O'Sullivan, Oliver
(2025)
Investigating the value of serum biomarkers in predicting the development of post-traumatic osteoarthritis of the knee.
PhD thesis, University of Nottingham.
Abstract
Osteoarthritis (OA) significantly impacts the lives of those who live with it, physically, psychologically, and occupationally. Age, sex and body mass index are traditionally seen as the main risk factors for OA development, and with a global increasing life expectancy and increased obesity epidemic, the number of cases are expected to rise exponentially. However, injury accounts for a significant proportion of OA, commonly occurring in a far younger population, especially in high-risk groups such as sportspeople and military personnel. There is a requirement to identify those at the highest risk of OA, potentially with the use of biological markers (biomarkers), enabling interventions to prevent it or slow it. This PhD thesis entitled Investigating the value of serum biomarkers in predicting the development of post-traumatic osteoarthritis of the knee aims to understand the predictive utility of a panel of pre-selected serum candidate biomarkers in a cohort of young, male, British military personnel, half of whom sustained traumatic battlefield injuries.
The initial part of the thesis sets the context with the definition, classification and epidemiology of OA, use of biomarkers and population of interest, before outlining the thesis hypothesis. The current evidence regarding molecular and imaging biomarkers a year or more from injury is reviewed, before a cross-sectional and three-year predictive analysis of serum biomarkers within the longitudinal Armed Services Trauma Rehabilitation Outcome (ADVANCE) cohort is performed for knee radiographic OA (rOA), knee pain and functional outcomes. The latter chapters will address new questions, the novel methodology and results of a pilot study to enhance biomarker sensitivity, and use of biomechanics, before the final chapter outlines clinical and research translation and implementation.
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