On the importance of considering porosity when simulating the fatigue of bone cement

Fatigue cracking in the cement mantle of total hip replacement has been identified as a possible cause of implant loosening. Retrieval studies and in vitro tests have found porosity in the cement may facilitate fatigue cracking of the mantle. The fatigue process has been simulated computationally using a finite element/continuum damage mechanics (FE/CDM) method and used as a preclinical testing tool, but has not considered the effects of porosity. In this study, experimental tensile and four-point bend fatigue tests were performed. The tensile fatigue S-N data were used to drive the computational simulation (FE/CDM) of fatigue in finite element models of the tensile and four-point bend specimens. Porosity was simulated in the finite element models according to the theory of elasticity and using Monte Carlo methods. The computational fatigue simulations generated variability in the fatigue life at any given stress level, due to each model having a unique porosity distribution. The fracture site also varied between specimens. Experimental validation was achieved for four-point bend loading, but only when porosity was included. This demonstrates that the computational simulation of fatigue, driven by uniaxial S-N data can be used to simulate nonuniaxial loadcases. Further simulations of bone cement fatigue should include porosity to better represent the realities of experimental models.     

Pore Direction in Relation to Anisotropy of Mechanical Strength in a Cubic Starch Compact

The purpose of this research was to evaluate the relation between preferential direction of pores and mechanical strength of cubic starch compacts. The preferential pore direction was quantified in SEM images of cross sections of starch compacts using a previously described algorithm for determination of the quotient of transitions (Q). This parameter and the mechanical strength were evaluated in compacts of different porosities. Starch was chosen as a model compound for materials with ductile behaviour of which tablets with low porosities can be made and which shows some elastic recovery after compaction. At medium and high porosity Q was significantly higher in the images providing a side view of the compact than in the images providing a top view (0.973 vs. 0.927 and 0.958 vs. 0.874 at 0 mm from the side of the compact and 0.956 vs. 0.854 and 0.951 vs. 0.862 at 3.5 mm), indicating that the pores were mainly oriented in the direction perpendicular to the direction of compression. This was accompanied by a lower crushing force in this direction. This could be explained by considering the pores as cracks which propagate through the sample during crushing. For both directions the crushing force decreased with increasing porosity. The yield strength of the compacts also decreased with increasing porosity, but this parameter was not dependent on the direction of crushing when the porosity was below 10%. The results show that pore direction significantly influences the crushing force but does not influence the yield strength, at porosities below 10%.     

Relative Bioavailability of Chlorothiazide from Mucoadhesive Compacts in Pigs

The relative bioavailability of chlorothiazide from mucoadhesive polymeric compacts is compared to commercial oral suspension in pigs. A single-dose randomized study was conducted in 12 healthy pigs that are 9–10 weeks old. After overnight fasting, pigs were divided into two groups of six animals. To the first group, a reference product containing 50 mg of chlorothiazide suspension, and in the second group, test product (mucoadhesive compacts) chlorothiazide (50 mg) was administered with 75 mL of water via gastric tubes. Blood samples were collected between 0 to 24 h using catheters inserted into the jugular vein. Plasma was separated by protein precipitation, and chlorothiazide concentrations were determined using a high-performance liquid chromatography method. The mean T_max and the C_max of chlorothiazide following the administration of oral suspension and mucoadhesive compacts were 0.58 ± 0.20 h and 682.97 ± 415.69 ng/mL and 2.17 ± 0.98 h and 99.42 ± 124.08 ng/mL, respectively. The K_el and T_1/2 of chlorothiazide were found to be 1.06 ± 0.28 h⁻¹ and 0.70 ± 0.21 h from suspension and 0.95 ± 1.11 h⁻¹ and 2.05 ± 1.90 h from the compacts, respectively. The T_max of mucoadhesive compacts were significantly longer (p < 0.05; 2.17 h) than the reference products (0.58 h), whereas the C_max of compacts were significantly lower (99 ng/mL) than the reference product (683 ng/mL; p < 0.05). The area under the curve (AUC) of compacts accounts only 50.15% (404.32 ± 449.93 ng h/mL) of the reference product’s AUC (806.27 ± 395.97 ng h/mL). The relative bioavailability of the compacts was lower than that of the suspension, and this may be due to the narrow window of absorption for chlorothiazide.Key words: bioavailability, chlorothiazide, mucoadhesive compacts, pigs     

Diametral compression of non-circular diaphyseal bone sections

Many research endeavors involve strength testing of long bones, frequently using whole-bone four-point bending models. Recently, diametral compression of short sections has been used to quantify local mechanical parameters and effects of treatment, but testing of biologically derived samples entails a number of added complications, such as the non-circularity of bone sections, ambiguity of load orientation during testing, thickness variation in a section, and size and shape variation between sections in a single sample. In order to quantify the effects of these confounding factors, finite element diametral compression models of a number of bone sections were compared with simplified circular and elliptical sections. Each anatomic section was tested in all rotationally stable load configurations. A high degree of correlation was observed between the anatomic sections and their circular and elliptic analogs, indicating that meaningful comparisons may be made between bone sections of disparate geometry. The aspect ratio and shape of the bone sections did not have a significant impact on the maximum in-plane principal stresses, whereas stresses were strongly dependant on the mean thickness and spatial thickness variation. Some variation due to load orientation was observed. These results indicate that diametral ring compression testing of anatomic sections can be used effectively to measure structural and material parameters of long bones, and that anatomic variation can be successfully accommodated. The ability to use diametral compression testing should allow researchers to obtain many more samples from each specimen than whole-bone bending without the difficulty of extracting solid core or dog-bone samples.     

Effects of intracortical porosity on fracture toughness in aging human bone: a microCT-based cohesive finite element study

The extent to which increased intracortical porosity affects the fracture properties of aging and osteoporotic bone is unknown. Here, we report the development and application of a microcomputed tomography based finite element approach that allows determining the effects of intracortical porosity on bone fracture by blocking all other age-related changes in bone. Previously tested compact tension specimens from human tibiae were scanned using microcomputed tomography and converted to finite element meshes containing three-dimensional cohesive finite elements in the direction of the crack growth. Simulations were run incorporating age-related increase in intracortical porosity but keeping cohesive parameters representing other age-related effects constant. Additional simulations were performed with reduced cohesive parameters. The results showed a 6% decrease in initiation toughness and a 62% decrease in propagation toughness with a 4% increase in porosity. The reduction in toughnesses became even more pronounced when other age-related effects in addition to porosity were introduced. The initiation and propagation toughness decreased by 51% and 83%, respectively, with the combined effect of 4% increase in porosity and decrease in the cohesive properties reflecting other age-related changes in bone. These results show that intracortical porosity is a significant contributor to the fracture toughness of the cortical bone and that the combination of computational modeling with advanced imaging improves the prediction of the fracture properties of the aged and the osteoporotic cortical bone.     

Reliable simulations of the human proximal femur by high-order finite element analysis validated by experimental observations

Background: The mechanical response of patient-specific bone to various load conditions is of major clinical importance in orthopedics. Herein we enhance the methods presented in Yosibash et al. [2007. A CT-based high-order finite element analysis of the human proximal femur compared to in-vitro experiments. ASME Journal of Biomechanical Engineering 129(3), 297–309.] for the reliable simulations of the human proximal femur by high-order finite elements (FEs) and validate the simulations by experimental observations.

Method of approach: A fresh-frozen human femur was scanned by quantitative computed tomography (QCT) and thereafter loaded (in vitro experiments) by a quasi-static force of up to 1250 N. QCT scans were manipulated to generate a high-order FE bone model with distinct cortical and trabecular regions having inhomogeneous isotropic elastic properties with Young's modulus represented by continuous spatial functions. Sensitivity analyses were performed to quantify parameters that mostly influence the mechanical response. FE results were compared to displacements and strains measured in the experiments.

Results: Young moduli correlated to QCT Hounsfield Units by relations in Keyak and Falkinstein [2003. Comparison of in situ and in vitro CT scan-based finite element model predictions of proximal femoral fracture load. Medical Engineering and Physics 25, 781–787.] were found to provide predictions that match the experimental results closely. Excellent agreement was found for both the displacements and strains. The presented study demonstrates that reliable and validated high-order patient-specific FE simulations of human femurs based on QCT data are achievable for clinical computer-aided decision making.     

Evaluation of the Performance Characteristics of Bilayer Tablets: Part I. Impact of Material Properties and Process Parameters on the Strength of Bilayer Tablets

Bilayer tableting technology has gained popularity in recent times, as bilayer tablets offer several advantages over conventional tablets. There is a dearth of knowledge on the impact of material properties and process conditions on the performance of bilayer tablets. This paper takes a statistical approach to develop a model that will determine the effect of the material properties and bilayer compression process parameters on the bonding strength and mode of breakage of bilayer tablets. Experiments were carried out at pilot scale to simulate the commercial manufacturing conditions. As part of this endeavor, a seven-factor half-fraction factorial (2⁷⁻¹) design was executed to study the effect of bilayer tablet compression process factors on the bonding strength of bilayer tablets. Factors studied in this work include: material properties (plastic and brittle), layer ratio, dwell time, layer sequence, first- and second-layer forces, and lubricant concentration. Bilayer tablets manufactured in this study were tested using the axial tester, as it considers both the interfacial and individual layer bonding strengths. Responses of the experiments were analyzed using PROC GLM of SAS (SAS Institute Inc, Cary, North Carolina). A model was fit using all the responses to determine the significant interactions (p < 0.05). The results of this study indicated that nature of materials played a critical role on the strength of bilayer compacts and also on mode of fracture. Bilayer tablets made with brittle materials in both the layers are strongest, and fracture occurred in the first layer indicating that interface is stronger than layers. Significant interactions were observed between the selected factors and these results will provide an insight into the interplay of material properties, process parameters, and lubricant concentration on the bonding strength and mode of breakage of bilayer tablets.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-012-9845-9) contains supplementary material, which is available to authorized users.KEY WORDS: axial tester, bilayer tablets, DOE, interfacial strength, process parameters     

Effects of oxidative stress-induced changes in the actin cytoskeletal structure on myoblast damage under compressive stress: confocal-based cell-specific finite element analysis

Muscle cells are frequently subjected to both mechanical and oxidative stresses in various physiological and pathological situations. To explore the mechanical mechanism of muscle cell damage under loading and oxidative stresses, we experimentally studied the effects of extrinsic hydrogen peroxides on the actin cytoskeletal structure in C2C12 myoblasts and presented a finite element (FE) analysis of how such changes in the actin cytoskeletal structure affected a myoblast’s capability to resist damage under compression. A confocal-based cell-specific FE model was built to parametrically study the effects of stress fiber density, fiber cross-sectional area, fiber tensile prestrain, as well as the elastic moduli of the stress fibers, actin cortex, nucleus and cytoplasm. The results showed that a decrease in the elastic moduli of both the stress fibers and actin cortex could increase the average tensile strain on the actin cortex–membrane structure and reduce the apparent cell elastic modulus. Assuming the cell would die when a certain percentage of membrane elements were strained beyond a threshold, a lower elastic modulus of actin cytoskeleton would compromise the compressive resistance of a myoblast and lead to cell death more readily. This model was used with a Weibull distribution function to successfully describe the extent of myoblasts damaged in a monolayer under compression.     

Accuracy of specimen-specific nonlinear finite element analysis for evaluation of radial diaphysis strength in cadaver material

The feasibility of a user-specific finite element model for predicting the in situ strength of the radius after implantation of bone plates for open fracture reduction was established. The effect of metal artifact in CT imaging was characterized. The results were verified against biomechanical test data. Fourteen cadaveric radii were divided into two groups: (1) intact radii for evaluating the accuracy of radial diaphysis strength predictions with finite element analysis and (2) radii with a locking plate affixed for evaluating metal artifact. All bones were imaged with CT. In the plated group, radii were first imaged with the plates affixed (for simulating digital plate removal). They were then subsequently imaged with the locking plates and screws removed (actual plate removal). Fracture strength of the radius diaphysis under axial compression was predicted with a three-dimensional, specimen-specific, nonlinear finite element analysis for both the intact and plated bones (bones with and without the plate captured in the scan). Specimens were then loaded to failure using a universal testing machine to verify the actual fracture load. In the intact group, the physical and predicted fracture loads were strongly correlated. For radii with plates affixed, the physical and predicted (simulated plate removal and actual plate removal) fracture loads were strongly correlated. This study demonstrates that our specimen-specific finite element analysis can accurately predict the strength of the radial diaphysis. The metal artifact from CT imaging was shown to produce an overestimate of strength.     

Human evolution and osteoporosis-related spinal fractures

The field of evolutionary medicine examines the possibility that some diseases are the result of trade-offs made in human evolution. Spinal fractures are the most common osteoporosis-related fracture in humans, but are not observed in apes, even in cases of severe osteopenia. In humans, the development of osteoporosis is influenced by peak bone mass and strength in early adulthood as well as age-related bone loss. Here, we examine the structural differences in the vertebral bodies (the portion of the vertebra most commonly involved in osteoporosis-related fractures) between humans and apes before age-related bone loss occurs. Vertebrae from young adult humans and chimpanzees, gorillas, orangutans, and gibbons (T8 vertebrae, n = 8–14 per species, male and female, humans: 20–40 years of age) were examined to determine bone strength (using finite element models), bone morphology (external shape), and trabecular microarchitecture (micro-computed tomography). The vertebrae of young adult humans are not as strong as those from apes after accounting for body mass (p<0.01). Human vertebrae are larger in size (volume, cross-sectional area, height) than in apes with a similar body mass. Young adult human vertebrae have significantly lower trabecular bone volume fraction (0.26±0.04 in humans and 0.37±0.07 in apes, mean ± SD, p<0.01) and thinner vertebral shells than apes (after accounting for body mass, p<0.01). Since human vertebrae are more porous and weaker than those in apes in young adulthood (after accounting for bone mass), even modest amounts of age-related bone loss may lead to vertebral fracture in humans, while in apes, larger amounts of bone loss would be required before a vertebral fracture becomes likely. We present arguments that differences in vertebral bone size and shape associated with reduced bone strength in humans is linked to evolutionary adaptations associated with bipedalism.     

Prediction of Colles’ fracture load in human radius using cohesive finite element modeling

Osteoporotic and age-related fractures are a significant public health problem. One of the most common osteoporotic fracture sites in the aging population is distal radius. There is evidence in the literature that distal radius fractures (Colles’ fracture) are an indicative of increased risk of future spine and hip fractures. In this study, a nonlinear fracture mechanics-based finite element method is applied to human radius to assess its fracture load as a function of cortical bone geometry and material properties. Seven three-dimensional finite element models of radius were created and the fracture loads were determined by using cohesive finite element modeling which explicitly represents the crack and the fracture process zone behavior. The fracture loads found in the simulations (731–6793 N) were in the range of experimental values reported in the literature. The fracture loads predicted by the simulations decreased by 4–5% per decade based only on material level changes and by 6–20% per decade when geometrical changes were also included. Cortical polar moment of inertia at 15% distal radius showed the highest correlation to fracture load (r²=0.97). These findings demonstrate the strength of fracture mechanics-based finite element modeling and show that combining geometrical and material properties provides a better assessment of fracture risk in human radius.     

Simulating distal radius fracture strength using biomechanical tests: a modeling study examining the influence of boundary conditions

Distal radius fracture strength has been quantified using in vitro biomechanical testing. These tests are frequently performed using one of two methods: (1) load is applied directly to the embedded isolated radius or (2) load is applied through the hand with the wrist joint intact. Fracture loads established using the isolated radius method are consistently 1.5 to 3 times greater than those for the intact wrist method. To address this discrepancy, a validated finite element modeling procedure was used to predict distal radius fracture strength for 22 female forearms under boundary conditions simulating the isolated radius and intact wrist method. Predicted fracture strength was highly correlated between methods (r = 0.94; p < 0.001); however, intact wrist simulations were characterized by significantly reduced cortical shell load carriage and increased stress and strain concentrations. These changes resulted in fracture strength values less than half those predicted for the isolated radius simulations (2274 ± 824 N for isolated radius, 1124 ± 375 N for intact wrist; p < 0.001). The isolated radius method underestimated the mechanical importance of the trabecular compartment compared to the more physiologically relevant intact wrist scenario. These differences should be borne in mind when interpreting the physiologic importance of mechanical testing and simulation results.     

3D Simulation of Internal Tablet Strength During Tableting

This study presents a new approach to model powder compression during tableting. The purpose of this study is to introduce a new discrete element simulation model for particle–particle bond formation during tablet compression. This model served as the basis for calculating tablet strength distribution during a compression cycle. Simulated results were compared with real tablets compressed from microcrystalline cellulose/theophylline pellets with various compression forces. Simulated and experimental compression forces increased similarly. Tablet-breaking forces increased with the calculated strengths obtained from the simulations. The calculated bond strength distribution inside the tablets showed features similar to those of the density and pressure distributions in the literature. However, the bond strength distributions at the center of the tablets varied considerably between individual tablets.     

Effect of starting material particle size on its agglomeration behavior in high shear wet granulation

The effect of anhydrous lactose particle size distribution on its performance in the wet granulation process was evaluated. Three grades of anhydrous lactose were used in the study: “as is” manufacturer grade and 2 particle size fractions obtained by screening of the 60M lactose. Particle growth behavior of the 3 lactose grades was evaluated in a high shear mixer. Compactibility and porosity of the resulting granules were also evaluated. A uniaxial compression test on moist agglomerates of the 3 lactose grades was performed in an attempt to explain the mechanism of particle size effect observed in the high shear mixer. Particle growth of anhydrous lactose in the high shear mixer was inversely related to the particle size of the starting material. In addition, granulation manufactured using the grade with the smallest particle size was more porous and demonstrated enhanced compactibility compared with the other grades. Compacts with similar porosity and low liquid saturation demonstrated brittle behavior and their breakage strength was inversely related to lactose particle size in the uniaxial compression test, suggesting that material with smaller particle size may exhibit more pronounced nucleation behavior during wet granulation. On the other hand, compacts prepared at higher liquid saturation and similar compression force exhibited more plastic behavior and showed lower yield stress for the grade with smallest particle size. The lower yield stress of compacts prepared with this grade may indicate a higher coalescence tendency for its granules during wet granulation.     

Prediction of strength and strain of the proximal femur by a CT-based finite element method

Hip fractures are the most serious complication of osteoporosis and have been recognized as a major public health problem. In elderly persons, hip fractures occur as a result of increased fragility of the proximal femur due to osteoporosis. It is essential to precisely quantify the strength of the proximal femur in order to estimate the fracture risk and plan preventive interventions. CT-based finite element analysis could possibly achieve precise assessment of the strength of the proximal femur. The purpose of this study was to create a simulation model that could accurately predict the strength and surface strains of the proximal femur using a CT-based finite element method and to verify the accuracy of our model by load testing using fresh frozen cadaver specimens. Eleven right femora were collected. The axial CT scans of the proximal femora were obtained with a calibration phantom, from which the 3D finite element models were constructed. Materially nonlinear finite element analyses were performed. The yield and fracture loads were calculated, while the sites where elements failed and the distributions of the principal strains were determined. The strain gauges were attached to the proximal femoral surfaces. A quasi-static compression test of each femur was conducted. The yield loads, fracture loads and principal strains of the prediction significantly correlated with those measured (r=0.941, 0.979, 0.963). Finite element analysis showed that the solid elements and shell elements in undergoing compressive failure were at the same subcapital region as the experimental fracture site.     

Multi-axial mechanical properties of human trabecular bone

In the context of osteoporosis, evaluation of bone fracture risk and improved design of epiphyseal bone implants rely on accurate knowledge of the mechanical properties of trabecular bone. A multi-axial loading chamber was designed, built and applied to explore the compressive multi-axial yield and strength properties of human trabecular bone from different anatomical locations. A thorough experimental protocol was elaborated for extraction of cylindrical bone samples, assessment of their morphology by micro-computed tomography and application of different mechanical tests: torsion, uni-axial traction, uni-axial compression and multi-axial compression. A total of 128 bone samples were processed through the protocol and subjected to one of the mechanical tests up to yield and failure. The elastic data were analyzed using a tensorial fabric–elasticity relationship, while the yield and strength data were analyzed with fabric-based, conewise generalized Hill criteria. For each loading mode and more importantly for the combined results, strong relationships were demonstrated between volume fraction, fabric and the elastic, yield and strength properties of human trabecular bone. Despite the reviewed limitations, the obtained results will help improve the simulation of the damage behavior of human bones and bone-implant systems using the finite element method.     

The relative contributions of non-enzymatic glycation and cortical porosity on the fracture toughness of aging bone

The risk of fracture increases with age due to the decline of bone mass and bone quality. One of the age-related changes in bone quality occurs through the formation and accumulation of advanced glycation end-products (AGEs) due to non-enzymatic glycation (NEG). However as a number of other changes including increased porosity occur with age and affect bone fragility, the relative contribution of AGEs on the fracture resistance of aging bone is unknown. Using a high-resolution nonlinear finite element model that incorporate cohesive elements and micro-computed tomography-based 3d meshes, we investigated the contribution of AGEs and cortical porosity on the fracture toughness of human bone. The results show that NEG caused a 52% reduction in propagation fracture toughness (R-curve slope). The combined effects of porosity and AGEs resulted in an 88% reduction in propagation toughness. These findings are consistent with previous experimental results. The model captured the age-related changes in the R-curve toughening by incorporating bone quantity and bone quality changes, and these simulations demonstrate the ability of the cohesive models to account for the irreversible dynamic crack growth processes affected by the changes in post-yield material behavior. By decoupling the matrix-level effects due to NEG and intracortical porosity, we are able to directly determine the effects of NEG on fracture toughness. The outcome of this study suggests that it may be important to include the age-related changes in the material level properties by using finite element analysis towards the prediction of fracture risk.     

Finite element models predict cancellous apparent modulus when tissue modulus is scaled from specimen CT-attenuation

High-resolution architecture-based finite element models are commonly used for characterizing the mechanical behavior of cancellous bone. The vast majority of studies use homogeneous material properties to model trabecular tissue. The objectives of this study were to demonstrate that inhomogeneous finite element models that account for microcomputed tomography-measured tissue modulus variability more accurately predict the apparent stiffness of cancellous bone than homogeneous models, and to examine the sensitivity of an inhomogeneous model to the degree of tissue property variability. We tested five different material cases in finite element models of ten cancellous cubes in simulated uniaxial compression. Three of these cases were inhomogeneous and two were homogeneous. Four of these cases were unique to each specimen, and the remaining case had the same tissue modulus for all specimens. Results from all simulations were compared with measured elastic moduli from previous experiments. Tissue modulus variability for the most accurate of the three inhomogeneous models was then artificially increased to simulate the effects of non-linear CT-attenuation-modulus relationships. Uniqueness of individual models was more critical for model accuracy than level of inhomogeneity. Both homogeneous and inhomogeneous models that were unique to each specimen had at least 8% greater explanatory power for apparent modulus than models that applied the same material properties to all specimens. The explanatory power for apparent modulus of models with a tissue modulus coefficient of variation (COV) range of 21-31% was 13% greater than homogeneous models (COV=0). The results of this study indicate that inhomogenous finite element models that have tissue moduli unique to each specimen more accurately predict the elastic behavior of cancellous cubic specimens than models that have common tissue moduli between all specimens.     

Heterogeneous linear elastic trabecular bone modelling using micro-CT attenuation data and experimentally measured heterogeneous tissue properties

High-resolution voxel-based finite element software, such as FEEBE developed at the NCBES, is widely used for studying trabecular bone at the micro-scale. A new approach to determine heterogeneous bone tissue material properties for computational models was proposed in this study. The specimen-specific range of tissue moduli across strut width was determined from nanoindentation testing. This range was mapped directly using linear interpolation to that specimen's micro-computed tomography (microCT) grey value range as input material properties for finite element analysis. The method was applied to cuboid trabecular bone samples taken from eight, 4-year-old (skeletally mature) ovine L5 vertebrae. Before undergoing experimental uniaxial compression tests, the samples were microCT scanned and 30 microm resolution finite element models were generated. The linear elastic finite element models were compressed to 1% strain. This material property assignment method for computational models accurately reproduced the experimentally determined apparent modulus and concentrations of stress at locations of failure.     

Cohesive finite element modeling of age-related toughness loss in human cortical bone

Although the age-related loss of bone quality has been implicated in bone fragility, a mechanistic understanding of the relationship is necessary for developing diagnostic and treatment modalities in the elderly population at risk of fracture. In this study, a finite element based cohesive zone model is developed and applied to human cortical bone in order to capture the experimentally shown rising crack growth behavior and age-related loss of bone toughness. The cohesive model developed here is based on a traction–crack opening displacement relationship representing the fracture processes in the vicinity of a propagating crack. The traction–displacement curve, defining the cohesive model, is composed of ascending and descending branches that incorporate material softening and nonlinearity. The results obtained indicate that, in contrast to initiation toughness, the finite element simulations of crack growth in compact tension (CT) specimens successfully capture the rising R-curve (propagation toughness) behavior and the age-related loss of bone toughness. In close correspondence with the experimentally observed decrease of 14–15% per decade, the finite element simulation results show a decrease of 13% in the R-curve slope per decade. The success of the simulations is a result of the ability of cohesive models to capture and predict the parameters related to bone fracture by representing the physical processes occurring in the vicinity of a propagating crack. These results illustrate that fracture mechanisms in the process zone control bone toughness and any modification to these would cause age-related toughness loss.