| Summary: | Femoroacetabular impingement (FAI) represents a mechanism by which subtle deformity causes hip osteoarthritis (OA). Early intervention may delay progression of OA, but biomarkers of early disease are needed to evaluate effectiveness. Identification of at-risk individuals will enable construction of cohorts to validate biomarkers. Genetic influences are important in OA aetiology. Therefore at-risk cohorts can be identified through knowledge of heredity and joint morphology. Cohorts at risk for developing hip OA ('sibkids', n=123) and FAI ('FAI siblings', n=96) were compared with spouse controls (n=157). The review of the sibkids was a five-year follow-up from initial recruitment. Genetic predisposition to hip OA was confirmed (odds ratio (OR) 2.7). Sibkids demonstrated clinical progression (OR 4.8), confirming their use for development of OA biomarkers. Using controls with 'normal hips', reference intervals of radiographic parameters of joint morphology were constructed. Genetic predisposition to deformity was observed, particularly for cam deformity of the proximal femur (OR 2.1). Individuals with genetic risk were more likely to develop clinical features, given similar severity of radiographic OA (OR 3.4) or deformity without OA (relative risk 6.3). Two biomarker modalities were investigated. Delayed Gadolinium-enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) was highly sensitive in detecting localised cartilage damage in asymptomatic hips with cam deformity. Serum and urine biomarkers were deficient and unable to differentiate various stages of early OA, defined by dGEMRIC. The novel findings of this Thesis are that: subjects with a family history of degenerative hip disease are likely to develop it themselves; heredity and joint morphology are associated; an additional genetic component is involved in the development of clinically progressive disease; joint-specific imaging is more useful as a biomarker of early OA than currently available serum and urine assays. The importance of deformity is interesting as this remains the only readily modifiable aetiological factor in hip OA.
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