Mechanical Behavior Of Bone Research Articles

Mechanics of Mineralized Collagen Fibrils upon Transient Loads.

Collagen is a key structural protein in the human body, which undergoes mineralization during the formation of hard tissues. Earlier studies have described the mechanical behavior of bone at different scales, highlighting material features across hierarchical structures. Here we present a study that aims to understand the mechanical properties of mineralized collagen fibrils upon tensile/compressive transient loads, investigating how the kinetic energy propagates and it is dissipated at the molecular scale, thus filling a gap of knowledge in this area. These specific features are the mechanisms that nature has developed to passively dissipate stress and prevent structural failures. In addition to the mechanical properties of the mineralized fibrils, we observe distinct nanomechanical behaviors for the two regions (i.e., overlap and gap) of the D-period to highlight the effect of the mineralization. We notice decreasing trends for both wave speeds and Young's moduli over input velocity with a marked strengthening effect in the gap region due to the accumulation of the hydroxyapatite. In contrast, the dissipative behavior is not affected by either loading conditions or the mineral percentage, showing a stronger damping effect upon faster inputs compatible to the bone behavior at the macroscale. Our results offer insights into the dissipative behavior of mineralized collagen composites to design and characterize bioinspired composites for replacement devices (e.g., prostheses for sound transmission or conduction) or optimized structures able to bear transient loads, for example, impact, fatigue, in structural applications.

Anisotropic elastic properties of human cortical bone tissue inferred from inverse homogenization and resonant ultrasound spectroscopy

Bone extravascular matrix (EVM) elasticity at several tens micrometer scale plays a key role in the mechanical behavior of bone at different length scales with implications on bone biology through mechanotransduction. The elastic properties of cortical bone EVM have been evaluated by several experimental methods, including nanoindentation, scanning acoustic microscopy (SAM) and mechanical testing on µm sized bone specimens. Nevertheless, these methods hardly give access to elastic anisotropy. In this work, we propose a novel inverse homogenization method to evaluate the anisotropic elastic properties of cortical bone EVM based on the transverse isotropic elastic tensor of millimeter-sized bone specimens measured by using resonant ultrasound spectroscopy and Fast Fourier Transform homogenization method. With the inverse homogenization method, the anisotropic EVM stiffness constants were evaluated on 50 human femoral cortical bone specimens from an elderly group. To our knowledge, this is the first time that the whole set of the EVM stiffness tensor is evaluated on the same specimen and on a large number of samples. Further comparison with the results from SAM and the degree of mineralization of bone (DMB) showed the potential of this method. Empirical laws between DMB and EVM anisotropic stiffness constants were also provided for the first time. With the anisotropic elasticity evaluated by the proposed method, more accurate models can be developed to better understand bone mechanics and biology, such as mechanotransduction.

Application of an enhanced homogenization technique to the structural multiscale analysis of a femur bone

Bone is a complex hierarchical material that can be characterized from the microscale to macroscale. This work demonstrates the application of an enhanced homogenization methodology to the multiscale structural analysis of a femoral bone. The use of this homogenization technique allows to remove subjectivity and reduce the computational cost associated with the iterative process of creating a heterogeneous mesh. Thus, it allows to create simpler homogenized meshes with its mechanical properties defined using information directly from the mesh source: the medical images. Therefore, this methodology is capable to accurately predict bone mechanical behavior in a fraction of the time required by classical approaches. The results show that using the homogenization technique, despite the differences between the used homogeneous and heterogeneous meshes, its mechanical behavior is similar. The proposed homogenization technique is useful for a multiscale modelling and it is computationally efficient.

Increasing fluoride content deteriorates rat bone mechanical properties.

Elevation of bone fluoride levels due to drinking beverages with high fluoride content or other means such as inhalation can result in skeletal fluorosis and lead to increased joint pain, skeletal deformities, and fracture. Because skeletal fluorosis alters bone's mineral composition, it is likely to affect bone's tissue-level mechanical properties with consequent effects on whole bone mechanical behavior. To investigate this, we determined whether incubation with in vitro sodium fluoride (NaF) altered bone's mechanical behavior at both the tissue- and whole bone-levels using cyclic reference point indentation (cRPI) and traditional 3-point bending, respectively. Forty-two ulnas from female adult rats (5-6months) were randomly divided into 5 groups (vehicle, 0.05M NaF, 0.25M NaF, 0.75M NaF, and 1.5M NaF). Bones were washed in a detergent solution to remove organic barriers to ion exchange and incubated in respective treatment solutions (12h, 23°C). Cortical tissue mineral density (TMD) and geometry at the mid-diaphysis were determined by microCT. cRPI was performed on the distal diaphysis (9N, 2Hz, 10cycles), and then bones were tested in 3-point bending to assess whole bone mechanical properties. The incubations in vehicle (0M) up to 1.5M in vitro NaF concentrations achieved bone fluoride levels ranging from approximately 0.70 to 15.8ppm. NaF-incubated bones had significantly greater indentation distances, higher displacement-to-maximum force, and lower estimated elastic modulus, ultimate stress, and bending rigidity with increasing NaF concentration compared to vehicle-incubated bones. cRPI variables were moderately correlated to whole bone mechanical properties such that higher indentation distances were associated with lower estimated elastic modulus, ultimate stress, and bending rigidity. In conclusion, in vitro NaF incubation mostly has a deleterious effect on bone mechanical behavior with increasing NaF levels that is independent of bone turnover and reflected, in part, by less resistance of the tissue to cRPI-based indentation.

The Paradox of Fragile but Dense Bones in Type 2 Diabetes

Epidemiologic evidence from the past decade has demonstrated that increased bone fracture risk is one of the myriad clinical complications of type 2 diabetes mellitus (T2DM). Counterintuitively, the increased fracture risk in T2DM occurs despite greater bone mineral density, and persists after accounting for potential confounders like body mass index, neuropathies, and falls. Therefore, T2DM may alter aspects of bone’s intrinsic resistance to fracture beyond bone mineral density, such as material properties or microarchitecture, thereby increasing bone fragility independently of bone mass. Although the mechanisms that underlie bone fragility in T2DM are not yet well established, a multiplicity of factors, including hyperglycemia, altered bone remodeling, and non‐enzymatic collagen crosslinking in the bone matrix are implicated. In this work we elucidate the factors that influence fragility in T2DM by characterizing the biochemical, material, microarchitectural, and mechanical properties of bone from a clinical population of men with and without T2DM. The cancellous bone from patients with T2DM had greater concentrations of the advanced glycation endproduct pentosidine and sugars bound to the collagen matrix, had greater mineral content, and trended toward a greater bone volume fraction than the non‐DM specimens. Surprisingly, the T2DM specimens had similar strength and toughness as those from non‐DM controls. Regression modeling of the mechanical outcomes revealed competing effects of T2DM on bone mechanical behavior. The trend toward greater bone volume fraction and greater mineral content of the T2DM specimens increased strength, while the greater concentrations of pentosidine in the T2DM group increased brittleness. These data suggest that high concentrations of AGEs can increase fragility by reducing the ability of bone to absorb energy prior to failure, especially for the subset of T2DM patients with low bone volume fraction. Further, our model shows that an increase in bone volume fraction offers a protective effect for T2DM patients, even with the inferior intrinsic quality of the T2DM bone, whereas loss of bone volume fraction substantially increases risk of bone fragility for T2DM patients. The primary clinical implications of these findings are that preservation of bone volume fraction is critical in patients with T2DM.Support or Funding InformationSupported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01 AR064314)

Anisotropic computational modelling of bony structures from CT data: An almost automatic procedure

Background and objectiveThe use of modelling techniques that combine CT data and bone tissue micromechanics is spreading in computational biomechanics. Finite Element models show great potential in surgical planning of intervention and in prediction of stress and strain fields through a non-invasive method. The main challenge pertains to the reliable characterization of bone mechanical behaviour. An almost automatic procedure is here defined, which provides computational models of bony structures considering the actual anisotropy of bone tissue response. The innovative aspect resides on the automatic detection of the directions of anisotropy as the eigenvectors of a three-dimensional distribution matrix of HU values. Methods:The procedure combines CT data and micromechanics modelling techniques. Regarding a specific location, the procedure reports both the orthotropic elastic constants, by the analysis of the local HU value, and the anisotropic material directions, by the analysis of the HU values distribution around the specific location. ResultsThe procedure returns the distribution of bone tissue orthotropic elasticity tensor. The procedure proves to correctly respect the differentiation between cortical and trabecular bone. Principal directions show to be consistent with experimental data from ultrasound measurements. Regarding the material mapping from voxel to FE model, the developed strategies show to be reliable, leading to marginal errors (lower than 10%) for most of CT voxels (more than 90%). The computational analyses of typical structural loading conditions lead to strain values that are comparable with results from strain gauges experimentations. The development and the exploitation of FE models of different bony structures allow assessing the reliability of the procedure for cortical bone. ConclusionsThe results highlight the potentialities of the procedure in providing accurate patient-specific biomechanical models of bony structures starting from CT data. The accuracy and the automatism of the procedure are important factors for the development of real time clinical tools. The main limitations of this work remain the not fully automatism and the reliability assessment, which is based mainly on cortical bone regions only.

In Vitro-Induced High Sugar Environments Deteriorate Human Cortical Bone Elastic Modulus and Fracture Toughness.

Advanced glycation end-products (AGEs) have been suggested to contribute to bone fragility in type 2 diabetes (T2D). AGEs can be induced through in vitro sugar incubations but there is limited data on the effect of total fluorescent AGEs on mechanical properties of human cortical bone, which may have altered characteristics in T2D. Thus, to examine the effect of AGEs on bone directly in T2D patients with uncontrolled sugar levels, it is essential to first understand the fundamental mechanisms by studying the effects of controlled in vitro-induced AGEs on cortical bone mechanical behavior. Here, human cortical bone specimens from female cadaveric tibias (ages 57-87) were incubated in an in vitro 0.6 M ribose or vehicle solution (n = 20/group) for 10 days at 37°C, their mechanical properties were assessed by microindentation and fracture toughness tests, and induced AGE levels were quantified through a fluorometric assay. Results indicated that ribose-incubated bone had significantly more AGEs (+81%, p ≤ 0.005), lower elastic modulus assessed by traditional microindentation, and lower fracture toughness compared with vehicle controls. Furthermore, based on pooled data, increased AGEs were significantly correlated with deteriorated mechanical properties. The findings presented here show that the accumulation of AGEs allows for lower stiffness and increased ability to initiate a crack in human cortical bone. Statement of clinical significance: High sugar levels as in T2D results in deteriorated bone quality via AGE accumulation with a consequent weakening in bone's mechanical integrity. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:972-983, 2020.

FEM-Based Compression Fracture Risk Assessment in Osteoporotic Lumbar Vertebra L1

This paper presents a finite element method (FEM)-based fracture risk assessment in patient-specific osteoporotic lumbar vertebra L1. The influence of osteoporosis is defined by variation of parameters such as thickness of the cortical shell, the bone volume–total volume ratio (BV/TV), and the trabecular bone score (TBS). The mechanical behaviour of bone is defined using the Ramberg–Osgood material model. This study involves the static and nonlinear dynamic calculations of von Mises stresses and follows statistical processing of the obtained results in order to develop the patient-specific vertebra reliability. In addition, different scenarios of parameters show that the reliability of the proposed model of human vertebra highly decreases with low levels of BV/TV and is critical due to the thinner cortical bone, suggesting high trauma risk by reason of osteoporosis.

Altered Tissue Composition, Microarchitecture, and Mechanical Performance in Cancellous Bone From Men With Type 2 Diabetes Mellitus

People with type 2 diabetes mellitus (T2DM) have normal-to-high BMDs, but, counterintuitively, have greater fracture risks than people without T2DM, even after accounting for potential confounders like BMI and falls. Therefore, T2DM may alter aspects of bone quality, including material properties or microarchitecture, that increase fragility independently of bone mass. Our objective was to elucidate the factors that influence fragility in T2DM by comparing the material properties, microarchitecture, and mechanical performance of cancellous bone in a clinical population of men with and without T2DM. Cancellous specimens from the femoral neck were collected during total hip arthroplasty (T2DM: n = 31, age = 65 ± 8 years, HbA1c = 7.1 ± 0.9%; non-DM: n = 34, age = 62 ± 9 years, HbA1c = 5.5 ± 0.4%). The T2DM specimens had greater concentrations of the advanced glycation endproduct pentosidine (+ 36%, P < 0.05) and sugars bound to the collagen matrix (+ 42%, P < 0.05) than the non-DM specimens. The T2DM specimens trended toward a greater bone volume fraction (BV/TV) (+ 24%, NS, P = 0.13) and had greater mineral content (+ 7%, P < 0.05) than the non-DM specimens. Regression modeling of the mechanical outcomes revealed competing effects of T2DM on bone mechanical behavior. The trend of higher BV/TV values and the greater mineral content observed in the T2DM specimens increased strength, whereas the greater values of pentosidine in the T2DM group decreased postyield strain and toughness. The long-term medical management and presence of osteoarthritis in these patients may influence these outcomes. Nevertheless, our data indicate a beneficial effect of T2DM on cancellous microarchitecture, but a deleterious effect of T2DM on the collagen matrix. These data suggest that high concentrations of advanced glycation endproducts can increase fragility by reducing the ability of bone to absorb energy before failure, especially for the subset of T2DM patients with low BV/TV. © 2019 American Society for Bone and Mineral Research.

CROSS-LINKS MULTISCALE EFFECTS ON BONE ULTRASTRUCTURE BIOMECHANICAL BEHAVIOR

Bone is a multiscale combination of collagen molecules merged with mineral crystals. Its high rigidity and stability stem amply from its polymeric organic matrix and secondly from the connections established between interdifferent and intradifferent scale components through cross-links. Several studies have shown that the cross-links inhibition results in a reduction in strength of bone but they do not quantify the degree to which these connections contribute to the bone rigidity and toughness. This report is classified among the few works that measure the cross-links multiscale impact on the ultrastructure bone mechanical behavior. This work aims firstly to study the effect of cross-links at the molecule scale and secondly to gather from literature studies results handling with cross-links effects on the other bone ultrastructure scales in order to reveal the multiscale effect of cross-links. This study proves that cross-links increasing number improves the mechanical performance of each scale of bone ultrastructure. On the other hand, cross-links have a multiscale contribution that depends on its rank related to existing cross-links connecting the same geometries and it depends on mechanical characteristics of geometries connected.

INFLUENCE OF THE BONE MORPHOLOGY ON MECHANICAL BEHAVIOR OF HUMAN SKULL FOR TWO STRAIN RATE CASES

Modeling the mechanical behavior of bone is very complex due to substantial variability of the mechanical response of bone. The objective of this study is to investigate the link between morphology of the human parietal bone and its mechanical behavior in compression with two different strain rates. Five formalin-preserved human skulls were used, and 10 specimens were taken from the parietal bone of each subject. The internal geometry of the osseous material was studied with a micro-tomography device. For mechanical testing, quasi-static (0.02 s–1) tests on a conventional compression machine and dynamic tests (1500 s–1) on a split Hopkinson pressure bar (SHPB) were conducted on 9 mm diameter samples. The results were used to examine relationships between the morphological parameters to find morphological correlations. Linkages between mechanical behavior and morphology of the human parietal bone were also analyzed to develop a behavior model based on micro-structure parameters as determined by micro-scanning.

Relationships between human cortical bone toughness and collagen cross-links on paired anatomical locations.

Human cortical bone fracture processes depend on the internal porosity network down to the lacunar length scale. Recent results show that at the collagen scale, the maturation of collagen cross-links may have a negative influence on bone mechanical behavior. While the effect of pentosidine on human cortical bone toughness has been studied, the influence of mature and immature enzymatic cross-links has only been studied in relation to strength and work of fracture. Moreover, these relationships have not been studied on different paired anatomical locations. Thus, the aim of the current study was to assess the relationships between both enzymatic and non-enzymatic collagen cross-links and human cortical bone toughness, on four human paired anatomical locations. Single Edge Notched Bending toughness tests were performed for two loading conditions: a quasi-static standard condition, and a condition representative of a fall. These tests were done with 32 paired femoral diaphyses, femoral necks and radial diaphyses (18 women, age 81 ± 12 y.o.; 14 men, age 79 ± 8 y.o.). Collagen enzymatic and non-enzymatic crosslinks were measured on the same bones. Maturation of collagen was defined as the ratio between immature and mature cross-links (CX). The results show that there was a significant correlation between collagen cross-link maturation and bone toughness when gathering femoral and radial diaphyses, but not when considering each anatomical location individually. These results show that the influence of collagen enzymatic and non-enzymatic cross-links is minor when considering human cortical bone crack propagation mechanisms.

LOX-related collagen crosslink changes act as an initiator of bone fragility in a ZDF rats model

Diabetes mellitus type 2 (DM2) results in bone abnormalities that manifest as increased bone fragility. Bone consists of two phases, the mineral phase and the matrix phase, and disorders in both are seen in DM2. However, the phase in which DM2 mediated bone fragility is initiated is still unknown. In this study, a male Zucker diabetic fatty (fa/fa) (ZDF) rat model was used to investigate the underlying mechanism initiating DM2 mediated bone fragility. The fracture surface morphology, pre- and post-yield bone mechanical behavior, insoluble collagen volume, lysyl oxidase family (LOX) enzyme levels and correlation analysis was performed to determine the relationship between insoluble collagen and post-yield behavior. Four weeks after the induction of diabetes, insoluble collagen was decreased in only the matrix phase in diabetic rats. Consistently, mechanical testing of the bone showed changes only in post-yield behavior. Diabetic rats also had decreased levels of enzymes involved in insoluble collagen formation (LOX and LOXL1 families). Correlation analysis demonstrated that insoluble collagen was a positive regressor of post-yield displacement (R = 0.894, P < 0.001) and post-yield energy (R = 0.918, P < 0.001). Together, these findings suggest that bone fragility in DM2 is initiated in the matrix phase and that the LOX family may play a critical part in the pathogenesis of DM2 mediated bone fragility.

Towards assessing cortical bone porosity using low-frequency quantitative acoustics: A phantom-based study.

PurposeCortical porosity is a key characteristic governing the structural properties and mechanical behaviour of bone, and its quantification is therefore critical for understanding and monitoring the development of various bone pathologies such as osteoporosis. Axial transmission quantitative acoustics has shown to be a promising technique for assessing bone health in a fast, non-invasive, and radiation-free manner. One major hurdle in bringing this approach to clinical application is the entanglement of the effects of individual characteristics (e.g. geometry, porosity, anisotropy etc.) on the measured wave propagation. In order to address this entanglement problem, we therefore propose a systematic bottom-up approach, in which only one bone property is varied, before addressing interaction effects. This work therefore investigated the sensitivity of low-frequency quantitative acoustics to changes in porosity as well as individual pore characteristics using specifically designed cortical bone phantoms.Materials and methods14 bone phantoms were designed with varying pore size, axial-, and radial pore number, resulting in porosities (bone volume fraction) between 0% and 15%, similar to porosity values found in human cortical bone. All phantoms were manufactured using laser sintering, measured using axial-transmission acoustics and analysed using a full-wave approach. Experimental results were compared to theoretical predictions based on a modified Timoshenko theory.ResultsA clear dependence of phase velocity on frequency and porosity produced by increasing pore size or radial pore number was demonstrated, with the velocity decreasing by between 2–5 m/s per percent of additional porosity, which corresponds to -0.5% to -1.0% of wave speed. While the change in phase velocity due to axial pore number was consistent with the results due to pore size and radial pore number, the relative uncertainties for the estimates were too high to draw any conclusions for this parameter.ConclusionsThis work has shown the capability of low-frequency quantitative acoustics to reflect changes in porosity and individual pore characteristics and demonstrated that additive manufacturing is an appropriate method that allows the influence of individual bone properties on the wave propagation to be systematically assessed. The results of this work opens perspectives for the efficient development of a multi-frequency, multi-mode approach to screen, diagnose, and monitor bone pathologies in individuals.

Increased intrinsic stiffness and mineralization in femurs of adult rats after high intensity treadmill running training.

Physical activity plays a tremendous role in determining bone mechanical behavior, which is superimposed to gravidity. Compare the geometric and material responses of the rat femur to a high intensity treadmill running training of a relatively short duration, as assessed by 3-point mechanical test. Mature male rats (180.0± 30g) were assigned (7rats/group) to no exercise (NE) or treadmill exercise (EX). After a preconditioning period, the running speed was set at 45cm.seg-1 during 2wks, frequency 5d/wk, 2-hour sessions/day. Body weight and weight of the crural quadriceps were registered at euthanasia. The right femur was mechanically tested through 3-point bending. The left femur was ashed to estimate bone mineral content. Geometric and material bone properties were estimated directly or calculated by appropriate equations. 1)Final body weight was 14% reduced in EX rats, while the crural quadriceps was 47% increased. Yield and fracture loads, and structural stiffness were significantly higher in the EX rats, as were the apparent elastic modulus, the bone mineral content and the degree of mineralization. Geometric properties were not affected. High intensity treadmill running training increases bone strength and stiffness by increasing material stiffness and mineralization, without affecting geometric bone parameters.

Two-Way Coupled Multiscale Model for Predicting Mechanical Behavior of Bone Subjected to Viscoelastic Deformation and Fracture Damage

This paper presents a two-way linked computational multiscale model and its application to predict the mechanical behavior of bone subjected to viscoelastic deformation and fracture damage. The model is based on continuum thermos-mechanics and is implemented through the finite element method (FEM). Two physical length scales (the global scale of bone and local scale of compact bone) were two-way coupled in the framework by linking a homogenized global object to heterogeneous local-scale representative volume elements (RVEs). Multiscaling accounts for microstructure heterogeneity, viscoelastic deformation, and rate-dependent fracture damage at the local scale in order to predict the overall behavior of bone by using a viscoelastic cohesive zone model incorporated with a rate-dependent damage evolution law. In particular, age-related changes in material properties and geometries in bone were considered to investigate the effect of aging, loading rate, and damage evolution characteristics on the mechanical behavior of bone. The model successfully demonstrated its capability to predict the viscoelastic response and fracture damage due to different levels of aging, loading conditions (such as rates), and microscale damage evolution characteristics with only material properties of each constituent in the RVEs.

New three-dimensional model based on finite element method of bone nanostructure: single TC molecule scale level

At the macroscopic scale, the bone mechanical behavior (fracture, elastic) depends mainly on its components’ nature at the nanoscopic scale (collagen, mineral). Thus, an understanding of the mechanical behavior of the elementary components is demanded to understand the phenomena that can be observed at the macroscopic scale. In this article, a new numerical model based on finite element method is proposed in order to describe the mechanical behavior of a single Tropocollagen molecule. Furthermore, a parametric study with different geometric properties covering the molecular composition and the rate hydration influence is presented. The proposed model has been tested under tensile loading. While focusing on the entropic response, the geometric parameter variation effect on the mechanical behavior of Tropocollagen molecule has been revealed using the model. Using numerical and experimental testing, the obtained numerical simulation results seem to be acceptable, showing a good agreement with those found in literature.

Dealloying-based interpenetrating-phase nanocomposites matching the elastic behavior of human bone

The long-term performance of orthopedic implants depends crucially on a close match between the mechanical behavior of bone and of the implant material. Yet, the present man-made materials with the required biocompatibility and strength are substantially stiffer than bone. This mismatch results in stress shielding, which can lead to the loss of bone mass and may even lead to a revision surgery. Here we report a new materials design strategy towards metal-polymer composites that are based on constituents with established biocompatibility and that can be matched to bone. Ti-based nanoporous alloys, prepared by liquid-metal dealloying, are infiltrated with epoxy to form interpenetrating-phase nanocomposites. At up to 260 MPa, their yield strength is technologically interesting for a deformable light-weight material. More importantly, Young’s modulus can be adjusted between 4.4 and 24 GPa, which affords matching to bone. As another parallel to bone, the strength of the composite materials is strain-rate dependent. These findings suggest that the novel composite materials may provide the basis for promising future implant materials.

In vivo bone remodeling rates determination and compressive stiffness variations before, during 60 days bed rest and two years follow up: A micro-FE-analysis from HR-pQCT measurements of the berlin Bed Rest Study-2

Bed rest studies are used for simulation and study of physiological changes as observed in unloading/non-gravity environments. Amongst others, bone mass reduction, similar as occurring due to aging osteoporosis, combined with bio-fluids redistribution and muscle atrophy have been observed and analyzed. Advanced radiological methods of high resolution such as HR-pQCT (XtremeCT) allow 3D-visualizing in vivo bone remodeling processes occurring during absence/reduction of mechanical stimuli (0 to <1g) as simulated by bed rest. Induced bone micro-structure (e.g. trabecular number, cortical thickness, porosity) and density variations can be quantified. However, these parameters are average values of each sample and important information regarding bone mass distribution and within bone mechanical behaviour is lost. Finite element models with hexa-elements of identical size as the HR-pQCT measurements (0.082mm×0.082mm×0.082mm, ca. 7E6 elements/sample) can be used for subject-specific in vivo stiffness calculation. This technique also allows quantifying if bone microstructural changes represent a risk of mechanical bone collapse (fracture). Materials and methodsIn the Berlin Bed Rest Study-2, 23 male subjects (20–50 YO) were maintained 60 days under restricted bed rest (6° HDT) aiming to test a - for this study specifically designed - vibration resistive exercise regime for maintenance of bone mass and muscle functionality at normal levels (base line measurements). For comparison a resistive exercise without vibration and a control group were included. Base line HR-pQCT measurements (3 days before bed rest: base line), as well as during 30 days bed rest (BR30 and BR59, 3 days of recovery (R3), R15, R30, R90, R180, R360, and R720 were performed. CT-scan voxels were converted into finite elements (hexa-82µm edge length) for calculating in vivo compressive stiffness during the experiment duration. Histograms of stresses and strains distributions as well as anatomical regions susceptible for mechanical failure were identified and compared. Results:Resistive vibration exercises (RVE) were able to maintain in the majority of the subjects compressive bone strength as determined after modelling a compressive test using finite element models. Compressive bone stiffness using FEA was monitored through analysis of the internal deformation on the trabecular structures and cortical bone, reaction forces, and minimum principal strains on the in vivo CT measured bone regions during the experiment duration. Stress distributions (main stresses) and von Mises stress distribution remained comparable with those determined in the base line measurements for the RVE-group. However, no major differences were found in the group with resistive exercise training alone. Without mechanical stimuli an increment of bone regions with high stress concentration was observed and a reduction of up to 10% of bone compressive stiffness was quantified by using subject-specific finite-element analysis. Anatomically von Mises stress concentrations, thus bone regions susceptible to fail mechanically, were observed at the center of the cancellous bone and at the antero- posterior region of the cortical bone. Conclusions:Finite element simulations from bed rest studies are an invaluable tool to determine subject-specific in vivo compressive stiffness and anatomical mechanically compromised regions under controlled mechanical conditions (unloading) which - until now - are not possible to be determined with any other method. Vibration exercise combined with a resistive compressive force was able to maintain bone structure and density even during 60 days of bed rest.

Numerical simulation of the femur fracture under static loading

Bone is a living material with a complex hierarchical structure that gives it remarkable mechanical properties. Bone constantly undergoes mechanical. Its quality and resistance to fracture is constantly changing over time through the process of bone remodeling. Numerical modeling allows the study of the bone mechanical behavior and the prediction of different trauma caused by accidents without expose humans to real tests. The aim of this work is the modeling of the femur fracture under static solicitation to create a numerical model to simulate this element fracture. This modeling will contribute to improve the design of the indoor environment to be better safe for the passengers\' transportation means. Results show that vertical loading leads to the femur neck fracture and horizontal loading leads to the fracture of the femur diaphysis. The isotropic consideration of the bone leads to bone fracture by crack propagation but the orthotropic consideration leads to the fragmentation of the bone.