Degeneration of the nucleus pulposus affects the internal volumetric strains and failure location of adjacent human metastatic vertebral bodies.

Intervertebral disc (IVD) degeneration is suspected to affect the distribution of stress and strain near the vertebral endplates and in the underlying bone. This scenario is worsened by the presence of metastatic lesions on the vertebrae (primarily thoracic vertebrae (60-80%)) which increase the risk of fracture. As such, this study aimed to evaluate the effect of IVD degeneration on the internal volumetric strains and failure modes of human metastatic vertebral bodies.

A novel framework for elucidating the effect of mechanical loading on the geometry of ovariectomized mouse tibiae using principal component analysis.

Introduction: Murine models are used to test the effect of anti-osteoporosis treatments as they replicate some of the bone phenotypes observed in osteoporotic (OP) patients. The effect of disease and treatment is typically described as changes in bone geometry and microstructure over time. Conventional assessment of geometric changes relies on morphometric scalar parameters.

A novel mean shape based post-processing method for enhancing deep learning lower-limb muscle segmentation accuracy.

This study aims at improving the lower-limb muscle segmentation accuracy of deep learning approaches based on Magnetic Resonance Imaging (MRI) scans, crucial for the diagnostic and therapeutic processes in musculoskeletal diseases. In general, segmentation methods such as U-Net deep learning neural networks can achieve good Dice Similarity Coefficient (DSC) values, e.g.

Automatic segmentation of lower limb muscles from MR images of post-menopausal women based on deep learning and data augmentation.

Individual muscle segmentation is the process of partitioning medical images into regions representing each muscle. It can be used to isolate spatially structured quantitative muscle characteristics, such as volume, geometry, and the level of fat infiltration. These features are pivotal to measuring the state of muscle functional health and in tracking the response of the body to musculoskeletal and neuromusculoskeletal disorders.

The loading direction dramatically affects the mechanical properties of the mouse tibia.

The 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 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.

Combining PTH(1-34) and mechanical loading has increased benefit to tibia bone mechanics in ovariectomised mice.

Combined treatment with PTH(1-34) and mechanical loading confers increased structural benefits to bone than monotherapies. However, it remains unclear how this longitudinal adaptation affects the bone mechanics. This study quantified the individual and combined longitudinal effects of PTH(1-34) and mechanical loading on the bone stiffness and strength evaluated in vivo with validated micro-finite element (microFE) models.

Cortical thickness adaptation to combined mechanical loading and parathyroid hormone treatments is site specific and synergistic in the mouse tibia model.

In this study, we aimed to quantify the localised effects of mechanical loading (ML), low (20 μg/kg/day), moderate (40 μg/kg/day) or high (80 μg/kg/day) dosages of parathyroid hormone (PTH), and combined (PTHML) treatments on cortical bone adaptation in healthy 19-week old female C57BL/6 mice. To this end, we utilise a previously reported image analysis algorithm on μCT data of the mouse tibia published by Sugiyama et al. (2008) to measure changes in cortical area, marrow cavity area and local cortical thickness measures (ΔCt.

Cortical bone adaptation response is region specific, but not peak load dependent: insights from CT image analysis and mechanostat simulations of the mouse tibia loading model.

The two major aims of the present study were: (i) quantify localised cortical bone adaptation at the surface level using contralateral endpoint imaging data and image analysis techniques, and (ii) investigate whether cortical bone adaptation responses are universal or region specific and dependent on the respective peak load. For this purpose, we re-analyse previously published CT data of the mouse tibia loading model that investigated bone adaptation in response to sciatic neurectomy and various peak load magnitudes (F = 0, 2, 4, 6, 8, 10, 12 N). A beam theory-based approach was developed to simulate cortical bone adaptation in different sections of the tibia, using longitudinal strains as the adaptive stimuli.

The role of bone metastases on the mechanical competence of human vertebrae.

Spine is the most common site for bone metastases. The evaluation of the mechanical competence and failure location in metastatic vertebrae is a biomechanical and clinical challenge. Little is known about the failure behaviour of vertebrae with metastatic lesions.

Bone metastases do not affect the measurement uncertainties of a global digital volume correlation algorithm.

Measurement uncertainties of Digital Volume Correlation (DVC) are influenced by several factors, like input images quality, correlation algorithm, bone type, etc. However, it is still unknown if highly heterogeneous trabecular microstructures, typical of lytic and blastic metastases, affect the precision of DVC measurements. Fifteen metastatic and nine healthy vertebral bodies were scanned twice in zero-strain conditions with a micro-computed tomography (isotropic voxel size = 39 μm).

Deformable image registration based on single or multi-atlas methods for automatic muscle segmentation and the generation of augmented imaging datasets.

Muscle segmentation is a process relied upon to gather medical image-based muscle characterisation, useful in directly assessing muscle volume and geometry, that can be used as inputs to musculoskeletal modelling pipelines. Manual or semi-automatic techniques are typically employed to segment the muscles and quantify their properties, but they require significant manual labour and incur operator repeatability issues. In this study an automatic process is presented, aiming to segment all lower limb muscles from Magnetic Resonance (MR) imaging data simultaneously using three-dimensional (3D) deformable image registration (single inputs or multi-atlas).

Effect of radiation-induced damage of trabecular bone tissue evaluated using indentation and digital volume correlation.

Exposure to X-ray radiation for an extended amount of time can cause damage to the bone tissue and therefore affect its mechanical properties. Specifically, high-resolution X-ray Computed Tomography (XCT), in both synchrotron and lab-based systems, has been employed extensively for evaluating bone micro-to-nano architecture. However, to date, it is still unclear how long exposures to X-ray radiation affect the mechanical properties of trabecular bone, particularly in relation to lab-XCT systems.

Comparison of linear and nonlinear stepwise μFE displacement predictions to digital volume correlation measurements of trabecular bone biopsies.

Digital volume correlation (DVC) enables to evaluate the ability of μFE models in predicting experimental results on the mesoscale. In this study predicted displacement fields of three different linear and materially nonlinear μFE simulation methods were compared to DVC measured displacement fields at specific load steps in the elastic regime (Step) and after yield (Step). Five human trabecular bone biopsies from a previous study were compressed in several displacement steps until failure.

Digital volume correlation for the characterization of musculoskeletal tissues: Current challenges and future developments.

Biological tissues are complex hierarchical materials, difficult to characterise due to the challenges associated to the separation of scale and heterogeneity of the mechanical properties at different dimensional levels. The Digital Volume Correlation approach is the only image-based experimental approach that can accurately measure internal strain field within biological tissues under complex loading scenarios. In this minireview examples of DVC applications to study the deformation of musculoskeletal tissues at different dimensional scales are reported, highlighting the potential and challenges of this relatively new technique.

Reproducibility of Densitometric and Biomechanical Assessment of the Mouse Tibia From Micro-CT Images.

Interventions for bone diseases (e.g. osteoporosis) require testing in animal models before clinical translation and the mouse tibia is among the most common tested anatomical sites.

Geroprotectors and Skeletal Health: Beyond the Headlines.

Osteoporosis and osteoarthritis are the most common age-related diseases of the musculoskeletal system. They are responsible for high level of healthcare use and are often associated with comorbidities. Mechanisms of ageing such as senescence, inflammation and autophagy are common drivers for both diseases and molecules targeting those mechanisms (geroprotectors) have potential to prevent both diseases and their co-morbidities.

Subchondral Bone Microarchitectural and Mineral Properties and Expression of Key Degradative Proteinases by Chondrocytes in Human Hip Osteoarthritis.

Background: The purpose of this study was to investigate the relationship between the expression of key degradative enzymes by chondrocytes and the microarchitectural and mineral properties of subchondral bone across different stages of cartilage degradation in human hip osteoarthritis (OA).

Methods: Osteochondral samples at different stages of cartilage degradation were collected from 16 femoral heads with OA. Osteochondral samples with normal cartilage were collected from seven femoral heads with osteoporosis.

MicroFE models of porcine vertebrae with induced bone focal lesions: Validation of predicted displacements with digital volume correlation.

The evaluation of the local mechanical behavior as a result of metastatic lesions is fundamental for the characterization of the mechanical competence of metastatic vertebrae. Micro finite element (microFE) models have the potential of addressing this challenge through laboratory studies but their predictions of local deformation due to the complexity of the bone structure compromized by the lesion must be validated against experiments. In this study, the displacements predicted by homogeneous, linear and isotropic microFE models of vertebrae were validated against experimental Digital Volume Correlation (DVC) measurements.

Positive interactions of mechanical loading and PTH treatments on spatio-temporal bone remodelling.

Osteoporosis is one of the most common skeletal diseases, but current therapies are limited to generalized antiresorptive or anabolic interventions, which do not target regions that would benefit from improvements to skeletal health. To improve the evaluation of treatment plans, we used a spatio-temporal multiscale approach that combines longitudinal in vivo micro-computed tomography (micro-CT) and in silico subject-specific finite element modeling to quantitatively map bone adaptation changes due to disease and treatment at high resolution. Our findings show time and region-dependent modifications in bone remodelling following one and two sets of mechanical loading and/or pharmacological interventions.

The Role of the Loading Condition in Predictions of Bone Adaptation in a Mouse Tibial Loading Model.

The mouse tibial loading model is used to evaluate the effectiveness of mechanical loading treatment against skeletal diseases. Although studies have correlated bone adaptation with the induced mechanical stimulus, predictions of bone remodeling remained poor, and the interaction between external and physiological loading in engendering bone changes have not been determined. The aim of this study was to determine the effect of passive mechanical loading on the strain distribution in the mouse tibia and its predictions of bone adaptation.

Scientific and regulatory evaluation of mechanistic in silico drug and disease models in drug development: Building model credibility.

The value of in silico methods in drug development and evaluation has been demonstrated repeatedly and convincingly. While their benefits are now unanimously recognized, international standards for their evaluation, accepted by all stakeholders involved, are still to be established. In this white paper, we propose a risk-informed evaluation framework for mechanistic model credibility evaluation.

Type, size, and position of metastatic lesions explain the deformation of the vertebrae under complex loading conditions.

Background: Bone metastases may lead to spine instability and increase the risk of fracture. Scoring systems are available to assess critical metastases, but they lack specificity, and provide uncertain indications over a wide range, where most cases fall. The aim of this work was to use a novel biomechanical approach to evaluate the effect of lesion type, size, and location on the deformation of the metastatic vertebra.