Perry, Daniel C. (2011) The aetiology and epidemiology of Perthes’ disease of the hip. Doctoral thesis, University of Liverpool.
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Introduction: Perthes’ disease is an idiopathic osteonecrosis of a juvenile hip that frequently precipitates premature osteoarthritis. The year 2010 marked a century since Perthes’ disease was first described, but the aetiology and mechanism remain unknown. The incidence of Perthes’ disease varies widely, and it has been suggested that differential exposure to adverse socioeconomic circumstances may be a key precipitant. This work seeks to further the understanding of the distribution and determinants of Perthes’ disease, by exploring temporal and geographic patterns using a case register from Merseyside, discharge data from Scotland and the world’s largest community disease register. Analytical studies are then used to test hypotheses and investigate a disease mechanism. Methods: The descriptive studies were based on data from the Merseyside Perthes’ Disease Register (1976 – 2008), the General Practice Research Database (1990 – 2008) and hospital discharge data for Scotland (2000 – 2009). A systematic review of the published literature was used to explore international variations in incidence. Two case-control studies were used to test hypotheses. The first used a community population derived from the General Practice Research Database to investigate comorbid disease associations. The second used a hospital population to examine tobacco smoke exposure, anthropometric markers of prenatal androgenisation, hyperactivity and impaired endothelial function as a possible disease mechanism. Results: There was a graduated North-South divide in the UK incidence of Perthes’ disease, with rates in Scotland more than twice those in London. All three descriptive studies demonstrated a sustained fall in disease frequency across the study periods. There was a marked association with area deprivation, which was independent of the urban environment. Internationally a North-South divide persisted with equatorial regions being relatively unaffected by disease, and Northern Europe having the highest disease incidence. The international disease distribution was primarily a function of race, although latitude remained an independent predictor of incidence. Analytic studies revealed an association with congenital genitourinary tract anomalies and an association with asthma. There was no clinically apparent hyperactive tendency, though a more subtle abnormality in behavioural profiles was apparent. Exposure to tobacco smoke was a notable risk factor for Perthes’ disease, which was independent of individual or area deprivation measures. Arterial caliber was reduced amongst cases with a corresponding generalised reduction in arterial flow, though endothelial function appeared normal. Conclusions: Within the UK the incidence of Perthes’ disease is in decline. The geographic distribution suggests that variation in disease incidence is related principally to deprivation, though the underlying determinant(s) remain unclear. Latitude may hold an additional ‘risk’ in the disease aetiology, though the specific component(s) of latitude similarly remain unclear. Additional independent risk factors include sex, ethnicity, genitourinary disease and tobacco smoke exposure. Factors acting early in the development of the child appear to offer important insights into the disease aetiology, with particular interest on the influence of prenatal sex hormones. Reduced arterial caliber may have a role in the disease mechanism, and wider implications to vascular health. The aetiological factor in Perthes’ disease remains elusive, but it is likely that unraveling this enigma will unlock additional secrets relating to the fetal origins of diseases.
|Item Type:||Thesis (Doctoral)|
|Uncontrolled Keywords:||Epidemiology; Perthes Disease; Smoking; Aetiology; Avascular Necrosis|
|Subjects:||R Medicine > RJ Pediatrics|
|Departments, Research Centres and Related Units:||Academic Faculties, Institutes and Research Centres > Faculty of Medicine > School of Population, Community & Behavioural Sciences|
|Deposited On:||10 Jan 2012 10:32|
|Last Modified:||30 May 2012 09:28|
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