Modelling trajectories and mechanisms of childhood hip dysplasia

Introduction

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.

Risk Factors for Osteoarthritis

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.

Current Screening Practices

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.

Prevalence of Hip Dysplasia

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.

Proposed Research Program

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.

Research Methodology

In a birth cohort of 8000 children (followed from fetal life until adulthood), I will first uniquely build a 5D growth model on how hip shape develops over time from age 2-18 years.

1. I will gain novel knowledge regarding causal factors of dysplastic growth.
2. I will investigate whether there are various phenotypes that have different underlying mechanisms.
3. I will study how and when dysplastic growth will already impact the integrity of the young adult joint.
4. I will discover very early signs of joint aberration leading to OA.

Computational Modeling

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.