An accurate estimation of bone density improves the accuracy of subject-specific finite element models

An experimental-numerical study was performed to investigate the relationships between computed tomography (CT)-density and ash density, and between ash density and apparent density for bone tissue, to evaluate their influence on the accuracy of subject-specific FE models of human bones. Sixty cylindrical bone specimens were examined. CT-densities were computed from CT images while apparent and ash densities were measured experimentally. The CT/ash-density and ash/apparent-density relationships were calculated. Finite element models of eight human femurs were generated considering these relationships to assess their effect on strain prediction accuracy. CT and ash density were linearly correlated (R(2)=0.997) over the whole density range but not equivalent (intercep t <0, slope >1). A constant ash/apparent-density ratio (0.598+/-0.004) was found for cortical bone. A lower ratio, with a larger dispersion, was found for trabecular bone (0.459+/-0.100), but it became less dispersed, and equal to that of cortical tissue, when testing smaller trabecular specimens (0.598+/-0.036). This suggests that an experimental error occurred in apparent-density measurements for large trabecular specimens and a constant ratio can be assumed valid for the whole density range. Introducing the obtained relationships in the FE modelling procedure improved strain prediction accuracy (R(2)=0.95, RMSE=7%). The results suggest that: (i) a correction of the densitometric calibration should be used when evaluating bone ash-density from clinical CT scans, to avoid ash-density underestimation and overestimation for low- and high-density bone tissue, respectively; (ii) the ash/apparent-density ratio can be assumed constant in human femurs and (iii) the correction improves significantly the model accuracy and should be considered in subject-specific bone modelling.     

A New Computational Efficient Approach for Trabecular Bone Analysis using Beam Models Generated with Skeletonized Graph Technique

Micro-finite element (FE) analysis is a well established technique for the evaluation of the elastic properties of trabecular bone, but is limited in its application due to the large number of elements that it requires to represent the complex internal structure of the bone. In this paper, we present an alternative FE approach that makes use of a recently developed 3D-Line Skeleton Graph Analysis (LSGA) technique to represent the complex internal structure of trabecular bone as a network of simple straight beam elements in which the beams are assigned geometrical properties of the trabeculae that they represent. Since an enormous reduction of cputime can be obtained with this beam modeling approach, ranging from approximately 1,200 to 3,600 for the problems investigated here, we think that the FE modeling technique that we introduced could potentially constitute an interesting alternative for the evaluation of the elastic mechanical properties of trabecular bone.     

A new computational efficient approach for trabecular bone analysis using beam models generated with skeletonized graph technique

Micro-finite element (FE) analysis is a well established technique for the evaluation of the elastic properties of trabecular bone, but is limited in its application due to the large number of elements that it requires to represent the complex internal structure of the bone. In this paper, we present an alternative FE approach that makes use of a recently developed 3D-Line Skeleton Graph Analysis (LSGA) technique to represent the complex internal structure of trabecular bone as a network of simple straight beam elements in which the beams are assigned geometrical properties of the trabeculae that they represent. Since an enormous reduction of cputime can be obtained with this beam modeling approach, ranging from approximately 1,200 to 3,600 for the problems investigated here, we think that the FE modeling technique that we introduced could potentially constitute an interesting alternative for the evaluation of the elastic mechanical properties of trabecular bone.     

Validation of a voxel-based FE method for prediction of the uniaxial apparent modulus of human trabecular bone using macroscopic mechanical tests and nanoindentation

Assessment of the mechanical properties of trabecular bone is of major biological and clinical importance for the investigation of bone diseases, fractures and their treatments. Finite element (FE) methods are getting increasingly popular for quantifying the elastic and failure properties of trabecular bone. In particular, voxel-based FE methods have been previously used to calculate the effective elastic properties of trabecular microstructures. However, in most studies, bone tissue moduli were assumed or back-calculated to match the apparent elastic moduli from experiments, which often lead to surprisingly low values when compared to nanoindentation results. In this study, voxel-based FE analysis of trabecular bone is combined with physical measures of volume fraction, micro-CT (microCT) reconstructions, uniaxial mechanical tests and specimen-specific nanoindentation tests for proper validation of the method. Cylindrical specimens of cancellous bone were extracted from human femurs and their volume fraction determined with Archimede's method. Uniaxial apparent modulus of the specimens was measured with an improved tension-compression testing protocol that minimizes boundary artefacts. Their microCT reconstructions were segmented to match the measured bone volume fraction and used to create full-size voxel models with 30-45 microm element size. For each specimen, linear isotropic elastic material properties were defined based on specific nanoindentation measurements of its embedded bone tissue. Linear FE analyses were finally performed to simulate the uniaxial mechanical tests. Additional parametric analyses were performed to evaluate the potential errors on the predicted apparent modulus arising from variations in segmentation threshold, tissue modulus, and the use of 125-mm(3) cubic sub-regions. The results demonstrate an excellent correspondence between experimental measures and FE predictions of uniaxial apparent modulus. In conclusion, the adopted voxel-based FE approach is found to be a robust method to predict the linear elastic properties of human cancellous bone, provided segmentation of the microCT reconstructions is carefully calibrated, tissue modulus is known a priori and the entire region of interest is included in the analysis.     

Fast and accurate specimen-specific simulation of trabecular bone elastic modulus using novel beam-shell finite element models

Elastic modulus and strength of trabecular bone are negatively affected by osteoporosis and other metabolic bone diseases. Micro-computed tomography-based beam models have been presented as a fast and accurate way to determine bone competence. However, these models are not accurate for trabecular bone specimens with a high number of plate-like trabeculae. Therefore, the aim of this study was to improve this promising methodology by representing plate-like trabeculae in a way that better reflects their mechanical behavior. Using an optimized skeletonization and meshing algorithm, voxel-based models of trabecular bone samples were simplified into a complex structure of rods and plates. Rod-like and plate-like trabeculae were modeled as beam and shell elements, respectively, using local histomorphometric characteristics. To validate our model, apparent elastic modulus was determined from simulated uniaxial elastic compression of 257 cubic samples of trabecular bone (4mm×4mm×4mm; 30μm voxel size; BIOMED I project) in three orthogonal directions using the beam-shell models and using large-scale voxel models that served as the gold standard. Excellent agreement (R(2)=0.97) was found between the two, with an average CPU-time reduction factor of 49 for the beam-shell models. In contrast to earlier skeleton-based beam models, the novel beam-shell models predicted elastic modulus values equally well for structures from different skeletal sites. It allows performing detailed parametric analyses that cover the entire spectrum of trabecular bone microstructures.     

The effect of specimen geometry on the mechanical behaviour of trabecular bone specimens.

The effect of specimen geometry on the mechanical behaviour of trabecular bone specimens was studied by non-destructive uniaxial compression to 0.4% strain using cylindrical specimens with different sizes and length-to-diameter ratios, and by comparing cubic and cylindrical specimens with the same cross-sectional area. Both the length and the cross-sectional area of the specimen had a highly significant influence on the mechanical behaviour (p less than 0.0001). Within the actual range of length (2.75-11.0 mm) the normalized stiffness (Young's modulus) was related nearly linearly to the specimen length. This dependency on specimen length is suggested to be caused mainly by structural disintegrity of the trabecular specimens near the surface. The normalized stiffness (Young's modulus) was also positively correlated to the cross-sectional area. This dependency on cross-sectional area is probably due to friction-induced stress inhomogeneity at the platen-specimen interface. A cube with side length 6.5 mm or a cylindrical specimen with 7.5 mm diameter and 6.5 mm length are suggested as standard specimens for comparative studies on trabecular bone mechanics.     

A global relationship between trabecular bone morphology and homogenized elastic properties.

An alternative concept of the relationship between morphological and elastic properties of trabecular bone is presented and applied to human tissue from several anatomical locations using a digital approach. The three-dimensional morphology of trabecular bone was assessed with a microcomputed tomography system and the method of directed secants as well as the star volume procedure were used to compute mean intercept length (MIL) and average bone length (ABL) of 4 mm cubic specimens. Assuming isotropic elastic properties for the trabecular tissue, the general elastic tensors of the bone specimens were determined using the homogenization method and the closest orthotropic tensors were calculated with an optimization algorithm. The assumption of orthotropy for trabecular bone was found to improve with specimen size and hold within 6.1 percent for a 4 mm cube size. A strong global relationship (r2 = 0.95) was obtained between fabric and the orthotropic elastic tensor with a minimal set of five constants. Mean intercept length and average bone length provided an equivalent power of prediction. These results support the hypothesis that the elastic properties of human trabecular bone from an arbitrary anatomical location can be estimated from an approximation of the anisotropic morphology and a prior knowledge of tissue properties.     

Subject-specific finite element model of the pelvis: development, validation and sensitivity studies

A better understanding of the three-dimensional mechanics of the pelvis, at the patient-specific level, may lead to improved treatment modalities. Although finite element (FE) models of the pelvis have been developed, validation by direct comparison with subject-specific strains has not been performed, and previous models used simplifying assumptions regarding geometry and material properties. The objectives of this study were to develop and validate a realistic FE model of the pelvis using subject-specific estimates of bone geometry, location-dependent cortical thickness and trabecular bone elastic modulus, and to assess the sensitivity of FE strain predictions to assumptions regarding cortical bone thickness as well as bone and cartilage material properties. A FE model of a cadaveric pelvis was created using subject-specific computed tomography image data. Acetabular loading was applied to the same pelvis using a prosthetic femoral stem in a fashion that could be easily duplicated in the computational model. Cortical bone strains were monitored with rosette strain gauges in ten locations on the left hemipelvis. FE strain predictions were compared directly with experimental results for validation. Overall, baseline FE predictions were strongly correlated with experimental results (r2=0.824), with a best-fit line that was not statistically different than the line y=x (experimental strains = FE predicted strains). Changes to cortical bone thickness and elastic modulus had the largest effect on cortical bone strains. The FE model was less sensitive to changes in all other parameters. The methods developed and validated in this study will be useful for creating and analyzing patient-specific FE models to better understand the biomechanics of the pelvis.     

Indirect determination of trabecular bone effective tissue failure properties using micro-finite element simulations

Trabecular bone strength is marked not only by the onset of local yielding, but also by post-yield behavior. To study and predict trabecular bone elastic and yield properties, micro-finite element (micro-FE) models were successfully applied. However, trabecular bone strength predictions require micro-FE models incorporating post-yield behavior of trabecular bone tissue. Due to experimental difficulties, such data is currently not available. Here we used micro-FE modeling to determine failure behavior of trabecular bone tissue indirectly, by iteratively fitting FE simulation to experimental results. Failure parameters were fitted to an isotropic plasticity model based on Hill's yield function, using materially and geometrically nonlinear micro-FE models of seven bovine trabecular bone specimens. The predictive value of the averaged effective tissue properties was subsequently tested. The results showed that compression softening had to be included on the tissue level in order to accurately describe the apparent-level behavior of the bone specimens. A sensitivity study revealed that the simulated response was less sensitive to variations in the post-yield properties of the bone tissue than variations in the elastic and yield properties. Due to fitting of the tissue properties, apparent-level behavior could be accurately reproduced for each specimen separately. Predictions based on the averaged and fixed tissue properties were less accurate, due to inter-specimen variations in the tissue properties.     

Detection of trabecular bone microdamage by micro-computed tomography

Microdamage is an important component of bone quality and affects bone remodeling. Improved techniques to assess microdamage without the need for histological sectioning would provide insight into the role of microdamage in trabecular bone strength by allowing the spatial distribution of damage within the trabecular microstructure to be measured. Nineteen cylindrical trabecular bone specimens were prepared and assigned to two groups. The specimens in group I were damaged to 3% compressive strain and labeled with BaSO(4). Group II was not loaded, but was labeled with BaSO(4). Micro-computed tomography (Micro-CT) images of the specimens were obtained at 10 microm resolution. The median intensity of the treated bone tissue was compared between groups. Thresholding was also used to measure the damaged area fraction in the micro-CT scans. The histologically measured damaged area fraction, the median CT intensity, and the micro-CT measured damaged area fraction were all higher in the loaded group than in the unloaded group, indicating that the micro-CT images could differentiate the damaged specimen group from the unloaded specimens. The histologically measured damaged area fraction was positively correlated with the micro-CT measured damaged area fraction and with the median CT intensity of the bone, indicating that the micro-CT images can detect microdamage in trabecular bone with sufficient accuracy to differentiate damage levels between samples. This technique provides a means to non-invasively assess the three-dimensional distribution of microdamage within trabecular bone test specimens and could be used to gain insight into the role of trabecular architecture in microdamage formation.     

Comparison of the elastic and yield properties of human femoral trabecular and cortical bone tissue

The ability to determine trabecular bone tissue elastic and failure properties has biological and clinical importance. To date, trabecular tissue yield strains remain unknown due to experimental difficulties, and elastic moduli studies have reported controversial results. We hypothesized that the elastic and tensile and compressive yield properties of trabecular tissue are similar to those of cortical tissue. Effective tissue modulus and yield strains were calibrated for cadaveric human femoral neck specimens taken from 11 donors, using a combination of apparent-level mechanical testing and specimen-specific, high-resolution, nonlinear finite element modeling. The trabecular tissue properties were then compared to measured elastic modulus and tensile yield strain of human femoral diaphyseal cortical bone specimens obtained from a similar cohort of 34 donors. Cortical tissue properties were obtained by statistically eliminating the effects of vascular porosity. Results indicated that mean elastic modulus was 10% lower (p<0.05) for the trabecular tissue (18.0+/-2.8 GPa) than for the cortical tissue (19.9+/-1.8 GPa), and the 0.2% offset tensile yield strain was 15% lower for the trabecular tissue (0.62+/-0.04% vs. 0.73+/-0.05%, p<0.001). The tensile-compressive yield strength asymmetry for the trabecular tissue, 0.62 on average, was similar to values reported in the literature for cortical bone. We conclude that while the elastic modulus and yield strains for trabecular tissue are just slightly lower than those of cortical tissue, because of the cumulative effect of these differences, tissue strength is about 25% greater for cortical bone.     

Validation of composite finite elements efficiently simulating elasticity of trabecular bone

Patient-specific analyses of the mechanical properties of bones become increasingly important for the management of patients with osteoporosis. The potential of composite finite elements (CFEs), a novel FE technique, to assess the apparent stiffness of vertebral trabecular bone is investigated in this study. Segmented volumes of cylindrical specimens of trabecular bone are compared to measured volumes. Elasticity under uniaxial loading conditions is simulated; apparent stiffnesses are compared to experimentally determined values. Computational efficiency is assessed and recommendations for simulation parameters are given. Validating apparent uniaxial stiffnesses results in concordance correlation coefficients 0.69 ≤ r_𝒸 ≤ 0.92 for resolutions finer than 168 μm, and an average error of 5.8% between experimental and numerical results at 24 μm resolution. As an application, the code was used to compute local, macroscopic stiffness tensors for the trabecular structure of a lumbar vertebra. The presented technique allows for computing stiffness using smooth FE meshes at resolutions that are well achievable in peripheral high resolution quantitative CT. Therefore, CFEs could be a valuable tool for the patient-specific assessment of bone stiffness.     

Elastic modulus of trabecular bone material

An ultrasonic technique was used to measure both the elastic modulus (Young's modulus) of trabecular bone material and the elastic modulus of the cancellous structure. The average trabecular modulus, measured on specimens obtained from three human and one bovine distal femora, was 13.0 GPa (S.D. 1.47) and 10.9 GPa (S.D. 1.57), respectively. On human specimens the structural elastic modulus was found to be related to the structural (apparent) density raised to the 1.88 power. The elastic modulus from the bovine specimens showed a more linear relationship with the density of the cancellous structure (density raised to the 1.57 power).     

In vitro and in silico characterization of open-cell structures of trabecular bone

This work aimed to perform a detailed in vitro and in silico characterization of open-cell structures, which resemble trabecular bone, to elucidate osteoporosis failure mechanisms. Experimental and image-based computational methods were used to estimate Young′s modulus and porosities of different open-cell structures (Sawbones; Malmö, Sweden). Three different open-cell structures with different porosities were characterized. Additionally, some open-cell structures were scanned using a microcomputed tomography system (μCT) to non-destructively predict specimen Young′s modulus of the structures by developing voxel-based and tetrahedral finite element (FE) models. A 3D reconstruction and FE analyses were used. The experimental and computational results with different element types (linear and quadratic tetrahedrons and voxel-based meshes) were compared with Sawbones data (Sawbones; Malmö, Sweden) revealing important differences in Young′s modulus and porosities. The specimens with high and low volume fractions were best represented by linear and quadratic tetrahedrons, respectively. These results could be used to develop new osteoporosis-prevention strategies.     

Characterization of bone-implant fixation using modal analysis: Application to a press-fit implant model

Orthopaedic implant fixation is strongly dependant upon the effective mechanical properties of newly formed tissue. In this study, we evaluated the potential of modal analysis to derive viscoelastic properties of periprosthetic tissue. We hypothesized that Young's modulus and loss factor could be obtained by a combined theoretical, computational and experimental modal analysis approach. This procedure was applied to ex vivo specimens from a cylindrical experimental implant placed in cancellous bone in an unloaded press-fit configuration, obtained after a four week observation period. Four sections each from seven textured titanium implants were investigated. The first resonant frequency and loss factor were measured. Average experimentally determined loss factor was 2% (SD 0.4%) and average first resonant frequency was 2.1 KHz (SD: 50). A 2D axisymmetric finite element (FE) model identified effective Young's modulus of tissue using experimental resonant frequencies as input. Average value was 42 MPa (SD: 2.4) and no significant difference between specimens was observed.In this pilot study, the non-destructive method allowed accurate measure of dynamic loss factor and resonant frequency and derivation of effective Young's modulus. Prior to implementing this dynamic protocol for broader mechanical evaluation of experimental implant fixation, further work is needed to determine if this affects results from subsequent destructive shear push-out tests.     

A novel in vivo mouse model for mechanically stimulated bone adaptation--a combined experimental and computational validation study

To facilitate the investigation of bone formation, in vivo, in response to mechanical loading a caudal vertebra axial compression device (CVAD) has been developed to deliver precise mechanical loads to the fifth caudal vertebra (C5) of the C57BL/6 female mouse. A combined experimental and computational approach was used to quantify the micro-mechanical strain induced in trabecular and cortical components following static and dynamic loading using the CVAD. Cortical bone strains were recorded using micro-strain gages. Finite element (FE) models based on micro-computed tomography were constructed for all C5 vertebrae. Both theoretical and experimental cortical strains correlated extremely well (R(2)>0.96) for a Young's modulus of 14.8 GPa, thus validating the FE model. In this study, we have successfully applied mechanical loads to the C5 murine vertebrae, demonstrating the potential of this model to be used for in vivo loading studies aimed at stimulating both trabecular and cortical bone adaptation.     

Finite element analysis of trabecular bone structure: a comparison of image-based meshing techniques

In this study, we investigate if finite element (FE) analyses of human trabecular bone architecture based on 168 μm images can provide relevant information about the bone mechanical characteristics. Three human trabecular bone samples, one taken from the femoral head, one from the iliac crest, and one from the lumbar spine, were imaged with micro-computed tomography (micro-CT) using a 28 μm resolution. After reconstruction the resolution was coarsened to 168 μm. First, all reconstructions were thresholded and directly converted to FE-models built of hexahedral elements. For the coarser resolutions of two samples, this resulted in a loss of trabecular connections and a subsequent loss of stiffness. To reduce this effect, a tetrahedral element meshing based on the marching cubes algorithm, as well as a modified hexahedron meshing, which thresholds the image such that load carrying bone mass is preserved, were employed. For each sample elastic moduli and tissue Von Mises stresses of the three different 168 μm models were compared to those from the hexahedron 28 μm model. For one sample the hexahedron meshing at 168 μm produced excellent results. For the other two samples the results obtained from the hexahedral models at 168 μm resolution were poor. Considerably better results were attained for these samples when using the mass-compensated or tetrahedron meshing techniques. We conclude that the accuracy of the FE-models at 168 μm strongly depends on the bone morphology, in particular its trabecular thickness. A substantial loss of trabecular connections during the hexahedron meshing process indicates that poor FE results will be obtained. In this case the tetrahedron or mass-compensated hexahedron meshing techniques can reduce the loss of connections and produce better results than the plain hexahedron meshing techniques.     

A Three-Dimensional Finite Element Scheme to Investigate the Apparent Mechanical Properties of Trabecular Bone

A computational technique is described for investigating the apparent mechanical properties of trabecular bone based on tissue geometry obtained from the marching cubes volume rendering scheme. Using this scheme, a 3D representation of the trabecular bone was extracted from two-dimensional cross-sections of the tissue originating from a quantitative serial sectioning procedure. Surface information consists of node coordinates and polygon connectivity in a 3D space. A custom, adaptive mesh generation technique using a normal offset was used to prepare 3D finite element volume meshes (4-node tetrahedral elements) of variable mesh density from the extracted surface geometry. Nine target mesh resolutions (32 μm to 107 μm) were examined for a (1.5 mmx 1.5 mmx 2 mm) volume of trabecular bone. A mesh density of 50,000 elements/mm(3) of bone tissue was found to be adequate for convergence of apparent (bulk) modulus for 1% uniaxial compression. For this convergent case, the maximum local normal compressive tissue stress was 400 MPa which was six hundred-fold greater than the computed apparent stress. Variation in the apparent modulus was less than 5% when Poisson's ratio values were varied between 0.1 and 0.4. Poisson's ratio values greater than 0.4 had a more marked effect on the apparent modulus. Based upon these results, approximately 1 million, 4-node tetrahedral elements are required to analyze a continuum scale model of trabecular bone (5 mm cube).     

Dynamic finite element knee simulation for evaluation of knee replacement mechanics

In vitro pre-clinical testing of total knee replacement (TKR) devices is a necessary step in the evaluation of new implant designs. Whole joint knee simulators, like the Kansas knee simulator (KKS), provide a controlled and repeatable loading environment for comparative evaluation of component designs or surgical alignment under dynamic conditions. Experimental testing, however, is time and cost prohibitive for design-phase evaluation of tens or hundreds of design variations. Experimentally-verified computational models provide an efficient platform for analysis of multiple components, sizes, and alignment conditions. The purpose of the current study was to develop and verify a computational model of a dynamic, whole joint knee simulator. Experimental internal-external and valgus-varus laxity tests, followed by dynamic deep knee bend and gait simulations in the KKS were performed on three cadaveric specimens. Specimen-specific finite element (FE) models of posterior-stabilized TKR were created from magnetic resonance images and CAD geometry. The laxity data was used to optimize mechanical properties of tibiofemoral soft-tissue structures on a specimen-specific basis. Each specimen was subsequently analyzed in a computational model of the experimental KKS, simulating both dynamic activities. The computational model represented all joints and actuators in the experimental setup, including a proportional-integral-derivative (PID) controller to drive quadriceps actuation. The computational model was verified against six degree-of-freedom patellofemoral (PF) and tibiofemoral (TF) kinematics and actuator loading during both deep knee bend and gait activities, with good agreement in trends and magnitudes between model predictions and experimental kinematics; differences were less than 1.8 mm and 2.2° for PF and TF translations and rotations. The whole joint FE simulator described in this study can be applied to investigate a wide range of clinical and research questions.