The effect of surface roughness on the stress adaptation of trabecular architecture around a cylindrical implant

The effect of implant-bone bonding and the effect of implant surface roughness on bone remodeling near the bone-implant interface were studied by using a surface remodeling theory and the boundary element method. The study has shown that implant attachment plays an important role in bone remodeling near the implant. It has been observed in animal experiments and in clinical situations that the remodeled trabecular bone architecture around a cylindrical implant could vary, on one hand, from a hub surrounding the implant with a set of external spokes to, on the other hand, a hubless situation in which a set of spokes attach directly to the implant. It is shown here that the difference in these structures may be attributed to differences in implant attachment. The results show that the bone with perfect bonding or roller boundary condition without a gap remodeled to a hubless spoke trabecular bone architecture. On the other hand, the roller boundary condition with a specified gap yielded a spoke trabecular architecture with a hub or ring surrounding the implant. These quantitative results mirror the experimental and clinical observations. It is concluded that the hub is a consequence of the gap and not a consequence of the lack of friction between the implant and the bone.     

Trabecular bone remodeling around smooth and porous implants in an equine patellar model

The objective of this investigation was to examine the stress-morphology relationships for trabecular bone around implants with different surface characteristics. Stainless steel spheres with either a polished surface or a sintered-bead porous coating were implanted unilaterally into equine patellae and maintained for a 6 month period. Stereological methods were used to quantify the trabecular bone morphology and finite element analyses were performed to predict the trabecular bone stresses. In general, the remodeling response around the smooth implants was greater than that around those porous implants that exhibited bone ingrowth. In accordance with these differences, the finite element models predicted greater changes in the stresses adjacent to the smooth implants due to the nonlinear boundary conditions. However, it did not appear that the trajectorial theory, in its simplest form, was applicable to the remodeling induced by the implants. A linear relationship between the change in bone areal density and the change in von Mises effective stress provides support for the hypothesis that the architecture of trabecular bone corresponds to an optimal structure. The results also demonstrated that, under certain circumstances, small changes in the stress state may result in large changes in the principal material orientation.     

Can deterministic mechanical size effects contribute to fracture and microdamage accumulation in trabecular bone?

Failure of bone under monotonic and cyclic loading is related to the bone mineral density, the quality of the bone matrix, and the evolution of microcracks. The theory of linear elastic fracture mechanics has commonly been applied to describe fracture in bone. Evidence is presented that bone failure can be described through a non-linear theory of fracture. Thereby, deterministic size effects are introduced. Concepts of a non-linear theory are applied to discern how the interaction among bone matrix constituents (collagen and mineral), microcrack characteristics, and trabecular architecture can create distinctively differences in the fracture resistance at the bone tissue level. The non-linear model is applied to interpret pre-clinical data concerning the effects of anti-osteoporotic agents on bone properties. The results show that bisphosphonate (BP) treatments that suppress bone remodeling will change trabecular bone in ways such that the size of the failure process zone relative to the trabecular thickness is reduced. Selective estrogen receptor modulators (SERMs) that suppress bone remodeling will change trabecular bone in ways such that the size of the failure process zone relative to the trabecular thickness is increased. The consequences of these changes are reflected in bone mechanical response and predictions are consistent with experimental observations in the animal model which show that BP treatment is associated with more brittle fracture and microcracks without altering the average length of the cracks, whereas SERM treatments lead to a more ductile fracture and mainly increase crack length with a smaller increase in microcrack density. The model suggests that BPs may be more effective in cases in which bone mass is very low, whereas SERMS may be more effective when milder osteoporotic symptoms are present.     

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.     

Variation of surface density and other parameters in remodeling of trabecular bone in various conditions

To appreciate the remodeling of the trabecular bone, the static morphometric parameters of surface density (SV(TRAB/BONE] and volumetric fraction (VV(TRAB/BONE] of cancellous bone were measured and compared to remodeling parameters, i.e., the surface extents of active/inactive resorption, active bone formation and nonmineralized bone. Iliac bone biopsies from 28 subjects with spasmophilia, osteoporosis and primary hyperparathyroidism were studied by means of a Nachet-France NS 2000 automatic image analyzer and a Zeiss ocular integrator; the results obtained in each group showed comparable values for the two methods (r = .8 for each group, with P less than .01). The remodeling parameters measured by means of the ocular integrator were compared with the variation measurements of the trabecular surface density, SV(TRAB/BONE). The correlation between the inactive osteoid surface and the coefficient of variation of the mean (CVM of SV(TRAB/BONE] on sections was significant for the three pathologic groups. The average mean values and standard errors of the mean of this latter parameter for the spasmophilia and hyperparathyroidic groups were, respectively, 0.063 +/- 0.008 and 0.092 +/- 0.012. Analysis of the experimental data shows that the simple global measurement of CVM (SV(TRAB/BONE] by means of an automatic image analyzer supplies information on the skeletal state during tissue remodeling.     

Trabecular surface remodeling simulation for cancellous bone using microstructural voxel finite element models

A computational simulation method for three-dimensional trabecular surface remodeling was proposed, using voxel finite element models of cancellous bone, and was applied to the experimental data. In the simulation, the trabecular microstructure was modeled based on digital images, and its morphological changes due to surface movement at the trabecular level were directly expressed by removing/adding the voxel elements from/to the trabecular surface. A remodeling simulation at the single trabecular level under uniaxial compressive loading demonstrated smooth morphological changes even though the trabeculae were modeled with discrete voxel elements. Moreover, the trabecular axis rotated toward the loading direction with increasing stiffness, simulating functional adaptation to the applied load. In the remodeling simulation at the trabecular structural level, a cancellous bone cube was modeled using a digital image obtained by microcomputed tomography (microCT), and was uniaxially compressed. As a result, the apparent stiffness against the applied load increased by remodeling, in which the trabeculae reoriented to the loading direction. In addition, changes in the structural indices of the trabecular architecture coincided qualitatively with previously published experimental observations. Through these studies, it was demonstrated that the newly proposed voxel simulation technique enables us to simulate the trabecular surface remodeling and to compare the results obtained using this technique with the in vivo experimental data in the investigation of the adaptive bone remodeling phenomenon.     

Computational simulation of simultaneous cortical and trabecular bone change in human proximal femur during bone remodeling

In this study, we developed a numerical framework that computationally determines simultaneous and interactive structural changes of cortical and trabecular bone types during bone remodeling, and we investigated the structural correlation between the two bone types in human proximal femur. We implemented a surface remodeling technique that performs bone remodeling in the exterior layer of the cortical bone while keeping its interior area unchanged. A micro-finite element (μFE) model was constructed that represents the entire cortical bone and full trabecular architecture in human proximal femur. This study simulated and compared the bone adaptation processes of two different structures: (1) femoral bone that has normal cortical bone shape and (2) perturbed femoral bone that has an artificial bone lump in the inferomedial cortex. Using the proposed numerical method in conjunction with design space optimization, we successfully obtained numerical results that resemble actual human proximal femur. The results revealed that actual cortical bone, as well as the trabecular bone, in human proximal femur has structurally optimal shapes, and it was also shown that a bone abnormality that has little contribution to bone structural integrity tends to disappear. This study also quantitatively determined the structural contribution of each bone: when the trabecular adaptation was complete, the trabecular bone supported 54% of the total load in the human proximal femur while the cortical bone carried 46%.     

Invited Review: Pathogenesis of osteoporosis.

Patients with fragility fractures may have abnormalities in bone structural and material properties such as larger or smaller bone size, fewer and thinner trabeculae, thinned and porous cortices, and tissue mineral content that is either too high or too low. Bone models and remodels throughout life; however, with advancing age, less bone is replaced than was resorbed within each remodeling site. Estrogen deficiency at menopause increases remodeling intensity: a greater proportion of bone is remodeled on its endosteal (inner) surface, and within each of the many sites even more bone is lost as more bone is resorbed while less is replaced, accelerating architectural decay. In men, there is no midlife increase in remodeling. Bone loss within each remodeling site proceeds by reduced bone formation, producing trabecular and cortical thinning. Hypogonadism in 20-30% of elderly men contributes to bone loss. In both sexes, calcium malabsorption and secondary hyperparathyroidism increase remodeling: more bone is removed from an ever-diminishing bone mass. As bone is removed from the endosteal envelope, concurrent bone formation on the periosteal (outer) bone surface during aging partly offsets bone loss and increases bone's cross-sectional area. Periosteal apposition is less in women than in men; therefore, women have more net bone loss because they gain less on the periosteal surface, not because they resorb more on the endosteal surface. More women than men experience fractures because their smaller skeleton incurs greater architectural damage and adapts less by periosteal apposition.     

Comparison of different hip prosthesis shapes considering micro-level bone remodeling and stress-shielding criteria using three-dimensional design space topology optimization

Since the late 1980s, computational analysis of total hip arthroplasty (THA) prosthesis components has been completed using macro-level bone remodeling algorithms. The utilization of macro-sized elements requires apparent bone densities to predict cancellous bone strength, thereby, preventing visualization and analysis of realistic trabecular architecture. In this study, we utilized a recently developed structural optimization algorithm, design space optimization (DSO), to perform a micro-level three-dimensional finite element bone remodeling simulation on the human proximal femur pre- and post-THA. The computational simulation facilitated direct performance comparison between two commercially available prosthetic implant stems from Zimmer Inc.: the Alloclassic and the Mayo conservative. The novel micro-level approach allowed the unique ability to visualize the trabecular bone adaption post-operation and to quantify the changes in bone mineral content by region. Stress-shielding and strain energy distribution were also quantified for the immediate post-operation and the stably fixated, post-remodeling conditions. Stress-shielding was highest in the proximal region and remained unchanged post-remodeling; conversely, the mid and distal portions show large increases in stress, suggesting a distal shift in the loadpath. The Mayo design conserves bone mass, while simultaneously reducing the incidence of stress-shielding compared to the Alloclassic, revealing a key benefit of the distinctive geometry. Several important factors for stable fixation, determined in clinical evaluations from the literature, were evident in both designs: high levels of proximal bone loss and distal bone densification. The results suggest this novel computational framework can be utilized for comparative hip prosthesis shape, uniquely considering the post-operation bone remodeling as a design criterion.     

Computational determination of the critical microcrack size that causes a remodeling response in a trabecula: a feasibility study

Bone is a living tissue, which undergoes continuous renewal to repair local defects. Two separate processes, adaptation and remodeling, are involved when a defect appears. The defect produces stress concentrations that provoke regional adaptation, and is gradually repaired, first by resorption and then by deposition of new bone. Using a mathematical formulation of the adaptation mechanism in trabeculae of cancellous bone, we hypothesize that in some cases, where a microcrack is small enough relative to the dimensions of the trabecula, the adaptation response of the whole trabecula may be sufficient to regain homeostatic mechanical conditions (with no need for a remodeling process). The simulation results showed that for trabeculae with nominal length of 900 microm and nominal thickness of 80-800 microm, a microcrack with minimal length of 48 microm and minimal depth of 13% of the trabecula's thickness was required to initiate a remodeling process. A longer (100 microm) but shallower (depth of 7% of the trabecula's thickness) crack also triggered remodeling. These computational results support our hypothesis that when a microcrack small enough relative to the dimensions of the trabecula occurs, adaptation of the whole trabecula may be sufficient to regain homeostatic mechanical conditions with no need for a local remodeling process.     

Effects of Materials of Cementless Femoral Stem on the Functional Adaptation of Bone

The objective of this paper is to identify the effects of materials of cementless femoral stem on the functional adaptive behaviors of bone.The remodeling behaviors of a two-dimensional simplified model of cementless hip prosthesis with stiff stem,flexible 'iso-elastic' stem,one-dimensional Functionally Graded Material (FGM) stem and two-dimensional FGM stem for the period of four years after prosthesis replacement were quantified by incorporating the bone remodeling algorithm with finite element analysis.The distributions of bone density,von Mises stress,and interface shear stress were obtained.The results show that two-dimensional FGM stem may produce more mechanical stimuli and more uniform interface shear stress compared with the stems made of other materials,thus the host bone is well preserved.Accordingly,the two-dimensional FGM stem is an appropriate femoral implant from a biomechanical point of view.The numerical simulation in this paper can provide a quantitative computational paradigm for the changes of bone morphology caused by implants,which can help to improve the design of implant to reduce stress shielding and the risk of bone-prosthesis interface failure.     

Osteoclast-osteoblast communication

Cells in osteoclast and osteoblast lineages communicate with each other through cell-cell contact, diffusible paracrine factors and cell-bone matrix interaction. Osteoclast-osteoblast communication occurs in a basic multicellular unit (BMU) at the initiation, transition and termination phases of bone remodeling. At the initiation phase, hematopoietic precursors are recruited to the BMU. These precursors express cell surface receptors including c-Fms, RANK and costimulatory molecules, such as osteoclast-associated receptor (OSCAR), and differentiate into osteoclasts following cell-cell contact with osteoblasts, which express ligands. Subsequently, the transition from bone resorption to formation is mediated by osteoclast-derived ‘coupling factors’, which direct the differentiation and activation of osteoblasts in resorbed lacunae to refill it with new bone. Bidirectional signaling generated by interaction between ephrinB2 on osteoclasts and EphB4 on osteoblast precursors facilitates the transition. Such interaction is likely to occur between osteoclasts and lining cells in the bone remodeling compartment (BRC). At the termination phase, bone remodeling is completed by osteoblastic bone formation and mineralization of bone matrix. Here, we describe molecular communication between osteoclasts and osteoblasts at distinct phases of bone remodeling.     

Capturing microscopic features of bone remodeling into a macroscopic model based on biological rationales of bone adaptation

To understand Wolff’s law, bone adaptation by remodeling at the cellular and tissue levels has been discussed extensively through experimental and simulation studies. For the clinical application of a bone remodeling simulation, it is significant to establish a macroscopic model that incorporates clarified microscopic mechanisms. In this study, we proposed novel macroscopic models based on the microscopic mechanism of osteocytic mechanosensing, in which the flow of fluid in the lacuno-canalicular porosity generated by fluid pressure gradients plays an important role, and theoretically evaluated the proposed models, taking biological rationales of bone adaptation into account. The proposed models were categorized into two groups according to whether the remodeling equilibrium state was defined globally or locally, i.e., the global or local uniformity models. Each remodeling stimulus in the proposed models was quantitatively evaluated through image-based finite element analyses of a swine cancellous bone, according to two introduced criteria associated with the trabecular volume and orientation at remodeling equilibrium based on biological rationales. The evaluation suggested that nonuniformity of the mean stress gradient in the local uniformity model, one of the proposed stimuli, has high validity. Furthermore, the adaptive potential of each stimulus was discussed based on spatial distribution of a remodeling stimulus on the trabecular surface. The theoretical consideration of a remodeling stimulus based on biological rationales of bone adaptation would contribute to the establishment of a clinically applicable and reliable simulation model of bone remodeling.     

Over-expression of fibroblast growth factor-2 causes defective bone mineralization and osteopenia in transgenic mice

Over-expression of human FGF-2 cDNA linked to the phosphoglycerate kinase promoter in transgenic (TgFGF2) mice resulted in a dwarf mouse with premature closure of the growth plate and shortening of bone length. This study was designed to further characterize bone structure and remodeling in these mice. Bones of 1-6 month-old wild (NTg) and TgFGF2 mice were studied. FGF-2 protein levels were higher in bones of TgFGF2 mice. Bone mineral density was significantly decreased as early as 1 month in femurs from TgFGF2 mice compared with NTg mice. Micro-CT of trabecular bone of the distal femurs from 6-month-old TgFGF2 mice revealed significant reduction in trabecular bone volume, trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Osteoblast surface/bone surface, double-labeled surface, mineral apposition rate, and bone formation rates were all significantly reduced in TgFGF2 mice. There were fewer TRAP positive osteoclasts in calvaria from TgFGF2 mice. Quantitative histomorphometry showed that total bone area was similar in both genotypes, however percent osteoclast surface, and osteoclast number/bone surface were significantly reduced in TgFGF2 mice. Increased replication of TgFGF2 calvarial osteoblasts was observed and primary cultures of bone marrow stromal cells from TgFGF2 expressed markers of mature osteoblasts but formed fewer mineralized nodules. The data presented indicate that non-targeted over-expression of FGF-2 protein resulted in decreased endochondral and intramembranous bone formation. These results are consistent with FGF-2 functioning as a negative regulator of postnatal bone growth and remodeling in this animal model.     

A Femur-Implant Model for the Prediction of Bone Remodeling Behavior Induced by Cementless Stem

Bone remodeling simulation is an effective tool for the prediction of long-term effect of implant on the bone tissue, as well as the selection of an appropriate implant in terms of architecture and material. In this paper, a finite element model of proximal femur was developed to simulate the structures of internal trabecular and cortical bones by incorporating quantitative bone functional adaptation theory with finite element analysis. Cementless stems made of titanium, two types of Functionally Graded Material (FGM) and flexible ‘iso-elastic’ material as comparison were implanted in the structure of proximal femur respectively to simulate the bone remodeling behaviors of host bone. The distributions of bone density, von Mises stress, and interface shear stress were obtained. All the prosthetic stems had effects on the bone remodeling behaviors of proximal femur, but the degrees of stress shielding were different. The amount of bone loss caused by titanium implant was in agreement with the clinical observation. The FGM stems caused less bone loss than that of the titanium stem, in which FGM I stem (titanium richer at the top to more HAP/Col towards the bottom) could relieve stress shielding effectively, and the interface shear stresses were more evenly distributed in the model with FGM I stem in comparison with those in the models with FGM II (titanium and bioglass) and titanium stems. The numerical simulations in the present study provided theoretical basis for FGM as an appropriate material of femoral implant from a biomechanical point of view. The next steps are to fabricate FGM stem and to conduct animal experiments to investigate the effects of FGM stem on the remodeling behaviors using animal model.     

A quantitative comparison of a bone remodeling model with dual-energy X-ray absorptiometry and analysis of the inter-individual biological variability of femoral neck T-score

The development of consistent procedures with the inclusion of patient-specific data is essential in the computational modeling of biological processes, in order to achieve clinical relevant data. In this work, these issues are addressed with the development of a methodology that combines the gold standard technique for bone mineral density measurement and osteoporosis diagnosis, Dual energy X-ray absorptiometry (DXA), with a computational model for bone remodeling simulation. The DXA results were divided in three samples constituted from proximal femur DXA exams of patients in different stages of bone mineral density (normal, osteopenia and osteoporosis). These results were quantitatively compared with computational model results. A correlation study was performed between femoral neck T-score and a parameter from the model to ascertain the hypothesis of adjusting the model accordingly to biological variables. The results evidenced the predictive ability of the computational model in the estimation of femoral neck bone mineral content (BMC), with a maximum relative error of 3.92%. On the other hand, a strong correlation (R=?0.862) was found between the variables in study and a mathematical relationship was obtained to estimate the range of values for a model parameter that leads to biological relevant results. The methodology developed and the results obtained represent a solid and reliable basis to further studies on bone quality, ensuring the validity of the computational model in the simulation of bone remodeling process.     

Bone remodeling of diaphyseal surfaces by torsional loads: theoretical predictions

A theory of surface bone remodeling is extended to include the effects of shearing strains as well as normal strains. It is shown that the surface velocity can only depend upon the square of shearing strains, but that it can be linear as well as quadratic in the normal strains. The theory is applied to predict the surface bone remodeling in the diaphysis of a long bone under combined axial and torsional loading. In the general case the diaphysis of the long bone is modeled as a hollow thin-walled cylinder of arbitrary cross-section and, in a special case, as a right circular thin-walled tube. It is shown here that if a thin-walled right circular cylinder capable of surface remodeling is subjected to an axial compressive load and a twisting torque, then the effect of increasing the torque is the same as the effect of decreasing the axial compressive load, namely the mean radius of the cross-section increases and the wall width thins. Conversely, the effect of reducing the torque is the same as the effect of increasing the axial compressive load, namely the mean radius of the cross-section decreases and the wall width thickens.     

Role of Cbl-PI3K Interaction during Skeletal Remodeling in a Murine Model of Bone Repair

Mice in which Cbl is unable to bind PI3K (YF mice) display increased bone volume due to enhanced bone formation and repressed bone resorption during normal bone homeostasis. We investigated the effects of disrupted Cbl-PI3K interaction on fracture healing to determine whether this interaction has an effect on bone repair. Mid-diaphyseal femoral fractures induced in wild type (WT) and YF mice were temporally evaluated via micro-computed tomography scans, biomechanical testing, histological and histomorphometric analyses. Imaging analyses revealed no change in soft callus formation, increased bony callus formation, and delayed callus remodeling in YF mice compared to WT mice. Histomorphometric analyses showed significantly increased osteoblast surface per bone surface and osteoclast numbers in the calluses of YF fractured mice, as well as increased incorporation of dynamic bone labels. Furthermore, using laser capture micro-dissection of the fracture callus we found that cells lacking Cbl-PI3K interaction have higher expression of Osterix, TRAP, and Cathepsin K. We also found increased expression of genes involved in propagating PI3K signaling in cells isolated from the YF fracture callus, suggesting that the lack of Cbl-PI3K interaction perhaps results in enhanced PI3K signaling, leading to increased bone formation, but delayed remodeling in the healing femora.