Abstract
Acetabular dysplasia (AD), cam and pincer morphology have been associated with hip osteoarthritis (HOA) in observational studies but inferring causation from such studies is difficult. I aimed to derive hip shape and radiographic HOA (rHOA) from dual-energy absorptiometry (DXA) scans before applying genetic and epidemiologic approaches to further elucidate the role of abnormal hip shape in the development of HOA.I developed and applied novel methods to derive rHOA and AD, cam and pincer morphology from DXA scans in UK Biobank (UKB) (Chapter 4 & Chapter 5). I showed DXA-derived rHOA was associated with hip pain, and that osteophytes were more strongly associated with hip pain than joint space narrowing (Chapter 6). I then examined cross-sectional associations between AD, cam and pincer morphology and rHOA. This showed strong evidence of associations between cam morphology and rHOA but similar associations were not seen with pincer morphology nor AD (Chapter 7).
Subsequently, I devised and applied a novel scoring system for rHOA to all left hip DXA scans in UKB, before showing strong and progressive associations between increasing rHOA grades and clinical outcomes including hip pain, hospital diagnosed HOA and total hip replacement (THR) (Chapter 8). I then conducted a genome-wide association study for alpha angle (AA), a proxy for cam morphology, identifying 8 independent genetic loci. Mendelian randomisation showed a bidirectional relationship between AA and HOA reflecting either causal effects in both directions and/or shared underlying genetic pathways (Chapter 9).
This work suggests DXA-derived rHOA and hip shape could be useful in predicting THR risk. The bi-directional causal effects seen between AA and HOA suggest that the well-established relationship between cam morphology and HOA is not simply due to cam morphology causing HOA. Rather alterations in hip shape are likely to be an integral part of the development of HOA.
| Date of Award | 6 Dec 2022 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | George Davey Smith (Supervisor) & Jonathan H Tobias (Supervisor) |