Tissue stresses and strain in trabeculae of a canine proximal femur can be quantified from computer reconstructions

A quantitative assessment of bone tissue stresses and strains is essential for the understanding of failure mechanisms associated with osteoporosis, osteoarthritis, loosening of implants and cell- mediated adaptive bone-remodeling processes. According to Wolff's trajectorial hypothesis, the trabecular architecture is such that minimal tissue stresses are paired with minimal weight. This paradigm at least suggests that, normally, stresses and strains should be distributed rather evenly over the trabecular architecture. Although bone stresses at the apparent level were determined with finite element analysis (FEA), by assuming it to be continuous, there is no data available on trabecular tissue stresses or strains of bones in situ under physiological loading conditions. The objectives of this project were to supply reasonable estimates of these quantities for the canine femur, to compare trabecular-tissue to apparent stresses, and to test Wolff's hypothesis in a quantitative sense. For that purpose, the newly developed method of large-scale micro-FEA was applied in conjunction with micro-CT structural measurements. A three-dimensional high-resolution computer reconstruction of a proximal canine femur was made using a micro-CT scanner. This was converted to a large-scale FE-model with 7.6 million elements, adequately refined to represent individual trabeculae. Using a special-purpose FE-solver, analyses were conducted for three different orthogonal hip-joint loading cases, one of which represented the stance-phase of walking. By superimposing the results, the tissue stress and strain distributions could also be calculated for other force directions. Further analyses of results were concentrated on a trabecular volume of interest (VOI) located in the center of the head. For the stance phase of walking an average tissue principal strain in the VOI of 279 strain was found, with a standard deviation of 212 microstrain. The standard deviation depended not only on the hip-force magnitude, but also on its direction. In more than 95% of the tissue volume the principal stresses and strains were in a range from zero to three times the averages, for all hip-force directions. This indicates that no single load creates even stress or strain distributions in the trabecular architecture. Nevertheless, excessive values occurred at few locations only, and the maximum tissue stress was approximately half the value reported for the tissue fatigue strength. These results thus indicate that trabecular bone tissue has a safety factor of approximately two for hip-joint loads that occur during normal activities.     

Trabecular bone microdamage and microstructural stresses under uniaxial compression

The balance between local remodeling and accumulation of trabecular bone microdamage is believed to play an important role in the maintenance of skeletal integrity. However, the local mechanical parameters associated with microdamage initiation are not well understood. Using histological damage labeling, micro-CT imaging, and image-based finite element analysis, regions of trabecular bone microdamage were detected and registered to estimated microstructural von Mises effective stresses and strains, maximum principal stresses and strains, and strain energy density (SED). Bovine tibial trabecular bone cores underwent a stepwise uniaxial compression routine in which specimens were micro-CT imaged following each compression step. The results indicate that the mode of trabecular failure observed by micro-CT imaging agreed well with the polarity and distribution of stresses within an individual trabecula. Analysis of on-axis subsections within specimens provided significant positive relationships between microdamage and each estimated tissue stress, strain and SED parameter. In a more localized analysis, individual microdamaged and undamaged trabeculae were extracted from specimens loaded within the elastic region and to the apparent yield point. As expected, damaged trabeculae in both groups possessed significantly higher local stresses and strains than undamaged trabeculae. The results also indicated that microdamage initiation occurred prior to apparent yield at local principal stresses in the range of 88-121 MPa for compression and 35-43 MPa for tension and local principal strains of 0.46-0.63% in compression and 0.18-0.24% in tension. These data provide an important step towards understanding factors contributing to microdamage initiation and establishing local failure criteria for normal and diseased trabecular bone.     

Three-dimensional micro-level computational study of Wolff's law via trabecular bone remodeling in the human proximal femur using design space topology optimization

The law of bone remodeling, commonly referred to as Wolff's Law, asserts that the internal trabecular bone adapts to external loadings, reorienting with the principal stress trajectories to maximize mechanical efficiency creating a naturally optimum structure. The goal of the current study was to utilize an advanced structural optimization algorithm, called design space optimization (DSO), to perform a micro-level three-dimensional finite element bone remodeling simulation on the human proximal femur and analyse the results to determine the validity of Wolff's hypothesis. DSO optimizes the layout of material by iteratively distributing it into the areas of highest loading, while simultaneously changing the design domain to increase computational efficiency. The result is a "fully stressed" structure with minimized compliance and increased stiffness. The large-scale computational simulation utilized a 175 μm mesh resolution and the routine daily loading activities of walking and stair climbing. The resulting anisotropic trabecular architecture was compared to both Wolff's trajectory hypothesis and natural femur samples from literature using a variety of visualization techniques, including radiography and computed tomography (CT). The results qualitatively revealed several anisotropic trabecular regions, that were comparable to the natural human femurs. Quantitatively, the various regional bone volume fractions from the computational results were consistent with quantitative CT analyses. The global strain energy proceeded to become more uniform during optimization; implying increased mechanical efficiency was achieved. The realistic simulated trabecular geometry suggests that the DSO method can accurately predict bone adaptation due to mechanical loading and that the proximal femur is an optimum structure as the Wolff hypothesized.     

Variations in mineralization affect the stress and strain distributions in cortical and trabecular bone

The mechanical properties of bone depend largely on its degree and distribution of mineralization. The present study analyzes the effect of an inhomogeneous distribution of mineralization on the stress and strain distributions in the human mandibular condyle during static clenching. A condyle was scanned with a micro-CT scanner to create a finite element model. For every voxel the degree of mineralization (DMB) was determined from the micro-CT scan. The Young's moduli of the elements were calculated from the DMB using constant, linear, and cubic relations, respectively. Stresses, strains, and displacements in cortical and trabecular bone, as well as the condylar deformation (extension along the antero-posterion axis) and compliance were compared. Over 90% of the bone mineral was located in the cortical bone. The DMB showed large variations in both cortical bone (mean: 884, SD: 111 mg/cm(3)) and trabecular bone (mean: 738, SD: 101 mg/cm(3)). Variations of the stresses and the strains were small in cortical bone, but large in trabecular bone. In the cortical bone an inhomogeneous mineral distribution increased the stresses and the strains. In the trabecular bone, however, it decreased the stresses and increased the strains. Furthermore, the condylar compliance remained relatively constant, but the condylar deformation doubled. It was concluded that neglect of the inhomogeneity of the mineral distribution results in a large underestimation of the stresses and strains of possibly more than 50%. The stiffness of trabecular bone strongly influences the condylar deformation. Vice versa, the condylar deformation largely determines the magnitude of the strains in the trabecular bone.     

Incorporating tissue anisotropy and heterogeneity in finite element models of trabecular bone altered predicted local stress distributions

Trabecular bone is composed of organized mineralized collagen fibrils, which results in heterogeneous and anisotropic mechanical properties at the tissue level. Recently, biomechanical models computing stresses and strains in trabecular bone have indicated a significant effect of tissue heterogeneity on predicted stresses and strains. However, the effect of the tissue-level mechanical anisotropy on the trabecular bone biomechanical response is unknown. Here, a computational method was established to automatically impose physiologically relevant orientation inherent in trabecular bone tissue on a trabecular bone microscale finite element model. Spatially varying tissue-level anisotropic elastic properties were then applied according to the bone mineral density and the local tissue orientation. The model was used to test the hypothesis that anisotropy in both homogeneous and heterogeneous models alters the predicted distribution of stress invariants. Linear elastic finite element computations were performed on a 3 mm cube model isolated from a microcomputed tomography scan of human trabecular bone from the distal femur. Hydrostatic stress and von Mises equivalent stress were recorded at every element, and the distributions of these values were analyzed. Anisotropy reduced the range of hydrostatic stress in both tension and compression more strongly than the associated increase in von Mises equivalent stress. The effect of anisotropy was independent of the spatial redistribution high compressive stresses due to tissue elastic heterogeneity. Tissue anisotropy and heterogeneity are likely important mechanisms to protect bone from failure and should be included for stress analyses in trabecular bone.     

Computational study of Wolff's law with trabecular architecture in the human proximal femur using topology optimization

In the field of bone adaptation, it is believed that the morphology of bone is affected by its mechanical loads, and bone has self-optimizing capability; this phenomenon is well known as Wolff's law of the transformation of bone. In this paper, we simulated trabecular bone adaptation in the human proximal femur using topology optimization and quantitatively investigated the validity of Wolff's law. Topology optimization iteratively distributes material in a design domain producing optimal layout or configuration, and it has been widely and successfully used in many engineering fields. We used a two-dimensional micro-FE model with 50 microm pixel resolution to represent the full trabecular architecture in the proximal femur, and performed topology optimization to study the trabecular morphological changes under three loading cases in daily activities. The simulation results were compared to the actual trabecular architecture in previous experimental studies. We discovered that there are strong similarities in trabecular patterns between the computational results and observed data in the literature. The results showed that the strain energy distribution of the trabecular architecture became more uniform during the optimization; from the viewpoint of structural topology optimization, this bone morphology may be considered as an optimal structure. We also showed that the non-orthogonal intersections were constructed to support daily activity loadings in the sense of optimization, as opposed to Wolff's drawing.     

Spatial correlations of trabecular bone microdamage with local stresses and strains using rigid image registration

Although microdamage is known to accumulate in trabecular bone with overloading and aging, the tissue-level stresses and strains associated with local bone failure are not well known. Local correlation of microdamage with microstructural stresses and strains requires methods to accurately register histological sections with micro-computed tomography (micro-CT) based finite element models. In addition, the resolution of correlation (i.e., grid size) selected for analysis may affect the observed results. Therefore, an automated, repeatable, and accurate image registration algorithm was developed to determine the range of local stresses and strains associated with microdamage initiation. Using a two-dimensional rigid registration algorithm, bone structures from histology and micro-CT imaging were aligned. Once aligned, microdamaged regions were spatially correlated with local stresses and strains obtained from micro-CT based finite element analysis. Using this more sophisticated registration technique, we were able to analyze the effects of varying spatial grid resolution on local stresses and strains initiating microdamage. The results indicated that grid refinement to the individual pixel level (pixel-by-pixel method) more precisely defined the range of microdamage initiation compared to manually selected individual damaged and undamaged trabeculae. Using the pixel-by-pixel method, we confirmed that trabecular bone from younger cows sustained higher local strains prior to microdamage initiation compared to older bone.     

Wolff's law of trabecular architecture at remodeling equilibrium

An elastic constitutive relation for cancellous bone tissue is developed. This relationship involves the stress tensor T, the strain tensor E and the fabric tensor H for cancellous bone. The fabric tensor is a symmetric second rank tensor that is a quantitative stereological measure of the microstructural arrangement of trabeculae and pores in the cancellous bone tissue. The constitutive relation obtained is part of an algebraic formulation of Wolff's law of trabecular architecture in remodeling equilibrium. In particular, with the general constitutive relationship between T, H and E, the statement of Wolff's law at remodeling equilibrium is simply the requirement of the commutativity of the matrix multiplication of the stress tensor and the fabric tensor at remodeling equilibrium, T*H* = H*T*. The asterisk on the stress and fabric tensor indicates their values in remodeling equilibrium. It is shown that the constitutive relation also requires that E*H* = H*E*. Thus, the principal axes of the stress, strain and fabric tensors all coincide at remodeling equilibrium.     

The limitations of canine trabecular bone as a model for human: a biomechanical study

Distal canine femurs were sectioned into 8 mm cubic specimens. Orthogonal compression tests were performed to preyield in two or three directions and to failure in a third. Apparent density and ash weight density were measured for a subset of specimens. The results were compared to the human distal femur results of Ciarelli et al. (Transactions of the 32nd Annual Meeting of the Orthopaedic Research Society, Vol. 11, p. 42, 1986). Quantitative similarities existed in the fraction of components comprising the trabecular tissue of the two species. Qualitative similarities were seen in the positional and anisotropic variation of the mechanical properties, and also in the form and strength of the relationships between the mean modulus and bone density, ultimate stress and density, and ultimate stress and modulus. However, significantly different regression equations resulted for the mean modulus-density, and ultimate stress modulus relationships, indicating that for the same density, canine trabecular bone displays a lower modulus than human, and may achieve greater compressive strains before failure.     

Finite element analysis of a hemi-pelvis: the effect of inclusion of cartilage layer on acetabular stresses and strain

An appropriate method of application of the hip-joint force and stress analysis of the pelvic bone, in particular the acetabulum, is necessary to investigate the changes in load transfer due to implantation and to calculate the reference stimulus for bone remodelling simulations. The purpose of the study is to develop a realistic 3D finite element (FE) model of the hemi-pelvis and to assess stress and strain distribution during a gait cycle. The FE modelling approach of the pelvic bone was based on CT scan data and image segmentation of cortical and cancellous bone boundaries. Application of hip-joint force through an anatomical femoral head having a cartilage layer was found to be more appropriate than a perfectly spherical head, thereby leading to more accurate stress–strain distribution in the acetabulum. Within the acetabulum, equivalent strains varied between 0.1% and 0.7% strain in the cancellous bone. High compressive (15–30 MPa) and low tensile (0–5 MPa) stresses were generated within the acetabulum. The hip-joint force is predominantly transferred from the acetabulum through the lateral cortex to the sacroiliac joint and the pubic symphysis. The study is useful to understand the load transfer within the acetabulum and for further investigations on acetabular prosthesis.     

Detection of trabecular bone microdamage by micro-computed tomography

Microdamage is an important component of bone quality and affects bone remodeling. Improved techniques to assess microdamage without the need for histological sectioning would provide insight into the role of microdamage in trabecular bone strength by allowing the spatial distribution of damage within the trabecular microstructure to be measured. Nineteen cylindrical trabecular bone specimens were prepared and assigned to two groups. The specimens in group I were damaged to 3% compressive strain and labeled with BaSO(4). Group II was not loaded, but was labeled with BaSO(4). Micro-computed tomography (Micro-CT) images of the specimens were obtained at 10 microm resolution. The median intensity of the treated bone tissue was compared between groups. Thresholding was also used to measure the damaged area fraction in the micro-CT scans. The histologically measured damaged area fraction, the median CT intensity, and the micro-CT measured damaged area fraction were all higher in the loaded group than in the unloaded group, indicating that the micro-CT images could differentiate the damaged specimen group from the unloaded specimens. The histologically measured damaged area fraction was positively correlated with the micro-CT measured damaged area fraction and with the median CT intensity of the bone, indicating that the micro-CT images can detect microdamage in trabecular bone with sufficient accuracy to differentiate damage levels between samples. This technique provides a means to non-invasively assess the three-dimensional distribution of microdamage within trabecular bone test specimens and could be used to gain insight into the role of trabecular architecture in microdamage formation.     

Application of homogenization theory to the study of trabecular bone mechanics.

It is generally accepted that the strength and stiffness of trabecular bone is strongly affected by trabecular microstructure. It has also been hypothesized that stress induced adaptation of trabecular bone is affected by trabecular tissue level stress and/or strain. At this time, however, there is no generally accepted (or easily accomplished) technique for predicting the effect of microstructure on trabecular bone apparent stiffness and strength or estimating tissue level stress or strain. In this paper, a recently developed mechanics theory specifically designed to analyze microstructured materials, called the homogenization theory, is presented and applied to analyze trabecular bone mechanics. Using the homogenization theory it is possible to perform microstructural and continuum analyses separately and then combine them in a systematic manner. Stiffness predictions from two different microstructural models of trabecular bone show reasonable agreement with experimental results, depending on metaphyseal region, (R2 greater than 0.5 for proximal humerus specimens, R2 less than 0.5 for distal femur and proximal tibia specimens). Estimates of both microstructural strain energy density (SED) and apparent SED show that there are large differences (up to 30 times) between apparent SED (as calculated by standard continuum finite element analyses) and the maximum microstructural or tissue SED. Furthermore, a strut and spherical void microstructure gave very different estimates of maximum tissue SED for the same bone volume fraction (BV/TV). The estimates from the spherical void microstructure are between 2 and 20 times greater than the strut microstructure at 10-20% BV/TV.     

Stress-concentrating effect of resorption lacunae in trabecular bone

Analyses of the distributions of stress and strain within individual bone trabeculae have not yet been reported. In this study, four trabeculae were imaged and finite elements models were generated in an attempt to quantify the variability of stress/strain in real trabeculae. In three of these trabeculae, cavities were identified with depths comparable to values reported for resorption lacunae ( approximately 50 microm)-although we cannot be certain, it is most probable that they are indeed resorption lacunae. A tensile load was applied to each trabeculum to simulate physiological loading and to ensure that bending was minimized. The force carried by each trabecula was calculated from this value using the average cross sectional area of each trabecula. The analyses predict that very high stresses (>100 MPa) existed within bone trabecular tissue. Stress and strain distributions were highly heterogeneous in all cases, more so in trabeculae with the presumptive resorption lacunae where at least 30% of the tissue had a strain greater than 4000 micoepsilon in all cases. Stresses were elevated at the pit of the lacunae, and peak stress concentrations were located in the longitudinal direction ahead of the lacunae. Given these high strains, we suggest that microdamage is inevitable around resorption lacunae in trabecular bone, and may cause the bone multicellular unit to proceed to resorb a packet of bone in the trabeculum rather than just resorb whatever localized area was initially targeted.     

Mineral heterogeneity affects predictions of intratrabecular stress and strain

Knowledge of the influence of mineral variations (i.e., mineral heterogeneity) on biomechanical bone behavior at the trabecular level is limited. The aim of this study is to investigate how this material property affects the intratrabecular distributions of stress and strain in human adult trabecular bone. Two different sets of finite element (FE) models of trabecular samples were constructed; tissue stiffness was either scaled to the local degree of mineralization of bone as measured with microCT (heterogeneous) or tissue stiffness was assumed to be homogeneous. The influence of intratrabecular mineral heterogeneity was analyzed by comparing both models. Interesting effects were seen regarding intratrabecular stress and strain distributions. In the homogeneous model, the highest stresses were found at the surface with a significant decrease towards the core. Higher superficial stresses could indicate a higher predicted fracture risk in the trabeculae. In the heterogeneous model this pattern was different. A significant increase in stress with increasing distance from the trabecular surface was found followed by a significant decrease towards the core. This suggests trabecular bending during a compression. In both models a decrease in strain values from surface to core was predicted, which is consistent with trabecular bending. When mineral heterogeneity was taken into account, the predicted intratrabecular patterns of stress and strain are more consistent with the expected biomechanical behavior as based on mineral variations in trabeculae. Our findings indicate that mineral heterogeneity should not be neglected when performing biomechanical studies on topics such as the (long-term or dose dependent) effects of antiresorptive treatments.     

Quantification of a rat tail vertebra model for trabecular bone adaptation studies

A feedback controlled loading apparatus for the rat tail vertebra was developed to deliver precise mechanical loads to the eighth caudal vertebra (C8) via pins inserted into adjacent vertebrae. Cortical bone strains were recorded using strain gages while subjecting the C8 in four cadaveric rats to mechanical loads ranging from 25 to 100 N at 1 Hz with a sinusoidal waveform. Finite element (FE) models, based on micro computed tomography, were constructed for all four C8 for calculations of cortical and trabecular bone tissue strains. The cortical bone strains predicted by FE models agreed with strain gage measurements, thus validating the FE models. The average measured cortical bone strain during 25-100 N loading was between 298 +/- 105 and 1210 +/- 297 microstrain (muepsilon). The models predicted average trabecular bone tissue strains ranging between 135 +/- 35 and 538 +/- 138 mu epsilon in the proximal region, 77 +/- 23-307 +/- 91 muepsilon in the central region, and 155 +/- 36-621 +/- 143 muepsilon in the distal region for 25-100 N loading range. Although these average strains were compressive, it is also interesting that the trabecular bone tissue strain can range from compressive to tensile strains (-1994 to 380 mu epsilon for a 100 N load). With this novel approach that combines an animal model with computational techniques, it could be possible to establish a quantitative relationship between the microscopic stress/strain environment in trabecular bone tissue, and the biosynthetic response and gene expression of bone cells, thereby study bone adaptation.     

Biaxial failure behavior of bovine tibial trabecular bone

Multiaxial failure properties of trabecular bone are important for modeling of whole bone fracture and can provide insight into structure-function relationships. There is currently no consensus on the most appropriate form of multiaxial yield criterion for trabecular bone. Using experimentally validated, high-resolution, non-linear finite element models, biaxial plain strain boundary conditions were applied to seven bovine tibial specimens. The dependence of multiaxial yield properties on volume fraction was investigated to quantify the interspecimen heterogeneity in yield stresses and strains. Two specimens were further analyzed to determine the yield properties for a wide range of biaxial strain loading conditions. The locations and quantities of tissue level yielding were compared for on-axis, transverse, and biaxial apparent level yielding to elucidate the micromechanical failure mechanisms. As reported for uniaxial loading of trabecular bone, the yield strains in multiaxial loading did not depend on volume fraction, whereas the yield stresses did. Micromechanical analysis indicated that the failure mechanisms in the on-axis and transverse loading directions were mostly independent. Consistent with this, the biaxial yield properties were best described by independent curves for on-axis and transverse loading. These findings establish that the multiaxial failure of trabecular bone is predominantly governed by the strain along the loading direction, requiring separate analytical expressions for each orthotropic axis to capture the apparent level yield behavior.     

Accuracy and precision of digital volume correlation in quantifying displacements and strains in trabecular bone

Strain measurement is an essential tool in the study of trabecular bone structure-function relationships. Digital volume correlation (DVC) is a measurement technique that quantifies strains throughout the interior of a specimen, rather than simply those on the surface. DVC relies on tracking the movement of microstructural features, and as such, the accuracy and precision of this technique may depend on trabecular structure. This study quantified displacement and strain measurement errors in six types of trabecular bone that spanned a wide range of volume fraction and trabecular architecture. Accuracy and precision were compared across bone type and also across three DVC methods. Both simulated and real displacement fields were analyzed using micro-computed tomography images of specimens from the bovine distal femur, bovine proximal tibia, rabbit distal femur, rabbit proximal tibia, rabbit vertebra, and human vertebra. Differences as large as three-fold in accuracy and precision of the displacements and strains were found among DVC methods and among bone types. The displacement precision and the strain accuracy and precision were correlated with measures of trabecular structure such as structural model index. These results demonstrate that the performance of the DVC technique can depend on trabecular structure. Across all bone types, the displacement and strain errors ranged 1.86-3.39 microm and 345-794 microepsilon, respectively. For specimens from the human vertebra and bovine distal femur, the measurement errors were approximately 20 times smaller than the yield strain. In these cases, DVC is a viable technique for measuring pre- and post-yield strains throughout trabecular bone specimens and the trabecular compartment of whole bones.     

Fatigue of bovine trabecular bone

Fatigue loading of bone, from the activities of daily living in the elderly, or from prolonged exercise in the young, can lead to increased risk of fracture. Elderly patients with osteoporosis are particularly prone to fragility fractures of the vertebrae, where load is carried primarily by trabecular bone. In this study, specimens of bovine trabecular bone were loaded in compressive fatigue at four different normalized stresses to one of six maximum strains. The resulting change in modulus and residual strain accumulation were measured over the life of the fatigue test. The number of cycles to reach a given maximum compressive strain increased with decreasing normalized stress. Modulus reduction and specimen residual strain increased with increasing maximum compressive strain, but few differences were observed between specimens loaded to the same maximum strain at different normalized stresses.     

Hip-joint and abductor-muscle forces adequately represent in vivo loading of a cemented total hip reconstruction.

Using finite element analyses, we investigated which muscle groups acting around the hip-joint most prominently affected the load distributions in cemented total hip reconstructions with a bonded and debonded femoral stem. The purpose was to determine which muscle groups should be included in pre-clinical tests, predicting bone adaptation and mechanical failure of cemented reconstructions, ensuring an adequate representation of in vivo loading of the reconstruction. Loads were applied as occurring during heel-strike, mid-stance and push-off phases of gait. The stress/strain distributions within the reconstruction, produced by the hip-joint contact force, were compared to ones produced after sequentially including the abductors, the iliotibial tract and the adductors and vastii. Inclusion of the abductors had the most pronounced effect. They neutralized lateral bending of the reconstruction at heel-strike and increased medial bending at mid-stance and push-off. Bone strains and stem stresses were changed accordingly. Peak tensile cement stresses were reduced during all gait phases by amounts up to 50% around a bonded stem and 11% around a debonded one. Additional inclusion of the iliotibial tract, the adductors and the vastii produced relatively small effects during all gait phases. Their most prominent effect was a slight reduction of bone strains at the level of the stem tip during heel-strike. These results suggest that a loading configuration including the hip-joint contact force and the abductor forces can adequately reproduce in vivo loading of cemented total hip reconstructions in pre-clinical tests.     

Functional adaptation of cancellous bone in human proximal femur predicted by trabecular surface remodeling simulation toward uniform stress state

Two-dimensional simulation of trabecular surface remodeling was conducted for a human proximal femur to investigate the structural change of cancellous bone toward a uniform stress state. Considering that a local mechanical stimulus plays an important role in cellular activities in bone remodeling, local stress nonuniformity was assumed to drive trabecular structural change to seek a uniform stress state. A large-scale pixel-based finite element model was used to simulate structural changes of individual trabeculae over the entire bone. As a result, the initial structure of trabeculae changed from isotropic to anisotropic due to trabecular microstructural changes caused by surface remodeling according to the mechanical environment in the proximal femur. Under a single-loading condition, it was shown that the apparent structural property evaluated by fabric ellipses corresponded to the apparent stress state in cancellous bone. As is observed in the actual bone, a distributed trabecular structure was obtained under a multiple-loading condition. Through these studies, it was concluded that trabecular surface remodeling toward a local uniform stress state at the trabecular level could naturally bring about functional adaptation phenomenon at the apparent tissue level. The proposed simulation model would be capable of providing insight into the hierarchical mechanism of trabecular surface remodeling at the microstructural level up to the apparent tissue level.