ORCID Profile
0000-0001-9183-530X
Current Organisation
Queensland University of Technology
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Biomedical Engineering | Biomechanical Engineering | Biomaterials | Human Movement and Sports Science | Biomedical Engineering Not Elsewhere Classified | Biomechanics | Medical Devices | Biomechanical Engineering | Civil Engineering | Timber, Pulp and Paper | Orthopaedics | Numerical modelling and mechanical characterisation | Biomechanical engineering | Nanomedicine | Biomedical engineering | Manufacturing Engineering | Construction Engineering | Geotechnical Engineering | Nanotechnology | Manufacturing Processes and Technologies (excl. Textiles) | Numerical Modelling and Mechanical Characterisation | Petroleum and Reservoir Engineering | Motor Control | Sports Medicine | Nanofabrication, Growth and Self Assembly
ANZSRC Socio-Economic Objective (SEO)
Skeletal system and disorders (incl. arthritis) | Health related to ageing | Expanding Knowledge in the Medical and Health Sciences | Skeletal System and Disorders (incl. Arthritis) | Manufacturing not elsewhere classified | Expanding Knowledge in Technology | Fabricated Metal Products not elsewhere classified | Oil and Gas Extraction | Wood, Wood Products and Paper not elsewhere classified | Human Pharmaceutical Products not elsewhere classified | Waste management |
Related Links
Publications
Poromechanical stimulation of bone remodeling: A continuum micromechanics-based mathematical model and experimental validation
Publisher: No publisher found
Date: 2013
High dose dietary vitamin D3 increases bone mass and strength in mice
Publisher: Elsevier BV
Date: 06-2017
A systems approach to understanding bone cell interactions in health and disease
Publisher: InTech
Date: 10-10-2012
DOI: 10.5772/51149
Coupled mechanical consolidation and contaminant transport modelling of composite barrier systems
Publisher: American Society of Civil Engineers
Date: 07-03-2008
Mathematical modelling of basic multicellular units: The functional units of bone remodeling
Publisher: CRC Press
Date: 30-03-2015
DOI: 10.1201/B18320-4
Effects of PTH glandular and external dosing patterns on bone cell activity using a two-state receptor model—Implications for bone disease progression and treatment
Publisher: Public Library of Science (PLoS)
Date: 30-03-2023
DOI: 10.1371/JOURNAL.PONE.0283544
Abstract: Temporal aspects of ligand specificity have been shown to play a significant role in the case of pulsatile hormone secretion, as exemplified by parathyroid hormone (PTH) binding to its receptor (PTH1R), a G-protein-coupled receptor expressed on surfaces of osteoblasts and osteocytes. The latter binding reaction regulates intracellular signalling and subsequently modulates skeletal homeostasis via bone remodelling. PTH glandular secretion patterns dictate bone cellular activity. In healthy humans, 70% of PTH is secreted in a tonic fashion, whereas 30% is secreted in low- litude and high-frequency bursts occurring every 10–20 min, superimposed on the tonic secretion. Changes in the PTH secretion patterns have been associated with various bone diseases. In this paper, we analyse PTH glandular secretion patterns for healthy and pathological states and their link to bone cellular responsiveness ( α R ). We utilise a two-state receptor ligand binding model of PTH to PTH1R together with a cellular activity function which is able to distinguish various aspects of the stimulation signal including peak dose, time of ligand exposure, and exposure period. Formulating and solving several constrained optimisation problems, we investigate the potential of pharmacological manipulation of the diseased glandular secretion and via clinical approved external PTH injections to restore healthy bone cellular responsiveness. Based on the mean experimentally reported data, our simulation results indicate cellular responsiveness in healthy subjects is sensitive to the tonic baseline stimulus and it is 28% of the computed maximum responsiveness. Simulation results for pathological cases of glucocorticoid-induced osteoporosis, hyperparathyroidism, initial and steady state hypocalcemia cl tests indicate α R values significantly larger than the healthy baseline (1.7, 2.2, 4.9 and 1.9-times, respectively). Manipulation of the pulsatile glandular secretion pattern, while keeping the mean PTH concentration constant, allowed restoration of healthy baseline values from these catabolic bone diseases. Conversely, PTH glandular diseases that led to maximum bone cellular responsiveness below the healthy baseline value can’t be restored to baseline via glandular manipulation. However, external PTH injections allowed restoration of these latter cases.
Multiscale bone mechanobiology
Publisher: Elsevier
Date: 2019
Statistical Quantification of the Effects of Marker Misplacement and Soft-Tissue Artifact on Shoulder Kinematics and Kinetics
Publisher: MDPI AG
Date: 31-05-2022
DOI: 10.3390/LIFE12060819
Abstract: The assessment of shoulder kinematics and kinetics are commonly undertaken biomechanically and clinically by using rigid-body models and experimental skin-marker trajectories. However, the accuracy of these trajectories is plagued by inherent skin-based marker errors due to marker misplacements (offset) and soft-tissue artifacts (STA). This paper aimed to assess the in idual contribution of each of these errors to kinematic and kinetic shoulder outcomes computed using a shoulder rigid-body model. Baseline experimental data of three shoulder planar motions in a young healthy adult were collected. The baseline marker trajectories were then perturbed by simulating typically observed population-based offset and/or STA using a probabilistic Monte-Carlo approach. The perturbed trajectories were then used together with a shoulder rigid-body model to compute shoulder angles and moments and study their accuracy and variability against baseline. Each type of error was studied in idually, as well as in combination. On average, shoulder kinematics varied by 3%, 6% and 7% due to offset, STA or combined errors, respectively. Shoulder kinetics varied by 11%, 27% and 28% due to offset, STA or combined errors, respectively. In conclusion, to reduce shoulder kinematic and kinetic errors, one should prioritise reducing STA as they have the largest error contribution compared to marker misplacements.
Foreword to the special issue on Bone and cartilage mechanobiology across the scales
Publisher: Springer Science and Business Media LLC
Date: 25-01-2016
Study of the combined effects of PTH treatment and mechanical loading in postmenopausal osteoporosis using a new mechanistic PK-PD model
Publisher: Springer Science and Business Media LLC
Date: 25-02-2020
Three-Dimensional Quantification of Glenoid Bone Loss in Anterior Shoulder Instability: The Anatomic Concave Surface Area Method
Publisher: SAGE Publications
Date: 06-2021
DOI: 10.1177/23259671211011058
Abstract: Recurrent shoulder instability may be associated with glenoid erosion and bone loss. Accurate quantification of bone loss significantly influences the contemplation of surgical procedure. In addition, assessment of bone loss is crucial for surgical planning and accurate graft placement during surgery. To quantify the concave surface area of glenoid bone loss by using 3-dimensional (3D) segmented models of the scapula and to compare this method with the best-fit circle and glenoid height/width methods, which use the glenoid rim for bone loss estimations. Cohort study (diagnosis) Level of evidence, 2. A total of 36 consecutive preoperative bilateral computed tomography scans of patients eligible for a primary Latarjet procedure were selected from our institutional surgical database (mean patient age, 29 ± 9 years 31 men and 5 women). The 3D models of both scapulae were generated using medical segmentation software and were used to map the anatomic concave surface area (ACSA) of the inferior glenoid using the diameter of the best-fit circle of the healthy glenoid. Bone loss was calculated as a ratio of the difference between surface areas of both glenoids (healthy and pathological) against the anatomic circular surface area of the healthy glenoid (the ACSA method). These results were compared with bone loss calculations using the best-fit circle and glenoid height/width methods. Inter- and intraobserver reliability were also calculated. The mean (± SD) bone loss calculated using the ACSA, the best-fit circle, and glenoid height/width methods was 9.4% ± 6.7%, 14.3% ± 6.8%, and 17.6% ± 7.3%, respectively. The ACSA method showed excellent interobserver reliability, with an intraclass correlation coefficient (ICC) of 0.95 versus those for the best-fit circle (ICC, 0.71) and glenoid height/width (ICC, 0.79) methods. Quantification of instability-related glenoid bone loss is reliable using the 3D ACSA method.
Theoretical analysis of the influence of a diffuse double-layer on Darcy's law
Publisher: Springer-Verlag
Date: 2005
Cortical Bone Porosity in Rabbit Models of Osteoporosis
Publisher: Wiley
Date: 22-09-2020
DOI: 10.1002/JBMR.4124
Micro-poro-elasticity of baghdadite-based bone tissue engineering scaffolds: A unifying approach based on ultrasonics, nanoindentation, and homogenization theory
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.MSEC.2014.10.072
Abstract: Microstructure-elasticity relations for bone tissue engineering scaffolds are key to rational biomaterial design. As a contribution thereto, we here report comprehensive length measuring, weighing, and ultrasonic tests at 0.1MHz frequency, on porous baghdadite (Ca3ZrSi2O9) scaffolds. The resulting porosity-stiffness relations further confirm a formerly detected, micromechanically explained, general relationship for a great variety of different polycrystals, which also allows for estimating the zero-porosity case, i.e. Young modulus and Poisson ratio of pure (dense) baghdadite. These estimates were impressively confirmed by a physically and statistically independent nanoindentation c aign comprising some 1750 indents. Consequently, we can present a remarkably complete picture of porous baghdadite elasticity across a wide range of porosities, and, thanks to the micromechanical understanding, reaching out beyond classical elasticity, towards poroelastic properties, quantifying the effect of pore pressure on the material system behavior.
Theoretical investigation of the role of the RANK-RANKL-OPG system in bone remodeling
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.JTBI.2009.09.021
Abstract: The RANK-RANKL-OPG system is an essential signaling pathway involved in bone cell-cell communication, with le evidence that modification of the RANK-RANKL-OPG signaling pathway has major effects on bone remodeling. The first focus of this paper is to demonstrate that a theoretical model of bone cell-cell interactions is capable of qualitatively reproducing changes in bone associated with RANK-RANKL-OPG signaling. To do this we consider either biological experiments or bone diseases related to receptor and/or ligand deficiencies, including RANKL over-expression, ablation of OPG production and/or RANK receptor modifications. The second focus is to investigate a wide range of possible therapeutic strategies for re-establishing bone homeostasis for various pathologies of the RANK-RANKL-OPG pathway. These simulations indicate that bone diseases associated with the RANK-RANKL-OPG pathway are very effective in triggering bone resorption compared to bone formation. These results align with Hofbauer's "convergence hypothesis", which states that catabolic bone diseases most effectively act through the RANK-RANKL-OPG system. Additionally, we demonstrate that severity of catabolic bone diseases strongly depends on how many components of this pathway are affected. Using optimization algorithms and the theoretical model, we identify a variety of successful "virtual therapies" for different disease states using both single and dual therapies.
The effects of anatomical errors on shoulder kinematics computed using multi-body models
Publisher: Springer Science and Business Media LLC
Date: 22-07-2022
DOI: 10.1007/S10237-022-01606-0
Abstract: Joint motion calculated using multi-body models and inverse kinematics presents many advantages over direct marker-based calculations. However, the sensitivity of the computed kinematics is known to be partly caused by the model and could also be influenced by the participants’ anthropometry and sex. This study aimed to compare kinematics computed from an anatomical shoulder model based on medical images against a scaled-generic model and quantify the effects of anatomical errors and participants’ anthropometry on the calculated joint angles. Twelve participants have had planar shoulder movements experimentally captured in a motion lab, and their shoulder anatomy imaged using an MRI scanner. A shoulder multi-body dynamics model was developed for each participant, using both an image-based approach and a scaled-generic approach. Inverse kinematics have been performed using the two different modelling procedures and the three different experimental motions. Results have been compared using Bland–Altman analysis of agreement and further analysed using multi-linear regressions. Kinematics computed via an anatomical and a scaled-generic shoulder models differed in average from 3.2 to 5.4 degrees depending on the task. The MRI-based model presented smaller limits of agreement to direct kinematics than the scaled-generic model. Finally, the regression model predictors, including anatomical errors, sex, and BMI of the participant, explained from 41 to 80% of the kinematic variability between model types with respect to the task. This study highlighted the consequences of modelling precision, quantified the effects of anatomical errors on the shoulder kinematics, and showed that participants' anthropometry and sex could indirectly affect kinematic outcomes.
Bone refilling in basic multicellular units: Insights into tetracycline double labelling from a computational model
Publisher: Springer Science and Business Media LLC
Date: 30-04-2014
DOI: 10.1007/S10237-013-0495-Y
Abstract: Bone remodelling is carried out by 'bone multicellular units' ([Formula: see text]s) in which active osteoclasts and active osteoblasts are spatially and temporally coupled. The refilling of new bone by osteoblasts towards the back of the [Formula: see text] occurs at a rate that depends both on the number of osteoblasts and on their secretory activity. In cortical bone, a linear phenomenological relationship between matrix apposition rate and [Formula: see text] cavity radius is found experimentally. How this relationship emerges from the combination of complex, nonlinear regulations of osteoblast number and secretory activity is unknown. Here, we extend our previous mathematical model of cell development within a single cortical [Formula: see text] to investigate how osteoblast number and osteoblast secretory activity vary along the [Formula: see text]'s closing cone. The mathematical model is based on biochemical coupling between osteoclasts and osteoblasts of various maturity and includes the differentiation of osteoblasts into osteocytes and bone lining cells, as well as the influence of [Formula: see text] cavity shrinkage on osteoblast development and activity. Matrix apposition rates predicted by the model are compared with data from tetracycline double labelling experiments. We find that the linear phenomenological relationship observed in these experiments between matrix apposition rate and [Formula: see text] cavity radius holds for most of the refilling phase simulated by our model, but not near the start and end of refilling. This suggests that at a particular bone site undergoing remodelling, bone formation starts and ends rapidly, supporting the hypothesis that osteoblasts behave synchronously. Our model also suggests that part of the observed cross-sectional variability in tetracycline data may be due to different bone sites being refilled by [Formula: see text]s at different stages of their lifetime. The different stages of a [Formula: see text]'s lifetime (such as initiation stage, progression stage, and termination stage) depend on whether the cell populations within the [Formula: see text] are still developing or have reached a quasi-steady state whilst travelling through bone. We find that due to their longer lifespan, active osteoblasts reach a quasi-steady distribution more slowly than active osteoclasts. We suggest that this fact may locally enlarge the Haversian canal diameter (due to a local lack of osteoblasts compared to osteoclasts) near the [Formula: see text]'s point of origin.
Assessment of thoracic spinal curvatures in static postures using spatially tracked 3D ultrasound volumes: a proof-of-concept study
Publisher: Springer Science and Business Media LLC
Date: 10-01-2023
DOI: 10.1007/S13246-022-01210-7
Abstract: The assessment of spinal posture is a difficult endeavour given the lack of identifiable bony landmarks for placement of skin markers. Moreover, potentially significant soft tissue artefacts along the spine further affect the accuracy of marker-based approaches. The objective of this proof-of-concept study was to develop an experimental framework to assess spinal postures by using three-dimensional (3D) ultrasound (US) imaging. A phantom spine model immersed in water was scanned using 3D US in a neutral and two curved postures mimicking a forward flexion in the sagittal plane while the US probe was localised by three electromagnetic tracking sensors attached to the probe head. The obtained anatomical ‘coarse’ registrations were further refined using an automatic registration algorithm and validated by an experienced sonographer. Spinal landmarks were selected in the US images and validated against magnetic resonance imaging data of the same phantom through image registration. Their position was then related to the location of the tracking sensors identified in the acquired US volumes, enabling the localisation of landmarks in the global coordinate system of the tracking device. Results of this study show that localised 3D US enables US-based anatomical reconstructions comparable to clinical standards and the identification of spinal landmarks in different postures of the spine. The accuracy in sensor identification was 0.49 mm on average while the intra- and inter-observer reliability in sensor identification was strongly correlated with a maximum deviation of 0.8 mm. Mapping of landmarks had a small relative distance error of 0.21 mm (SD = ± 0.16) on average. This study implies that localised 3D US holds the potential for the assessment of full spinal posture by accurately and non-invasively localising vertebrae in space.
Poromicromechanics reveals that physiological bone strains induce osteocyte-stimulating lacunar pressure
Publisher: Springer Science and Business Media LLC
Date: 30-07-2016
Design, fabrication and validation of a precursor pulsed electromagnetic field device for bone fracture repair
Publisher: IEEE
Date: 07-2018
Handheld Co-Axial Bioprinting: Application to in situ surgical cartilage repair
Publisher: Springer Science and Business Media LLC
Date: 19-07-2017
DOI: 10.1038/S41598-017-05699-X
Abstract: Three-dimensional (3D) bioprinting is driving major innovations in the area of cartilage tissue engineering. Extrusion-based 3D bioprinting necessitates a phase change from a liquid bioink to a semi-solid crosslinked network achieved by a photo-initiated free radical polymerization reaction that is known to be cytotoxic. Therefore, the choice of the photocuring conditions has to be carefully addressed to generate a structure stiff enough to withstand the forces phisiologically applied on articular cartilage, while ensuring adequate cell survival for functional chondral repair. We recently developed a handheld 3D printer called “Biopen”. To progress towards translating this freeform biofabrication tool into clinical practice, we aimed to define the ideal bioprinting conditions that would deliver a scaffold with high cell viability and structural stiffness relevant for chondral repair. To fulfill those criteria, free radical cytotoxicity was confined by a co-axial Core/Shell separation. This system allowed the generation of Core/Shell GelMa/HAMa bioscaffolds with stiffness of 200KPa, achieved after only 10 seconds of exposure to 700 mW/cm 2 of 365 nm UV-A, containing % viable stem cells that retained proliferative capacity. Overall, the Core/Shell handheld 3D bioprinting strategy enabled rapid generation of high modulus bioscaffolds with high cell viability, with potential for in situ surgical cartilage engineering.
Poromechanical stimulation of bone remodeling: A continuum micromechanics-based mathematical model and experimental validation
Publisher: American Society of Civil Engineers
Date: 18-06-2013
Algorithmic formulation of bone fabric evolution based on the dissipation principle
Publisher: Springer International Publishing
Date: 2020
Spatio-temporal structure of cell distribution in cortical bone multicellular units: a mathematical model
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.BONE.2010.12.009
Abstract: Bone remodelling maintains the functionality of skeletal tissue by locally coordinating bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts) in the form of Bone Multicellular Units (BMUs). Understanding the emergence of such structured units out of the complex network of biochemical interactions between bone cells is essential to extend our fundamental knowledge of normal bone physiology and its disorders. To this end, we propose a spatio-temporal continuum model that integrates some of the most important interaction pathways currently known to exist between cells of the osteoblastic and osteoclastic lineage. This mathematical model allows us to test the significance and completeness of these pathways based on their ability to reproduce the spatio-temporal dynamics of in idual BMUs. We show that under suitable conditions, the experimentally observed structured cell distribution of cortical BMUs is retrieved. The proposed model admits travelling-wave-like solutions for the cell densities with tightly organised profiles, corresponding to the progression of a single remodelling BMU. The shapes of these spatial profiles within the travelling structure can be linked to the intrinsic parameters of the model such as differentiation and apoptosis rates for bone cells. In addition to the cell distribution, the spatial distribution of regulatory factors can also be calculated. This provides new insights on how different regulatory factors exert their action on bone cells leading to cellular spatial and temporal segregation, and functional coordination.
Failure assessment of anchor bolts by means of nonlinear finite element analyses
Publisher: Springer Netherlands
Date: 2001
Femoral shaft strains during daily activities: Implications for atypical femoral fractures
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.CLINBIOMECH.2014.08.001
Abstract: Atypical femoral fractures are low-energy fractures initiating in the lateral femoral shaft. We hypothesized that atypical femoral fracture onset is associated with daily femoral strain patterns. We examined femoral shaft strains during daily activities. We analyzed earlier calculations of femoral strain during walking, sitting and rising from a chair, stair ascent, stair descent, stepping up, and squatting based on anatomically consistent musculoskeletal and finite-element models from a single donor and motion recordings from a body-matched volunteer. Femoral strains in the femoral shaft were extracted for the different activities and compared. The dependency between femoral strains in the lateral shaft and kinetic parameters was studied using multi-parametric linear regression analysis. Tensile strain in the lateral femoral shaft varied from 327 με (squatting) to 2004 με (walking). Walking and stair descent imposed tensile loading on the lateral shaft, whereas the other activities mainly imposed tensile loads on the anterior shaft. The multi-parametric linear regression showed a moderately strong correlation between tensile strains in the lateral shaft and the motion kinetic (joint moments and ground reaction force) in the proximal (R(2)=0.60) and the distal shaft (R(2)=0.46). Bone regions subjected to tensile strains are associated with atypical femoral fractures. Walking is the daily activity that induces the highest tensile strain in the lateral femoral shaft. The kinetics of motion explains 46%-50% of the tensile strain variation in the lateral shaft, whereas the unexplained part is likely to be attributed to the way joint moments are decomposed into muscle forces.
Electrodiffusive transport in charged porous media: From the particle-level scale to the macroscopic scale using volume averaging
Publisher: Begell House
Date: 2009
Shapes of loading surfaces of concrete models and their influence on the peak load and failure mode in structural analyses
Publisher: Elsevier BV
Date: 08-2003
A hydrological study of on-site soil absorption systems
Publisher: Thomas Telford Ltd.
Date: 2013
Abstract: The use of on-site soil absorption systems (OSASs) to dispose of domestic wastewater is common in rural and semi-rural areas in Australia as well as in many other developed and developing countries. A need exists for an improved method of evaluating OSAS performance and predicting potential impacts of OSASs on public health and environmental quality. This paper focuses on the hydrological prediction of saturated and unsaturated moisture flow patterns of wastewater dispersed into soil adjacent to OSAS disposal trenches. It presents field and laboratory measurements obtained during an extensive investigation conducted at eight OSAS sites on predominantly silty soil in Victoria, Australia. A numerical moisture flow model was also employed to predict how the hydrological performance of OSAS might be affected by a variety of site specific conditions including soil properties, climatic data, and hydraulic loading rates. The model was fine-tuned using both published data and data from the eight study sites. The predictions show that over 50%, and in some instances over 80%, of water received by an OSAS is lost by way of evapotranspiration. This highlights the importance of evapotranspiration in determining soil absorption capacity and moisture flow patterns around an OSAS, something that is not accounted for in existing OSAS design guidelines.
Theoretical analysis of the spatio-temporal structure of bone multicellular units
Publisher: IOP Publishing
Date: 06-2010
Differences in Hip and Knee Running Moments across Female Pubertal Development
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2018
Atypical femoral fractures are associated with high cyclic tensile strain regions during walking (Conference Abstract)
Publisher: Springer Science and Business Media LLC
Date: 04-2014
Functional adaptation of bone: The mechanostat and beyond
Publisher: Springer International Publishing
Date: 21-06-2018
Solute transport in cartilage undergoing cyclic deformation
Publisher: Informa UK Limited
Date: 08-2007
DOI: 10.1080/10255840701309163
Abstract: There are no blood vessels in cartilage to transport nutrients and growth factors to chondrocytes dispersed throughout the cartilage matrix. Insulin-like growth factor-I (IGF-I) is a large molecule with an important role in cartilage growth and metabolism, however, it first must reach the chondrocytes to exert its effect. While diffusion of IGF-I through cartilage is possible, it has been speculated that cyclic loading can enhance the rate of solute transport within cartilage. To better understand this process, here a one-dimensional axisymmetric mathematical model is developed to examine the transport of solutes through a cylindrical plug of cartilage undergoing cyclic axial deformation in the range of 10(-3) -1 Hz. This study has revealed the role of timescales in interpreting transport results in cartilage. It is shown that dynamic strains can either enhance or inhibit IGF-I transport at small timescales (< 20 min after onset of loading), depending on loading frequency. However, on longer timescales it is found that dynamic loading has negligible effect on IGF-I transport. Most importantly, in all cases examined the steady state IGF-I concentration did not exceed the fixed boundary value, in contrast to the predictions of Mauk et al. (2003).
Application of disease system analysis to osteoporosis: From temporal to spatio-temporal assessment of disease progression and intervention
Publisher: Springer International Publishing
Date: 21-06-2018
Mathematical modeling of postmenopausal osteoporosis and its treatment by the anti-catabolic drug denosumab.
Publisher: Wiley
Date: 30-08-2014
DOI: 10.1002/CNM.2584
Estimation of load conditions and strain distribution for in vivo murine tibia compression loading using experimentally informed finite element models
Publisher: Elsevier BV
Date: 2021
A thermodynamically consistent model of bone rotary remodeling: a 2D study
Publisher: Informa UK Limited
Date: 27-10-2017
Computational modeling of interactions between multiple myeloma and the bone microenvironment
Publisher: Public Library of Science (PLoS)
Date: 08-11-2011
Microscopic effects on chloride diffusivity of cement pastes--a scale-transition analysis
Publisher: Elsevier BV
Date: 12-2004
Anterior deltoid muscle reflection using a deltopectoral approach is safe and does not influence outcome of reverse shoulder arthroplasty
Publisher: Elsevier BV
Date: 06-2023
Experimental-based mechanobiological modeling of the anabolic and catabolic effects of breast cancer on bone remodeling
Publisher: Springer Science and Business Media LLC
Date: 24-08-2022
DOI: 10.1007/S10237-022-01623-Z
Abstract: Bone is a biological tissue characterized by its hierarchical organization. This material has the ability to be continually renewed, which makes it highly adaptative to external loadings. Bone renewing is managed by a dynamic biological process called bone remodeling (BR), where continuous resorption of old bone and formation of new bone permits to change the bone composition and microstructure. Unfortunately, because of several factors, such as age, hormonal imbalance, and a variety of pathologies including cancer metastases, this process can be disturbed leading to various bone diseases. In this study, we have investigated the effect of breast cancer (BC) metastases causing osteolytic bone loss. BC has the ability to affect bone quantity in different ways in each of its primary and secondary stages. Based on a BR mathematical model, we modeled the BC cells' interaction with bone cells to assess their effect on bone volume fraction (BV/TV) evolution during the remodeling process. Some of the parameters used in our model have been determined experimentally using the enzyme-linked immune-sorbent assay (ELISA) and the MTT assay. Our numerical simulations show that primary BC plays a significant role in enhancing bone-forming cells' activity leading to a 6.22% increase in BV/TV over 1 year. On the other hand, secondary BC causes a noticeable decrease in BV/TV reaching 15.74% over 2 years.
Wideband Polarized Radio Emission from the Newly Revived Magnetar XTE J1810–197
Publisher: American Astronomical Society
Date: 27-03-2019
Geometry and bone mineral density determinants of femoral neck strength changes following exercise
Publisher: Springer Science and Business Media LLC
Date: 21-10-2023
DOI: 10.1007/S10237-022-01642-W
Abstract: Physical exercise induces spatially heterogeneous adaptation in bone. However, it remains unclear where the changes in BMD and geometry have the greatest impact on femoral neck strength. The aim of this study was to determine the principal BMD-and-geometry changes induced by exercise that have the greatest effect on femoral neck strength. Pre- and post-exercise 3D-DXA images of the proximal femur were collected of male participants from the LIFTMOR-M exercise intervention trial. Meshes with element-by-element correspondence were generated by morphing a template mesh to each bone to calculate changes in BMD and geometry. Finite element (FE) models predicted femoral neck strength changes under single-leg stance and sideways fall load. Partial least squares regression (PLSR) models were developed with BMD-only, geometry-only, and BMD-and-geometry changes to determine the principal modes that explained the greatest variation in neck strength changes. The PLSR models explained over 90% of the strength variation with 3 PLS components using BMD-only ( R 2 0.92, RMSE 0.06 N) and 8 PLS components with geometry-only ( R 2 0.93, RMSE 0.06 N). Changes in the superior neck and distal cortex were most important during single-leg stance while the superior neck, medial head, and lateral trochanter were most important during a sideways fall. Local changes in femoral neck and head geometry could differentiate the exercise groups from the control group. Exercise interventions may target BMD changes in the superior neck, inferior neck, and greater trochanter for improved femoral neck strength in single-leg stance and sideways fall.
Comparison of the moulding ability of Plaster of Paris and polyester cast material in the healthy adult forearm
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.INJURY.2017.08.010
Abstract: To quantify the moulding ability of Plaster of Paris and polyester cast materials as assessed by the novel use of peripheral quantitative computed tomography. A prospective crossover study was performed in 25 healthy volunteers aged 18-65 years. Participants' non-dominant wrist was immobilized using a synthetic polyester cast followed by a Plaster of Paris cast with three point moulding to simulate reduction of a dorsally angulated distal radius fracture. The novel use of peripheral quantitative computed tomography was used to measure the closeness of fit of each cast on an axial tomographic slice. Plaster of Paris casts were able to achieve a closer mould than polyester when measured between the bone and the cast (p=0.002), as well as between the skin and the cast (p=0.001). There was no difference when stratified on BMI. Using pQCT assessment, a closely moulded fit was able to be more consistently achieved when using Plaster of Paris when compared to polyester casts of the distal radius. III.
Numerical particle-scale study of swelling pressure in clays
Publisher: Springer Science and Business Media LLC
Date: 24-06-2009
A computational approach to understanding functional behaviour of bone multicellular units (Conference Abstracts)
Publisher: Springer Science and Business Media LLC
Date: 09-2011
Effect of Polyester and Plaster of Paris Casts on Determination of Volumetric Bone Mineral Density Assessed by Peripheral Quantitative Computed Tomography (pQCT)
Publisher: Springer Science and Business Media LLC
Date: 12-07-2016
DOI: 10.1007/S00223-016-0169-8
Abstract: Peripheral quantitative computed tomography (pQCT) is a non-invasive, low-radiation tool for measuring volumetric bone mineral density. It has potential for use in fracture healing applications however, the unknown attenuation effects of cast material on peripheral quantitative computed tomography have contributed to its limited use in this area. The effect of two common cast materials, polyester and Plaster of Paris was investigated by performing both in vitro and in vivo studies. The in vitro study tested the effect of increasing layers of cast material on bone density measurements performed on a hydroxyapatite phantom. Cast thickness was directly associated with a reduction in bone mineral density, with twelve layers of polyester and Plaster of Paris resulting in a 0.55 and 2.21 % decrease in bone density measurements. Precision error in situ with polyester cast material was 0.71 %, and 2.31 % with Plaster of Paris cast material. The in vivo study comprised a prospective trial with 28 healthy adult participants to evaluate the effect of the two cast materials. Trabecular bone mineral density was increased by 0.5 % in the presence of a polyester cast and decreased by 4.22 % in the presence of a Plaster of Paris cast. Cortical bone mineral density was decreased by 3.46 and 5.54 % for polyester and Plaster of Paris, respectively. This study quantified the effects of orthopaedic casts on pQCT-derived bone parameters. The results suggest applicability of commonly utilised cast materials in combination with pQCT to assess fracture healing.
Structural and Material Changes of Human Cortical Bone With Age: Lessons from the Melbourne Femur Research Collection
Publisher: Elsevier
Date: 2018
Latarjet's muscular alterations increase glenohumeral joint stability
Publisher: Elsevier BV
Date: 06-2023
The effect of the third invariant in computational plasticity
Publisher: Emerald
Date: 08-2003
DOI: 10.1108/02644400310488844
Abstract: In this paper, we examine the influence of the third invariant in computational plasticity. For this purpose we consider the extended Leon model, an elasto‐plastic model for concrete materials which accounts for the difference of shear strength in triaxial compression and triaxial extension. Consequently, the deviatoric trace of the loading surface is no longer circular like in von Mises and Drucker‐Prager plasticity. In the limit it approaches the triangular shape of the Rankine condition of maximum direct stress. Thereby, elliptic functions describe the out‐of‐roundness of the circular trace in terms of C 1 ‐continuous functions of the Lode angle. The algorithmic aspects of the third invariant considerably complicate the computational implementation since the radial return method of J 2 ‐plasticity does no longer maintain normality leading to loss of deviatoric associativity. The paper will focus on the computational issues near the three regions with high curvature at the compressive meridians with special attention on the lack of convergence of the plastic return algorithm and its slow rate of convergence in these regions. The algorithmic discussion at the constitutive level will be augmented by the axial plane‐strain compression test in order to illustrate the effect of the third invariant at the structural level of finite element analysis.
Atypical femoral fractures are associated with high cyclic tensile strain regions during walking
Publisher: Wiley
Date: 02-2013
DOI: 10.1002/JBMR.2201
Assessment of romosozumab efficacy in the treatment of postmenopausal osteoporosis: Results from a mechanistic PK-PD mechanostat model of bone remodeling
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.BONE.2020.115223
Abstract: This paper introduces a theoretical framework for the study of the efficacy of romosozumab, a humanized monoclonal antibody targeting sclerostin for the treatment of osteoporosis. We developed a comprehensive mechanistic pharmacokinetic-pharmacodynamic (PK-PD) model of the effect of drug treatment on bone remodeling in postmenopausal osteoporosis (PMO). We utilized a one-compartment PK model to represent subcutaneous injections of romosozumab and subsequent absorption into serum. The PD model is based on a recently-developed bone cell population model describing the bone remodeling process at the tissue scale. The latter accounts for mechanical feedback by incorporating nitric oxide (NO) and sclerostin (Scl) as biochemical feedback molecules. Utilizing a competitive binding model, where Wnt and Scl compete for binding to LRP5/6, allows to regulate anabolic bone remodeling responses. Here, we extended this model with respect to romosozumab binding to sclerostin. For the currently approved monthly injections of 210 mg, the model predicted a 6.59%, 10.38% and 15.25% increase in BMD at the lumbar spine after 6, 12 and 24 months, respectively. These results are in good agreement with the data reported in the literature. Our model is also able to distinguish the bone-site specific drug effects. For instance, at the femoral neck, our model predicts a BMD increase of 3.85% after 12 months of 210 mg injections, which is consistent with literature observations. Finally, our simulations indicate rapid bone loss after treatment discontinuation, indicating that some additional interventions such as use of bisphosphonates are required to maintain bone mass.
A mathematical model for targeting chemicals to tissues by exploiting complex degradation
Publisher: Springer Science and Business Media LLC
Date: 2011
Engineering the perfect mattress: The influence of substrate mechanics on deep tissue stresses in supine
Publisher: Elsevier BV
Date: 12-2023
A new model of bone remodeling and turnover set up in the framework of generalized continuum mechanics
Publisher: SAGE Publications
Date: 28-01-2021
Abstract: In the past few decades, numerous studies have attempted to address the various phenomena that take place simultaneously during bone remodeling. Drawing from Frost’s “mechanostat theory,” multiple phenomenological models of varying complexity have been developed to describe bone remodeling in terms of evolution of bone porosity, tissue properties, and mineralization. The main goal of this paper is to present the general theory of a novel macroscopic and comprehensive model of bone remodeling accounting for the interactions of mechanics and biochemistry at the microscale. Two independent remodeling mechanisms are considered: the rotation of the material axes and the turnover of bone material. The former mechanism is related to the change of orientation of bone microstructure. Bone turnover refers to the dynamic process of bone resorption by osteoclasts, formation of unmineralized bone by osteoblasts, and mineralization. The model is set up in the framework of generalized continuum mechanics. The evolution of bone tissue is thus described through its macroscopic deformation as well as macroscopic variables related to the orientation of bone microstructure and bone tissue composition (porosity, unmineralized and mineralized bone matrix). Thermodynamically consistent evolution laws of bone material are obtained by enforcing suitable statements of the virtual power principle and of the dissipation principle. Moreover, additional constitutive hypotheses are formulated to develop a phenomenological law of bone turnover. The turnover model is discussed on the basis of a number of numerical simulations. Although the model can capture the main features of bone turnover, it cannot describe satisfactorily the complexity of the underlying biological crosstalk, highlighting the need of a more refined mechanobiological constitutive theory of bone turnover.
Investigation of nutrient transport mechanisms in the lacunae-canaliculi system
Publisher: IOP Publishing
Date: 06-2014
Investigation of Donnan equilibrium in charged porous materials - A scale transition analysis
Publisher: Springer Science and Business Media LLC
Date: 14-12-2007
Lacunar-canalicular network in femoral cortical bone is reduced in aged women and is predominantly due to a loss of canalicular porosity
Publisher: Elsevier BV
Date: 12-2017
Mechanistic PK-PD model of alendronate treatment of postmenopausal osteoporosis predicts bone site-specific response
Publisher: Frontiers Media SA
Date: 17-08-2022
DOI: 10.3389/FBIOE.2022.940620
Abstract: Alendronate is the most widely used drug for postmenopausal osteoporosis (PMO). It inhibits bone resorption, affecting osteoclasts. Pharmacokinetics (PK) and pharmacodynamics (PD) of alendronate have been widely studied, but few mathematical models exist to simulate its effect. In this work, we have developed a PK model for alendronate, valid for short- and long-term treatments, and a mechanistic PK-PD model for the treatment of PMO to predict bone density gain (BDG) at the hip and lumbar spine. According to our results, at least three compartments are required in the PK model to predict the effect of alendronate in both the short and long terms. Clinical data of a 2-year treatment of alendronate, reproduced by our PK-PD model, demonstrate that bone response is site specific (hip: 7% BDG, lumbar spine: 4% BDG). We identified that this BDG is mainly due to an increase in tissue mineralization and a decrease in porosity. The difference in BDG between sites is linked to the different loading and dependence of the released alendronate on the bone-specific surface and porosity. Osteoclast population diminishes quickly within the first month of alendronate treatment. Osteoblast population lags behind but also falls due to coupling of resorption and formation. Two dosing regimens were studied (70 mg weekly and 10 mg daily), and both showed very similar BDG evolution, indicating that alendronate accumulates quickly in bone and saturates. The proposed PK-PD model could provide a valuable tool to analyze the effect of alendronate and to design patient-specific treatments, including drug combinations.
Concrete Subjected to Triaxial Stress States: Application to Pull-Out Analyses
Publisher: American Society of Civil Engineers (ASCE)
Date: 12-2004
A multiscale mechanobiological model of bone remodelling predicts site-specific bone loss in the femur during osteoporosis and mechanical disuse
Publisher: Springer Science and Business Media LLC
Date: 04-08-2016
DOI: 10.1007/S10237-015-0705-X
Abstract: We propose a multiscale mechanobiological model of bone remodelling to investigate the site-specific evolution of bone volume fraction across the midshaft of a femur. The model includes hormonal regulation and biochemical coupling of bone cell populations, the influence of the microstructure on bone turnover rate, and mechanical adaptation of the tissue. Both microscopic and tissue-scale stress/strain states of the tissue are calculated from macroscopic loads by a combination of beam theory and micromechanical homogenisation. This model is applied to simulate the spatio-temporal evolution of a human midshaft femur scan subjected to two deregulating circumstances: (i) osteoporosis and (ii) mechanical disuse. Both simulated deregulations led to endocortical bone loss, cortical wall thinning and expansion of the medullary cavity, in accordance with experimental findings. Our model suggests that these observations are attributable to a large extent to the influence of the microstructure on bone turnover rate. Mechanical adaptation is found to help preserve intracortical bone matrix near the periosteum. Moreover, it leads to non-uniform cortical wall thickness due to the asymmetry of macroscopic loads introduced by the bending moment. The effect of mechanical adaptation near the endosteum can be greatly affected by whether the mechanical stimulus includes stress concentration effects or not.
Efficacy of novel synthetic bone substitutes in the reconstruction of large segmental bone defects in sheep tibiae
Publisher: IOP Publishing
Date: 19-02-2016
DOI: 10.1088/1748-6041/11/1/015016
Abstract: The treatment of large bone defects, particularly those with segmental bone loss, remains a significant clinical challenge as current approaches involving surgery or bone grafting often do not yield satisfactory long-term outcomes. This study reports the evaluation of novel ceramic scaffolds applied as bone graft substitutes in a clinically relevant in vivo model. Baghdadite scaffolds, unmodified or modified with a polycaprolactone coating containing bioactive glass nanoparticles, were implanted into critical-sized segmental bone defects in sheep tibiae for 26 weeks. Radiographic, biomechanical, μ-CT and histological analyses showed that both unmodified and modified baghdadite scaffolds were able to withstand physiological loads at the defect site, and induced substantial bone formation in the absence of supplementation with cells or growth factors. Notably, all s les showed significant bridging of the critical-sized defect (average 80%) with evidence of bone infiltration and remodelling within the scaffold implant. The unmodified and modified baghdadite scaffolds achieved similar outcomes of defect repair, although the latter may have an initial mechanical advantage due to the nanocomposite coating. The baghdadite scaffolds evaluated in this study hold potential for use as purely synthetic bone graft substitutes in the treatment of large bone defects while circumventing the drawbacks of autografts and allografts.
Assessment of Strategies for Safe Drug Discontinuation and Transition of Denosumab Treatment in PMO-Insights From a Mechanistic PK/PD Model of Bone Turnover
Publisher: Frontiers Media SA
Date: 17-06-2022
DOI: 10.3389/FBIOE.2022.886579
Abstract: Denosumab (Dmab) treatment against postmenopausal osteoporosis (PMO) has proven very efficient in increasing bone mineral density (BMD) and reducing the risk of bone fractures. However, concerns have been recently raised regarding safety when drug treatment is discontinued. Mechanistic pharmacokinetic-pharmacodynamic (PK-PD) models are the most sophisticated tools to develop patient specific drug treatments of PMO to restore bone mass. However, only a few PK-PD models have addressed the effect of Dmab drug holidays on changes in BMD. We showed that using a standard bone cell population model (BCPM) of bone remodelling it is not possible to account for the spike in osteoclast numbers observed after Dmab discontinuation. We show that inclusion of a variable osteoclast precursor pool in BCPMs is essential to predict the experimentally observed rapid rise in osteoclast numbers and the associated increases in bone resorption. This new model also showed that Dmab withdrawal leads to a rapid increase of damage in the bone matrix, which in turn decreases the local safety factor for fatigue failure. Our simulation results show that changes in BMD strongly depend on Dmab concentration in the central compartment. Consequently, bone weight (BW) might play an important factor in calculating effective Dmab doses. The currently clinically prescribed constant Dmab dose of 60 mg injected every 6 months is less effective in increasing BMD for patients with high BW (2.5% for 80 kg in contrast to 8% for 60 kg after 6 years of treatment). However, bone loss observed 24 months after Dmab withdrawal is less pronounced in patients with high BW (3.5% for 80kg and 8.5% for 60 kg). Finally, we studied how to safely discontinue Dmab treatment by exploring several transitional and combined drug treatment strategies. Our simulation results indicate that using transitional reduced Dmab doses are not effective in reducing rapid bone loss. However, we identify that use of a bisphosphonate (BP) is highly effective in avoiding rapid bone loss and increase in bone tissue damage compared to abrupt withdrawal of Dmab. Furthermore, the final values of BMD and damage were not sensitive to the time of administration of the BP.
Differences in Hip and Knee Landing Moments across Female Pubertal Development
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2019
DOI: 10.1249/MSS.0000000000001753
Abstract: The higher prevalence of knee injuries among adolescent females may be related to female pubertal development. The aim of this study was to determine whether girls exhibit higher triplanar knee and hip moments with more advanced pubertal development during a single-limb landing. Lower-limb biomechanics of 93 females grouped according to prepubertal ( n = 31), early/midpubertal ( n = 31) and late ostpubertal ( n = 31) development performed a single-limb drop lateral jump. Peak triplanar knee moments and hip moments at the time of peak knee moments were derived from a Vicon motion analysis system and concealed force plate. Joint moments were normalized to body mass (N·m·kg −1 ), height (N·m·kg −1 ·m −1 ) and body mass by height (N·m·kg −1 ·m −1 ). Between-group differences were analyzed using a one-way ANOVA with Pearson correlations used to explore relationships between joint moments and anthropometrics. Girls at latter stages of puberty landed with higher triplanar knee moments and hip flexion moment at time of peak knee flexion moment when normalized separately to body mass and to height ( P 0.05). In contrast, hip internal rotation moments at time of peak knee internal rotation moment normalized to body mass and to body mass by height were lower in late ostpubertal girls compared to their early/midpubescent ( P = 0.01) and prepubescent ( P = 0.01) counterparts. Positive correlations were identified between triplanar knee moments and body mass ( r = 0.73–0.91, P 0.001) and height ( r = 0.61–0.89, P 0.001) for all participants. Higher triplanar knee and sagittal plane hip moments with more advanced pubertal stage is attributed to growth-related increases in body mass and height. Given that growth is a crucial element of puberty, further research is required to quantify the impact of pubertal growth-related changes on risk of adolescent female anterior cruciate ligament injury.
Spatio-temporal simulations of bone remodelling using a bone cell population model based on cell availability
Publisher: Frontiers Media SA
Date: 07-03-2023
DOI: 10.3389/FBIOE.2023.1060158
Abstract: Here we developed a spatio-temporal bone remodeling model to simulate the action of Basic Multicelluar Units (BMUs). This model is based on two major extensions of a temporal-only bone cell population model (BCPM). First, the differentiation into mature resorbing osteoclasts and mature forming osteoblasts from their respective precursor cells was modelled as an intermittent process based on precursor cells availability. Second, the interaction between neighbouring BMUs was considered based on a “metabolic cost” argument which warrants that no new BMU will be activated in the neighbourhood of an existing BMU. With the proposed model we have simulated the phases of the remodelling process obtaining average periods similar to those found in the literature: resorption ( ∼ 22 days)—reversal (∼8 days)—formation (∼65 days)—quiescence (560–600 days) and an average BMU activation frequency of ∼1.6 BMUs/year/mm 3 . We further show here that the resorption and formation phases of the BMU become coordinated only by the presence of TGF-β (transforming growth factor β ), i.e., a major coupling factor stored in the bone matrix. TGF-β is released through resorption so upregulating osteoclast apoptosis and accumulation of osteoblast precursors, i.e., facilitating the transition from the resorption to the formation phase at a given remodelling site. Finally, we demonstrate that this model can explain targeted bone remodelling as the BMUs are steered towards damaged bone areas in order to commence bone matrix repair.
Treatment with a long-acting chimeric CSF1 molecule enhances fracture healing of healthy and osteoporotic bones
Publisher: Elsevier BV
Date: 08-2021
Beam theory for rapid strain estimation in the mouse tibia compression model
Publisher: Springer Science and Business Media LLC
Date: 04-01-2022
DOI: 10.1007/S10237-021-01546-1
Abstract: The mouse tibia compression model is a leading model for studying bone's mechanoadaptive response to load. In studying this mechanoadaptive response, (FE) modelling is often used to determine the stress/strain within the tibia. The development of such models can be challenging and computationally expensive. An alternate approach is to use continuum mechanics based analytical theories, such as beam theory (BT). However, applying BT to the mouse tibia requires the fibula be neglected, introducing error in the stress/strain distribution. While several studies have applied BT to the mouse tibia, no study has explored the accuracy of this approach. To address these questions, this work investigates the use of BT in determining stress/strain within the mouse tibia. By comparing BT against FE modelling, it was found that BT can accurately predict tibial stress/strain if correction factors are applied to account for the effect of the fibula. The 25, 37, 50 and 75% cross sections are studied. Focusing on the 37% cross section, without correction, BT can have errors of approximately 21.6%. With correction, this is reduced to 6.6%. Such correction factors are presented. The developed BT model is applicable in the diaphysis and distal metaphysis, where the assumptions of BT are valid. This work verifies BT for determining localised strains in a mouse tibia compression model. This is anticipated to provide efficiency idends, allowing for high throughput modelling of the mouse tibia, advancing study of bone's mechanoadaptive response.
Model structure and control of bone remodeling: A theoretical study
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.BONE.2008.03.025
Abstract: It is generally accepted that RANKL is highly expressed in osteoblast precursor cells while OPG is highly expressed in mature osteoblasts, but to date no functional utility to the BMU has been proposed for this particular ligand-decoy-receptor expression profile. As discovered in the mid 90s, the RANK-RANKL-OPG signaling cascade is a major signaling pathway regulating bone remodeling. In this paper we study theoretically the functional implications of particular RANKL/OPG expression profiles on bone volume. For this purpose we formulate an extended bone-cell dynamics model describing functional behaviour of basic multicellular units (BMUs) responsible for bone resorption and formation. This model incorporates the RANK-RANKL-OPG signaling together with the regulating action of TGF-beta on bone cells. The bone-cell population model employed here builds on the work of Lemaire et al. (2004) [1], but incorporates the following significant modifications: (i) addition of a rate equation describing changes in bone volume with time as the key 'output function' tracking functional behaviour of BMUs, (ii) a rate equation describing release of TGF-beta from the bone matrix, (iii) expression of OPG and RANKL on both osteoblastic cell lines, and (iv) modified activator/repressor functions. Using bone volume as a functional selection criterion, we find that there is a preferred arrangement for ligand expression on particular cell types, and further, that this arrangement coincides with biological observations. We then investigate the model parameter space combinatorially, searching for preferred 'groupings' of changes in differentiation rates of various cell types. Again, a criterion of bone volume change is employed to identify possible ways of optimally controlling BMU responses. While some combinations of changes in differentiation rates are clearly unrealistic, other combinations of changes in differentiation rates are potentially functionally significant. Most importantly, the combination of parameter changes representing the signaling pathway for TGF-beta gives a unique result that appears to have a clear biological rationale. The methodological approach for the investigation of model structure described here offers a theoretical explanation as to why TGF-beta has its particular suite of biological effects on bone-cell differentiation rates.
Two-scale model for electro-diffusive transport through charged porous materials
Publisher: IOP Publishing
Date: 06-2014
Cortical Thickness Adaptive Response to Mechanical Loading Depends on Periosteal Position and Varies Linearly With Loading Magnitude
Publisher: Frontiers Media SA
Date: 18-06-2021
DOI: 10.3389/FBIOE.2021.671606
Abstract: The aim of the current study was to quantify the local effect of mechanical loading on cortical bone formation response at the periosteal surface using previously obtained μCT data from a mouse tibia mechanical loading study. A novel image analysis algorithm was developed to quantify local cortical thickness changes (ΔCt.Th) along the periosteal surface due to different peak loads (0N ≤ F ≤ 12N) applied to right-neurectomised mature female C57BL/6 mice. Furthermore, beam analysis was performed to analyse the local strain distribution including regions of tensile, compressive, and low strain magnitudes. Student’s paired t -test showed that ΔCt.Th in the proximal (25%), proximal/middle (37%), and middle (50%) cross-sections (along the z-axis of tibia) is strongly associated with the peak applied loads. These changes are significant in a majority of periosteal positions, in particular those experiencing high compressive or tensile strains. No association between F and ΔCt.Th was found in regions around the neutral axis. For the most distal cross-section (75%), the association of loading magnitude and ΔCt.Th was not as pronounced as the more proximal cross-sections. Also, bone formation responses along the periosteum did not occur in regions of highest compressive and tensile strains predicted by beam theory. This could be due to complex experimental loading conditions which were not explicitly accounted for in the mechanical analysis. Our results show that the bone formation response depends on the load magnitude and the periosteal position. Bone resorption due to the neurectomy of the loaded tibia occurs throughout the entire cross-sectional region for all investigated cortical sections 25, 37, 50, and 75%. For peak applied loads higher than 4 N, compressive and tensile regions show bone formation however, regions around the neutral axis show constant resorption. The 50% cross-section showed the most regular ΔCt.Th response with increased loading when compared to 25 and 37% cross-sections. Relative thickness gains of approximately 70, 60, and 55% were observed for F = 12 N in the 25, 37, and 50% cross-sections. ΔCt.Th at selected points of the periosteum follow a linear response with increased peak load no lazy zone was observed at these positions.
Investigation of nanoscale electrohydrodynamic transport phenomena in charged porous materials
Publisher: Wiley
Date: 2005
DOI: 10.1002/NME.1353
Bone orthotropic remodeling as a thermodynamically-driven evolution
Publisher: World Scientific Pub Co Pte Lt
Date: 05-2020
DOI: 10.1142/S0219519419500842
Abstract: In this paper, we present and discuss a model of bone remodeling set up in the framework of the theory of generalized continuum mechanics which was first introduced by DiCarlo et al. [Sur le remodelage des tissus osseux anisotropes, Comptes Rendus Mécanique 334(11):651–661, 2006]. Bone is described as an orthotropic body experiencing remodeling as a rotation of its microstructure. Thus, the complete kinematic description of a material point is provided by its position in space and a rotation tensor describing the orientation of its microstructure. Material motion is driven by energetic considerations, namely by the application of the Clausius–Duhem inequality to the microstructured material. Within this framework of orthotropic remodeling, some key features of the remodeling equilibrium configurations are deduced in the case of homogeneous strain or stress loading conditions. First, it is shown that remodeling equilibrium configurations correspond to energy extrema. Second, stability of the remodeling equilibrium configurations is assessed in terms of the local convexity of the strain and complementary energy functionals hence recovering some classical energy theorems. Eventually, it is shown that the remodeling equilibrium configurations are not only highly dependent on the loading conditions, but also on the material properties.
Cortical bone adaptation response is region specific, but not peak load dependent
Publisher: Springer Science and Business Media LLC
Date: 18-10-2023
Integrated model of IGF-I mediated biosynthesis in a deformed articular cartilage
Publisher: American Society of Civil Engineers (ASCE)
Date: 05-2009
Novel pressure inlet and outlet boundary conditions for Smoothed Particle Hydrodynamics, applied to real problems in porous media flow
Publisher: Elsevier BV
Date: 03-2021
New insights into therapeutic drug interventions for catabolic bone diseases using an in-silico modeling approach
Publisher: Elsevier BV
Date: 05-2009
A biomechanical analysis of double-screw, double-button, and screw-button fixation constructs in patient-specific instrument–guided Latarjet procedure
Publisher: Elsevier BV
Date: 07-2023
Modeling the sorption of fluoride onto alumina
Publisher: American Society of Civil Engineers (ASCE)
Date: 02-2006
Theoretical analysis of anion exclusion and diffusive transport through platy-clay soils
Publisher: Springer Science and Business Media LLC
Date: 12-2004
Toward Patient Specific Models of Pediatric IVDs: A Parametric Study of IVD Mechanical Properties
Publisher: Frontiers Media SA
Date: 15-02-2021
DOI: 10.3389/FBIOE.2021.632408
Abstract: Patient specific finite element (FE) modeling of the pediatric spine is an important challenge which offers to revolutionize the treatment of pediatric spinal pathologies, for ex le adolescent idiopathic scoliosis (AIS). In particular, modeling of the intervertebral disc (IVD) is a unique challenge due to its structural and mechanical complexity. This is compounded by limited ability to non-invasively interrogate key mechanical parameters of a patient's IVD. In this work, we seek to better understand the link between mechanical properties and mechanical behavior of patient specific FE models of the pediatric lumbar spine. A parametric study of IVD parameter was conducted, coupled with insights from current knowledge of the pediatric IVD. In particular, the combined effects of parameters was investigated. Recommendations are made toward areas of importance in patient specific FE modeling of the pediatric IVD. In particular, collagen fiber bundles of the IVD are found to dominate IVD mechanical behavior and are thus recommended as an area of primary focus for patient specific FE models. In addition, areas requiring further experimental research are identified. This work provides a valuable building block toward the development of patient specific models of the pediatric spine.
Modelling the anabolic response of bone using a cell population model
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.JTBI.2012.04.019
Abstract: To maintain bone mass during bone remodelling, coupling is required between bone resorption and bone formation. This coordination is achieved by a network of autocrine and paracrine signalling molecules between cells of the osteoclastic lineage and cells of the osteoblastic lineage. Mathematical modelling of signalling between cells of both lineages can assist in the interpretation of experimental data, clarify signalling interactions and help develop a deeper understanding of complex bone diseases. Several mathematical models of bone cell interactions have been developed, some including RANK-RANKL-OPG signalling between cells and systemic parathyroid hormone PTH. However, to our knowledge these models do not currently include key aspects of some more recent biological evidence for anabolic responses. In this paper, we further develop a mathematical model of bone cell interactions by Pivonka et al. (2008) to include the proliferation of precursor osteoblasts into the model. This inclusion is important to be able to account for Wnt signalling, believed to play an important role in the anabolic responses of bone. We show that an increased rate of differentiation to precursor cells or an increased rate of proliferation of precursor osteoblasts themselves both result in increased bone mass. However, modelling these different processes separately enables the new model to represent recent experimental discoveries such as the role of Wnt signalling in bone biology and the recruitment of osteoblast progenitor cells by transforming growth factor β. Finally, we illustrate the power of the new model's capabilities by applying the model to prostate cancer metastasis to bone. In the bone microenvironment, prostate cancer cells are believed to release some of the same signalling molecules used to coordinate bone remodelling (i.e.,Wnt and PTHrP), enabling the cancer cells to disrupt normal signalling and coordination between bone cells. This disruption can lead to either bone gain or bone loss. We demonstrate that the new computational model developed here is capable of capturing some key observations made on the evolution of the bone mass due to metastasis of prostate cancer to the bone microenvironment.
Computational model of the dual action of PTH - Application to a rat model of osteoporosis
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JTBI.2019.04.020
Abstract: This paper presents a pharmacokinetic harmacodynamic (PK/PD) model of the action of PTH(1-34) on bone modelling and remodelling, developed for quantitatively investigating the dose- and administration pattern-dependency of the bone tissue response to this drug. Firstly, a PK model of PTH(1-34) was developed, accounting for administration via subcutaneous injections. Subsequently, the PK model was coupled to a (mechanistic) bone cell population model of bone modelling and remodelling, taking into account the effects of PTH(1-34) on the differentiation of lining cells into active osteoblasts, on the apoptosis of active osteoblasts, and on proliferation of osteoblast precursors, as well as on the key regulatory pathways of bone cell activities. Numerical simulations show that the coupled PK/PD model is able to distinguish between continuous and intermittent administration patterns of PTH(1-34), in terms of yielding both catabolic bone responses (if drug administration is carried out continuously) and anabolic bone responses (if drug administration is carried out intermittently). The model also features a non-linear relation between bone gain and drug dose (as known from experiments) doubling the dose from 80 μg/kg/day to 160 μg/kg/day induced a 1.3-fold increase of the bone volume-to-total volume ratio. Furthermore, the model presented in this paper confirmed that bone modelling represents an essential mechanism of the anabolic response of bone to PTH(1-34) administration in rat models, and that the large amount of bone formation observed in such models cannot be explained via remodelling alone.
Effect of neglecting passive spinal structures
Publisher: Frontiers Media SA
Date: 31-05-2023
DOI: 10.3389/FPHYS.2023.1135531
Abstract: Purpose: Inverse-dynamics (ID) analysis is an approach widely used for studying spine biomechanics and the estimation of muscle forces. Despite the increasing structural complexity of spine models, ID analysis results substantially rely on accurate kinematic data that most of the current technologies are not capable to provide. For this reason, the model complexity is drastically reduced by assuming three degrees of freedom spherical joints and generic kinematic coupling constraints. Moreover, the majority of current ID spine models neglect the contribution of passive structures. The aim of this ID analysis study was to determine the impact of modelled passive structures (i.e., ligaments and intervertebral discs) on remaining joint forces and torques that muscles must balance in the functional spinal unit. Methods: For this purpose, an existing generic spine model developed for the use in the demoa software environment was transferred into the musculoskeletal modelling platform OpenSim . The thoracolumbar spine model previously used in forward-dynamics (FD) simulations provided a full kinematic description of a flexion-extension movement. By using the obtained in silico kinematics, ID analysis was performed. The in idual contribution of passive elements to the generalised net joint forces and torques was evaluated in a step-wise approach increasing the model complexity by adding in idual biological structures of the spine. Results: The implementation of intervertebral discs and ligaments has significantly reduced compressive loading and anterior torque that is attributed to the acting net muscle forces by −200% and −75%, respectively. The ID model kinematics and kinetics were cross-validated against the FD simulation results. Conclusion: This study clearly shows the importance of incorporating passive spinal structures on the accurate computation of remaining joint loads. Furthermore, for the first time, a generic spine model was used and cross-validated in two different musculoskeletal modelling platforms, i.e., demoa and OpenSim , respectively. In future, a comparison of neuromuscular control strategies for spinal movement can be investigated using both approaches.
Quantifying Muscle Size Asymmetry in Adolescent Idiopathic Scoliosis Using Three-dimensional Magnetic Resonance Imaging
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-07-2023
DOI: 10.1097/BRS.0000000000004715
Abstract: This is a case-control study of prospectively collected data. To quantify paraspinal muscle size asymmetry in adolescent idiopathic scoliosis (AIS) and determine if this asymmetry is i) greater than observed in adolescent controls with symmetrical spines and ii) positively associated with skeletal maturity using Risser grade, scoliosis severity using the Cobb angle, and chronological age in years. AIS is a three-dimensional deformity of the spine which occurs in 2.5-3.7% of the Australian population. There is some evidence of asymmetry in paraspinal-muscle activation and morphology in AIS. Asymmetrical paraspinal muscle forces may facilitate asymmetrical vertebral growth during adolescence. An asymmetry index [Ln(concave/convex volume)] of i) deep and ii) superficial paraspinal-muscle volumes, at the level of the i) major curve apex (Thoracic 8-9 th vertebral level) and ii) lower-end vertebrae ( LEV , Thoracic 10-12 th vertebral level), was determined from 3D Magnetic Resonance Imaging (MRI) of 25 adolescents with AIS (all right thoracic curves), and 22 healthy controls (convex=left) all female, 10-16 years. Asymmetry index of deep paraspinal-muscle volumes was greater in AIS (0.16±0.20) than healthy spine controls (-0.06±0.13) at the level of the apex ( P .01, linear mixed-effects analysis), but not LEV ( P .05). Asymmetry index was positively correlated with Risser grade (r=0.50, P .05) and scoliosis Cobb angle (r=0.45, P .05), but not age (r=0.34, P .05). There was no difference in the asymmetry index of superficial paraspinal muscle volumes between AIS and controls ( P .05). The asymmetry of deep apical paraspinal-muscle volume in AIS at the scoliosis apex is greater than that observed at equivalent vertebral levels in controls and may play a role in the pathogenesis of AIS.
A comparison of optimization methods and knee joint degrees of freedom on muscle force predictions during single-leg hop landings
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.JBIOMECH.2014.07.027
Abstract: The aim of this paper was to compare the effect of different optimisation methods and different knee joint degrees of freedom (DOF) on muscle force predictions during a single legged hop. Nineteen subjects performed single-legged hopping manoeuvres and subject-specific musculoskeletal models were developed to predict muscle forces during the movement. Muscle forces were predicted using static optimisation (SO) and computed muscle control (CMC) methods using either 1 or 3 DOF knee joint models. All sagittal and transverse plane joint angles calculated using inverse kinematics or CMC in a 1 DOF or 3 DOF knee were well-matched (RMS error<3°). Biarticular muscles (hamstrings, rectus femoris and gastrocnemius) showed more differences in muscle force profiles when comparing between the different muscle prediction approaches where these muscles showed larger time delays for many of the comparisons. The muscle force magnitudes of vasti, gluteus maximus and gluteus medius were not greatly influenced by the choice of muscle force prediction method with low normalised root mean squared errors (<48%) observed in most comparisons. We conclude that SO and CMC can be used to predict lower-limb muscle co-contraction during hopping movements. However, care must be taken in interpreting the magnitude of force predicted in the biarticular muscles and the soleus, especially when using a 1 DOF knee. Despite this limitation, given that SO is a more robust and computationally efficient method for predicting muscle forces than CMC, we suggest that SO can be used in conjunction with musculoskeletal models that have a 1 or 3 DOF knee joint to study the relative differences and the role of muscles during hopping activities in future studies.
Mathematical Modeling in Bone Biology: from Intracellular Signalling to Tissue Mechanics
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.BONE.2010.04.601
Abstract: Although conceptual and experimental models are historically well incorporated in bone biology studies, mathematical modeling has been much less-frequently utilized. This review aims to introduce mathematical modeling to readers who are not familiar with the concept underlying this methodology, to outline how mathematical models can help to improve current understanding of bone biology and to discuss ex les where mathematical modeling was used to provide new insights into important questions of bone biology.
Estimating vertical and lateral pressures in periodically structured montmorillonite clay particles
Publisher: FapUNIFESP (SciELO)
Date: 03-2010
DOI: 10.1590/S0001-37652010000100003
Abstract: Given a montmorillonitic clay soil at high porosity and saturated by monovalent counterions, we investigate the particle level responses of the clay to different external loadings. As analytical solutions are not possible for complex arrangements of particles, we employ computational micromechanical models (based on the solution of the Poisson-Nernst-Planck equations) using the finite element method, to estimate counterion and electrical potential distributions for particles at various angles and distances from one another. We then calculate the disjoining pressures using the Van't Hoff relation and Maxwell stress tensor. As the distance between the clay particles decreases and double-layers overlap, the concentration of counterions in the micropores among clay particles increases. This increase lowers the chemical potential of the pore fluid and creates a chemical potential gradient in the solvent that generates the socalled 'disjoining' or 'osmotic' pressure. Because of this disjoining pressure, particles do not need to contact one another in order to carry an 'effective stress'. This work may lead towards theoretical predictions of the macroscopic load deformation response of montmorillonitic soils based on micromechanical modelling of particles.
Coupling systems biology with multiscale mechanics, for computer simulations of bone remodeling
Publisher: Elsevier BV
Date: 02-2013
Investigation of bone resorption within a cortical basic multicellular unit using a lattice-based computational model
Publisher: Elsevier BV
Date: 2012
Effects of geometric individualisation of a human spine model on load sharing: neuro-musculoskeletal simulation reveals significant differences in ligament and muscle contribution
Publisher: Springer Science and Business Media LLC
Date: 05-01-2023
DOI: 10.1007/S10237-022-01673-3
Abstract: In spine research, two possibilities to generate models exist: generic (population-based) models representing the average human and subject-specific representations of in iduals. Despite the increasing interest in subject specificity, in idualisation of spine models remains challenging. Neuro-musculoskeletal (NMS) models enable the analysis and prediction of dynamic motions by incorporating active muscles attaching to bones that are connected using articulating joints under the assumption of rigid body dynamics. In this study, we used forward-dynamic simulations to compare a generic NMS multibody model of the thoracolumbar spine including fully articulated vertebrae, detailed musculature, passive ligaments and linear intervertebral disc (IVD) models with an in idualised model to assess the contribution of in idual biological structures. In idualisation was achieved by integrating skeletal geometry from computed tomography and custom-selected muscle and ligament paths. Both models underwent a gravitational settling process and a forward flexion-to-extension movement. The model-specific load distribution in an equilibrated upright position and local stiffness in the L4/5 functional spinal unit (FSU) is compared. Load sharing between occurring internal forces generated by in idual biological structures and their contribution to the FSU stiffness was computed. The main finding of our simulations is an apparent shift in load sharing with in idualisation from an equally distributed element contribution of IVD, ligaments and muscles in the generic spine model to a predominant muscle contribution in the in idualised model depending on the analysed spine level.
On the role of diffusible binding partners in modulating the transport and concentration of proteins in tissues
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.JTBI.2009.11.023
Abstract: Here a reactive-diffusion transport model is used to demonstrate two previously undescribed functional roles for diffusible binding partners in the transport of molecules into tissues. The uptake of the insulin-like growth (IGF) and its binding partner the IGF binding protein (IGFBP3) into cartilage is used a specific tissue ex le to demonstrate a general principal. First, we show that reversible binding between free protein (IGF) and its diffusible binding partner (free IGFBPs) increases the rate of protein uptake into the tissue. Second, selective degradation of the binding partner can increase the transient and steady state free protein in tissues, well above the concentration at the source boundary, with the maximum free concentration occurring distant from the source boundary, deep within the tissue. This finding is very much at odds with expectations based on a traditional diffusion analysis. In cartilage, using realistic parameters, these new mechanisms raise the free IGF concentration by an order of magnitude deep within the tissue. As the increase in free protein is 'tunable' by cells, our analyses are postulated to demonstrate a general regulatory principle that may operate in any tissues throughout the body.
Drug diffusion, integration, and stability of nanoengineered drug-releasing implants in bone ex-vivo
Publisher: Wiley
Date: 20-11-2016
DOI: 10.1002/JBM.A.35595
Abstract: To treat skeletal conditions such as bone infections, osteoporotic fractures, and osteosarcoma, it would be ideal to introduce drugs directly to the affected site. Localized drug delivery from the bone implants is a promising alternative to systemic drug administration. In this study we investigated electrochemically nanoengineered Ti wire implants with titania nanotubes (TNTs), as minimally invasive drug-releasing implants for the delivery of drugs directly into the bone tissue. Since trabecular bone in vivo contains a highly interconnected bone marrow, we sought to determine the influence of marrow on drug release and diffusion. Electrochemical anodization of Ti wires (length 10 mm) was performed to create an oxide layer with TNTs on the surface, followed by loading with a fluorescent model drug, Rhodamine B (RhB). Cores of bovine trabecular bone were generated from the sternum of a young steer, and were processed to have an intact bone marrow, or the marrow was removed. RhB-loaded TNTs/Ti wires were inserted into the bone cores, which were then cultured ex vivo using the ZetOS™ bioreactor system to maintain bone viability. Release and diffusion of RhB inside the bone was monitored using fluorescence imaging and different patterns of drug transport in the presence or absence of marrow were observed. Scanning electron microscopy of the implants after retrieval from bone cores confirmed survival of the TNTs structures. Histological investigation showed the presence of bone cells adherent on the implants. This study shows a potential of Ti drug-releasing implants based on TNTs technology towards localized bone therapy. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 714-725, 2016.
Mathematical modelling of bone adaptation of the metacarpal subchondral bone in racehorses
Publisher: Springer Science and Business Media LLC
Date: 17-01-2018
DOI: 10.1007/S10237-017-0998-Z
Abstract: In Thoroughbred racehorses, fractures of the distal limb are commonly catastrophic. Most of these fractures occur due to the accumulation of fatigue damage from repetitive loading, as evidenced by microdamage at the predilection sites for fracture. Adaptation of the bone in response to training loads is important for fatigue resistance. In order to better understand the mechanism of subchondral bone adaptation to its loading environment, we utilised a square root function defining the relationship between bone volume fraction [Formula: see text] and specific surface [Formula: see text] of the subchondral bone of the lateral condyles of the third metacarpal bone (MCIII) of the racehorse, and using this equation, developed a mathematical model of subchondral bone that adapts to loading conditions observed in vivo. The model is expressed as an ordinary differential equation incorporating a formation rate that is dependent on strain energy density. The loading conditions applied to a selected subchondral region, i.e. volume of interest, were estimated based on joint contact forces sustained by racehorses in training. For each of the initial conditions of [Formula: see text] we found no difference between subsequent homoeostatic [Formula: see text] at any given loading condition, but the time to reach equilibrium differed by initial [Formula: see text] and loading condition. We found that the observed values for [Formula: see text] from the mathematical model output were a good approximation to the existing data for racehorses in training or at rest. This model provides the basis for understanding the effect of changes to training strategies that may reduce the risk of racehorse injury.
Corrigendum to Modelling the anabolic response of bone using a cell population model [J. Theor. Biol. 307 (2012) 42-52]
Publisher: Elsevier BV
Date: 09-2012
Are drug holidays a safe option in treatment of osteoporosis? — Insights from an in silico mechanistic PK–PD model of denosumab treatment of postmenopausal osteoporosis
Publisher: Elsevier BV
Date: 2021
The effect of cyclic deformation and solute binding on solute transport in cartilage
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.ABB.2006.10.007
Abstract: Diffusive transport must play an important role in transporting nutrients into cartilage due to its avascular nature. Recent theoretical studies generally support the idea that cyclic loading enhances large molecule transport through advection. However, to date, reactive transport, i.e. the effects of solute binding, has not yet been taken into consideration in cyclically deformed cartilage. In the present study, we develop a reactive transport model to describe the potential role of binding of solute within cyclically deformed cartilage. Our results show that binding does have a significant effect on transport, particularly for the low IGF-I concentrations typical of synovial fluid. A dynamic loading regime of high strain magnitudes (up to 10%) in combination with high frequencies (e.g. 1 Hz) was seen to produce the most dramatic results with enhanced total uptake ratio as high as 25% averaged over the first 5h of cyclic loading.
Assessment of femoral neck strength and bone mineral density changes following exercise using 3D-DXA images
Publisher: Elsevier BV
Date: 04-2021
Numerical estimation of effective diffusion coefficients for charged porous materials based on micro-scale analyses
Publisher: Elsevier BV
Date: 04-2010
Muscular coordination of single-leg hop landing in uninjured and anterior cruciate ligament-reconstructed individuals
Publisher: Human Kinetics
Date: 08-2020
Abstract: This study compared lower-limb muscle function, defined as the contributions of muscles to center-of-mass support and braking, during a single-leg hopping task in anterior cruciate ligament-reconstructed (ACLR) in iduals and uninjured controls. In total, 65 ACLR in iduals and 32 controls underwent a standardized anticipated single-leg forward hop. Kinematics and ground reaction force data were input into musculoskeletal models to calculate muscle forces and to quantify muscle function by decomposing the vertical (support) and fore-aft (braking) ground reaction force components into contributions by in idual lower-limb muscles. Four major muscles, the vasti, soleus, gluteus medius, and gluteus maximus, were primarily involved in support and braking in both ACLR and uninjured groups. However, although the ACLR group demonstrated lower peak forces for these muscles (all P s .001, except gluteus maximus, P = .767), magnitude differences in these muscles’ contributions to support and braking were not significant. ACLR in iduals demonstrated higher erector spinae ( P = .012) and hamstrings forces ( P = .085) to maintain a straighter, stiffer landing posture with more forward lumbar flexion. This altered landing posture may have enabled the ACLR group to achieve similar muscle function to controls, despite muscle force deficits. Our findings may benefit rehabilitation and the development of interventions to enable faster and safer return to sport.
Computer Simulation-Based Modeling of the Pharmaceutical Intervention of Postmenopausal Osteoporosis by Denosumab
Publisher: American Society of Mechanical Engineers
Date: 02-07-2012
Abstract: Postmenopausal osteoporosis (PMO), leading to a higher bone fracture risk, is characterized by a significantly increasing bone porosity. Recently, denosumab, which is able to efficiently interfere with bone resorption, has been approved for the treatment of PMO. In order to optimize the design of drug administration regimes, we propose a computational methodology, based on mechanistic mathematical modeling of bone remodeling, considering the governing biochemical and biomechanical regulation mechanisms, and the targeted action of denosumab. The time-dependent serum concentration of denosumab, obtained from a pharmacokinetics model, is fed into a bone cell population model, allowing for prediction of porosity evolution in PMO patients. In order to account for the mechanobiology of bone remodeling, we utilize the concept of continuum micromechanics, which accurately provides the actual (microscopic) strain state of the investigated bone. Finally, different drug administration regimes are simulated, and their effect on the bone microarchitecture is discussed.
Society for Development Biology 64th Annual Meeting
Publisher: Elsevier BV
Date: 07-2005
Pose Quality Prediction for Vision Guided Robotic Shoulder Arthroplasty
Publisher: IEEE
Date: 29-05-2023
Cerebral small vessel disease genomics and its implications across the lifespan
Publisher: Springer Science and Business Media LLC
Date: 08-12-2020
DOI: 10.1038/S41467-020-19111-2
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older in iduals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk in iduals and for genetically-informed prioritization of drug targets for prevention trials.
Electro-diffusive transport in macroscopic porous media: Estimation of effective transport properties using numerical upscaling
Publisher: Elsevier BV
Date: 03-2013
The relationship between porosity and specific surface in human cortical bone is subject specific
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.BONE.2014.11.016
Abstract: A characteristic relationship for bone between bone volume fraction (BV/TV) and specific surface (BS/TV) has previously been proposed based on 2D histological measurements. This relationship has been suggested to be bone intrinsic, i.e., to not depend on bone type, bone site and health state. In these studies, only limited data comes from cortical bone. The aim of this paper was to investigate the relationship between BV/TV and BS/TV in human cortical bone using high-resolution micro-CT imaging and the correlations with subject-specific biometric data such as height, weight, age and sex. Images from femoral cortical bone s les of the Melbourne Femur Collection were obtained using synchrotron radiation micro-CT (SPring8, Japan). Sixteen bone s les from thirteen in iduals were analysed in order to find bone volume fraction values ranging from 0.20 to 1. Finally, morphological models of the tissue microstructure were developed to help explain the relationship between BV/TV and BS/TV. Our experimental findings indicate that the BV/TV vs BS/TV relationship is subject specific rather than intrinsic. Sex and pore density were statistically correlated with the in idual curves. However no correlation was found with body height, weight or age. Experimental cortical data points deviate from interpolating curves previously proposed in the literature. However, these curves are largely based on data points from trabecular bone s les. This finding challenges the universality of the curve: highly porous cortical bone is significantly different to trabecular bone of the same porosity. Finally, our morphological models suggest that changes in BV/TV within the same s le can be explained by an increase in pore area rather than in pore density. This is consistent with the proposed mechanisms of age-related endocortical bone loss. In addition, these morphological models highlight that the relationship between BV/TV and BS/TV is not linear at high BV/TV as suggested in the literature but is closer to a square root function.
Accuracy of a novel marker tracking approach based on the low-cost Microsoft Kinect v2 sensor
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.MEDENGPHY.2018.04.020
Abstract: Microsoft Kinect for Windows v2 is a motion analysis system that features a markerless human pose estimation algorithm. Given its affordability and portability, Kinect v2 has potential for use in biomechanical research and within clinical settings however, recent studies suggest high inaccuracy of the markerless algorithm compared to marker-based motion capture systems. A novel tracking method was developed using Kinect v2, employing custom-made colored markers and computer vision techniques. The aim of this study was to test the accuracy of this approach relative to a conventional Vicon motion analysis system, performing a Bland-Altman analysis of agreement. Twenty participants were recruited, and markers placed on bony prominences near hip, knee and ankle. Three-dimensional coordinates of the markers were recorded during treadmill walking and running. The limits of agreement (LOA) of marker coordinates were narrower than - 10 and 10 mm in most conditions, however a negative relationship between accuracy and treadmill speed was observed along Kinect depth direction. LOA of the surrogate knee angles were within - 1.8°, 1.7° for flexion in all conditions and - 2.9°, 1.7° for adduction during fast walking. The proposed methodology exhibited good agreement with a marker-based system over a range of gait speeds and, for this reason, may be useful as low-cost motion analysis tool for selected biomechanical applications.
Modeling of electro-diffusive ion transport through charged porous materials using a multiscale iterative approach
Publisher: AIP
Date: 2010
DOI: 10.1063/1.3453832
In situ handheld three-dimensional bioprinting for cartilage regeneration
Publisher: Hindawi Limited
Date: 25-08-2018
DOI: 10.1002/TERM.2476
Abstract: Articular cartilage injuries experienced at an early age can lead to the development of osteoarthritis later in life. In situ three-dimensional (3D) printing is an exciting and innovative biofabrication technology that enables the surgeon to deliver tissue-engineering techniques at the time and location of need. We have created a hand-held 3D printing device (biopen) that allows the simultaneous coaxial extrusion of bioscaffold and cultured cells directly into the cartilage defect in vivo in a single-session surgery. This pilot study assessed the ability of the biopen to repair a full-thickness chondral defect and the early outcomes in cartilage regeneration, and compared these results with other treatments in a large animal model. A standardized critical-sized full-thickness chondral defect was created in the weight-bearing surface of the lateral and medial condyles of both femurs of six sheep. Each defect was treated with one of the following treatments: (i) hand-held in situ 3D printed bioscaffold using the biopen (HH group), (ii) preconstructed bench-based printed bioscaffolds (BB group), (iii) microfractures (MF group) or (iv) untreated (control, C group). At 8 weeks after surgery, macroscopic, microscopic and biomechanical tests were performed. Surgical 3D bioprinting was performed in all animals without any intra- or postoperative complication. The HH biopen allowed early cartilage regeneration. The results of this study show that real-time, in vivo bioprinting with cells and scaffold is a feasible means of delivering a regenerative medicine strategy in a large animal model to regenerate articular cartilage.
Role of mathematical modeling in bone fracture healing
Publisher: Portico
Date: 14-11-2012
Theoretical investigation of the effects of consolidation on contaminant transport through clay barriers
Publisher: Wiley
Date: 2009
DOI: 10.1002/NAG.708
Effects of long-term treatment of denosumab on bone mineral density: insights from an in-silico model of bone mineralization
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.BONE.2019.04.022
Abstract: Denosumab is one of the most commonly prescribed anti-resorptive drugs for the treatment of postmenopausal osteoporosis. The therapeutic effect of denosumab is to inhibit osteoclast differentiation and consequently bone resorption. Gains in bone mineral density (BMD) are achieved based on the ability of the bone matrix to undergo secondary mineralization. Experimental data show that the increase of BMD after commencing denosumab treatment are bone site specific. In this paper, we developed a comprehensive mechanistic pharmacokinetic-pharmacodymamic (PK-PD) model of the effect of denosumab on bone remodeling in postmenopausal osteoporosis (PMO). The PD model is based on a bone cell population model describing the bone remodeling process at the tissue scale. The conceptual model of the bone mineralization process, originally proposed by Boivin and Meunier, is quantitatively incorporated using a FIFO (First-In-First-Out) queue algorithm. The latter takes into account the balance of mineral within bone tissue due to the mineralization process, distinguishing the primary and secondary phases and removal of bone matrix due to bone resorption. The numerical simulations show that the model is able to predict the bone-site specific increase in BMD as was observed in the experimental data of Bone et al. 2008 for a typical denosumab administration pattern of 60 mg every 6 months. At the hip a 5 % increase in BMD was observed, while at the lumbar spine a 7.5 % increase of BMD was achieved after a 2 year treatment period. The difference in BMD is due to the fact that bone turnover at the hip is lower compared to lumbar spine and consequently has less potential for secondary mineralization. Parametric studies revealed that the rate of bone mineralization is an essential parameter regulating BMD gains. If mineralization is neglected only minimal increases in BMD are observed.
Combined Effects of Exercise and Denosumab Treatment on Local Failure in Post-menopausal Osteoporosis–Insights from Bone Remodelling Simulations Accounting for Mineralisation and Damage
Publisher: Frontiers Media SA
Date: 04-06-2021
DOI: 10.3389/FBIOE.2021.635056
Abstract: Denosumab has been shown to increase bone mineral density (BMD) and reduce the fracture risk in patients with post-menopausal osteoporosis (PMO). Increase in BMD is linked with an increase in bone matrix mineralisation due to suppression of bone remodelling. However, denosumab anti-resorptive action also leads to an increase in fatigue microdamage, which may ultimately lead to an increased fracture risk. A novel mechanobiological model of bone remodelling was developed to investigate how these counter-acting mechanisms are affected both by exercise and long-term denosumab treatment. This model incorporates Frost's mechanostat feedback, a bone mineralisation algorithm and an evolution law for microdamage accumulation. Mechanical disuse and microdamage were assumed to stimulate RANKL production, which modulates activation frequency of basic multicellular units in bone remodelling. This mechanical feedback mechanism controls removal of excess bone mass and microdamage. Furthermore, a novel measure of bone local failure due to instantaneous overloading was developed. Numerical simulations indicate that trabecular bone volume fraction and bone matrix damage are determined by the respective bone turnover and homeostatic loading conditions. PMO patients treated with the currently WHO-approved dose of denosumab (60 mg administrated every 6 months) exhibit increased BMD, increased bone ash fraction and damage. In untreated patients, BMD will significantly decrease, as will ash fraction while damage will increase. The model predicted that, depending on the time elapsed between the onset of PMO and the beginning of treatment, BMD slowly converges to the same steady-state value, while damage is low in patients treated soon after the onset of the disease and high in patients having PMO for a longer period. The simulations show that late treatment PMO patients have a significantly higher risk of local failure compared to patients that are treated soon after the onset of the disease. Furthermore, overloading resulted in an increase of BMD, but also in a faster increase of damage, which may consequently promote the risk of fracture, specially in late treatment scenarios. In case of mechanical disuse, the model predicted reduced BMD gains due to denosumab, while no significant change in damage occurred, thus leading to an increased risk of local failure compared to habitual loading.
Parametric sensitivity analysis of coupled mechanical consolidation
Publisher: Elsevier BV
Date: 2009
Modelling Human Locomotion to Inform Exercise Prescription for Osteoporosis
Publisher: Springer Science and Business Media LLC
Date: 25-04-2020
DOI: 10.1007/S11914-020-00592-5
Abstract: We review the literature on hip fracture mechanics and models of hip strain during exercise to postulate the exercise regimen for best promoting hip strength. The superior neck is a common location for hip fracture and a relevant exercise target for osteoporosis. Current modelling studies showed that fast walking and stair ambulation, but not necessarily running, optimally load the femoral neck and therefore theoretically would mitigate the natural age-related bone decline, being easily integrated into routine daily activity. High intensity jumps and hopping have been shown to promote anabolic response by inducing high strain in the superior anterior neck. Multidirectional exercises may cause beneficial non-habitual strain patterns across the entire femoral neck. Resistance knee flexion and hip extension exercises can induce high strain in the superior neck when performed using maximal resistance loadings in the average population. Exercise can stimulate an anabolic response of the femoral neck either by causing higher than normal bone strain over the entire hip region or by causing bending of the neck and localized strain in the superior cortex. Digital technologies have enabled studying interdependences between anatomy, bone distribution, exercise, strain and metabolism and may soon enable personalized prescription of exercise for optimal hip strength.
Computer-assisted pre-operative automatic segmentation and registration tool for malunited radius osteotomy: A proof-of-concept study
Publisher: Elsevier BV
Date: 09-2023
Numerical calculation of permeability of periodic porous materials: Application to periodic arrays of spheres and 3D scaffold microstructures
Publisher: Wiley
Date: 12-03-2019
DOI: 10.1002/NME.6037
IGF uptake with competitive binding in articular cartilage
Publisher: World Scientific Pub Co Pte Ltd
Date: 06-2008
DOI: 10.1142/S0218339008002575
Abstract: Experiments on the transport of radiolabeled Insulin-like Growth Factors (IGF-I and -II) into bovine articular cartilage show differential uptake depending on the relative proportion of IGF-I and -II. In this study, we present a mathematical model describing both the transport and competition of IGF-I and -II for binding sites represented by two functional groupings of IGF binding proteins (IGFBPs). The first grouping has approximately similar binding affinity to both IGF-I and -II (i.e. IGFBPs 1–5), whereas the second group has significantly higher binding preference for IGF-II compared to IGF-I (i.e. IGFBP-6). Using nonlinear least squares, it is shown that the experimental equilibrium competitive binding results can be described using a reversible Langmuir sorption isotherm involving two dominant IGFBP functional groups. After coupling the sorption model with a poromechanical continuum model, parametric studies are carried out to investigate the effect of model changes including IGF boundary conditions and the ratios of the two IGFBP functional groups. The results show that ignoring competitive binding leads to a significant overestimation of total IGF-I uptake, but an underestimation the rate of "free" (physiologically active) IGF-I within the cartilage. An increase of first group of IGFBPs (i.e. IGFBPs 1–5) as has been reported for osteoarthritis, is observed to hinder the bioavailability of free IGF-I in cartilage, even though the total IGF-I uptake is enhanced. Furthermore, the combination of dynamic compression and competitive binding is seen to enhance the IGF-I uptake within cartilage, but this enhancement is overestimated if competitive binding is neglected.
A Multiscale Framework Based on the Physiome Markup Languages for Exploring the Initiation of Osteoarthritis at the Bone–Cartilage Interface
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 12-2011
Sequential MRI reveals vertebral body wedging significantly contributes to coronal plane deformity progression in adolescent idiopathic scoliosis during growth
Publisher: Springer Science and Business Media LLC
Date: 25-05-2020
On the emergence of the spatio-temporal structure of Bone Multicellular Units (Conference Abstract)
Publisher: Elsevier BV
Date: 03-2010
Direct Assessment of Rabbit Cortical Bone Basic Multicellular Unit Longitudinal Erosion Rate
Publisher: Wiley
Date: 03-01-2022
DOI: 10.1002/JBMR.4700
Abstract: Cortical bone remodeling is carried out by basic multicellular units (BMUs), which couple resorption to formation. Although fluorochrome labeling has facilitated study of BMU formative parameters since the 1960s, some resorptive parameters, including the longitudinal erosion rate (LER), have remained beyond reach of direct measurement. Indeed, our only insights into this spatiotemporal parameter of BMU behavior come from classical studies that indirectly inferred LER. Here, we demonstrate a 4D in vivo method to directly measure LER through in‐line phase contrast synchrotron imaging. The tibias of rabbits ( n = 15) dosed daily with parathyroid hormone were first imaged in vivo (synchrotron micro‐CT day 15) and then ex vivo 14 days later (conventional micro‐CT day 29). Mean LER assessed by landmarking the co‐registered scans was 23.69 ± 1.73 μm/d. This novel approach holds great promise for the direct study of the spatiotemporal coordination of bone remodeling, its role in diseases such as osteoporosis, as well as related treatments. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Computational simulation of the mechanobiological regulation of bone remodeling by means of a coupled systems biology-micromechanical approach
Publisher: ACTAPRESS
Date: 2012
A novel algorithm to resolve lack of convergence and checkerboard instability in bone adaptation simulations using non-local averaging
Publisher: Wiley
Date: 09-12-2021
DOI: 10.1002/CNM.3419
Biomechanical Markers of Forward Hop-Landing After ACL-Reconstruction
Publisher: Springer Science and Business Media LLC
Date: 31-01-2022
DOI: 10.1007/S10439-022-02921-4
Abstract: Biomechanical changes after anterior cruciate ligament reconstruction (ACLR) may be detrimental to long-term knee-joint health. We used pattern recognition to characterise biomechanical differences during the landing phase of a single-leg forward hop after ACLR. Experimental data from 66 in iduals 12-24 months post-ACLR (28.2 ± 6.3 years) and 32 controls (25.2 ± 4.8 years old) were input into a musculoskeletal modelling pipeline to calculate joint angles, joint moments and muscle forces. These waveforms were transformed into principal components (features), and input into a pattern recognition pipeline, which found 10 main distinguishing features (and 8 associated features) between ACLR and control landing biomechanics at significance $$\\alpha =0.05$$ α = 0.05 . Our process identified known biomechanical characteristics post-ACLR: smaller knee flexion angle less knee extensor moment lower vasti, rectus femoris and hamstrings forces. Importantly, we found more novel and less well-understood adaptations: smaller ankle plantar flexor moment lower soleus forces and altered patterns of knee rotation angle, hip rotator moment and knee abduction moment. Crucially, we identified, with high certainty, subtle aberrations indicating landing instability in the ACLR group for: knee flexion and internal rotation angles and moments hip rotation angles and moments and lumbar rotator and bending moments. Our findings may benefit rehabilitation and assessment for return-to-sport 12–24 months post-ACLR.
Investigation of determinants of atypical femoral fractures using Multiscale computational modeling
Publisher: Springer International Publishing
Date: 2014
Multiscale mechanobiology of bone remodeling and adaptation (CISM International Centre for Mechanical Sciences, Volume 578)
Publisher: Springer International Publishing
Date: 2018
Discussion of Parametric study of one-dimensional solute transport in deformable porous Media by Akram N. Alshawabkeh and Nima Rahbar
Publisher: American Society of Civil Engineers (ASCE)
Date: 03-2008
Characterization of drug-release kinetics in trabecular bone from titania nanotube implants
Publisher: Informa UK Limited
Date: 09-2012
DOI: 10.2147/IJN.S33655
The Use of EOS Imaging to Assess Curve Magnitude Changes in Adolescent Idiopathic Scoliosis Undertaking Brace Management
Publisher: Acta Scientific Publications Pvt. Ltd.
Date: 04-2022
Computer simulation-based modeling of the pharmaceutical intervention of postmenopausal osteoporosis by denosumab (Conference Abstract)
Publisher: Springer Science and Business Media LLC
Date: 09-2011
The femoral neck mechanoresponse to hip extensors exercise: A case study
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/5219541
Abstract: Physical activity is recommended to prevent age-related bone loss. However, the proximal femur mechanoresponse is variable, possibly because of a muscle-dependant mechanoresponse. We compared the proximal femur response with the femoral strain pattern generated by the hip extensor muscles. A healthy participant underwent a six-month unilateral training of the hip extensor muscles using a resistance weight regularly adjusted to the 80% of the one-repetition maximum weight. DXA-based measurements of the areal Bone Mineral Density (aBMD) in the exercise leg were adjusted for changes in the control leg. The biomechanical stimulus for bone adaptation (BS) was calculated using published models of the musculoskeletal system and the average hip extension moment in elderly participants. Volumetric (ΔvBMD) and areal (ΔaBMD) BMD changes were calculated. The measured and calculated BMD changes consistently showed a positive and negative effect of exercise in the femoral neck (ΔaBMD = +0.7% ΔvBMD = +0.8%) and the trochanter region (ΔaBMD = −4.1% ΔvBMD = −0.5%), respectively. The 17% of the femoral neck exceeded the 75th percentile of the spatially heterogeneous BS distribution. Hip extensor exercises may be beneficial in the proximal femoral neck but not in the trochanteric region. DXA-based measurements may not capture significant aBMD local changes.
Corrigendum to “The relationship between porosity and specific surface in human cortical bone is subject specific” [Bone 72 (2015), 109–117]
Publisher: Elsevier BV
Date: 06-2015
The transport of insulin-like growth factor through cartilage
Publisher: CRC Press
Date: 24-08-2010
Daily administration of parathyroid hormone slows the progression of basic multicellular units in the cortical bone of the rabbit distal tibia
Publisher: Elsevier BV
Date: 11-2023
Estimation of anisotropic permeability in trabecular bone based on microCT imaging and pore-scale fluid dynamics simulations
Publisher: Elsevier BV
Date: 06-2017
The Application of Pulsed Electromagnetic Fields (PEMFs) for Bone Fracture Repair: Past and Perspective Findings
Publisher: Springer Science and Business Media LLC
Date: 22-01-2018
DOI: 10.1007/S10439-018-1982-1
Abstract: Bone fractures are one of the most commonly occurring injuries of the musculoskeletal system. A highly complex physiological process, fracture healing has been studied extensively. Data from in vivo, in vitro and clinical studies, have shown pulsed electromagnetic fields (PEMFs) to be highly influential in the fracture repair process. Whilst the underlying mechanisms acting to either inhibit or advance the physiological processes are yet to be defined conclusively, several non-invasive point of use devices have been developed for the clinical treatment of fractures. With the complexity of the repair process, involving many components acting at different time steps, it has been a challenge to determine which PEMF exposure parameters (i.e., frequency of field, intensity of field and dose) will produce the most optimal repair. In addition, the development of an evidence-backed device comes with challenges of its own, with many elements (including process of exposure, construct materials and tissue densities) being highly influential to the field exposed. The objective of this review is to provide a broad recount of the applications of PEMFs in bone fracture repair and to then demonstrate what is further required for enhanced therapeutic outcomes.
The influence of bone surface availability in bone remodelling-A mathematical model including coupled geometrical and biomechanical regulations of bone cells
Publisher: Elsevier BV
Date: 02-2013
Deep Learning-Based Automatic Segmentation for Reconstructing Vertebral Anatomy of Healthy Adolescents and Patients With Adolescent Idiopathic Scoliosis (AIS) Using MRI Data
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2021
Comparative study of methods used to estimate ionic diffusion coefficients using migration tests
Publisher: Elsevier BV
Date: 08-2007
Editorial
Publisher: Frontiers Media SA
Date: 08-06-2023
A mathematical multiscale model of bone remodeling, accounting for pore space-specific mechanosensation
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.BONE.2017.11.009
Abstract: While bone tissue is a hierarchically organized material, mathematical formulations of bone remodeling are often defined on the level of a millimeter-sized representative volume element (RVE), "smeared" over all types of bone microstructures seen at lower observation scales. Thus, there is no explicit consideration of the fact that the biological cells and biochemical factors driving bone remodeling are actually located in differently sized pore spaces: active osteoblasts and osteoclasts can be found in the vascular pores, whereas the lacunar pores host osteocytes - bone cells originating from former osteoblasts which were then "buried" in newly deposited extracellular bone matrix. We here propose a mathematical description which considers size and shape of the pore spaces where the biological and biochemical events take place. In particular, a previously published systems biology formulation, accounting for biochemical regulatory mechanisms such as the rank-rankl-opg pathway, is cast into a multiscale framework coupled to a poromicromechanical model. The latter gives access to the vascular and lacunar pore pressures arising from macroscopic loading. Extensive experimental data on the biological consequences of this loading strongly suggest that the aforementioned pore pressures, together with the loading frequency, are essential drivers of bone remodeling. The novel approach presented here allows for satisfactory simulation of the evolution of bone tissue under various loading conditions, and for different species including scenarios such as mechanical dis- and overuse of murine and human bone, or in osteocyte-free bone.
Comparative studies of 3D-constitutive models for concrete: Application to mixed-mode fracture
Publisher: Wiley
Date: 26-04-2004
DOI: 10.1002/NME.975
Modal analysis of nanoindentation data, confirming that reduced bone turnover may cause increased tissue mineralization/elasticity
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.JMBBM.2018.05.014
Abstract: It is widely believed that the activities of bone cells at the tissue scale not only govern the size of the vascular pore spaces (and hence, the amount of bone tissue available for actually carrying the loads), but also the characteristics of the extracellular bone matrix itself. In this context, increased mechanical stimulation (in mediolateral regions of human femora, as compared to anteroposterior regions) may lead to increased bone turnover, lower bone matrix mineralization, and therefore lower tissue modulus. On the other hand, resorption-only processes (in endosteal versus periosteal regions) may have the opposite effect. A modal analysis of nanoindentation data obtained on femurs from the Melbourne Femur Research Collection (MFRC) indeed confirms that bone is stiffer in endosteal regions compared to periosteal regions (E̅
Mechanobiological osteocyte feedback drives mechanostat regulation of bone in a multiscale computational model
Publisher: Springer Science and Business Media LLC
Date: 13-05-2019
DOI: 10.1007/S10237-019-01158-W
Abstract: Significant progress has been made to identify the cells and signaling molecules involved in the mechanobiological regulation of bone remodeling. It is now well accepted that osteocytes act as mechanosensory cells in bone expressing several signaling molecules such as nitric oxide (NO) and sclerostin (Scl) which are able to control bone remodeling responses. In this paper, we present a comprehensive multiscale computational model of bone remodeling which incorporates biochemical osteocyte feedback. The mechanostat theory is quantitatively incorporated into the model using mechanical feedback to control expression levels of NO and Scl. The catabolic signaling pathway RANK-RANKL-OPG is co-regulated via (continuous) PTH and NO, while the anabolic Wnt signaling pathway is described via competitive binding reactions between Wnt, Scl and the Wnt receptors LRP5/6. Using this novel model of bone remodeling, we investigate the effects of changes in the mechanical loading and hormonal environment on bone balance. Our numerical simulations show that we can calibrate the mechanostat anabolic and catabolic regulatory mechanisms so that they are mutually exclusive. This is consistent with previous models that use a Wolff-type law to regulate bone resorption and formation separately. Furthermore, mechanical feedback provides an effective mechanism to obtain physiological bone loss responses due to mechanical disuse and/or osteoporosis.
Endocortical bone loss in osteoporosis: the role of bone surface availability
Publisher: Wiley
Date: 07-2013
DOI: 10.1002/CNM.2567
Abstract: Age-related bone loss and postmenopausal osteoporosis are due to a dysregulation of bone remodelling in which less bone is reformed than resorbed. This dysregulation of bone remodelling does not occur with equal strength in all bone regions. Loss of bone is more pronounced near the endocortical surface. This leads to thinning of the cortical wall proceeding from the endosteum, a process sometimes called 'trabecularisation'. In this paper, we investigate the influence of the nonuniform distribution of bone surface within bone tissue for osteoporotic bone losses. We use a spatio-temporal computational model of bone remodelling in which microstructural changes of bone tissue are represented by a phenomenological relationship between bone specific surface and bone porosity. The simulation of an osteoporotic condition by our model shows that the evolution of bone porosity within a bone cross section is significantly influenced by the nonuniform availability of bone surface. Greater bone loss occurs near the endocortical wall, leading to cortical wall thinning and to an expansion of the medullary cavity similar to cross-sectional observations from human femur midshafts. Our model suggests that the rate of cortical wall thinning is fast/slow in the presence/absence of an adjacent trabecular or trabecularised bone compartment.
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