Multi-scale models for the prediction of bone remodelling due to musculoskeletal interventions

Bone is a dynamic tissue that constantly adapts to biomechanical and biochemical stimuli. Imbalances in the bone remodelling processes underlie skeletal diseases such as osteoporosis and myeloma bone disease, leading to increased fracture risk. This thesis aimed to develop and utilise in silico biomechanical models to enhance the understanding of how these diseases affect the bone properties.

A literature review highlighted the limitations in existing in silico biomechanical models of osteoporotic bone. The current research demonstrated that the micro-finite element (micro-FE) models used to calculate the strain distribution and, hence, predict the bone properties usually only investigate one loading condition. It is assumed that any load applied is axial to the bone, and hence, they ignore any uncertainties in the loading direction and magnitude from experimental measurements. To address this, a sensitivity analysis of the loading direction on the mechanical properties and strain distributions within the mouse tibia was conducted. This analysis is crucial for optimising the protocols for in vivo loading experiments and provides insights into how the loading direction influences bone remodelling.

Furthermore, the literature review revealed a lack of accurate predictions of bone resorption in biomechanical models coupled with mechanoregulation algorithms. To address this, an exploratory multi-scale model was developed, integrating validated micro-FE models with a bone cell population model. This model enabled an investigation of the sensitivity of biochemical stimuli on bone remodelling over time, providing insights into the model's complexity and potential for simplification.

Finally, a scarcity of micro-FE models based on high-resolution images depicting osteocyte lacunae was identified. To address this, the tools developed in the previous chapters were adapted to create a micro-FE model of bone tissue that included osteocyte lacunae. This enabled the investigation of the effect of osteocyte lacunae on local bone properties in both healthy and myeloma-affected mice.