How does high tibial osteotomy affect osteoarthritis in the adult human knee?

Kinghorn, Alison 2022. How does high tibial osteotomy affect osteoarthritis in the adult human knee? MD Thesis, Cardiff University. Item availability restricted.

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Abstract

Introduction: Knee osteoarthritis (OA) is an extremely common, debilitating condition but there remain significant gaps of understanding regarding its pathogenesis and management. For medial compartment OA, high tibial osteotomy (HTO) offers joint preservation with good clinical outcomes. However little is known about how its clinical effects are achieved. This cross-disciplinary project aimed to link bioscientific, mechanical and clinical data to investigate how HTO influences knee OA. The first strand investigated the biological environment (including glutaminergic pathways potentially related to OA). The second, analysed changes in the mechanical environment resultant from HTO and the third looked for potential links between the two. Methods: Firstly, samples of subchondral bone were taken from the tibial plateau at time of HTO surgery and plate removal. These were analysed by reverse transcription PCR (RT-qPCR), looking for proportional changes in expression pre- to post-operatively in selected markers related to OA (EAAT1, EAAT3, NR2D, GRIK4, SOST, IL-6). Secondly, clinical radiographs were measured to examine the relationship between proximal tibial morphology, limb alignment and potential compensatory changes at the hip, ankle and subtalar joints. Finally, principal component analysis was employed to investigate potential correlations between the biological, radiological and mechanical data. Results: Results showed potential downregulation in expression of NR2D, GRIK4 and SOST within the quadrant of the tibial plateau where loading is most reduced by HTO. Radiographic analysis suggested that although change of proximal tibial shape by HTO is related to change in limb alignment, these measures are iii not as closely related as expected and there are changes in subtalar alignment and stance width which may modulate the effect. PCA and correlation analysis identified potential phenotypic groups, markers of outcome and links between the biological and mechanical changes seen in HTO. Conclusion: This thesis has identified novel biological and mechanical changes resultant from HTO surgery, in addition to revealing potential linking mechanisms between them. It supports the theory that HTO causes measurable change to the pathology underpinning OA; potentially halting, slowing or reversing progression. By enhancing understanding of both HTO and OA, and by providing promising avenues for further research, it will enable clinicians to better counsel patients and therefore have a direct positive impact on patient care.

Item Type:	Thesis (MD)
Date Type:	Completion
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	24 April 2023
Last Modified:	25 Apr 2023 15:21
URI:	https://orca.cardiff.ac.uk/id/eprint/159003

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