Intra- and inter-subject variability of femoral growth plate stresses in typically developing children and children with cerebral palsy.

Little is known about the influence of mechanical loading on growth plate stresses and femoral growth. A multi-scale workflow based on musculoskeletal simulations and mechanobiological finite element (FE) analysis can be used to estimate growth plate loading and femoral growth trends. Personalizing the model in this workflow is time-consuming and therefore previous studies included small sample sizes (N < 4) or generic finite element models. The aim of this study was to develop a semi-automated toolbox to perform this workflow and to quantify intra-subject variability in growth plate stresses in 13 typically developing (TD) children and 12 children with cerebral palsy (CP). Additionally, we investigated the influence of the musculoskeletal model and the chosen material properties on the simulation results. Intra-subject variability in growth plate stresses was higher in cerebral palsy than in typically developing children. The highest osteogenic index (OI) was observed in the posterior region in 62% of the TD femurs while in children with CP the lateral region was the most common (50%). A representative reference osteogenic index distribution heatmap generated from data of 26 TD children's femurs showed a ring shape with low values in the center region and high values at the border of the growth plate. Our simulation results can be used as reference values for further investigations. Furthermore, the code of the developed GP-Tool ("Growth Prediction-Tool") is freely available on GitHub (https://github.com/WilliKoller/GP-Tool) to enable peers to conduct mechanobiological growth studies with larger sample sizes to improve our understanding of femoral growth and to support clinical decision making in the near future.