Cortical and trabecular mechanical properties in the femoral neck vary differently with changes in bone mineral density.

Graphical Abstract.

Critical loss of primary implant stability in osteosynthesis locking screws under cyclic overloading.

Primary implant stability, which refers to the stability of the implant during the initial healing period is a crucial factor in determining the long-term success of the implant and lays the foundation for secondary implant stability achieved through osseointegration. Factors affecting primary stability include implant design, surgical technique, and patient-specific factors like bone quality and morphology. In vivo, the cyclic nature of anatomical loading puts osteosynthesis locking screws under dynamic loads, which can lead to the formation of micro cracks and defects that slowly degrade the mechanical connection between the bone and screw, thus compromising the initial stability and secondary stability of the implant. Monotonic quasi-static loading used for testing the holding capacity of implanted screws is not well suited to capture this behavior since it cannot capture the progressive deterioration of peri­implant bone at small displacements. In order to address this issue, this study aims to determine a critical point of loss of primary implant stability in osteosynthesis locking screws under cyclic overloading by investigating the evolution of damage, dissipated energy, and permanent deformation. A custom-made test setup was used to test implanted 2.5 mm locking screws under cyclic overloading test. For each loading cycle, maximum forces and displacement were recorded as well as initial and final cycle displacements and used to calculate damage and energy dissipation evolution. The results of this study demonstrate that for axial, shear, and mixed loading significant damage and energy dissipation can be observed at approximately 20 % of the failure force. Additionally, at this load level, permanent deformations on the screw-bone interface were found to be in the range of 50 to 150 mm which promotes osseointegration and secondary implant stability. This research can assist surgeons in making informed preoperative decisions by providing a better understanding of the critical point of loss of primary implant stability, thus improving the long-term success of the implant and overall patient satisfaction.

The 2-layer elasto-visco-plastic rheological model for the material parameter identification of bone tissue extended by a damage law.

The response of bone tissue to mechanical load is complex and includes plastic hardening, viscosity and damage. The quantification of these effects plays a mayor role in bone research and in biomechanical clinical trials as to better understand related diseases. In this study, the damage growth in individual wet human trabeculae subjected to cyclic overloading is quantified by inverse rheological modeling. Therefore, an already published rheological material model, that includes linear elasticity, plasticity and viscosity is extended by a damage law. The model is utilized in an optimization process to identify the corresponding material parameters and damage growth in single human trabeculae under tensile load. Results show that the damage model is leading to a better fit of the test data with an average root-mean-square-error (RMSE) of 2.52 MPa compared to the non-damage model with a RMSE of 3.03 MPa. Although this improvement is not significant, the damage model qualitatively better represents the data as it accounts for the visible stiffness reduction along the load history. It returns realistic stiffness values of 11.92 GPa for the instantaneous modulus and 5.73 GPa for the long term modulus of wet trabecular human bone. Further, the growth of damage in the tissue along the load history is substantial, with values above 0.8 close to failure. The relative loss of stiffness per cycle is in good agreement with comparable literature. Inverse rheological modeling proves to be a valuable tool for quantifying complex constitutive behavior from a single mechanical measurement. The evolution of damage in the tissue can be identified continuously over the load history and separated from other effects.

A parameter reduced adaptive quasi-linear viscoelastic model for soft biological tissue in uniaxial tension.

Mechanical characterisation of soft viscous materials is essential for many applications including aerospace industries, material models for surgical simulation, and tissue mimicking materials for anatomical models. Constitutive material models are, therefore, necessary to describe soft biological tissues in physiologically relevant strain ranges. Hereby, the adaptive quasi-linear viscoelastic (AQLV) model enables accurate modelling of the strain-dependent non-linear viscoelastic behaviour of soft tissues with a high flexibility. However, the higher flexibility produces a large number of model parameters. In this study, porcine muscle and liver tissue samples were modelled in the framework of the originally published AQLV (3-layers of Maxwell elements) model using four incremental ramp-hold experiments in uniaxial tension. AQLV model parameters were reduced by decreasing model layers (M) as well as the number of experimental ramp-hold steps (N). Leave One out cross validation tests show that the original AQLV model (3M4N) with 19 parameters, accurately describes porcine muscle tissue with an average R2 of 0.90 and porcine liver tissue, R2 of 0.86. Reducing the number of layers (N) in the model produced acceptable model fits for 1-layer (R2 of 0.83) and 2-layer models (R2 of 0.89) for porcine muscle tissue and 1-layer (R2 of 0.84) and 2-layer model (R2 of 0.85) for porcine liver tissue. Additionally, a 2 step (2N) ramp-hold experiment was performed on additional samples of porcine muscle tissue only to further reduce model parameters. Calibrated spring constant values for 2N ramp-hold tests parameters k1 and k2 had a 16.8% and 38.0% deviation from those calibrated for a 4 step (4N) ramp hold experiment. This enables further reduction of material parameters by means of step reduction, effectively reducing the number of parameters required to calibrate the AQLV model from 19 for a 3M4N model to 8 for a 2M2N model, with the added advantage of reducing the time per experiment by 50%. This study proposes a 'reduced-parameter' AQLV model (2M2N) for the modelling of soft biological tissues at finite strain ranges. Sequentially, the comparison of model parameters of soft tissues is easier and the experimental burden is reduced.

Experimental validation of a micro-CT finite element model of a human cadaveric mandible rehabilitated with short-implant-supported partial dentures.

PURPOSE: This study aimed to address the predictive value of a micro-computed tomography (µCT)-based finite element (µFE) model of a human cadaveric edentulous posterior mandible, rehabilitated by short dental implants. Hereby, three different prosthetic/implant configurations of fixed partial dentures ("Sp"-3 splinted crowns on 3 implants, "Br" - Bridge: 3 splinted crowns on 2 implants, and "Si"- 3 single crowns) were analysed by comparing the computational predictions of the global stiffness with experimental data. METHODS: Experimental displacement of the bone/implant/prosthesis system was measured under axial and oblique loads of 100 N using an optical deformation system (GOM Aramis) and the overall movement of the testing machine (Zwick Z030). Together with the measured machine force, an "Aramis" (optical markers) and "Zwick" (test machine) stiffness were calculated. FE models were created based on µCT-scans of the cadaveric mandible sample (n = 1) before and after implantation and using stl-files of the crowns. The same load tests and boundary conditions were simulated on the models and the µFE-results were compared to experimental data using linear regression analysis. RESULTS: The regression line through a plot of pooled stiffness values (N/mm) for the optical displacement recording (true local displacement) and the test machine (machine compliance included) had a slope of 0.57 and a correlation coefficient R2 of 0.82. The average pooled correlation of global stiffness between the experiment and FE-analysis (FEA) showed a R2 of 0.80, but the FEA-stiffness was 7.2 times higher. The factor was highly dependent on the test configuration. Sp-configuration showed the largest stiffness followed by Br-configuration (17% difference in experiment and 21% in FEA). CONCLUSIONS: The current study showed good qualitative agreement between the experimental and predicted global stiffness of different short implant configurations. It could be deduced that 1:1 splinting of the short implants by the crowns is most favorable for the stiffness of the implant/prosthesis system. However, in the clinical context, the absolute in silico readings must be interpreted cautiously, as the FEA showed a considerable overestimation of the values.

Effects of Osteoporosis on Bone Morphometry and Material Properties of Individual Human Trabeculae in the Femoral Head.

Osteoporosis is the most common bone disease and is conventionally classified as a decrease of total bone mass. Current diagnosis of osteoporosis is based on clinical risk factors and dual energy X-ray absorptiometry (DEXA) scans, but changes in bone quantity (bone mass) and quality (trabecular structure, material properties, and tissue composition) are not distinguished. Yet, osteoporosis is known to cause a deterioration of the trabecular network, which might be related to changes at the tissue scale-the material properties. The goal of the current study was to use a previously established test method to perform a thorough characterization of the material properties of individual human trabeculae from femoral heads in cyclic tensile tests in a close to physiologic, wet environment. A previously developed rheological model was used to extract elastic, viscous, and plastic aspects of material behavior. Bone morphometry and tissue mineralization were determined with a density calibrated micro-computed tomography (µCT) set-up. Osteoporotic trabeculae neither showed a significantly changed material or mechanical behavior nor changes in tissue mineralization, compared with age-matched healthy controls. However, donors with osteopenia indicated significantly reduced apparent yield strain and elastic work with respect to osteoporosis, suggesting possible initial differences at disease onset. Bone morphometry indicated a lower bone volume to total volume for osteoporotic donors, caused by a smaller trabecular number and a larger trabecular separation. A correlation of age with tissue properties and bone morphometry revealed a similar behavior as in osteoporotic bone. In the range studied, age does affect morphometry but not material properties, except for moderately increased tissue strength in healthy donors and moderately increased hardening exponent in osteoporotic donors. Taken together, the distinct changes of trabecular bone quality in the femoral head caused by osteoporosis and aging could not be linked to suspected relevant changes in material properties or tissue mineralization. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Effects of anti-resorptive treatment on the material properties of individual canine trabeculae in cyclic tensile tests.

Osteoporosis is defined as a decrease of bone mass and strength, as well as an increase in fracture risk. It is conventionally treated with antiresorptive drugs, such as bisphosphonates (BPs) and selective estrogen receptor modulators (SERMs). Although both drug types successfully decrease the risk of bone fractures, their effect on bone mass and strength is different. For instance, BP treatment causes an increase of bone mass, stiffness and strength of whole bones, whereas SERM treatment causes only small (4%) increases of bone mass, but increased bone toughness. Such improved mechanical behavior of whole bones can be potentially related to the bone mass, bone structure or material changes. While bone mass and architecture have already been investigated previously, little is known about the mechanical behavior at the tissue/material level, especially of trabecular bone. As such, the goal of the work presented here was to fill this gap by performing cyclic tensile tests in a wet, close to physiologic environment of individual trabeculae retrieved from the vertebrae of beagle dogs treated with alendronate (a BP), raloxifene (a SERM) or without treatments. Identification of material properties was performed with a previously developed rheological model and of mechanical properties via fitting of envelope curves. Additionally, tissue mineral density (TMD) and microdamage formation were analyzed. Alendronate treatment resulted in a higher trabecular tissue stiffness and strength, associated with higher levels of TMD. In contrast, raloxifene treatment caused a higher trabecular toughness, pre-dominantly in the post-yield region. Microdamage formation during testing was not affected by either anti-resorptive treatment regimens. These findings highlight that the improved mechanical behavior of whole bones after anti-resorptive treatment is at least partly caused by improved material properties, with different mechanisms for alendronate and raloxifene. This study further shows the power of performing a mechanical characterization of trabecular bone at the level of individual trabeculae for better understanding of clinically relevant mechanical behavior of bone.

A Review on Recent Advances in the Constitutive Modeling of Bone Tissue.

PURPOSE OF REVIEW: Image-based finite element analysis (FEA) to predict and understand the biomechanical response has become an essential methodology in musculoskeletal research. An important part of such simulation models is the constitutive material model of which recent advances are summarized in this review. RECENT FINDINGS: The review shows that existing models from other fields were introduced, such as cohesion zone (cortical bone) or phase-field models (trabecular bone). Some progress has been made in describing cortical bone involving physical mechanisms such as microcracks. Problems with validations at different length scales remain a problem. The improvement of recent constitutive models is partially obscured by uncertainties that affect overall predictions, such as image quality and calibration or boundary conditions. Nevertheless, in vivo CT-based FEA simulations based on a sophisticated constitutive behavior are a very valuable tool for clinical-related osteoporosis research.

Correction to: A two­layer elasto­visco­plastic rheological model for the material parameter identification of bone tissue.

In the original publication of the article.

A two-layer elasto-visco-plastic rheological model for the material parameter identification of bone tissue.

The ability to measure bone tissue material properties plays a major role in diagnosis of diseases and material modeling. Bone's response to loading is complex and shows a viscous contribution to stiffness, yield and failure. It is also ductile and damaging and exhibits plastic hardening until failure. When performing mechanical tests on bone tissue, these constitutive effects are difficult to quantify, as only their combination is visible in resulting stress-strain data. In this study, a methodology for the identification of stiffness, damping, yield stress and hardening coefficients of bone from a single cyclic tensile test is proposed. The method is based on a two-layer elasto-visco-plastic rheological model that is capable of reproducing the specimens' pre- and postyield response. The model's structure enables for capturing the viscously induced increase in stiffness, yield, and ultimate stress and for a direct computation of the loss tangent. Material parameters are obtained in an inverse approach by optimizing the model response to fit the experimental data. The proposed approach is demonstrated by identifying material properties of individual bone trabeculae that were tested under wet conditions. The mechanical tests were conducted according to an already published methodology for tensile experiments on single trabeculae. As a result, long-term and instantaneous Young's moduli were obtained, which were on average 3.64 GPa and 5.61 GPa, respectively. The found yield stress of 16.89 MPa was lower than previous studies suggest, while the loss tangent of 0.04 is in good agreement. In general, the two-layer model was able to reproduce the cyclic mechanical test data of single trabeculae with an root-mean-square error of 2.91 ± 1.77 MPa. The results show that inverse rheological modeling can be of great advantage when multiple constitutive contributions shall be quantified based on a single mechanical measurement.

Computational and experimental methodology for site-matched investigations of the influence of mineral mass fraction and collagen orientation on the axial indentation modulus of lamellar bone.

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

Principal stiffness orientation and degree of anisotropy of human osteons based on nanoindentation in three distinct planes.

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

Elastic anisotropy of bone lamellae as a function of fibril orientation pattern.

In this study, the homogenized anisotropic elastic properties of single bone lamellae are computed using a finite element unit cell method. The resulting stiffness tensor is utilized to calculate indentation moduli for multiple indentation directions in the lamella plane which are then related to nanoindentation experiments. The model accounts for different fibril orientation patterns in the lamellae--the twisted and orthogonal plywood pattern, a 5-sublayer pattern and an X-ray diffraction-based pattern. Three-dimensional sectional views of each pattern facilitate the comparison to transmission electron (TEM) images of real lamella cuts. The model results indicate, that the 5-sublayer- and the X-ray diffraction-based patterns cause the lamellae to have a stiffness maximum between 0° and 45° to the osteon axis. Their in-plane stiffness characteristics are qualitatively matching the experimental findings that report a higher stiffness in the osteon axis than in the circumferential direction. In contrast, lamellae owning the orthogonal or twisted plywood fibril orientation patterns have no preferred stiffness alignment. This work shows that the variety of fibril orientation patterns leads to qualitative and quantitative differences in the lamella elastic mechanical behavior. The study is a step toward a deeper understanding of the structure-mechanical function relationship of bone lamellae.

Sensitivity analysis and parametric study of elastic properties of an unidirectional mineralized bone fibril-array using mean field methods.

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