| Summary: | Early knee osteoarthritis (EKOA) is common, hard to treat and can be debilitating for symptomatic individuals. Whilst end-stage osteoarthritis is treated reliably with knee replacement surgery, such surgery is not routinely offered to those with less severe OA as it is associated with a poorer outcome. These patients are said to be in a 'treatment gap' and they are the primary focus of this thesis. A series of large epidemiological studies were designed to clarify the natural history of symptomatic EKOA. A prospective cohort study including 1,634 symptomatic knees with EKOA found that malalignment was the most potent risk factor for structural progression. A subsequent study, which included a detailed assessment of lower limb alignment, established that this structural progression was driven by the alignment of the proximal tibia. Using semi-quantitive MRI analysis it was found that the increased structural progression seen in subjects with proximal tibia vara, was due to more full thickness cartilage loss in the central medial tibia. These are novel observations which have implications for future research as the alignment of the proximal tibia can be corrected with surgery. Following this epidemiological description of EKOA, attention was turned to intervention and treatment. A systematic review of the literature identified moderate to very low quality evidence to support the role of surgery in treating symptomatic EKOA. A single-centre prospective cohort study for patients undergoing a novel neutralising high tibial osteotomy was established and excellent early (1yr) and mid-term (3-5 years) clinical outcomes are reported. A retrospective study was designed to investigate whether full thickness cartilage loss on magnetic resonance imaging, but not on plain film radiographs, is sufficient to warrant proceeding to unicompartmental knee arthroplasty (UKA). Outcomes for this cohort of patients were excellent, highlighting the usefulness of MR for the early identification of patients suitable for UKA. In summary, this thesis has reported the natural history of symptomatic EKOA and identified proximal tibia vara as a potent risk factor for structural progression. The paucity of trials investigating subjects with this disease has been highlighted and surgical interventions which are safe and clinically effective have been identified. The direction of future research in this area has been proposed.
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