Dieter H. Pahr

Improvements in vertebral body strength under teriparatide treatment assessed in vivo by finite element analysis: results from the EUROFORS study.

Monitoring of osteoporosis therapy based solely on DXA is insufficient to assess antifracture efficacy. Estimating bone strength as a variable closely linked to fracture risk is therefore of importance. Finite element (FE) analysis–based strength measures were used to monitor a teriparatide therapy and the associated effects on whole bone and local fracture risk. In 44 postmenopausal women with established osteoporosis participating in the EUROFORS study, FE models based on high‐resolution CT (HRCT) of T12 were evaluated after 0, 6, 12, and 24 mo of teriparatide treatment (20 μg/d). FE‐based strength and stiffness calculations for three different load cases (compression, bending, and combined compression and bending) were compared with volumetric BMD (vBMD) and apparent bone volume fraction (app. BV/TV), as well as DXA‐based areal BMD of the lumbar spine. Local damage of the bone tissue was also modeled. Highly significant improvements in all analyzed variables as early as 6 mo after starting teriparatide were found. After 24 mo, bone strength in compression was increased by 28.1 ± 4.7% (SE), in bending by 28.3 ± 4.9%, whereas app. BV/TV was increased by 54.7 ± 8.8%, vBMD by 19.1 ± 4.0%, and areal BMD of L1–L4 by 10.2 ± 1.2%. When comparing standardized increases, FE changes were significantly larger than those of densitometry and not significantly different from app. BV/TV. The size of regions at high risk for local failure was significantly reduced under teriparatide treatment. Treatment with teriparatide leads to bone strength increases for different loading conditions of close to 30%. FE is a suitable tool for monitoring bone anabolic treatment in groups or individual patients and offers additional information about local failure modes. FE variables showed a higher standardized response to changes than BMD measurements, but further studies are needed to show that the higher response represents a more accurate estimate of treatment‐induced fracture risk reduction.

QCT-based finite element models predict human vertebral strength in vitro significantly better than simulated DEXA

SummaryWhile dual energy X-ray absorptiometry (DXA) is considered the gold standard to evaluate fracture risk in vivo, in the present study, the quantitative computed tomography (QCT)-based finite element modeling has been found to provide a quantitative and significantly improved prediction of vertebral strength in vitro. This technique might be used in vivo considering however the much larger doses of radiation needed for QCT.IntroductionVertebral fracture is a common medical problem in osteoporotic individuals. Bone mineral density (BMD) is the gold standard measure to evaluate fracture risk in vivo. QCT-based finite element (FE) modeling is an engineering method to predict vertebral strength. The aim of this study was to compare the ability of FE and clinical diagnostic tools to predict vertebral strength in vitro using an improved testing protocol.MethodsThirty-seven vertebral sections were scanned with QCT and high resolution peripheral QCT (HR-pQCT). Bone mineral content (BMC), total BMD (tBMD), areal BMD from lateral (aBMD-lat), and anterior-posterior (aBMD-ap) projections were evaluated for both resolutions. Wedge-shaped fractures were then induced in each specimen with a novel testing setup. Nonlinear homogenized FE models (hFE) and linear micro-FE (μFE) were generated from QCT and HR-pQCT images, respectively. For experiments and models, both structural properties (stiffness, ultimate load) and material properties (apparent modulus and strength) were computed and compared.ResultsBoth hFE and μFE models predicted material properties better than structural ones and predicted strength significantly better than aBMD computed from QCT and HR-pQCT (hFE: R² = 0.79, μFE: R² = 0.88, aBMD-ap: R² = 0.48−0.47, aBMD-lat: R² = 0.41−0.43). Moreover, the hFE provided reasonable quantitative estimations of the experimental mechanical properties without fitting the model parameters.ConclusionsThe QCT-based hFE method provides a quantitative and significantly improved prediction of vertebral strength in vitro when compared to simulated DXA. This superior predictive power needs to be verified for loading conditions that simulate even more the in vivo case for human vertebrae.

Human-like hand use in Australopithecus africanus

Getting a grip The evolution of the hand—particularly the opposable thumb—was key to the success of early humans. Without a precise grip, involving forceful opposition of thumb with fingers, tool technology could not have emerged. Skinner et al. analyzed the internal bone structure of Pliocene Australopithecus hands, dated at 3.2 million years old. Internal bone structure reveals the patterns and directions of forces operating on the hand, providing clues to the kinds of activities performed. Modern human-like hand postures consistent with the habitual use of tools appeared about half a million years earlier than the first archaeological evidence of stone tools. Science, this issue p. 395 The internal bone structure of Pliocene australopiths suggests that precision grip evolved 3.2 million years ago. The distinctly human ability for forceful precision and power “squeeze” gripping is linked to two key evolutionary transitions in hand use: a reduction in arboreal climbing and the manufacture and use of tools. However, it is unclear when these locomotory and manipulative transitions occurred. Here we show that Australopithecus africanus (~3 to 2 million years ago) and several Pleistocene hominins, traditionally considered not to have engaged in habitual tool manufacture, have a human-like trabecular bone pattern in the metacarpals consistent with forceful opposition of the thumb and fingers typically adopted during tool use. These results support archaeological evidence for stone tool use in australopiths and provide morphological evidence that Pliocene hominins achieved human-like hand postures much earlier and more frequently than previously considered.

A nonlinear QCT-based finite element model validation study for the human femur tested in two configurations in vitro.

PURPOSE Femoral fracture is a common medical problem in osteoporotic individuals. Bone mineral density (BMD) is the gold standard measure to evaluate fracture risk in vivo. Quantitative computed tomography (QCT)-based homogenized voxel finite element (hvFE) models have been proved to be more accurate predictors of femoral strength than BMD by adding geometrical and material properties. The aim of this study was to evaluate the ability of hvFE models in predicting femoral stiffness, strength and failure location for a large number of pairs of human femora tested in two different loading scenarios. METHODS Thirty-six pairs of femora were scanned with QCT and total proximal BMD and BMC were evaluated. For each pair, one femur was positioned in one-legged stance configuration (STANCE) and the other in a sideways configuration (SIDE). Nonlinear hvFE models were generated from QCT images by reproducing the same loading configurations imposed in the experiments. For experiments and models, the structural properties (stiffness and ultimate load), the failure location and the motion of the femoral head were computed and compared. RESULTS In both configurations, hvFE models predicted both stiffness (R(2)=0.82 for STANCE and R(2)=0.74 for SIDE) and femoral ultimate load (R(2)=0.80 for STANCE and R(2)=0.85 for SIDE) better than BMD and BMC. Moreover, the models predicted qualitatively well the failure location (66% of cases) and the motion of the femoral head. CONCLUSIONS The subject specific QCT-based nonlinear hvFE model cannot only predict femoral apparent mechanical properties better than densitometric measures, but can additionally provide useful qualitative information about failure location.

From high-resolution CT data to finite element models: development of an integrated modular framework

New ideas for the extraction of finite element (FE) models from high-resolution computed tomography datasets are presented. The multi-step approach starts with a 3D region-growing algorithm in order to extract the outer voxel based iso-surface. This information is used to compute a voxel model of the cortical shell. The next step provides triangulated surfaces of the outer bone contour. Three-dimensional deformable models using a gradient vector flow and a multi-level mesh resampling are used. These meshes are self-regularising and of high quality. A further step contains a new self correcting cortical shell thickness evaluation algorithm, which results in topological conform smooth inner and outer compact bone iso-surface meshes. Such iso-surfaces can be used for numerically efficient FE models, which are of bio-mechanical and clinical importance. Details of the approach are described and applications with respect to a human proximal femur and vertebral body are shown.

Human-like hand-use in the hand of Australopithecus africanus

Getting a grip The evolution of the hand—particularly the opposable thumb—was key to the success of early humans. Without a precise grip, involving forceful opposition of thumb with fingers, tool technology could not have emerged. Skinner et al. analyzed the internal bone structure of Pliocene Australopithecus hands, dated at 3.2 million years old. Internal bone structure reveals the patterns and directions of forces operating on the hand, providing clues to the kinds of activities performed. Modern human-like hand postures consistent with the habitual use of tools appeared about half a million years earlier than the first archaeological evidence of stone tools. Science, this issue p. 395 The internal bone structure of Pliocene australopiths suggests that precision grip evolved 3.2 million years ago. The distinctly human ability for forceful precision and power “squeeze” gripping is linked to two key evolutionary transitions in hand use: a reduction in arboreal climbing and the manufacture and use of tools. However, it is unclear when these locomotory and manipulative transitions occurred. Here we show that Australopithecus africanus (~3 to 2 million years ago) and several Pleistocene hominins, traditionally considered not to have engaged in habitual tool manufacture, have a human-like trabecular bone pattern in the metacarpals consistent with forceful opposition of the thumb and fingers typically adopted during tool use. These results support archaeological evidence for stone tool use in australopiths and provide morphological evidence that Pliocene hominins achieved human-like hand postures much earlier and more frequently than previously considered.

A comparison of enhanced continuum FE with micro FE models of human vertebral bodies.

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 muFE 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 muFE models which are cropped from the trabecular centrums of the investigated vertebral bodies. Two different boundary conditions-kinematic [Van Rietbergen et al., 1995. 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 muFE. Taken together, the proposed enhanced homogenized surface-based FE model is structurally more accurate than density-only models.

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures

Transiliac bone biopsies, while widely considered to be the standard for the analysis of bone microstructure, are typically restricted to specialized centers. The benefit of Trabecular Bone Score (TBS) in addition to areal bone mineral density (aBMD) for fracture risk assessment has been documented in cross-sectional and prospective studies. The aim of this study was to test if TBS may be useful as a surrogate to histomorphometric trabecular parameters of transiliac bone biopsies. Transiliac bone biopsies from 80 female patients (median age 39.9 years-interquartile range, IQR 34.7; 44.3) and 43 male patients (median age 42.7 years-IQR 38.9; 49.0) with idiopathic osteoporosis and low traumatic fractures were included. Micro-computed tomography values of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structural model index (SMI) as well as serum bone turnover markers (BTMs) sclerostin, intact N-terminal type 1 procollagen propeptide (P1NP) and cross-linked C-telopeptide (CTX) were investigated. TBS values were higher in females (1.282 vs 1.169, p< 0.0001) with no differences in spine aBMD, whereas sclerostin levels (45.5 vs 33.4 pmol/L) and aBMD values at the total hip (0.989 vs 0.971 g/cm(2), p<0.001 for all) were higher in males. Multiple regression models including: gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R(2) values of 69.1% for SMI, 79.5% for Tb.N, 68.4% for Tb.Sp, and 83.3% for BV/TV. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for Tb.N. TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture and should be implemented as an additional tool for the determination of trabecular bone properties.

Finite element analysis for prediction of bone strength.

Finite element (FE) analysis has been applied for the past 40 years to simulate the mechanical behavior of bone. Although several validation studies have been performed on specific anatomical sites and load cases, this study aims to review the predictability of human bone strength at the three major osteoporotic fracture sites quantified in recently completed in vitro studies at our former institute. Specifically, the performance of FE analysis based on clinical computer tomography (QCT) is compared with the ones of the current densitometric standards, bone mineral content, bone mineral density (BMD) and areal BMD (aBMD). Clinical fractures were produced in monotonic axial compression of the distal radii, vertebral sections and in side loading of the proximal femora. QCT-based FE models of the three bones were developed to simulate as closely as possible the boundary conditions of each experiment. For all sites, the FE methodology exhibited the lowest errors and the highest correlations in predicting the experimental bone strength. Likely due to the improved CT image resolution, the quality of the FE prediction in the peripheral skeleton using high-resolution peripheral CT was superior to that in the axial skeleton with whole-body QCT. Because of its projective and scalar nature, the performance of aBMD in predicting bone strength depended on loading mode and was significantly inferior to FE in axial compression of radial or vertebral sections but not significantly inferior to FE in side loading of the femur. Considering the cumulated evidence from the published validation studies, it is concluded that FE models provide the most reliable surrogates of bone strength at any of the three fracture sites.

A nonlinear finite element model validation study based on a novel experimental technique for inducing anterior wedge-shape fractures in human vertebral bodies in vitro

Vertebral compression fracture is a common medical problem in osteoporotic individuals. The quantitative computed tomography (QCT)-based finite element (FE) method may be used to predict vertebral strength in vivo, but needs to be validated with experimental tests. The aim of this study was to validate a nonlinear anatomy specific QCT-based FE model by using a novel testing setup. Thirty-seven human thoracolumbar vertebral bone slices were prepared by removing cortical endplates and posterior elements. The slices were scanned with QCT and the volumetric bone mineral density (vBMD) was computed with the standard clinical approach. A novel experimental setup was designed to induce a realistic failure in the vertebral slices in vitro. Rotation of the loading plate was allowed by means of a ball joint. To minimize device compliance, the specimen deformation was measured directly on the loading plate with three sensors. A nonlinear FE model was generated from the calibrated QCT images and computed vertebral stiffness and strength were compared to those measured during the experiments. In agreement with clinical observations, most of the vertebrae underwent an anterior wedge-shape fracture. As expected, the FE method predicted both stiffness and strength better than vBMD (R(2) improved from 0.27 to 0.49 and from 0.34 to 0.79, respectively). Despite the lack of fitting parameters, the linear regression of the FE prediction for strength was close to the 1:1 relation (slope and intercept close to one (0.86 kN) and to zero (0.72 kN), respectively). In conclusion, a nonlinear FE model was successfully validated through a novel experimental technique for generating wedge-shape fractures in human thoracolumbar vertebrae.