Overload arthrosis: strain patterns in the equine metacarpal condyle

An overload arthrosis occurs consistently in the palmar region of the metacarpal condyle of the equine fetlock (metacarpophalangeal) joint characterized by subchondral bone sclerosis, devitalization and mechanical failure leading to collapse of the overlying articular cartilage. Samples were selected of joints with mild, moderate, and severe subchondral sclerosis, in which cartilage collapse had not yet occurred. An additional group that had severe sclerosis with focal rarefaction suggesting impending collapse was also studied (n=5/group). Parasagittal slices were milled to 2.0 mm thickness and subjected to palmar forces 50 to 200% of those applied by the sesamoid bone at angles corresponding to early, mid and late stance support phases of the gait cycle. From contact radiographs in the loaded and unloaded samples, strains were determined by recognizing displacements in the trabecular patterns using texture correlation analysis. Failure did not occur in any of the samples. Strains were generally proportional to the forces applied and greatest at midstance. Strain patterns varied between samples and with the different loading positions. With increased subchondral bone sclerosis there was greater shear strain in overlying trabeculae. Strain patterns were not consistently different within the sclerotic bone at the site of failure. Focally higher strains at the surface were sometimes related to the edge of the platen which was molded to mimic the sesamoid bone in vivo. These results indicate that sclerotic thickening of subchondral bone transmits stresses to overlying trabeculae. No consistent strain pattern was recognized where devitalization and mechanical failure occurs. Focally higher strains related to the edge of the opposing sesamoid bone may play a role.     

Doxycycline effects on mechanical and morphometrical properties of early- and late-stage osteoarthritic bone following anterior cruciate ligament injury.

As posttraumatic osteoarthritis (OA) progresses, the mechanical and morphometrical properties of the subchondral bone change and may be linked to damage of the articular cartilage. Potentially to slow that progression, doxycycline was administered orally twice daily (4 mg.kg(-1).day(-1)) in skeletally mature canines after anterior cruciate ligament transection (ACLX). To test if doxycycline significantly altered the structure and function of OA bone, we tested cancellous bone mechanical properties, measured bone mineral content, and analyzed bone structure by microcomputed tomography. Our investigation focused on subchondral trabecular bone changes in the medial femoral condyle at 36 and 72 wk after ACLX. Significant mechanical changes discovered at 36 wk post-ACLX were less obvious at 72 wk in both treated and ACLX groups. Doxycycline treatment conserved bone strain energy density at 72 wk. Doxycycline had little effect on the degradation of superficial osseous tissue at 36 wk post-ACLX; by 72 wk, doxycycline in an ACLX model limited subchondral bone loss within the first 3 mm of periarticular bone with established OA. Significant bone loss occurred in the deeper trabecular bone for all groups. Substantial architectural adaptation within deeper trabecular bone accompanied changes in mechanics in early and established OA.     

Separate modeling of cortical and trabecular bone offers little improvement in FE predictions of local structural stiffness at the proximal tibia

Abstract

Quantitative computed tomography-based finite element (QCT-FE) modeling has potential to clarify the role of altered subchondral bone stiffness in osteoarthritis. The objective of this research was to evaluate different QCT-FE modeling and thresholding approaches to identify the method which best predicted experimentally measured local subchondral structural stiffness with highest explained variance and least error. Our results showed that separate modeling of proximal tibial cortical and trabecular bone offered little improvement in QCT-FE-predicted stiffness (0% to +3% improvement in explained variance) when compared to modeling the proximal tibia as a single structure. Based on the results of this study, we do not recommend separate modeling of cortical bone and trabecular bone when developing QCT-FE models of the proximal tibia for predicting subchondral bone stiffness.     

Quantification of subchondral bone changes in a murine osteoarthritis model using micro-CT

In the past few years there has been a considerable interest in the role of bone in osteoarthritis. Despite the increasing evidence of the involvement of bone in osteoarthritis, it remains very difficult to attribute the cause or effect of changes in subchondral bone to the process of osteoarthritis. Although osteoarthritis in mice provides a useful model to study changes in the subchondral bone, detailed quantification of these changes is lacking. Therefore, the goal of this study was to quantify subchondral bone changes in a murine osteoarthritis model by use of micro-computed tomography (micro-CT). We induced osteoarthritis-like characteristics in the knee joints of mice using collagenase injections, and after four weeks we calculated various 3D morphometric parameters in the epiphysis of the proximal tibia. The collagenase injections caused cartilage damage, visible in histological sections, particularly on the medial tibial plateau. Micro-CT analysis revealed that the thickness of the subchondral bone plate was decreased both at the lateral and the medial side. The trabecular compartment demonstrated a small but significant reduction in bone volume fraction compared to the contralateral control joints. Trabeculae in the collagenase-injected joints were thinner but their shape remained rod-like. Furthermore, the connectivity between trabeculae was reduced and the trabecular spacing was increased. In conclusion, four weeks after induction of osteoarthritis in the murine knee subtle but significant changes in subchondral bone architecture could be detected and quantified in 3D with micro-CT analysis.     

Comparison of the linear finite element prediction of deformation and strain of human cancellous bone to 3D digital volume correlation measurements

The mechanical properties of cancellous bone and the biological response of the tissue to mechanical loading are related to deformation and strain in the trabeculae during function. Due to the small size of trabeculae, their motion is difficult to measure. To avoid the need to measure trabecular motions during loading the finite element method has been used to estimate trabecular level mechanical deformation. This analytical approach has been empirically successful in that the analytical models are solvable and their results correlate with the macroscopically measured stiffness and strength of bones. The present work is a direct comparison of finite element predictions to measurements of the deformation and strain at near trabecular level. Using the method of digital volume correlation, we measured the deformation and calculated the strain at a resolution approaching the trabecular level for cancellous bone specimens loaded in uniaxial compression. Smoothed results from linearly elastic finite element models of the same mechanical tests were correlated to the empirical three-dimensional (3D) deformation in the direction of loading with a coefficient of determination as high as 97% and a slope of the prediction near one. However, real deformations in the directions perpendicular to the loading direction were not as well predicted by the analytical models. Our results show, that the finite element modeling of the internal deformation and strain in cancellous bone can be accurate in one direction but that this does not ensure accuracy for all deformations and strains.     

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.     

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.     

Adaptation of subchondral bone in osteoarthritis

Osteoarthritis is a chronic joint disease with pathological changes in the articulating cartilage and all other tissues that occupy the joint. Radin and coworkers have suggested the involvement of subchondral bone in the disease process. However, evidence for an essential role in the etiology has never been proven. Recent studies showing reduced chemical and mechanical properties of subchondral bone in various stages of the disease have invigorated interest in the role of subchondral bone in the development and progression of the disease. The current study showed that the concept of bone adaptation might explain subchondral stiffening, a process where subchondral bone becomes typically sclerotic in osteoarthritis. In addition, we report reduced mechanical matrix tissue properties as well as an increase in denatured collagen content. In conclusion, although osteoarthritic bone tissue contains increased denatured collagen and has reduced matrix mechanical properties, the widely accepted concept of subchondral stiffening is compatible with the process of normal bone adaptation.     

Finite element analysis of a three-dimensional open-celled model for trabecular bone

Based on a regular array of cubic unit cells, each containing a body-centered spherical void, we created an idealized three-dimensional model for both subchondral trabecular bone and a class of porous foams. By considering only face-to-face stacking of unit cells, the inherent symmetry was such that, except at the surface, the displacements and stresses within any one unit cell were representative of the entire porous structure. Using prescribed displacements the model was loaded in both uniaxial compressive strain and uniaxial shear strain. Based on the response to these loads, we found the tensor of elastic constants for an equivalent homogeneous elastic solid with cubic symmetry. We then compared the predicted modulus with our experimental values for bovine trabecular bone and literature values for an open-celled latex rubber foam.     

On shear properties of trabecular bone under torsional loading: effects of bone marrow and strain rate

To further improve our understanding of trabecular bone mechanical behavior in torsion, our objective was to determine the effects of strain rate, apparent density, and presence of bone marrow on trabecular bone shear material properties. Torsion tests of cylindrical trabecular bone specimens from sheep lumbar vertebrae with and without bone marrow were conducted. The bones with marrow were divided into two groups and tested at shear strain rates of 0.002 and 0.05s(-1) measured at the specimen perimeter. The bones without marrow were divided into three groups and tested at shear strain rates of 0.002, 0.015, and 0.05s(-1). Comparing the results of bones with and without marrow tested at low (0.002s(-1)) and high (0.05s(-1)) strain rates, presence of bone marrow did not have any significant effect on trabecular bone shear modulus and strength. In specimens without marrow, power relationships were used to define shear strength and modulus as dependent variables in terms of strain rate and apparent density as independent variables. The shear strength was proportional to the apparent density raised to the 1.02 power and to the strain rate raised to the 0.13 power. The shear modulus was proportional to the apparent density raised to the 1.08 power and to the strain rate raised to the 0.07 power. This study provides further insight into the mechanism of bone failure in trauma as well as failure at the interface between bone and implants as it relates to prediction of trabecular bone shear properties.     

The elastic moduli of human subchondral, trabecular, and cortical bone tissue and the size-dependency of cortical bone modulus

The elastic moduli of human subchondral, trabecular, and cortical bone tissue from a proximal tibia were experimentally determined using three-point bending tests on a microstructural level. The mean modulus of subchondral specimens was 1.15 GPa, and those of trabecular and cortical specimens was 4.59 GPa and 5.44 GPa respectively. Significant differences were found in the modulus values between bone tissues, which may have mainly resulted from the differences in the microstructures of each bone tissue rather than in the mineral density. Furthermore, the size-dependency of the modulus was examined using eight different sizes of cortical specimens (heights h = 100-1000 microns). While the modulus values for relatively large specimens (h greater than 500 microns) remained fairly constant (approximately 15 GPa), the values decreased as the specimens became smaller. A significant correlation was found between the modulus and specimen size. The surface area to volume ratio proved to be a key variable to explain the size-dependency.     

Validity of photoelastic strain measurement on cadaveric proximal femora

Rosette strain gages indicate shear and principal strains at specific points, whereas photoelastic coatings provide shear strain information over a broad area. Information regarding bone loading and load transfer from a prosthetic implant to adjacent bone can be obtained using either strain-measuring technique on loaded femora. This study compared proximal femoral strains derived from photoelastic coatings to those obtained from rosette strain gages applied directly to the bone in order to determine the relationships between photoelastic shear strains and rosette shear and principal strains. Photoelastic shear strains underestimated rosette shear strains and exceeded the larger of the rosette principal strains. Principal strains derived from photoelastic coatings augmented with strain separator gages underestimated their rosette counterparts in most instances. Correlation was strong and nearly linear for all measures, indicating that photoelastic coatings can accurately express proportional strain changes despite imperfect agreement in absolute strain magnitudes. The best agreement between absolute strain magnitudes occurred in the proximal medial, or calcar, region. Understanding the relationships between the various measures obtained using the two strain measurement methods will allow more accurate estimates of actual strains to be made from photoelastic coatings.     

Altered architecture and cell populations affect bone marrow mechanobiology in the osteoporotic human femur

Age-related increases in trabecular bone porosity, as seen in osteoporosis, not only affect the strength and stiffness, but also potentially the mechanobiological response of bone. The mechanical interaction between trabecular bone and bone marrow is one source of mechanobiological signaling, as many cell populations in marrow are mechanosensitive. However, measuring the mechanics of this interaction is difficult, due to the length scales and geometric complexity of trabecular bone. In this study, a multi-scale computational scheme incorporating high-resolution, tissue-level, fluid–structure interaction simulations with discrete cell-level models was applied to characterize the potential effects of trabecular porosity and marrow composition on marrow mechanobiology in human femoral bone. First, four tissue-level models with different volume fractions (BV/TV) were subjected to cyclic compression to determine the continuum level shear stress in the marrow. The calculated stress was applied to three detailed models incorporating individual cells and having differing adipocyte fractions. At the tissue level, compression of the bone along its principal mechanical axis induced shear stress in the marrow ranging from 2.0 to 5.6 Pa, which increased with bone volume fraction and strain rate. The shear stress was amplified at the cell level, with over 90% of non-adipocyte cells experiencing higher shear stress than the applied tissue-level stress. The maximum shear stress decreased by 20% when the adipocyte volume fraction (AVF) increased from 30%, as seen in young healthy marrow, to 45 or 60% AVF typically found in osteoporotic patients. The results suggest that increasing AVF has similar effects on the mechanobiological signaling in bone marrow as decreased volume fraction.     

A dynamic finite element analysis of impulsive loading of the extension-splinted rabbit knee

A dynamic nonlinear finite element model was developed to study juxtarticular stresses in the splinted rabbit knee, an established laboratory model for creating osteoarthrosis due to impulsive loading. Plane strain finite element results were validated by comparison with corresponding experimental data. Parametric effects studied included the input tibial displacement speed, the local bone density distribution, and the modulus of cartilage and subchondral bone. While the computed resultant contact force magnitude was sensitive to a number of model parameters, the stress patterns, when normalized to a given resultant force magnitude, were not. Despite comparable force peaks, the finite element results showed approximately six-fold higher effective strain rate levels for a severely impulsive loading protocol known to induce rapid osteoarthrosis, versus those for a mildly impulsive loading protocol not usually associated with cartilage damage. A propensity for elevated shear in the deep cartilage layer near the contact periphery, observed in nearly all computed stress distributions, is consistent with previous experimental findings of fissuring at that level in the impulsively loaded rabbit knee.     

Fatigue microdamage in bovine trabecular bone

Microdamage, in the form of small cracks, may accumulate in trabecular bone loaded in fatigue. Specimens of bovine trabecular bone were loaded in compressive fatigue at one of four normalized stresses and loading was stopped after the specimens reached one of six maximum strains. Microdamage was identified using a fluorochrome staining technique, and microdamage parameters, including the number of damaged trabeculae and the damaged area fraction, were measured. No microdamage was observed during loading to strains below the yield strain; at higher strains, all microdamage parameters increased with increasing maximum compressive strain. Few significant differences were observed in the type or amount of microdamage accumulation between specimens loaded to the same maximum strain at different normalized stresses; however, more trabecular fractures were observed at high numbers of cycles, which corresponded to low normalized stresses.     

Simulation of vertebral trabecular bone loss using voxel finite element analysis

Trabecular bone loss in human vertebral bone is characterised by thinning and eventual perforation of the horizontal trabeculae. Concurrently, vertical trabeculae are completely lost with no histological evidence of significant thinning. Such bone loss results in deterioration in apparent modulus and strength of the trabecular core. In this study, a voxel-based finite element program was used to model bone loss in three specimens of human vertebral trabecular bone. Three sets of analyses were completed. In Set 1, strain adaptive resorption was modelled, whereby elements which were subject to the lowest mechanical stimulus (principal strain) were removed. In Set 2, both strain adaptive and microdamage mechanisms of bone resorption were included. Perforation of vertical trabeculae occurred due to microdamage resorption of elements with strains that exceeded a damage threshold. This resulted in collapse of the trabecular network under compression loading for two of the specimens tested. In Set 3, the damage threshold strain was gradually increased as bone loss progressed, resulting in reduced levels of microdamage resorption. This mechanism resulted in trabecular architectures in which vertical trabeculae had been perforated and which exhibited similar apparent modulus properties compared to experimental values reported in the literature. Our results indicate that strain adaptive remodelling alone does not explain the deterioration in mechanical properties that have been observed experimentally. Our results also support the hypothesis that horizontal trabeculae are lost principally by strain adaptive resorption, while vertical trabeculae may be lost due to perforation from microdamage resorption followed by rapid strain adaptive resorption of the remaining unloaded trabeculae.     

Microdamage propagation in trabecular bone due to changes in loading mode

Microdamage induced by falls or other abnormal loads that cause shear stress in trabecular bone could impair the mechanical properties of the proximal femur or spine. Existing microdamage may also increase the initiation and propagation of further microdamage during subsequent normal, on-axis, loading conditions, resulting in atraumatic or "spontaneous" fractures. Microdamage formation due to shear and compressive strains was studied in 14 on-axis cylindrical bovine tibial trabecular bone specimens. Microdamage was induced by a torsional overload followed by an on-axis compressive overload and quantified microscopically. Fluorescent agents were used to label microdamage and differentiate damage due to the two loading modes. Both the microcrack density and diffuse damage area caused by the torsional overload increased with increasing shear strain from the center to the edge of the specimen. However, the mean microcrack length was uniform across the specimen, suggesting that microcrack length is limited by microstructural features. The mean density of microcracks caused by compressive overloading was slightly higher near the center of the specimen, and the diffuse damage area was uniform across the specimen. Over 20% of the microcracks formed in the initial torsional overloading propagated during compression. Moreover the propagating microcracks were, on average, longer than microcracks formed by a single overload. As such, changes in loading mode can cause propagation of microcracks beyond the microstructural barriers that normally limit the length. Damage induced by in vivo off-axis loads such as falls may similarly propagate during subsequent normal loading, which could affect both remodeling activity and fracture susceptibility.     

Mechanical properties of single bovine trabeculae are unaffected by strain rate

For a better understanding of traumatic bone fractures, knowledge of the mechanical behavior of bone at high strain rates is required. Importantly, it needs to be clarified how quasistatic mechanical testing experiments relate to real bone fracture. This merits investigating the mechanical behavior of bone with an increase in strain rate. Various studies examined how cortical and trabecular bone behave at varying strain rates, but no one has yet looked at this question using individual trabeculae. In this study, three-point bending tests were carried out on bovine single trabeculae excised from a proximal femur to test the trabecular material's strain rate sensitivity. An experimental setup was designed, capable of measuring local strains at the surface of such small specimens, using digital image correlation. Microdamage was detected using the bone whitening effect. Samples were tested through two orders of magnitude, at strain rates varying between 0.01 and 3.39 s(-1). No linear relationship was observed between the strain rate and the Young's modulus (1.13-16.46 GPa), the amount of microdamage, the maximum tensile strain at failure (14.22-61.65%) and at microdamage initiation (1.95-12.29%). The results obtained in this study conflict with previous studies reporting various trends for macroscopic cortical and trabecular bone samples with an increase in strain rate. This discrepancy might be explained by the bone type, the small sample geometry, the limited range of strain rates tested here, the type of loading and the method of microdamage detection. Based on the results of this study, the strain rate can be ignored when modeling trabecular bone.     

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.     

A poroelastic finite element model of the bone–cartilage unit to determine the effects of changes in permeability with osteoarthritis

The changes experienced in synovial joints with osteoarthritis involve coupled chemical, biological, and mechanical processes. The aim of this study was to investigate the consequences of increasing permeability in articular cartilage (AC), calcified cartilage (CC), subchondral cortical bone (SCB), and subchondral trabecular bone (STB) as observed with osteoarthritis. Two poroelastic finite element models were developed using a depth-dependent anisotropic model of AC with strain-dependent permeability and poroelastic models of calcified tissues (CC, SCB, and STB). The first model simulated a bone-cartilage unit (BCU) in uniaxial unconfined compression, while the second model simulated spherical indentation of the AC surface. Results indicate that the permeability of AC is the primary determinant of the BCU’s poromechanical response while the permeability of calcified tissues exerts no appreciable effect on the force-indentation response of the BCU. In spherical indentation simulations with osteoarthritic permeability properties, fluid velocities were larger in magnitude and distributed over a smaller area compared to normal tissues. In vivo, this phenomenon would likely lead to chondrocyte death, tissue remodeling, alterations in joint lubrication, and the progression of osteoarthritis. For osteoarthritic and normal tissue permeability values, fluid flow was predicted to occur across the osteochondral interface. These results help elucidate the consequences of increases in the permeability of the BCU that occur with osteoarthritis. Furthermore, this study may guide future treatments to counteract osteoarthritis.