Modelling trajectories and mechanisms of childhood hip dysplasia
With 40 million patients in Europe, osteoarthritis (OA) is the most common chronic and disabling disease. OA is incurable, and symptomatic treatments have limited effect. Therefore, prevention by identifying and targeting asymptom...
With 40 million patients in Europe, osteoarthritis (OA) is the most common chronic and disabling disease. OA is incurable, and symptomatic treatments have limited effect. Therefore, prevention by identifying and targeting asymptomatic persons that develop a clear OA risk factor is sorely needed. Hip dysplasia is the strongest risk factor for hip OA. Hip dysplasia is a condition of mechanical instability of the hip caused by insufficient coverage of the femoral head (ball) by a shallow or obliquely oriented acetabulum (socket). This results in high cartilage stress, and subsequent hip OA. In Europe we screen for developmental hip dysplasia in infants (prevalence 2%), enabling early treatment. However, we discovered that hip dysplasia can (further) develop during skeletal maturation and thus remains unrecognized. In 1100 Dutch 9-year-old children we found a 6% and 26% prevalence of marked and mild hip dysplasia, respectively. Hip dysplasia can be influenced until the stage where hip growth plates close at about age 13. I propose a novel research program (HIPSTAR) where I will uniquely unravel the mechanisms behind late childhood hip dysplasia in order to pave the way for devising preventive measures that reduce the prevalence of adult hip dysplasia and, thus, hip OA. In a birth cohort of 8000 children (followed from foetal life until adulthood), I will first uniquely built a 5D growth model on how hip shape develops over time from age 2-18 years. I will gain novel knowledge regarding causal factors of dysplastic growth, and whether there are various phenotypes that have different underlying mechanisms. I also will study how and when dysplastic growth will already impact on the integrity of the young adult joint, and discover very early signs of joint aberration leading to OA. Finally, in a computational model, I will test the influence of loading factors on dysplastic growth mechanistically, and provide detailed information regarding the potential remedial options.ver más
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