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As our population ages, more individuals suffer from osteoporosis. This disease leads to impaired trabecular architecture and increased fracture risk. It is essential to understand how morphological and mechanical properties of the cancellous bone are related. Morphology-elasticity relationships based on bone volume fraction (BV/TV) and fabric anisotropy explain up to 98% of the variation in elastic properties. Yet, other morphological variables such as individual trabeculae segmentation (ITS) and trabecular bone score (TBS) could improve the stiffness predictions. A total of 743 micro-computed tomography (μCT) reconstructions of cubic trabecular bone samples extracted from femur, radius, vertebrae, and iliac crest were analyzed. Their morphology was assessed via 25 variables and their stiffness tensor (CFE) was computed from six independent load cases using micro finite element (μFE) analyses. Variance inflation factors were calculated to evaluate collinearity between morphological variables and decide upon their inclusion in morphology-elasticity relationships. The statistically admissible morphological variables were included in a multiple linear regression model of the dependent variable CFE. The contribution of each independent variable was evaluated (ANOVA). Our results show that BV/TV is the best determinant of CFE(r(2) adj  = 0.889), especially in combination with fabric anisotropy (r(2) adj  = 0.968). Including the other independent predictors hardly affected the amount of variance explained by the model (r(2) adj  = 0.975). Across all anatomical sites, BV/TV explained 87% of the variance of the bone elastic properties. Fabric anisotropy further described 10% of the bone stiffness, but the improvement in variance explanation by adding other independent factors was marginal (<1%). These findings confirm that BV/TV and fabric anisotropy are the best determinants of trabecular bone stiffness and show, against common belief, that other morphological variables do not bring any further contribution. These overall conclusions remain to be confirmed for specific bone diseases and postelastic properties., (© 2015 American Society for Bone and Mineral Research.)

Mechanical properties of human trabecular bone play an important role in age-related bone fragility and implant stability. Microfinite element (lFE) 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 5.3mm were extracted from three proximal femora and analyzed using lFE 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 (r2adj) 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.

With improving clinical CT scanning technology, the accuracy of CT-based finite element (FE) models of the human skeleton may be ameliorated by an enhanced description of apparent level bone mechanical properties. Micro-finite element (μFE) modeling can be used to study the apparent elastic behavior of human cancellous bone. In this study, samples from the femur, radius and vertebral body were investigated to evaluate the predictive power of morphology-elasticity relationships and to compare them across different anatomical regions. μFE models of 701 trabecular bone cubes with a side length of 5.3 mm were analyzed using kinematic boundary conditions. Based on the FE results, four morphology-elasticity models using bone volume fraction as well as full, limited or no fabric information were calibrated for each anatomical region. The 5 parameter Zysset-Curnier model using full fabric information showed excellent predictive power with coefficients of determination ([Formula: see text]) of 0.98, 0.95 and 0.94 of the femur, radius and vertebra data, respectively, with mean total norm errors between 14 and 20%. A constant orthotropy model and a constant transverse isotropy model, where the elastic anisotropy is defined by the model parameters, yielded coefficients of determination between 0.90 and 0.98 with total norm errors between 16 and 25%. Neglecting fabric information and using an isotropic model led to [Formula: see text] between 0.73 and 0.92 with total norm errors between 38 and 49%. A comparison of the model regressions revealed minor but significant (p<0.01) differences for the fabric-elasticity model parameters calibrated for the different anatomical regions. The proposed models and identified parameters can be used in future studies to compute the apparent elastic properties of human cancellous bone for homogenized FE models.

Purpose: Vertebroplasty restores stiffness and strength of fractured vertebral bodies, but alters their stress transfer. This unwanted effect may be reduced by using more compliant cements. However, systematic experimental comparison of structural properties between standard and low-modulus augmentation needs to be done. This study investigated how standard and low-modulus cement augmentation affects apparent stiffness, strength, and endplate pressure distribution of vertebral body sections., Methods: Thirty-nine human thoracolumbar vertebral body sections were prepared by removing cortical endplates and posterior elements. The specimens were scanned with a HR-pQCT system and loaded in the elastic range. After augmentation with standard or low-modulus cement they were scanned again and tested in two steps. First, the contact pressure distribution between specimen and loading plates was measured with pressure-sensitive films. Then, they were loaded again in the elastic range and compressed until failure. Apparent stiffness was compared before and after augmentation, whereas apparent strength of augmented specimens was compared to a non-augmented reference group., Results: Vertebral body sections with fillings connecting both endplates were on average 33% stiffer and 47% stronger with standard cement, and 27% stiffer and 30% stronger with low-modulus cement. In contrast, partial fillings showed no significant strengthening for both cements and only a slight stiffness increase (<16%). The averaged endplate pressure above/below the cement was on average 15% lower with low-modulus cement compared to standard cement., Conclusion: Augmentation connecting both endplates significantly strengthened and stiffened vertebral body sections also with low-modulus cement. A trend of reduced pressure concentrations above/below the cement was observed with low-modulus cement.

The key parameters determining the elastic properties of an unidirectional mineralized bone fibril-array decomposed in two further hierarchical levels are investigated using mean field methods. Modeling of the elastic properties of mineralized micro- and nanostructures requires accurate information about the underlying topology and the constituents' material properties. These input data are still afflicted by great uncertainties and their influence on computed elastic constants of a bone fibril-array remains unclear. In this work, mean field methods are applied to model mineralized fibrils, the extra-fibrillar matrix and the resulting fibril-array. The isotropic or transverse isotropic elastic constants of these constituents are computed as a function of degree of mineralization, mineral distribution between fibrils and extra-fibrillar matrix, collagen stiffness and fibril volume fraction. The linear sensitivity of the elastic constants was assessed at a default set of the above parameters. The strain ratios between the constituents as well as the axial and transverse indentation moduli of the fibril-array were calculated for comparison with experiments. Results indicate that the degree of mineralization and the collagen stiffness dominate fibril-array elasticity. Interestingly, the stiffness of the extra-fibrillar matrix has a strong influence on transverse and shear moduli of the fibril-array. The axial strain of the intra-fibrillar mineral platelets is 30-90% of the applied fibril strain, depending on mineralization and collagen stiffness. The fibril-to-fibril-array strain ratio is essentially ~1. This study provides an improved insight in the parameters, which govern the fibril-array stiffness of mineralized tissues such as bone.

The identification of anisotropic elastic properties of lamellar bone based on nanoindentation data is an open problem. Therefore, the purpose of this study was to develop a method to estimate the orthotropic elastic constants of human cortical bone secondary osteons using nanoindentation in two orthogonal directions. Since the indentation modulus depends on all elastic constants and, for anisotropic materials, also on the indentation direction, a theoretical model quantifying the indentation modulus from the stiffness tensor of a given material was implemented numerically (Swadener and Pharr, 2001, "Indentation of Elastically Anisotropic Half-Spaces by Cones and Parabolae of Revolution," Philos. Mag. A, 81(2), pp. 447-466). Nanoindentation was performed on 22 osteons of the distal femoral shaft: A new holding system was designed in order to indent the same osteon in two orthogonal directions. To interpret the experimental results and identify orthotropic elastic constants, an inverse procedure was developed by using a fabric-based elastic model for lamellar bone. The experimental indentation moduli were found to vary with the indentation direction and showed a marked anisotropy. The estimated elastic constants showed different degrees of anisotropy among secondary osteons of the same bone and these degrees of anisotropy were also found to be different than the one of cortical bone at the macroscopic level. Using the log-Euclidean norm, the relative distance between the compliance tensors of the estimated mean osteon and of cortical bone at the macroscopic level was 9.69%: Secondary osteons appeared stiffer in their axial and circumferential material directions, and with a greater bulk modulus than cortical bone, which is attributed to the absence of vascular porosity in osteonal properties. The proposed method is suitable for identification of elastic constants from nanoindentation experiments and could be adapted to other (bio)materials, for which it is possible to describe elastic properties using a fabric-based model.

Due to the inherent limitations of DXA, assessment of the biomechanical properties of vertebral bodies relies increasingly on CT-based finite element (FE) models, but these often use simplistic material behaviour and/or single loading cases. In this study, we applied a novel constitutive law for bone elasticity, plasticity and damage to FE models created from coarsened pQCT images of human vertebrae, and compared vertebral stiffness, strength and damage accumulation for axial compression, anterior flexion and a combination of these two cases. FE axial stiffness and strength correlated with experiments and were linearly related to flexion properties. In all loading modes, damage localised preferentially in the trabecular compartment. Damage for the combined loading was higher than cumulated damage produced by individual compression and flexion. In conclusion, this FE method predicts stiffness and strength of vertebral bodies from CT images with clinical resolution and provides insight into damage accumulation in various loading modes.

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]

An efficient solver for large-scale linear μ FE simulations was extended for nonlinear material behavior. The material model included damage-based tissue degradation and fracture. The new framework was applied to 20 trabecular biopsies with a mesh resolution of 36 μ m . Suitable material parameters were identified based on two biopsies by comparison with axial tension and compression experiments. The good parallel performance and low memory footprint of the solver were preserved. Excellent correlation of the maximum apparent stress was found between simulations and experiments ( R 2 > 0.97 ). The development of local damage regions was observable due to the nonlinear nature of the simulations. A novel elasticity limit was proposed based on the local damage information. The elasticity limit was found to be lower than the 0.2% yield point. Systematic differences in the yield behavior of biopsies under apparent compression and tension loading were observed. This indicates that damage distributions could lead to more insight into the failure mechanisms of trabecular bone. [ABSTRACT FROM AUTHOR]

Boundary conditions (BCs) and sample size affect the measured elastic properties of cancellous bone. Samples too small to be representative appear stiffer under kinematic uniform BCs (KUBCs) than under periodicity-compatible mixed uniform BCs (PMUBCs). To avoid those effects, we propose to determine the effective properties of trabecular bone using an embedded configuration. Cubic samples of various sizes (2.63, 5.29, 7.96, 10.58 and 15.87 mm) were cropped from $$\mu \hbox {CT}$$ scans of femoral heads and vertebral bodies. They were converted into $$\mu \hbox {FE}$$ models and their stiffness tensor was established via six uniaxial and shear load cases. PMUBCs- and KUBCs-based tensors were determined for each sample. 'In situ' stiffness tensors were also evaluated for the embedded configuration, i.e. when the loads were transmitted to the samples via a layer of trabecular bone. The Zysset-Curnier model accounting for bone volume fraction and fabric anisotropy was fitted to those stiffness tensors, and model parameters $$\nu _{0}$$ (Poisson's ratio) $$E_{0}$$ and $$\mu _{0}$$ (elastic and shear moduli) were compared between sizes. BCs and sample size had little impact on $$\nu _{0}$$ . However, KUBCs- and PMUBCs-based $$E_{0}$$ and $$\mu _{0}$$ , respectively, decreased and increased with growing size, though convergence was not reached even for our largest samples. Both BCs produced upper and lower bounds for the in situ values that were almost constant across samples dimensions, thus appearing as an approximation of the effective properties. PMUBCs seem also appropriate for mimicking the trabecular core, but they still underestimate its elastic properties (especially in shear) even for nearly orthotropic samples. [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]

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]

In the perspective of predicting mechanical from morphological properties of human trabecular bone, the theoretical and experimental relationships between volume fraction, fabric and elastic properties were reviewed.Five data sets of human trabecular bone and two data sets of idealized cells were obtained from various investigators and analyzed statistically with one isotropic and four anisotropic models. For each model, multiple linear regressions were performed to fit the components of both the compliance and the stiffness tensors using volume fraction and in some cases fabric. The adjusted coefficients of determination of the regressions and the average relative errors of the reported versus the predicted tensor norms were calculated. The three anisotropic models that implied a log transformation of the data showed the best results. Excluding the idealized cell data, the adjusted coefficients of determination of these models ranged from 0.80 to 0.95 for the compliance and from 0.80 to 0.94 for the stiffness tensors, while the average relative errors varied between 16% and 55% for the compliance and between 25% and 62% for the stiffness data. The use of volume fraction alone in the isotropic model decreased the adjusted coefficients of determination by 0.03–0.25 and increased the average relative errors by 5–27%.This review confirms the potential of morphology–elasticity relationships for estimation of elastic properties of human trabecular bone using peripheral quantitative computed tomography or magnetic resonance imaging, but emphasizes the need for standardized measurements of mechanical properties at both continuum and tissue level. [Copyright &y& Elsevier]

Titanium implants are widely used in dental and orthopedic surgeries. However, implant failures still occur because of a lack of implant stability. The biomechanical properties of bone tissue located around the implant need to be assessed to better understand the osseointegration phenomena and anticipate implant failure. The aim of this study was to explore the spatiotemporal variation of the microscopic elastic properties of newly formed bone tissue close to an implant. Eight coin-shaped Ti6Al4V implants were inserted into rabbit tibiae for 7 and 13?weeks using an in vivo model allowing the distinction between mature and newly formed bone in a standardized configuration. Nanoindentation and micro-Brillouin scattering measurements were carried out in similar locations to measure the indentation modulus and the wave velocity, from which relative variations of bone mass density were extracted. The indentation modulus, the wave velocity and mass density were found to be higher (1) in newly formed bone tissue located close to the implant surface, compared to mature cortical bone tissue, and (2) after longer healing time, consistently with an increased mineralization. Within the bone chamber, the spatial distribution of elastic properties was more heterogeneous for shorter healing durations. After 7?weeks of healing, bone tissue in the bone chamber close to the implant surface was 12.3% denser than bone tissue further away. Bone tissue close to the chamber edge was 16.8% denser than in its center. These results suggest a bone spreading pathway along tissue maturation, which is confirmed by histology and consistent with contact osteogenesis phenomena. [ABSTRACT FROM AUTHOR]

Current clinical methods of bone health assessment depend to a great extent on bone mineral density (BMD) measurements. However, these methods only act as a proxy for bone strength and are often only carried out after the fracture occurs. Besides BMD, composition and tissue-level mechanical properties are expected to affect the whole bone's strength and toughness. While the elastic properties of the bone extracellular matrix (ECM) have been extensively investigated over the past two decades, there is still limited knowledge of the yield properties and their relationship to composition and architecture. In the present study, morphological, compositional and micropillar compression bone data was collected from patients who underwent hip arthroplasty. Femoral neck samples from 42 patients were collected together with anonymous clinical information about age, sex and primary diagnosis (coxarthrosis or hip fracture). The femoral neck cortex from the inferomedial region was analyzed in a site-matched manner using a combination of micromechanical testing (nanoindentation, micropillar compression) together with micro-CT and quantitative polarized Raman spectroscopy for both morphological and compositional characterization. Mechanical properties, as well as the sample-level mineral density, were constant over age. Only compositional properties demonstrate weak dependence on patient age: decreasing mineral to matrix ratio (p = 0.02, R2 = 0.13, 2.6 % per decade) and increasing amide I sub-peak ratio I ∼ 1660 /I ∼ 1683 (p = 0.04, R2 = 0.11, 1.5 % per decade). The patient's sex and diagnosis did not seem to influence investigated bone properties. A clear zonal dependence between interstitial and osteonal cortical zones was observed for compositional and elastic bone properties (p < 0.0001). Site-matched microscale analysis confirmed that all investigated mechanical properties except yield strain demonstrate a positive correlation with the mineral fraction of bone. The output database is the first to integrate the experimentally assessed microscale yield properties, local tissue composition and morphology with the available patient clinical information. The final dataset was used for bone fracture risk prediction in-silico through the principal component analysis and the Naïve Bayes classification algorithm. The analysis showed that the mineral to matrix ratio, indentation hardness and micropillar yield stress are the most relevant parameters for bone fracture risk prediction at 70 % model accuracy (0.71 AUC). Due to the low number of samples, further studies to build a universal fracture prediction algorithm are anticipated with the higher number of patients (N > 200). The proposed classification algorithm together with the output dataset of bone tissue properties can be used for the future comparison of existing methods to evaluate bone quality as well as to form a better understanding of the mechanisms through which bone tissue is affected by aging or disease. [Display omitted] • Multimodal framework for human compact bone characterization at the microscale • First high-throughput micropillar compressions of human cortical bone • Microscale yield and elastic bone properties are nearly constant for 45–89 y.o. patients. • Only compositional properties demonstrate weak dependence on patient age. [ABSTRACT FROM AUTHOR]

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]

Osteogenesis Imperfecta (OI) is an inherited form of bone fragility characterised by impaired synthesis of type I collagen, altered trabecular bone architecture and reduced bone mass. High resolution peripheral computed tomography (HR-pQCT) is a powerful method to investigate bone morphology at peripheral sites including the weight-bearing distal tibia. The resulting 3D reconstructions can be used as a basis of micro-finite element (FE) or homogenized finite element (hFE) models for bone strength estimation. The hFE scheme uses homogenized local bone volume fraction (BV/TV) and anisotropy information (fabric) to compute healthy bone strength within a reasonable computation time using fabric-elasticity relationships. However, it is unclear if these relationships quantified previously for healthy controls are valid for trabecular bone from OI patients. Thus, the aim of this study is to investigate fabric-elasticity relationships in OI trabecular bone compared to healthy controls. In the present study, the morphology of distal tibiae from 50 adults with OI were compared to 120 healthy controls using second generation HR-pQCT. Six cubic regions of interest (ROIs) were selected per individual in a common anatomical region. A first matching between OI and healthy control group was performed by selecting similar individuals to obtain identical mean and median age and sex distribution. It allowed us to perform a first morphometric analysis and compare the outcome with literature. Then, stiffness tensors of the ROIs were computed using μFE and multiple linear regressions were performed with the Zysset-Curnier orthotropic fabric-elasticity model. An initial fit was performed on both the OI group and the healthy control group using all extracted ROIs. Then, data was filtered according to a fixed threshold for a defined coefficient of variation (CV) assessing ROI heterogeneity and additional linear regressions were performed on these filtered data sets. These full and filtered data were in turn compared with previous results from μCT reconstructions obtained in other anatomical locations. Finally, the ROIs of both groups were matched according to their BV/TV and degree of anisotropy (DA). Linear regressions were performed using these matched data to detect statistical differences between the two groups. Compared to healthy controls, we found the OI samples to have significantly lower BV/TV and trabecular number (Tb.N.), significantly higher CV, trabecular separation (Tb.Sp.) and trabecular separation standard deviation (Tb.Sp.SD), but no differences in trabecular thickness (Tb.Th.). These results are in agreement with previous studies. The stiffnesses of highly heterogeneous ROIs were randomly lower with respect to the fabric-elasticity relationships, which reflects the limit of validity of the computational homogenisation methodology. This limitation does not challenge the fabric-elasticity relationship, which extrapolation to heterogeneous ROIs is probably reasonable but can simply not be evaluated with the employed homogenisation methodology. Moreover, due to their low BV/TV, the potential (unknown) errors on these heterogeneous ROIs would have negligible influence on whole bone stiffness in comparison to homogeneous ROIs which are orders of magnitude stiffer. The filtering of highly heterogeneous ROIs removed these low stiffness ROIs and led to similar correlation coefficients for both OI and healthy groups. Finally, the BV/TV and DA matched data revealed no significant differences in fabric-elasticity parameters between OI and healthy individuals. Moreover, the filtering step did not exclude a particular OI type. Compared to previous studies, the stiffness constants from the 61 μm resolution HR-pQCT ROIs were lower than for the 36 μm resolution μCT ROIs. In conclusion, OI trabecular bone of the distal tibia was shown to be significantly more heterogeneous and have a lower BV/TV than healthy controls. Despite the reduced linear regression parameters found for HR-pQCT images, the fabric-elasticity relationships between OI and healthy individuals are similar when the trabecular bone ROIs are sufficiently homogeneous to perform the computational stiffness analysis. Accordingly, the elastic properties used for FEA of healthy bones are also valid for OI bones. [Display omitted] • Osteogenesis Imperfecta (OI) bone tissue is more mineralized compared to healthy. • OI trabecular bone presents lower bone volume fraction and higher heterogeneity. • OI trabecular architecture is not degraded for BV/TV and fabric similar to healthy. • HR-pQCT-based homogenized FE can be used for OI trabecular bone stiffness analysis. • Coarser scan resolution (HR-pQCT vs μCT) leads to lower stiffness constants. [ABSTRACT FROM AUTHOR]