The impact of androgen deprivation therapy on bone microarchitecture in men with prostate cancer: A longitudinal observational study (The ANTELOPE Study).

Introduction: Androgen Deprivation Therapy (ADT) for prostate cancer (PC) has substantial negative impacts on the musculoskeletal system and body composition. Many studies have focused on the effects of ADT on areal bone mineral density (aBMD), but aBMD does not capture key determinants of bone strength and fracture risk, for example volumetric bone density (vBMD), geometry, cortical thickness and porosity, trabecular parameters and rate of remodelling. More specialist imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) have become available to evaluate these parameters. Although it has previously been demonstrated that bone microarchitectural deterioration occurs in men undergoing ADT, the aim of the ANTELOPE study was to examine longitudinal changes in bone microstructure alongside a range of musculoskeletal parameters and frailty, comparing men with PC receiving ADT alone or ADT plus chemotherapy for metastatic disease, with a healthy age-matched population. Methods: We used HR-pQCT to investigate effects of 12 months of ADT on vBMD and microstructural parameters, complemented by assessment of changes in aBMD, serum bone turnover markers, sex hormones, body composition, grip strength, physical and muscle function, frailty and fracture risk. We studied three groups: Group A - men with localised/locally advanced PC due to commence ADT; Group B - men with newly diagnosed hormone-sensitive, metastatic PC, starting ADT alongside docetaxel chemotherapy and steroids; Group C - healthy, age-matched men. The primary endpoint was change in vBMD (Group A vs Group C) at the distal radius. Results: Ninety-nine participants underwent baseline study assessments (Group A: n = 38, Group B: n = 30 and Group C: n = 31). Seventy-five participants completed all study assessments (Group A (29), Group B (18), Group C (28). At baseline, there were no significant differences between Groups A and C in any of the BMD or bone microstructure outcomes of interest. After 12 months of ADT treatment, there was a significantly greater decrease in vBMD (p < 0.001) in Group A (mean 12-month change = -13.7 mg HA/cm3, -4.1 %) compared to Group C (mean 12-month change = -1.3 mg HA/cm3, -0.4 %), demonstrating achievement of primary outcome. Similar effects were observed when comparing the change in vBMD between Group B (mean 12-month change = -13.5 mg HA/cm3, -4.3 %) and Group C. These changes were mirrored in aBMD. ADT resulted in microstructural deterioration, a reduction in estimated bone strength and an increase in bone turnover. There was evidence of increase in total fat mass and trunkal fat mass in ADT-treated patients, with marked loss in upper limb mass, along with BMI gain. Frailty increased and physical performance and strength deteriorated in both ADT groups, relative to the healthy control group. Conclusion: The study showed that ADT has profound effects on vBMD, aBMD, bone microstructure and strength and body composition, and important impacts on frailty and physical performance. Whilst DXA remains a valuable tool (changes in aBMD are of the same magnitude as those observed for vBMD), HR-pQCT should be considered for assessing the effects of anti-androgens and other newer PC therapies on bone, as well as potential mitigation by bone-targeted agents.

A Novel Viscoelastic Deformation Mechanism Uncovered during Vickers Hardness Study of Bone.

This study investigates the viscoelastic deformation mechanisms of bone as a response to Vickers hardness indentation. We utilized advanced high-resolution scanning electron microscopy (SEM) to investigate a distinct deformation pattern that originates from the indentation site within the bone matrix. The focus of our research was to analyze a unique deformation mechanism observed in bone tissue, which has been colloquially termed as "screw-like" due to its resemblance to a screw thread when viewed under an optical microscope. The primary goals of this research are to investigate the distinctive characteristics of the "screw-like" deformation pattern and to determine how the microstructure of bone influences the initiation and control of this mechanism. These patterns, emerging during the dwell period of indentation, underscore the viscoelastic nature of bone, indicating its propensity for energy dissipation and microstructural reconfiguration under load. This study uncovered a direct correlation between the length of the "screw-like" deformation and the duration of the indentation dwell time, providing quantifiable evidence of the bone's viscoelastic behavior. This finding is pivotal in understanding the mechanical properties of bone, including its fracture toughness, as it relates to the complex interplay of factors such as energy dissipation, microstructural reinforcement, and stress distribution. Furthermore, this study discusses the implications of viscoelastic properties on the bone's ability to resist mechanical challenges, underscoring the significance of viscoelasticity in bone research.

The pseudosuchian record in paleohistology: A small review.

Archosauria originated around the Earth's largest biotic crisis that severely affected all ecosystems globally, the Permotriassic Mass extinction event, and comprises two crown-group lineages: the bird-lineage and the crocodylian lineage. The bird lineage includes the iconic pterosaurs, as well as dinosaurs and birds, whereas the crocodylian lineage includes clades such as aetosaurs, poposaurs, "rauisuchians," as well as Crocodylomorpha; the latter being represented today only by less than 30 extant species of Crocodylia. Despite playing important roles during Mesozoic and Cenozoic ecosystems, both on land and in water, Pseudosuchia received far less attention compared to the bird-lineage, which is also reflected in number and scope of histological studies so far. Lately, the field has seen a shift of focus toward pseudosuchians, however, and the symposium on "Paleohistological Inferences of Paleobiological Traits in Pseudosuchia" held during the International Congress of Vertebrate Morphology 2023 in Cairns, Queensland, Australia, is the latest proof of that. To put these novel aspects of paleohistological and paleobiological research into context, an overview of the non-extant pseudosuchian taxa whose postcranial bones were studied so far is provided here (c. 80 species out of a total of more than 700 extinct species described) and recent trends in pseudosuchian osteohistology are highlighted. In addition, histological studies on cranial and dental material and other potential hard tissues, such as eggshells and otoliths, are briefly reviewed as well.

Associations of global biomarkers of oxidative stress with osteoporosis, bone microstructure and bone turnover: Evidence from human and animal studies.

PURPOSE: Human evidence on the association between oxidative stress and osteoporosis is inconsistent. Fluorescent Oxidation Products (FlOPs) are global biomarkers of oxidative stress. We examined the associations of FlOPs (excitation/emission wavelengths 320/420 nm for FlOP_320, 360/420 nm for FlOP_360, and 400/475 nm for FlOP_400) with osteoporosis, bone microstructure, and bone turnover markers in humans and rats. METHODS: In humans, we conducted a 1:2 age, sex, hospital, and specimen-matched case-control study to test the association between FlOPs and osteoporosis diagnosed from dual-energy X-ray absorptiometry. In eight-week-old male Wistar rats, we administrated D-galactose and 0.9 % saline for 90 days in treatment and control groups (n = 8/group); micro-CT was used to determine bone microstructure. RESULTS: In humans, higher levels of FlOP_320 (OR for per 1 SD increase = 1.49, 95 % CI: 1.01-2.20) and FlOP_360 (OR for per 1 SD increase = 1.59, 95 % CI: 1.07-2.37) were associated with increased odds of osteoporosis. FlOP_400 were not associated with osteoporosis. D-galactose treated rats, as compared with control rats, showed higher levels of FlOP_320 and MDA, and lower P1NP levels during 90 days of experiment (all P < 0.05). The D-galactose group had lower trabecular bone volume fraction (0.07 ± 0.03 vs. 0.13 ± 0.05; P = 0.008) and volumetric BMD (225.4 ± 13.8 vs. 279.1 ± 33.2 mg HA/cm3; P = 0.001) than the control group. CONCLUSION: In conclusion, higher FlOP_320 levels were associated with increased odds of osteoporosis, impaired bone microstructure and decreased bone formation.

Mechanical Stress Via Muscle Contractile Exercise Suppresses Atrophic Alterations of Bone-microstructure in Immobilized Rat Femurs.

OBJECTIVES: This study aimed to determine whether mechanical stress via muscle contractile exercise with belt electrode-skeletal muscle electrical stimulation (B-SES) device effectively prevents immobilization-induced bone atrophy. METHODS: Wistar rats were randomly divided into the control (CON) group, immobilization (IM) group (immobilized treatment only), HES and LES groups (immobilized treatment and high or low-intensity electrical muscular stimulation through B-SES device). Bilateral femurs were used for X-ray micro-CT and biomechanical tests. RESULTS: The maximum load value was significantly lower in the IM and HES groups than in the CON group and significantly higher in the LES group than in the IM group. The maximum crushing load was significantly lower in the IM, HES, and LES groups than in the CON group, and significantly higher in the HES and LES groups than that in the IM group. In micro-CT, the mechanical stress by B-SES device did not affect degenerative microstructural changes in the cortical bone, but prevented those changes in the cancellous bone. CONCLUSIONS: Applying mechanical stress via B-SES device suppressed the loss of cancellous bone density and degenerative microstructural changes caused by immobilization, which in turn suppressed the reduction of bone strength. From these findings, muscle contractile exercise may be effective in preventing immobilization-induced bone atrophy.

Chromium Picolinate Regulates Bone Metabolism and Prevents Bone Loss in Diabetic Rats.

Diabetic osteoporosis (DOP) is an abnormal metabolic disease caused by long-term hyperglycemia. In this study, a model rat of streptozotocin (STZ)-induced diabetes was established, and chromium picolinate (5 mg·kg-1) was given; the changes in blood glucose and body weight were detected before and after administration; and bone mineral density (BMD), bone morphology, bone turnover markers, inflammatory cytokines, and oxidative stress indicators were observed in each group. We found that after chromium picolinate (CP) intervention for 8 weeks, the blood glucose level was decreased; the BMD, the bone histomorphology parameters, and the pathological structure were improved; the expression of bone resorption-related proteins was downregulated; and the expression of bone formation-related proteins was upregulated. Meanwhile, serum antioxidant activity was increased, and inflammatory cytokine levels were decreased. In conclusion, CP could alleviate DOP by anti-oxidation, inhibition of bone turnover, anti-inflammation, and regulation of the OPG/RANKL/RANK signaling pathway. Therefore, CP has important application values for further development as a functional food or active medicine in DOP treatment.

Effects of Tenofovir Disoproxil Fumarate on Bone Quality beyond Bone Density-A Scoping Review of the Literature.

Tenofovir disoproxil fumarate (TDF) is a widely used pharmacological agent for the treatment of human immunodeficiency virus infection. While prolonged exposure to TDF has been associated with a decrease in bone mineral density (BMD) and increased fracture risk, limited discussion exists on its effects on various aspects of bone quality. This scoping review aims to provide a comprehensive overview of the impact of TDF on bone quality beyond BMD. A literature search was conducted using the PubMed and Scopus databases to identify studies investigating the effects of TDF on bone quality. Original research articles written in English, irrespective of study type or publication year, were included in the review. Seven articles met the inclusion criteria. Findings indicate that prolonged exposure to TDF adversely affects bone microarchitecture and strength, impeding fracture healing and skeletal microdamage repair. The observed effects suggest a complex interplay involving bone cell signalling, cytokines and bone remodelling processes as potential mechanisms underlying TDF's impact on bone quality. As a conclusion, TDF impairs bone remodelling and microarchitecture by influencing dynamic bone cell behaviour and signalling pathways. Future studies should delve deeper into understanding the intricate negative effects of TDF on bone and explore strategies for reversing these effects.

Quinoa alleviates osteoporosis in ovariectomized rats by regulating gut microbiota imbalance.

BACKGROUND: Postmenopausal osteoporosis (PMO) is associated with dysregulation of bone metabolism and gut microbiota. Quinoa is a grain with high nutritional value, and its effects and potential mechanisms on PMO have not been reported yet. Therefore, the purpose of this study is to investigate the bone protective effect of quinoa on ovariectomy (OVX) rats by regulating bone metabolism and gut microbiota. RESULTS: Quinoa significantly improved osteoporosis-related biochemical parameters of OVX rats and ameliorated ovariectomy-induced bone density reduction and trabecular structure damage. Quinoa intervention may repair the intestinal barrier by upregulating the expression of tight junction proteins in the duodenum. In addition, quinoa increased the levels of Firmicutes, and decreased the levels of Bacteroidetes and Prevotella, reversing the dysregulation of the gut microbiota. This may be related to estrogen signaling pathway, secondary and primary bile acid biosynthesis, benzoate degradation, synthesis and degradation of ketone bodies, NOD-like receptor signaling pathway and biosynthesis of tropane, piperidine and pyridine alkaloids. Correlation analysis showed that there is a strong correlation between gut microbiota with significant changes in abundance and parameters related to osteoporosis. CONCLUSION: Quinoa could significantly reverse the high intestinal permeability and change the composition of gut microbiota in OVX rats, thereby improving bone microstructure deterioration and bone metabolism disorder, and ultimately protecting the bone loss of OVX rats. © 2024 Society of Chemical Industry.

Effects of 25-hydroxycholecalciferol on performance, gut health, and bone quality of broilers fed with reduced calcium and phosphorus diet during Eimeria challenge.

This study evaluated the effects of 25-hydroxycholecalciferol (25-OHD) on performance, gut health, and bone quality of broilers fed with reduced calcium (Ca) and phosphorus (P) diet during Eimeria spp. challenge. A total of 576 fourteen-day-old Cobb 500 male chicks were randomly distributed in a 2 × 2 × 2 factorial arrangement, with 6 replicates of 12 birds each. The main factors were 25-OHD level (0 or 3,000 IU/kg of feed), mineral level (0.84% of Ca/0.42% of P, the levels recommended for the grower phase (NOR) or 0.64% of Ca/0.22% of P (RED), and mid-high mixed Eimeria challenge or nonchallenge. 25-OHD improved phosphorus retention (P = 0.019), bone ash weight (P = 0.04), cortical bone trabecular connectivity (P = 0.043) during coccidiosis. For birds fed with reduced mineral levels, 25-OHD supplementation increased bone ash weight (P = 0.04). However, 25-OHD did not improve bone ash weight when birds were challenged and fed with reduced mineral levels. The dietary 3,000 IU of 25-OHD supplementation did not improve performance or gut morphology but support bone health during coccidiosis. Future investigations are needed for better understand 25-OHD role on bone microarchitecture and oxidative metabolism during coccidiosis.

Prevention of bone deterioration by whole-body vibration in a rat model of pre-type 2 diabetes.

OBJECTIVES: To examine effects of whole-body vibration (WBV) on bone properties in pre-type 2 diabetes mellitus (T2DM) rats. METHODS: Six-week-old male Hos:ZFDM-Lepr fa, fa/fa (DM) and Hos:ZFDM-Leprfa,fa/+ (CON; untreated non-DM) rats were used in the experiments. Half of DM rats were subjected to WBV (45 Hz, 0.5 g, 15 min/day, 5 days/week) for 8 weeks (WBV group), and the other half was not (DM group). RESULTS: Bone mass, trabecular bone microstructure (TBMS), and cortical bone geometry (CBG) parameters were worse in the DM and WBV groups compared with the CON group. Maximum load was significantly decreased in the DM group compared with the CON group, and the break point was significantly higher in the WBV group compared with the DM group. Serum levels of bone specific alkaline phosphatase were significantly lower in the WBV group compared with the CON group. Glycemic control was not worse in the WBV group compared with the DM group, but not the same levels as the CON group. CONCLUSIONS: These findings suggest that WBV can potentially delay the decrease in maximum load, although it does not prevent the deterioration of bone mass, TBMS, and CBG parameters.

Characterization of mechanical stiffness using additive manufacturing and finite element analysis: potential tool for bone health assessment.

BACKGROUND: Bone health and fracture risk are known to be correlated with stiffness. Both micro-finite element analysis (µFEA) and mechanical testing of additive manufactured phantoms are useful approaches for estimating mechanical properties of trabecular bone-like structures. However, it is unclear if measurements from the two approaches are consistent. The purpose of this work is to evaluate the agreement between stiffness measurements obtained from mechanical testing of additive manufactured trabecular bone phantoms and µFEA modeling. Agreement between the two methods would suggest 3D printing is a viable method for validation of µFEA modeling. METHODS: A set of 20 lumbar vertebrae regions of interests were segmented and the corresponding trabecular bone phantoms were produced using selective laser sintering. The phantoms were mechanically tested in uniaxial compression to derive their stiffness values. The stiffness values were also derived from in silico simulation, where linear elastic µFEA was applied to simulate the same compression and boundary conditions. Bland-Altman analysis was used to evaluate agreement between the mechanical testing and µFEA simulation values. Additionally, we evaluated the fidelity of the 3D printed phantoms as well as the repeatability of the 3D printing and mechanical testing process. RESULTS: We observed good agreement between the mechanically tested stiffness and µFEA stiffness, with R2 of 0.84 and normalized root mean square deviation of 8.1%. We demonstrate that the overall trabecular bone structures are printed in high fidelity (Dice score of 0.97 (95% CI, [0.96,0.98]) and that mechanical testing is repeatable (coefficient of variation less than 5% for stiffness values from testing of duplicated phantoms). However, we noticed some defects in the resin microstructure of the 3D printed phantoms, which may account for the discrepancy between the stiffness values from simulation and mechanical testing. CONCLUSION: Overall, the level of agreement achieved between the mechanical stiffness and µFEA indicates that our µFEA methods may be acceptable for assessing bone mechanics of complex trabecular structures as part of an analysis of overall bone health.

The Utility of Preclinical Models in Understanding the Bone Health of Transgender Individuals Undergoing Gender-Affirming Hormone Therapy.

PURPOSE OF REVIEW: To summarise the evidence regarding the effects of gender-affirming hormone therapy (GAHT) on bone health in transgender people, to identify key knowledge gaps and how these gaps can be addressed using preclinical rodent models. RECENT FINDINGS: Sex hormones play a critical role in bone physiology, yet there is a paucity of research regarding the effects of GAHT on bone microstructure and fracture risk in transgender individuals. The controlled clinical studies required to yield fracture data are unethical to conduct making clinically translatable preclinical research of the utmost importance. Novel genetic and surgical preclinical models have yielded significant mechanistic insight into the roles of sex steroids on skeletal integrity. Preclinical models of GAHT have the potential inform clinical approaches to preserve skeletal integrity and prevent fractures in transgender people undergoing GAHT. This review highlights the key considerations required to ensure the information gained from preclinical models of GAHT are informative.

Transcriptomics reveals the molecular regulation of Chinese medicine formula on improving bone quality in broiler.

Skeletal disorder is of concern to the poultry industry as it affects animal welfare and production performance. Traditional Chinese medicine could improve bone quality and reduce the incidence of bone disease, but the molecular regulation of Chinese medicine formula (CMF) on improving bone quality in broilers is still unclear. This study was performed to research the effects of CMF on skeletal performance of Cobb broilers and reveal the molecular regulation. A total of 120 one-day-old Cobb broilers were randomly allocated into 4 equal groups of 30 chickens, with 5 replicates and 6 chickens in each replicate. The control (CON) group was fed a diet without CMF, while the CMF1, CMF2, and CMF3 groups were supplemented with different CMF at 6,000 mg/kg diet, respectively. The broilers were raised to 60 d of age, then bone tissues were collected for biomechanical properties, micro-CT detection and transcriptomic sequencing analysis. The results showed that CMF3 improved the biomechanical properties of broiler tibia, via increasing the elastic modulus (P < 0.05), yield strength (P > 0.05), maximum stress (P < 0.05) and fracture stress (P < 0.05) of the tibia. Micro-CT analysis indicated that CMF3 increased the bone mineral density (BMD), bone volume/total volume (BV/TV), bone surface density (BS/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and decreased the trabecular separation (Tb.Sp) of femur cancellous bone (P < 0.05). RNA-seq analysis revealed 2,177 differentially expressed genes (DEGs) (|log2FoldChange| ≥ 1, FDR < 0.05) between the CMF3 group and CON group. Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis showed 13 pathways mostly associated with bone growth and development and bone metabolism, and we identified 39 bone-related DEGs. This study suggests that CMF3 could improve bone strength and bone microstructure of broilers, and showed a positive effect on bone performance. Our research could provide a theoretical reference for the development of pollution-free feed additives to improve the skeletal performance of broilers, which could help promote healthy farming of chickens.

Long-term reproducibility of opportunistically assessed vertebral bone mineral density and texture features in routine clinical multi-detector computed tomography using an automated segmentation framework.

Background: To investigate reproducibility of texture features and volumetric bone mineral density (vBMD) extracted from trabecular bone in the thoracolumbar spine in routine clinical multi-detector computed tomography (MDCT) data in a single scanner environment. Methods: Patients who underwent two routine clinical thoraco-abdominal MDCT exams at a single scanner with a time interval of 6 to 26 months (n=203, 131 males; time interval mean, 13 months; median, 12 months) were included in this observational study. Exclusion criteria were metabolic and hematological disorders, bone metastases, use of bone-active medications, and history of osteoporotic vertebral fractures (VFs) or prior diagnosis of osteoporosis. A convolutional neural network (CNN)-based framework was used for automated spine labeling and segmentation (T5-L5), asynchronous Hounsfield unit (HU)-to-BMD calibration, and correction for the intravenous contrast medium phase. Vertebral vBMD and six texture features [varianceglobal, entropy, short-run emphasis (SRE), long-run emphasis (LRE), run-length non-uniformity (RLN), and run percentage (RP)] were extracted for mid- (T5-T8) and lower thoracic (T9-T12), and lumbar vertebrae (L1-L5), respectively. Relative annual changes were calculated in texture features and vBMD for each vertebral level and sorted by sex, and changes were checked for statistical significance (P<0.05) using paired t-tests. Root mean square coefficient of variation (RMSCV) and root mean square error (RMSE) were calculated as measures of variability. Results: SRE, LRE, RLN, and RP exhibited substantial reproducibility with RMSCV-values below 2%, for both sexes and at all spine levels, while vBMD was less reproducible (RMSCV =11.9-16.2%). Entropy showed highest variability (RMSCV =4.34-7.69%) due to statistically significant increases [range, mean ± standard deviation: (4.40±5.78)% to (8.36±8.66)%, P<0.001]. RMSCV of varianceglobal ranged from 1.60% to 3.03%. Conclusions: Opportunistic assessment of texture features in a single scanner environment using the presented CNN-based framework yields substantial reproducibility, outperforming vBMD reproducibility. Lowest scan-rescan variability was found for higher-order texture features. Further studies are warranted to determine, whether microarchitectural changes to the trabecular bone may be assessed through texture features.

An integrated experimental-computational framework to assess the influence of microstructure and material properties on fracture toughness in clinical specimens of human femoral cortical bone.

Microstructural and compositional changes that occur due to aging, pathological conditions, or pharmacological treatments alter cortical bone fracture resistance. However, the relative importance of these changes to the fracture resistance of cortical bone has not been quantified in detail. In this technical note, we developed an integrated experimental-computational framework utilizing human femoral cortical bone biopsies to advance the understanding of how fracture resistance of cortical bone is modulated due to modifications in its microstructure and material properties. Four human biopsy samples from individuals with varying fragility fracture history and osteoporosis treatment status were converted to finite element models incorporating specimen-specific material properties and were analyzed using fracture mechanics-based modeling. The results showed that cement line density and osteonal volume had a significant effect on crack volume. The removal of cement lines substantially increased the crack volume in the osteons and interstitial bone, representing straight crack growth, compared to models with cement lines due to the lack of crack deflection in the models without cement lines. Crack volume in the osteons and interstitial bone increased when mean elastic modulus and ultimate strength increased and mean fracture toughness decreased. Crack volume in the osteons and interstitial bone was reduced when material property heterogeneity was incorporated in the models. Although both the microstructure and the heterogeneity of the material properties of the cortical bone independently increased the fracture toughness, the relative contribution of the microstructure was more significant. The integrated experimental-computational framework developed here can identify the most critical microscale features of cortical bone modulated by pathological processes or pharmacological treatments that drive changes in fracture resistance and improve our understanding of the relative influence of microstructure and material properties on fracture resistance of cortical bone.

Differentiation of benign and malignant vertebral fractures using a convolutional neural network to extract CT-based texture features.

PURPOSE: To assess the diagnostic performance of three-dimensional (3D) CT-based texture features (TFs) using a convolutional neural network (CNN)-based framework to differentiate benign (osteoporotic) and malignant vertebral fractures (VFs). METHODS: A total of 409 patients who underwent routine thoracolumbar spine CT at two institutions were included. VFs were categorized as benign or malignant using either biopsy or imaging follow-up of at least three months as standard of reference. Automated detection, labelling, and segmentation of the vertebrae were performed using a CNN-based framework ( https://anduin.bonescreen.de ). Eight TFs were extracted: Varianceglobal, Skewnessglobal, energy, entropy, short-run emphasis (SRE), long-run emphasis (LRE), run-length non-uniformity (RLN), and run percentage (RP). Multivariate regression models adjusted for age and sex were used to compare TFs between benign and malignant VFs. RESULTS: Skewnessglobal showed a significant difference between the two groups when analyzing fractured vertebrae from T1 to L6 (benign fracture group: 0.70 [0.64-0.76]; malignant fracture group: 0.59 [0.56-0.63]; and p = 0.017), suggesting a higher skewness in benign VFs compared to malignant VFs. CONCLUSION: Three-dimensional CT-based global TF skewness assessed using a CNN-based framework showed significant difference between benign and malignant thoracolumbar VFs and may therefore contribute to the clinical diagnostic work-up of patients with VFs.

Study on the association of the microstructure and bone metabolism in the osteoporotic femoral head.

BACKGROUND: We compared the bone microstructure and metabolism of the femoral heads in patients with osteoporosis (OP) and non-OP patients to investigate the pathologic mechanism of OP and guide clinical treatment. METHODS AND RESULTS: From January 2020 to June 2021, we obtained femoral head samples from 30 patients undergoing hip replacement due to femoral neck fracture. All patients were women aged approximately 67 to 80 years (mean age, 74 years). According to the dual-energy X-ray results, the femoral head samples were divided into the OP (T< - 2.5) and non-OP (T > - 1.5) groups. Microcomputed tomography scanning, bone metrology analysis, hematoxylin and eosin staining, and Masson's trichrome staining were used to compare the local bone trabecular microstructure changes. Quantitative reverse transcription PCR was performed to identify changes in the osteogenesis-related genes and the osteoclast-related genes in specific regions to reflect osteogenic and osteoclastic activities. Femoral heads with OP showed significant changes in the local bone microstructure. Bone density, bone volume fraction, and the number and thickness of the bone trabeculae decreased. Local bone metabolism was imbalanced in the areas with microstructural changes in femoral heads with OP, with increased osteoclast activity and decreased osteoblast activity. CONCLUSIONS: Deterioration of bone microstructure is closely related to abnormal bone metabolism associated with the activity of osteoblasts and osteoclasts in osteoporotic femoral heads. Promoting bone formation by improving local bone metabolism, enhancing osteogenic activity and inhibiting osteoclast activity may be a promising way of preventing local OP and osteoporotic fractures.

Microcystin-leucine-arginine impairs bone microstructure and biomechanics by activating osteoimmune response and inhibiting osteoblasts maturation in developing rats.

Microcystin-LR (MC-LR) affects bone health in adult mice via osteo-immunomodulation. However, its effect on osteoblasts and bone development is unclear. This study investigated the effect of MC-LR on bone osteoimmune and osteoblasts in the developing period. 18 Four-week-old male Sprague Dawley rats were divided into two groups (n = 9 per group) and exposed to 0 (control) and 1 µg/kg b.w. MC-LR (exposure) by intraperitoneal injection for four weeks. The heart blood was collected for serological examination, and the femur for morphological, histopathological, and biomechanical analysis. MC-LR exposure significantly weakened bone microstructures (bone volume, bone volume/total volume, bone trabecular number, connectivity density) and biomechanics (maximum loads and maximum deflection) (P < 0.05). Besides, MC-LR decreased serum procollagen type І car-boxy-terminal propeptide, osteocalcin, bone morphogenetic protein-2, osteoprotegerin, and receptor activator of nuclear factor κB ligand, while elevating osteoclasts number, matrix metalloproteinase-9, ß-catenin, Runt-related transcription factor 2, and osterix in bone, and bone alkaline phosphate, C-terminal cross-linked telopeptide of type-I collagen, tartrate-resistant acid phosphatase-5b in serum (P < 0.05). Moreover, MC-LR increased CD4+ T-cells, CD4+/CD8+, M1 and M2 macrophages, and cells apoptosis in the bone marrow, interleukin-6, interleukin-17, and tumor necrosis factor-α in serum, decreased serum interleukin-10 (P < 0.05). Overall, MC-LR can promote bone resorption by activating osteoclasts via osteoimmunology, which may involve macrophages besides lymphocytes. MC-LR may inhibit bone formation by stopping the osteoblasts at an immature stage. Thus, MC-LR weakened bone microstructure and biomechanics in developing period. Its risk on bone development needs further study.

Effects of soybean isoflavone aglycone on osteoporosis in ovariectomized rats.

Postmenopausal osteoporosis is one of the most common metabolic diseases in old women, and supplementing estrogen through bioactive substances is one of the important ways to improve menopausal syndrome. Some studies have confirmed that soybean isoflavone has estrogenic activity, and the main active component of soybean isoflavones is isoflavone aglycones. However, few studies have investigated the improvement effect of high-purity soy isoflavone aglycones on postmenopausal osteoporosis. Thus, the effect of different doses of high-purity soybeans isoflavone aglycone on the ovariectomized female osteoporosis rat model was evaluated by oral gavage. The rats were divided into seven experimental groups including SHAM, OVX, EE, SIHP, AFDP-L, AFDP-M, and AFDP-H, which was administered for 60 days from 30 days after ovariectomy. We collected blood from the abdominal aorta of rats on the 30th, 60th, and 90th days respectively, analyzed its serum biochemistry, and took out the femur for micro-CT imaging and bone microstructure parameter analysis. Results showed that the intervention effect of AFDP-H group on osteoporosis rats at 60 and 90 days was similar to that of EE group, and superior to the OVX group, SIHP group, AFDP-L group, AFDP-M group. The AFDP-H group inhibited the decrease in serum bone markers, bone density, trabeculae quantity, trabeculae thickness, and bone volume fraction, and increased the trabecular separation caused by ovariectomy, thereby significantly improving bone microstructure. It also prevented continuous weight gain and increased cholesterol levels in female rats. This study provided theoretical to application of soybean isoflavone aglycone in the intervention of osteoporosis. and confirmed that could replace chemical synthetic estrogen drugs.

Low-intensity pulsed ultrasound enhances the positive effects of high-intensity treadmill exercise on bone in rats.

INTRODUCTION: Moderate exercise benefits bone health, but excessive loading leads to bone fatigue and a decline in mechanical properties. Low-intensity pulsed ultrasound (LIPUS) can stimulate bone formation. The purpose of this study was to explore whether LIPUS could augment the skeletal benefits of high-intensity exercise. MATERIALS AND METHODS: MC3T3-E1 osteoblasts were treated with LIPUS at 80 mW/cm2 or 30 mW/cm2 for 20 min/day. Forty rats were divided into sham treatment normal control (Sham-NC), sham treatment high-intensity exercise (Sham-HIE), 80 mW/cm2 LIPUS (LIPUS80), and high-intensity exercise combined with 80 mW/cm2 LIPUS (LIPUS80-HIE). The rats in HIE group were subjected to 30 m/min slope treadmill exercise for 90 min/day, 6 days/week for 12 weeks. The LIPUS80-HIE rats were irradiated with LIPUS (1 MHz, 80 mW/cm2) for 20 min/day at bilateral hind limb after exercise. RESULTS: LIPUS significantly accelerated the proliferation, differentiation, mineralization, and migration of MC3T3-E1 cells. Compared to 30 mW/cm2 LIPUS, 80 mW/cm2 LIPUS got better promotion effect. 12 weeks of high-intensity exercise significantly reduced the muscle force, which was significantly reversed by LIPUS. Compared with the Sham-NC group, Sham-HIE group significantly optimized bone microstructure and enhanced mechanical properties of femur, and LIPUS80-HIE further enhanced the improvement effect on bone. The mechanisms may be related to activate Wnt/ß-catenin signal pathway and then up-regulate the protein expression of Runx2 and VEGF, the key factors of osteogenesis and angiogenesis. CONCLUSION: LIPUS could augment the skeletal benefits of high-intensity exercise through Wnt/ß-catenin signal pathway.