High-resolution three-dimensional micro-computed tomography assessment of micro-architectural patterns in non-adults with cribra orbitalia: Correlation between macro- and micro-scale bone features.

Skeletal porous lesions such as cribra orbitalia (CO) have long been of interest to bioanthropologists worldwide, mainly due to their high prevalence in osteological material. Previous studies considered CO as an external morphological manifestation, and therefore, research has mainly focused on visible (macroscopic) CO patterns. However, the understanding of CO-induced micro-scale bone changes is still scarce. Therefore, we performed high-resolution micro-computed tomography imaging to investigate three-dimensional CO-induced micro-architectural patterns in non-adults, with a particular focus on the correlation between macroscopic and micro-architectural orbital features. Cortical and trabecular micro-architectural changes in the orbital roof were analyzed in non-adults younger than 15 years, using orbital roof samples with and without macroscopic traces of CO (n = 28). A widely accepted five-grade macroscopic CO scoring system was applied to analyze CO severity. Areas affected with CO (area 1) and areas without macroscopic CO traces (area 2) were analyzed separately. The conducted high-resolution analysis showed that cortical and trabecular micro-architecture varied with CO presence, lesion severity (CO grade), and the analyzed area. Inter-grade comparisons suggested that most of the analyzed micro-architectural parameters were not significantly different between adjacent CO grades. Based on the micro-architectural evaluation of areas 1 and 2, the porous lesions were much more extensive than revealed by gross examination. In addition, micro-architectural differences were particularly pronounced in younger non-adults. In summary, our pilot study suggests that the macroscopic examination of CO reflects only the tip of the iceberg, as the micro-architectural changes seem to be much larger than macroscopically identified. RESEARCH HIGHLIGHTS: Cribra orbitalia (CO) represents orbital porous lesions. A high-resolution microscopic assessment of CO-induced changes in non-adults was done by micro-computed tomography. The microarchitecture was affected by CO presence, CO grade, area, and age.

Investigating the three-dimensional myocardial micro-architecture in the laminar structure using X-ray phase-contrast microtomography.

A comprehensive grasp of the myocardial micro-architecture is essential for understanding diverse heart functions. This study aimed to investigate three-dimensional (3D) cardiomyocyte arrangement in the laminar structure using X-ray phase-contrast microtomography. Using the ID-19 beamline at the European Synchrotron Radiation Facility, we imaged human left ventricular (LV) wall transparietal samples and reconstructed them with an isotropic voxel edge length of 3.5 µm. From the reconstructed volumes, we extracted different regions to analyze the orientation distribution of local cardiomyocyte aggregates, presenting findings in terms of helix and intrusion angles. In regions containing one sheetlet population, we observed cardiomyocyte aggregates running along the local LV wall's radial direction at the border of sheetlets, branching and merging into a complex network around connecting points of different sheetlets, and bending to accommodate vessel passages. In regions with two sheetlet populations, the helix angle of local cardiomyocyte aggregates experiences a nonmonotonic change, and some cardiomyocyte aggregates run along the local radial direction. X-ray phase-contrast microtomography is a valuable technique for investigating the 3D local myocardial architecture at microscopic level. The arrangement of local cardiomyocyte aggregates in the LV wall proves to be both regional and complex, intricately linked to the local laminar structure.

Predicting the Fracture Toughness of Human Cancellous Bone in Fractured Neck of Femur Patients Using Bone Volume and Micro-Architecture.

The current protocol used to determine if an individual is osteoporotic relies on assessment of the individual's bone mineral density (BMD), which allows clinicians to judge the condition of a patient with respect to their peers. This, in essence, evaluates a person's fracture risk, because BMD is a good surrogate measure for strength and stiffness. In recent studies, the authors were the first to produce fracture toughness (FT) data from osteoporotic (OP) and osteoarthritic (OA) patients, by using a testing technique which basically analyzes the prerequisite stress conditions for the onset of growth of a major crack through cancellous bone tissue. FT depends mainly on bone quantity (BV/TV, bone volume/tissue volume), but also on bone micro-architecture (mArch), the inner trabecular design of the bone. The working research hypothesis of the present study is that mArch offers added prediction power to BV/TV in determining FT parameters. Consequently, our aim was to investigate the use of predictive models for fracture toughness and also to investigate if there are any significant differences between the models produced from samples loaded across (AC, transverse to) the main trabecular orientation and along (AL, in parallel) the trabeculae. In multilinear regression analysis, we found that the strength of the relationships varied for a crack growing in these two orthogonal directions. Adding mArch variables in the Ac direction helped to increase the R2 to 0.798. However, in the AL direction, adding the mArch parameters did not add any predictive power to using BV/TV alone; BV/TV on its own could produce R2 = 0.730. The present results also imply that the anisotropic layout of the trabeculae makes it more difficult for a major crack to grow transversely across them. Cancellous bone models and remodels itself in a certain way to resist fracture in a specific direction, and thus, we should be mindful that architectural quality as well as bone quantity are needed to understand the resistance to fracture.

Electroencephalographic slowing during REM sleep in older adults with subjective cognitive impairment and mild cognitive impairment.

STUDY OBJECTIVES: In older adults with Alzheimer's disease, slowing of electroencephalographic (EEG) activity during REM sleep has been observed. Few studies have examined EEG slowing during REM in those with mild cognitive impairment (MCI) and none have examined its relationship with cognition in this at-risk population. METHODS: Two hundred and ten older adults (mean age = 67.0, SD = 8.2 years) underwent comprehensive neuropsychological, medical, and psychiatric assessment and overnight polysomnography. Participants were classified as subjective cognitive impairment (SCI; n = 75), non-amnestic MCI (naMCI, n = 85), and amnestic MCI (aMCI, n = 50). REM EEG slowing was defined as (δ + θ)/(α + σ + ß) power and calculated for frontal, central, parietal, and occipital regions. Analysis of variance compared REM EEG slowing between groups. Correlations between REM EEG slowing and cognition, including learning and memory, visuospatial and executive functions, were examined within each subgroup. RESULTS: The aMCI group had significantly greater REM EEG slowing in the parietal and occipital regions compared to the naMCI and SCI groups (partial η2 = 0.06, p < 0.05 and 0.06, p < 0.05, respectively), and greater EEG slowing in the central region compared to SCI group (partial η2 = 0.03, p < 0.05). Greater REM EEG slowing in parietal (r = -0.49) and occipital regions (r = -0.38 [O1/M2] and -0.33 [O2/M1]) were associated with poorer visuospatial performance in naMCI. CONCLUSIONS: REM EEG slowing may differentiate older adults with memory impairment from those without. Longitudinal studies are now warranted to examine the prognostic utility of REM EEG slowing for cognitive and dementia trajectories.

Hypergravity stimulates mechanical behavior and micro-architecture of tibia in rats.

INTRODUCTION: The bone tissue is susceptible to hypergravity (+ G) environment. It is necessary to discuss the extent to which specific + G values are beneficial or detrimental to bone tissue. The objective of this study was to characterize the effects of high + G values on mechanical properties, microstructures, and cellular metabolism of bone. MATERIALS AND METHODS: 30 male Wistar rats aged 12 weeks were randomly divided into 5 groups, and bore different + G (namely + 1G, + 4G, + 8G, + 10G and + 12G) environments respectively for 4 weeks, 5 days each week, and 3 minutes each day. The macro-mechanical parameters, microstructure parameters, and mRNA transcription levels of the tibia were determined through the three-point bending method, micro-CT detection, and q-PCR analysis, respectively. RESULTS: As the + G value increases, hypergravity becomes increasingly detrimental to the macro-mechanical performance of rat tibia. Concerning the microstructure of cancellous bone, there appears to be a favorable trend at + 4G, followed by a progressively detrimental trend at higher G values. In addition, the mRNA transcription levels of OPG and RANKL show an initial tendency of enhanced bone absorption at +4G, followed by an increase in bone remodeling capacity as G value increases. CONCLUSION: The higher G values correspond to poorer macro-mechanical properties of the tibia, and a + 4G environment benefits the microstructure of the tibia. At the cellular level, bone resorption is enhanced in the + 4G group, but the bone remodeling capability gradually increases with further increments in G values.

Assessing sleep architecture and cognition in older adults with depressive symptoms attending a memory clinic.

BACKGROUND: While depression is intrinsically and bidirectionally linked with both sleep disturbance and cognition, the inter-relationships between sleep, cognition, and brain integrity in older people with depression, especially those with late-onset depression are undefined. METHODS: One hundred and seventy-two older adults (mean age 64.3 ± 6.9 years, Depression: n = 66, Control: n = 106) attending a memory clinic underwent a neuropsychological battery of declarative memory, executive function tasks, cerebral magnetic resonance imaging and overnight polysomnography with quantitative electroencephalography. RESULTS: The time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep, slow-wave activity, sleep spindles, hippocampal volume and prefrontal cortex thickness did not differ between depression and control and depression onset groups. However, sleep onset latency (p = 0.005) and REM onset latency (p = 0.02) were later in the Depression group compared to controls. Less SWS was associated with poorer memory (r = 0.31, p = 0.023) in the depression group, and less SWS was related to better memory in the control group (r = -0.20, p = 0.043; Fishers r-to-z = -3.19). LIMITATIONS: Longitudinal studies are needed to determine if changes in sleep in those with depressive symptoms predict cognitive decline and illness trajectory. CONCLUSION: Older participants with depressive symptoms had delayed sleep initiation, suggestive of delayed sleep phase. The association between SWS and memory suggests SWS may be a useful target for cognitive intervention in older adults with depression symptoms. Reduced hippocampal volumes did not mediate this relationship, indicating a broader distributed neural network may underpin these associations.

Longitudinal trajectories of spectral power during sleep in middle-aged and older adults.

Age-related changes in sleep appear to contribute to cognitive aging and dementia. However, most of the current understanding of sleep across the lifespan is based on cross-sectional evidence. Using data from the Sleep Heart Health Study, we investigated longitudinal changes in sleep micro-architecture, focusing on whether such age-related changes are experienced uniformly across individuals. Participants were 2,202 adults (ageBaseline = 62.40 ± 10.38, 55.36 % female, 87.92 % White) who completed home polysomnography assessment at two study visits, which were 5.23 years apart (range: 4-7 years). We analyzed NREM and REM spectral power density for each 0.5 Hz frequency bin, including slow oscillation (0.5-1 Hz), delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), and beta-1 (15-20 Hz) bands. Longitudinal comparisons showed a 5-year decline in NREM delta (p <.001) and NREM sigma power density (p <.001) as well as a 5-year increase in theta power density during NREM (p =.001) and power density for all frequency bands during REM sleep (ps < 0.05). In contrast to the notion that sleep declines linearly with advancing age, longitudinal trajectories varied considerably across individuals. Within individuals, the 5-year changes in NREM and REM power density were strongly correlated (slow oscillation: r = 0.46; delta: r = 0.67; theta r = 0.78; alpha r = 0.66; sigma: r = 0.71; beta-1: r = 0.73; ps < 0.001). The convergence in the longitudinal trajectories of NREM and REM activity may reflect age-related neural de-differentiation and/or compensation processes. Future research should investigate the neurocognitive implications of longitudinal changes in sleep micro-architecture and test whether interventions for improving key sleep micro-architecture features (such as NREM delta and sigma activity) also benefit cognition over time.

Texture Parameters Measured by UHF-MRI and CT Scan Provide Information on Bone Quality in Addition to BMD: A Biomechanical Ex Vivo Study.

The current definition of osteoporosis includes alteration of bone quality. The assessment of bone quality is improved by the development of new texture analysis softwares. Our objectives were to assess if proximal femoral trabecular bone texture measured in Ultra high field (UHF) 7 Tesla MRI and CT scan were related to biomechanical parameters, and if the combination of texture parameters and areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry provided a better prediction of femoral failure than aBMD alone. The aBMD of 16 proximal femur ends from eight cadavers were investigated. Nineteen textural parameters were computed in three regions or volumes of interest for each specimen on UHF MRI and CT scan. Then, the corresponding failure load and failure stress were calculated thanks to mechanical compression test. aBMD was not correlated to failure load (R2 = 0.206) and stress (R2 = 0.153). The failure load was significantly correlated with ten parameters in the greater trochanter using UHF MRI, and with one parameter in the neck and the greater trochanter using CT scan. Eight parameters in the greater trochanter using UHF MRI combined with aBMD improved the failure load prediction, and seven parameters improved the failure stress prediction. Our results suggest that textural parameters provide additional information on the fracture risk of the proximal femur when aBMD is not contributive.

Hydrangea-like NiMoO4-Ag/rGO as Battery-type electrode for hybrid supercapacitors with superior stability.

It is a great challenge to design electrode materials with good stability and high specific capacitance for supercapacitors. Herein, a three-dimensional (3D) hydrangea-like NiMoO4 micro-architecture with Ag nanoparticles anchored on the surface has been designed by adding EDTA-2Na, which was assembled with reduced graphene oxide (rGO) and named as NiMoO4-Ag/rGO composite. Benefiting from the synergetic contributions of structural and componential properties, NiMoO4-Ag/rGO composite exhibits a high specific capacitance of 566.4 C g-1 at 1 A g-1, and great cycling performance with 90.5% capacitance retention after 1000 cycles at 10 A g-1. The NiMoO4-Ag/rGO electrode shows an enhanced cycling stability due to the two-dimensional towards two-dimensional (2D-2D) interface coupling between rGO and NiMoO4 nanosheets, and the stable 3D hydrangea-like micro-architecture. Moreover, NiMoO4-Ag/rGO with 5-15 nm pore structure and enhanced conductivity exhibits improved charge transfer and ions diffusion. Besides, NiMoO4-Ag/rGO//AC capacitor displays an outstanding energy density of 40.98 Wh kg-1 at 800 kW kg-1, and an excellent cycling performance with 73.3% capacitance retention at 10 A g-1 after 8000 cycles. The synthesis of NiMoO4-Ag/rGO composite can provide an effective strategy to solve the poor electrochemical stability and slow electron/ion transfer of NiMoO4 material as supercapacitors electrode.

Jintiange Capsule Alleviates Rheumatoid Arthritis and Reverses Changes of Serum Metabolic Profile in Collagen-Induced Arthritic Rats.

PURPOSE: Jintiange capsule (JTG), an approved drug developed as a substitute for tiger bone (TB), has been clinically applied for osteoporosis therapy since 2003. The drug is composed of bionic TB powder, in which peptides and proteins are primarily enriched from other bone extracts. However, as a precious material of traditional Chinese medicine (TCM), TB has been mainly understood and used in TCM to relieve osteoporosis, rheumatoid arthritis and bone injury. Inspired by those, the purpose of this study was to investigate whether JTG also had an effect on relieving rheumatoid arthritis in collagen-induced arthritic (CIA) rats and explore potential mechanism from the perspective of serum metabolic profile changes. METHODS: JTG was analyzed using Nano LC-MS/MS and orally administered in CIA rats for 6 weeks. After administration, intervention effects of JTG on synovial inflammation, bone micro-architecture and bone metabolism were studied, and the impact of JTG on serum metabolic profiles in CIA rats was investigated by metabolomics. RESULTS: Nine bioactive peptides were identified in JTG. In animal treatments, JTG alleviated paw swelling (P < 0.01), arthritic severity (P < 0.01) and synovial tissue proliferation, as well as inflammatory cell infiltration of ankle joint, decreased bone loss, improved microstructure of bone in CIA rats by regulating bone absorption and formation, specifically increasing bone mineral density (BMD) (P < 0.05), bone volume fraction (BVF) (P < 0.05), trabecular number (Tb.N) (P < 0.05) and decreasing trabecular separation (Tb.Sp) (P < 0.05). Besides, serum IL-6 was down-regulated remarkably in CIA rats (P < 0.05). Furthermore, metabolomics analysis revealed that 32 metabolites were regulated significantly (P < 0.05) by comparison between CIA model and JTG in 360 mg/kg dose. The pathway analysis implied that JTG was involved in regulation of biosynthesis of phenylalanine. CONCLUSION: JTG alleviates rheumatoid arthritis and reverses changes in serum metabolic profile in CIA rats.

Is the Jaw Bone Micro-Structure Altered in Response to Osteoporosis and Bisphosphonate Treatment? A Micro-CT Analysis.

The aim of the study was to quantify the micro-architectural changes of the jaw bone in response to ovariectomy, exposed or not to bisphosphonate treatment. A total of 47 Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and exposed to osteoporosis preventive treatment for eight weeks either with bisphosphonates (alendronate, ALN; group OVX-ALN) three days/week at a dose of 2 mg/kg or with saline solution (untreated control condition; group OVX). The bone morphometric parameters of the trabecular jaw bone were assessed using ex vivo micro-computed tomography. The regions of interest investigated in the maxilla were the inter-radicular septum of the second molar and the tuber. The regions quantified in the mandible included the three molar regions and the condyle. A one-way analysis of variance followed by pairwise comparison using Tukey's HSD and the Games-Howell test was conducted to explore significant differences between the groups. In the maxilla, OVX decreased the bone volume in the inter-radicular septum of the second molar. Bisphosphonate treatment was able to prevent this deterioration of the jaw bone. The other investigated maxillary regions were not affected by (un)treated ovariectomy. In the mandible, OVX had a significant negative impact on the jaw bone in the buccal region of the first molar and the inter-radicular region of the third molar. Treatment with ALN was able to prevent this jaw bone loss. At the condyle site, OVX significantly deteriorated the trabecular connectivity and shape, whereas preventive bisphosphonate treatment showed a positive effect on this trabecular bone region. No significant results between the groups were observed for the remaining regions of interest. In summary, our results showed that the effects of ovariectomy-induced osteoporosis are manifested at selected jaw bone regions and that bisphosphonate treatment is capable to prevent these oral bone changes.

An Ultra-Low-Power Embedded Processor with Variable Micro-Architecture.

Embedded processors are widely used in various systems working on different tasks with different workloads. A more complex micro-architecture leads to better peak performance and worse power consumption. Shutting down the units designed for performance enhancement could improve energy efficiency in low-workload scenarios. In this paper, we evaluated the energy distribution in various embedded processors. According to the analysis, pipeline registers and the dynamic branch predictor, which are employed for better peak performance, have great impacts on energy efficiency. Thus, we proposed an ultra-low-power processor with variable micro-architecture. The processor is based on a 4-stage pipeline core with a Gshare branch predictor, and all units work in high-performance mode. In normal mode, the Gshare predictor is shut down and Always-Not-Taken prediction is used. In low-power mode, some of the pipeline registers are bypassed to avoid unnecessary energy dissipation and improve executing efficiency. A mode register (MR) is designed to indicate current working mode. Switching between different modes is controlled by the software. The proposed core is implemented in 40 nm technology and simulated with the traces of 17 benchmarks in Embench. The average amounts of power consumed by the respective modes are 41.7 µW, 59.7 µW and 71.1 µW. The results show that normal mode (N-mode) and low-power mode (L-mode) consume 16.08% and 41.37% less power than high-performance mode (H-mode) on average. In best case scenarios, they could save 25.36% and 49.30% more power than H-mode. Considering the execution efficiency evaluated by instructions per cycle (IPC), the proposed processor consumes 7.78% or 51.57% less energy for each instruction than the baseline core. The area of the proposed processor is only 7.19% larger than the baseline core, and only 3.08% more power is consumed in H-mode.

Bone health in children and youth with ASD: a systematic review and meta-analysis.

Higher risk of fracture reported in individuals with autism spectrum disorder (ASD) might be linked to poor bone health and development in childhood. This study aimed to systematically review studies comparing imaged bone outcomes between children with ASD and typically developing children (TDC) or reference data, and to perform a meta-analysis comparing commonly reported bone outcomes. We searched articles published since August 2020 from PubMed, Cochrane Library, Web of Science, EMBASE, and Scopus databases. We included studies comparing areal bone mineral density (aBMD) between children with ASD and TDC in the qualitative analysis (meta-analysis), and evaluated other imaged bone outcomes qualitatively. Seven publications were identified for the systematic review, and four studies were included in the meta-analysis. The meta-analysis indicated lower aBMD at the total body (standardized mean difference = - 0.77; 95% CI, - 1.26 to - 0.28), lumbar spine (- 0.69; - 1.00 to - 0.39), total hip (- 1.00; - 1.82 to - 0.17), and femoral neck (- 1.07; - 1.54 to - 0.60) in children with ASD compared to TDC. Based on our qualitative review, limited evidence suggested 13% lower bone mineral content at the total body and 10-20% lower cortical area, cortical and trabecular thickness, and bone strength at the distal radius and tibia in children with ASD. Children with ASD have lower aBMD at the total body, lumbar spine, and hip and femoral neck compared to TDC. Limited evidence also suggests deficits in bone mineral content, micro-architecture, and strength in children with ASD.

Communication-avoiding micro-architecture to compute Xcorr scores for peptide identification.

Database algorithms play a crucial part in systems biology studies by identifying proteins from mass spectrometry data. Many of these database search algorithms incur huge computational costs by computing similarity scores for each pair of sparse experimental spectrum and candidate theoretical spectrum vectors. Modern MS instrumentation techniques which are capable of generating high-resolution spectrometry data require comparison against an enormous search space, further emphasizing the need of efficient accelerators. Recent research has shown that the overall cost of scoring, and deducing peptides is dominated by the communication costs between different hierarchies of memory and processing units. However, these communication costs are seldom considered in accelerator-based architectures leading to inefficient DRAM accesses, and poor data-utilization due to irregular memory access patterns. In this paper, we propose a novel communication-avoiding micro-architecture to compute cross-correlation based similarity score by utilizing efficient local cache, and peptide pre-fetching to minimize DRAM accesses, and a custom-designed peptide broadcast bus to allow input reuse. An efficient bus arbitration scheme was designed, and implemented to minimize synchronization cost and exploit parallelism of processing elements. Our simulation results show that the proposed micro-architecture performs on average 24x better than a CPU implementation running on a 3.6 GHz Intel i7-4970 processor with 16GB memory.

Metabolomics profiling reveals Echinops latifolius Tausch improves the trabecular micro-architecture of ovariectomized rats mainly via intervening amino acids and glycerophospholipids metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Echinops latifolius Tausch (ELT) is traditional Mongolian medicine in China, and often used to against osteoporosis, strengthen tendons and bones, clear bones heat. AIM OF THE STUDY: To study efficacy of ELT on ovariectomized (OVX) rats and underly metabolic pathways related to trabecular micro-architecture changing of OVX. MATERIALS AND METHODS: Three-month-old female Wistar rats were randomly divided into 4 groups (n = 6) including normal group (without surgery), sham group (bilateral laparotomy), OVX group (bilateral ovariectomy), and ELT-treated groups (ELT-treated after bilateral ovariectomy). The effects of ELT on trabecular micro-architecture and biochemical markers of OVX rat were investigated by dual-energy X-ray absorptiometry machine and Enzyme-linked immunosorbent assay (ELISA), respectively. Untargeted metabolomics strategy was applied to discover the potential biomarkers and related metabolic pathways involving the progression of OVX-induced osteoporosis. RESULTS: The trabecular micro-architecture and biochemical markers of OVX rats were improved by ELT. We found 36 potential biomarkers and 21 related metabolic pathways were involved in progression of OVX-induced osteoporosis. Amino acids metabolism and glycerophospholipids metabolism were mainly intervened in ELT treatment on ovariectomized rats. The disordered amino acids and glycerophospholipids metabolism closely related to the imbalance between bone resorption and formation were reversed by administration of ELT, indicating that the influences of ELT on OVX rats' trabecular micro-architecture may possible be associated with intervening amino acids and glycerophospholipids metabolism. CONCLUSIONS: This approach may provide the metabolomic perspective to link metabolic alterations and anti-osteoporosis action of ELT, to further explain how ELT works in postmenopausal patients with bone loss.

The micro-structural analysis of lumbar vertebrae in alcoholic liver cirrhosis.

Although vertebral fracture is more common among alcoholic liver cirrhosis patients when compared to general population, current data on three-dimensional micro-architecture are scarce. Our study showed significant trabecular deterioration in lumbar vertebrae obtained from alcoholic liver cirrhosis donors, suggesting that they should be advised to undergo early-stage screening for osteoporosis. PURPOSE: Recent studies showed an increased incidence of vertebral fractures in alcoholic liver cirrhosis (ALC) patients, while data about vertebral micro-structure are still limited. The aim of this study was to compare trabecular and cortical micro-architecture of lumbar vertebrae between ALC patients and healthy age- and sex-matched controls. METHODS: Our study included lumbar vertebral samples of male cadaveric donors, divided into ALC (n = 20, age: 59 ± 6 years) and control group (n = 20, age: 59 ± 8 years). Following pathohistological verification of liver cirrhosis, trabecular and cortical bone micro-architecture was analyzed by micro-computed tomography (micro-CT). RESULTS: Micro-CT evaluation of the trabecular bone in lumbar vertebrae showed a significant decrease in bone volume fraction, trabecular thickness, trabecular number, and connectivity (p < 0.01). In contrast to trabecular deterioration, prominent alteration in cortical parameters was not observed in lumbar vertebrae of ALC patients (p > 0.05). CONCLUSIONS: Our data indicate that susceptibility to non-traumatic fractures in ALC patients could be explained by alterations in trabecular bone micro-architecture. Thus, we genuinely recommend osteological screening of the lumbar spine for all ALC patients in order to evaluate individual fracture risk. Graphical abstract.

Micro-architecture study of the normal odontoid with micro-computed tomography.

Introduction: Odontoid fractures easily lead to instability, causing spinal cord injury. The aim of this study was to measure and analyze the micro-architecture and morphometric parameters of the normal odontoid with high-resolution three-dimensional (3D) micro-computed tomography (micro-CT).Methods: Micro-CT scans were obtained from five normal odontoid processes. The scanned data were reconstructed with micro-CT software, and the nutrient foramina and the ossification center of the base of the odontoid were revealed. The trabeculae of the odontoid were measured and divided into four parts to obtain the volume fraction of regions of interest.Results: High-resolution 3D images of the micro-structures' parameters were obtained from the odontoid using micro-CT software. The images demonstrated sponge-like trabecular bone, with the trabeculae showing a complex, net-like micro-construction. The subchondral bone plate was of lamella-like, compact construction and extended and transformed into a net-like structure with rod-shaped trabeculae arranged radially in all directions. There was a statistically significant difference in the volume fraction compared with the region of interest in the fourth part of the trabeculae and the first part of the odontoid (P < 0.05). The nutrient foramina and the ossification center of the odontoid were also observed.Conclusions: It is feasible to use high-resolution 3D micro-CT to evaluate the micro-architecture of the normal odontoid. Other studies can benefit from use of the micro-CT images, such as finite element evaluations.

Texture analysis of trabecular bone around RM-Pressfit cementless acetabulum in a series of 46 patients during a 5 year period.

BACKGROUND: Cementless total hip arthroplasty (THA) is a common procedure producing excellent clinical results. Their long-term survival is nevertheless burdened by loosening of the acetabular part caused by changes in the distribution of strains around the cup. In this context the RM-Pressfit® cup has been developed, resulting in a more harmonious distribution of the strains. HYPOTHESIS: Texture analysis of X-ray films can evaluate the evolution of trabecular bone micro-architecture during the five years following THA with a RM-Pressfit® cup. MATERIAL AND METHOD: A monocentric series of 46 hips was reviewed regularly within five years post- surgery. Radiographic evaluation of the operated hip was done on frontal digitized radiographs of the pelvis to follow evolution of bone micro-architecture in the #2 zone of De Lee and Charnley. Texture analysis using fractal algorithms was done at D0, 6 months, 1, 2 and 5 years post-THA. The fractal methods used included the skyscrapers and the dynamic blanket methods with 3 different structuring elements (a cross, a horizontal and a vertical vector). RESULTS: The RM-Pressfit® caused significant changes in the distribution of strains around the acetabulum that preserved the bone volume over a 5-year period post-surgery. This corresponds to an improvement of the trabecular micro-architecture around the acetabular cups. CONCLUSION: A statistically significant increase in the four fractal dimensions considered corresponded to an improved trabecular bone micro-architecture revealed by texture analysis, a non-invasive method that can be used on digitized X-ray images. LEVEL OF EVIDENCE: IIIb, Case control study, retrospective design.

Comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients: study protocol for an open-label randomized controlled trial by HR-pQCT.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints, causes joint destruction, and leads to physical disability. Advances in the treatment of RA, such as biologic disease-modifying anti-rheumatic drugs (DMARDs), have provided better clinical outcomes, including the achievement of remission for patients with RA, but some patients cannot receive these treatments because of their side effects and high cost, and not all patients achieve remission. Although the efficacy of denosumab, which is a human IgG2 monoclonal antibody with a high affinity for the receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), in the treatment of RA has been reported in clinical trials, the efficacy of denosumab in both preventing joint destruction and improving disease activity has not been evaluated in a real-world setting. METHODS/DESIGN: This open-label, randomized, parallel-group study will compare the continued use of conventional synthetic DMARDs (csDMARDs) alone with the combined use of csDMARDs and denosumab in patients whose RA is treated with csDMARDs. In total, 44 patients with RA will be randomly assigned to receive additional treatment with denosumab or to continue RA treatment without additional denosumab. The duration of the intervention will be 12 months. To analyze bone erosion and bone micro-architecture precisely, high-resolution peripheral quantitative computed tomography (HR-pQCT) will be performed every 6 months. The primary endpoint is changes in the depth of bone erosion as measured by HR-pQCT from baseline to 6 months. Important secondary endpoints are the changes from baseline in the width and volume of bone erosion as measured by HR-pQCT and changes from baseline in the depth of bone erosion at 12 months. Changes in bone micro-architecture will also be analyzed as an exploratory endpoint. DISCUSSION: The results of this study are expected to provide strong evidence regarding the usefulness of denosumab for the treatment of RA. Moreover, by using HR-pQCT, this study will also reveal the effect of denosumab not only on bone erosion but also on bone micro-architecture. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000030575 on December 26, 2017.

Functional disuse initiates medullary endosteal micro-architectural impairment in cortical bone characterized by nanoindentation.

In this study, we evaluated the effect of functional disuse-induced bone remodeling on its mechanical properties, individually at periosteum and medullary endosteum regions of the cortical bone. Left middle tibiae were obtained from 5-month-old female Sprague-Dawley rats for the baseline control as well as hindlimb suspended (disuse) groups. Micro-nano-mechanical elastic moduli (at lateral region) was evaluated along axial (Z), circumferential (C) and radial (R) orientations using nanoindentation. Results indicated an anisotropic microstructure with axial orientation having the highest and radial orientation with the lowest moduli at periosteum and medullary endosteum for both baseline control as well as disuse groups. Between the groups: at periosteum, an insignificant difference was evaluated for each of the orientations (p > 0.05) and at endosteum, a significant decrease of elastic moduli in the radial (p < 0.0001), circumferential (p < 0.001) and statistically insignificant difference in axial (p > 0.05) orientation. For the moduli ratios between groups: at periosteum, only significant difference in the Z/R (p < 0.05) anisotropy ratio, whereas at endosteum, a statistically significant difference in Z/C (p < 0.001), and Z/R (p < 0.001), as well as C/R (p < 0.05) anisotropy ratios, was evaluated. The results suggested initial bone remodeling impaired bone micro-architecture predominantly at the medullary endosteum with possible alterations in the geometric orientations of collagen and mineral phases inside the bone. The findings could be significant for studying the mechanotransduction pathways involved in maintaining the bone micro-architecture and possibly have high clinical significance for drug use against impairment from functional disuse.