Trabecular Bone Architecture Research Articles

Investigation Of Trabecular Bone Strength, Density, And Architecture

Bone density measurements are frequently used to access the quality of a person's bone. However, bone density values do not give complete information on the bone's mechanical characteristics which ultimately determine the likelihood of bone fracture. PURPOSE: To investigate the relationship between bone density, bone strength and trabecular bone architecture. METHODS: Twelve femurs were harvested from six mature rabbits. Each femur's bone mineral density (BMD) was measured using DXA. Femur compression strength was determined using an Instron with a sample of the distal end of one femur per rabbit. Two thin cross-sections of the other femur were prepared for imaging with a scanning electron microscope of three regions (medial, middle and lateral) per sample. BoneJ software was used to compute various measurements of trabecular architecture for each region: ratio of bone volume to trabecular volume, trabecular thickness, and trabecular separation. For each of these three values the median value between the three regions was used for analysis. Pearson correlation coefficients were analyzed (p < 0.05). RESULTS: Strength and stiffness measurements were positively correlated (r = 0.995), while bone ratio and trabecular separation were negatively correlated (r = -0.849). BMD and trabecular thickness were positively correlated (r = 0.792), but BMD and strength were not. CONCLUSIONS: High bone mineral density values do not necessarily indicate good bone quality. Additionally, it was confirmed that trabecular architecture is not uniform within a cross-section or even within a specific region of that cross-section. This further raises the concern for using BMD values to make conclusions about a particular bone's quality when it is clear that trabecular bone is not a homogenous tissue. Supported by NSF grant # NSF-UBM 0634592.

Increased serum IGF-1 levels protect the musculoskeletal system but are associated with elevated oxidative stress markers and increased mortality independent of tissue igf1 gene expression

Although the literature suggests a protective (anabolic) effect of insulin-like growth factor-1 (IGF-1) on the musculoskeletal system during growth and aging, there is evidence that reductions in IGF-1 signaling are advantageous for promoting an increase in life span through reduction in oxidative stress-induced tissue damage. To better understand this paradox, we utilized the hepatocyte-specific IGF-1 transgenic (HIT) mice, which exhibit 3-fold increases in serum IGF-1, with normal IGF-1 expression in other tissues, and mice with an IGF-1 null background that exclusively express IGF-1 in the liver, which thereby deliver IGF-1 by the endocrine route only (KO-HIT mice). We found that in the total absence of tissue igf1 gene expression (KO-HIT), increases in serum IGF-1 levels were associated with increased levels of lipid peroxidation products in serum and increased mortality rate at 18 months of age in both genders. Surprisingly, however, we found that in female mice, tissue IGF-1 plays an important role in preserving trabecular bone architecture as KO-HIT mice show bone loss in the femoral distal metaphysis. Additionally, in male KO-HIT mice, increases in serum IGF-1 levels were insufficient to protect against age-related muscle loss.

Serum IGF-1 Affects Skeletal Acquisition in a Temporal and Compartment-Specific Manner

Insulin-like growth factor-1 (IGF-1) plays a critical role in the development of the growing skeleton by establishing both longitudinal and transverse bone accrual. IGF-1 has also been implicated in the maintenance of bone mass during late adulthood and aging, as decreases in serum IGF-1 levels appear to correlate with decreases in bone mineral density (BMD). Although informative, mouse models to date have been unable to separate the temporal effects of IGF-1 depletion on skeletal development. To address this problem, we performed a skeletal characterization of the inducible LID mouse (iLID), in which serum IGF-1 levels are depleted at selected ages. We found that depletion of serum IGF-1 in male iLID mice prior to adulthood (4 weeks) decreased trabecular bone architecture and significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th) by 16 weeks (adulthood). Likewise, depletion of serum IGF-1 in iLID males at 8 weeks of age, resulted in significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th) by 32 weeks (late adulthood), but had no effect on trabecular bone architecture. In contrast, depletion of serum IGF-1 after peak bone acquisition (at 16 weeks) resulted in enhancement of trabecular bone architecture, but no significant changes in cortical bone properties by 32 weeks as compared to controls. These results indicate that while serum IGF-1 is essential for bone accrual during the postnatal growth phase, depletion of IGF-1 after peak bone acquisition (16 weeks) is compartment-specific and does not have a detrimental effect on cortical bone mass in the older adult mouse.

Numerical procedure for multiscale bone adaptation prediction based on neural networks and finite element simulation

A human femur is composed of cortical and trabecular bone organized in a hierarchical way. In this paper, a multiscale procedure based on finite element simulation and neural network computation was developed to link mesoscopic and macroscopic scales to simulate trabecular bone adaptation process. The finite element calculation is performed at macroscopic level and trained neural networks are employed as numerical devices for substituting the finite element computation needed for the mesoscale prediction. Based on a set of mesoscale simulations of representative volume element of bone, a neural network is trained to approximate the responses. The input data for the artificial neural network are boundary conditions and the applied stress. The output data are some averaged bone properties. A macroscale constitutive model is obtained by homogenization of the mesoscale responses. The proposed approach is able to predict in rapid way some relevant outputs related to bone adaptation process such as trabecular bone density, elastic modulus and accumulation of apparent fatigue damage of 3D trabecular bone architecture at a given bone site. The proposed rapid multiscale method was able to predict final proximal femur trabecular bone adaption similar to the patterns observed in a human proximal femur.

Apparent damage accumulation in cancellous bone using neural networks

In this paper, a neural network model is developed to simulate the accumulation of apparent fatigue damage of 3D trabecular bone architecture at a given bone site during cyclic loading. The method is based on five steps: (i) performing suitable numerical experiments to simulate fatigue accumulation of a 3D micro-CT trabecular bone samples taken from proximal femur for different combinations of loading conditions; (ii) averaging the sample outputs in terms of apparent damage at whole specimen level based on local tissue damage; (iii) preparation of a proper set of corresponding input–output data to train the network to identify apparent damage evolution; (iv) training the neural network based on the results of step (iii); (v) application of the neural network as a tool to estimate rapidly the apparent damage evolution at a given bone site. The proposed NN model can be incorporated into finite element codes to perform fatigue damage simulation at continuum level including some morphological factors and some bone material properties. The proposed neural network based multiscale approach is the first model, to the author’s knowledge, that incorporates both finite element analysis and neural network computation to rapidly simulate multilevel fatigue of bone. This is beneficial to develop enhanced finite element models to investigate the role of damage accumulation on bone damage repair during remodelling.

In Vivo CT Quantification of Trabecular Bone Dynamics in Mice after Sciatic Neurectomy Using Monochromatic Synchrotron Radiation

We demonstrated the capability of in vivo synchrotron radiation CT (SRCT) in analyzing short-term changes in trabecular bone architecture (TBA) and the degree of bone mineralization (DBM) in small animals. Mice underwent unilateral sciatic neurectomy (SN) and sham operation on the contralateral side (SO) at 13 weeks of age. In vivo SRCT scans (11.7-μm cubic voxel) were made of both knees 7 and 17 days (group 1, n = 7) or only 17 days (group 2, n = 6) after surgery. In three mice in group 2, one knee was scanned twice on the same day in different orientations for reproducibility testing. Two scan data sets of the tibial proximal metaphysis acquired at different time points (group 1) or at the same time point (group 2) were registered for detecting differences in volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), connectivity density (Conn.D), and mean DBM (mDBM). The reproducibility test showed small errors of <2.5% in the TBA indexes and <3.0% in mDBM, while mismatched bone regions amounted to >25%. In group 1, Tb.Th increased but Tb.N and Conn.D decreased in both SN and SO; BV/TV and mDBM increased only in SO; accordingly, BV/TV, Tb.Th, and mDBM became lower in SN than in SO. No significant interaction between SN and irradiation was found; the SN effects on TBA and DBM were similar between groups 1 and 2, although synchrotron irradiation led to higher Tb.Th and lower Tb.N in group 1. In conclusion, in vivo SRCT has potential use for detecting short-term bone dynamics of small animals.

Chlorthalidone improves vertebral bone quality in genetic hypercalciuric stone-forming rats

We have bred a strain of rats to maximize urine (u) calcium (Ca) excretion and model hypercalciuric nephrolithiasis. These genetic hypercalciuric stone-forming (GHS) rats excrete more uCa than control Sprague-Dawley rats, uniformly form kidney stones, and similar to patients, demonstrate lower bone mineral density. Clinically, thiazide diuretics reduce uCa and prevent stone formation; however, whether they benefit bone is not clear. We used GHS rats to test the hypothesis that the thiazide diuretic chlorthalidone (CTD) would have a favorable effect on bone density and quality. Twenty GHS rats received a fixed amount of a 1.2% Ca diet, and half also were fed CTD (4 to 5 mg/kg/d). Rats fed CTD had a marked reduction in uCa. The axial and appendicular skeletons were studied. An increase in trabecular mineralization was observed with CTD compared with controls. CTD also improved the architecture of trabecular bone. Using micro-computed tomography (µCT), trabecular bone volume (BV/TV), trabecular thickness, and trabecular number were increased with CTD. A significant increase in trabecular thickness with CTD was confirmed by static histomorphometry. CTD also improved the connectivity of trabecular bone. Significant improvements in vertebral strength and stiffness were measured by vertebral compression. Conversely, a slight loss of bending strength was detected in the femoral diaphysis with CTD. Thus results obtained in hypercalciuric rats suggest that CTD can favorably influence vertebral fracture risk. CTD did not alter formation parameters, suggesting that the improved vertebral bone strength was due to decreased bone resorption and retention of bone structure.

Assessment of Trabecular Bone Architecture and Intrinsic Properties of Cortical bone Tissue in a Mouse Model of Chronic Kidney Disease

Chronic kidney disease (CKD) is often associated with increased fracture risk; however, the CKD-effects on bone microstructure and intrinsic material properties have not been fully elucidated. This study was undertaken to evaluate the time course of trabecular architectural changes and material properties of cortical bone in the tibia of a mouse model of high-turnover CKD. Male mice subjected to 5/6 nephrectomy (Nx, n=8) and those sham-operated (Sham, n=8) were used. Starting at 8 weeks of age (2 weeks after surgery), Nx mice were fed with high phosphate diet. The tibial metaphysis was scanned by in vivo micro-computed tomography (μCT) for trabecular architecture analysis from 10 to 26 weeks of age with 4-week interval. Then, the animal was blood-sampled before sacrifice, and the scanned tibia was harvested. The midlayer of a cortical cross-section was evaluated for mineral-to-matrix ratio, mineral maturity, and collagen maturity by Fourier transform infrared microspectroscopy and for stiffness and hardness by the nanoindentation test. Serum chemicals showed the successful induction of high-turnover CKD in Nx. The age-related regression of trabecular network was observed in both groups but to the higher degree in Nx. In vivo μCT revealed significant interactions between age and CKD in trabecular number, thickness, and separation. On the other hand, the chemical and mechanical properties of cortical bone did not differ significantly between Nx and Sham. Thus, the compromised trabecular architecture will be contributory to bone fragility in high-turnover CKD.

Simulated evolution of the vertebral body based on basic multicellular unit activities

A numerical model based on the theory of bone remodeling is proposed to predict the evolution of trabecular bone architecture within the vertebral body and to investigate the process of degeneration in vertebral bone. In this study, particular attention is paid on the description of microstructure changes during the aging process. To take into account the effect of basic multicellular units (BMUs), a set of computational algorithms has been developed. It is assumed that BMU activation probability depends on the state of damaged bone tissue (damage accumulation, ω), which is evaluated according to previous research concerning bone fatigue damage. Combining these algorithms with the finite-element method (FEM), the microstructure of vertebral bone has been predicted for up to 8 simulated years. Moreover, biomechanical material properties have been monitored to investigate the changes of vertebral bone with age. This study shows that the simulation based on BMU activities has the potential to define and predict the morphological evolution of the vertebral body. It can be concluded that the novel algorithms incorporating the coupled effects of both adaptive remodeling and microdamage remodeling could be utilized to gain greater insight into the mechanism of bone loss in the elderly population.

Increasing duration of type 1 diabetes perturbs the strength–structure relationship and increases brittleness of bone

Type 1 diabetes (T1DM) increases the likelihood of a fracture. Despite serious complications in the healing of fractures among those with diabetes, the underlying causes are not delineated for the effect of diabetes on the fracture resistance of bone. Therefore, in a mouse model of T1DM, we have investigated the possibility that a prolonged state of diabetes perturbs the relationship between bone strength and structure (i.e., affects tissue properties). At 10, 15, and 18weeks following injection of streptozotocin to induce diabetes, diabetic male mice and age-matched controls were examined for measures of skeletal integrity. We assessed 1) the moment of inertia (IMIN) of the cortical bone within diaphysis, trabecular bone architecture of the metaphysis, and mineralization density of the tissue (TMD) for each compartment of the femur by micro-computed tomography and 2) biomechanical properties by three-point bending test (femur) and nanoindentation (tibia). In the metaphysis, a significant decrease in trabecular bone volume fraction and trabecular TMD was apparent after 10weeks of diabetes. For cortical bone, type 1 diabetes was associated with decreased cortical TMD, IMIN, rigidity, and peak moment as well as a lack of normal age-related increases in the biomechanical properties. However, there were only modest differences in material properties between diabetic and normal mice at both whole bone and tissue-levels. As the duration of diabetes increased, bone toughness decreased relative to control. If the sole effect of diabetes on bone strength was due to a reduction in bone size, then IMIN would be the only significant variable explaining the variance in the maximum moment. However, general linear modeling found that the relationship between peak moment and IMIN depended on whether the bone was from a diabetic mouse and the duration of diabetes. Thus, these findings suggest that the elevated fracture risk among diabetics is impacted by complex changes in tissue properties that ultimately reduce the fracture resistance of bone.

Structural Adaptation of Trabecular Bone Revealed by Position Resolved Analysis of Proximal Femora of Different Primates

The anisotropic arrangement of trabeculae in the proximal femur of humans and primates is seen as striking evidence for the functional adaptation of trabecular bone architecture. Quantitative evidence to demonstrate this adaptation for trabecular bone is still scarce, because experimental design of controlled load change is difficult. In this work, we use the natural variation of loading caused by a different main locomotor behavior of primates. Using high-resolution computed tomography and advanced image analysis techniques, we analyze the heterogeneity of the architecture in four proximal femora of four primate species. Although the small sample number does not allow an interspecies comparison, the very differently loaded bones are well suited to search for common structural features as a result of adaptation. A cubic volume of interest of size (5 mm)(3) was moved through the proximal femur and a morphometric analysis including local anisotropy was performed on 209 positions on average. The correlation of bone volume fraction (BV/TV) with trabecular number (Tb.N) and trabecular thickness (Tb.Th) leads to the suggestion of two different mechanisms of trabecular bone adaptation. Higher values of BV/TV in highly loaded regions of the proximal femur are due to a thickening of the trabeculae, whereas Tb.N does not change. In less loaded regions, however, lower values of BV/TV are found, caused by a reduction of the number of the trabeculae, whereas Tb.Th remains constant. This reduction in Tb.N goes along with an increase in the degree of anisotropy, indicating an adaptive selection of trabeculae.

Improvement of Femoral Bone Quality After Low-Magnitude, High-Frequency Mechanical Stimulation in the Ovariectomized Rat as an Osteopenia Model

The treatment and prevention of osteoporosis involve great challenges. Nonpharmacological and supportive therapy procedures, sport, and physical exercises seem to prevent bone loss and improve bone mass. In the present study, we examined the effect of whole-body vertical vibration (WBVV) on femoral intertrochanteric bone quality in the rat osteoporosis model. Sixty female Sprague–Dawley rats, 3-month old, were ovariectomized (OVX) or sham-operated. After 3 months, each group was divided into two subgroups. In one of the subgroups, rats were treated with WBVV at 90 Hz (3.9 g) for 35 days; the second subgroup remained untreated. After killing the animals, biomechanical strength and trabecular bone architecture of the proximal region of femurs were analyzed. New cortical bone appositions and mineral density of femurs were additionally measured. Treatment with WBVV resulted in improved biomechanical properties. Maximal load and stiffness of the intertrochanteric region of femurs after WBVV were significantly enhanced. Maximal load and stiffness in treated OVX animals reached the levels observed in untreated sham rats. WBVV significantly improved all measured histomorphometric parameters in the trabecular area. Treated rats showed significantly improved mineral content in ashed femurs compared to untreated animals. A comparison of widths of fluorescence bands in cortical bone of subtrochanteric cross sections did not show any significant differences between the groups after WBVV. Low-magnitude, high-frequency mechanical stimulation improves bone strength in the proximal femur and may be a possible nonpharmacologic treatment option for postmenopausal osteoporosis.

Methodological considerations for analyzing trabecular architecture: an example from the primate hand.

Micro-computed tomographic analyses of trabecular bone architecture have been used to clarify the link between positional behavior and skeletal anatomy in primates. However, there are methodological decisions associated with quantifying and comparing trabecular anatomy across taxa that vary greatly in body size and morphology that can affect characterizations of trabecular architecture, such as choice of the volume of interest (VOI) size and location. The potential effects of these decisions may be amplified in small, irregular-shaped bones of the hands and feet that have more complex external morphology and more heterogeneous trabecular structure compared to, for example, the spherical epiphysis of the femoral head. In this study we investigate the effects of changes in VOI size and location on standard trabecular parameters in two bones of the hand, the capitate and third metacarpal, in a diverse sample of nonhuman primates that vary greatly in morphology, body mass and positional behavior. Results demonstrate that changes in VOI location and, to a lesser extent, changes in VOI size had a dramatic affect on many trabecular parameters, especially trabecular connectivity and structure (rods vs. plates), degree of anisotropy, and the primary orientation of the trabeculae. Although previous research has shown that some trabecular parameters are susceptible to slight variations in methodology (e.g. VOI location, scan resolution), this study provides a quantification of these effects in hand bones of a diverse sample of primates. An a priori understanding of the inherent biases created by the choice of VOI size and particularly location is critical to robust trabecular analysis and functional interpretation, especially in small bones with complex arthroses.

Disruption of bone development and homeostasis by trisomy in Ts65Dn Down syndrome mice

Down syndrome (DS) is a genetic disorder resulting from trisomy 21 that causes cognitive impairment, low muscle tone and craniofacial alterations. Morphometric studies of the craniofacial and appendicular skeleton in individuals with DS suggest that bone development and homeostasis are affected by trisomy. The Ts65Dn mouse model has three copies of approximately half the genes found on human chromosome 21 and exhibits craniofacial skeletal and size differences similar to those observed in humans with DS. We hypothesized that Ts65Dn and euploid mice have distinct differences in bone development and homeostasis influencing both the craniofacial and appendicular skeletal phenotypes. Quantitative assessment of structural and mechanical properties of the femur in Ts65Dn and control mice at 6 and 16 weeks of age revealed significant deficiencies in trabecular and cortical bone architecture, bone mineral density, bone formation, and bone strength in trisomic bone. Furthermore, bone mineral density and dynamic dentin formation rate of the skull and incisor, respectively, were also reduced in Ts65Dn mice, demonstrating that trisomy significantly affects both the craniofacial and appendicular skeleton.

Comparative in vivo forefoot kinematics of Homo sapiens and Pan paniscus

The human metatarsophalangeal joints play a key role in weight transmission and propulsion during bipedal gait, but at present, the identification of when a habitual, human-like metatarsi-fulcrimating mechanism first appeared in the fossil record is debated. Part of this debate can be attributed to the absence of certain detailed quantitative data distinguishing human and great ape forefoot form and function. The aim of this study is to quantitatively test previous observations that human metatarsophalangeal joints exhibit greater amounts of dorsal excursion (i.e., dorsiflexion) than those of Pan at the terminal stance phase of terrestrial locomotion. Video recordings were made in order to measure sagittal excursions of the medial metatarsophalangeal joints in habitually shod/unshod adult humans and adult bonobos ( Pan paniscus). Results indicate that the human first and second metatarsophalangeal joints usually dorsiflex more than those of bonobos. When timing of maximum excursion of the first metatarsophalangeal joint is coupled with existing plantar pressure data, the unique role of the human forefoot as a key site of leverage and weight transmission is highlighted. These results support hypotheses that significant joint functional differences between great apes and humans during gait underlie taxonomic distinctions in trabecular bone architecture of the forefoot.

Virtual repair of fossil CT scan data

X-ray micro-tomography (XMT) and 3D image-based modelling software has unlocked the ability to digitally repair distorted or broken fossil specimens, thus permitting interpretation of previously unusable finds in finite element analyses (FEA). A fossilized terminal ungual phalanx from the manus of the dromaeosaur Velociraptor mongoliensis (Manchester Museum, University of Manchester, specimen LL.12392) was scanned at the Henry Moseley X-ray Imaging Facility. Inspection of radiographs revealed the Velociraptor manual ungual was broken in several places, previously going unnoticed due to cement repair of the fossil. After conducting a high resolution scan of the ungual the increased sensitivity of the apparatus enabled separation of areas of differing density, in this case the fossilized bone and cement. Image-based modelling software produced by Simpleware (Simpleware Ltd, Rennes Drive, Exeter, EX4 4RN, UK.) allowed slice-by-slice repair in three planes, resulting in a complete, fully stitched 3D digital model of the ungual, whilst maintaining internal cavities and the micron resolution reconstruction of trabecular bone architecture. This software also has the capability to digitally re-inflate specimens that have been compressed during fossilization, restoring skeletons to their original shape and dimension. 3D dissections on geometrically precise reconstructions allow the interpretation of previously unusable specimens and reinterpretation of already described fossils. Further, use of Simpleware software to convert repaired fossils into microstructurally-faithful finite element meshes enable the biomechanical testing of these repaired structures. Testing of fossil structure and function is already underway at the University of Manchester and is adding to our knowledge of the mechanical behaviour of extinct animal biomaterials.

Caloric restriction leads to high marrow adiposity and low bone mass in growing mice

The effects of caloric restriction (CR) on the skeleton are well studied in adult rodents and include lower cortical bone mass but higher trabecular bone volume. Much less is known about how CR affects bone mass in young, rapidly growing animals. This is an important problem because low caloric intake during skeletal acquisition in humans, as in anorexia nervosa, is associated with low bone mass, increased fracture risk, and osteoporosis in adulthood. To explore this question, we tested the effect of caloric restriction on bone mass and microarchitecture during rapid skeletal growth in young mice. At 3 weeks of age, we weaned male C57Bl/6J mice onto 30% caloric restriction (10% kcal/fat) or normal diet (10% kcal/fat). Outcomes at 6 (n = 4/group) and 12 weeks of age (n = 8/group) included body mass, femur length, serum leptin and insulin-like growth factor 1 (IGF-1) values, whole-body bone mineral density (WBBMD, g/cm(2)), cortical and trabecular bone architecture at the midshaft and distal femur, bone formation and cellularity, and marrow fat measurement. Compared with the normal diet, CR mice had 52% and 88% lower serum leptin and 33% and 39% lower serum IGF-1 at 6 and 12 weeks of age (p < .05 for all). CR mice were smaller, with lower bone mineral density, trabecular, and cortical bone properties. Bone-formation indices were lower, whereas bone-resorption indices were higher (p < .01 for all) in CR versus normal diet mice. Despite having lower percent of body fat, bone marrow adiposity was elevated dramatically in CR versus normal diet mice (p < .05). Thus we conclude that caloric restriction in young, growing mice is associated with impaired skeletal acquisition, low leptin and IGF-1 levels, and high marrow adiposity. These results support the hypothesis that caloric restriction during rapid skeletal growth is deleterious to cortical and trabecular bone mass and architecture, in contrast to potential skeletal benefits of CR in aging animals.

Comparative forefoot trabecular bone architecture in extant hominids

The appearance of a forefoot push-off mechanism in the hominin lineage has been difficult to identify, partially because researchers disagree over the use of the external skeletal morphology to differentiate metatarsophalangeal joint functional differences in extant great apes and humans. In this study, we approach the problem by quantifying properties of internal bone architecture that may reflect different loading patterns in metatarsophalangeal joints in humans and great apes. High-resolution x-ray computed tomography data were collected for first and second metatarsal heads of Homo sapiens (n = 26), Pan paniscus (n = 17), Pan troglodytes (n = 19), Gorilla gorilla (n = 16), and Pongo pygmaeus (n = 20). Trabecular bone fabric structure was analyzed in three regions of each metatarsal head. While bone volume fraction did not significantly differentiate human and great ape trabecular bone structure, human metatarsal heads generally show significantly more anisotropic trabecular bone architectures, especially in the dorsal regions compared to the corresponding areas of the great ape metatarsal heads. The differences in anisotropy between humans and great apes support the hypothesis that trabecular architecture in the dorsal regions of the human metatarsals are indicative of a forefoot habitually used for propulsion during gait. This study provides a potential route for predicting forefoot function and gait in fossil hominins from metatarsal head trabecular bone architecture.

Diffraction Enhanced X-ray Imaging of the Distal Radius: A Novel Approach for Visualization of Trabecular Bone Architecture

In Canada, osteoporotic fractures result in direct health care costs that exceed CAD$1.3 billion annually [1]. Fractures are related to compromised bone strength, a parameter that reflects both density (quantity) and architecture (quality) [2]. The current clinical standard for bone assessment, dual energy x-ray absorptiometry, provides only a 2-dimensional areal measurement of density and no architectural information [3]; therefore, the development of improved methods for visualizing and quantifying of bone architecture remains an important goal with respect to improving detection and treatment of osteoporosis. Advances are currently being sought in the development of new technologies [3], such as high-resolution peripheral quantitative tomography [4], and through texture-based analysis of trabecular structure from radiographs [5]. In this pictorial essay, we explore the use of x-rayebased diffraction enhanced imaging (DEI) by using synchrotron radiation [6] as a novel means of visualizing the internal architecture of the human distal radius, a clinically significant fracture site. Imaging for this study was conducted at the Canadian Light Source (CLS) synchrotron during commissioning of the BioMedical Imaging and Therapy (BMIT) bending magnet beam line [7]. As such, our goal here is 2-fold: (1) establishment of proof-of-principle

Anabolic and Antiresorptive Drugs Improve Trabecular Microarchitecture and Reduce Fracture Risk following Radiation Therapy

Many patients with symptomatic bone metastases receive radiation therapy, even though radiation is known to have potential adverse effects on bone. We hypothesized that the concurrent use of a bisphosphonate drug (zoledronic acid, ZA) or a combination of ZA plus an anabolic agent (parathyroid hormone, PTH) would lead to improvements in the microarchitecture and mechanical properties of irradiated bone. Human breast cancer cells were injected into the distal femur of 56 female nude mice, which were then divided into four groups: no treatment (0 Gy), radiation administered 4 weeks postinjection (20 Gy), radiation plus ZA (12.5 microg/kg weekly from weeks 4 to 12) (20 Gy + ZA), and radiation followed by ZA (25 microg/kg weekly from weeks 4 to 8) and PTH(1-34) (100 microg microg/kg daily from weeks 8 to 12) (20 Gy + ZA + PTH). Left limbs served as normal control bones. Bone loss over the 12-week study was tracked with serial radiography and bone densitometry. At the end of the study, micro-computed tomography and mechanical testing were used to quantify bone microarchitecture and bone strength. Radiation alone failed to prevent tumor-induced decreases in bone mineral density (BMD), trabecular bone volume, and bone strength. Treatment with 20 Gy + ZA or 20 Gy + ZA + PTH as adjuncts to radiation was effective at preserving trabecular bone architecture and bone strength at normal levels. ZA reduced the risk of mechanical fragility following irradiation of a lytic bone lesion. Supplemental use of PTH did not result in further increases in bone strength but was associated with significant increases in BMD and bone mass, suggesting that it may be beneficial in enhancing bone architecture following radiation therapy.