sulcus angle was associated with increased medial patella cartilage volume compared to a deeper femoral sulcus angle. Papers 6 and 7 describe the natural history and significance of bone marrow lesions (BMLs) in healthy participants with no clinical knee OA. BMLs developed in 12% of people over 2 years. Increased weight and body mass index were risk factors for incident BMLs. Incident BMLs were also associated with the development of knee pain in a population where all participants were free of pain at the beginning of the study. Approximately half of the BMLs present at baseline resolved over the 2 year study period. In addition within this asymptomatic population, the development of new BMLs was associated with adverse effects on knee cartilage, while resolution of BMLs was associated with improvement in cartilage. Papers 8, 9 and 10 examine the relationships between cigarette smoking, dietary fatty acids and serum lipids and BMLs in asymptomatic clinically healthy populations. In a cohort of asymptomatic, community based adults, a history of smoking (current and past) was associated with increased medial tibial, but not lateral tibial or patella cartilage loss over 2 years. In addition there was a dose-response relationship between ‘pack-years’ smoked and increased medial tibial cartilage loss. For individuals who had a BML at baseline, smoking was associated with the persistence of the BML over 2 years. The persistence of the BML was found to partially mediate the relationship between smoking and cartilage loss. In the same population a higher intake of saturated fatty acids was found to be associated with an increased likelihood of developing BMLs over 2 years. In a cohort of asymptomatic middle-aged women with no clinical knee OA, serum cholesterol and triglyceride levels were found to be associated with the incidence of BMLs over 2 years. This thesis examined the effect of biomechanical and systemic risk factors on knee cartilage, meniscal tears and bone and the significance of their change over time in both symptomatic/healthy subjects and those with knee OA. It identified a number of modifiable factors that influence changes indicative of disease development as well as disease progression. This thesis has contributed to the identification of knee structural changes in both the pre-diseased and diseased state as well as risk factors for these changes. Further work will be required to better understand the role of these different structural changes in the early disease and their associated risk factors in order to more effectively prevent and treat knee OA. [Appendices not included in PDF]