Developing and Validating a Model of Humeral Stem Primary Stability, Intended for In Silico Clinical Trials.

In silico clinical trials (ISCT) can contribute to demonstrating a device's performance via credible computational models applied on virtual cohorts. Our purpose was to establish the credibility of a model for assessing the risk of humeral stem loosening in total shoulder arthroplasty, based on a twofold validation scheme involving both benchtop and clinical validation activities, for ISCT applications. A finite element model computing bone-implant micromotion (benchtop model) was quantitatively compared to a bone foam micromotion test (benchtop comparator) to ensure that the physics of the system was captured correctly. The model was expanded to a population-based approach (clinical model) and qualitatively evaluated based on its ability to replicate findings from a published clinical study (clinical comparator), namely that grit-blasted stems are at a significantly higher risk of loosening than porous-coated stems, to ensure that clinical performance of the stem can be predicted appropriately. Model form sensitivities pertaining to surgical variation and implant design were evaluated. The model replicated benchtop micromotion measurements (52.1 ± 4.3 µm), without a significant impact of the press-fit ("Press-fit": 54.0 ± 8.5 µm, "No press-fit": 56.0 ± 12.0 µm). Applied to a virtual population, the grit-blasted stems (227 ± 78µm) experienced significantly larger micromotions than porous-coated stems (162 ± 69µm), in accordance with the findings of the clinical comparator. This work provides a concrete example for evaluating the credibility of an ISCT study. By validating the modeling approach against both benchtop and clinical data, model credibility is established for an ISCT application aiming to enrich clinical data in a regulatory submission.

[Enriching in vivo clinical trials with in silico models for orthopedic implants]. / Enrichissement des essais cliniques par simulations numériques - L'exemple des prothèses orthopédiques1.

Clinical trials are used by the medical device industry to confirm products safety, performance, and clinical benefits. Traditional clinical studies typically follow a limited number of volunteers, which prevents capturing the full breath of patient demographics and implant use. New tools are required to overcome the limitations of traditional trials while fulfilling increasingly demanding regulatory requirements. Computer simulations have the potential to enrich traditional clinical trials with so called in silico clinical trials (ISCT) by providing data on a much broader spectrum of patients, clinical conditions and implant configurations. The historical use of simulation in the orthopedic device industry is described here to explain how it is now technically possible to model virtual populations. We also discuss the multiple benefits of such a translational research approach for the patients, healthcare systems, and manufacturers, but also the challenges to overcome. A more detailed version is available in English [1].

TITLE: Enrichissement des essais cliniques par simulations numériques - L'exemple des prothèses orthopédiques1. ABSTRACT: Les fabricants de dispositifs médicaux doivent démontrer, bien souvent au moyen d'essais cliniques, la sécurité, la performance et les avantages cliniques de leurs produits. Pour pallier les limitations des essais cliniques traditionnels, tout en satisfaisant des exigences réglementaires devenues plus strictes, des données supplémentaires peuvent être acquises par le biais de simulations informatiques. Dans cette revue, l'utilisation de la simulation sera mise en perspective afin d'expliquer comment, à partir de l'exemple de l'industrie des prothèses orthopédiques, il est désormais techniquement possible de modéliser des populations virtuelles de patients. Nous décrivons ainsi les multiples avantages de cette approche de recherche translationnelle, ainsi que les défis qui restent à relever.

In Silico Clinical Trials in the Orthopedic Device Industry: From Fantasy to Reality?

The orthopedic device industry relies heavily on clinical evaluation to confirm the safety, performance, and clinical benefits of its implants. Limited sample size often prevents these studies from capturing the full spectrum of patient variability and real-life implant use. The device industry is accustomed to simulating benchtop tests with numerical methods and recent developments now enable virtual "in silico clinical trials" (ISCT). In this article, we describe how the advancement of computer modeling has naturally led to ISCT; outline the potential benefits of ISCT to patients, healthcare systems, manufacturers, and regulators; and identify how hurdles associated with ISCT may be overcome. In particular, we highlight a process for defining the relevant patient risks to address with ISCT, the utility of a versatile software pipeline, the necessity to ensure model credibility, and the goal of limiting regulatory uncertainty. By complementing-not replacing-traditional clinical trials with computational evidence, ISCT provides a viable technical and regulatory strategy for characterizing the full spectrum of patients, clinical conditions, and configurations that are embodied in contemporary orthopedic implant systems.

Conventional finite element models estimate the strength of metastatic human vertebrae despite alterations of the bone's tissue and structure.

INTRODUCTION: Pathologic vertebral fractures are a major clinical concern in the management of cancer patients with metastatic spine disease. These fractures are a direct consequence of the effect of bone metastases on the anatomy and structure of the vertebral bone. The goals of this study were twofold. First, we evaluated the effect of lytic, blastic and mixed (both lytic and blastic) metastases on the bone structure, on its material properties, and on the overall vertebral strength. Second, we tested the ability of bone mineral content (BMC) measurements and standard FE methodologies to predict the strength of real metastatic vertebral bodies. METHODS: Fifty-seven vertebral bodies from eleven cadaver spines containing lytic, blastic, and mixed metastatic lesions from donors with breast, esophageal, kidney, lung, or prostate cancer were scanned using micro-computed tomography (µCT). Based on radiographic review, twelve vertebrae were selected for nanoindentation testing, while the remaining forty-five vertebrae were used for assessing their compressive strength. The µCT reconstruction was exploited to measure the vertebral BMC and to establish two finite element models. 1) a micro finite element (µFE) model derived at an image resolution of 24.5 µm and 2) homogenized FE (hFE) model derived at a resolution of 0.98 mm. Statistical analyses were conducted to measure the effect of the bone metastases on BV/TV, indentation modulus (Eit), ratio of plastic/total work (WPl/Wtot), and in vitro vertebral strength (Fexp). The predictive value of BMC, µFE stiffness, and hFE strength were evaluated against the in vitro measurements. RESULTS: Blastic vertebral bodies exhibit significantly higher BV/TV compared to the mixed (p = 0.0205) and lytic (p = 0.0216) vertebral bodies. No significant differences were found between lytic and mixed vertebrae (p = 0.7584). Blastic bone tissue exhibited a 5.8% lower median Eit (p< 0.001) and a 3.3% lower median Wpl/Wtot (p<0.001) compared to non-involved bone tissue. No significant differences were measured between lytic and non-involved bone tissues. Fexp ranged from 1.9 to 13.8 kN, was strongly associated with hFE strength (R2=0.78, p< 0.001) and moderately associated with BMC (R2=0.66, p< 0.001) and µFE stiffness (R2=0.66, p< 0.001), independently of the lesion type. DISCUSSION: Our findings show that tumour-induced osteoblastic metastases lead to slightly, but significantly lower bone tissue properties compared to controls, while osteolytic lesions appear to have a negligible impact. These effects may be attributed to the lower mineralization and woven nature of bone forming in blastic lesions whilst the material properties of bone in osteolytic vertebrae appeared little changed. The moderate association between BMC- and FE-based predictions to fracture strength suggest that vertebral strength is affected by the changes of bone mass induced by the metastatic lesions, rather than altered tissue properties. In a broader context, standard hFE approaches generated from CTs at clinical resolution are robust to the lesion type when predicting vertebral strength. These findings open the door for the development of FE-based prediction tools that overcomes the limitations of BMC in accounting for shape and size of the metastatic lesions. Such tools may help clinicians to decide whether a patient needs the prophylactic fixation of an impending fracture.

Finite element models can reproduce the effect of nucleotomy on the multi-axial compliance of human intervertebral discs.

Finite element (FE) models can unravel the link between intervertebral disc (IVD) degeneration and its mechanical behaviour. Nucleotomy may provide the data required for model verification. Three human IVDs were scanned with MRI and tested in multiple loading scenarios, prior and post nucleotomy. The resulting data was used to generate, calibrate, and verify the FE models. Nucleotomy increased the experimental range of motion by 26%, a result reproduced by the FE simulation within a 5% error. This work demonstrates the ability of FE models to reproduce the mechanical compliance of human IVDs prior and post nucleotomy.

"Peroperative estimation of bone quality and primary dental implant stability".

OBJECTIVES: Dental implants are widely used to restore function and appearance. It may be essential to choose the appropriate drilling protocol and implant design in order to optimise primary stability. This could be achieved based on an assessment of the implantation site with respect to bone quality and objective biomechanical descriptors such as stiffness and strength of the bone-implant system. The aim of this ex vivo study is to relate these descriptors with bone quality, with a pre-implantation indicator of implant stability: pilot-hole drilling force (Fdrilling), and with two post-implantation indicators: maximal implantation torque (Timplantation) and resonance frequency analysis (RFA). METHODS: Eighty trabecular bone specimens were cored from human vertebrae and bovine tibiae. Bone volume fraction (BV/TV), a representative for bone quality, was obtained through micro-computed tomography scans. Implants were kept in controlled laboratory conditions following standard surgical procedures. Forces and torques were recorded and RFA was assessed after implantation. Off-axis compression tests were conducted on the implants until failure. Implant stability was identified by stiffness and ultimate force (Fultimate). The relationships between BV/TV, Stiffness, Fultimate and Fdrilling, Timplantation, RFA were established. RESULTS: Fdrilling correlated well with BV/TV of the implantation site (r2 = 0.81), stiffness (r2 = 0.75) and Fultimate (r2 = 0.80). Timplantation correlated better with stiffness (r2 = 0.86) and Fultimate (r2 = 0.94) than RFA (r2 = 0.77 and r2 = 0.74, respectively). CONCLUSION: Our results indicate that BV/TV and bone-implant stability can be directly estimated by the force needed for the pilot drilling that occurs during the site preparation before implantation. Moreover, implantation torque outperforms RFA for evaluating the mechanical competence of the bone-implant system.

Supervised learning for bone shape and cortical thickness estimation from CT images for finite element analysis.

Knowledge about the thickness of the cortical bone is of high interest for fracture risk assessment. Most finite element model solutions overlook this information because of the coarse resolution of the CT images. To circumvent this limitation, a three-steps approach is proposed. 1) Two initial surface meshes approximating the outer and inner cortical surfaces are generated via a shape regression based on morphometric features and statistical shape model parameters. 2) The meshes are then corrected locally using a supervised learning model build from image features extracted from pairs of QCT (0.3-1 mm resolution) and HRpQCT images (82 µm resolution). As the resulting meshes better follow the cortical surfaces, the cortical thickness can be estimated at sub-voxel precision. 3) The meshes are finally regularized by a Gaussian process model featuring a two-kernel model, which seamlessly enables smoothness and shape-awareness priors during regularization. The resulting meshes yield high-quality mesh element properties, suitable for construction of tetrahedral meshes and finite element simulations. This pipeline was applied to 36 pairs of proximal femurs (17 males, 19 females, 76 ±â€¯12 years) scanned under QCT and HRpQCT modalities. On a set of leave-one-out experiments, we quantified accuracy (root mean square error = 0.36 ±â€¯0.29 mm) and robustness (Hausdorff distance = 3.90 ±â€¯1.57 mm) of the outer surface meshes. The error in the estimated cortical thickness (0.05 ±â€¯0.40 mm), and the tetrahedral mesh quality (aspect ratio = 1.4 ±â€¯0.02) are also reported. The proposed pipeline produces finite element meshes with patient-specific bone shape and sub-voxel cortical thickness directly from CT scans. It also ensures that the nodes and elements numbering remains consistent and independent of the morphology, which is a distinct advantage in population studies.

Variogram-based evaluations of DXA correlate with vertebral strength, but do not enhance the prediction compared to aBMD alone.

Ancillary evaluation of spinal Dual-energy X-ray Absorptiometry (DXA) via variogram-based texture evaluation (e.g., Trabecular Bone Score) is used for improving the fracture risk assessment, despite no proven relationship with vertebral strength. The purpose of this study was thus to determine whether classical variogram-based parameters (sill variance and correlation length) evaluated from simulated DXA scans could help predicting the in vitro vertebral strength. Experimental data of thirteen human full vertebrae (i.e., with posterior elements) and twelve vertebral bodies were obtained from two existing studies. Areal bone mineral density (aBMD) was calculated from 2D projection images of the 3D HR-pQCT scan of the specimens mimicking clinical DXA scans. Stochastic predictors, sill variance and correlation length, were calculated from their experimental variogram. Vertebral strength was measured as the maximum failure load of human vertebrae and vertebral bodies from mechanical tests. Vertebral strength correlated significantly with sill variance (r = 0.727) and correlation length (r = 0.727) for the vertebral bodies, and with correlation length (r = 0.593) for full vertebrae. However, the stochastic predictors improved the strength prediction made by aBMD alone by only 11% for the vertebral bodies while no improvement was observed for the full vertebrae. Despite a correlation, classical variogram parameters such as sill variance and correlation length do not enhance the prediction of in vitro vertebral strength beyond aBMD. It remains unclear why some variogram-based evaluations of DXA improve fracture prediction without a proven relationship with vertebral strength.

Integrating MRI-based geometry, composition and fiber architecture in a finite element model of the human intervertebral disc.

Intervertebral disc degeneration is a common disease that is often related to impaired mechanical function, herniations and chronic back pain. The degenerative process induces alterations of the disc's shape, composition and structure that can be visualized in vivo using magnetic resonance imaging (MRI). Numerical tools such as finite element analysis (FEA) have the potential to relate MRI-based information to the altered mechanical behavior of the disc. However, in terms of geometry, composition and fiber architecture, current FE models rely on observations made on healthy discs and might therefore not be well suited to study the degeneration process. To address the issue, we propose a new, more realistic FE methodology based on diffusion tensor imaging (DTI). For this study, a human disc joint was imaged in a high-field MR scanner with proton-density weighted (PD) and DTI sequences. The PD image was segmented and an anatomy-specific mesh was generated. Assuming accordance between local principal diffusion direction and local mean collagen fiber alignment, corresponding fiber angles were assigned to each element. Those element-wise fiber directions and PD intensities allowed the homogenized model to smoothly account for composition and fibrous structure of the disc. The disc's in vitro mechanical behavior was quantified under tension, compression, flexion, extension, lateral bending and rotation. The six resulting load-displacement curves could be replicated by the FE model, which supports our approach as a first proof of concept towards patient-specific disc modeling.

Estimation of the effective yield properties of human trabecular bone using nonlinear micro-finite element analyses.

Micro-finite element ([Formula: see text]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 [Formula: see text]CT reconstructions of human vertebrae and femora and converted into [Formula: see text]FE models. An isotropic elasto-plastic material model was chosen for bone tissue, and nonlinear [Formula: see text]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.

µCT-based trabecular anisotropy can be reproducibly computed from HR-pQCT scans using the triangulated bone surface.

The trabecular structure can be assessed at the wrist or tibia via high-resolution peripheral quantitative computed tomography (HR-pQCT). Yet on this modality, the performance of the existing methods, evaluating trabecular anisotropy is usually overlooked, especially in terms of reproducibility. We thus proposed to compare the TRI routine used by SCANCO Medical AG (Brüttisellen, Switzerland), the classical mean intercept length (MIL), and the grey-level structure tensor (GST) to the mean surface length (MSL), a new method for evaluating a second-order fabric tensor based on the triangulation of the bone surface. The distal radius of 24 fresh-frozen human forearms was scanned three times via HR-pQCT protocols (61µm, 82µm nominal voxel size), dissected, and imaged via micro computed tomography (µCT) at 16µm nominal voxel size. After registering the scans, we compared for each resolution the fabric tensors, determined by the mentioned techniques for 182 trabecular regions of interest. We then evaluated the reproducibility of the fabric information measured by HR-pQCT via precision errors. On µCT, TRI and GST were respectively the best and worst surrogates for MILµCT (MIL computed on µCT) in terms of eigenvalues and main direction of anisotropy. On HR-pQCT, however, MSL provided the best approximation of MILµCT. Surprisingly, surface-based approaches (TRI, MSL) also proved to be more precise than both MIL and GST. Our findings confirm that MSL can reproducibly estimate MILµCT, the current gold standard. MSL thus enables the direct mapping of the fabric-dependent material properties required in homogenised HR-pQCT-based finite element models.

Not only stiffness, but also yield strength of the trabecular structure determined by non-linear µFE is best predicted by bone volume fraction and fabric tensor.

The micro-architecture of cancellous bone is considered a major determinant of the fracture risk. Yet, if morphometry tells about alterations of the trabecular network, its elastic behaviour is best described by bone volume fraction (BV/TV) and the fabric tensor, which gives the anisotropy of the trabecular structure. This remains to be proven for yield strength, the onset of bone failure. The microstructure of 126 samples extracted from femoral heads of two female subjects was evaluated on micro-computed tomography scans via 25 structural indices. Parameters such as plate and rod decomposition via ITS and textural analyses by ISV, similar to the trabecular bone score, were also examined. The degree of collinearity between indices was assessed. The indices considered sufficiently independent were included in multi-linear regression models predicting stiffness or yield strength measured via nonlinear micro finite element analyses. The models' accuracy was checked and the contributions of all explanatory variables to the prediction were compared. Our results show that BV/TV alone explained most of the predicted yield strength (76%) and stiffness (89%). BV/TV together with the fabric tensor explained more than 98% of both measures! The fabric tensor also had a larger impact on yield strength (23%) than on the stiffness predictions (9%). On the other hand, the predictive value of the other independent factors (Tb.Th.SD, Tb.Sp.SD, rTb.Th, RR.Junc.D, ISV) was negligible (<1%). In conclusion, just as stiffness, yield strength of femoral trabecular bone is also best explained by BV/TV and trabecular anisotropy, the latter being even more relevant in its post-elastic behaviour.

The effective elastic properties of human trabecular bone may be approximated using micro-finite element analyses of embedded volume elements.

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 [Formula: see text] scans of femoral heads and vertebral bodies. They were converted into [Formula: see text] 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 [Formula: see text] (Poisson's ratio) [Formula: see text] and [Formula: see text] (elastic and shear moduli) were compared between sizes. BCs and sample size had little impact on [Formula: see text]. However, KUBCs- and PMUBCs-based [Formula: see text] and [Formula: see text], 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.

Head-Neck Osteoplasty has Minor Effect on the Strength of an Ovine Cam-FAI Model: In Vitro and Finite Element Analyses.

BACKGROUND: Osteochondroplasty of the head-neck region is performed on patients with cam femoroacetabular impingement (FAI) without fully understanding its repercussion on the integrity of the femur. Cam-type FAI can be surgically and reproducibly induced in the ovine femur, which makes it suitable for studying corrective surgery in a consistent way. Finite element models built on quantitative CT (QCT) are computer tools that can be used to predict femoral strength and evaluate the mechanical effect of surgical correction. QUESTIONS/PURPOSES: We asked: (1) What is the effect of a resection of the superolateral aspect of the ovine femoral head-neck junction on failure load? (2) How does the failure load after osteochondroplasty compare with reported forces from activities of daily living in sheep? (3) How do failure loads and failure locations from the computer simulations compare with the experiments? METHODS: Osteochondroplasties (3, 6, 9 mm) were performed on one side of 18 ovine femoral pairs with the contralateral intact side as a control. The 36 femurs were scanned via QCT from which specimen-specific computer models were built. Destructive compression tests then were conducted experimentally using a servohydraulic testing system and numerically via the computer models. Safety factors were calculated as the ratio of the maximal force measured in vivo by telemeterized hip implants during the sheep's walking and running activities to the failure load. The simulated failure loads and failure locations from the computer models were compared with the experimental results. RESULTS: Failure loads were reduced by 5% (95% CI, 2%-8%) for the 3-mm group (p = 0.0089), 10% (95% CI, 6%-14%) for the 6-mm group (p = 0.0015), and 19% (95% CI, 13%-26%) for the 9-mm group (p = 0.0097) compared with the controls. Yet, the weakest specimen still supported more than 2.4 times the peak load during running. Strong correspondence was found between the simulated and experimental failure loads (R2 = 0.83; p < 0.001) and failure locations. CONCLUSIONS: The resistance of ovine femurs to fracture decreased with deeper resections. However, under in vitro testing conditions, the effect on femoral strength remains small even after 9 mm correction, suggesting that femoral head-neck osteochondroplasty could be done safely on the ovine femur. QCT-based finite element models were able to predict weakening of the femur resulting from the osteochondroplasty. CLINICAL RELEVANCE: The ovine femur provides a seemingly safe platform for scientific evaluation of FAI. It also appears that computer models based on preoperative CT scans may have the potential to provide patient-specific guidelines for preventing overcorrection of cam FAI.

Identification of elastic properties of human patellae using micro-finite element analysis.

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 (5.3mm 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.

The Initial Slope of the Variogram, Foundation of the Trabecular Bone Score, Is Not or Is Poorly Associated With Vertebral Strength.

Trabecular bone score (TBS) rests on the textural analysis of dual-energy X-ray absorptiometry (DXA) to reflect the decay in trabecular structure characterizing osteoporosis. Yet, its discriminative power in fracture studies remains incomprehensible because prior biomechanical tests found no correlation with vertebral strength. To verify this result possibly owing to an unrealistic setup and to cover a wide range of loading scenarios, the data from three previous biomechanical studies using different experimental settings were used. They involved the compressive failure of 62 human lumbar vertebrae loaded 1) via intervertebral discs to mimic the in vivo situation ("full vertebra"); 2) via the classical endplate embedding ("vertebral body"); or 3) via a ball joint to induce anterior wedge failure ("vertebral section"). High-resolution peripheral quantitative computed tomography (HR-pQCT) scans acquired from prior testing were used to simulate anterior-posterior DXA from which areal bone mineral density (aBMD) and the initial slope of the variogram (ISV), the early definition of TBS, were evaluated. Finally, the relation of aBMD and ISV with failure load (F(exp)) and apparent failure stress (σexp) was assessed, and their relative contribution to a multilinear model was quantified via ANOVA. We found that, unlike aBMD, ISV did not significantly correlate with F(exp) and σexp , except for the "vertebral body" case (r(2) = 0.396, p = 0.028). Aside from the "vertebra section" setup where it explained only 6.4% of σexp (p = 0.037), it brought no significant improvement to aBMD. These results indicate that ISV, a replica of TBS, is a poor surrogate for vertebral strength no matter the testing setup, which supports the prior observations and raises a fortiori the question of the deterministic factors underlying the statistical relationship between TBS and vertebral fracture risk.

Finite element analysis predicts experimental failure patterns in vertebral bodies loaded via intervertebral discs up to large deformation.

Vertebral compression fractures are becoming increasingly common. Patient-specific nonlinear finite element (FE) models have shown promise in predicting yield strength and damage pattern but have not been experimentally validated for clinically relevant vertebral fractures, which involve loading through intervertebral discs with varying degrees of degeneration up to large compressive strains. Therefore, stepwise axial compression was applied in vitro on segments and performed in silico on their FE equivalents using a nonlocal damage-plastic model including densification at large compression for bone and a time-independent hyperelastic model for the disc. The ability of the nonlinear FE models to predict the failure pattern in large compression was evaluated for three boundary conditions: healthy and degenerated intervertebral discs and embedded endplates. Bone compaction and fracture patterns were predicted using the local volume change as an indicator and the best correspondence was obtained for the healthy intervertebral discs. These preliminary results show that nonlinear finite element models enable prediction of bone localisation and compaction. To the best of our knowledge, this is the first study to predict the collapse of osteoporotic vertebral bodies up to large compression using realistic loading via the intervertebral discs.

Bone volume fraction and fabric anisotropy are better determinants of trabecular bone stiffness than other morphological variables.

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.

Compressive strength of elderly vertebrae is reduced by disc degeneration and additional flexion.

Computer tomography (CT)-based finite element (FE) models assess vertebral strength better than dual energy X-ray absorptiometry. Osteoporotic vertebrae are usually loaded via degenerated intervertebral discs (IVD) and potentially at higher risk under forward bending, but the influences of the IVD and loading conditions are generally overlooked. Accordingly, magnetic resonance imaging was performed on 14 lumbar discs to generate FE models for the healthiest and most degenerated specimens. Compression, torsion, bending, flexion and extension conducted experimentally were used to calibrate both models. They were combined with CT-based FE models of 12 lumbar vertebral bodies to evaluate the effect of disc degeneration compared to a loading via endplates embedded in a stiff resin, the usual experimental paradigm. Compression and lifting were simulated, load and damage pattern were evaluated at failure. Adding flexion to the compression (lifting) and higher disc degeneration reduces the failure load (8-14%, 5-7%) and increases damage in the vertebrae. Under both loading scenarios, decreasing the disc height slightly increases the failure load; embedding and degenerated IVD provides respectively the highest and lowest failure load. Embedded vertebrae are more brittle, but failure loads induced via IVDs correlate highly with vertebral strength. In conclusion, osteoporotic vertebrae with degenerated IVDs are consistently weaker-especially under lifting, but clinical assessment of their strength is possible via FE analysis without extensive disc modelling, by extrapolating measures from the embedded situation.

Finite element analyses of human vertebral bodies embedded in polymethylmethalcrylate or loaded via the hyperelastic intervertebral disc models provide equivalent predictions of experimental strength.

Quantitative computer tomography (QCT)-based finite element (FE) models of vertebral body provide better prediction of vertebral strength than dual energy X-ray absorptiometry. However, most models were validated against compression of vertebral bodies with endplates embedded in polymethylmethalcrylate (PMMA). Yet, loading being as important as bone density, the absence of intervertebral disc (IVD) affects the strength. Accordingly, the aim was to assess the strength predictions of the classic FE models (vertebral body embedded) against the in vitro and in silico strengths of vertebral bodies loaded via IVDs. High resolution peripheral QCT (HR-pQCT) were performed on 13 segments (T11/T12/L1). T11 and L1 were augmented with PMMA and the samples were tested under a 4° wedge compression until failure of T12. Specimen-specific model was generated for each T12 from the HR-pQCT data. Two FE sets were created: FE-PMMA refers to the classical vertebral body embedded model under axial compression; FE-IVD to their loading via hyperelastic IVD model under the wedge compression as conducted experimentally. Results showed that FE-PMMA models overestimated the experimental strength and their strength prediction was satisfactory considering the different experimental set-up. On the other hand, the FE-IVD models did not prove significantly better (Exp/FE-PMMA: R²=0.68; Exp/FE-IVD: R²=0.71, p=0.84). In conclusion, FE-PMMA correlates well with in vitro strength of human vertebral bodies loaded via real IVDs and FE-IVD with hyperelastic IVDs do not significantly improve this correlation. Therefore, it seems not worth adding the IVDs to vertebral body models until fully validated patient-specific IVD models become available.