A comparative study of orthotropic and isotropic bone adaptation in the femur.

Functional adaptation of the femur has been studied extensively by embedding remodelling algorithms in finite element models, with bone commonly assumed to have isotropic material properties for computational efficiency. However, isotropy is insufficient in predicting the directionality of bone's observed microstructure. A novel iterative orthotropic 3D adaptation algorithm is proposed and applied to a finite element model of the whole femur. Bone was modelled as an optimised strain-driven adaptive continuum with local orthotropic symmetry. Each element's material orientations were aligned with the local principal stress directions and their corresponding directional Young's moduli updated proportionally to the associated strain stimuli. The converged predicted density distributions for a coronal section of the whole femur were qualitatively and quantitatively compared with the results obtained by the commonly used isotropic approach to bone adaptation and with ex vivo imaging data. The orthotropic assumption was shown to improve the prediction of bone density distribution when compared with the more commonly used isotropic approach, whilst producing lower comparative mass, structurally optimised models. It was also shown that the orthotropic approach can provide additional directional information on the material properties distributions for the whole femur, an advantage over isotropic bone adaptation. Orthotropic bone models can help in improving research areas in biomechanics where local structure and mechanical properties are of key importance, such as fracture prediction and implant assessment. © 2014 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons, Ltd

Consideration of multiple load cases is critical in modelling orthotropic bone adaptation in the femur

Functional adaptation of the femur has been investigated in several studies by embedding bone remodelling algorithms in finite element (FE) models, with simpli- fications often made to the representation of bone’s material symmetry and mechanical environment. An orthotropic strain-driven adaptation algorithm is proposed in order to predict the femur’s volumetric material property distribution and directionality of its internal structures within a continuum. The algorithm was applied to a FE model of the femur, with muscles, ligaments and joints included explicitly. Multiple load cases representing distinct frames of two activities of daily living (walking and stair climbing) were considered. It is hypothesised that low shear moduli occur in areas of bone that are simply loaded and high shear moduli in areas subjected to complex loading conditions. In addition, it is investigated whether material properties of different femoral regions are stimulated by different activities. The loading and boundary conditions were considered to provide a physiological mechanical environment. The resulting volumetric material property distribution and directionalities agreed with ex vivo imaging data for the whole femur. Regions where non-orthogonal trabecular crossing has been documented coincided with higher values of predicted shear moduli. The topological influence of the different activities modelled was analysed. The influence of stair climbing on the properties of the femoral neck region is highlighted. It is recommended that multiple load cases should be considered when modelling bone adaptation. The orthotropic model of the complete femur is released with this study

Structural Optimisation: Biomechanics of the Femur

A preliminary iterative 3D meso-scale structural model of the femur was developed, in which bar and shell elements were used to represent trabecular and cortical bone respectively. The cross-sectional areas of the bar elements and the thickness values of the shell elements were adjusted over successive iterations of the model based on a target strain stimulus, resulting in an optimised construct. The predicted trabecular architecture, and cortical thickness distribution showed good agreement with clinical observations, based on the application of a single leg stance load case during gait. The benefit of using a meso-scale structural approach in comparison to micro or macro-scale continuum approaches to predictive bone modelling was achievement of the symbiotic goals of computational efficiency and structural description of the femur.Comment: Accepted by Engineering and Computational Mechanics (Proceedings of the ICE

The application of digital volume correlation (DVC) to evaluate strain predictions generated by finite element models of the osteoarthritic humeral head

Continuum-level finite element models (FEMs) of the humerus offer the ability to evaluate joint replacement designs preclinically; however, experimental validation of these models is critical to ensure accuracy. The objective of the current study was to quantify experimental full-field strain magnitudes within osteoarthritic (OA) humeral heads by combining mechanical loading with volumetric microCT imaging and digital volume correlation (DVC). The experimental data was used to evaluate the accuracy of corresponding FEMs. Six OA humeral head osteotomies were harvested from patients being treated with total shoulder arthroplasty and mechanical testing was performed within a microCT scanner. MicroCT images (33.5 µm isotropic voxels) were obtained in a pre- and post-loaded state and BoneDVC was used to quantify full-field experimental strains (≈ 1 mm nodal spacing, accuracy = 351 µstrain, precision = 518 µstrain). Continuum-level FEMs with two types of boundary conditions (BCs) were simulated: DVC-driven and force-driven. Accuracy of the FEMs was found to be sensitive to the BC simulated with better agreement found with the use of DVC-driven BCs (slope = 0.83, r2 = 0.80) compared to force-driven BCs (slope = 0.22, r2 = 0.12). This study quantified mechanical strain distributions within OA trabecular bone and demonstrated the importance of BCs to ensure the accuracy of predictions generated by corresponding FEMs

Parametric design optimisation of proximal humerus plates based on finite element method

Optimal treatment of proximal humerus fractures remains controversial. Locking plates offer theoretical advantages but are associated with complications in the clinic. This study aimed to perform parametric design optimisation of proximal humerus plates to enhance their mechanical performance. A finite element (FE) model was developed that simulated a two-part proximal humerus fracture that had been treated with a Spatial Subchondral Support (S3) plate and subjected to varus bending. The FE model was validated against in vitro biomechanical test results. The predicted load required to apply 5 mm cantilever varus bending was only 0.728% lower. The FE model was then used to conduct a parametric optimisation study to determine the orientations of inferomedial plate screws that would yield minimum fracture gap change (i.e. optimal stability). The feasible design space was automatically identified by imposing clinically relevant constraints, and the creation process of each FE model for the design optimisation was automated. Consequently, 538 FE models were generated, from which the obtained optimal model had 4.686% lower fracture gap change (0.156 mm) than that of the manufacturer’s standard plate. Whereas its screws were oriented towards the inferomedial region and within the range of neck-shaft angle of a healthy subject. The methodology presented in this study promises future applications in patient-specific design optimisation of implants for other regions of the human body

Neuromuscular abnormality and autonomic dysfunction in patients with cerebrotendinous xanthomatosis

<p>Abstract</p> <p>Background</p> <p>Cerebrotendinous xanthomatosis (CTX) is a rare lipid-storage disease. Neuromuscular abnormality and autonomic system (ANS) dysfuction in CTX are rarely examined in large-scale studies in the literature. We studied the peripheral nervous system, myopathology, and autonomic system of four CTX patients and performed a literature review of the reported CTX patients with peripheral neuropathy.</p> <p>Methods</p> <p>Four biochemically and genetically confirmed CTX patients, belonging to two families, were included for study and all received nerve conduction study (NCS), muscle biopsy for histopathologic and ultrastructural study, skin biopsy for intraepidermal nerve fiber (INEF) density measurement, autonomic testings including sympathetic skin response, R-R interval variation and head-up tilt test using an automated tilt table to record the changes of blood pressure and heart rate in different postures. The Q-Sweat test was also applied for the detection of sweat amount and onset time of response. The clinical characteristics, study methods and results of 13 studies of peripheral neuropathy in CTX patients in the literature were also recorded for analysis.</p> <p>Results</p> <p>The results of NCS study showed axonal sensory-motor polyneuropathy in three CTX cases and mixed axonal and demyelinating sensor-motor polyneuropathy in one. The myopathological and histopathologic studies revealed mild denervation characteristics, but the ultrastructural study revealed changes of mitochondria and the membranous system, and increased amounts of glycogen, lipofuscin and lipid deposition. The ANS study revealed different degrees of abnormalities in the applied tests and the INEF density measurement showed small fiber neuropathy in three of the four CTX patients. The literature review of peripheral neuropathy in CTX revealed different types of peripheral neuropathy, of which axonal peripheral neuropathy was the most common.</p> <p>Conclusions</p> <p>Peripheral neuropathy, especially the subtype of axonal sensori-motor neuropathy, is common in patients with CTX. Evidence of lipid metabolic derangement in CTX can be reflected in ultrastructural studies of muscles. With an adequate multi-parametric evaluation, a high incidence of ANS abnormalities can be seen in this rare lipid-storage disease, and a high incidence of small fiber involvement is also reflected in the IENF density measurement of skin biopsies.</p

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure