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Osteogenesis imperfecta (OI) is a genetic, collagen‐related bone disease that increases the incidence of bone fractures. Still, the origin of this brittle mechanical behavior remains unclear. The extracellular matrix (ECM) of OI bone exhibits a higher degree of bone mineralization (DBM), whereas compressive mechanical properties at the ECM level do not appear to be inferior to healthy bone. However, it is unknown if collagen defects alter ECM tensile properties. This study aims to quantify the tensile properties of healthy and OI bone ECM. In three transiliac biopsies (healthy n = 1, OI type I n = 1, OI type III n = 1), 23 microtensile specimens (gauge dimensions 10 × 5 × 2 μm3) were manufactured and loaded quasi‐statically under tension in vacuum condition. The resulting loading modulus and ultimate strength were extracted. Interestingly, tensile properties in OI bone ECM were not inferior compared to controls. All specimens revealed a brittle failure behavior. Fracture surfaces were graded according to their mineralized collagen fibers (MCF) orientation into axial, mixed, and transversal fracture surface types (FST). Furthermore, tissue mineral density (TMD) of the biopsy cortices was extracted from micro–computed tomogra[hy (μCT) images. Both FST and TMD are significant factors to predict loading modulus and ultimate strength with an adjusted R2 of 0.556 (p = 2.65e−05) and 0.46 (p = 2.2e−04), respectively. The influence of MCF orientation and DBM on the mechanical properties of the neighboring ECM was further verified with quantitative polarized Raman spectroscopy (qPRS) and site‐matched nanoindentation. MCF orientation and DBM were extracted from the qPRS spectrum, and a second mechanical model was developed to predict the indentation modulus with MCF orientation and DBM (R2 = 67.4%, p = 7.73e−07). The tensile mechanical properties of the cortical bone ECM of two OI iliac crest biopsies are not lower than the one from a healthy and are primarily dependent on MCF orientation and DBM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The development of treatment strategies for skeletal diseases relies on the understanding of bone mechanical properties in relation to its structure at different length scales. At the microscale, indention techniques can be used to evaluate the elastic, plastic, and fracture behaviour of bone tissue. Here, we combined in situ high-resolution SRµCT indentation testing and digital volume correlation to elucidate the anisotropic crack propagation, deformation, and fracture of ovine cortical bone under Berkovich and spherical tips. Independently of the indenter type we observed significant dependence of the crack development due to the anisotropy ahead of the tip, with lower strains and smaller crack systems developing in samples indented in the transverse material direction, where the fibrillar bone ultrastructure is largely aligned perpendicular to the indentation direction. Such alignment allows to accommodate the strain energy, inhibiting crack propagation. Higher tensile hoop strains generally correlated with regions that display significant cracking radial to the indenter, indicating a predominant Mode I fracture. This was confirmed by the three-dimensional analysis of crack opening displacements and stress intensity factors along the crack front obtained for the first time from full displacement fields in bone tissue. The X-ray beam significantly influenced the relaxation behaviour independent of the tip. Raman analyses did not show significant changes in specimen composition after irradiation compared to non-irradiated tissue, suggesting an embrittlement process that may be linked to damage of the non-fibrillar organic matrix. This study highlights the importance of three-dimensional investigation of bone deformation and fracture behaviour to explore the mechanisms of bone failure in relation to structural changes due to ageing or disease. Characterising the three-dimensional deformation and fracture behaviour of bone remains essential to decipher the interplay between structure, function, and composition with the aim to improve fracture prevention strategies. The experimental methodology presented here, combining high-resolution imaging, indentation testing and digital volume correlation, allows us to quantify the local deformation, crack propagation, and fracture modes of cortical bone tissue. Our results highlight the anisotropic behaviour of osteonal bone and the complex crack propagation patterns and fracture modes initiating by the intricate stress states beneath the indenter tip. This is of wide interest not only for the understanding of bone fracture but also to understand other architectured (bio)structures providing an effective way to quantify their toughening mechanisms in relation to their main mechanical function. [Display omitted] [ABSTRACT FROM AUTHOR]

Tissue fixation is a prevalent method for bone conservation. Bone biopsies are typically fixed in formalin, dehydrated in ethanol, and infiltrated with polymethyl methacrylate (PMMA) Since some experiments can only be performed on fixed bone samples, it is essential to understand how fixation affects the measured material properties. The aim of this study was to quantify the influence of tissue fixation on the mechanical properties of cortical ovine bone at the extracellular matrix (ECM) level with state-of-the-art micromechanical techniques. A small section from the middle of the diaphysis of two ovine tibias (3.5 and 5.5 years old) was cut in the middle and polished on each side, resulting in a pair of mirrored surfaces. For each pair, one specimen underwent a fixation protocol involving immersion in formalin, dehydration with ethanol, and infiltration with PMMA. The other specimen (mirrored) was air-dried. Six osteons were selected in both pairs, which could be identified in both specimens. The influence of fixation on the mechanical properties was first analyzed using micropillar compression tests and nanoindentation in dry condition. Additionally, changes in the degree of mineralization were evaluated with Raman spectroscopy in both fixed and native bone ECM. Finally, micro tensile experiments were conducted in the 3.5-year fixed ovine bone ECM and compared to reported properties of unfixed dry ovine bone ECM. Interestingly, we found that tissue fixation does not alter the mechanical properties of ovine cortical bone ECM compared to experiments in dry state. However, animal age increases the degree of mineralization (p = 0.0159) and compressive yield stress (p = 0.041). Tissue fixation appears therefore as a valid conservation technique for investigating the mechanical properties of dehydrated bone ECM. [Display omitted] • Influence of fixation on the mechanical and mineralization properties was examined in dry ovine bone extracellular matrix. • Novel micro mechanical tests were applied to compare the mechanical properties in fixed and native dry ovine bone biopsies. • Mechanical properties of fixed bone were not statistically different compared to native dry bone extracellular matrix. [ABSTRACT FROM AUTHOR]

• Development, calibration, and validation of a method for quantitative collagen fibril orientation estimation based on polarized Raman spectroscopy (qPRS). • Micropillar compression experiments at the length scale of a single bone lamella under hydrated conditions combined with collagen orientation analysis. • Elastic modulus and yield stress were found to be strongly affected by mineralized collagen fibril (MCF) orientation. • Failure modes and post yield behavior of isolated bone lamellae in compression depend on MCF orientation with a transition between softening to hardening behavior at θ = 48 ∘ − 54 ∘. Bone is a natural composite possessing outstanding mechanical properties combined with a lightweight design. The key feature contributing to this unusual combination of properties is the bone hierarchical organization ranging from the nano- to the macro-scale. Bone anisotropic mechanical properties from two orthogonal planes (along and perpendicular to the main bone axis) have already been widely studied. In this work, we demonstrate the dependence of the microscale compressive mechanical properties on the angle between loading direction and the mineralized collagen fibril orientation in the range between 0° and 82°. For this, we calibrated polarized Raman spectroscopy for quantitative collagen fibril orientation determination and validated the method using widely used techniques (small angle X-ray scattering, micro-computed tomography). We then performed compression tests on bovine cortical bone micropillars with known mineralized collagen fibril angles. A strong dependence of the compressive micromechanical properties of bone on the fibril orientation was found with a high degree of anisotropy for both the elastic modulus (E a / E t = 3.80) and the yield stress (σ a y / σ t y = 2.54). Moreover, the post-yield behavior was found to depend on the MCF orientation with a transition between softening to hardening behavior at approximately 50°. The combination of methods described in this work allows to reliably determine structure-property relationships of bone at the microscale, which may be used as a measure of bone quality. Image, graphical abstract [ABSTRACT FROM AUTHOR]

In this study, 3D finite element analyses (FEA) are conducted to quantify the orthotropic elastic properties and investigate the load transfer mechanism of bone at the sub-lamellar level. Three finite element (FE) unit cells with periodic boundary conditions are presented to model a two-scale microstructure of bone including a mineralized collagen fibril (MCF), the extrafibrillar matrix (EFM) and the resulting fibril array (FAY) under arbitrary loading. The axial and transverse elastic properties of the FAY computed by FEA are calibrated with unique experimental results on ovine micro-samples showing a coherent fibril orientation. They are then systematically compared with those calculated using analytical methods including the basic Voigt, Reuss and shear-lag models, the Mori–Tanaka scheme and the upper and lower bounds by Hashin and Shtrikman. The predicted axial strain ratios between the two-scales are discussed with respect to a recent small-angle X-ray scattering and wide-angle X-ray diffraction study. Beyond apparent elastic properties, the FE models provide stress distributions at both hierarchical levels, confirm the shear lag mechanisms within the MCF and between MCF and EFM and identify potential damage sites under arbitrary loading conditions. A comprehensive sensitivity analysis shows that mineral volume fraction in the fibril array is the dominant parameter on the axial and transverse elastic moduli, while the MCF volume fraction in FAY is the most sensitive variable for the ratio of axial versus transverse elastic modulus followed by the elastic moduli of hydroxyapatite and collagen. The FE model of the FAY developed and calibrated in the current study represents an anatomically realistic, experimentally validated and computationally efficient basis for investigating the apparent yield, post-yield and failure behaviors of lamellar bone in future research. [ABSTRACT FROM AUTHOR]

Micro-finite element ( $$\upmu $$ FE) analyses are often used to determine the apparent mechanical properties of trabecular bone volumes. Yet, these apparent properties depend strongly on the applied boundary conditions (BCs) for the limited size of volumes that can be obtained from human bones. To attenuate the influence of the BCs, we computed the yield properties of samples loaded via a surrounding layer of trabecular bone ('embedded configuration'). Thirteen cubic volumes (10.6 mm side length) were collected from $$\upmu $$ CT reconstructions of human vertebrae and femora and converted into $$\upmu $$ FE models. An isotropic elasto-plastic material model was chosen for bone tissue, and nonlinear $$\upmu $$ FE analyses of six uniaxial, shear, and multi-axial load cases were simulated to determine the yield properties of a subregion (5.3 mm side length) of each volume. Three BCs were tested. Kinematic uniform BCs (KUBCs: each boundary node is constrained with uniform displacements) and periodicity-compatible mixed uniform BCs (PMUBCs: each boundary node is constrained with a uniform combination of displacements and tractions mimicking the periodic BCs for an orthotropic material) were directly applied to the subregions, while the embedded configuration was achieved by applying PMUBCs on the larger volumes instead. Yield stresses and strains, and element damage at yield were finally compared across BCs. Our findings indicate that yield strains do not depend on the BCs. However, KUBCs significantly overestimate yield stresses obtained in the embedded configuration (+43.1 ± 27.9%). PMUBCs underestimate (−10.0 ± 11.2%), but not significantly, yield stresses in the embedded situation. Similarly, KUBCs lead to higher damage levels than PMUBCs (+51.0 ± 16.9%) and embedded configurations (+48.4 ± 15.0%). PMUBCs are better suited for reproducing the loading conditions in subregions of the trabecular bone and deliver a fair estimation of their effective (asymptotic) yield properties. [ABSTRACT FROM AUTHOR]

The scaphoid is the most often fractured carpal bone. Scaphoid fracture repair with a headless compression screw allows for early functional recovery. The rotational stability of a single screw may be limited, having a potential negative impact on the healing process. Two novel screws have been designed to provide improved rotational stability compared to the existing ones. Using a computational finite element model of a scaphoid osteotomy, we compared the efficacy of one simple screw and the two new screws in restricting inter-fragmentary motion (IFM) in three functional positions of the wrist and as a function of inter-fragmentary compression force. The in-plane IFM was primary rotational and was better restricted by the new screws compared to the conventional one when the inter-fragmentary compression force was below 15–20 N, but provided no clear benefit in total flexion independently of the compression force. To better understand the differences in the non-compressed case, we analyzed the acting moments and investigated the effects of the bending and torsional screw stiffness on IFM. By efficiently restricting the inter-fragmentary shear, the new screws may be clinically advantageous when the inter-fragmentary compression force is partially or completely lost and may provide further benefits toward earlier and better healing of transverse waist fractures of the scaphoid. [ABSTRACT FROM AUTHOR]

Preclinical studies often require animal models for in vivo experiments. Particularly in dental research, pig species are extensively used due to their anatomical similarity to humans. However, there is a considerable knowledge gap on the multiscale morphological and mechanical properties of the miniature pigs' jawbones, which is crucial for implant studies and a direct comparison to human tissue. In the present work, we demonstrate a multimodal framework to assess the jawbone quantity and quality for a minipig animal model that could be further extended to humans. Three minipig genotypes, commonly used in dental research, were examined: Yucatan, Göttingen, and Sinclair. Three animals per genotype were tested. Cortical bone samples were extracted from the premolar region of the mandible, opposite to the teeth growth. Global morphological, compositional, and mechanical properties were assessed using micro-computed tomography (micro-CT) together with Raman spectroscopy and nanoindentation measurements, averaged over the sample area. Local mineral-mechanical relationships were investigated with the site-matched Raman spectroscopy and micropillar compression tests. For this, a novel femtosecond laser ablation protocol was developed, allowing high-throughput micropillar fabrication and testing without exposure to high vacuum. At the global averaged sample level, bone relative mineralization demonstrated a significant difference between the genotypes, which was not observed from the complementary micro-CT measurements. Moreover, bone hardness measured by nanoindentation showed a positive trend with the relative mineralization. For all genotypes, significant differences between the relative mineralization and elastic properties were more pronounced within the osteonal regions of cortical bone. Site-matched micropillar compression and Raman spectroscopy highlighted the differences between the genotypes' yield stress and mineral to matrix ratios. The methods used at the global level (averaged over sample area) could be potentially correlated to the medical tools used to assess jawbone toughness and morphology in clinics. On the other hand, the local analysis methods can be applied to quantify compressive bone mechanical properties and their relationship to bone mineralization. [Display omitted] • A multimodal framework for bone characterization was developed in an animal model that could be further extended to humans. • Jawbone mineralization, morphology, and mechanical properties were assessed in Yucatan, Göttingen and Sinclair minipigs. • A novel femtosecond laser ablation protocol was established for bone micropillar fabrication. • Site-matched micropillar compression and Raman spectroscopy revealed bone microscale structure-properties relationship. [ABSTRACT FROM AUTHOR]

Abstract: Relationships between mineralization, collagen orientation and indentation modulus were investigated in bone structural units from the mid-shaft of human femora using a site-matched design. Mineral mass fraction, collagen fibril angle and indentation moduli were measured in registered anatomical sites using backscattered electron imaging, polarized light microscopy and nano-indentation, respectively. Theoretical indentation moduli were calculated with a homogenization model from the quantified mineral densities and mean collagen fibril orientations. The average indentation moduli predicted based on local mineralization and collagen fibers arrangement were not significantly different from the average measured experimentally with nanoindentation (p=0.9). Surprisingly, no substantial correlation of the measured indentation moduli with tissue mineralization and/or collagen fiber arrangement was found. Nano-porosity, micro-damage, collagen cross-links, non-collagenous proteins or other parameters affect the indentation measurements. Additional testing/simulation methods need to be considered to properly understand the variability of indentation moduli, beyond the mineralization and collagen arrangement in bone structural units. [Copyright &y& Elsevier]

Abstract: Haversian systems or ‘osteons’ are cylindrical structures, formed by bone lamellae, that make up the major part of human cortical bone. Despite their discovery centuries ago in 1691 by Clopton Havers, their mechanical properties are still poorly understood. The objective of this study is a detailed identification of the anisotropic elastic properties of the secondary osteon in the lamella plane. Additionally, the principal material orientation with respect to the osteon is assessed. Therefore a new nanoindentation method was developed which allows the measurement of indentation data in three distinct planes on a single osteon. All investigated osteons appeared to be anisotropic with a preferred stiffness alignment along the axial direction with a small average helical winding around the osteon axis. The mean degree of anisotropy was 1.75 ± 0.36 and the mean helix angle was 10.3°±0.8°. These findings oppose two well established views of compact bone microstructure: first, the generally clear axial stiffness orientation contradicts a regular ‘twisted plywood’ collagen fibril orientation pattern in lamellar bone that would lead to a more isotropic behavior. Second, the class of transverse osteons were not observed from the mechanical point of view. [Copyright &y& Elsevier]

The mechanical properties of bone extracellular matrix have become of increasing interest for the understanding of vertebral fracture risk. Depth-sensing indentation techniques allow the measurement of directional elastic properties of trabecular bone ex vivo with a high spatial resolution. Transverse isotropic elastic properties of vertebral trabecular bone obtained from two orthogonal directions were investigated using microindentation under dry conditions focusing on the influence of microanatomical location, age, gender, vertebral level, and anatomic direction on these properties. Biopsies were obtained from 104 human vertebrae (T1–L3) with a median age of 65 (21–94) years. Significantly, higher indentation moduli were found for indentations on axial than on transverse cross-sections of trabeculae (p < 0.01). Indentation moduli in the core were 1.05 to 1.12 times higher than in the periphery (p < 0.01). No difference in stiffness could be detected between males and females (p > 0.05) and different ages (p > 0.5). Vertebral level showed a weak correlation (p = 0.073, r2 ≈ 0.17). These results provide insights in the transverse isotropic properties of trabecular bone matrix related to age, gender, microanatomical location, and anatomic direction for a broad spectrum of human vertebrae. [ABSTRACT FROM AUTHOR]

Abstract: Continuum finite element (FE) models are standard tools for determination of biomechanical properties of bones and bone-implant systems. This study investigates the accuracy of an enhanced continuum FE model by taking as the gold standard. The enhanced continuum models account for trabecular bone morphology (density and fabric) as well as for an anatomically correct cortical shell. Vertebral body slice models are extracted from high-resolution CT images using an algorithm proposed in [Pahr and Zysset, 2008b. From high-resolution CT data to FE models: development of an integrated modular framework. Computer Methods in Biomechanics and Biomedical Engineering, in press.]. Three different models are generated: the proposed enhanced density-fabric-based model with a subject-specific cortex and two classical isotropic density-only models, with and without explicit modeling of the cortical shell. The material property errors of the used morphology-elasticity relationship are minimized by using elasticity tensors from 60 cubical models which are cropped from the trabecular centrums of the investigated vertebral bodies. Two different boundary conditions—kinematic [. A new method to determine trabecular bone elastic properties and loading using micromechanical FE models. Journal of Biomechanics 28 (1), 69–81] and mixed [Pahr, D.H., Zysset, P.K., 2008a. Influence of boundary conditions on computed apparent elastic properties of cancellous bone. Biomechanics and Modeling in Mechanobiology 7, 463–476.]—are used in these FE models. After removal of the endplates, compressive and antero–posterior shear loading is applied on the investigated vertebral bodies. Individual error sources are studied in more detail by loading also the trabecular centrum (removed shell) and the cortical shell alone. It is found that the cortex-only models need a correction of the shell thickness when transforming from a voxel to a smooth description. The trabecular centrum alone gives too stiff and too soft a response using material calibration with kinematic and mixed boundary conditions, respectively. A comparison of the whole vertebral body stiffnesses shows that an orthotropic cancellous bone material calibrated with kinematic boundary conditions corresponds best with . Taken together, the proposed enhanced homogenized surface-based FE model is structurally more accurate than density-only models. [Copyright &y& Elsevier]

Abstract: Even though mechanical properties depend strongly on the arrangement of collagen fibers in mineralized tissues, it is not yet well resolved. Only a few semi-quantitative evaluations of the fiber arrangement in bone, like spectroscopic techniques or circularly polarized light microscopy methods are available. In this study the out-of-plane collagen arrangement angle was calibrated to the linear birefringence of a longitudinally fibered mineralized turkey leg tendon cut at variety of angles to the main axis. The calibration curve was applied to human cortical bone osteons to quantify the out-of-plane collagen fibers arrangement. The proposed calibration curve is normalized to sample thickness and wavelength of the probing light to enable a universally applicable quantitative assessment. This approach may improve our understanding of the fibrillar structure of bone and its implications on mechanical properties. [Copyright &y& Elsevier]

Osteoporosis-related vertebral body fractures involve large compressive strains of trabecular bone. The small strain mechanical properties of the trabecular bone such as the elastic modulus or ultimate strength can be estimated using the volume fraction and a second order fabric tensor, but it remains unclear if similar estimations may be extended to large strain properties. Accordingly, the aim of this work is to identify the role of volume fraction and especially fabric in the large strain compressive behavior of human trabecular bone from various anatomical locations. Trabecular bone biopsies were extracted from human T12 vertebrae (n=31), distal radii (n=43), femoral head (n=44), and calcanei (n=30), scanned using microcomputed tomography to quantify bone volume fraction (BV/TV) and the fabric tensor (M), and tested either in unconfined or confined compression up to very large strains (~70%). The mechanical parameters of the resulting stress-strain curves were analyzed using regression models to examine the respective influence of BV/TV and fabric eigenvalues. The compressive stress-strain curves demonstrated linear elasticity, yielding with hardening up to an ultimate stress, softening toward a minimum stress, and a steady rehardening followed by a rapid densification. For the pooled experiments, the average minimum stress was 1.89±1.77 MPa, while the corresponding mean strain was 7.15±1.84%. The minimum stress showed a weaker dependence with fabric as the elastic modulus or ultimate strength. For the confined experiments, the stress at a logarithmic strain of 1.2 was 8.08±7.91 MPa, and the dissipated energy density was 5.67±4.42 MPa. The latter variable was strongly related to the volume fraction (R2=0.83) but the correlation improved only marginally with the inclusion of fabric (R2=0.84). The influence of fabric on the mechanical properties of human trabecular bone decreases with increasing strain, while the role of volume fraction remains important. In particular, the ratio of the minimum versus the maximum stress, i.e., the relative amount of softening, decreases strongly with fabric, while the dissipated energy density is dominated by the volume fraction. The collected results will prove to be useful for modeling the softening and densification of the trabecular bone using the finite element method. [ABSTRACT FROM AUTHOR]

Abstract: For understanding the fracture risk of vertebral bodies the macroscopic mechanical properties of the cancellous core are of major interest. Due to the hierarchical nature of bone, these depend in turn on the micromechanical properties of bone extracellular matrix which is at least linear elastic transverse isotropic. The experimental determination of local elastic properties of bone ex vivo necessitates a high spatial resolution which can be provided by depth-sensing indentation techniques. Using microindentation, this study investigated the effects of rehydration on the transverse isotropic elastic properties of vertebral trabecular bone matrix obtained from two orthogonal directions with a view to microanatomical location, age, gender, vertebral level and anatomic direction in a conjoint statistics. Biopsies were gained from 104 human vertebrae (T1–L3) with a median age of 65 years (21–94). Wet elastic moduli were 29% lower (p <0.05) than dry elastic moduli. For wet indentation the ratio of mean elastic moduli tested in axial to those tested in transverse indentation direction were 1.13 to 1.23 times higher than for dry indentation. The ratio of elastic moduli tested in the core to those tested in the periphery of trabeculae was 1.05 to 1.16 times higher when testing wet. Age and gender did not show any influence on the elastic moduli for wet and dry measurements. The correlation between vertebral level and elastic moduli became weaker after rehydration (p wet <0.09, r wet 2 =0.14) and (p dry <0.01, r wet 2 =0.38). Elastic and dissipated energies were similarly affected by rehydration compared to the elastic modulus. No significant difference in the energies could be found for gender (p >0.05). Significant differences in the energies were found for age (p <0.05) after rehydration. Qualitative and quantitative insights into the transverse isotropic elastic properties of trabecular bone matrix under two testing conditions over a broad spectrum of vertebrae could be given. This study could help to further improve understanding of the mechanical properties of vertebral trabecular bone. [Copyright &y& Elsevier]

Current homogenized finite element (hFE) models of the patella lack a validated material law and mostly overlook trabecular anisotropy. The objective of this study was to identify the elastic constants of patellar trabecular bone. Using μCT scans of 20 fresh-frozen cadaveric patellae, we virtually extracted 200 trabecular cubes (5.3 mm side length). Bone volume fraction and fabric tensor were measured. The elastic constants were identified from six independent load cases using micro finite element (μFE) analyses. Both anisotropic and isotropic material laws were considered. The elastic constants were validated by comparing stiffness, strain and stress between hFE and μFE predictions of 18 patellar sections and six load cases. The hFE section models were built from μCT (anisotropic law) and CT (isotropic law) scans. The homogenized anisotropic model induced less error (13±5%) in the global stiffness prediction than the isotropic one (18±6%), and less error in the prediction of local apparent strain, stress, and strain energy, compared to the isotropic one. This validated hFE model could be used for future applications, either with the anisotropic constants, or with the isotropic ones when the trabecular fabric is unavailable. [ABSTRACT FROM AUTHOR]

Mechanical properties of human trabecular bone play an important role in age-related bone fragility and implant stability. Microfinite element (µFE) analysis allows computing the apparent elastic properties of trabecular bone for use in homogenized FE (hFE) analysis, but the results depend unfortunately on the type of applied boundary conditions (BCs). In this study, 167 human femoral trabecular cubic regions with a side length of 5.3 mm were extracted from three proximal femora and analyzed using µFE analysis to compare systematically their stiffness with kinematic uniform BCs (KUBCs) and periodicity-compatible mixed uniform BCs (PMUBCs). The obtained elastic constants were then used in the volume fraction and fabric-based orthotropic Zysset-Curnier model to identify their respective model parameters. As expected, PMUBCs lead to more compliant apparent elastic properties than KUBCs, especially in shear. The differences in stiffness decreased with bone volume fraction and mean intercept length (MIL). Unlike KUBCs, PMUBCs were sensitive to heterogeneity of the biopsies. The Zysset-Curnier model fitted the apparent elastic constants successfully in both cases with adjusted coefficients of determination (radj² ) of 0.986 for KUBCs and 0.975 for PMUBCs. The proper use of these BCs for hFE analysis of whole bones will need to be investigated in future work. [ABSTRACT FROM AUTHOR]

Abstract: In the 1920s and 1930s, Terzaghi and coworkers realized that the failure of various porous geomaterials under internal pore pressure is given through evaluating the failure function for the same materials at zero pressure, with ‘total stress plus pore pressure’ instead of ‘total stress alone’ as argument. As to check, probably for the first time, the relevance of this (‘Terzaghi''s’) failure criterion for trabecular bone, a series of poromechanical and ultrasonic tests was conducted on bovine and human trabecular bone samples. Evaluation of respective experimental results within the theoretical framework of microporomechanics showed that (i) Terzaghi''s effective stress indeed governs trabecular bone failure, (ii) deviatoric stress states at the level of the solid bone matrix (also called tissue level) are primary candidates for initiating bone failure, and (iii) the high heterogeneity of these deviatoric tissue stresses, which increases with increasing intertrabecular porosity, governs the overall failure of trabecular bone. Result (i) lets us use the widely documented experimental results for strength values of bone samples without pore pressure, as to predict failure of the same bone samples under internal pore pressure. Result (ii) suggests a favorable mode for strength modeling of solid bone matrix. Finally, result (iii) underlines the suitability of microfinite element simulations for trabecular bone microstructures. [Copyright &y& Elsevier]

Micro finite element analysis (μFE) is a widely applied tool in biomedical research for assessing in vivo mechanical properties of bone at measurement sites, including the ultra-distal radius and tibia. A finite element approach (hFE) based on homogenized constitutive models for trabecular bone offers an attractive alternative for clinical use, as it is computationally less expensive than traditional μFE. The respective patient-specific models for in vivo bone strength estimation are usually based on standard clinical high-resolution peripheral quantitative CT (HR-pQCT) measurements. They include a scan region of roughly 10 mm in height and are referred to as single-sections. It has been shown, that these small peripheral bone sections don't reliably cover the fracture line in Colles' fractures and therefore the weakest region at the radius. Recently introduced multiple section (multiple adjacent single-sections) measurements might improve the evaluation of bone strength, but little is known about the repeatability of hFE estimations in general, and especially for multiple section measurement protocols. Accordingly, the aim of the present work is to quantify repeatability of clinical in vivo bone strength measurement by hFE on multiple section HR-pQCT reconstructions at the distal radius and tibia. Nineteen healthy Swiss women (43.6y ± 17.8y) and twenty men (48.2y ± 19.4y) were examined with HR-pQCT at 61 μm isotropic voxel resolution. Each subject was first scanned three times using a double-section (336 slices) at the distal radius and then three times using a triple-section (504 slices) at the distal tibia. The multiple section HR-pQCT reconstructions were graded for motion artefacts and non-linear hFE models (radius and tibia) and linear μFE models (only radius) were generated for estimation of stiffness and ultimate load. Then in vivo repeatability errors were computed in terms of root mean square coefficients of variation (CV). In vivo repeatability errors of non-linear hFE stiffness (S) and ultimate load (F) were significantly higher at the radius (S: 2.71% and F: 2.97%) compared to the tibia (S: 1.21%, F: 1.45%). Multiple section linear μFE at the radius resulted in substantially higher repeatability errors (S: 5.38% and F: 10.80%) compared to hFE. Repeatability errors of hFE outcomes based on multiple section measurements at the distal radius and tibia were generally lower compared to respective reported single-section μFE repeatability errors. Therefore, hFE is an attractive alternative to today's gold standard of μFE models and should especially be encouraged when analyzing multiple section measurements. Unlabelled Image • Clinical hFE repeatability was below 3% at the radius and below 1.5% at the tibia. • hFE repeatability errors are significantly lower at the tibia than at the radius. • hFE models should be encouraged when analyzing multiple section measurement. [ABSTRACT FROM AUTHOR]

As a dedicated experimentalist, John Currey praised the high potential of finite element (FE) analysis but also recognized its critical limitations. The application of the FE methodology to bone tissue is reviewed in the light of his enthusiastic and colorful statements. In the past decades, FE analysis contributed substantially to the understanding of structure-function properties in the hierarchical organization of bone and to the simulation of bone adaptation. The systematic experimental validation of FE analysis of bone strength in anatomical locations at risk of fracture led to its application in clinical studies to evaluate efficacy of antiresorptive or anabolic treatment of bone fragility. Beyond the successful analyses of healthy or osteoporotic bone, FE analysis becomes increasingly involved in the investigation of other fragility-related bone diseases. The case of osteogenesis imperfecta (OI) is exposed, the multiscale alterations of the bone tissue and the effect of treatment summarized. A few FE analyses attempting to answer open questions in OI are then reported. An original study is finally presented that explored the structural properties of the Brtl/+ murine model of OI type IV subjected to sclerostin neutralizing antibody treatment using microFE analysis. The use of identical material properties in the four-point bending FE simulations of the femora reproduced not only the experimental values but also the statistical comparisons examining the effect of disease and treatment. Further efforts are needed to build upon the extraordinary legacy of John Currey and clarify the impact of different bone diseases on the hierarchical mechanical properties of bone. • The application of the finite element (FE) method to bone is reviewed in the light of John Currey's statements • The use of FE to investigate osteogenesis imperfecta (OI) is targeted • The multiscale alterations of the bone tissue in OI and the effect of treatment are reviewed • An original study is presented to predict bone strength in a murine OI model treated with sclerostin neutralizing antibody • microFE models with identical material properties well predict experimental strength independent of disease and treatment [ABSTRACT FROM AUTHOR]