Changes In Bone Structure Research Articles

The Investigation of Radiographic Findings of Mandibles on Panoramic Radiographs of Patients with Primary Hyperparathyroidism Using Fractal Analysis.

The basis of the research is the application of fractal analysis (FA) to panoramic radiographs of patients with primary hyperparathyroidism (PHPT). In addition, the relationship between the relevant biochemistry parameters and fractal values of healthy controls and patients with PHPT will be evaluated. In the current study, FA was performed with ImageJ program on panoramic radiographs of 48 patients diagnosed with PHPT. Fractal dimension (FD) values of the patients and 48 healthy subjects were compared. In addition, biochemical [parathyroid hormone (PTH), serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and vitamin D] parameters and FD values of both groups were analyzed with Mann-Whitney U-tests and Pearson correlation coefficient (P < .05). FD values of four different angular areas were significantly lower in the patient group than in the healthy group (P < .05). There was no statistically significant difference between the patient and control groups in the measurements between the apexes of the right and left premolar and molar teeth. The mean PTH, Ca, P, and vitamin D values of the patients with PHPT and control group were highly significant, and all the parameters of the patient group showed higher values than the control group except for the P values (P < .001). In the patient group and control group, there was no significant difference between mean ALP values (P = .48). No correlation was found between the two groups. Bone biopsy is the gold standard method for the diagnosis of bone structure changes in patients with PHPT. However, it is not used routinely because it is an invasive method. The FA method applied to panoramic radiographs may be used as a noninvasive, easy-to-apply method to reveal the changes in the trabecular structure of the jaw bones of the patients.

Reconstitution of the host holobiont in germ-free born male rats acutely increases bone growth and affects marrow cellular content.

Integration of microbiota in a host begins at birth and progresses during adolescence, forming a multidirectional system of physiological interactions. Here, we present an instantaneous effect of natural, bacterial gut colonization on the acceleration of longitudinal and radial bone growth in germ-free born, 7-wk-old male rats. Changes in bone mass and structure were analyzed after 10 days following the onset of colonization through cohousing with conventional rats and revealed unprecedented acceleration of bone accrual in cortical and trabecular compartments, increased bone tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in the tibia diaphysis. In addition, the number of small in size adipocytes increased, whereas the number of megakaryocytes decreased, in the bone marrow of conventionalized germ-free rats indicating that not only bone mass but also bone marrow environment is under control of gut microbiota signaling. The changes in bone status paralleled with a positive shift in microbiota composition toward short-chain fatty acids (SCFA)-producing microbes and a considerable increase in cecal SCFA concentrations, specifically butyrate. Furthermore, reconstitution of the host holobiont increased hepatic expression of IGF-1 and its circulating levels. Elevated serum levels of 25-hydroxy vitamin D and alkaline phosphatase pointed toward an active process of bone formation. The acute stimulatory effect on bone growth occurred independently of body mass increase. Overall, the presented model of conventionalized germ-free rats could be used to study microbiota-based therapeutics for combatting dysbiosis-related bone disorders.

Sonographic and Duplex Evaluation of Synovial activity in Wrist and Hand Joints in Rheumatoid Arthritis

Abstract Background Rheumatoid arthritis is a long-term autoimmune disease and inflammatory disorder. The damaging effect on cartilage, bone, ligaments, and tendons has raised the importance of the accurate diagnosis of structural damage, disease activity and severity assessment to enable therapeutic decisions and to evaluate disease outcome. US is non invasive, relatively cheap and widely accessible imaging tool that facilitates the detection of synovitis joint effusin and erosions more better than clinical, laboratory investigations alone and x-ray. Aim of the Work assess the role of of gray-scale and Doppler ultrasound early detection and characterization of synovitis and structural bone changes in wrist and hand joints in patients with Rheumatoid Arthritis by comparing qualitative and quantitative US parameters with clinical and laboratory indicators of disease activity. Patients and Methods A cross sectional study conducted onthirty five adult patients with RA . All the patients were diagnosed according to the 2010 ACR/European League . The patients were recruited from the Rheumatology and Rehabilitation Outpatient Clinic, Faculty of Medicine, Ain Shams Hospitals .The study was approved by the ethical committee, and consents were taken from all patients enrolled in the study. Patients assessed by history taking, Clinical examination, Laboratory investigations and US gray scale and US power Doppler was done for each patient. Results This study included 35 patients with established RA, 27 females (77.1%) and 8 males (22.9%). Ranged in age between 20-70 years with mean age [45.66±12.76],the mean CDAS28 was [4.62±1.37], ESR [44.93±20.79], CRP [15.92±9.03], 33 patients (94.3%) were found to have synovial thickening, 14 patient (40%) were found to have increased vascularity by PD, joint effusion was detected in 12 patient (34.3%) particularly in MCP joints, 13 (37.1%) had bone erosion and only 9 patients (25.7%) had Tenosynovitis, most of them were detected at the extensor compartment of the wrist joint.positive correlations found between the clinical disease activity indices, laboratory investigations, duration of illness and components of the US findings. Conclusion Ultrasound is non invasive, relatively cheap and widely accessible imaging tool that facilitates the detection of synovitis and erosions,, high resolution gray scale images combined with Doppler technique have made it possible to detect slow low volume blood flow, thus improving the outcome of the standard clinical assessment in Rheumatoid synovial inflammation.

Long-term use of glucocorticoid exacerbates bone lesions in postmenopausal women with rheumatoid arthritis

Glucocorticoid-induced osteoporosis is osteoporosis arising due to long-term use of glucocorticoids. Despite decades of intense research, the effects of long-term use of glucocorticoids in humans on bone cells and bone structural changes remain unclear. We performed post-mortem histomorphometric analysis of bone from two female patients with rheumatoid arthritis aged 64 and 85years. Our two patients had been treated with glucocorticoids for 19 and 14 years, respectively. In Case 1, all markers of cancellous bone volume were markedly decreased compared with the age-matched reference range. Connectivity of cancellous bone trabecula was absent. Only a few island bones were noted. There was prominent thinning of the cortical bone and extension of the bone marrow cavity into the cortical bone with prominent cortical porosis. Cortical nodes between the endocortical surface and the trabecula disappeared due to endocortical resorption. Stoppage of lamellar structure was observed because the bone resorption by osteoclasts surpassed bone formation by osteoblasts. Empty lacunae characterised by disappearance of osteocytes were visible. In Case 2, all volume markers of cancellous bone were decreased to the same extent as Case 1. However, cortical porosis was more prominent than Case 1. These two cases suggest that use of glucocorticoid therapy >10years can induce severe osteoporosis in elderly rheumatoid arthritis women with higher disease activity and that the disappearance of cancellous bone is the common characteristic. The 85-year-old woman was characterised by cortical porosis.

Torus Mandibularis in Patients Receiving Hemodialysis.

Reports on the prevalence of torus mandibularis among dialysis patients have been limited and inconclusive. A wide variety of oral manifestations has been found in patients with hyperparathyroidism. Furthermore, uremia-related changes in facial bone structures have been described in the literature. This prospective observational study examined 322 hemodialysis patients treated at the Chang Gung Memorial Hospital from 1 August to 31 December 2016. Two subgroups were identified: patients with torus mandibularis (n = 25) and those without (n = 297). Clinical oral examinations including inspection and palpation were employed. Our study found that most mandibular tori were symmetric (84.0%), nodular (96.0%), less than 2 cm in size (96.0%), and located in the premolar area (92.0%). Poor oral hygiene was observed among these patients, with 49.7% and 24.5% scoring 3 and 4, respectively, on the Quigley-Hein plaque index. More than half (55.0%) of patients lost their first molars. Multivariate logistic regression analysis revealed that blood phosphate level (odds ratio = 1.494, p = 0.029) and younger age (odds ratio = 0.954, p = 0.009) correlated significantly with torus mandibularis. The prevalence of torus mandibularis in patients receiving hemodialysis in this study was 7.8%. Younger age and a higher blood phosphate level were predictors for torus mandibularis in these patients.

Fractures in patients with chronic kidney disease

Abstract. Despite rapid progress in improving dialysis technology in recent years, the mortality of patients treated with renal replacement therapy remains quite high. Mineral and bone disease is omnipresent in patients with chronic kidney disease (CKD) and leads to a diverse range of clinical manifestations, including bone pain and fractures. Mineral bone disorders (MBD), as well as changes in bone structure, develop at the beginning of CKD. Osteoporosis can progress according to declining of the glomerular filtration rate and contribute to the deterioration of bone strength resulted in a high risk of fracture. In CKD patients, the most common are hip fractures, femur, humerus, compression fractures of the vertebrae and pelvic fractures. CKD-MBD is characterized by disorders of calcium, phosphate, parathyroid hormone and/or vitamin D metabolism, as well as, bone regeneration, mineralization, volume, linear growth and strength violation, calcification of blood vessels, or other soft tissues. Medications that correct systemic mineral metabolism can improve bone histology in patients with CKD. However, clinical and biochemical targets used in clinical practice remain controversial, resulting in an undermanagement of bone fragility. The clarifying of the appropriateness of medicines that act directly on the bone or affect the mineral and hormonal metabolism could be a promising strategy to prevent pathological fractures due to fragility among CKD patients.

CD14, A toll-like receptor co-factor, influences osteoclast differentiation and activity, but does not alter osteoblastic potential of bone-marrow preursors in mice

Purpose: Changes in subchondral bone structure occur in osteoarthritis (OA), and are visible by imaging as subchondral sclerosis on radiographs, and bone marrow lesions (BMLs) by MRI. These changes are the result of active bone remodeling that occurs in OA. BMLs in particular are correlated with pain in OA patients. We previously demonstrated that bone remodeling was significantly reduced after joint injury in mice deficient in CD14. CD14 enhances Toll-like receptor (TLR) mediated inflammation by acting as a co-receptor for multiple TLRs, increasing TLR sensitivity to damage associated molecular patterns (DAMPS) to activate proinflammatory signaling pathways. Soluble CD14, TLRs, and DAMPs (TLR ligands) are all elevated in OA patients, and sCD14 has been implicated as a biomarker of symptom and structural severity in OA. Increasing evidence suggestions CD14/TLR signaling influences bone remodeling as well, through activation of osteoclast precursor cells. Here, we investigate the potential mechanism by which CD14 influences bone remodeling through in vitro analysis of osteoclastogenic and osteoblastic potential and function. Methods: Bone marrow (BM) hematopoietic and mesenchymal precursors were isolated from long bones of 12-week-old male wild-type C57BL/6 (WT) and CD14-deficient (CD14-/-) mice. Briefly, BM was flushed from the femurs and tibia, and cells were cultured for 24 hours to separate non-adherent from adherent population. For osteoclastic differentiation, the non-adherent cells were seeded at a density of 26,000 cells per cm2 and were cultured in presence of monocyte/macrophage colony-stimulating factor (M-CSF; 35 ng/ml) and receptor activator of nuclear factor kβ ligand (RANKL; 100 ng/ml) for 9 days. Osteoblastic differentiation was accomplished by seeding the adherent BM cells at 30,000 cells per cm2 and culturing in the presence of 10 mM β-glycerophosphate ,50 μM ascorbic acid, and 100 nM Dexamethasone for up to 19 days. Osteoclasts were identified as multinucleated cells with positive TRAP staining. The resorptive ability of osteoclasts was assayed by quantifying resorption pits formed on bone slices. For osteoblast differentiation, Alizarin red was used to detect mineralized bone matrix. At the completion of each assay RNA was isolated from cultures and Real-time quantitative PCR analysis was performed to detect changes in mRNA levels of osteoclast (i.e. calcitonin receptor/CTR and cathepsin K/Ctsk) and osteoblast (i.e. osteopontin/OPN and osteocalcin/BLAP) differentiation markers. Results: Cells from CD14-/- mice demonstrated decreased percentages of TRAP positive cells and multi-nucleated cells (p value = 0.01; Fig. 1 A-D) and reduced Ctsk mRNA (p value = 0.03; Fig. 1 E&F), compared to WT controls. CD14-/- cells showed a 50% reduction in resorption pits and area compared to WT (Fig. 1 G&I). No significant differences were observed between strains in osteoblastic potential measured by mineralization and gene expression of osteoblastic markers (Fig. 2). Conclusions: CD14-/- BM precursor cells have reduced capacity to differentiate into functional osteoclasts, while osteoblastic potential is retained. This suggests that the reduced capacity of CD14-deficient osteoclastic cells may lead to the reduced bone remodeling in response to joint injury seen in the DMM model, by disrupting the balance between resorption and formation. Future experiments will determine the influence of DAMPs on osteoclast differentiation and activity, and the density of osteoclasts in SCB after DMM injury. These experiments will lead to a better understanding of the role of CD14 and TLR pathways on bone remodeling in response to joint injury and OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Characterization of structural changes in modern and archaeological burnt bone: Implications for differential preservation bias.

Structural and thermodynamic factors which may influence burnt bone survivorship in archaeological contexts have not been fully described. A highly controlled experimental reference collection of fresh, modern bone burned in temperature increments 100-1200˚C is presented here to document the changes to bone tissue relevant to preservation using Fourier transform infrared spectroscopy and X-ray diffraction. Specific parameters investigated here include the rate of organic loss, amount of bone mineral recrystallization, and average growth in bone mineral crystallite size. An archaeological faunal assemblage ca. 30,000 years ago from Tolbor-17 (Mongolia) is additionally considered to confirm visibility of changes seen in the modern reference sample and to relate structural changes to commonly used zooarchaeological scales of burning intensity. The timing of our results indicates that the loss of organic components in both modern and archaeological bone burnt to temperatures up to 700˚C are not accompanied by growth changes in the average crystallite size of bone mineral bioapatite, leaving the small and reactive bioapatite crystals of charred and carbonized bone exposed to diagenetic agents in depositional contexts. For bones burnt to temperatures of 700˚C and above, two major increases in average crystallite size are noted which effectively decrease the available surface area of bone mineral crystals, decreasing reactivity and offering greater thermodynamic stability despite the mechanical fragility of calcined bone. We discuss the archaeological implications of these observations within the context of Tolbor-17 and the challenges of identifying anthropogenic fire.

Structural changes in the trabecular bone of the mandibular condyle of growing patients with sagittal jaw discrepancy treated with the twin-block appliance.

The objective of this study was to evaluate the structural changes in the trabecular bone of the mandibular condyles in patients treated with the Twin-block functional orthopaedic appliance that act by promoting condylar growth and to compare the fractal dimension (FD) of condylar trabecular bone structure prior to treatment (T0) and after orthopaedic functional treatment (T1). This retrospective study included panoramic images of 112 individuals with a mean age of 11.04±1.30years in the study group (32 girls and 24 boys) and 11.6±.80years in the control group (29 girls and 27 boys). The standardized region of interest was selected as the right and left condylar areas close to the articulation surfaces from the twin-block (TB) group, which included patients who completed functional orthopaedic treatment and the control group, which included untreated individuals. FD values in the condylar region were analysed from the panoramic radiographs of both groups using a box-counting method with ImageJ software (version 1.52a, US National Institutes of Health). There was a significant decrease in the FD values of the right (-.038) and left (-.022) condylar region at T0 and T1 in the TB group. Between-group FD comparisons demonstrated that the TB group showed changes in the condylar region (right, P=.004; left, P=.022) compared to the control group. Functional orthopaedic forces caused a decrease in the trabecular structure of the condylar area examined.

Abstract 1392: Synergistic antitumor efficacy of radium-223 in combination with enzalutamide in the intratibial LNCaP prostate cancer xenograft model

Abstract Radium-223 dichloride (Ra-223) is a targeted alpha therapy that binds to newly formed bone matrix in bone metastases and induces DNA double-strand breaks in cancer cells, osteoblasts and osteoclasts. It is used for treating men with castration-resistant prostate cancer (CRPC) and bone metastases. Enzalutamide is a second-generation androgen receptor inhibitor also used for treating the same patient population, and the combination of Ra-223 and enzalutamide is currently being investigated in clinical trials. We evaluated the antitumor efficacy of Ra-223 and enzalutamide in the LNCaP intratibial model mimicking prostate cancer metastasized to bone. LNCaP prostate cancer cells were inoculated into the right tibia of male NOD.scid mice. The mice were randomized (n=9/group) based on serum PSA and treated with vehicle, Ra-223 (330 kBq/kg, i.v., Q4W x 2), enzalutamide (30 mg/kg, p.o., QD) or with a combination treatment of Ra-223 and enzalutamide, for 28 days. Serum PSA levels were analyzed at the end of the study and compared to the pre-treatment levels. Serum bone formation and resorption biomarkers, PINP and CTX, respectively, were measured during the study. Tumor-induced abnormal bone area, Ra-223 uptake and bone formation were determined by X-ray, gamma counter and histomorphometry, respectively. The healthy tibiae were evaluated by microCT. Combination treatment showed synergistic antitumor efficacy as observed by lower PSA levels when compared to the vehicle, Ra-223 or enzalutamide monotherapies (p=0.04, p=0.008 and p=0.002, respectively). A statistical interaction between Ra-223 and enzalutamide treatments was found (p=0.003), confirming the synergistic effect. In combination treatment, the serum PSA change relative to pre-treatment levels was 18% of the vehicle. Accordingly, a decreasing trend (p=0.08) in tumor-induced abnormal bone changes was associated with the combination treatment in the tumor-bearing tibiae (46% of the vehicle), whereas no changes in total bone structure were observed in the healthy tibiae. The serum levels of PINP and CTX were lowest in mice treated with the combination treatment. Compared to Ra-223 monotherapy, concurrent administration of enzalutamide with Ra-223 did not affect either Ra-223 uptake or bone formation rate in tumor-bearing or healthy tibiae, respectively. Compared to Ra-223 and enzalutamide monotherapies, the combination treatment demonstrated synergistic antitumor efficacy by decreasing PSA levels in the LNCaP intratibial model. Despite of prominent effects on tumor growth, the combination treatment was not observed to compromise bone health in the healthy tibiae. In conclusion, these preclinical results support the ongoing phase 3 trials PEACE III (NCT02194842) &amp; ESCALATE (NCT04237584) of this combination. Citation Format: Mari I. Suominen, Matias Knuuttila, Jukka Vääräniemi, Birgitta Sjöholm, Esa Alhoniemi, Dominik Mumberg, Sanna-Maria Käkönen, Arne Scholz. Synergistic antitumor efficacy of radium-223 in combination with enzalutamide in the intratibial LNCaP prostate cancer xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1392.

Interleukin (IL)-10 Is Important in the Maintenance of Trabecular and Cortical Bone and Protects Against Western Diet-Induced Disruption in Bone Remodeling in Mice

ObjectivesThe purpose of this study was to investigate if consumption of a western diet (WD) exacerbates the effects of loss of function of IL-10, an anti-inflammatory cytokine, on biomarkers of bone metabolism and microarchitecture. MethodsSix-week-old male B6.129P2-Il10tm1Cgn/J (IL-10 KO) and C57BL/6 mice (WT) were randomized to treatment in a 2 × 2 factorial with diet (AIN-93 control diet CD vs WD) and strain (IL-10 KO vs WT) as factors. Due to potential influence of high fat on intestinal Ca absorption, a WD diet with added Ca (1.2 g/kg) was used. After 12 wks, whole body dual-energy x-ray absorptiometry scans were performed to assess bone density and body composition, and micro-computed x-ray tomography was used to evaluate trabecular and cortical bone microarchitecture in the femur and lumbar vertebra. Serum biomarkers of bone formation, procollagen 1 intact N-terminal propeptide (P1NP), and resorption, c-terminal telopeptide of type I collagen (CTX-1) were assessed. ResultsBody weight, but not % body fat, was lower (P < 0.05) in IL-10 KO mice relative to WT controls. 12 weeks of WD increased (P < 0.05) body weight and % fat, but the response was not as great in the IL-10 KO mice. Bone mineral density and content were lower in IL-10 KO mice compared to WT, and the WD had no effect on these parameters. The IL-10 KO mice exhibited a decrease in trabecular bone volume, thickness, and number, and an increase in trabecular separation and structure model index compared to WT mice within the femur and vertebrae. The WD had no effect on these trabecular bone parameters. Cortical bone thickness and area were reduced (P < 0.05) and porosity increased in both the femur and vertebra of IL-10 KO mice relative to their WT counterparts. This strain effect was not altered by the WD. IL-10 KO mice exhibited a significantly lower serum PINP and higher CTX-1 compared to the WT mice. Despite the lack of structural changes in bone after 12 wks, the WD increased (P < 0.05) CTX-1 and tended to suppress P1NP (P = 0.051) in the IL-10 KO mice compared to WT. ConclusionsWe conclude that IL-10 plays an important role in bone metabolism and maintaining structural properties and in the absence of IL-10, WD negatively affects both osteoclast and osteoblast activity. Further studies are warranted to determine if structural changes occur with longer exposure to WD. Funding SourcesOklahoma Agricultural Experiment Station.

Gut Microbiota Accelerates Bone Growth and Marrow Adiposity of the Adolescent Gnotobiotic Rat

Skeletal growth and bone homeostasis are significant holobiome components strongly tied to the gut microbiota. We aimed to explore the requirement of gut microbiome for skeletal maturation in an adolescent organism. For our approach, we co-housed young (7-week-old) germ-free (GF) rats with conventional rats of the same age, sex (male), and strain (Sprague Dawley) for 10 days to naturally conventionalize GF (GFC) rats with the gut microbiota by coprophagy. Bone morphometry by micro-CT scanning and histological staining revealed accelerated longitudinal and radial bone growth in GFC rats when compared to GF rats. Changes in bone mass and structure for GFC rats encompassed an increase of bone accrual in cortical and trabecular compartments, greater tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in the tibia diaphysis. Analysis of bone marrow at the tibia midshaft depicted more adipocyte number, greater adipocyte density, and altered cell size distribution to favor small adipocytes, but reduced megakaryocytes, in GFC rats. Interestingly, putative effector genes responsible for bone mass accumulation were found to be comparable between GF and GFC rats, which shifted our focus onto systemic host and microbial regulatory factors. Assessment of serum markers indicated that the active bone formation could be due to elevated levels of 25-hydroxy vitamin D and alkaline phosphatase. Importantly, 16S ribosomal RNA gene sequencing demonstrated that the prominent bacterial colonizers were Clostridiaceae and Clostridium members, which are potent short chain fatty acid (SCFA) producers. 1H-NMR metabolomics in the cecal contents showed a dramatic increase of SCFA, specifically butyrate, following bacterial colonization. In relation with the literature, our observation of increased hepatic insulin-like growth factor-1 (IGF-1) expression and systemic IGF-1 levels suggest that butyrate promotes bone growth through the somatotropic axis. Collectively, our study demonstrates that gut microbiota can deliver signals to the skeleton for accelerating bone expansion and accumulating marrow fat.

Effects of anti-resorptive treatment on the material properties of individual canine trabeculae in cyclic tensile tests.

Osteoporosis is defined as a decrease of bone mass and strength, as well as an increase in fracture risk. It is conventionally treated with antiresorptive drugs, such as bisphosphonates (BPs) and selective estrogen receptor modulators (SERMs). Although both drug types successfully decrease the risk of bone fractures, their effect on bone mass and strength is different. For instance, BP treatment causes an increase of bone mass, stiffness and strength of whole bones, whereas SERM treatment causes only small (4%) increases of bone mass, but increased bone toughness. Such improved mechanical behavior of whole bones can be potentially related to the bone mass, bone structure or material changes. While bone mass and architecture have already been investigated previously, little is known about the mechanical behavior at the tissue/material level, especially of trabecular bone. As such, the goal of the work presented here was to fill this gap by performing cyclic tensile tests in a wet, close to physiologic environment of individual trabeculae retrieved from the vertebrae of beagle dogs treated with alendronate (a BP), raloxifene (a SERM) or without treatments. Identification of material properties was performed with a previously developed rheological model and of mechanical properties via fitting of envelope curves. Additionally, tissue mineral density (TMD) and microdamage formation were analyzed. Alendronate treatment resulted in a higher trabecular tissue stiffness and strength, associated with higher levels of TMD. In contrast, raloxifene treatment caused a higher trabecular toughness, pre-dominantly in the post-yield region. Microdamage formation during testing was not affected by either anti-resorptive treatment regimens. These findings highlight that the improved mechanical behavior of whole bones after anti-resorptive treatment is at least partly caused by improved material properties, with different mechanisms for alendronate and raloxifene. This study further shows the power of performing a mechanical characterization of trabecular bone at the level of individual trabeculae for better understanding of clinically relevant mechanical behavior of bone.

Skeletal microenvironment system utilising bovine bone scaffold co-cultured with human osteoblasts and osteoclast-like cells.

A three-dimensional ex vivo bone cell culture system mimicking the skeletal system is useful for bone tissue engineering and as drug discovery platforms. The present study aimed to establish a three-dimensional skeletal culture system using native bovine bone scaffolds and human bone cells. Bovine bone scaffolds were cultured with human foetal osteoblasts 1.19 and human peripheral blood mononuclear cells for 21 days under standard culture conditions. The following groups were established: Decalcified unseeded bone scaffold (DUBS) as baseline control, decalcified seeded bone scaffold (DSBS) to mimic osteoporosis condition and undecalcified seeded bone scaffold to mimic normal condition. The scaffold's porosity and cell attachment on the scaffolds were determined using scanning electron microscopy. Histological evaluation was used to examine changes in trabecular bone structure. Dual-energy X-ray absorptiometry analysis was performed to determine the bone mineral density (BMD) and bone mineral content (BMC) of the scaffolds. A compression test was performed to examine the total biomechanical strength of the scaffolds. The trabecular thickness and number increased, while the trabecular separationwas reduced slightly in DSBS than in DUBS (P>0.05). The BMD and BMC increased significantly (P<0.05), while the compressive strength only increased slightly in DSBS than in DUBS (P>0.05). In conclusion, the ex vivo skeletal microenvironment comprising native bovine bone scaffolds seeded with bone cells is structurally, functionally and mechanically comparable with natural bone. This system may be used as a platform to understand bone physiology and screen for potential drug candidates.

Axial Spondyloarthritis: Mimics and Pitfalls of Imaging Assessment

Axial spondyloarthritis (axSpA) is a chronic inflammatory disorder that predominantly involves the axial skeleton. Imaging findings of axSpA can be divided into active changes, which include bone marrow edema, synovitis, enthesitis, capsulitis, and intra-articular effusion, and structural changes, which include erosions, sclerosis, bone fatty infiltration, fat deposition in an erosion cavity, and bone bridging or ankylosis. The ability to distinguish between imaging lesions suggestive of axSpA and artifacts or lesions suggestive of other disorders is critical for the accurate diagnosis of axSpA. Diagnosis may be challenging, particularly in early-stage disease and magnetic resonance imaging (MRI) plays a key role in the detection of subtle or inflammatory changes. MRI also allows the detection of structural changes in the subchondral bone marrow that are not visible on conventional radiography and is of prognostic and monitoring value. However, bone structural changes are more accurately depicted using computed tomography. Conventional radiography, on the other hand, has limitations, but it is easily accessible and may provide insight on gross changes as well as rule out other pathological features of the axial skeleton. This review outlines the imaging evaluation of axSpA with a focus on imaging mimics and potential pitfalls when assessing the axial skeleton.

Cigarette smoke-associated inflammation impairs bone remodeling through NF\u03baB activation

BackgroundCigarette smoking constitutes a major lifestyle risk factor for osteoporosis and hip fracture. It is reported to impair the outcome of many clinical procedures, such as wound infection treatment and fracture healing. Importantly, although several studies have already demonstrated the negative correlation between cigarette consume and impaired bone homeostasis, there is still a poor understanding of how does smoking affect bone health, due to the lack of an adequately designed animal model. Our goal was to determine that cigarette smoke exposure impairs the dynamic bone remodeling process through induction of bone resorption and inhibition of bone formation.MethodsWe developed cigarette smoke exposure protocols exposing mice to environmental smoking for 10 days or 3 months to determine acute and chronic smoke exposure effects. We used these models, to demonstrate the effect of smoking exposure on the cellular and molecular changes of bone remodeling and correlate these early alterations with subsequent bone structure changes measured by microCT and pQCT. We examined the bone phenotype alterations in vivo and ex vivo in the acute and chronic smoke exposure mice by measuring bone mineral density and bone histomorphometry. Further, we measured osteoclast and osteoblast differentiation gene expression levels in each group. The function changes of osteoclast or osteoblast were evaluated.ResultsSmoke exposure caused a significant imbalance between bone resorption and bone formation. A 10-day exposure to cigarette smoke sufficiently and effectively induced osteoclast activity, leading to the inhibition of osteoblast differentiation, although it did not immediately alter bone structure as demonstrated in mice exposed to smoke for 3 months. Cigarette smoke exposure also induced DNA-binding activity of nuclear factor kappaB (NFκB) in osteoclasts, which subsequently gave rise to changes in bone remodeling-related gene expression.ConclusionsOur findings suggest that smoke exposure induces RANKL activation-mediated by NFκB, which could be a “smoke sensor” for bone remodeling.

The mitigation effect of boron on the occurrence of osteoporosis in ovariectomized rats

<p indent="0mm">In recent years, unhealthy lifestyles and diet habits have resulted in poor bone growth and development, as well as bone metabolism disorders in adolescents. At the same time, bone metabolism disorder represented by osteoporosis has become the second disease that threatens human health after cardiovascular disease. The bone metabolism disease is a persistent problem in the livestock husbandry and pet industry, which has caused the death and elimination of livestock and poultry and has brought huge economic losses. Therefore, bone metabolic diseases not only threaten human health, but also seriously affect the economic benefits of the pet industry and livestock husbandry. While people focus on the prevention of animal bone metabolism diseases, they mainly focus on various vitamins and major elements, but ignore the trace element “boron” with a wide range of uses. Boron is a non-metal element, and its unique physical and chemical properties make it widely involved in the metabolic regulation activities of human and animal bodies. It promotes the immune function, antioxidant capacity, mineral and hormone metabolism, growth and production performance of animals, especially in bone metabolism which is essential trace element. A large number of studies have shown that boron deficiency will not only lead to bone dysplasia and even deformity, but also lead to bone structural changes, and disorders in bone formation and bone repair. Appropriate boron supplementation has positive effects on bone development and bone maintenance of humans and animals. In this study, the ovariectomized (OVX) rats were selected to establish an osteoporosis model, and the effects of boron on osteoporosis were studied by boron supplementation in drinking water during 22 weeks. Through the microscopic observation of the femoral metaphysis tissue structure in different periods (the 9th and 22nd week after boron supplementation), boron could slow down but not completely prevent the occurrence of osteoporosis. For a long time after the rats’ ovaries were removed, the removal of the ovaries resulted in severe estrogen deficiency in rats. Although studies have shown that boron has an estrogen-like effect and could make up for the lack of estrogen, but not completely replace estrogen. Boron could inhibit the TRAP activity and reduce the bone resorption process, but the bone metabolism including bone resorption and bone formation of the OVX rat has also entered a steady state, ALP activity was still decreased and the osteogenesis effect was weakened. In addition, boron supplementation maintained the content of the serum Ca, P and Mg in the OVX rats, and those three elements mainly derived from the bone minerals of the skeletal system. Therefore, the rat body has been in a state of losing Ca, P, and Mg for a long time, and bone minerals loss will lead to osteoporosis if it goes on. The improvement of antioxidant capacity in OVX rats in the boron supplementation groups could slow down the damage of oxidative stress to osteoblasts and osteocytes, inhibit the differentiation and proliferation of osteoclasts, reduce the damage to the skeletal system, and delay the occurrence of osteoporosis. Therefore, boron could slow down but not completely prevent the occurrence of osteoporosis in OVX rats.

Trabecular subchondral bone analysis of the distal radius at ultra-high field (7t) MRI: comparison with 3T MRI and radiography

Purpose: Bone fractal signature analysis (FSA) is a tool assessing structural changes that may relate to clinical outcomes and function. Bone structural changes play a role in onset and progression of several musculoskeletal diseases, and FSA has been applied to different anatomic body regions. However, its applicability in a routine clinical environment has not been extensively explored. Our aim was to evaluate and compare bone texture analysis of the distal radius in patients and controls using radiography, 3 Tesla (T) and 7T magnetic resonance imaging (MRI).

Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs.

Type 2 diabetes (T2D) results in physiological and structural changes in bone, contributing to poor fracture healing. T2D compromises microvascular performance, which can negatively impact bone regeneration as angiogenesis is required for new bone formation. We examined the effects of bone morphogenetic protein-2 (BMP-2) administered locally at the time of femoral segmental bone defect (SBD) surgery, and its angiogenic impacts on endothelial cells (ECs) isolated from the ipsilateral or contralateral tibia in T2D mice. Male C57BL/6 mice were fed either a low-fat diet (LFD) or high-fat diet (HFD) starting at 8 weeks. After 12 weeks, the T2D phenotype in HFD mice was confirmed via glucose and insulin tolerance testing and echoMRI, and all mice underwent SBD surgery. Mice were treated with BMP-2 (5 µg) or saline at the time of surgery. Three weeks postsurgery, bone marrow ECs were isolated from ipsilateral and contralateral tibias, and proliferation, angiogenic potential, and gene expression of the cells was analyzed. BMP-2 treatment increased EC proliferation by two fold compared with saline in LFD contralateral tibia ECs, but no changes were seen in surgical tibia EC proliferation. BMP-2 treatment enhanced vessel-like structure formation in HFD mice whereas, the opposite was observed in LFD mice. Still, in BMP-2 treated LFD mice, ipsilateral tibia ECs increased expression of CD31, FLT-1, ANGPT1, and ANGPT2. These data suggest that the modulating effects of T2D and BMP-2 on the microenvironment of bone marrow ECs may differentially influence angiogenic properties at the fractured limb versus the contralateral limb.

Theaflavin-3,3'-Digallate Promotes the Formation of Osteoblasts Under Inflammatory Environment and Increases the Bone Mass of Ovariectomized Mice.

Postmenopausal osteoporosis is a disease of bone mass reduction and structural changes due to estrogen deficiency, which can eventually lead to increased pain and fracture risk. Chronic inflammatory microenvironment leading to the decreased activation of osteoblasts and inhibition of bone formation is an important pathological factor that leads to osteoporosis. Theaflavin-3,3′-digallate (TFDG) is an extract of black tea, which has potential anti-inflammatory and antiviral effects. In our study, we found that TFDG significantly increased the bone mass of ovariectomized (OVX) mice by micro-CT analysis. Compared with OVX mice, TFDG reduced the release of proinflammatory cytokines and increased the expression of osteogenic markers in vivo. In vitro experiments demonstrated that TFDG could promote the formation of osteoblasts in inflammatory environment and enhance their mineralization ability. In this process, TFDG activated MAPK, Wnt/β-Catenin and BMP/Smad signaling pathways inhibited by TNF-α, and then promoted the transcription of osteogenic related factors including Runx2 and Osterix, promoting the differentiation and maturation of osteoblasts eventually. In general, our study confirmed that TFDG was able to promote osteoblast differentiation under inflammatory environment, enhance its mineralization ability, and ultimately increase bone mass in ovariectomized mice. These results suggested that TFDG might have the potential to be a more effective treatment of postmenopausal osteoporosis.