The limitations of canine trabecular bone as a model for human: a biomechanical study

Distal canine femurs were sectioned into 8 mm cubic specimens. Orthogonal compression tests were performed to preyield in two or three directions and to failure in a third. Apparent density and ash weight density were measured for a subset of specimens. The results were compared to the human distal femur results of Ciarelli et al. (Transactions of the 32nd Annual Meeting of the Orthopaedic Research Society, Vol. 11, p. 42, 1986). Quantitative similarities existed in the fraction of components comprising the trabecular tissue of the two species. Qualitative similarities were seen in the positional and anisotropic variation of the mechanical properties, and also in the form and strength of the relationships between the mean modulus and bone density, ultimate stress and density, and ultimate stress and modulus. However, significantly different regression equations resulted for the mean modulus-density, and ultimate stress modulus relationships, indicating that for the same density, canine trabecular bone displays a lower modulus than human, and may achieve greater compressive strains before failure.     

On the streets of San Francisco: highlights from the ISSCR Annual Meeting 2010

The 2010 Annual Meeting of the International Society for Stem Cell Research (ISSCR) was held in San Francisco in June with an exciting program covering a wealth of stem cell research from basic science to clinical research.     

The epigenetics of the cell

A report on the 42nd Annual Meeting of the American Society for Cell Biology, San Francisco, 14-18 December 2002.     

Understanding embryonic development: from screens to genes

A report on the 64th Annual Meeting of the Society for Developmental Biology, San Francisco, USA, 27 July-1 August 2005.     

Linear poroelastic cancellous bone anisotropy: trabecular solid elastic and fluid transport properties

The mechanical performance of cancellous bone is characterized using experiments which apply linear poroelasticity theory. It is hypothesized that the anisotropic organization of the solid and pore volumes of cancellous bone can be physically characterized separately (no deformable boundary interactive effects) within the same bone sample. Due to its spongy construction, the in vivo mechanical function of cancellous or trabecular bone is dependent upon fluid and solid materials which may interact in a hydraulic, convective fashion during functional loading. This project provides insight into the organization of the tissue, ie., the trabecular connectivity, by defining the separate nature of this biphasic performance. Previous fluid flow experiments [Kohles et al., 2001, Journal of Biomechanics, 34(11), pp. 1197-1202] describe the pore space via orthotropic permeability. Ultrasonic wave propagation through the trabecular network is used to describe the solid component via orthotropic elastic moduli and material stiffness coefficients. The linear poroelastic nature of the tissue is further described by relating transport (fluid flow) and elasticity (trabecular load transmission) during regression analysis. In addition, an empirical relationship between permeability and porosity is applied to the collected data. Mean parameters in the superior-inferior (SI) orientation of cubic samples (n=20) harvested from a single bovine distal femur were the largest (p<0.05) in comparison to medial-lateral (ML) and anterior-posterior (AP) orientations: Apparent elastic modulus (2,139 MPa), permeability (4.65x10(-10) m2), and material stiffness coefficient (13.6 GPa). A negative correlation between permeability as a predictor of structural elastic modulus supported a parametric relationship in the ML (R2=0.4793), AP (R2=0.3018), and SI (R2=0.6445) directions (p<0.05).     

Distinguished Lecture in Archeology: Beyond Criticizing New Archeology

This article was presented as the Distinguished Lecture in Archeology at the 91st Annual Meeting of the American Anthropological Association, December 4, 1992, in San Francisco.     

Distinguished Lecture in General Anthropology: The Anthropology of Trouble

This essay was presented as the Distinguished Lecture in General Anthropology at the 91st Annual Meeting of the American Anthropological Association, December 4, 1992, in San Francisco, California.     

Distinguished Lecture: Coming into Focus

This essay was presented as the Distinguished Lecture at the 91st Annual Meeting of the American Anthropological Association, December 5, 1992, in San Francisco, California.     

Beyond a 'skeleton': understanding cellular functions of the cytoskeleton

A report on the cytoskeleton sessions of the 40^th Annual Meeting of the American Society for Cell Biology, San Francisco, 9-13 December 2000.     

The fracture toughness of cancellous bone

The mechanical capacity and integrity of cancellous bone is crucial in osteoporosis, a condition which is set to become more prevalent with increasing lifespan and population sizes. The fracture toughness (FT) of cancellous bone has never been examined before and the conditions associated with the growth of a major crack through the lattice of cancellous bone, a cellular solid, may improve our understanding for structural integrity of this material. The aim of this study is to provide (i) basic data on cancellous bone FT and (ii) the experimental support for the hypothesis of Gibson, L.J., Ashby, M.F. [1997a. Chapter 10: Wood. In: Cellular Solids: Structure and Properties, second ed. Cambridge University Press, pp. 387–428; Gibson, L.J., Ashby, M.F., 1997b. Chapter 11: Cancellous Bone. In: Cellular Solids: Structure and Properties, second ed. Cambridge University Press, pp. 429–52] that the FT of cancellous bone tissue is governed by the density of the tissue to a power function of between one and two. 294 SENB and 121 DC(T) specimen were manufactured from 45 human femoral heads, 37 osteoporotic and 8 osteoarthritic, as well as 19 equine thoracic vertebrae. The samples were manufactured in two groups: the first aligned with the trabecular structure (A_∥), the second orientated at 90° to the main trabecular orientation (A_⊥). The samples were tested in either tensile or bending mode to provide values of the stress intensity factor (K). The results which were obtained show a strong and significant link between the density of the cancellous bone tissue and that the critical stress intensity values are governed by the density of the tissue to a power function of between 1 and 2 (K_Q vs. apparent density: A_⊥=1.58, A_∥=1.6). Our results provide some fundamental values for the critical stress intensity factor for cancellous bone and also support the previous hypothesis as set by Gibson, L.J., Ashby, M.F., 1997a. Chapter 10: Wood. In: Cellular Solids: Structure and Properties, second ed. Cambridge University Press, pp. 387–428; Gibson, L.J., Ashby, M.F., (1997b). Chapter 11: Cancellous Bone. In: Cellular Solids: Structure and Properties, second ed. Cambridge University Press, pp. 429–52.     

A theoretical model to predict distribution of the fabric tensor and apparent density in cancellous bone

 The adaptation of cancellous bone to mechanical forces is well recognized. Theoretical models for predicting cancellous bone architecture have been developed and have mainly focused on the distribution of trabecular mass or the apparent density. The purpose of this study was to develop a theoretical model which can simultaneously predict the distribution of trabecular orthotropy/orientation, as represented by the fabric tensor, along with apparent density. Two sets of equations were derived under the assumption that cancellous bone is a biological self-optimizing material which tends to minimize strain energy. The first set of equations provide the relationship between the fabric tensor and stress tensor, and have been verified to be consistent with Wolff’s law of trabecular architecture, that is, the principal directions of the fabric tensor coincide with the principal stress trajectories. The second set of equations yield the apparent density from the stress tensor, which was shown to be identical to those obtained based on local optimization with strain energy density of true bone tissue as the objective function. These two sets of equations, together with elasticity field equations, provide a complete mathematical formulation for the adaptation of cancellous bone. Received: 25 February 1997/Revised version: 23 September 1997     

Comparative effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats.

The purpose of the present study was to compare the effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats. Twenty-six female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into four groups: the sham-operated control (Sham) group and the three ovariectomy (OVX) groups, namely, OVX + vehicle, OVX + alendronate (2.5 mg/kg, p.o., daily), and OVX + alfacalcidol (0.5 mug/kg, p.o., daily). At the end of the 8-week experimental period, bone histomorphometric analyses of cancellous bone at the proximal tibial metaphysis and cortical bone at the tibial diaphysis were performed, and the mechanical properties of the femoral distal metaphysis and femoral diaphysis were evaluated. OVX decreased cancellous bone volume per total tissue volume (BV/TV), and the maximum load of the femoral distal metaphysis, as a result of increases in serum osteocalcin (OC) levels, and also the number of osteoclasts (N.Oc), osteoclast surface (OcS) and bone formation rate (BFR) per bone surface (BS), and BFR/BV, without any effect on cortical area (Ct Ar), or maximum load of the femoral diaphysis. Alendronate prevented this decrease in cancellous BV/TV by suppressing increases in N.Oc/BS, OcS/BS, BFR/BS, and BFR/BV, without any apparent effect on Ct Ar, or maximum load of the femoral distal metaphysis and femoral diaphysis. On the other hand, alfacalcidol increased cancellous BV/TV, Ct Ar, and the maximum load of the femoral distal metaphysis and femoral diaphysis, by mildly decreasing trabecular BFR/BV, maintaining trabecular mineral apposition rate and osteoblast surface per BS, increasing periosteal and endocortical BFR/BS, and preventing an increase in endocortical eroded surface per BS. The present study clearly showed the differential skeletal effects of alendronate and alfacalcidol in ovariectomized rats. Alendronate prevented OVX-induced cancellous bone loss by suppressing bone turnover, while alfacalcidol improved cancellous and cortical bone mass and bone strength by suppressing bone resorption and maintaining or even increasing bone formation.     

The mechanical heterogeneity of the hard callus influences local tissue strains during bone healing: a finite element study based on sheep experiments

During secondary fracture healing, various tissue types including new bone are formed. The local mechanical strains play an important role in tissue proliferation and differentiation. To further our mechanobiological understanding of fracture healing, a precise assessment of local strains is mandatory. Until now, static analyses using Finite Elements (FE) have assumed homogenous material properties. With the recent quantification of both the spatial tissue patterns (Vetter et al., 2010) and the development of elastic modulus of newly formed bone during healing (Manjubala et al., 2009), it is now possible to incorporate this heterogeneity. Therefore, the aim of this study is to investigate the effect of this heterogeneity on the strain patterns at six successive healing stages. The input data of the present work stemmed from a comprehensive cross-sectional study of sheep with a tibial osteotomy (Epari et al., 2006). In our FE model, each element containing bone was described by a bulk elastic modulus, which depended on both the local area fraction and the local elastic modulus of the bone material. The obtained strains were compared with the results of hypothetical FE models assuming homogeneous material properties. The differences in the spatial distributions of the strains between the heterogeneous and homogeneous FE models were interpreted using a current mechanobiological theory (Isakson et al., 2006). This interpretation showed that considering the heterogeneity of the hard callus is most important at the intermediate stages of healing, when cartilage transforms to bone via endochondral ossification.     

The role of an effective isotropic tissue modulus in the elastic properties of cancellous bone.

Conceptually, the elastic characteristics of cancellous bone could be predicted directly from the trabecular morphology--or architecture--and by the elastic properties of the tissue itself. Although hardly any experimental evidence exists, it is often implicitly assumed that tissue anisotropy has a negligible effect on the apparent elastic properties of cancellous bone. The question addressed in this paper is whether this is actually true. If it is, then micromechanical finite element analysis (micro-FEA) models, representing trabecular architecture, using an 'effective isotropic tissue modulus' should be able to predict apparent elastic properties of cancellous bone. To test this, accurate multi-axial compressive mechanical tests of 29 whale bone specimens were simulated with specimen-specific micro-FEA computer models built from true three-dimensional reconstructions. By scaling the micro-FEA predictions by a constant tissue modulus, 92% of the variation of Young's moduli determined experimentally could be explained. The correlation even increased to 95% when the micro-FEA moduli were scaled to the isotropic tissue moduli of individual specimens. Excellent agreement was also found in the elastic symmetry axes and anisotropy ratios. The prediction of Poisson's ratios was somewhat less precise at 85% correlation. The results support the hypothesis; for practical purposes, the concept of an 'effective isotropic tissue modulus' concept is a viable one. They also suggest that the value of such a modulus for individual cases might be inferred from the average tissue density, hence the degree of mineralization. Future studies must clarify how specific the tissue modulus should be for different types of bone if adequate predictions of elastic behavior are to be made in this way.     

The miracle of microarray data analysis

A report on the tenth Annual Bioinformatics and Genome Research meeting of the Cambridge Healthtech Institute's Beyond Genome 2001 series, San Francisco, USA, 17-19 June 2001.     

饲养条件下川金丝猴群中主雄的移除和替换对社群行为的影响

在上海野生动物园对一群半散养的川金丝猴进行了为期一年的行为学研究。在此期间,猴群中发生了4起家庭主雄被移除和替代事件和一个雌性群因繁殖需要引入一个成年雄猴的事件,该过程在饲养条件下首次被完整记录。观察发现,繁殖群中,在家庭主雄猴的健康状况良好期间,群中各雄性成员间的社会等级关系相当稳定,很少变动。主雄猴有效地控制着群体的秩序,并严格地看护着其家庭中的雌猴免受其他雄猴的侵扰,而且它也很少对其他低序位雄猴主动攻击。全雄群中则再由一个高序位雄猴控制其他低序位雄猴。疾病、衰老、前主雄猴的存在以及被饲养人员从群中移除进行治疗等都可能引起猴群社会发生很大动荡,尤其是全雄群中各雄猴的社会等级序位发生剧烈改变,甚至发生家庭主雄的替代。在本报道中,人为因素在主雄替代过程中起着主要作用。主雄替代一旦成功,新主雄会把原主雄赶入全雄群,攻击追撵其他低序位雄猴,并彻底与全雄群完全脱离。对于每一个新主雄,家庭中的雌猴对其的接纳表现出明显的选择倾向。雌性性选择可能是野生猴群中新家庭群建立一种内在基础机制,同时提示偷配发生的可能性。     

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

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

Effect of gender on bone turnover in adult rats during simulated weightlessness.

Prologned spaceflight results in bone loss in astronauts, but there is considerable individual variation. The goal of this rat study was to determine whether gender influences bone loss during simulated weightlessness. Six-month-old Fisher 344 rats were hindlimb unweighted for 2 wk, after which the proximal tibiae were evaluated by histomorphometry. There were gender differences in tibia length, bone area, cancellous bone architecture, and bone formation. Compared with female rats, male rats had an 11.6% longer tibiae, a 27.8% greater cortical bone area, and a 37.6% greater trabecular separation. Conversely, female rats had greater cortical (316%) and cancellous (145%) bone formation rates, 28.6% more cancellous bone, and 30% greater trabecular number. Hindlimb unweighting resulted in large reductions in periosteal bone formation and mineral apposition rate in both genders. Unweighting also caused cancellous bone loss in both genders; trabecular number was decreased, and trabecular separation was increased. There was, however, no change in trabecular thickness in either gender. These architectural changes in cancellous bone were associated with decreases in bone formation and steady-state mRNA levels for bone matrix proteins and cancellous bone resorption. In conclusion, there are major gender-related differences in bone mass and turnover; however, the bone loss in hindlimb unweighted adult male and female rats appears to be due to similar mechanisms.     

Preventive effects of risedronate and calcitriol on cancellous osteopenia in rats treated with high-dose glucocorticoid.

We compared the effects of risedronate (Ris) and calcitriol (Cal) on cancellous osteopenia in rats treated with high-dose glucocorticoid (GC). Forty female Sprague-Dawley rats, 4 months of age, were randomized by the stratified weight method into four groups of 10 rats each according to the following treatment schedule: intact control, and GC administration with vehicle, Ris, or Cal. The GC (methylprednisolone sodium succinate, 5.0 mg/kg, s.c.), Ris (10 microg/kg, s.c.), and Cal (0.1 microg/kg, p.o.) were administered 3 times a week. At the end of the 4-week treatment period, bone histomorphometric analysis was performed for cancellous bone of the proximal tibial metaphysis. The GC administration decreased cancellous bone volume (BV/total tissue volume [TV]), trabecular number (Tb N), and trabecular thickness (Tb Th), as a result of increased bone resorption and decreased bone formation. Ris treatment markedly increased cancellous BV/TV and Tb N above the control level as a result of suppressed bone turnover. On the other hand, Cal treatment attenuated the GC-induced decrease in cancellous BV/TV and Tb Th as a result of suppressed bone resorption and maintained bone formation. This study showed the differential effects of Ris and Cal on cancellous osteopenia in rats treated with high-dose GC.