In silico biology of bone modelling and remodelling: adaptation

Abstract

Modelling and remodelling are the processes by which bone adapts its shape and internal structure to external influences. However, the cellular mechanisms triggering osteoclastic resorption and osteoblastic formation are still unknown. In order to investigate current biological theories, in silico models can be applied. In the past, most of these models were based on the continuum assumption, but some questions related to bone adaptation can be addressed better by models incorporating the trabecular microstructure. In this paper, existing simulation models are reviewed and one of the microstructural models is extended to test the hypothesis that bone adaptation can be simulated without particular knowledge of the local strain distribution in the bone. Validation using an experimental murine loading model showed that this is possible. Furthermore, the experimental model revealed that bone formation cannot be attributed only to an increase in trabecular thickness but also to structural reorganization including the growth of new trabeculae. How these new trabeculae arise is still an unresolved issue and might be better addressed by incorporating other levels of hierarchy, especially the cellular level. The cellular level sheds light on the activity and interplay between the different cell types, leading to the effective change in the whole bone. For this reason, hierarchical multi-scale simulations might help in the future to better understand the biomathematical laws behind bone adaptation.

In silicobiology of bone modelling and remodelling: regeneration

“…This remodelling takes place for a prolonged period of time, gradually reverting the blood supply to a normal state and restoring the bone at the regeneration site to its original shape and strength. More information on the biology and in silico modelling of the remodelling process can be found elsewhere in this issue (Gerhard et al 2009). …”

“…The calculated tissue-level mechanical stimuli are used to adapt the biological parameters, whereas in reality a substantial difference is measured between tissue-level and cellular-level stimuli. You et al (2001) proposed a model to explain (and calculate) the observed strain amplification phenomenon in the osteocytes' processes (see also Gerhard et al 2009). These osteocytes are considered the main mechanosensors in bone (Mullender & Huiskes 1997;Burger & Klein-Nulend 1999).…”

“…Potential causes of osteoporosis and the use of mathematical models in designing preventive treatment strategies are discussed elsewhere in this issue by Gerhard et al (2009). The current paper focuses on the (in silico) biology of the bone regeneration process, taking place after bone traumata such as fractures or implant placement.…”

Challenges in longitudinal measurements with HR-pQCT: Evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility

“…Our first validation step was to carefully visually check the registration result by overlying segmented baseline and transformed follow-up images into one image and color-code the result [34] for all patients. The quality of the registration was further quantified by the final value of the correlation coefficient between images.…”

Multiscale modelling and nonlinear finite element analysis as clinical tools for the assessment of fracture risk

“…The temporal changes in bone microarchitecture and material properties attributed to age, disease and treatment have not yet been incorporated into FE simulations. However, several computational approaches exist that attempt to simulate these catabolic and anabolic changes in bone as reviewed elsewhere (Gerhard et al 2009). While these models are not yet fully validated, they could be integrated into a multiscale approach aimed at monitoring the long-term fracture risk of patients.…”