Trabecular bone volume fraction in Holocene and Late Pleistocene humans.

Research suggests that recent modern humans have gracile skeletons in having low trabecular bone volume fraction (BV/TV) and that gracilization of the skeleton occurred in the last 10,000 years. This has been attributed to a reduction in physical activity in the Holocene. However, there has been no thorough sampling of BV/TV in Pleistocene humans due to limited access to high resolution images of fossil specimens. Therefore, our study investigates the gracilization of BV/TV in Late Pleistocene humans and recent (Holocene) modern humans to improve our understanding of the emergence of gracility. We used microcomputed tomography to measure BV/TV in the femora, humeri and metacarpals of a sample of Late Pleistocene humans from Dolní Vestonice (Czech Republic, ∼26 ka, n = 6) and Ohalo II (Israel, ∼19 ka, n = 1), and a sample of recent humans including farming groups (n = 39) and hunter-gatherers (n = 6). We predicted that 1) Late Pleistocene humans would exhibit greater femoral and humeral head BV/TV compared with recent humans and 2) among recent humans, metacarpal head BV/TV would be greater in hunter-gatherers compared with farmers. Late Pleistocene humans had higher BV/TV compared with recent humans in both the femur and humerus, supporting our first prediction, and consistent with previous findings that Late Pleistocene humans are robust as compared to recent humans. However, among recent humans, there was no significant difference in BV/TV in the metacarpals between the two subsistence groups. The results highlight the similarity in BV/TV in the hand of two human groups from different geographic locales and subsistence patterns and raise questions about assumptions of activity levels in archaeological populations and their relationships to trabecular BV/TV.

Backscatter measurement of cancellous bone using the ultrasound transit time spectroscopy.

Recently, ultrasound transit time spectroscopy (UTTS) was proposed as a promising method for bone quantitative ultrasound measurement. Studies have showed that UTTS could estimate the bone volume fraction and other trabecular bone structure in ultrasonic through-transmission measurements. The goal of this study was to explore the feasibility of UTTS to be adapted in ultrasonic backscatter measurement and further evaluate the performance of backscattered ultrasound transit time spectrum (BS-UTTS) in the measurement of cancellous bone density and structure. First, taking ultrasonic attenuation into account, the concept of BS-UTTS was verified on ultrasonic backscatter signals simulated from a set of scatterers with different positions and intensities. Then, in vitro backscatter measurements were performed on 26 bovine cancellous bone specimens. After a logarithmic compression of the BS-UTTS, a linear fitting of the log-compressed BS-UTTS versus ultrasonic propagated distance was performed and the slope and intercept of the fitted line for BS-UTTS were determined. The associations between BS-UTTS parameters and cancellous bone features were analyzed using simple linear regression. The results showed that the BS-UTTS could make an accurate deconvolution of the backscatter signal and predict the position and intensity of the simulated scatterers eliminating phase interference, even the simulated backscatter signal was with a relatively low signal-to-noise ratio. With varied positions and intensities of the scatterers, the slope of the fitted line for the log-compressed BS-UTTS versus ultrasonic propagated distance (i.e., slope of BS-UTTS for short) yield a high agreement (r2 = 99.84%-99.96%) with ultrasonic attenuation in simulated backscatter signal. Compared with the high-density cancellous bone, the low-density specimen showed more abundant backscatter impulse response in the BS-UTTS. The slope of BS-UTTS yield a significant correlation with bone mineral density (r = 0.87; p < 0.001), BV/TV (r = 0.87; p < 0.001), and cancellous bone microstructures (r up to 0.87; p < 0.05). The intercept of BS-UTTS was also significantly correlated with bone densities (r = -0.87; p < 0.001) and trabecular structures (|r|=0.43-0.80; p < 0.05). However, the slope of the BS-UTTS underestimated attenuation when measurements were performed experimentally. In addition, a significant non-linear relationship was observed between the measured attenuation and the attenuation estimated by the slope of the BS-UTTS. This study demonstrated that the UTTS method could be adapted to ultrasonic backscatter measurement of cancellous bone. The derived slope and intercept of BS-UTTS could be used in the measurement of bone density and microstructure. The backscattered ultrasound transit time spectroscopy might have potential in the diagnosis of osteoporosis in the clinic.

Quantitative analysis of trabecular bone tissue cryosections via a fully automated neural network-based approach.

Cryosectioning is known as a common and well-established histological method, due to its easy accessibility, speed, and cost efficiency. However, the creation of bone cryosections is especially difficult. In this study, a cryosectioning protocol for trabecular bone that offers a relatively cheap and undemanding alternative to paraffin or resin embedded sectioning was developed. Sections are stainable with common histological dying methods while maintaining sufficient quality to answer a variety of scientific questions. Furthermore, this study introduces an automated protocol for analysing such sections, enabling users to rapidly access a wide range of different stainings. Therefore, an automated 'QuPath' neural network-based image analysis protocol for histochemical analysis of trabecular bone samples was established, and compared to other automated approaches as well as manual analysis regarding scattering, quality, and reliability. This highly automated protocol can handle enormous amounts of image data with no significant differences in its results when compared with a manual method. Even though this method was applied specifically for bone tissue, it works for a wide variety of different tissues and scientific questions.

Current Management of Acute and Posttraumatic Critical Bone Defects.

SUMMARY: Limb reconstruction in patients with critical-sized bone defects remains a challenge due to the availability of various technically demanding treatment options and a lack of standardized decision algorithms. Although no consensus exists, it is apparent from the literature that the combination of patient, surgeon, and institutional collaborations is effective in providing the most efficient care pathway for these patients. Success relies on choosing a particular surgical approach that manages infection, soft tissue defects, stability, and alignment. Recent systematic reviews demonstrate high success rates with the following management options: Ilizarov bone transport, Masquelet (induced membrane) technique, cancellous bone grafting, and vascularized bone grafts.

Theoretical and experimental study of attenuation in cancellous bone.

Significance: Photoacoustic (PA) technology shows great potential for bone assessment. However, the PA signals in cancellous bone are complex due to its complex composition and porous structure, making such signals challenging to apply directly in bone analysis. Aim: We introduce a photoacoustic differential attenuation spectrum (PA-DAS) method to separate the contribution of the acoustic propagation path to the PA signal from that of the source, and theoretically and experimentally investigate the propagation attenuation characteristics of cancellous bone. Approach: We modified Biot's theory by accounting for the high frequency and viscosity. In parallel with the rabbit osteoporosis model, we build an experimental PA-DAS system featuring an eccentric excitation differential detection mechanism. Moreover, we extract a PA-DAS quantization parameter-slope-to quantify the attenuation of high- and low-frequency components. Results: The results show that the porosity of cancellous bone can be evaluated by fast longitude wave attenuation at different frequencies and the PA-DAS slope of the osteoporotic group is significantly lower compared with the normal group (**p<0.01). Conclusions: Findings demonstrate that PA-DAS effectively differentiates osteoporotic bone from healthy bone, facilitating quantitative assessment of bone mineral density, and osteoporosis diagnosis.

Effect of density grading on the mechanical behaviour of advanced functionally graded lattice structures.

Lattice structures have found significant applications in the biomedical field due to their interesting combination of mechanical and biological properties. Among these, functionally graded structures sparked interest because of their potential of varying their mechanical properties throughout the volume, allowing the design of biomedical devices able to match the characteristics of a graded structure like human bone. The aim of this works is the study of the effect of the density grading on the mechanical response and the failure mechanisms of a novel functionally graded lattice structure, namely Triply Arranged Octagonal Rings (TAOR). The mechanical behaviour was compared with the same lattice structures having constant density ratio. Electron Beam Melting technology was used to manufacture titanium alloy specimens with global relative densities from 10% to 30%. Functionally graded structures were obtained by increasing the relative density along the specimen, by individually designing the lattice's layers. Scanning electron and a digital microscopy were used to evaluate the dimensional mismatch between actual and designed structures. Compressive tests were carried out to obtain the mechanical properties and to evaluate the collapse modes of the structures in relation to their average relative density and lattice grading. Open-source Digital Image Correlation algorithm was applied to evaluate the deformation behaviour of the structures and to calculate their elastic moduli. The results showed that uniform density structures provide higher mechanical properties than functionally graded ones. The Digital Image Correlation results showed the possibility of effectively designing the different layers of functionally graded structures selecting desired local mechanical properties to mimic the different characteristics of cortical and cancellous bone.

Modelling the Effects of Growth and Remodelling on the Density and Structure of Cancellous Bone.

A two-stage model is proposed for investigating remodelling characteristics in bone over time and distance to the growth plate. The first stage comprises a partial differential equation (PDE) for bone density as a function of time and distance from the growth plate. This stage clarifies the contributions to changes in bone density due to remodelling and growth processes and tracks the rate at which new bone emanates from the growth plate. The second stage consists of simulating the remodelling process to determine remodelling characteristics. Implementing the second stage requires the rate at which bone moves away from the growth plate computed during the first stage. The second stage is also needed to confirm that remodelling characteristics predicted by the first stage may be explained by a realistic model for remodelling and to compute activation frequency. The model is demonstrated on microCT scans of tibia of juvenile female rats in three experimental groups: sham-operated control, oestrogen deprived, and oestrogen deprived followed by treatment. Model predictions for changes in bone density and remodelling characteristics agree with the literature. In addition, the model provides new insight into the role of treatment on the density of new bone emanating from the growth plate and provides quantitative descriptions of changes in remodelling characteristics beyond what has been possible to ascertain by experimentation alone.

The Effect of Structural Characteristics of Deproteinized Spongy Bone on Activity of Adipose Tissue Mesenchymal Stromal Cells.

We studied the effect of structural properties of deproteinized spongy bone (DSB) on functional activity of adipose tissue mesenchymal stromal cells of (MSC) for the potential use of these materials as components of a combined tissue-engineered construct. The porosity of the structure of DSB samples and the pore size promote MSC adhesion, migration, and proliferation on their surface and in the depth, revealing the architectonics of this bone matrix. The depth of cell penetration into the samples (from 273 to 702 µm) and an increase in the total number of cells (from 302 on day 1 to 1744 on day 7) demonstrated MSC adhesion, migration, and proliferation. The viability of cultured MSC was preserved for up to 7 days. The obtained results prove the possibility of using allogeneic DSB from femoral heads as a bone matrix in tissue-engineered constructs in combination with MSC. Such constructs can be used to efficiently restore the structural and functional integrity of the bone tissue in abnormal processes of various etiopathogenesis associated with the formation of bone defects or bone tissue deficiency.

Functional analysis of the human perivascular subarachnoid space.

The human subarachnoid space harbors the cerebrospinal fluid, which flows within a landscape of blood vessels and trabeculae. Functional implications of subarachnoid space anatomy remain far less understood. This study of 75 patients utilizes a cerebrospinal fluid tracer (gadobutrol) and consecutive magnetic resonance imaging to investigate features of early (i.e. within 2-3 h after injection) tracer propagation within the subarachnoid space. There is a time-dependent perivascular pattern of enrichment antegrade along the major cerebral artery trunks; the anterior-, middle-, and posterior cerebral arteries. The correlation between time of first enrichment around arteries and early enrichment in nearby cerebral cortex is significant. These observations suggest the existence of a compartmentalized subarachnoid space, where perivascular ensheathment of arteries facilitates antegrade tracer passage towards brain tissue. Periarterial transport is impaired in subjects with reduced intracranial pressure-volume reserve capacity and in idiopathic normal pressure hydrocephalus patients who also show increased perivascular space size.

Strain rate of stretch affects crossbridge detachment during relaxation of intact cardiac trabeculae.

Mechanical Control of Relaxation refers to the dependence of myocardial relaxation on the strain rate just prior to relaxation, but the mechanisms of enhanced relaxation are not well characterized. This study aimed to characterize how crossbridge kinetics varied with strain rate and time-to-stretch as the myocardium relaxed in early diastole. Ramp-stretches of varying rates (amplitude = 1% muscle length) were applied to intact rat cardiac trabeculae following a load-clamp at 50% of the maximal developed twitch force, which provides a first-order estimate of ejection and coupling to an afterload. The resultant stress-response was calculated as the difference between the time-dependent stress profile between load-clamped twitches with and without a ramp-stretch. The stress-response exhibited features of the step-stretch response of activated, permeabilized myocardium, such as distortion-dependent peak stress, rapid force decay related to crossbridge detachment, and stress recovery related to crossbridge recruitment. The peak stress was strain rate dependent, but the minimum stress and the time-to-minimum stress values were not. The initial rapid change in the stress-response indicates enhanced crossbridge detachment at higher strain rates during relaxation in intact cardiac trabeculae. Physiologic considerations, such as time-varying calcium, are discussed as potential limitations to fitting these data with traditional distortion-recruitment models of crossbridge activity.

LumVertCancNet: A novel 3D lumbar vertebral body cancellous bone location and segmentation method based on hybrid Swin-transformer.

Lumbar vertebral body cancellous bone location and segmentation is crucial in an automated lumbar spine processing pipeline. Accurate and reliable analysis of lumbar spine image is expected to advantage practical medical diagnosis and population-based analysis of bone strength. However, the design of automated algorithms for lumbar spine processing is demanding due to significant anatomical variations and scarcity of publicly available data. In recent years, convolutional neural network (CNN) and vision transformers (Vits) have been the de facto standard in medical image segmentation. Although adept at capturing global features, the inherent bias of locality and weight sharing of CNN constrains its capacity to model long-range dependency. In contrast, Vits excel at long-range dependency modeling, but they may not generalize well with limited datasets due to the lack of inductive biases inherent to CNN. In this paper, we propose a deep learning-based two-stage coarse-to-fine solution to address the problem of automatic location and segmentation of lumbar vertebral body cancellous bone. Specifically, in the first stage, a Swin-transformer based model is applied to predict the heatmap of lumbar vertebral body centroids. Considering the characteristic anatomical structure of lumbar spine, we propose a novel loss function called LumAnatomy loss, which enforces the order and bend of the predicted vertebral body centroids. To inherit the excellence of CNN and Vits while preventing their respective limitations, in the second stage, we propose an encoder-decoder network to segment the identified lumbar vertebral body cancellous bone, which consists of two parallel encoders, i.e., a Swin-transformer encoder and a CNN encoder. To enhance the combination of CNNs and Vits, we propose a novel multi-scale attention feature fusion module (MSA-FFM), which address issues that arise when fusing features given at different encoders. To tackle the issue of lack of data, we raise the first large-scale lumbar vertebral body cancellous bone segmentation dataset called LumVBCanSeg containing a total of 185 CT scans annotated at voxel level by 3 physicians. Extensive experimental results on the LumVBCanSeg dataset demonstrate the proposed algorithm outperform other state-of-the-art medical image segmentation methods. The data is publicly available at: https://zenodo.org/record/8181250. The implementation of the proposed method is available at: https://github.com/sia405yd/LumVertCancNet.

Gaussian random field-based characterization and reconstruction of cancellous bone microstructure considering the constraint of correlation structure.

The macro scale physical properties of cancellous bone materials are governed by the microstructural features, which is of great significance for the multi-scale research of cancellous bone and the inverse design of bone-mimicking materials. Therefore, it is essential to characterize the natural cancellous bone samples, and reconstruct the microstructures with the biomimetic osteointegration and mechanical properties. In this research, a novel approach for the characterization and reconstruction of cancellous bone was proposed, based on the medical image analysis and anisotropic three-dimensional Gaussian random field (GRF). The geometric similarity, i.e. the interface curvature distribution (ISD), was meticulously studied, which is important to the osteointegration ability. And the mechanical properties were validated by the stress-strain curves under the large compressive strain simulated by the smoothed particle hydrodynamic (SPH) method. In addition, the effects of the generation parameters of GRF-based biomimetic microstructures on the apparent properties were analyzed. The ISD results demonstrated that both GRF and micro-CT groups had the similar columnar morphological properties, while the latter had more hyperbolic features. And it was found that the GRF-based biomimetic microstructures and the natural bone samples based on micro-CT (MCT) had the similar failure mode. The concordance correlation coefficient between MCT and GRF pairs was 0.8685, with a Pearson ρ value of 0.8804, and significance level p<0.0001. The Bland-Altman LoA was 0.1647 MPa with 95 % (1.96SD) lower and upper bound value between -0.2892 and 0.6185 MPa. The two groups had almost the same elastic modulus with the mean absolute percentage error (MAPE) of 7.84 %. While the yield stress and total conversion energy of the GRF-based samples were lower than those of the natural bone samples, and the MAPE were 16.99 % and 16.27 %, respectively. Although it meant the lower structural efficiency, the huge design space of this approach and advanced 3D printing technology can provide great potential for the design of orthopedic implants.

Open the pores - Polydimethylsiloxane influences the porous structure of cancellous bone surrogates for biomechanical testing of osteosyntheses.

Synthetic materials used for valid and reliable implant testing and design should reflect the mechanical and morphometric properties of human bone. Such bone models are already available on the market, but they do not reflect the population variability of human bone, nor are they open-celled porous as human bone is. Biomechanical studies aimed at cementing the fracture or an implant cannot be conducted with them. The aim of this study was to investigate the influence of a cell stabilizer on polyurethane-based cancellous synthetic bone in terms of morphology, compressive mechanics, and opening of the cancellous bone structure for bone cement application. Mechanical properties of cylindrical specimens of the bone surrogates were determined by static compression tests to failure. Furthermore, a morphometric analysis was performed using microcomputed tomography. To prove the open-cell nature of the bone surrogates, an attempt was made to apply bone cement. Effects on the mechanical properties of the polyurethane-based bone surrogates were observed by the addition of polydimethylsiloxane. All mechanical parameters like Young's modulus, ultimate stress and yield stress increased statistically significantly with increasing amounts of cell stabilizer (all p > 0.001), except for yield stress. The analysis of morphometric parameters showed a decrease in trabecular thickness, spacing and connectivity density, which was accompanied by an increase in trabecular number and an increase in pore size. The open-cell nature was proven by the application and distribution of bone cement in specimens with stabilizer, which was visualized by X-ray. In conclusion, the results show that by adding a cell stabilizer, polyurethane-based cancellous bone substrates can be produced that have an open-cell structure similar to human bone. This makes these bone surrogates suitable for biomechanical testing of osteosyntheses and for osteosynthesis cementation issues.

Bone Density and Trabecular Bone Score Decline Rapidly in the First Year After Bone Marrow Transplantation with a Marked Increase in 10-Year Fracture Risk.

As outcomes from allogeneic bone marrow transplantation (BMT) have improved, prevention of long-term complications, such as fragility fractures, has gained importance. We aimed to assess areal bone mineral density (aBMD) and trabecular bone score (TBS) changes post BMT, and determine their relationship with fracture prevalence. Patients who attended the Royal Melbourne Hospital (RMH) BMT clinic between 2005-2021 were included. Patient characteristics and dual-energy X-ray absorptiometry (DXA) values were collected from the electronic medical record and a survey. TBS iNsight™ was used to calculate TBS for DXA scans performed from 2019 onwards. 337 patients with sequential DXAs were eligible for inclusion. Patients were primarily male (60%) and mean age ± SD was 45.7 ± 13.4 years. The annualised decline in aBMD was greater at the femoral neck (0.066g/cm2 (0.0038-0.17)) and total hip (0.094g/cm2 (0.013-0.19)), compared to the lumbar spine (0.049g/cm2 (- 0.0032-0.16)), p < 0.0001. TBS declined independently of aBMD T-scores at all sites. Eighteen patients (5.3%) sustained 19 fractures over 3884 person-years of follow-up post-transplant (median follow-up 11 years (8.2-15)). This 5.3% fracture prevalence over the median 11-year follow-up period is higher than what would be predicted with FRAX® estimates. Twenty-two patients (6.5%) received antiresorptive therapy, and 9 of 18 (50%) who fractured received or were on antiresorptive therapy. In BMT patients, aBMD and TBS decline rapidly and independently in the first year post BMT. However, FRAX® fracture probability estimates incorporating these values significantly underestimate fracture rates, and antiresorptive treatment rates remain relatively low.

Mechanical loading of ex vivo bovine trabecular bone in 3D printed bioreactor chambers.

Previous ex vivo bone culture methods have successfully implemented polycarbonate (PC) bioreactors to investigate bone adaptation to mechanical load; however, they are difficult to fabricate and have been limited to a 5 mm maximum specimen height. The objective of this study was to validate a custom-made 3D printed MED610TM bioreactor system that addresses the limitations of the PC bioreactor and assess its efficacy in ex vivo bone culture. Twenty-three viable trabecular bone cores (10 mm height by 10 mm diameter) from an 18-month-old bovine sternum were cultured in MED610TM bioreactors with culture medium at 37 °C and 5% CO2 for 21-days. Bone cores were ranked based on their day 0 apparent elastic modulus (Eapp) and evenly separated into a "Load" group (n = 12) and a control group (n = 11). The Load group was loaded five times per week with a sinusoidal strain waveform between -1000 and -5000 µÎµ for 120 cycles at 2 Hz. Eapp was assessed on day 0, 8, and 21 using quasi-static tests with a -4000 µÎµ applied strain. Over 21-days, the Eapp of Load group samples tended to increase by more than double the control group (53.4% versus 20.9%) and no visual culture contamination was observed. This study demonstrated that bone organ culture in 3D printed MED610TM bioreactors replicated Eapp trends found in previous studies with PC bioreactors. However, further studies are warranted with a larger sample size to increase statistical power and histology to assess cell viability and bone mineral apposition rate.

Controlled mechanical loading affects the osteocyte transcriptome in porcine trabecular bone in situ.

INTRODUCTION: Osteocytes modulate bone adaptation in response to mechanical stimuli imparted by the deforming bone tissue in which they are encased by communicating with osteoclasts and osteoblasts as well as other osteocytes in the lacuna-canalicular network through secreted cytokines and chemokines. Understanding the transcriptional response of osteocytes to mechanical stimulation in situ could identify new targets to inhibit bone loss or enhance bone formation in the presence of diseases like osteoporosis or metastatic cancer. We compared the mechanically regulated transcriptional response of osteocytes in trabecular bone following one or three days of controlled mechanical loading. METHODS: Porcine trabecular bone explants were cultured in a bioreactor for 48 h and subsequently loaded twice a day for one day or 3 days. RNA was isolated and sequenced, and the Tuxedo suite was used to identify differentially expressed genes and pathway analysis was conducted using Ingenuity Pathway Analysis (IPA). RESULTS: There were about 4000 differentially expressed genes following in situ culture relative to fresh bone. One hundred six genes were differentially expressed between the loaded and non-loaded groups following one day of loading compared to 913 genes after 3 d of loading. Only 45 of these were coincident between the two time points, indicating an evolving transcriptome. Clustering and principal component analysis indicated differences between the loaded and non-loaded groups after 3 d of loading. DISCUSSION: With sustained loading, there was a nine-fold increase in the number of differentially expressed genes, suggesting that osteocytes respond to loading through sequential activation of downstream genes in the same pathways. The differentially expressed genes were related to osteoarthritis, osteocyte, and chondrocyte signaling pathways. We noted that NFkB and TNF signaling are affected by early loading and this may drive downstream effects on the mechanobiological response. Moreover, these genes may regulate catabolic effects of mechanical disuse through their actions on pre-osteoclasts in the bone marrow niche.

Quantification of long-term nonlinear stress relaxation of bovine trabecular bone.

The reliability of computational models in orthopedic biomechanics depends often on the accuracy of the bone material properties. It is widely recognized that the mechanical response of trabecular bone is time-dependent, yet it is often ignored for the sake of simplicity. Previous investigations into the viscoelastic properties of trabecular bone have not explored the relationship between nonlinear stress relaxation and bone mineral density. The inclusion of this behavior could enhance the accuracy of simulations of orthopedic interventions, such as of primary fixation of implants. Although methods to quantify the viscoelastic behavior are known, the time period during which the viscoelastic properties should be investigated to obtain reliable predictions is currently unclear. Therefore, this study aimed to: 1) Investigate the duration of stress relaxation in bovine trabecular bone; 2) construct a material model that describes the nonlinear viscoelastic behavior of uniaxial stress relaxation experiments on trabecular bone; and 3) implement bone density into this model. Uniaxial compressive stress relaxation experiments were performed with cylindrical bovine femoral trabecular bone samples (n = 16) with constant strain held for 24 h. Additionally, multiple stress relaxation experiments with four ascending strain levels with a holding time of 30 min, based on the results of the 24-h experiment, were executed on 18 bovine bone cores. The bone specimens used in this study had a mean diameter of 12.80 mm and a mean height of 28.70 mm. A Schapery and a Superposition model were used to capture the nonlinear stress relaxation behavior in terms of applied strain level and bone mineral density. While most stress relaxation happened in the first 10 min (up to 53 %) after initial compression, the stress relaxation continued even after 24 h. Up to 69 % of stress relaxation was observed at 24 h. Extrapolating the results of 30 min of experimental data to 24 h provided a good fit for accuracy with much improved experimental efficiency. The Schapery and Superposition model were both capable of fitting the repeated stress relaxation in a sample-by-sample approach. However, since bone mineral density did not influence the time-dependent behavior, only the Superposition model could be used for a group-based model fit. Although the sample-by-sample approach was more accurate for an individual specimen, the group based approach is considered a useful model for general application.

Aromatase deficiency in transplanted bone marrow cells improves vertebral trabecular bone quantity, connectivity, and mineralization and decreases cortical porosity in murine bone marrow transplant recipients.

Estradiol is an important regulator of bone accumulation and maintenance. Circulating estrogens are primarily produced by the gonads. Aromatase, the enzyme responsible for the conversion of androgens to estrogen, is expressed by bone marrow cells (BMCs) of both hematopoietic and nonhematopoietic origin. While the significance of gonad-derived estradiol to bone health has been investigated, there is limited understanding regarding the relative contribution of BMC derived estrogens to bone metabolism. To elucidate the role of BMC derived estrogens in male bone, irradiated wild-type C57BL/6J mice received bone marrow cells transplanted from either WT (WT(WT)) or aromatase-deficient (WT(ArKO)) mice. MicroCT was acquired on lumbar vertebra to assess bone quantity and quality. WT(ArKO) animals had greater trabecular bone volume (BV/TV p = 0.002), with a higher trabecular number (p = 0.008), connectivity density (p = 0.017), and bone mineral content (p = 0.004). In cortical bone, WT(ArKO) animals exhibited smaller cortical pores and lower cortical porosity (p = 0.02). Static histomorphometry revealed fewer osteoclasts per bone surface (Oc.S/BS%), osteoclasts on the erosion surface (ES(Oc+)/BS, p = 0.04) and low number of osteoclasts per bone perimeter (N.Oc/B.Pm, p = 0.01) in WT(ArKO). Osteoblast-associated parameters in WT(ArKO) were lower but not statistically different from WT(WT). Dynamic histomorphometry suggested similar bone formation indices' patterns with lower mean values in mineral apposition rate, label separation, and BFR/BS in WT(ArKO) animals. Ex vivo bone cell differentiation assays demonstrated relative decreased osteoblast differentiation and ability to form mineralized nodules. This study demonstrates a role of local 17ß-estradiol production by BMCs for regulating the quantity and quality of bone in male mice. Underlying in vivo cellular and molecular mechanisms require further study.

Fluid-solid coupling numerical simulation of the effects of different doses of verapamil on cancellous bone in type 2 diabetic rats.

BACKGROUND: The purpose of this study was to investigate the effects of four different doses of verapamil on the mechanical behaviors of solid and the characteristics of fluid flow in cancellous bone of distal femur of type 2 diabetes rats under dynamic external load. METHODS: Based on the micro-CT images, the finite element models of cancellous bones and fluids at distal femurs of rats in control group, diabetes group, treatment groups VER 4, VER 12, VER 24, and VER 48 (verapamil doses of 4, 12, 24, and 48 mg/kg/day, respectively) were constructed. A sinusoidal time-varying displacement load with an amplitude of 0.8 µm and a period of 1s was applied to the upper surface of the solid region. Then, fluid-solid coupling numerical simulation method was used to analyze the magnitudes and distributions of von Mises stress, flow velocity, and fluid shear stress of cancellous bone models in each group. RESULTS: The results for mean values of von Mises stress, flow velocity and FSS (t = 0.25s) were as follows: their values in control group were lower than those in diabetes group; the three parameters varied with the dose of verapamil; in the four treatment groups, the values of VER 48 group were the lowest, they were the closest to control group, and they were smaller than diabetes group. Among the four treatment groups, VER 48 group had the highest proportion of the nodes with FSS = 1-3 Pa on the surface of cancellous bone, and more areas in VER 48 group were subjected to fluid shear stress of 1-3 Pa for more than half of the time. CONCLUSION: It could be seen that among the four treatment groups, osteoblasts on the cancellous bone surface in the highest dose group (VER 48 group) were more easily activated by mechanical loading, and the treatment effect was the best. This study might help in understanding the mechanism of verapamil's effect on the bone of type 2 diabetes mellitus, and provide theoretical guidance for the selection of verapamil dose in the clinical treatment of type 2 diabetes mellitus.

Regional variation of the cortical and trabecular bone material properties in the rabbit skull.

The material properties of some bones are known to vary with anatomical location, orientation and position within the bone (e.g., cortical and trabecular bone). Details of the heterogeneity and anisotropy of bone is an important consideration for biomechanical studies that apply techniques such as finite element analysis, as the outcomes will be influenced by the choice of material properties used. Datasets detailing the regional variation of material properties in the bones of the skull are sparse, leaving many finite element analyses of skulls no choice but to employ homogeneous, isotropic material properties, often using data from a different species to the one under investigation. Due to the growing significance of investigating the cranial biomechanics of the rabbit in basic science and clinical research, this study used nanoindentation to measure the elastic modulus of cortical and trabecular bone throughout the skull. The elastic moduli of cortical bone measured in the mediolateral and ventrodorsal direction were found to decrease posteriorly through the skull, while it was evenly distributed when measured in the anteroposterior direction. Furthermore, statistical tests showed that the variation of elastic moduli between separate regions (anterior, middle and posterior) of the skull were significantly different in cortical bone, but was not in trabecular bone. Elastic moduli measured in different orthotropic planes were also significantly different, with the moduli measured in the mediolateral direction consistently lower than that measured in either the anteroposterior or ventrodorsal direction. These findings demonstrate the significance of regional and directional variation in cortical bone elastic modulus, and therefore material properties in finite element models of the skull, particularly those of the rabbit, should consider the heterogeneous and orthotropic properties of skull bone when possible.