Characterisation of spatially discrete cortical bone adaptation in mice tibia due to dynamic mechanical loading

Introduction Studies in cortical bone adaptation aim to identify and quantify the resorption/formation response to various factors. The mechanostat theory suggests that bone tissue regulation is driven through changes to the habitual strain; this has been tested and confirmed in animal models, primarily on a macro level. However, sufficient correlations between dynamic mechanical stimuli and the localised bone formation response have not been made. This project aimed to investigate the adaptation response in spatially-discrete regions of mice tibiae through the creation of a custom image postprocessing algorithm. Materials and Methods Image processing was conducted on microCT data collected from seven groups of mice; each group was subjected to axial loading of the right tibia to simulate various intensities of use/disuse (F = 0, 2, 4, 6, 8, 10, 12N), with a right sciatic neurectomy performed to isolate the mechanical stimulus response. The image postprocessing algorithm compares the results of two measurement techniques to determine the cortical thickness (Ct.Th) around the periosteal perimeter. The Ct.Th was compared between the left (control) and right (loaded) limb to determine the percentage change (ΔCt.Th) at four cross-sections along the tibial length (25%, 37% and 50%, measured from the proximal end). Results and Discussion Results obtained show that in all tibial cross-sections analysed, the applied axial load elicits load dependant, region-specific bone growth/loss around the periosteal perimeter. The 25%, 37% and 50% cross-sections reveal the ΔCt.Th along the posterior and anterior surfaces of the tibia increases steadily with the applied load. The results also show two regions of consistent bone loss regardless of loading magnitude, located along the neutral bending axis of the tibia. By considering the bone as a simple mechanical beam, this can be attributed to a lack of shear strain that would be generated during typical habitual loading. Measurements in the 75% cross-section showed that significant bone loss occurs over a larger portion of the cortical shell. Increases to the loading magnitude lead to additional anabolic responses in less than half of the cross-section. The variation in results can be attributed to the configuration of bone at this region (i.e. the absence of a fibula) and the method of external loading, leading to an altered internal loading distribution in this cross section. Conclusion Investigation of the localised adaptation response indicates that the method of loading has a direct impact on the localised maintenance and formation of cortical bone tissue. Through understanding the mechanical relationship at a deeper level, further development of a predictive adaptation model can be used to guide treatments and prevention of degenerative bone diseases such as osteoporosis.