Novel and systemic risk factors for knee and hip osteoarthritis
2017-03-01T02:56:00Z (GMT) by
Osteoarthritis (OA) is a major public health problem and the most common cause of disability. Growing evidence suggests that OA is a disease of the whole joint. However, the etiology and risk factors of OA have not been fully elucidated, and there is no registered disease modifying drug to halt disease progression. Over recent years, new approaches and initiatives have been adapted for better understanding the disease pathology and mechanisms underlying the risk factors, such as the role of hormonal factors, metabolic and vascular factors, vitamin D and birth weight. This project attempted to investigate these systemic and novel risk factors for the incidence of knee and hip replacement for OA in linkage studies. In this thesis knee and hip replacement for OA were used as a surrogate for severe OA which provides evidence of the true problem and signifies the economic burden. The study populations were the participants of the Melbourne Collaborative Cohort Study and the Australian Diabetes, Obesity and Lifestyle Study which were linked to the Australian Orthopaedic Association National Joint Replacement Registry to determine the incidence of knee and hip replacement for OA. The initial focus of this thesis was on the association between hormonal factors and risk of total knee and hip replacement for OA. A lower estradiol concentration was a risk factor for total knee replacement for OA, while a lower androstenedione concentration and higher Sex Hormone Binding Globulin concentration were risk factors for total hip replacement for OA in women. Moreover, a lower index-to-ring finger length ratio, a proxy indicator of in-utero testosterone exposure, was associated with an increased risk of total knee replacement for OA but not the risk of total hip replacement for OA. The second part of this thesis examined the relationship between metabolic and vascular factors and the risk of knee and hip replacement for OA. The metabolic syndrome and cumulative number of metabolic syndrome components were both associated with increased risk of total knee replacement for OA, with no association observed for total hip replacement for OA. Additionally, retinal arteriolar narrowing was associated with increased risk of knee replacement for OA. These findings suggest that metabolic and vascular factors play a role in the pathogenesis of knee OA. The third part of this thesis examined the association between serum 25-hydroxy-vitamin D concentrations and the risk of hip replacement for OA. Higher serum 25-hydroxy-vitamin D concentrations were associated with an increased risk of hip replacement for OA in males but not in females. Finally, this thesis examined the association between birth weight and risk of knee and hip replacement for OA. Individuals born with low birth weight or preterm birth were at increased risk of hip replacement for OA but not knee replacement for OA in adult life. In conclusion, this thesis has made major contribution to the understanding of the role of hormonal factors, metabolic and vascular factors, serum 25-hydroxy-vitamin D concentration and birth weight in the pathogenesis of knee and hip OA. This thesis has highlighted the significant heterogeneity in terms of the risk factors for OA and that knee and hip OA are susceptible to different risk factors. This study has identified novel targets for the prevention and treatment of knee and hip OA separately that are likely to have an impact on this debilitating disease.