A Device for Long Term, <Emphasis Type="Italic">In Vitro</Emphasis> Loading of Three-Dimensional Natural and Engineered Tissues

In vitro studies of mechanical loads applied to three-dimensional tissue constructs are important to the design and production of functional, engineered bone tissue. This study reports the development and characterization of a mechanical device capable of subjecting a three-dimensional section of natural or engineered tissue to precise, reproducible four-point bending deformations over a range of programmable magnitudes and frequencies. To test the biological and mechanical capabilities of the system, a low-cycle (360 cycles/day), medium-range strain (2500 microstrain), long-term (16 day) loading regime was applied to rat bone marrow stromal cells cultured in porous DL-polylactic acid scaffolds. Cells proliferated in culture throughout the experiment, and with time showed an increase in alkaline phosphatase expression per cell. Calcium and phosphorus mineral deposition by the unloaded group was significantly greater (p < 0.05) than that deposited by the loaded group. The molar ratio of calcium to phosphorus in the unloaded group (0.94:1) was significantly greater (p < 0.05) than that of the loaded group (0.41:1). The loading device presented here is a tool which can be used to help elucidate contributions of mechanical loading/fatigue on biodegradable materials, as well as study the effects of mechanical loading on natural or engineered tissues in vitro. © 2003 Biomedical Engineering Society. PAC2003: 8768+z, 8780Rb     

A finite element analysis of bone plates available for prophylactic internal fixation of the radial osteocutaneous donor site using the sheep tibia model

IntroductionThe strengthening effect of prophylactic internal fixation (PIF) with a bone plate at the radial osteocutaneous flap donor site has previously been demonstrated using the sheep tibia model of the human radius. This study investigated whether a finite element (FE) model could accurately represent this biomechanical model and whether stress or strain based failure criteria are most appropriate.MethodsAn FE model of an osteotomised sheep tibia bone was strengthened using 4 types of plates with unilocking or bicortical screw fixation. Torsion and 4-point bending simulations were performed. The maximum von Mises stresses and strain failure criteria were studied.ResultsThe strengthening effects when applying stress failure criteria [factor 1.76–4.57 bending and 1.33–1.80 torsion] were comparable to the sheep biomechanical model [factor 1.73–2.43 bending and 1.54–2.63 torsion]. The strongest construct was the straight 3.5 mm stainless steel unilocking plate. Applying strain criteria the strongest construct was the straight 3.5 mm stainless DCP plate with bicortical screw fixation.ConclusionsThe FE model was validated by comparison with the sheep tibia model. The complex biomechanics at the bone-screw interface require further investigation. This FE modelling technique may be applied to a model of the human radius and other sites.     

Bone histomorphometric changes in the femoral neck of aging and ovariectomized rats

Background: This study characterizes the changes in cortical and cancellous bone and cross sectional moment of inertia of the femoral neck from aging and ovariectomized (ovx'd) rats to determine their role in the previously reported ovx-induced reduction of mechanical strength in the femoral neck. Methods: Undecalcified double-fluorescent lableled cross sections of femoral neck of 3.5-, 5.5-, 6.5-, and 8.5-month-old female rats and rats ovx'd at 3.5 months for 2, 3, and 5 months of 45 rats were studied. The estimated endocortical and trabecular surfaces, cortical and cancellous bone histomorphometry, and cortical moment of inertia were determined. Results: The femoral neck was adding cortical bone between 3.5 and 5.5 months of age by increasing cortical thickness and decreasing marrow cavity area. No change of cortical bone mass was found between 5.5 and 8.5 months and the same amount of cancellous bone was observed between 3.5 and 8.5 months of age. Ovariectomy-induced cancellous, but not cortical bone loss. The loss was due to a transient ovx-induced negative bone balance that by 5 months post-ovx produced a 42% loss in trabecular bone while the histomorphometry profiles were the same as controls. The crosssectional moment of inertia increased with age but did not differ significantly between ovx'd and controls. Conclusions: Our findings suggest that the ovx-induced cancellous bone loss could be a contributing factor to the reduced mechanical strength in the femoral neck of ovx'd rats reported previously. © 1995 Wiley-Liss, Inc.     

Perspectives: A vital biomechanical model of the endochondral ossification mechanism

Background: Mechanical usage effects could explain many features of endochondral ossification and related processes. Mineralization of growth plate cartilage could reduce its mechanical strains enough to make its resorption begin and to guide it in space. By removing most of its mineralized vertical septae, resorption could overload the remainder enough to increase woven bone formation on them and construct the primary spongiosa. After it finishes mineralizing, the primary spongiosa could become stiff enough to begin partial disuse in strain terms, so BMU-based remodeling would begin replacing it with lamellar bone. This would construct the secondary spongiosa. In transferring loads from the growth plate to the cortex, the central metaphyseal spongiosa becomes deloaded. This disuse would make remodeling remove it in the diaphyseal marrow space. Methods: The slow growth of epiphyses and apophyses gives their spongiosas more time to adapt to their loads than the metaphyseal spongiosa beneath faster growing growth plates. Compared to metaphyseal trabeculae, this leads to fewer and thicker epiphyseal trabeculae that turn over more slowly and should persist for life because they carry loads for life. Results: Rapid turnover of metaphyseal cortex in very young subjects could let it strain enough to form woven bone. Increased thickness and slower turnover of this cortex in older subjects could reduce its strains enough to make lamellar bone form there instead. This would compose this cortex mostly of woven bone in the very young and of lamellar bone in adults. Conclusions: This model assigns particular importance to the stiffness and strains of tissues (as distinguished from their strength and stresses), to the relative rates of some processes, and to responses of the skeleton's biologic mechanisms to a tissue's typical largest mechanical strains (as distinguished from their stresses). © 1994 Wiley-Liss, Inc.     

Late stages of mineralization and their signature on the bone mineral density distribution

ABSTRACT

Purpose: Experimental measurements of bone mineral density distributions (BMDDs) enable a determination of secondary mineralization kinetics in bone, but the maximum degree of mineralization and how this maximum is approached remain uncertain. We thus test computationally different hypotheses on late stages of bone mineralization by simulating BMDDs in low-turnover conditions. Materials and methods: An established computational model of the BMDD that accounts for mineralization and remodeling processes was extended to limit mineralization to various maximum calcium capacities of bone. Simulated BMDDs obtained by reducing turnover rate from the reference trabecular BMDD under different assumptions on late stage mineralization kinetics were compared with experimental BMDDs of low-turnover bone. Results: Simulations show that an abrupt stopping of mineralization near a maximum calcium capacity induces a pile-up of minerals in the BMDD statistics that is not observed experimentally. With a smooth decrease of mineralization rate, imposing low maximum calcium capacities helps to match peak location and width of simulated low-turnover BMDDs with peak location and width of experimental BMDDs, but results in a distinctive asymmetric peak shape. No tuning of turnover rate and maximum calcium capacity was able to explain the differences found in experimental BMDDs between trabecular bone (high turnover) and femoral cortical bone (low turnover). Conclusions: Secondary mineralization in human bone does not stop abruptly, but continues slowly up to a calcium content greater than 30 wt% Ca. The similar mineral heterogeneity seen in trabecular and femoral cortical bones at different peak locations was unexplained by the turnover differences tested.     

Subchondral osteopenia and accelerated bone remodelling post‐ovariectomy – a possible mechanism for subchondral microfractures in the aetiology of spontaneous osteonecrosis of the knee?

Osteopenia and subchondral microfractures are implicated in the aetiology of spontaneous osteonecrosis of the knee (SPONK). The ovine tibia shows significant alterations of the trabecular architecture within the subchondral bone of the medial tibial plateau post‐ovariectomy (OVX), including reduced trabecular bone volume fraction. We hypothesise that accelerated subchondral bone resorption may also play a role in increasing microfracture risk at this site. Twenty‐two sheep were examined in this study; 10 of the sheep underwent OVX, while the remainder (n = 13) were kept as controls (CON). Five fluorochrome dyes were administered intravenously at 12‐week intervals via the jugular vein to both groups, to label sites of bone turnover. These animals were then killed at 12 months post‐operatively. Bone turnover was significantly increased in the OVX group in both trabecular bone (2.024 vs. 1.047 no. mm^?2; P = 0.05) and within the subchondral bone plate (4.68 vs. 0.69 no. mm^?2; P < 0.001). In addition to the classically described turnover visible along trabecular surfaces, we also found visual evidence of intra‐trabecular osteonal remodelling. In conclusion, this study shows significant alterations in bone turnover in both trabecular bone and within the subchondral bone plate at 1 year post‐OVX. Remodelling of trabecular bone was due to both classically described hemi‐osteonal and intra‐trabecular osteonal remodelling. The presence of both localised osteopenia and accelerated bone remodelling within the medial tibial plateau provide a possible mechanism for subchondral microfractures in the aetiology of SPONK. Further utilisation of the OVX ewe may be useful for further study in this field.     

Knee-Loading Modality Drives Molecular Transport in Mouse Femur

Mechanical loading is well known to stimulate bone remodeling. Load-driven interstitial fluid flow and molecular transport have been postulated to play a role in the enhancement of bone formation. In order to evaluate load-driven molecular transport in a lacunocanalicular network, we conducted fluorescence recovery after photobleaching (FRAP) experiments using lacunae stained with uranine (376 Da). Loads were applied to a mouse femur ex vivo with a novel knee-loading modality, where the distal epiphysis was loaded with a sinusoidal force at 2 Hz. The lacunae in the diaphysis located 25% (∼4 mm) proximal to the loading site were photobleached and sequentially imaged, and a time constant for fluorescence recovery was determined both with and without knee loading. The time constant was estimated as the period to recover 63% of fluorescent intensity using a best-fit exponential curve. The results reveal that the applied loads shortened the time constant from 33 ± 9 s with non-loading control to 25 ± 11 s with knee loading (p = 0.0014). The strain in the measurement site was <100 μstain along the femoral midshaft, which was an order of magnitude smaller than the minimum effective strain threshold for bone remodeling. Taken together, the current study supports the notion that molecular transport in cortical bone is enhanced by the loads applied to the epiphysis without inducing significant in situ strain in the diaphysis.     

The Effect of Varying Magnitudes of Whole-Body Vibration on Several Skeletal Sites in Mice

It has been reported that whole-body vibration (WBV) is anabolic to trabecular bone in animal models and humans. It is likely that this anabolic response does not occur uniformly throughout the entire body. Two factors that may affect the observed anabolic response are vibration magnitude and skeletal site of interest. In this study, mice were loaded with WBV of varying magnitudes. After five weeks of loading, bone marrow was flushed from tibias in order to quantify osteoprogenitor cells. Staining with alizarin red (an indicator of mineralization) showed a significant decrease in percent stained area in the 0.3 g loaded group compared to the control group and the 1.0 g group. MicroCT analysis was performed at five skeletal sites: the proximal tibial metaphysis, femoral condyles, distal femoral metaphysis, proximal femur, and L5 vertebral body. Increasing magnitudes of WBV were associated with a non-dose-dependent increase in trabecular bone volume (BV/TV) at the proximal tibial metaphysis, although other sites were unresponsive. There were statistically significant increases in BV/TV in the 0.1 g group (32% increase) and 1.0 g group (43% increase) compared to control (p < 0.05). The 0.1 g and 1.0 g groups also had higher BV/TV than the 0.3 g loaded group. If this non-dose-dependent phenomenon is verified by future studies, it suggests that a range of magnitudes should be examined for each application of WBV.     

股骨头坏死中松质骨微观力学特性的演变规律

目的采用结合显微CT和显微有限元分析方法,即基于显微CT图像建立三维有限元模型并进行数值模拟仿真分析,无创研究不同分期的坏死股骨头松质骨的微结构和微观力学性能,以期了解在股骨头坏死的发展过程中,松质骨微结构和微观力学特性的变化规律,为临床预测股骨头坏死提供理论基础。方法采集10例股骨头坏死患者的股骨头标本的显微CT图像,按照国际骨循环研究学会分期标准分为Ⅱ期样本3例,Ⅲ期3例,Ⅳ期4例。将图像中骨组织进行阈值分割,分区域建立坏死区、侧向区、硬化区和远端区的松质骨块三维有限元模型(边长8 mm),并根据CT值赋予非均匀材料属性。利用ImageJ软件中的BoneJ插件通过识别显微CT组图像,计算测量各区域松质骨的微结构参数,包括骨体积分数、骨小梁厚度、骨小梁间隙、结构模型指数。对松质骨块施加表观应变为1%的压缩载荷,计算骨组织应力和松质骨表观刚度等参数,对比分析各分期、各分区结果。结果在松质骨微结构方面,Ⅳ期较Ⅱ期的股骨头内部硬化区和坏死区的变化最为明显,硬化区的骨体积分数不断上升,骨小梁间隙下降,结构模型指数减小,而坏死区域与之相反;在骨组织微观受力方面,Ⅱ期到Ⅲ期坏死区域的应力并没有明显变化,而硬化区域随着分期增加应力不断上升,侧向区的应力不断下降。表观刚度变化与应力变化一致。结论随着股骨头坏死程度的加剧,硬化区的松质骨微结构和力学性能变化最大,应作为临床早期诊断中重点关注的区域。此外,微结构参数并不能准确体现松质骨的力学行为,而股骨头塌陷最终取决于其力学特性,因此结合有限元分析方法可更加全面了解股骨头坏死的微观力学演变规律。     

股骨头坏死松质骨生物力学特征的空间分布规律

目的 探究股骨头坏死松质骨微观结构参数和力学性能的空间分布规律,为临床诊断中科学评估病灶对病情的影响提供理论依据。方法 结合影像学测量和数值模拟方法,定量分析不同区域松质骨的微观结构参数和力学性能,分别从冠状面、矢状面和水平面投影方向上探究松质骨生物力学特征的空间分布特点。结果 在股骨头冠状面和矢状面投影方向上,松质骨的微观结构特征与力学性能大致呈Y型分布,Y形区域内松质骨的力学性能高于其他区域,该分布特点与股骨头内的主压应力束的位置相吻合。结论 位于股骨头Y形区域内的坏死灶对股骨头内应力分布的影响程度会更大,更有可能导致病情恶化。临床诊断中应充分考虑坏死灶和Y形区域的位置关系。     

A study of the relationship between meniscal injury and bone microarchitecture in ACL reconstructed knees

Background

Anterior cruciate ligament (ACL) tears increase the risk of developing knee osteoarthritis. This risk increases further with concurrent meniscus injury. The role of bone changes during knee osteoarthritis development are not well-understood, but may be important to its etiology.

How to select the elastic modulus for cancellous bone in patient-specific continuum models of the spine

Patient-specific finite element (FE) modelling is a promising technology that is expected to support clinical assessment of the spine in the near future. To allow rapid, robust and economic patient-specific modelling of the whole spine or of large spine segments, it is practicable to consider vertebral cancellous bone in the spine as a continuum material, but the elastic modulus of that continuum material must reflect the quality of the individual vertebral bone. A numerical parametric model of lattice trabecular architecture has been developed for determining the apparent elastic modulus of cancellous bone E_cb in vertebrae. The model inputs were apparent morphological parameters (trabecular thickness Tb_Th and trabecular separation Tb_Sp) and the bone mineral density (BMD), which can all be measuredin vivo, using the spatial resolution of current clinical quantitative computed tomography (QCT) commercial whole-body scanners. The model predicted that E_cb values between 30 and 110 MPa represent normal morphology and BMD of human spinal cancellous bone. The present E_cb to Tb_Th, Tb_Sp and BMD relationships pave the way for automatic generation of patientspecific continuum FE spine models that consider the individual's osteoporotic or other degenerative condition of cancellous bone.     

3D Finite Element Analysis of a Man Hip Joint Femur under Impact Loads

Objective： The biomechanical characters of the bone fracture of the man femoral hip joint under impact loads are explored. Methods ：A biosystem model of the man femoral hip joint by using the GE （ General Electric） lightspeed multi-lay spiral CT is conducted. A 3D finite element model is established by employing the finite element software ANSYS. The FE analysis mainly concentrates on the effects of the impact directions arising from intense movements and the parenchyma on the femoral hip joint on the stress distributions of the proximal femur. Results：The parenchyma on the hip joint has relatively large relaxation effect on the impact loads. Conclusion：Effects of the angle δ of the impact load to the anterior direction and the angle γ of the impact load to the femur shaft on the bone fracture are given;δ has larger effect on the stress and strain distributions than the angle γ,which mainly represents the fracture of the upper femur including the femoral neck fracture when the posterolateral femur is impacted, consistent with the clinical resuits.     

The Effect of Mechanical Loading on the Metabolism of Growth Plate Chondrocytes

It is well known that mechanical loading influences the endochondral bone formation essential for the growth and development of longitudinal bones. The question was, however, asked whether the effect of mechanical loading on the chondrocyte metabolism is dependent on the loading frequency. This study was aimed at evaluating the effect of tensile loadings with various frequencies on the proliferation of growth plate chondrocytes and extracellular matrix synthesis. The chondrocytes obtained from rib growth plate cartilage of 4-week-old male Wistar strain rats were cultured by day 4 and day 11 and used as proliferating and matrix-forming chondrocytes, respectively. Intermittent tensile stresses with different frequencies were applied to each stage chondrocyte. DNA syntheses were examined by measuring the incorporation of [³H]thymidine into the cells. Furthermore, the rates of collagen and proteoglycan syntheses were determined by measuring the incorporation of [2,3-³H]proline and [³⁵S]sulfate into the cells, respectively. At the proliferating stage, intermittent tensions with the frequencies of 30 cycles/min and 150 cycles/min significantly (p < 0.05) upregulated the syntheses of DNA, which indicates the promotion of chondrocyte proliferation. At the matrix-forming stage, collagen, and proteoglycan syntheses also enhanced with increase of the loading frequency. In particular, the intermittent tension with the frequencies of 30 cycles/min and 150 cycles/min increased significantly (p < 0.05 or p < 0.01) both the collagen and proteoglycan syntheses. These results suggest that the proliferation and differentiation of growth plate chondrocytes are regulated by the mechanical loading and that the chondrocyte metabolism enhanced with increase of loading frequency. These may give more insight into the possible mechanism leading to endochondral bone formation.     

Time Dependent Behaviour of Trabecular Bone at Multiple Load Levels

The deformation of bone when subjected to loads is not instantaneous but varies with time. To investigate this time-dependent behaviour sixteen bovine trabecular bone specimens were subjected to compressive loading, creep, unloading and recovery at multiple load levels corresponding to apparent strains of 2000–25,000 με. We found that: the time-dependent response of trabecular bone comprises of both recoverable and irrecoverable strains; the strain response is nonlinearly related to applied load levels; and the response is linked to bone volume fraction. Although majority of strain is recovered after the load-creep-unload-recovery cycle some residual strain always exists. The analysis of results indicates that trabecular bone becomes stiffer initially and then experiences stiffness degradation with the increasing load levels. Steady state creep rate was found to be dependent on applied stress level and bone volume fraction with a power law relationship.     

Comparison of osteopenic changes in cancellous bone induced by ovariectomy and/or immobilization in adult rats

Background: Ovariectomy (OVX) and immobilization (IMM) in rats are useful models of osteopenia, replicating some aspects of osteoporosis in humans. The purpose of this study was to compare changes in cancellous bone after OVX and/or IMM. Methods: Differences in cancellous bone were determined at 6 and 12 weeks after OVX or IMM. Comparisons were also made when rats were ovariectomized or immobilized for 6 weeks and then immobilized (OVX/IMM) and ovariectomized (IMM/OVX), respectively, for 6 more weeks. The femurs were used to determine bone mineral content (BMC) using single photon absorptiometry (SPA) and for scanning electron microscopy (SEM). Tibias were collected for microradiography, image analysis, and histomorphometry of metaphyseal cancellous bone. Results: Six and 12 weeks after OVX, there was less cancellous bone mass, compared with controls, as indicated by SPA, SEM, microradiography, image analyses, and histomorphometry. Bone was lost primarily from the central metaphyseal regions in the OVX animals, whereas the loss occurred throughout the metaphyses in the IMM animals. There were more rodlike bone spicules and fewer platelike trabecule in the OVX and IMM groups compared with controls. Differences in the structural aspects of the cancellous bone, including differences in the types of bone struts and marrow star volumes, indicated less trabecular connectivity and greater trabecular separation in the OVX and IMM animals, compared with controls. Endochondral growth indices in the IMM groups tended to be less, whereas the OVX groups tended to be greater than controls. Cancellous bone formation rates were generally greater in the OVX groups but less in the IMM groups compared with controls. Osteoclastic resorption surfaces were substantially elevated in the IMM and OVX groups, particularly the IMM groups. Changes reflecting OVX and IMM, independently, were apparent in the OVX/IMM and IMM/OVX groups and indices of osteopenia were different from controls, including less bone mass, trabecular connectivity, and greater trabecular separation, bone turnover rates, and osteoclastic surface. Conclusions: These results demonstrate differences in the osteopenic changes that occur in cancellous bone following OVX or IMM. The changes were generally more dramatic in the IMM than in the OVX animals. When OVX and IMM were applied in combination, the osteopenic changes are particularly severe, emphasizing the importance of mechanical usage even with a deficiency of gonadal hormones. © 1994 Wiley-Liss, Inc.     

Progression of osteoporosis in cancellous bone depending on trabecular structure

Progression of osteoporosis is caused by a decline in bone formation activity relative to the resorption activity. In this paper, the authors carried out a theoretical analysis of the progression of osteoporosis to estimate the osteoporotic change in the upper end of the femur. According to this analysis, the progression rate of osteoporosis in cancellous bone depends on the product of remodeling activity,R _act, and the trabecular structure parameter,K _tr. To confirm that the theoretical results were reasonably comparable to actual osteoporotic change, these two factors were measured in rabbits. From the results, it was concluded that the highest progression rate was shown in bar/barlike trabecular structure (type 3); the next highest rate, was shown in plate/bar-like structure (type 2); and the plate/plate-like structure (type 1) was the most insensible. Furthermore, the bone volume fractions of cancellous bone were measured at the upper end of human femurs with and without osteoporosis. Then the measured value was compared with the theoretical value for each type of trabecular structure. Results showed that the decrease in bone volume fraction predicted by Eq. 7 was well in accord with the actual decrease.     

Characterization of bone quality using computer-extracted radiographic features.

Both bone mineral density (BMD) and trabecular structure are important determinates of bone mechanical properties. However, neither BMD or trabecular structural features can completely explain the variations in bone mechanical properties. In this study, we combine BMD and bone structural features to characterize bone mechanical behavior. Radiographs were obtained from 34 femoral neck specimens excised during total hip arthroplasties. Each neck radiograph was digitized and a region of interest (ROI) was selected from the medial side of the femoral neck. Textural features, the global Minkoswski dimension and trabecular orientation, were extracted from each ROI image using Minkowski dimension analysis. The BMD of each specimen was measured using dual-energy x-ray absorptiometry (DXA) and subsequently normalized by bone size as measured from a standard pelvis radiograph. Mechanical testing was performed on the trabecular bone cubes machined from each femoral neck to yield bone mechanical properties. Multiple regression was performed to select the best features to predict bone mechanical properties. The results suggest that, using multiple predictors including normalized BMD structural features, and patient age, the coefficients of determination (R2) improved over the use of BMD alone. For bone strength, the R2 was improved from 0.24 using conventional BMD to 0.48 using a four-predictor model. Similar results were obtained in the prediction of Young's modulus, i.e., the R2 was improved from 0.25 to 0.55 in going from the model using conventional BMD to a four-predictor model. This study demonstrates the contributions of normalized BMD, structural features, and age to bone mechanical properties, and suggests a potential method for the noninvasive evaluation of bone mechanical properties.     

Femoral peak bone mass and osteoclast number in an animal model of age-related spontaneous osteopenia

Background: SAMP6 was developed as a murine model of age-related spontaneous osteopenia characterized by low peak bone mass. A morphometric study of the growing femur in SAMP6 and sex-matched SAMP2 at 10 days to 4 months of age was done to examine the pathogenic process related to osteopenia. Methods: Age-related changes in cortical bone thickness, femur score, trabecular bone volume, thickness of epiphyseal growth plate, number of osteoclasts, and osteoclast surface were measured with a computerized image analyzer. Osteoclasts were examined cytomorphometrically after TRAP (tartrate resistant acid phosphatase) staining of the femoral sections. Results: Cortical bone thickness and femur score increased significantly with age, while trabecular bone volume decreased significantly. Comparing mean values of cortical bone thickness, femur score and trabecular bone volume, we noted significantly lower mean values in SAMP6 than in SAMP2 mice. These significant inter-stain differences first became evident in 20–40-day-old mice, but there was no significant difference in thickness of the epiphyseal growth plate between the two strains. The mean values of the number of osteoclasts per unit none surface length and of the osteoclast surface in SAMP6 were significantly greater than in age- and sex-matched SAMP2. Histograms of distribution of size of osteoclasts of 40-day-old male mice revealed that larger ones were more frequently seen in SAMP6. Furthermore, the ratio of osteoclasts/TRAP positive cells free in the bone marrow cavity was significantly higher in SAMP6 than in SAMP2. Conclusion: Activated bone resorption may play a role in the osteopenia seen in SAMP6. © 1995 Wiley-Liss, Inc.     

Trabecular Shear Stresses Predict <Emphasis Type="Italic">In Vivo</Emphasis> Linear Microcrack Density but not Diffuse Damage in Human Vertebral Cancellous Bone

Linear microcracks and diffuse damage (staining over a broad region) are two types of microscopic damage known to occur in vivo in human vertebral trabecular bone. These damage types might be associated with vertebral failure. Using microcomputed tomography and finite element analysis for specimens of cancellous bone, we estimated the stresses in the trabeculae of human vertebral tissue for inferosuperior loading. Microdamage was quantified histologically. The density of in vivo linear microcracks was, but the diffuse damage area was not, related to the estimates of von Mises stress distribution in the tissue. In vivo linear microcrack density increased with increasing coefficient of variation of the trabecular von Mises stress and with increasing average trabecular von Mises stress generated per superoinferior apparent axial stress. Nonlinear increase in linear crack density, similar to the increase of the coefficient of variation of trabecular shear stresses, with decreasing bone stiffness and bone volume fraction suggests that damage may accumulate rather rapidly in diseases associated with low bone density due to the dramatic increase of shear stresses in the tissue. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8719Xx, 8759Ls, 8759Fm, 8710+e