Bone Material Properties and Skeletal Fragility.

Deformations of vertebrae and sudden fractures of long bones caused by essentially normal loading are a characteristic problem in osteoporosis. If the loading is normal, then the explanation for and prediction of unexpected bone failure lies in understanding the mechanical properties of the whole bone-which come from its internal and external geometry, the mechanical properties of the hard tissue, and from how well the tissue repairs damage. Modern QCT and MRI imaging systems can measure the geometry of the mineralized tissue quite well in vivo-leaving the mechanical properties of the hard tissue and the ability of bone to repair damage as important unknown factors in predicting fractures. This review explains which material properties must be measured to understand why some bones fail unexpectedly despite our current ability to determine bone geometry and bone mineral content in vivo. Examples of how to measure the important mechanical properties are presented along with some analysis of potential drawbacks of each method. Particular attention is given to methods useful to characterize the loss of bone toughness caused by mechanical fatigue, drug side effects, and damage to the bone matrix.

Directional tortuosity as a predictor of modulus damage for vertebral cancellous bone.

There are many methods used to estimate the undamaged effective (apparent) moduli of cancellous bone as a function of bone volume fraction (BV/TV), mean intercept length(MIL), and other image based average microstructural measures. The MIL and BV/TV are both only functions of the cancellous microstructure and, therefore, cannot directly account for damage induced changes in the intrinsic trabecular hard tissue mechanical properties. Using a nonlinear finite element (FE) approximation for the degradation of effective modulus as a function of applied effective compressive strain, we demonstrate that a measurement of the directional tortuosity of undamaged trabecular hard tissue strongly predicts directional effective modulus (r2>0.90) and directional effective modulus degradation (r2>0.65). This novel measure of cancellous bone directional tortuosity has the potential for development into an anisotropic approach for calculating effective mechanical properties as a function of trabecular level material damage applicable to understanding how tissue microstructure and intrinsic hard tissue moduli interact to determine cancellous bone quality.

Trabecular bone loss at a distant skeletal site following noninvasive knee injury in mice.

Traumatic injuries can have systemic consequences, as the early inflammatory response after trauma can lead to tissue destruction at sites not affected by the initial injury. This systemic catabolism may occur in the skeleton following traumatic injuries such as anterior cruciate ligament (ACL) rupture. However, bone loss following injury at distant,unrelated skeletal sites has not yet been established. In the current study, we utilized a mouse knee injury model to determine whether acute knee injury causes a mechanically significant trabecular bone loss at a distant, unrelated skeletal site (L5 vertebral body).Knee injury was noninvasively induced using either high-speed (HS; 500 mm/s) or lowspeed(LS; 1 mm/s) tibial compression overload. HS injury creates an ACL rupture by midsubstance tear, while LS injury creates an ACL rupture with an associated avulsion bone fracture. At 10 days post-injury, vertebral trabecular bone structure was quantified using high-resolution microcomputed tomography (lCT), and differences in mechanical properties were determined using finite element modeling (FEM) and compressive mechanical testing. We hypothesized that knee injury would initiate a loss of trabecular bone structure and strength at the L5 vertebral body. Consistent with our hypothesis, we found significant decreases in trabecular bone volume fraction (BV/TV) and trabecular number at the L5 vertebral body in LS injured mice compared to sham (8.8% and 5.0%, respectively), while HS injured mice exhibited a similar, but lower magnitude response (5.1% and 2.5%, respectively). Contrary to our hypothesis, this decrease intrabecular bone structure did not translate to a significant deficit in compressive stiffness or ultimate load of the full trabecular body assessed by mechanical testing or FEM. However,we were able to detect significant decreases in compressive stiffness in both HS and LS injured specimens when FE models were loaded directly through the trabecular bone region (9.9% and 8.1%, and 3, respectively). This finding may be particularly important for osteoporotic fracture risk, as damage within vertebral bodies has been shown to initiate within the trabecular bone compartment. Altogether, these data point to a systemic trabecular bone loss as a consequence of fracture or traumatic musculoskeletal injury, which may be an underlying mechanism contributing to increased risk of refracture following an initial injury. This finding may have consequences for treatment of acute musculoskeletal injuries and the prevention of future bone fragility.

Training drives turnover rates in racehorse proximal sesamoid bones.

Focal bone lesions are often found prior to clinically relevant stress-fractures. Lesions are characterized by low bone volume fraction, low mineral density, and high levels of microdamage and are hypothesized to develop when bone tissue cannot sufficiently respond to damaging loading. It is difficult to determine how exercise drives the formation of these lesions because bone responds to mechanical loading and repairs damage. In this study, we derive steady-state rate constants for a compartment model of bone turnover using morphometric data from fractured and non-fractured racehorse proximal sesamoid bones (PSBs) and relate rate constants to racing-speed exercise data. Fractured PSBs had a subchondral focus of bone turnover and microdamage typical of lesions that develop prior to fracture. We determined steady-state model rate constants at the lesion site and an internal region without microdamage using bone volume fraction, tissue mineral density, and microdamage area fraction measurements. The derived undamaged bone resorption rate, damage formation rate, and osteoid formation rate had significant robust regression relationships to exercise intensity (rate) variables, layup (time out of exercise), and exercise 2-10 months before death. However, the direction of these relationships varied between the damaged (lesion) and non-damaged regions, reflecting that the biological response to damaging-loading differs from the response to non-damaging loading.

Acute bone loss following SARS-CoV-2 infection in mice.

The novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has infected more than 650 million people worldwide. Approximately 23% of these patients developed lasting "long-haul" COVID symptoms, including fatigue, joint pain, and systemic hyperinflammation. However, the direct clinical impact of SARS-CoV-2 infection on the skeletal system including bone and joint health has not been determined. Utilizing a humanized mouse model of COVID-19, this study provides the first direct evidence that SARS-CoV-2 infection leads to acute bone loss, increased osteoclast number, and thinner growth plates. This bone loss could decrease whole-bone mechanical strength and increase the risk of fragility fractures, particularly in older patients, while thinner growth plates may create growth disturbances in younger patients. Evaluating skeletal health in patients that have recovered from COVID-19 will be crucial to identify at-risk populations and develop effective countermeasures.

Exercise history predicts focal differences in bone volume fraction, mineral density and microdamage in the proximal sesamoid bones of Thoroughbred racehorses.

Medial proximal sesamoid bones (PSBs) from Thoroughbred racehorses that did (Case) or did not (Control) experience unilateral biaxial PSB fracture were evaluated for bone volume fraction (BVF), apparent mineral density (AMD), tissue mineral density (TMD), and microdamage in Case fractured, Case contralateral limb intact, and Control bones. A majority of Case bones had a subchondral lesion with high microdamage density, and low BVF, AMD, and TMD. Lesion microdamage and densitometric measures were associated with training history by robust linear regression. Exercise intensity was negatively related to BVF (0.07 ≤ R2 ≤ 0.12) and positively related to microcrack areal density (0.21 ≤ R2 ≤ 0.29) in the lesion; however, in an undamaged site, the relationships were opposite in direction. Regardless of location, TMD decreased with event frequency for both Case and Control, suggesting increased bone remodeling with exercise. Measures of how often animals were removed from active training (layups) predicted a decrease in TMD, AMD, BVF, and microdamage at regions away from the lesion site. A steady-state compartment model was used to organize the differences in the correlations between variables within the data set. The overall conclusions are that at the osteopenic lesion site, repair of microdamage by remodeling was not successful (e.g., lower bone mass, increased damage, and lower mineralization) but that in regions away from the lesion remodeling successfully controlled damage (e.g., higher bone mass, less microdamage, and lower mineralization).

In vitro motions of the medial and lateral proximal sesamoid bones under mid-stance load conditions are consistent with racehorse fracture configurations.

Proximal sesamoid bone (PSB) fractures in racehorses are likely fatigue fractures that occur due to repetitive loads and stress remodeling. The loading circumstances that may induce damage in the PSBs are not well understood. The goal of this study was to determine in three-dimensions, PSB motions relative to the opposing metacarpal condyle during simulated mid-stance loads. Seven equine cadaveric forelimbs were axially loaded in a material testing system to simulate standing and mid-stance walk, trot, and gallop load conditions (1.8-10.5 kN). Joint angles were determined by tracking the positions of bone-fixed kinematic markers. Internal-external rotation, abduction-adduction, and flexion-extension of each PSB relative to the third metacarpal condyle were compared between loads and between PSBs using an ANOVA with Tukey-Kramer post hoc tests for pairwise comparisons. The medial PSB rotated externally and the lateral PSB apex abducted during limb loading. Medial PSB external rotation was significantly greater at the gallop load condition than at the walk or trot load conditions. The medial and lateral PSB motions observed in this study are consistent with location of fatigue damage and fracture configurations frequently seen in medial and lateral PSBs from Thoroughbred racehorses. Specifically, medial PSB external rotation is consistent with the development of an abaxial subchondral medial PSB lesion that is reported in association with medial PSB transverse fracture and lateral PSB abduction is consistent with axial longitudinal fracture of the lateral PSB.

In vitro assessment of the motion of equine proximal sesamoid bones relative to the third metacarpal bone under physiologic midstance loads.

OBJECTIVE: To assess the motion of the proximal sesamoid bones (PSBs) relative to the third metacarpal bone (MC3) of equine forelimbs during physiologic midstance loads. SAMPLE: 8 musculoskeletally normal forelimbs (7 right and 1 left) from 8 adult equine cadavers. PROCEDURES: Each forelimb was harvested at the mid-radius level and mounted in a material testing system so the hoof could be moved in a dorsal direction while the radius and MC3 remained vertical. The PSBs were instrumented with 2 linear variable differential transformers to record movement between the 2 bones. The limb was sequentially loaded at a displacement rate of 5 mm/s from 500 N to each of 4 loads (1.8 [standing], 3.6 [walking], 4.5 [trotting], and 10.5 [galloping] kN), held at the designated load for 30 seconds while lateromedial radiographs were obtained, and then unloaded back to 500 N. The position of the PSBs relative to the transverse ridge of the MC3 condyle and angle of the metacarpophalangeal (fetlock) joint were measured on each radiograph. RESULTS: The distal edge of the PSBs moved distal to the transverse ridge of the MC3 condyle at 10.5 kN (gallop) but not at lower loads. The palmar surfaces of the PSBs rotated away from each other during fetlock joint extension, and the amount of rotation increased with load. CONCLUSIONS AND CLINICAL RELEVANCE: At loads consistent with a high-speed gallop, PSB translations may create an articular incongruity and abnormal bone stress distribution that contribute to focal subchondral bone lesions and PSB fracture in racehorses.

Subchondral focal osteopenia associated with proximal sesamoid bone fracture in Thoroughbred racehorses.

BACKGROUND: Proximal sesamoid bone (PSB) fracture is the most common fatal injury in Thoroughbred (TB) racehorses in the United States. Epidemiological and pathological evidence indicates PSB fracture is likely the acute culmination of a chronic stress-related process. However, the aetiopathogenesis of PSB fracture is poorly understood. OBJECTIVE: To characterise bone abnormalities that precede PSB fracture. STUDY DESIGN: Two retrospective case-control groups of PSBs from TB racehorses with, and without, unilateral biaxial PSB fracture. METHODS: Proximal sesamoid bones were harvested post-mortem from TB racehorses subjected to euthanasia for unilateral biaxial PSB fracture (cases) or causes unrelated to PSB fracture (controls) while racing or training. The fractured medial PSB (FX-PSB) and contralateral intact medial PSB (CLI-PSB) from racehorses that sustained PSB fracture, and an intact medial PSB (CTRL-PSB) from racehorses that did not have a PSB fracture were collected as case and control specimens. Study 1 distributions of morphological features were compared among case and control groups using visual examination, photographs, radiographs and histology of whole PSBs and serial sagittal sections (10 FX-PSB, 10 CLI-PSB and 10 CTRL-PSB). Study 2 local bone volume fraction and mineral densities were compared among case and control PSBs using microcomputed tomography (9 FX-PSB, 9 CLI-PSB and 9 CTRL-PSB). RESULTS: A focal subchondral lesion characterised by colocalised focal discoloration, radiolucency, osteopenia, low tissue mineral density and a surrounding region of dense cancellous bone was identified in most case horses but not in controls. This subchondral lesion was found in a slightly abaxial mid-body location and was bilaterally present in most case horses. MAIN LIMITATIONS: The post-mortem samples may not represent the spectrum of abnormalities that occur throughout the development of the subchondral lesion. Lateral PSBs were not examined, so their contribution to biaxial PSB fracture pathogenesis is unknown. CONCLUSION: Abaxial subchondral lesions are consistent with pre-existing injury and likely associated with PSB fracture.

Hypoxia decreases sclerostin expression and increases Wnt signaling in osteoblasts.

Mutations in sclerostin function or expression cause sclerosing bone dysplasias, involving decreased antagonism of Wnt/Lrp5 signaling. Conversely, deletion of the VHL tumor suppressor in osteoblasts, which stabilize HIF-alpha isoforms and thereby enables HIF-alpha/beta-driven gene transcription, increases bone mineral content and cross-sectional area compared to wild-type controls. We examined the influence of cellular hypoxia (1% oxygen) upon sclerostin expression and canonical Wnt signaling. Osteoblasts and osteocytes cultured under hypoxia revealed decreased sclerostin transcript and protein, and increased expression and nuclear localization of activated beta-catenin. Similarly, both hypoxia and the hypoxia mimetic DFO increased beta-catenin gene reporter activity. Hypoxia and its mimetics increased expression of the BMP antagonists gremlin and noggin and decreased Smad-1/5/8 phosphorylation. As a partial explanation for the mechanism of regulation of sclerostin by oxygen, MEF2 reporter assays revealed decreased activity. Modulation of VEGF signaling under normoxia or hypoxia revealed no influence upon Sost transcription. These data suggest that hypoxia inhibits sclerostin expression, through enhanced antagonism of BMP signaling independent of VEGF.

Temperature effects in articular cartilage biomechanics.

Articular cartilage is the soft tissue that covers contacting surfaces of bones in synovial joints. Cartilage is composed of chondrocytes and an extracellular matrix containing numerous biopolymers, cations and water. Healthy cartilage functions biomechanically to provide smooth and stable joint movement. Degenerative joint diseases such as osteoarthritis involve cartilage deterioration, resulting in painful and cumbersome joint motion. Temperature is a fundamental quantity in mechanics, yet the effects of temperature on cartilage mechanical behavior are unknown. This study addressed the questions of whether cartilage stiffness and stress relaxation change with temperature. Samples of middle-zone bovine calf patellofemoral cartilage were tested in unconfined compression first at 24°C and then again after heating to 60°C. The data reveal that when temperature increases: (1) both peak and equilibrium stiffness increase by 150 and 8%, respectively, and (2) stress relaxation is faster at higher temperature, as shown by a 60% decrease in the time constant. The increases in temperature-dependent stiffness are consistent with polymeric mechanisms of matrix viscoelasticity but not with interstitial fluid flow. The changes in the time constant are consistent with a combination of both fluid flow and matrix viscoelasticity. Furthermore, we discovered a novel phenomenon: at stress-relaxation equilibrium, compressive stress increased with temperature. These data demonstrate a rich area of cartilage mechanics that has previously been unexplored and emphasize the role of polymer dynamics in cartilage viscoelasticity. Further studies of cartilage polymer dynamics may yield additional insight into mechanisms of cartilage material behavior that could improve treatments for cartilage degeneration.

Cartilage stress-relaxation proceeds slower at higher compressive strains.

Articular cartilage is the connective tissue which covers bone surfaces and deforms during in vivo activity. Previous research has investigated flow-dependent cartilage viscoelasticity, but relatively few studies have investigated flow-independent mechanisms. This study investigated polymer dynamics as an explanation for the molecular basis of flow-independent cartilage viscoelasticity. Polymer dynamics predicts that stress-relaxation will proceed more slowly at higher volumetric concentrations of polymer. Stress-relaxation tests were performed on cartilage samples after precompression to different strain levels. Precompression increases the volumetric concentration of cartilage biopolymers, and polymer dynamics predicts an increase in relaxation time constant. Stress-relaxation was slower for greater precompression. There was a significant correlation between the stress-relaxation time constant and cartilage volumetric concentration. Estimates of the flow-dependent timescale suggest that flow-dependent relaxation occurs on a longer timescale than presently observed. These results are consistent with polymer dynamics as a mechanism of cartilage viscoelasticity.

Enzymatic digestion of articular cartilage results in viscoelasticity changes that are consistent with polymer dynamics mechanisms.

BACKGROUND: Cartilage degeneration via osteoarthritis affects millions of elderly people worldwide, yet the specific contributions of matrix biopolymers toward cartilage viscoelastic properties remain unknown despite 30 years of research. Polymer dynamics theory may enable such an understanding, and predicts that cartilage stress-relaxation will proceed faster when the average polymer length is shortened. METHODS: This study tested whether the predictions of polymer dynamics were consistent with changes in cartilage mechanics caused by enzymatic digestion of specific cartilage extracellular matrix molecules. Bovine calf cartilage explants were cultured overnight before being immersed in type IV collagenase, bacterial hyaluronidase, or control solutions. Stress-relaxation and cyclical loading tests were performed after 0, 1, and 2 days of incubation. RESULTS: Stress-relaxation proceeded faster following enzymatic digestion by collagenase and bacterial hyaluronidase after 1 day of incubation (both p < or = 0.01). The storage and loss moduli at frequencies of 1 Hz and above were smaller after 1 day of digestion by collagenase and bacterial hyaluronidase (all p < or = 0.02). CONCLUSION: These results demonstrate that enzymatic digestion alters cartilage viscoelastic properties in a manner consistent with polymer dynamics mechanisms. Future studies may expand the use of polymer dynamics as a microstructural model for understanding the contributions of specific matrix molecules toward tissue-level viscoelastic properties.

Cancellous bone properties and matrix content of TGF-beta2 and IGF-I in human tibia: a pilot study.

Transforming and insulin-like growth factors are important in regulating bone mass. Thus, one would anticipate correlations between matrix concentrations of growth factors and functional properties of bone. We therefore investigated the relationships of (1) TGF-beta2 and (2) IGF-I matrix concentrations with the trabecular microstructure, stress distribution, and mechanical properties of tibial cancellous bone from six male human cadavers. Trabecular stress amplification (VMExp/sigma(app)) and variability (VMCOV) were calculated using microcomputed tomography (muCT)-based finite element simulations. Bone volume fraction (BV/TV), surface/volume ratio (BS/BV), trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), connectivity (Eu.N), and anisotropy (DA) were measured using 3-D morphometry. Bone stiffness and strength were measured by mechanical testing. Matrix concentrations of TGF-beta2 and IGF-I were measured by ELISA. We found higher matrix concentrations of TGF-beta2 were associated with higher Tb.Sp and VMExp/sigma(app) for pooled data and within subjects. Similarly, a higher matrix concentration of IGF-I was associated with lower stiffness, strength, BV/TV and Tb.Th and with higher BS/BV, Tb.Sp, VMExp/sigma(app) and VMCOV for pooled data and within subjects. IGF-I and Tb.N were negatively associated within subjects. It appears variations of the stress distribution in cancellous bone correlate with the variation of the concentrations of TGF-beta2 and IGF-I in bone matrix: increased local matrix concentrations of growth factors are associated with poor biomechanical and architectural properties of tibial cancellous bone.

Age Dependence of Systemic Bone Loss and Recovery Following Femur Fracture in Mice.

The most reliable predictor of future fracture risk is a previous fracture of any kind. The etiology of this increased fracture risk is not fully known, but it is possible that fracture initiates systemic bone loss, leading to greater fracture risk at all skeletal sites. In this study, we investigated systemic bone loss and recovery after femoral fracture in young (3-month-old) and middle-aged (12-month-old) mice. Transverse femur fractures were created using a controlled impact, and whole-body bone mineral density (BMD), trabecular and cortical microstructure, bone mechanical properties, bone formation and resorption rates, mouse voluntary movement, and systemic inflammation were quantified at multiple time points post-fracture. We found that fracture led to decreased whole-body BMD in both young and middle-aged mice 2 weeks post-fracture; this bone loss was recovered by 6 weeks in young but not middle-aged mice. Similarly, trabecular bone volume fraction (BV/TV) of the L5 vertebral body was significantly reduced in fractured mice relative to control mice 2 weeks post-fracture (-11% for young mice, -18% for middle-aged mice); no significant differences were observed 6 weeks post-fracture. At 3 days post-fracture, we observed significant increases in serum levels of interleukin-6 and significant decreases in voluntary movement in fractured mice compared with control mice, with considerably greater changes in middle-aged mice than in young mice. At this time point, we also observed increased osteoclast number on L5 vertebral body trabecular bone of fractured mice compared with control mice. These data show that systemic bone loss occurs after fracture in both young and middle-aged mice, and recovery from this bone loss may vary with age. This systemic response could contribute to increased future fracture risk after fracture; these data may inform clinical treatment of fractures with respect to improving long-term skeletal health. © 2018 American Society for Bone and Mineral Research.

Molecular NMR T2 values can predict cartilage stress-relaxation parameters.

Articular cartilage lines synovial joints and functions as a low-friction deformable tissue to enable smooth and stable joint articulation. The objective of this study was to determine the relationships between cartilage stress-relaxation properties and the collagen and GAG NMR transverse relaxation times (T(2)) toward understanding mechanisms of cartilage viscoelasticity. Stress-relaxation tests were performed on both cultured and enzymatically digested bovine cartilage, followed by measurements of both the collagen and GAG T(2) using the Call-Purcell-Meiboom-Gill pulse sequence. The peak and equilibrium stresses were correlated with the GAG T(2), and the stress-relaxation time constant was correlated with the collagen T(2). Multiple linear regression models were successful in using the specific T(2) values to predict the stress-relaxation properties. As a model of osteoarthritis, enzymatic digestion with collagenase and testicular hyaluronidase had weak effects on T(2) values. These data present a complex picture of cartilage mechanical behavior, with cartilage stiffness associated with the GAG T(2) values and the stress-relaxation time constant associated with the collagen T(2).

Cancellous bone lamellae strongly affect microcrack propagation and apparent mechanical properties: separation of patients with osteoporotic fracture from normal controls using a 2D nonlinear finite element method (biomechanical stereology).

Biomechanical stereology is proposed as a two-dimensional (2D) finite element (FE) method to estimate the ability of bone tissue to sustain damage and to separate patients with osteoporotic fracture from normal controls. Briefly, 2D nonlinear compact tension FE models were created from quantitative back scattered electron images taken of iliac crest bone specimens collected from the individuals with or without osteoporotic fracture history. The effects of bone mineral microstructure on predicted bone fracture toughness and microcrack propagation were examined. The 2D FE models were used as surrogates for the real bone tissues. The calculated microcrack propagation results and bone mechanical properties were examined as surrogates for measurements from mechanical testing of actual specimens. The results for the 2D FE simulation separated patients with osteoporotic fracture from normal controls even though only the variability in tissue mineral microstructure was used to build the models. The models were deliberately created to ignore all differences in mean mineralization. Hence, the current results support the following hypotheses: (1) that material heterogeneity is important to the separation of patients with osteoporotic fracture from normal controls; and (2) that 2D nonlinear finite element modeling can produce surrogate mechanical parameters that separate patients with fracture from normal controls.

Trabecular shear stress amplification and variability in human vertebral cancellous bone: relationship with age, gender, spine level and trabecular architecture.

Trabecular shear stress magnitude and variability have been implicated in damage formation and reduced bone strength associated with bone loss for human vertebral bone. This study addresses the issue of whether these parameters change with age, gender or anatomical location, and if so whether this is independent of bone mass. Additionally, 3D-stereology-based architectural parameters were examined in order to establish the relationship between stress distribution parameters and trabecular architecture. Eighty cancellous bone specimens were cored from the anterior region of thoracic 12 and donor-matched lumbar 1 vertebrae from a randomly selected population of 40 cadavers. The specimens were scanned at 21-microm voxel size using microcomputed tomography (microCT) and reconstructed at 50microm. Bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), bone surface-to-volume ratio (BS/BV), degree of anisotropy (MIL1/MIL3), and connectivity density (-#Euler/Vol) were calculated directly from micro-CT images. Large-scale finite element models were constructed and superoinferior compressive loading was simulated. Apparent cancellous modulus (EFEM) was calculated. The average trabecular von Mises stress generated per uniaxial apparent stress (sigma (-)VM / sigmaapp) and coefficient of variation of trabecular von Mises stresses (COV) were calculated as measures of the magnitude and variability of shear stresses in the trabeculae. Mixed-models and regression were used for analysis. sigma(-)VM / sigmaapp and COV were not different between genders and vertebrae. Both sigma(-)VM / sigmaapp and COV increased with age accompanied by a decrease in BV/TV. Strong relationship of sigma(-)VM / sigmaapp with BV/TV was found whereas COV was strongly related to EFEM/(BV/TV). The results from T12 and L1 were not different and highly correlated with each other. The relationship of sigma(-)VM / sigmaapp with COV was observed to be different between males and females. This difference could not be explained by architectural parameters considered in this study. Our results support the relevance of trabecular shear stress amplification and variability in age-related vertebral bone fragility. The relationships found are expected to help understand the micro-mechanisms by which cancellous bone mass and mechanical properties are modulated through a collection of local stress parameters.

Identification of material parameters based on Mohr-Coulomb failure criterion for bisphosphonate treated canine vertebral cancellous bone.

Nanoindentation has been widely used to study bone tissue mechanical properties. The common method and equations for analyzing nanoindentation, developed by Oliver and Pharr, are based on the assumption that the material is linearly elastic. In the present study, we adjusted the constraint of linearly elastic behavior and use nonlinear finite element analysis to determine the change in cancellous bone material properties caused by bisphosphonate treatment, based on an isotropic form of the Mohr-Coulomb failure model. Thirty-three canine lumbar vertebrae were used in this study. The dogs were treated daily for 1 year with oral doses of alendronate, risedronate, or saline vehicle at doses consistent, on a mg/kg basis, to those used clinically for the treatment of post-menopausal osteoporosis. Two sets of elastic modulus and hardness values were calculated for each specimen using the Continuous Stiffness Measurement (CSM) method (E(CSM) and H(CSM)) from the loading segment and the Oliver-Pharr method (E(O-P) and H(O-P)) from the unloading segment, respectively. Young's modulus (E(FE)), cohesion (c), and friction angle (phi) were identified using a finite element model for each nanoindentation. The bone material properties were compared among groups and between methods for property identification. Bisphosphonate treatment had a significant effect on several of the material parameters. In particular, Oliver-Pharr hardness was larger for both the risedronate- and alendronate-treated groups compared to vehicle and the Mohr-Coulomb cohesion was larger for the risedronate-treated compared to vehicle. This result suggests that bisphosphonate treatment increases the hardness and shear strength of bone tissue. Shear strength was linearly predicted by modulus and hardness measured by the Oliver-Pharr method (r(2)=0.99). These results show that bisphosphonate-induced changes in Mohr-Coulomb material properties, including tissue shear cohesive strength, can be accurately calculated from Oliver-Pharr measurements of Young's modulus and hardness.

Postfailure modulus strongly affects microcracking and mechanical property change in human iliac cancellous bone: a study using a 2D nonlinear finite element method.

A two-dimensional (2D) finite element (FE) method was used to estimate the ability of bone tissue to sustain damage as a function of postfailure modulus. Briefly, 2D nonlinear compact-tension FE models were created from quantitative back-scattered electron images taken of human iliac crest bone specimens. The effects of different postfailure moduli on predicted microcrack propagation were examined. The 2D FE models were used as surrogates for real bone tissues. The crack number was larger in models with higher postfailure modulus, while mean crack length and area were smaller in these models. The rate of stiffness reduction was greater in the models with lower postfailure modulus. Hence, the current results supported the hypothesis that hard tissue postfailure properties have strong effects on bone microdamage morphology and the rate of change in apparent mechanical properties.