Mutual associations among microstructural,physical and mechanical properties of human cancellous bone

Previous studies have shown that low-density, rod-like trabecular structures develop in regions of low stress, whereas high-density, plate-like trabecular structures are found in regions of high stress. This phenomenon suggests that there may be a close relationship between the type of trabecular structure and mechanical properties. In this study, 160 cancellous bone specimens were produced from 40 normal human tibiae aged from 16 to 85 years at post-mortem. The specimens underwent micro-CT and the microstructural properties were calculated using unbiased three-dimensional methods. The specimens were tested to determine the mechanical properties and the physical/compositional properties were evaluated. The type of structure together with anisotropy correlated well with Young's modulus of human tibial cancellous bone. The plate-like structure reflected high mechanical stress and the rod-like structure low mechanical stress. There was a strong correlation between the type of trabecular structure and the bone-volume fraction. The most effective microstructural properties for predicting the mechanical properties of cancellous bone seem to differ with age.     

Human cancellous bone from T12-L1 vertebrae has unique microstructural and trabecular shear stress properties

Increase of trabecular stress variability with loss of bone mass has been implicated as a mechanism for increased cancellous bone fragility with age and disease. In the current study, a previous observation that trabecular shear stress estimates vary along the human spine such that the cancellous tissue from the thoracic 12 (T12)-lumbar 1 (L1) junction experiences the highest trabecular stresses for a given load was tested as a formal hypothesis using multiple human spines. Thoracic 4, T5, T7, T9, T10, T12, L1, L2, L4 and L5 vertebrae from 10 human cadaver spines were examined. One specimen in the central anterior region was cored in the supero-inferior (SI) direction and another in the postero-lateral region was cored in the transverse (TR) direction from each vertebra. Micro-CT-based large-scale finite element models were constructed for each specimen and compression in the long axis of the cylindrical specimens was simulated. Cancellous bone modulus and the mean, the standard deviation, variability and amplification of trabecular von Mises stresses were computed. Bone volume fraction, trabecular number, trabecular thickness, trabecular separation, connectivity density and degree of anisotropy were calculated using 3D stereology. The results were analyzed using a mixed model in which spine level was modeled using a quadratic polynomial. The maximum of trabecular shear stress amplification and minimum of bone volume fraction were found in the cancellous tissue from the T12-L1 location when results from the samples of the same vertebra were averaged. When groups were separated, microstructure and trabecular stresses varied with spine level, extrema being at the T12-L1 levels, for the TR specimens only. SI/TR ratio of measured parameters also had quadratic relationships with spine level, the extrema being located at T12-L1 levels for most parameters. For microstructural parameters, these ratios approached to a value of one at the T12-L1 level, suggesting that T12-L1 vertebrae have more uniform cancellous tissue properties than other levels. The mean intercept length in the secondary principal direction of trabecular orientation could account for the variation of all mechanical parameters with spine level. Our results support that cancellous tissue from T12-L1 levels is unique and may explain, in part, the higher incidence of vertebral fractures at these levels.     

Variability of trabecular microstructure is age-, gender-, race- and anatomic site-dependent and affects stiffness and stress distribution properties of human vertebral cancellous bone

Cancellous bone microstructure is an important determinant of the mechanical integrity of vertebrae. The numerous microstructural parameters that have been studied extensively are generally represented as a single value obtained as an average over a sample. The range of the intra-sample variability of cancellous microstructure and its effect on the mechanical properties of bone are less well-understood. The objectives of this study were to investigate the extent to which human cancellous bone microstructure within a vertebra i) is related to bone modulus and stress distribution properties and ii) changes along with age, gender and locations thoracic 12 (T12) vs lumbar 1 (L1).Vertebrae were collected from 15 male (66 ± 15 years) and 25 female (54 ± 16 years) cadavers. Three dimensional finite element models were constructed using microcomputed tomography images of cylindrical specimens. Linear finite element models were used to estimate apparent modulus and stress in the cylinders during uniaxial compression. The intra-specimen mean, standard deviation (SD) and coefficient of variation (CV) of microstructural variables were calculated.Mixed model statistical analysis of the results demonstrated that increases in the intra-specimen variability of the microstructure contribute to increases in the variability of trabecular stresses and decreases in bone stiffness. These effects were independent from the contribution from intra-specimen average of the microstructure. Further, the effects of microstructural variability on bone stiffness and stress variability were not accounted for by connectivity and anisotropy. Microstructural variability properties (SD, CV) generally increased with age, were greater in females than in males and in T12 than in L1. Significant interactions were found between age, gender, vertebra and race. These interactions suggest that microstructural variability properties varied with age differently between genders, races and vertebral levels.The current results collectively demonstrate that microstructural variability has a significant effect on mechanical properties and tissue stress of human vertebral cancellous bone. Considering microstructural variability could improve the understanding of bone fragility and improve assessment of vertebral fracture risk.     

Age-and region-dependent changes in three-dimensional microstructural properties of proximal femoral trabeculae

Summary  This study investigated regional variations in the 3D microstructure of trabecular bone in human proximal femur, with respect to aging. The results demonstrate that age-related changes in trabecular microstructure significantly varied from different sub-regions of the proximal femur. Introduction  We hypothesize that the age-related changes in trabecular bone microstructure appear to be varied from specific anatomic sub-regions of the proximal femur followed by non-uniform bone loss. The purpose of this study was therefore to explore regional variations in the 3D microstructure of trabecular bone in human proximal femur, with respect to aging. Methods  A total of 162 trabecular bone cores from six regions of 27 femora of male cadaver donors were scanned using micro-computed tomography (micro-CT). The following microstructural parameters were calculated: bone volume fraction (BV/TV), trabecular number (Tb.N), thickness (Tb.Th) and separation (Tb.Sp), structure model index (SMI), and degree of anisotropy (DOA). Results  Age-related changes in trabecular microstructure varied from different regions of the proximal femur. There was a significant decrease in bone volume fraction and an almost identical decrease in trabecular thickness associated with aging at any region. Regional analysis demonstrated a significant difference in BV/TV, Tb.Th, Tb.Sp, Tb.N and DOA between superior and inferior neck, as well as a significant difference in BV/TV, Tb.Sp, Tb.N, SMI and DOA between superior and inferior trochanter. Conclusions  Age-related changes in bone loss and trabecular microstructure within the male proximal femur are not uniform in this cadaveric population.     

Bone density does not reflect mechanical properties in early-stage arthrosis

Subchondral cancellous bone specimens were removed from 10 human postmortem early-stage arthrotic proximal tibiae (mean age 73 (63-81) years) and 10 age- and gender-matched normal proximal tibiae. The early-stage arthrosis was confirmed histologically and the specimens were divided into 4 groups: medial arthrosis, lateral control, normal medial and normal lateral controls. The specimens were tested in compression to determine mechanical properties and then physical/compositional properties. Compared to the normal medial control, we found reductions in ultimate stress, Young's modulus, and failure energy, and an increase in ultimate strain of arthrotic cancellous bone. Bone volume fraction, apparent density, apparent ash density, and collagen density were higher in cancellous bone with arthrosis, but no differences were found in tissue density, mineral and collagen concentrations between arthrotic cancellous bone and the 3 controls. None of the mechanical properties of arthrotic cancellous bone could be predicted by the physical/compositional properties measured. The increase in bone tissue in early-stage arthrotic cancellous bone did not make up for the loss of mechanical properties, which suggests a deterioration in the quality of arthrotic cancellous bone.     

Bone density does not reflect mechanical properties in early-stage arthrosis

Subchondral cancellous bone specimens were removed from 10 human postmortem early-stage arthrotic proximal tibiae (mean age 73 (63-81) years) and 10 age- and gender-matched normal proximal tibiae. The early-stage arthrosis was confirmed histologically and the specimens were divided into 4 groups: medial arthrosis, lateral control, normal medial and normal lateral controls. The specimens were tested in compression to determine mechanical properties and then physical/compositional properties. Compared to the normal medial control, we found reductions in ultimate stress, Young's modulus, and failure energy, and an increase in ultimate strain of arthrotic cancellous bone. Bone volume fraction, apparent density, apparent ash density, and collagen density were higher in cancellous bone with arthrosis, but no differences were found in tissue density, mineral and collagen concentrations between arthrotic cancellous bone and the 3 controls. None of the mechanical properties of arthrotic cancellous bone could be predicted by the physical/compositional properties measured. The increase in bone tissue in early-stage arthrotic cancellous bone did not make up for the loss of mechanical properties, which suggests a deterioration in the quality of arthrotic cancellous bone.     

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.     

Mechanical consequence of trabecular bone loss and its treatment: a three-dimensional model simulation

Age-related changes in the microstructure of trabecular bone, such as decreases in trabecular number and trabecular thickness, lead to reductions in mechanical properties, such as Young's modulus and strength. Current drug therapy, such as bisphosphonate or parathyroid hormone, improves the mechanical properties of bone mainly by increasing the trabecular thickness, but not increasing the trabecular number. However, the mechanical efficacy of these treatments has not been fully quantified using trabecular bone models. In this study, we used an idealized three-dimensional (3D) microstructural model of trabecular bone to create bone loss either through trabeculae thinning or random removal of trabeculae, and simulated treatment by increasing the trabeculae thickness of the remaining trabeculae. The reduction in either the Young's modulus or the strength due to trabeculae loss was proportional to a much higher power of reduction in bone volume fraction than due to trabeculae thinning. This indicates that bone loss due to trabeculae loss is much more detrimental to Young's modulus and strength of trabecular bone than due to trabeculae thinning, indicating the importance of trabecular number and connectivity in the mechanical integrity of trabecular bone. In general, treatments by increasing the trabecular thickness of remaining trabeculae after trabeculae loss cannot fully recover the initial mechanical properties of intact bone, even if bone loss is fully recovered, whereas trabecular thickening can fully restore the mechanical properties after bone loss by trabeculae thinning. The results also show that the residual loss in mechanical properties is dependent on the extent of trabeculae loss.     

Functional dependence of cancellous bone shear properties on trabecular microstructure evaluated using time‐lapsed micro‐computed tomographic imaging and torsion testing

When compressed axially, cancellous bone often fails at an oblique angle along well‐defined bands, highlighting the importance of cancellous bone shear properties. Torsion testing to determine shear properties of cancellous bone has often been conducted under conditions appropriate only for axisymmetric specimens comprised of homogeneous and isotropic materials. However, most cancellous bone specimens do not meet these stringent test conditions. Therefore, we studied the application of the stepwise torsion testing system in biologic specimens with viscoelastic behavior. We explore the functional dependence of cancellous bone shear properties on trabecular microstructure and its spatial distribution, specifically the contribution of the subregion with the minimum polar moment of inertia to the overall failure properties. Torsional properties of whale trabecular specimens obtained by the incremental application of stepwise torque were not different from those obtained via continuous testing. Average polar moment of inertia accounted for 82 and 67% of the variation in shear modulus and shear stress, respectively. However, torsional properties were better predicted by the subregion with minimum polar moment of inertia, describing 87 and 74% of the variation in shear modulus and shear stress. The use of a novel torsion testing system for nonhomogeneous, orthotropic cancellous bone using stepwise application of torsion and simultaneous micro‐computed tomographic imaging was further studied. Most importantly, a heterogeneous cancellous bone microstructural environment, the subregion with the minimum polar moment of inertia, hence the weakest spatial distribution of bone, predicted the shear properties for the entire bone volume. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1667–1674, 2009     

Quantification of age-related changes in the structure model type and trabecular thickness of human tibial cancellous bone

Structure model type and trabecular thickness are important characteristics in describing cancellous bone architecture. It has been qualitatively observed that a radical change of trabeculae from plate-like to rod-like occurs in aging, bone remodeling, and osteoporosis. Thickness of trabeculae has traditionally been measured using model-based histomorphometric methods on two-dimensional (2-D) sections. However, no quantitative study has been published based on three-dimensional (3-D) methods on the age-related changes in structure model type and trabecular thickness for human peripheral (tibial) cancellous bone. In this study, 160 human proximal tibial cancellous bone specimens from 40 normal donors, aged 16 to 85 years, were collected. These specimens were micro-computed tomography (micro-CT) scanned, then the micro-CT images were segmented using optimal thresholds. From accurate 3-D data sets, structure model type and trabecular thickness were quantified by means of novel 3-D methods. Structure model type was assessed by calculating the structure model index (SMI). The SMI was quantified based on a differential analysis of the triangulated bone surface of a structure. This technique allows quantification of structure model type, such as plate, rod objects, or mixture of plates or rods. Trabecular thickness is calculated directly from 3-D images, which is especially important for an a priori unknown or changing structure. Furthermore, 2-D trabecular thickness was also calculated based on the plate model. Our results showed that structure model type changed towards more rod-like in the elderly, and that trabecular thickness declined significantly with age. These changes become significant after 80 years of age for human tibial cancellous bone, whereas both properties seem to remain relatively unchanged between 20 and 80 years. Although a fairly close relationship was seen between 3-D trabecular thickness and 2-D trabecular thickness, real 3-D trabecular thickness was significantly underestimated using 2-D method.     

Changes in bone structure and mass with advancing age in the male C57BL/6J mouse.

To determine whether the mouse loses bone with aging and whether the changes mimic those observed in human aging, we examined the changes in the tibial metaphysis and diaphysis in the male C57BL/6J mouse over its life span using microcomputed tomography (microCT). Cancellous bone volume fraction (BV/TV) decreased 60% between 6 weeks and 24 months of age. Loss was characterized by decreased trabecular number (Tb.N), increased trabecular spacing (Tb.Sp), and decreased connectivity. Anisotropy decreased while the structure model index increased with age. Cortical bone thickness increased between 6 weeks and 6 months of age and then decreased continuously to 24 months (-12%). Cortical bone area (Ct.Ar) remained constant between 6 and 24 months. Fat-free weight reached a peak at 12 months and gradually declined to 24 months. Total mass lost between 12 and 24 months reached 10%. Overall, the age-related changes in skeletal mass and architecture in the mouse were remarkably similar to those seen in human aging. Furthermore, the rapid early loss of cancellous bone suggests that bone loss is not just associated with old age in the mouse but rather occurs as a continuum from early growth. We conclude that the C57BL/6J male mouse maybe a useful model to study at least some aspects of age-related bone loss in humans.     

Structural parameters and mechanical strength of cancellous bone in the femoral head in osteoarthritis do not depend on age

For normal bone, aging has been associated with a decrease of both density and failure strength, and with the development of pathologies such as osteoporosis. Conversely, it has been reported that another common disease, osteoarthritis, may alter these age-related changes in cancellous bone, suggesting that it may have a protective role against osteoporosis and the correspondent fracture risk. It was reported that in the principal compressive region of the femoral head in osteoarthritis the bone density does not depend on age. However, it is not clear if this independence on age of the cancellous bone density corresponds also to a reduced dependence on age of the strength to failure. The present work examined cancellous bone from the principal compressive region of the femoral head of 37 patients having severe osteoarthritis. The aim was (1) to investigate the dependence on age of both the structural parameters and the ultimate stress and (2) to investigate the relationships between the ultimate stress and the structural parameters. Using X-ray microcomputed tomography, three-dimensional structural parameters, such as bone volume fraction, direct trabecular thickness and structure model index were calculated. Then the specimens were compressed to failure to determine the ultimate stress. It was found that none of the investigated structural parameters did depend on age, and also the ultimate stress did not depend on age (p>0.05 for all regressions on age). In addition, the ultimate stress was significantly correlated with the structural parameters, primary with the minimum bone volume fraction and the average bone volume fraction (R(2)=0.95 and R(2)=0.84, respectively). These findings show that severe osteoarthritis or a related factor may change the age dependences of both the structural parameters and the mechanical properties usually reported for normal cancellous bone. These results suggest for this pathology to have a protective role against the age-related decrease in density, the age-related deterioration of the microarchitecture and the age-related decrease of the failure strength for the cancellous bone in the principal compressive region of the human femoral head.     

Cancellous Bone Properties and Matrix Content of TGF-β2 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-β2 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/σ_app) and variability (VMCOV) were calculated using microcomputed tomography (μCT)-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-β2 and IGF-I were measured by ELISA. We found higher matrix concentrations of TGF-β2 were associated with higher Tb.Sp and VMExp/σ_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/σ_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-β2 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.     

Bone density does not reflect mechanical properties in early-stage arthrosis

Subchondral cancellous bone specimens were removed from 10 human postmortem early-stage arthrotic proximal tibiae (mean age 73 (63-81) years) and 10 age- and gender-matched normal proximal tibiae. The early-stage arthrosis was confirmed histologically and the specimens were divided into 4 groups: medial arthrosis, lateral control, normal medial and normal lateral controls. The specimens were tested in compression to determine mechanical properties and then physical/compositional properties. Compared to the normal medial control, we found reductions in ultimate stress, Young's modulus, and failure energy, and an increase in ultimate strain of arthrotic cancellous bone. Bone volume fraction, apparent density, apparent ash density, and collagen density were higher in cancellous bone with arthrosis, but no differences were found in tissue density, mineral and collagen concentrations between arthrotic cancellous bone and the 3 controls. None of the mechanical properties of arthrotic cancellous bone could be predicted by the physical/compositional properties measured. The increase in bone tissue in early-stage arthrotic cancellous bone did not make up for the loss of mechanical properties, which suggests a deterioration in the quality of arthrotic cancellous bone.     

Properties of growing trabecular ovine bone. Part II: architectural and mechanical properties

We aimed to highlight the relationship between age and the architectural properties of trabecular bone, to outline the patterns in which the variations in these properties take place, and to investigate the influence of the architecture on the mechanical properties of trabecular bone in growing animals. We studied 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. They were serially sectioned and their architectural properties were determined. Similar cubes were obtained from the identical anatomical position of the contralateral tibia and their compressive mechanical properties measured. The values obtained from the skeletally immature and mature individuals were compared. Multiple regression analyses were performed between the architectural and the mechanical properties. The bone volume fraction, the mean trabecular volume, the architectural and the mechanical anisotropy, the elastic modulus, the bone strength, the energy absorption to failure, and the elastic energy correlated positively with increasing age whereas the connectivity density, the bone surface density, the ultimate strain, the absorption of viscoelastic energy and the relative loss of energy correlated inversely. The values of all variables were significantly different in the skeletally mature and immature groups. We determined the patterns in which the variations took place. The bone volume fraction of the trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the mean trabecular volume and the bone surface density, it explained 81% of the variations in the compressive elastic modulus of specimens obtained from the contralateral tibiae.     

Regional variations in microstructural properties of vertebral trabeculae with aging

The aim of this study was to identify regional variations in the three-dimensional microstructure of vertebral cancellous bones, and their relative differences with respect to aging. Ninety trabecular specimens were obtained from six normal L4 vertebral bodies of six male cadaver donors in two age groups, three aged 62 years and three aged 69 years; (n = 45, each). In each vertebral body, five trabecular columns, each of 8 × 8 × 25mm³, were cut from the anterior, posterior, central, right, and left regions. These columns were scanned, using high-resolution micro-computed tomography (µCT), three times, to obtain superior, middle, and inferior layers. Fifteen regions were obtained for each vertebral body. For all 90 trabecular specimens the bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), as well as the three radii of the mean intercept length (MIL) ellipsoid (H1, H2, and H3) were determined. Regional variations in different transverse layers and vertical columns within and between the two age groups were then analyzed. The results showed significant differences in BV/TV, Tb.N, DA, and H2/H3 between the two age groups. The BV/TV and Tb.N were decreased, while the anisotropic parameters were increased significantly with age, increasing from age 62 to 69. Change in Tb.Th was not statistically significant, although the average was slightly smaller in the 69-year group. Each microstructural parameter followed its own pattern of regional variation within each group, suggesting both mechanical and age-related adaptation. This is the first study that has provided microstructural data of the vertebral body in a Chinese sample. These data may help us to gain more insight into the mechanism of the occurrence of lumbar osteoporosis and the related regional fracture risks, and may provide a reference for better enhancement of fracture repair.     

The interrelation of trabecular microstructural parameters of the greater tubercle measured for different species

In the present study the trabecular microstructural parameters (bone volume fraction, trabecular thickness, trabecular separation, trabecular number, connectivity density, degree of anisotropy, and structure model index) of the greater tubercle of the humeral head were measured for human healthy, human osteopenic, ovine, bovine, and porcine bones using micro‐computed tomography. Except for trabecular thickness and degree of anisotropy the values of the trabecular microstructural parameters generally differed significantly between species. Thus, only the species for which the implant is designed should be used for in vitro mechanical tests on the stability of implants in trabecular bone. Multivariate regression analysis showed that the microstructural parameters have similar principal interrelations in all species. The most significant relations were found between trabecular thickness and bone volume fraction (median (over all species) p < 0.001), trabecular number and bone volume fraction (p = 0.001), the structural change from plates to rods and bone volume fraction (p < 0.001) as well as between connectivity density and trabecular number (p < 0.001). Trabecular thickness, trabecular number, and the structural change from plates to rods each contributed to the bone volume fraction approximately to the same extent. Based on the similar principal interrelations of the trabecular microstructural parameters found in all investigated species the design of trabecular microstructure in the greater tubercle follows similar phenomenological mechanisms in all species. Thus, in vivo experiments on trabecular bone healing and osteoporosis research for application in humans can be conducted in ovine, bovine, or porcine species. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:429–434, 2012     

Variations in three-dimensional cancellous bone architecture of the proximal femur in female hip fractures and in controls.

Cubes of cancellous bone were obtained from proximal femora of women with hip fractures (n = 26) and from female cadaveric controls (n = 32) to compare architecture and mechanics between groups. Specimens were scanned on a microcomputed tomography system. Stereologic algorithms and model-based estimates were applied to the data to characterize the three-dimensional cancellous microstructure. Cubes were mechanically tested to failure to obtain mechanical properties. Specimens from control subjects had significantly higher bone volume fraction, trabecular number, and connectivity than specimens from patients with hip fractures; no difference in trabecular thickness was observed between groups. Both maximum modulus and ultimate stress were significantly higher in the control than in the fracture group, consistent with the higher bone volume found in the control group. No statistical differences in any of these architectural or mechanical variables were found when groups were matched for bone volume. Specimens from both patients with hip fractures and controls demonstrated strong relationships between trabecular number and bone volume fraction that were statistically equivalent, suggesting that for a given bone mass, both groups have the same overall number of trabeculae. However, there was an architectural difference between fracture and control groups in terms of the three-dimensional spatial arrangement of trabeculae. Fracture specimens had a significantly more anisotropic (oriented) structure than control specimens, with proportionately fewer trabecular elements transverse to the primary load axis, even when matched for bone volume. Relationships between mechanical and architectural parameters were significantly different between groups, suggesting that fracture and control groups have different structure-mechanics relationships, which we hypothesize may be a consequence of the altered three-dimensional structure between groups.     

The interaction of microstructure and volume fraction in predicting failure in cancellous bone

Inroads have been made in the diagnosis and treatment of osteoporosis, yet dual-energy X-ray absorptiometry is still the primary diagnostic modality. This method provides 2D projections of an irregular 3D construct. However, human cancellous bone is highly heterogeneous with varying material properties. Therefore, to properly assess fracture risk, it is imperative to take into consideration microstructural indices besides subregional bone volume fraction (BV/TV).

A power law model with average BV/TV as the independent variable describes 38% of the variation in yield strength; however, this predictive power is increased to 56% when BV/TV of the weakest subregion is considered. Of twenty-five specimens studied, 76% had minimum BV/TV, maximum principal Eigen value of the fabric tensor (H₁) and minimum connectivity density (Conn.D) values within the visually determined failure regions. These three independent morphometric indices yielded significant differences between the failure and non-failure regions of each specimen.

From the results, we conclude that subregions with minimal BV/TV values are better predictors of mechanical failure in cancellous bone than average specimen BV/TV. Addition of microstructural indices augments this predictive power to generate a trabecular failure prediction model based on volume fraction and cancellous bone microstructure specifically in areas where trabecular failure is most likely to occur.