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• Dual-energy CT (DECT) can image and quantify urate deposition and bone erosions. • Intensive urate-lowering with pegloticase led to rapid urate depletion on DECT. • Deposited urate depletion was fastest during pegloticase treatment. • With urate depletion, bone remodeling occurred within 1 year in most erosions. Monosodium-urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT). Pegloticase lowers serum urate (SU) in uncontrolled gout patients, with methotrexate (MTX) co-therapy recommended to increase SU-lowering response rate and decrease infusion reaction risk. The literature on serial DECT-imaging during pegloticase + MTX co-therapy is sparse, with only 2 prior cases of rapid MSU deposition depletion with subsequent bone-erosion remodeling reported from a small open-label trial. Here, we report DECT findings during pegloticase treatment in a larger number of patients from a randomized controlled trial to confirm bone-erosion remodeling that follows MSU depletion with pegloticase. The influence of length-of-therapy is also explored. Patients received pegloticase (8 mg every 2 weeks) + MTX (15 mg/week orally) or pegloticase + placebo (PBO) during the MIRROR RCT trial. A subset underwent DECT-imaging on Day1 (first pegloticase infusion) and at Weeks 14, 24, and 52. Patients with paired baseline-Week 52 images were included. Imaged regions with baseline MSU-crystal volume (V MSU) < 0.5 cm3 were excluded to minimize artifact contributions. V MSU and bone-erosion remodeling were assessed. Eight patients (6 MTX, 2 PBO) were included. Included patients had received 52 weeks (5 MTX), 42 weeks (1 PBO), and 6 weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU < 6 mg/dL on allopurinol (n = 2)/febuxostat (n = 1). At Week 52, V MSU had markedly decreased in both the pegloticase + MTX and pegloticase + PBO treatment groups, with faster depletion during pegloticase therapy. Bone-erosion remodeling was observed in 29/42 (69%) evaluated erosions: 29 (69%) size decrease, 4 (9.5%) recortication, 3 (7.1%) new bone formation. Rapid V MSU depletion during pegloticase therapy was observed with concomitant bone remodeling within 1 year. Following pegloticase discontinuation, V MSU reduction slowed or stopped even when SU was maintained < 6 mg/dL with oral ULT. NCT03994731. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. It is known that aucubin (AU) exerts anti-inflammatory activity, but its effects and mechanisms in RA are unclear. This study investigated the anti-inflammatory effects and mechanisms of AU in vivo and in vitro. Human fibroblast-like synoviocyte cells from patients with RA (HFLS-RA), RAW264.7 cells, and MC3T3-E1 cells were used to evaluate the effects of AU on migration, invasion, apoptosis, osteoclast differentiation and production. Immunofluorescence was used to observe nuclear translocation of nuclear factor (NF)- κ B, the double luciferase reporter gene method was used to observe NF- κ B-p65 activity in AU-treated MC3T3-E1 cells. RT-qPCR was used to measure expression of bone metabolism and inflammation-related genes, and western blot was used to measure bone metabolism and NF- κ B protein expression levels. Collagen-induced arthritis (CIA) rat model was used for pharmacodynamics study. Arthritis indexes were measured in the ankle and knee, histological staining and Micro-computed tomography were performed on the ankle joints. Also, inflammatory factor gene expression and the levels of NF- κ B-related proteins were detected as in vitro. AU effectively inhibited HFLS-RA cell migration and invasion, promoted apoptosis, and inhibited RAW264.7 cell differentiation into osteoclasts, as well as inhibited NF- κ B-p65 activity in MC3T3-E1 cells. Notably, AU significantly reduced the gene expression levels of three cell-related inflammatory factors and bone metabolism factors, effectively inhibited the expression of p-I κκα β , p-I κ B α , and p-p65 proteins. In vivo , AU relieved joint inflammation, reduced related inflammatory factors, and inhibited NF- κ B signaling. It could be used to treat RA-related synovial inflammation and bone destruction through the NF- κ B pathway. [ABSTRACT FROM AUTHOR]

To identify and synthesize the evidence for the use and measurement properties of musculoskeletal ultrasound in assessing structural joint damage in patients with rheumatoid arthritis (RA). A systematic literature search (SLR) of the PubMed, Embase and Cochrane Library was performed. Original articles were included published in English reporting on ultrasound of bone erosion, cartilage damage and the measurement properties of ultrasound according to the OMERACT filter 2.1. Of the 1.495 identified articles 149 were included in the final review, most of which reported on cross-sectional studies and used the OMERACT definitions for ultrasonographic pathology. Among these, bone erosions were assessed in 139 (93.3%), cartilage damage in 24 (16.1%), enthesophytes in 8 (5.4%), osteophytes in 15 (10.1%) and malalignment and ankylosis in a single (0.9%) study, respectively. Most studies (126/149, 84.6%) assessed the joints of the hands. The overwhelming majority of studies (127/149, 85.2%) assessed structural joint damage bilaterally. Validity, reliability and responsiveness were assessed in 21 (14.1%), 34 (22.8%) and 17 (11.4%) studies, respectively. While the results of this SLR suggest that ultrasound is a sensitive, reliable and feasible tool to detect damage in RA, they also highlight the need for further research and validation. Findings of this SLR will inform the next steps of the OMERACT Ultrasound Working Group in developing an ultrasound score for assessing structural joint damage in patients with RA. [ABSTRACT FROM AUTHOR]

Our recent study showed that Nitazoxanide (NTZ), an FDA-approved anti-parasitic drug, prevents ovariectomy-induced bone loss by inhibiting osteoclast activity. However, there have been no investigations to determine whether NTZ has preventive potential in other bone resorbing diseases, especially rheumatoid arthritis (RA). In this study, the primary RA fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) murine model were used to evaluate the effect of NTZ. The results showed that NTZ potently inhibited proliferation, migration and invasion capacity of RA-FLS in a dose dependent manner by restraining cell entry into S phases, without induction of cell apoptosis. NTZ obviously reduced spontaneous mRNA expression of IL-1β, IL-6 and RANKL, as well as TNF-α-induced transcription of the IL-1β, IL-6, and MMP9 genes. In terms of molecular mechanism, NTZ significantly inhibited the basal or TNF-α-induced activation of JAK2/STAT3 (T705) and NF-κB pathway, but not MAPK and STAT3 (S727) phosphorylation. Moreover, NTZ ameliorated synovial inflammation and bone erosion in CIA mice through reducing the production of inflammatory mediators and osteoclast formation, respectively. Collectively, our findings indicate that NTZ exhibits anti-inflammatory and anti-erosive effects both ex vivo and in vivo, which provides promising evidence for the therapeutic application of NTZ as a novel therapeutic agent for RA. [Display omitted] • NTZ dose-dependently inhibits the proliferation, migration and invasion of RA-FLS. • NTZ prevents cell cycle progression and inflammatory cytokines mRNA expression. • NTZ inhibits basal or TNF-α-induced activation of JAK2/STAT3 and NF-κB pathways. • NTZ ameliorates synovial inflammation and bone erosion in CIA mice. [ABSTRACT FROM AUTHOR]

There is no standard to determine the most appropriate method of operation for the treatment of acute septic arthritis of the shoulder joint. We retrospectively reviewed 57 patients who underwent arthroscopic or open débridement for acute shoulder infection between 2001 and 2015. Arthroscopic débridement was performed in 27 patients, and open débridement in 30 patients. According to the presence of bone erosion and/or marginal erosion of cartilage of the humeral head on plain radiographs and magnetic resonance imaging (MRI) images, the cases were classified into 3 groups (group 1, n = 23, without erosions in x-ray and MRI; group 2, n = 21, erosions seen in MRI but not in x-ray; and group 3, n = 13, with erosions seen in both x-ray and MRI). The arthroscopic group had a reinfection rate of 55.6% (15/27), and the open group had a reinfection rate of 16.7% (5/30). The reinfection rates in the arthroscopic and the open groups were 10% (1/10) and 15.4% (2/13) in group 1; 75% (9/12) and 11.1% (1/9) in group 2; and 100% (5/5) and 25% (2/8) in group 3, respectively. At the last follow-up, the mean University of California at Los Angeles score and the average time until normalization of white blood cell, erythrocyte sedimentation rate, and C-reactive protein in the open group showed superior results in the open group (all P <.05). When preoperative MRI showed bone and/or cartilage erosion of humeral head, the reinfection rate after arthroscopic débridement was above 75%. Therefore, if preoperative MRI showed erosions, open débridement is more likely to be appropriate than arthroscopic débridement. [ABSTRACT FROM AUTHOR]

Idiopathic orbital inflammation developed in the right orbit of a woman in her mid-thirties, causing tearing, photophobia, diplopia, altered depth perception, proptosis, and pain on eye movements. Computed tomography disclosed a mass involving the intraconal and extraconal nasal right orbit, extending to the orbital apex with anterior displacement of the globe, effacement of the medial rectus muscle, portions of the fat plane, and the superior oblique muscle, and bone destruction with extension of the mass through the orbital floor into the superior maxillary sinus and through the lamina papyracea into the ethmoid sinus. Orbital biopsy disclosed dense fibrous connective tissue with numerous lymphocytes and macrophages. Immunohistochemical stains supported a diagnosis of idiopathic inflammatory pseudotumor involving the orbit and sinus mucosa. Treatment with a prednisone taper and a retrobulbar injection of triamcinolone acetonide have relieved her symptoms and diminished her proptosis. This patient highlights the rare potential of idiopathic orbital inflammation to erode though bone into adjacent cranial structures. [ABSTRACT FROM AUTHOR]

Background Atlantoaxial instability owing to bone erosions in a patient with ankylosing spondylitis (AS) is rare. We describe the radiographic characteristics, pathology, and treatment of a patient with this rare clinical manifestation and review the literature. Case Description A 36-year-old man with an 8-year history of AS presented with progressive neck pain, low back pain, hand numbness, and limited mobility of the neck. Cervical radiography showed anterior atlantoaxial subluxation with bone erosions at the odontoid process and a mass lateral to the atlas and edge of vertebrae. AS was diagnosed according to the modified New York criteria, and the patient underwent a posterior C0-C6 occipitocervical arthrodesis surgery and C3-C6 laminectomy to reconstruct atlantoaxial stability and relieve cervical compression. The symptoms of neck pain and hand numbness improved at the 1-year follow-up, and the patient completely resumed normal activities. Imaging showed realignment of C1-2 with complete decompression of the spinal cord and fusion of the atlantooccipital joint. The internal fixation has remained stable, and progressive bone erosion changes were not found after surgery. Conclusions Extensive cervical erosions with spontaneous atlantoaxial subluxation in AS is extremely rare. The erosive change of atlantoaxial bone may be an early feature of AS. Cervical spine radiographs are essential for patients with AS who present with neck pain. Complete decompression and internal fixation are necessary to prevent serious neurologic morbidity from spinal cord injury in such patients. [ABSTRACT FROM AUTHOR]

An elastofibroma is a rare, benign, slow-growing, progressive soft tissue neoplasm with distinct histopathological features consisting of collagen and coarse elastic fibers. When it occurs, it has a propensity for the subscapular region in elderly female patients. It can occur less commonly at other anatomical sites, and its exact etiology is unclear. The incidence of elastofibroma, especially in the foot, has been sporadically reported; however, the presentation of elastofibroma in the rearfoot has not been previously described in the literature. We present the first report of a 79-year-old female presenting with plantar heel pain secondary to an elastofibroma found at the insertion of the plantar fascia into the calcaneal tuberosity. The patient underwent surgical excision, and pathological analysis revealed the diagnosis of elastofibroma. We discuss the peculiar manifestation of elastofibroma in this case, the pathological diagnosis, and a review of the literature. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The current study aimed to target the delivery of p-coumaric acid (CA), a dietary polyphenol to the synovial macrophages of AIA rats via mannose incorporated liposomal delivery system (ML) with reference to osteoclastogenesis and bone resorption. In vivo imaging and in vitro drug release study indicated the efficiency of mannosylated liposomes to localize at the site of inflammation and increased sustain drug release respectively. Morphological assessment of isolated synovial macrophages with respect to CD86 (synovial macrophages) and CD51 (pre-/osteoclast) indicated that p-coumaric acid encapsulated mannosylated liposomes (ML-CA) inhibited the osteoclasts differentiation. ML-CA treatment inhibited the TRAP staining, downregulated the expression of MMP-9 and NFATc1 and inflammatory cytokines. The ex-vivo study specified the ability of CA to induce the OPG production in bone marrow stromal cell triggered macrophage-osteoclasts differentiation and to preserve the calcium content. Taken together, our results demonstrated that ML-CA could intervene in the osteoclast formation. [ABSTRACT FROM AUTHOR]

Background Spinal epidural hematoma (SEH) is a potentially devastating problem that requires rapid diagnosis and surgical intervention. A chronic course is rarely seen following SEH, and the clinical characteristics are quite different from acute cases. The epidemiology, clinical history, and radiologic findings of chronic SEH (CSEH) are not well understood, although the detection rate has increased with the widespread use of magnetic resonance imaging. The purpose of this article was to report 4 cases of surgically confirmed CSEH and clarify the radiologic features and clinical scenarios by reviewing all published cases of CSEH. Case Description All 4 patients presented with gradually worsening radicular pain in the lower extremities. Patients' mean age was 69.5 years (range, 55–85 years). Magnetic resonance imaging revealed an epidural mass in the lower lumbar spine that was heterogeneously enhanced after gadolinium administration. The rim of the mass was low intensity on T2*-weighted images. Local erosions of the adjacent cortical bone were seen with computed tomography in all cases. All patients' postoperative courses were satisfactory with complete disappearance of radicular symptoms. Conclusions CSEH is a rare disease, and it is difficult to diagnose preoperatively on the basis of diagnostic imaging. The incidence of a low-intensity rim on T2*-weighted images and bone erosions on computed tomography may help differentiate rare CSEH from other lumbar degenerative diseases and epidural space-occupying masses. Highlights • The clinical features of CSEH may be similar to those of spinal epidural tumor or lumbar spinal stenosis. • CSEH should be differentiated from facet cyst with intracystal hematoma, epidural cavernous hemangioma, and so on. • The incidence of a low-intensity rim on T2*-weighted images and bone erosions on CT may help differentiate rare CSEH. [ABSTRACT FROM AUTHOR]

Objective The comparison between different techniques to quantify the 3-dimensional size of inflammatory bone erosions in rheumatoid arthritis(RA) patients. Methods Anti-cyclic citrullinated peptide antibody(ACPA) positive RA patients received high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the metacarpophalangeal joints (MCP). Erosions were measured by three different segmentation techniques: (1) manual method with calculation by half-ellipsoid formula, (2) semi-automated modified Evaluation Script for Erosions (mESE), and (3) semi-automated Medical Image Analysis Framework (MIAF) software. Bland & Altman plots were used to describe agreement between methods. Furthermore, shape of erosions was classified as regular or irregular and then compared to the sphericity obtained by MIAF. Results A total of 76 erosions from 65 RA patients (46 females/19 males), median age 57 years, median disease duration 6.1 years and median disease activity score 28 of 2.8 units were analyzed. While mESE and MIAF showed good agreement in the measurement of erosion size, the manual method with calculation by half-ellipsoid formula underestimated erosions size, particularly with larger erosions. Accurate segmentation is particularly important in larger erosions, which are irregularly shaped. In all three segmentation techniques irregular erosions were larger in size than regular erosions (MIAF: 19.7 vs. 3.4 mm 3 ; mESE: 15.5 vs. 2.3 mm 3 ; manual = 7.2 vs. 1.52 mm 3 ; all p < 0.001). In accordance, sphericity of erosions measured by MIAF significantly decreased with their size ( p < 0.001). Conclusion MIAF and mESE allow segmentation of inflammatory bone erosions in RA patients with excellent inter reader reliability. They allow calculating erosion volume independent of erosion shape and therefore provide an attractive tool to quantify structural damage in individual joints of RA patients. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is a chronic progressive autoimmune disorder, characterised by destruction of cartilage and under line bones. Though exact etiology of rheumatoid arthritis (RA) remains unknown. It is believed that alteration in control of cellular or molecular responses is involved in the chronic inflammation. Earlier in RA patients it was observed the circulating RA specific biomarkers and immunoglobulin deposits in the synovial joints. Zinc Oxide Nanoparticles (ZnO NPs) is used as an anti-inflammatory and anticancer agent, however there is nil/very less scientific data shows the anti-arthritic activity of green synthesis ZnO nanoparticles (Ocimum sanctum water extract in-situ synthesis of ZnO NPs having active compound Caffeic acid and Rosmerinic acid). Hence, the present activity was planned to assess the anti-arthritic activity of ZnO NPs in CIA rats. Arthritis in rats were induced by subcutaneous injection of collagen type II (CII) (200 µl) at the base of tail on day 0 followed by booster dose on day 14. ZnO NPs were given (2 mg/kg b.wt./day) orally for 20 days. At the end of the study serum, joint homogenate was used to assess the level of biomarkers (RF, a-CCP, a-CII and CRP) and inflammatory mediators. In addition, m-RNA expression of various genes such as Nuclear factor-kB (NF-kB), inflammatory mediators like tumour necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) etc. were assayed in joint tissue. Finally all these biochemical and molecular results were confirmed by microscopic study of joint tissue. ZnO NPs, treated rats showed decrease in inflammation and clinical severity. This was related with decrease in the level of biomarkers (like RF, a-CCP and CRP), inflammatory mediators (TNF-α, COX-2) and activity of transcription factor NF-kB. All these findings were positively correlated with microscopic analysis of joint tissue that showed reduced inflammation and bone erosion in treated group. This study validates the anti-arthritic activity of ZnO NPs as it mitigates the arthritis related symptoms in CIA rats. ● This is first time we have reported the anti-arthritic effect of Zinc Oxide Nanoparticles (ZnO NPs) through inhibition of arthritic biomarkers. ● In our study we found that ZnO NPs preserved the arthritic severity in CIA rats not only through inhibition of permeation of inflammatory cell, also through inhibition of NF-kB. ● These results were finally confirmed by microscopic analysis of joint tissue which shows that ZnO NPs suppress the cartilage destruction and inflammation. ● These finding may become beneficial, to develop a new therapeutic strategy in the treatment of RA. [ABSTRACT FROM AUTHOR]

Bone erosion is a central feature of rheumatoid arthritis (RA) that is characterized by the infiltration of the synovial lining by osteoclasts and lymphocytes. In the present study, swertiamarin a major secoiridoid glycoside was evaluated for anti-osteoclastogenic property to prevent bone erosion in Freund's complete adjuvant (FCA) induced in-vivo model, in-vitro osteoblast and osteoclasts as well as in co-culture system and in-silico molecular docking analysis. The swertiamarin treatment decreased the expression of TRAP, RANKL, and RANK levels and increased the levels of OPG levels significantly in both in vitro and in vivo models. In in vitro , the compound treatment significantly increased the cell proliferation and ALP levels in osteoblast cells; the high proliferation (153.8600 ± 5.23%) and ALP release (165.6033 ± 4.13%) were observed at 50 μg/ml concentration of swertiamarin treatment. At the same time the treatment decreased the TRAP positive cells in osteoclast cells; the high reductions of TRAP positive cells (39.32 ± 3.19%) were observed at 50 μg/ml of swertiamarin treatment. The treatment modulated the levels of pro-inflammatory cytokines, MMPs and NF-κB levels in osteoblast and osteoclast co-culture system. In in silico analysis swertiamarin had affinity towards the proteins RANK, RANKL and OPG residues with low binding energy − 4.5, − 3.92 and − 5.77 kcal/mol respectively. Thus, the results of this study revealed the anti-osteoclastogenic activity of swertiamarin on the prevention of bone destruction. [ABSTRACT FROM AUTHOR]

Articular ultrasound of 6500 joint recesses was performed for the purpose of identifying which joint had the highest measurements among small-sized (SSJ), medium-sized (MSJ) and large-sized (LSJ) joints. Quantitative measurements of synovial hypertrophy (QSR) and semiquantitative measurements of synovial hypertrophy (SSH), power Doppler (SPD) and bone erosion (SBE) (score: 0-3) were made. Higher measurements (p < 0.01) of QSR were obtained in the second metatarsophalangeal joint (MTP), talonavicular joint, and hip. The highest SSH scores (2/3) were obtained in the second MTP, talonavicular joint, hip and knee; the highest SPD scores (1/2/3) in the first MTP, second MTP, dorsal second metacarpophalangeal (MCP) and radiocarpal recesses; and the highest SBE scores (2/3) in the radiocarpal, ulnocarpal and posterior recesses of the glenohumeral joint. In conclusion, higher measurements of synovial hypertrophy were found in the first and second MTPs (SSJ), talonavicular recess (MSJ) and hip (LSJ). Synovial blood flow was frequent in the first MTP and radiocarpal recess. Bone erosion stood out only in the glenohumeral joint. [ABSTRACT FROM AUTHOR]

Toll like receptors (TLR)s have a central role in regulating innate immunity and in the last decade studies have begun to reveal their significance in potentiating autoimmune diseases such as rheumatoid arthritis (RA). Earlier investigations have highlighted the importance of TLR2 and TLR4 function in RA pathogenesis. In this review, we discuss the newer data that indicate roles for TLR5 and TLR7 in RA and its preclinical models. We evaluate the pathogenicity of TLRs in RA myeloid cells, synovial tissue fibroblasts, T cells, osteoclast progenitor cells and endothelial cells. These observations establish that ligation of TLRs can transform RA myeloid cells into M1 macrophages and that the inflammatory factors secreted from M1 and RA synovial tissue fibroblasts participate in TH-17 cell development. From the investigations conducted in RA preclinical models, we conclude that TLR-mediated inflammation can result in osteoclastic bone erosion by interconnecting the myeloid and TH-17 cell response to joint vascularization. In light of emerging unique aspects of TLR function, we summarize the novel approaches that are being tested to impair TLR activation in RA patients. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a significant issue, particularly in bone health problems, because it can prolong diseases like secondary osteoporosis. Subsequently, the anchor of drug therapy for RA is methotrexate (MTX), which also has the potential to reduce the risk of secondary osteoporosis. This study aims to examine the effect of MTX on calcium levels, an important parameter for monitoring bone health and the risk of secondary osteoporosis in patients with RA. A retrospective study was carried out by collecting data from the medical records of patients, which included demographic and patient characteristics, treatment data (drug and dosage), duration of treatment, and calcium levels. All patients were diagnosed with RA and fell within the age range of 18 to 59 years. Additionally, the effectiveness of MTX therapy was compared with other treatments, categorizing patient data accordingly. Statistical analyses, such as χ2 and ordinal regression, using IBM-SPSS Statistics version 25 (IBM-SPSS Inc, Armonk, New York) were used to establish associations between MTX treatment and calcium levels, reporting odds ratio and 95% CI values. The data consisted of 123 patients with RA, comprising 99 who had a history of MTX use for more than 6 months and 24 who either did not use MTX or used it for <6 months. The majority of patients were women and their ages ranged between 40 and 59 years. MTX monotherapy was the most used with a dose range of 7.5 to 15 mg. Furthermore, this study observed that patients treated with MTX between 7.5 and 15 mg have lower serum calcium levels than those who received 17.5 to 25 mg (P = 0.022; odds ratio = 5.663; 95% CI, 0.251–3.218). Most patients with RA using MTX maintained normal calcium levels. No significant differences were observed between single MTX therapy and combination therapy. Although further investigation is needed, this study showed the potential properties of MTX in maintaining patients' serum calcium levels, which may help to reduce the risk of secondary osteoporosis in patients with RA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic and systemic autoimmune inflammatory disease. Typical pathological findings of RA include persistent synovitis and bone degradation in the peripheral joints. Equol, a metabolite of the major soybean isoflavone daidzein, shows superior bioactivity than other isoflavones. We investigated the effects of equol administration on inflammatory response and bone erosion in mice with collagen-induced arthritis (CIA). The severity of arthritis symptoms was significantly low in the equol-administered CIA mice. In addition, equol administration improved the CIA-induced bone mineral density decline. In the inflamed area of CIA mice, equol administration suppressed the expression of interleukin-6 and its receptor. Furthermore, equol reduced the expression of genes associated with bone formation inhibition, osteoclast and immature osteoblast specificity and cartilage destruction. These results suggest that equol suppresses RA development and RA-induced bone erosion by regulating inflammation and bone metabolism. [ABSTRACT FROM AUTHOR]

To determine ultrasound measurements indicative of abnormalities in small, medium and large joints, we conducted a cross-sectional study comparing 60 patients with rheumatoid arthritis (RA) and 78 healthy volunteers. A MyLab 60 ultrasound machine (Esaote) and a linear multifrequency probe were used. Quantitative measurements of synovial recesses and semiquantitative measurements of synovial hyperplasia, power Doppler and bone erosion (scores = 0–3) were performed. The cutoff values for synovial recesses indicating RA (receiver operating characteristic curve, area under the curve >0.800) were found to be (radiocarpal) 3.78 mm and (ulnocarpal) 3.07 mm. Those measurements with the greatest chance of indicating RA (logistic regression analysis expressed as odds ratios [ORs]) were ( p < 0.001) measurements of synovial hyperplasia (ulnocarpal, OR = 100, and radiocarpal, OR = 70); synovial power Doppler (radiocarpal, OR = 66); synovial bone erosion (radiocarpal, OR = 324); fifth metatarsophalangeal joint (OR = 100); and second metacarpophalangeal joint (OR = 92). We concluded that for both quantitative and semiquantitative ultrasound measurements, radiocarpal abnormalities increase the chance of detecting RA. [ABSTRACT FROM AUTHOR]

The term osteoimmunology describes an interdisciplinary research field that links the investigation of osteology (bone cells) with immunology. The crosstalk between innate and adaptive immune cells and cells involved in bone remodeling, mainly bone-resorbing osteoclasts and bone-forming osteoblasts, becomes particularly obvious in the inflammatory autoimmune disease rheumatoid arthritis (RA). Besides striking inflammation of the joints, RA causes bone loss, leading to joint damage and disabilities as well as generalized osteoporosis. Mechanistically, RA-associated immune cells (macrophages, T cells, B cells etc.) produce high levels of pro-inflammatory cytokines, receptor activator of nuclear factor κB ligand (RANKL) and autoantibodies that promote bone degradation and at the same time counteract new bone formation. Today, antirheumatic therapy effectively ceases joint inflammation and arrests bone erosion. However, the repair of established bone lesions still presents a challenging task and requires improved treatment options. In this review, we outline the knowledge gained over the past years about the immunopathogenesis of RA and the impact of a dysregulated immune system on bone metabolism. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cervical spine lacunae linked to vertebral artery tortuosities are described. [•] This case is specific because of its bilateral and multilevel lesions. [•] It follows a cervical sprain pattern linked to spinal instability by loss of bone. [•] Its dual interest lies with its comprehensive pathological manifestations and their biomechanical consequence. [Copyright &y& Elsevier]

Abstract: Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Transforming growth factor-β1 (TGF-β1) may be a promising candidate gene for susceptibility and severity in RA. We aimed to determine whether TGF-β1 polymorphism is associated with susceptibility to RA and progression of joint destruction, as well as to identify the interaction between TGF-β1 polymorphism and biochemical risk factor. Methods: A total of 160 RA patients and 168 healthy unrelated controls were tested for the TGF-β1 (869C/T) polymorphism using polymerase chain reaction. Results: The TGF-β1 T allele was associated with susceptibility to RA. Within the RA group, TGF-β1 T allele carriers had a significant increased risk to develop osteoporosis (OR=4.4, 95% CI=-2. 4–8.1, P<0.001), as well as more likely to develop bone erosion (OR=1.7, 95% CI=0. 99–2.7, P=0. 034). Better prediction was achieved when the TGF-β1 TT genotype was used in combination with either elevated, rheumatoid factor (RF) or C-reactive protein (CRP) (OR=6.8, 3.7 respectively). Also, they increased the risk to develop bone erosion in patients with rheumatoid arthritis (OR=3.3, 9.8, P=0.017, 0.001 respectively). Conclusion: Our results suggest that TGF-β1 TT genotype may determine the development of osteoporosis and bone erosion in RA. Also, our results points to a synergism between TGF-β1 TT genotype and elevated serum RF or elevated CRP that lead to the development of osteoporosis and bone erosion in patients with rheumatoid arthritis. [Copyright &y& Elsevier]

Abstract: Bone erosion and skull base invasion are often suggestive of a malignant mass in paranasal and nasal cavities. Nevertheless, forms of chronic rhinosinusitis, such as allergic fungal rhinosinusitis (AFRS), could mimic malignant features. Here, we report AFRS patient with orbital, anterior cranial fossa, Turkish saddle and clivus erosion. A 48-year-old Caucasian female with history of drug-resistant headache, nasal obstruction and anosmia was referred to our institution. Imaging showed hyperdense featureless tissue with signs of medial orbital wall, cribiform lamina and clivus erosions and encasement of right internal carotid artery. Massive amounts of thick and grayish mucoid material were evacuated during surgery. In case of bony erosion, malignancy should always be excluded. Often the correct diagnosis will be obtained only by operative specimens. AFRS could usually be managed endoscopically. Appropriate medical management of the AFRS should be administered in order to prevent relapses. [Copyright &y& Elsevier]

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Abstract: The objective of this study was to determine the effect of systemic delivery of prednisolone phosphate (PLP) encapsulated within long circulating ‘stealth’ liposomes on bone erosion and osteoclast activity during experimental antigen-induced arthritis (AIA). Liposomal PLP strongly suppressed knee joint swelling, synovial infiltrate and bone erosion in antigen-induced arthritis. The number of active osteoclasts was not only suppressed in bone lesions near inflamed synovium, but also within the trabecular bone of the tibia, suggesting a systemic suppression of osteoclast activation. Furthermore, liposomal PLP directly blocked osteoclast differentiation and bone resorption in vitro while it also suppressed expression of osteoclast differentiation factors M-CSF and RANKL in the synovium. Targeting studies showed that liposomes are most efficiently phagocytosed by macrophages and early precursors of osteoclasts in the bone marrow rather than by mature osteoclasts, indicating a possible inhibition of osteoclast differentiation from an early stage. Conclusion: Liposomal glucocorticoid delivery rather than free PLP offers a more efficacious way to inhibit both inflammation and bone erosion in rheumatoid arthritis. [Copyright &y& Elsevier]

Quantitative measures of rheumatoid arthritis (RA) disease progression can provide valuable tools for evaluation of new treatments during clinical trials. In this study, a novel multispectral (MS) MRI analysis method is presented to quantify changes in bone lesion volume (ΔBLV) in the hands of RA patients. Image registration and MS analysis were employed to identify MS tissue class transitions between two serial MRI exams. ΔBLV was determined from MS class transitions between two time points. The following three classifiers were investigated: (a) multivariate Gaussian (MVG), (b) k-nearest neighbor (k-NN), and (c) K-means (KM). Unlike supervised classifiers (MVG, k-NN), KM, an unsupervised classifier, does not require labeled training data, resulting in potentially greater clinical utility. All MS estimates of ΔBLV were linearly correlated (rp) with manual estimates. KM and k-NN estimates also exhibited a significant rank-order correlation (rs) with manual estimates. For KM, rp = 0.94 p < 0.0001, rs = 0.76 p = 0.002; for k-NN, rp = 0.86 p = 0.0001, rs = 0.69 p = 0.009; and for MVG, rp = 0.84 p = 0.0003, rs = 0.49 p = 0.09. Temporal classification rates were as follows: for KM, 90.1%; for MVG, 89.5%; and for k-NN, 86.7%. KM matched the performance of k-NN, offering strong potential for use in multicenter clinical trials. This study demonstrates that MS tissue class transitions provide a quantitative measure of ΔBLV. [Copyright &y& Elsevier]

Accumulating studies have indicated that reactive oxygen species (ROS) may be implicated into the destructive pathological events of rheumatoid arthritis (RA). As an effective antioxidant, artesunate (ARS) was reported to exert antiarthritic effects. However, whether ARS attenuates the bone erosion during RA progression by regulating ROS production remains to be defined. To address this problem, the inhibitive effects of ARS on osteoclastogenesis were observed in vitro. Mechanically, ARS significantly inhibited the NFATc1 signaling accompanied by markedly suppressing ROS production, which was abnormally enhanced during the pathological process of bone erosion. In addition, ARS may function as a potent ROS scavenger and significantly elevate the expression of HO-1 and NQO1 by activating Nrf2. Moreover, p62 accumulation induced by ARS was responsible for the activation of Nrf2, while the knockdown of p62 in osteoclast precursor cells diminished the suppressive effect of ARS on ROS production during osteoclastogenesis. Consistently, we also demonstrated that ARS effectively suppressed ROS production, leading to the inhibition of arthritic bone destruction by activating antioxidant enzyme and Nrf2/p62 signaling in the knee and ankle tissues of CIA rats. Collectively, our data offer the convincing evidence that ARS may inhibit osteoclastogenesis and ameliorate arthritic bone erosion through suppressing the generation of ROS via activating the p62/Nrf2 signaling. [Display omitted] • ARS may attenuate bone erosion of rheumatoid arthritis by blocking ROS. • ARS may inhibit ROS production via facilitating p62 accumulation-induced Nrf2 activation. • p62 may serve as a promising therapeutic target of ARS to inhibit bone destruction in RA. • ARS may be a promising antioxidative/antiarthritic candidate drug for the treatment of RA in the future. [ABSTRACT FROM AUTHOR]

Objectives: To analyse the performance of ultrasonography (US) to detect bone erosion progression at the patient level and at the joint level by the US score for erosions (USSe) in early-stage and late-stage rheumatoid arthritis (RA) over a 2-year follow-up.Methods: Clinical and demographic information was recorded at baseline, and hands and feet RX were scored according to the Sharp erosion score. USSe was performed at baseline and over 2 years of follow-up on six bilateral joints (MCP2, 3, 5; MTP2, 3, 5). Inter-examiner reproducibility was performed on 14 patients, and the smallest detectable change (SDC) was calculated. US progression was defined as a change in USSe > SDC.Results: 71 patients were included: 22 (31.0 %) early RA, and 49 (69.0 %) late RA. The intra-class correlation coefficient values of the USSe for intra- and inter-examiner studies were 0.96 (CI95: 0.93-0.98), and 0.92 (CI95: 0.75-0.97), respectively. On US, erosions prevailed at baseline in MTP5 joints followed by MCP2 and MCP5 joints. With an SDC calculated at 2.3, 28 patients (39.4 %) were classified as progressors, 30 (42.3 %) were stable, and 13 (18.3 %) were regressors during the follow-up. At the joint level, erosion progression was significant on the MCP2 and MTP5 joints in early RA (p < 0.01) and on the MCP5 and MTP5 joints for all RA (p < 0.05).Conclusions: US is a highly reproducible method that is able to detect erosion progression at the patient level for both early and late RA and at the joint level (MCP2 and MTP5) for only early RA. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We report on a patient who presented with complete ophthalmoplegia as a first symptom of fatal invasive aspergillosis. Case report: We present the clinical course of an immunocompromised 68-year-old man with unclear painless loss of vision, ptosis and ophthalmoplegia of the right eye lasting for 10 days which was referred from an ophthalmological outpatient clinic. He had a history of kidney transplantation after renal failure, diabetes mellitus II, and coronary heart disease. He was on immunsuppressive therapy with tacrolimus, mycophenolate and prednisolone since renal transplantation. The initial cranial magnetic resonance imaging (MRI) was unremarkable. The additional thin section computed tomography (CT) of the paranasal sinuses was suspicious for bone erosion of the superior wall of the right sphenoidal sinus. Initial laboratory testing and cerebrospinal fluid were without pathological findings. When the patient showed signs of generalised sepsis he was transferred to the intensive care unit. Due to fulminant sepsis it was not possible to perform the planned biopsy. The patient died a few days later of cardio-respiratory insufficiency. The consecutive autopsy revealed invasive aspergillosis of paranasal sinuses with infiltration into the orbita and intracranial spreading into sinus cavernosus. Autopsy also showed aspergillus pneumonia. Discussion: Invasive aspergillosis of the paranasal sinuses and the skull base is most often a lethal condition in immunocompromised patients. Therefore, rapid diagnostics applying radiological (CT and MRI) and surgical procedures (biopsy) and immediate ignition of antimycotic treatment can be life-saving. [Copyright &y& Elsevier]

• MiRNA and lncRNA can be used as potential biomarkers for gout. • Noncoding RNA mediates four pathogenesis processes of gout. • The possible therapeutic targets of miRNAs and lncRNAs in gout. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are both types of noncoding RNA. They have been demonstrated to be involved in the regulation of various human inflammatory diseases and can be used as biomarkers for disease diagnosis and prognosis, and even be developed into new drugs. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Recent studies have shown that miRNAs and lncRNAs mediate the progress of gout. Based on the pathogenesis of gout, including hyperuricemia, MSU deposition, acute gouty arthritis and gouty bone erosion, this paper reviewed the role of miRNAs and lncRNAs in the processes and the possible therapeutic targets of miRNAs and lncRNAs in gout. [ABSTRACT FROM AUTHOR]

Background: Receptor activator of NF-κB ligand (RANKL) facilitates differentiation of osteoclast precursors into osteoclasts, resulting in bone erosion in rheumatoid arthritis (RA) patients. Fibroblast-like synoviocytes (FLS) are the main cells for producing RANKL. Signal transducer and activator of transcription 3 (STAT3) signaling is activated in FLS of RA patients (RA-FLS), which has been linked to RANKL production. A two-herb formula (RL) comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos is traditionally used for treating RA in China. We have found that a standardized ethanolic extract of RL (RLE for short) alleviates bone erosion in collagen-induced arthritis (CIA) rats.Purpose: This study aimed to determine whether RLE inhibits RANKL production and osteoclastogenesis in cell and rat models, and to explore the involvement of the STAT3 pathway in this inhibition.Study Design and Methods: A CIA rat model, interleukin-6/soluble interleukin-6 receptor (IL-6/sIL-6R)-stimulated RA-FLS and a co-culture system (IL-6/sIL-6R-stimulated RA-FLS/peripheral blood mononuclear cells) were used to evaluate the effects of RLE. Micro-computed tomography analysis was used to observe bone erosion in CIA rats. Tartrate-resistant acid phosphatase staining was used to evaluate osteoclastogenesis. Western blotting and ELISA assays were employed to examine protein levels. RT-qPCR was used to detect mRNA levels. STAT3-over-activated RA-FLS were used to investigate the involvement of STAT3 signaling in the anti-osteoclastogenic effects of RLE.Results: RLE alleviated bone erosion in joints of CIA rats. In both synovial tissues of CIA rats and IL-6/sIL-6R-stimulated RA-FLS, RLE downregulated the protein level of RANKL. In the co-culture system, RLE significantly and dose-dependently inhibited IL-6/sIL-6R-induced osteoclastogenesis. Mechanistic studies revealed that RLE lowered the protein level of phospho-STAT3 (Tyr705) in synovial tissues of CIA rats. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited the activation/phosphorylation of a STAT3 upstream kinase Janus kinase 2 (Tyr1007/1008) and STAT3 (Tyr705), decreased the nuclear localization of STAT3, lowered mRNA levels of STAT3-transcriptionally regulated genes IL-1β and TNF-α. RLE's inhibitory effects on RANKL production in RA-FLS gradually decreased when IL-6/sIL-6R doses increased. Over-activation of STAT3 diminished the inhibitory effects of RLE on RANKL production in IL-6/sIL-6R-stimulated RA-FLS, and attenuated the anti-osteoclastogenic effects of RLE in the co-culture system.Conclusion: We, for the first time, demonstrated that suppressing STAT3 signaling contributes to the inhibition of RANKL production and osteoclastogenesis, and thereby supports the mechanisms responsible for the reduction in bone erosion in RLE-treated CIA rats. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug, and supports the notion that targeting STAT3 signaling is a viable strategy for managing bone erosion. [ABSTRACT FROM AUTHOR]

Meniscal cysts are uncommon cystic lesions around the knee, and pericruciate meniscal cysts are the most rare types. Here we present an unusual case of a pericruciate meniscal cyst located laterally to the anterior cruciate ligament (ACL), causing erosion of the adjacent tibial plateau. [Copyright &y& Elsevier]

Background: Bone destructive diseases like rheumatoid arthritis (RA), osteoporosis and bone metastatic tumors are mainly mediated by over-activated osteoclasts. Asperosaponin VI (AVI), isolated from the rhizome of Dipsacus asper, belongs to triterpenoid saponins. It has multiple physiological activities but its effects on RA, especially on osteoclast differentiation and activation are still unclear.Purpose: Explore the protective role of AVI on collagen induced arthritis (CIA) in vivo and RANKL induced osteoclastogenesis in vitro.Methods: The effects of AVI on cell viability and RANKL-induced osteoclastogenesis, actin ring formation, bone resorption activity as well as on osteoclast specific gene and protein expression were tested using bone marrow derived monocytes (BMMs). Paws from CIA mice were used for micro-CT, HE and TRAP staining, real-time PCR and western blot. Sera were used for cytokine analysis by ELISA. The signaling pathways were detected using western blot, real-time PCR and immunofluorescence assay.Results: AVI significantly inhibited RANKL-induced osteoclast formation and bone resorption activity by suppressing the formation of actin ring. It also inhibited the expression of various osteoclatogenesis marker genes and signaling pathways. AVI protected arthritis in vivo by suppressing inflammation and bone loss.Conclusion: AVI exerts its anti-osteoclastogenic activity both in vitro and in vivo by inhibiting RANKL-induced osteoclast differentiation and function. Thus, our studies demonstrate a potential therapeutic role for AVI in preventing or inhibiting RANKL-mediated osteolytic bone diseases. [ABSTRACT FROM AUTHOR]

Background Pseudomeningoceles are a rare cause of bone erosions. Development of such erosions in the C2 vertebral body and the odontoid process can lead to life-threatening instability. Treatment options to regain stability include atlantoaxial and occipitocervical fusion. For patients with a history of Chiari decompression and large C2 lesions, common fusion techniques are not always feasible. In addition, fusion surgery sacrifices physiologic motion and is therefore a disabling procedure, especially for young and active patients. Case Description We report a novel combined open operative and subsequent minimal invasive filling technique of several instable osteolytic/cystic areas within the C2 vertebra of a 28-year-old woman. The underlying cause for the lesions was a pseudomeningocele communicating with the vertebral body. This was an incidental finding 15 years after foramen magnum decompression with C1 and partial C2 laminectomy for Chiari malformation. Novel treatment included open posterior surgery with total laminectomy of the remaining C2 arch and refilling the odontoid with viscous beta tricalcium phosphate and polymethylmethacrylate bone cement. Postoperative 6- and 12-month follow-up computed tomography imaging showed a stable incorporation of the filling. Conclusions Life-threatening fractures at the occipitocervical junction are rare and often are due to high-impact trauma. Osteolytic changes at those bone compartments are a potential cause for pathologic fractures during normal daily activities. In this case, increased pressure on the bone due to a pseudomeningocele resulted in slow bone loss without symptoms. A novel combined technique of bone filling was applied successfully to stabilize the C2 vertebral bone. [ABSTRACT FROM AUTHOR]

Abstract: Rib tumors are uncommon and represent 5% to 10% of all bony tumors. Regarding the benign rib lesions, costal angioma is very rare in childhood. We report a case of a rare angioma of a rib complicated by bone erosion in a young boy. [Copyright &y& Elsevier]