Saira Mary Farage-O’rEilly

Understanding how bone adapts to external forces is fundamental for exploring potential biomechanical interventions against skeletal diseases. This can be studied preclinically, combining in vivo experiments in rodents and in silico mechanoregulation models. While the in vivo tibial loading model is widely used to study bone adaptation, the common assumption of purely axial loading may be a simplification. This study quantifies the effect of the loading direction on the strain energy density (SED) distribution in the mouse tibia, a commonly used input for mechanoregulated bone remodelling models. To achieve this, validated micro-finite element (micro-FE) models were used to test the differences in local SED when the bone was loaded along different loading directions. In vivo micro-computed tomography (micro-CT) images were acquired from the tibiae of eleven ovariectomised mice at 18 weeks old before intervention and at 20 weeks old, after six mice underwent external mechanical loading. Micro-CT-based micro-FE models were generated for each tibia at both time points and loaded with a unit load in each Cartesian direction independently. The results from these unit load models were linearly combined to simulate various loading directions, defined by angles θ (inferior-superior) and ϕ (anterior–posterior). The results revealed a high sensitivity of the mouse tibia to the loading direction across both groups and time points. Several loading directions (e.g., θ = 10 ° , ϕ = 205–210 ° ) resulted in lower medians of the top 5% SED values compared to those obtained for the nominal axial case ( θ = 0 ° , ϕ = 0 ° ). Conversely, higher values were observed for other directions (e.g., θ = 30 ° , ϕ = 35–50 ° ). These findings emphasise the importance of considering the loading direction in experimental and computational bone adaptation studies.

Introduction: The in vivo tibial loading mouse model has been extensively used to evaluate bone adaptation in the tibia after mechanical loading treatment. However, there is a prevailing assumption that the load is applied axially to the tibia. The aim of this in silico study was to evaluate how much the apparent mechanical properties of the mouse tibia are affected by the loading direction, by using a validated micro-finite element (micro-FE) model of mice which have been ovariectomized and exposed to external mechanical loading over a two-week period.Methods: Longitudinal micro-computed tomography (micro-CT) images were taken of the tibiae of eleven ovariectomized mice at ages 18 and 20 weeks. Six of the mice underwent a mechanical loading treatment at age 19 weeks. Micro-FE models were generated, based on the segmented micro-CT images. Three models using unitary loads were linearly combined to simulate a range of loading directions, generated as a function of the angle from the inferior-superior axis (θ, 0°–30° range, 5° steps) and the angle from the anterior-posterior axis (ϕ, 0°: anterior axis, positive anticlockwise, 0°–355° range, 5° steps). The minimum principal strain was calculated and used to estimate the failure load, by linearly scaling the strain until 10% of the nodes reached the critical strain level of −14,420 με. The apparent bone stiffness was calculated as the ratio between the axial applied force and the average displacement along the longitudinal direction, for the loaded nodes.Results: The results demonstrated a high sensitivity of the mouse tibia to the loading direction across all groups and time points. Higher failure loads were found for several loading directions (θ = 10°, ϕ 205°–210°) than for the nominal axial case (θ = 0°, ϕ = 0°), highlighting adaptation of the bone for loading directions far from the nominal axial one.Conclusion: These results suggest that in studies which use mouse tibia, the loading direction can significantly impact the failure load. Thus, the magnitude and direction of the applied load should be well controlled during the experiments.