Bone mineral density (BMD) is one of the important indicators used to characterise bone diseases, such as osteoporosis [1]. Two-dimensional areal BMD can be analysed through dual X-ray absorptiometry (DXA) which is the recommended method to diagnose osteoporosis by WHO [2]. However, an in-vivo method to detect three-dimensional localised BMD of trabecular bone is still absent. HR-pQCT enables the in-vivo assessments of 3D microstructure down to trabecular bone (TB). Therefore, in this study, a voxel-based density registration (VDR) method is proposed to analyse the longitudinal changes of trabecular-bone density distribution.Five healthy women aged between 55-70 years-old with more than one-year post menopause from a cohort of local dwelling were recruited into this 6-month longitudinal study. HR-pQCT scans were performed at the beginning and end of the study. Baseline and follow-up HR-pQCT (XtremeCT, Scanco Medical AG, Switzerland) scans were performed for all the recruited participant using the manufacturer's standard protocol (60 kVp, 1000 mA, 100-ms integration time). Four anatomical regions were defined (anterior, lateral, posterior, and medial) to observe the region-specific data, according to the previously published study [2]. The VDR method was programmed in-house using MATLAB 2020b to visualise and analyse the localised variation of TB density change at distal tibia after 6-month. The VDR programme contained 5main steps, involving a pre-processing with a Laplace-Hamming filter; three-dimensional (3D) mutual information rigid registration; BMD calibration using manufacturer provided phantom; voxel-base BMD calculation between baseline and follow-up images; colour contour was mapped and presented. To evaluate the statistically significant differences (p < 0.05) of tBMD for the four anatomical regions before and after 6 months, repeated measures ANOVA (RM-ANOVA) were performed using SPSS 20.0 software (IBM Corp., NY, USA).The time effect on localised changes of trabecular-bone mineral density was visualized and variations between different anatomical regions were quantified for the first time. Different distributions between anatomical regions were found in bone mineral density of trabecular bone (vBMDtrab), with a change of vBMDtrab at medial region (-0.56%) significantly higher than anterior (-1.58%) (p = 0.032). This study indicates that localised density changes might be used as a prior indicator for the effect of aging or other interventions.

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Adaptation is the process by which bone responses to changes in loading environment and modulates its properties and organization to meet the mechanical demands. Trabecular bone, the spongy component of many bones, undergoes significant adaptation when subjected to external forces. It was found that intensive mechanical stimulation results in thicker and mechanically stronger bones and bone morphology with individual elements of this bone tissue, trabeculae, aligned along the loading direction [1]. In contrast, a lack of mechanostimulation induces a bonemass reduction, thinning of trabeculae, and deterioration of mechanical properties [2]. Loadinduced adaptation is implemented through resorption of old and fractured bone and formation of a new bone material. These processes are hypothesized to be driven by mechanical stimuli of bone-matrix deformation sensed by bone mechanosensory cells [3]. The exact nature of mechanical stimuli triggering bone resorption and formation activities in response to external loads is currently unknown.This study aims to compare different mechanical stimuli on their ability to trigger load-induced adaptation in trabecular bone. To achieve this, developed 3D unit cells of trabecular lattice are developed with bone marrow in its intertrabecular space, reconstructed from two sets of highresolution peripheral computed tomography (HR-pQCT) scans. The first set includes baseline scans of distal tibia of a human participant, the second one comprised scans of the same participant after a six-months-long high-impact exercise. The finite-element method is implemented for the baseline model loaded in compression, tension, and shear to calculate the magnitudes of several mechanical stimuli that are widely considered as candidates to trigger the bone adaptation. A user-material subroutine is developed to relate the magnitude of each candidate to changes in mechanical properties and shape of trabeculae in the baseline model. The obtained adaptation results are qualitatively compared against the follow-up model.