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Denosumab is the world's first human monoclonal antibody for the treatment of osteoporosis and shares an active pathway with bisphosphonates, strongly suppressing osteoclast activities. This is the first case report describing a possible relationship between the development of osteonecrosis of external auditory canal and denosumab administration. We herein report an 81-year-old woman diagnosed with left osteonecrosis of external auditory canal who had a history of denosumab administration. She underwent left radical mastoidectomy due to being refractory to conservative treatment. No major complications or recurrence were observed in the left ear after surgery, but bone erosion in the right ear has continued to progress slowly despite the cessation of denosumab administration. Otolaryngologists should be aware of the association between osteonecrosis of external auditory canal and denosumab administration and consider performing long-term observation even after cessation.

AIM Fungal sinusitis is a disease that was previously considered a rare disease, but has recently been reported with increasing frequency in warm climates. Fungal sinusitis classification has evolved over the past two decades and is said to include five subtypes. Discrimination of different subtypes and knowing their radiological features are important for accurate and rapid diagnosis and initiation of appropriate treatment. In our study, we aimed to investigate whether there is a difference between the radiological findings of AFS with a newly defined finding that may help the diagnosis of AFS; serrated turbinate and those reported in the literature. MATERIALS AND METHODS Our study included 120 patients who underwent paranasal sinus computed tomography examination in our center between January 2019 and September 2021. Patients diagnosed with AFS as a result of allergic tests and/or fungal culture examinations were included in the first group, and patients diagnosed with non-AFS rhinosinusitis were included in the second group. Presence of serrated turbinate appearence, polyps, bone erosion, CT hyperdensity were evaluated in the images. RESULTS The radiological features of AFS and non-AFS were compaired and serrated turbinate appearence was found to be statistically signifant in AFS (p0.05). CONCLUSION Our findings showed that serrated turbinate appearence may be a useful radiological marker in the diagnosis of AFS. Bone erosion should be evaluated seperately from other morphological and structural changes in the bone structure, and the bone density measurements should be specified for sinus opacification.

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Objectives This study investigated changes in bone mineral density (BMD) and erosion after denosumab discontinuation in rheumatoid arthritis (RA) patients without osteoporosis who participated in the DESIRABLE study. Methods This multicentre observational study consisted of a prediscontinuation visit (date of final assessment in DESIRABLE) and a postdiscontinuation visit (2.5 years after the last administered dose of denosumab). Percentage change in lumbar spine (LS) BMD from baseline was assessed as the primary endpoint. Results Fifty-nine patients were enrolled. The percentage change in LS BMD decreased to baseline levels at the postdiscontinuation visit. Compared with baseline, C-telopeptide of type I collagen levels increased after denosumab discontinuation but most patients had levels within the reference range. Bone erosion scores were not significantly different between the on-treatment period and after denosumab discontinuation (p = .0666) but there was a numerical increase postdiscontinuation. The progression in bone erosion score was significantly reduced in patients whose disease activity was in remission versus those not in remission (p = .0195). Conclusions In RA patients without osteoporosis, denosumab discontinuation can be explored while considering patient background factors (disease activity and risk of fracture) and accounting for progression of bone erosion and LS BMD decrease after withdrawal.

A mucocele is a benign lesion that predominantly affects the paranasal sinuses, with a slow growth rate and expansive pattern. When infected, it is known as mucopyocele. Presentation of a frontal mucopyocele can be found more frequently in adults. In contrast, it is rarely seen in children since pneumatization of the sinuses usually takes place after age 7. This report aims to present one case of a frontal mucopyocele as an important complication of a pansinusitis in a 7-year-old child and discuss the diagnosis, surgical approach, and differentials. Endoscopic endonasal surgery is a safe approach and must be taken into consideration in these situations.

AIM The aim of this study was to compare OsiriX software with the previous published Medical Image Analysis Framework (MIAF) method to assess the volume of erosion in patients with rheumatoid arthritis (RA). METHODS Forty RA patients underwent high-resolution peripheral quantitative computed tomography scans of the second and third metacarpophalangeal joints, and thirty-four patients with any bone erosion were enrolled. Two techniques were applied to erosion evaluation: (a) semi-automated MIAF software, and (b) semi-automated segmentation by free open-source Digital Imaging and Communications in Medicine viewer, OsiriX software. MIAF has been published before, but this is the first time that OsiriX has been used in this way in rheumatology. Bland & Altman plots described agreement between methods. RESULTS Forty-eight erosions from 34 patients were analyzed. Mean age was 40.74 ± 5.32 years and mean disease duration was 10.68 ± 4.96 years. Both methods demonstrated a strong correlation regarding erosion volume (r = 0.96, P

Ligamentum flavum cyst of the lumbar spine has seldom been described. The mechanism of formation of these cysts remains unknown, but it is thought to be part of the degenerative process. Although they are clearly visible on imaging studies, these cysts are frequently wrongly diagnosed as ganglion or synovial cysts. Bone erosion is rarely associated with this pathology. Most common symptom is back and radicular pain due to nerve root compression. We report a case of ligamentum flavum cyst associated with bone remodeling presented with back and radicular pain. It was correctly diagnosed pre-operatively and treated surgically with satisfactory clinical outcome.

ObjectiveTo evaluate the effects of denosumab on erosion healing at 2–4 metacarpophalangeal (MCP) head as determined by high-resolution peripheral quantitative CT (HR-pQCT) in patients with rheumatoid arthritis (RA) with stable disease.MethodsThis was a randomised, placebo-controlled, double-blind study. Patients with RA with disease activity score 28 joints (DAS28) ≤5.1 were randomised (1:1) to subcutaneous denosumab 60 mg or placebo once every 6 months for 24 months. The primary outcome was erosion healing at MCP 2–4 on HR-pQCT at 12 months. The effects of denosumab on erosion and joint space parameters on HR-pQCT and radiographs, disease activity and health assessment questionnaire-disability index (HAQ-DI) were also examined.ResultsAt 24 months, HR-pQCT images were analysed in 98 patients. One-third of the patients achieved sustained low disease activity throughout the study. At 12 months, changes in erosion parameters on HR-pQCT were similar between the two groups. At 24 months, new erosions (19% vs 9%, p=0.009) and erosion progression (18% vs 8%, p=0.019) were more common in the placebo group than the denosumab group. Erosion healing was seen in a significantly higher proportion of patients in the denosumab group (20% vs 6%, p=0.045) at 24 months. No significant changes in joint space parameters on HR-pQCT, van der Heijde-Sharp erosion score, DAS28 and HAQ-DI were observed in the two groups at 12 and 24 months.ConclusionAlthough no differences in erosion parameters were observed at 12 months, denosumab was more efficacious than placebo in erosion repair on HR-pQCT after 24 months.Trial registration numberNCT03239080.

espanolLa artritis reumatoide es una enfermedad inflamatoria cronica sistemica que se caracteriza por una inflamacion poliarticular que causa la aparicion de erosiones oseas y disfuncion articular. Hoy en dia, para su tratamiento disponemos de farmacos modificadores de la enfermedad (FAME) sinteticos y biologicos. El objetivo con estos pacientes debe ser alcanzar la remision o, en su defecto, la baja actividad de la enfermedad, siguiendo la estrategia treat-to-target. EnglishRheumatoid arthritis is a systemic chronic inflammatory disease characterized by multi-articular inflammation that causes bone erosion and joint dysfunction. At present, biological and synthetic disease-modifying antirheumatic drugs (DMARDs) are available for its treatment. With these patients, the objective is to achieve remission or, if not that, a low level of disease activity, following the treat-to-target strategy.

Background High-resolution imaging receives increasing attention and leads to an improved understanding of skeletal diseases. Before the introduction of high-resolution peripheral quantitative computed tomography (HR-pQCT), the evaluation of bone microstructure was not feasible in vivo but required bone biopsies. Methods With HR-pQCT, it is possible to evaluate the bone microarchitecture three-dimensionally and with a high spatial resolution (60.7 μm voxel size). Results In multiple studies, relevant insights of bone microarchitecture have been revealed by HR-pQCT at the distal tibia and radius in both health and disease, accompanied by superior correlations with the incidence of fragility fractures compared to bone mineral density measurement by dual-energy X-ray absorptiometry. Conclusions Consequently, HR-pQCT offers great potential to improve the understanding of bone and joint diseases, especially in foot and ankle surgery, as it enables the evaluation of individualized bone regions at the microstructural level (e.g., bone erosion, fracture healing) within the clinical routine.

Rhinocerebral mucormycosis (RCM) may result in severe intracranial ischemic and hemorrhagic lesions. Both computed tomography (CT) and magnetic resonance imaging (MRI) play an essential role in the diagnosis of RCM, but whereas CT is better for assessing bone erosion, MRI is superior in evaluating soft tissue, intraorbital extension, and in assessing intracranial and vascular invasion. Specific CT and MRI techniques, such as CT angiography or enhanced MR angiography, and more advanced MRI sequences such as gadolinium-3D Black Blood imaging, contribute to the assessment of the extension of vascular invasion. In this pictorial review, we describe specific CT and MRI signs of RCM, mainly focusing on its life-threatening complications due to vascular involvement.

Schwannomas in the middle ear and external auditory canal are exceedingly rare. The facial nerve, chorda tympani nerve, and Jacobson’s nerve have rarely been reported as the origins of primary schwannomas in the middle ear cavity. We experienced a case of carotid sympathetic plexus (CSP) schwannoma that arose from the carotid canal and extended into the middle ear and external auditory canal. The tumor presented bone erosion of the carotid canal, and it adhered tightly to the internal carotid artery. This report represents the first documented case of a CSP schwannoma, which involved the middle ear and external auditory canal.

Context Alantolactone, the bioactive component in Inula helenium L. (Asteraceae), exhibits multiple biological effects. Objective We aimed to determine the anti-inflammatory effect of alantolactone in a collagen-induced arthritis (CIA) mouse model and its immunomodulatory effects on Th17 differentiation. Materials and methods A CIA mouse model was established with DBA/1 mice randomly divided into four groups (n = 6): healthy, vehicle and two alantolactone-treated groups (25 or 50 mg/kg), followed by oral administration of alantolactone to mice for 21 consecutive days after arthritis onset. The severity of CIA was evaluated by an arthritic scoring system and histopathological examination. Levels of cytokines and anti-CII antibodies as well as percentages of splenic Th17 and Th17 differentiation with or without alantolactone treatments (0.62, 1.2 or 2.5 μM) were detected with ELISA and flow cytometry, respectively. Western blot analysis was used to evaluate intracellular signalling in alantolactone-treated spleen cells. Results In CIA mice, alantolactone at 50 mg/kg attenuated RA symptoms, including high arthritis scores, infiltrating inflammatory cells, synovial hyperplasia, bone erosion and levels of the proinflammatory cytokines TNF-α, IL-6 and IL-17A, but not IL-10 in paw tissues. Alantolactone also reduced the number of splenic Th17 cells and the capability of naïve CD4+ T cells to differentiate into the Th17 subset by downregulating STAT3/RORγt signalling by as early as 24 h of treatment. Discussion and conclusions Alantolactone possesses an anti-inflammatory effect that suppresses murine CIA by inhibiting Th17 cell differentiation, suggesting alantolactone is an adjunctive therapeutic candidate to treat rheumatoid arthritis.

Background: This exploratory study compared the inhibition of bone erosion progression in rheumatoid arthritis (RA) patients treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab versus csDMARD therapy alone and investigated the effects of denosumab on bone micro-architecture and other bone-related parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: In this open-label, randomized, parallel-group study, patients with RA undergoing treatment with a csDMARD were randomly assigned (1:1) to continue csDMARD therapy alone or to continue csDMARDs with denosumab (60-mg subcutaneous injection once every 6 months) for 12 months. The primary endpoint was the change from baseline in the depth of bone erosion, measured by HR-pQCT, in the second and third metacarpal heads at 6 months after starting treatment. Exploratory endpoints were also evaluated, and adverse events (AEs) were monitored for safety. Results: In total, 46 patients were enrolled, and 43 were included in the full analysis set (csDMARDs plus denosumab, N = 21; csDMARD therapy alone, N = 22). Most patients were female (88.4%), and the mean age was 65.3 years. The adjusted mean (95% confidence interval) change from baseline in the depth of bone erosion, measured by HR-pQCT, in the 2–3 metacarpal heads at 6 months was − 0.57 mm (− 1.52, 0.39 mm) in the csDMARDs plus denosumab group vs − 0.22 mm (− 0.97, 0.53 mm) in the csDMARD therapy alone group (between-group difference: − 0.35 mm [− 1.00, 0.31]; P = 0.2716). Similar results were shown for the adjusted mean between-group difference in the width and volume of bone erosion of the 2–3 metacarpal heads. Significant improvements in bone micro-architecture parameters were shown. The incidence of AEs and serious AEs was similar between the csDMARDs plus denosumab and the csDMARD therapy alone groups (AEs: 52.2% vs 56.5%; serious AEs: 4.3% vs 8.7%). Conclusions: Although the addition of denosumab to csDMARDs did not find statistically significant improvements in bone erosion after 6 months of treatment, numerical improvements in these parameters suggest that the addition of denosumab to csDMARDs may be effective in inhibiting the progression of bone erosion and improving bone micro-architecture., Arthritis Research and Therapy, 24(1), art. no. 264; 2022

Papillary endothelial hyperplasia (PEH) is a reactive pseudoneoplastic proliferation of endothelial cells. They are typically well-circumscribed, indolent lesions and curable by complete excision. ...

Even though new drugs for the treatment of rheumatoid arthritis (RA) have been developed, methotrexate (MTX) remains a commonly used drug for RA management. In addition to monitoring disease activity during RA treatment, bone erosion should be closely assessed throughout long-term RA management. In this review article, we present a systematic review of MTX effectiveness in reducing the risk of bone erosion. We reviewed randomized controlled trial studies that involved MTX monotherapy or MTX in combination with placebo. Evaluation of the progression of bone erosion was examined by radiographic assessment such as total Sharp score (TSS) or van der Heijde score (SvdH or vdH TSS), joint space narrowing (JSN), erosion score (ERO), and proportion of radiographic nonprogressors. Several key factors were found to influence the response to MTX treatment, such as gene polymorphism. The exact mechanism of the prevention of bone erosion by MTX remains unclear, which warrants future investigations. The variability of RA disease activity in study subjects resulted in variations in the results reported by individual studies. Collective analysis suggests that MTX could slow down the progression of bone erosion based on a radiographic score of less than 0.5-1/year.

Imaging is essential for the assessment of bone and inflammatory joint diseases. There are several imaging techniques available that differ regarding resolution, radiation exposure, time expending,...

To investigate anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) in relation to ultrasound-detected joint inflammation and bone erosion in patients with rheumatoid arthritis (RA) as previous studies have mainly utilized radiographic damage as imaging outcomes.In this cross-sectional study, patients were grouped based on their Disease Activity Score at 28 joints (DAS28 3.2, DAS28 ≥ 3.2). Ultrasound variables (power Doppler and gray scale joint inflammation graded 0-3 semi-quantitatively; bone erosion graded Yes = 1/No = 0 dichotomously) were correlated with antibodies levels using Pearson correlation. Simple linear regression was used to characterize relationships between variables. Receiver operating characteristic (ROC) analysis was performed to determine statistically optimal cut-off values for identifying patient subgroups with ultrasound erosion scores25th,50th and75th percentiles.One thousand and eighty joints and 1800 joint recesses from 36 peripheral joint sites were scanned in 30 adult RA patients (mean disease duration, 70.3 months; 93.3% female; 93.3% anti-CCP positive; 93.3% RF positive). In the DAS28 3.2 group, no significant correlations were found between antibody levels and ultrasound variables. In the DAS28 ≥ 3.2 group, anti-CCP levels correlated significantly (r = 0.46, P = .048) and were predictive (P = .048) of ultrasound erosion scores. Area under the ROC curve based on cut-off anti-CCP level of ≥95.2 to identify patients with ultrasound erosion scores7 (75th percentile) was 0.72 (sensitivity = 83.3%, specificity = 53.8%).The association of anti-CCP and RF with joint damage appears to differ in RA. Among patients with at least moderate disease activity (DAS28 ≥ 3.2), anti-CCP-but not RF-is associated with joint damage, being moderately correlated with ultrasound-detected bone erosion.

Human cadaveric study has indicated that the metacarpal head (MCH) is intracapsular in location. We hypothesized that exposure to the intra-articular inflammatory milieu in psoriatic arthritis (PsA) will lead to bone loss in the MCH. To compare the bone structure and microstructure in the MCH between patients with PsA and healthy controls by high-resolution peripheral quantitative CT (HR-pQCT), and to ascertain factors associated with bone loss in PsA patients. Sixty-two PsA patients without joint destruction and 62 age-, gender-, and body mass index–matched healthy subjects underwent HR-pQCT imaging of the second and third MCH (MCH 2&3). The number and volume of bone erosion and enthesiophytes, as well as volumetric bone mineral density (vBMD) and microstructure at the MCH 2&3, were recorded. Correlation analysis and multivariable linear regression models were used to determine the association of demographic and disease-specific variables with compromised bone structure and microstructure in PsA. At the MCH 2&3, bone erosion (p = 0.003) and enthesiophyte (p = 0.000) volumes in PsA patients were significantly larger than healthy controls. In PsA patients, older age was associated with a larger erosion and enthesiophyte volume. Concerning the mean vBMD and microstructure at the MCH 2&3, PsA patients had significantly lower mean vBMD (average vBMD − 6.9%, trabecular vBMD − 8.8%, peri-trabecular vBMD − 7.7%, meta-trabecular vBMD − 9.8%), trabecular bone volume fraction (− 8.8%), and trabecular thickness (− 8.1%) compared with control subjects. Multivariable regression analysis revealed that older age and a higher C-reactive protein level were associated with trabecular bone loss. PsA patients had a higher burden of bone damages (erosions and enthesiophytes) and trabecular bone loss compared with healthy control at the MCH. Inflammation contributed to the deterioration in trabecular microstructure in these patients.

In current daily clinical practice, radiological imaging is essential for preoperative determination of the appropriate staging and treatment strategies for oral cancers. CT images with bone algorithms usually provide high specificity for bone erosion of the buccal and lingual cortices of the jaw. Contrast-enhanced CT images are useful for detecting regional lymphadenopathy. MR imaging is the best imaging modality for assessing size, depth, configuration, margin, location, and tumor extension of primary oral cancers. Fat-suppressed contrast-enhanced MR images are particularly beneficial in detecting perineural tumor spread. Diffusion-weighted MR images can predict tumor characteristics, including tumor cellularity, histological subtypes, and histological grades. 18F-fluorodeoxyglucose positron emission tomography/CT mainly contributes to identifying regional lymphadenopathy and distant metastasis. The appropriate use of diagnostic imaging is essential in the proper management of oral cancers and improvement of prognosis.

The complications of attico-antral type of Chronic Suppurative Otitis Media (CSOM) are severe due to underlying bone erosion. We describe a case of a 40-year-old lady with attico-antral CSOM and mastoiditis with a postauricular fistula, who underwent modified radical mastoidectomy with excision of the postauricular cutaneous mastoid fistula. Interestingly, another fistula over the dome of lateral semicircular canal was noted intraoperatively.Few reports of occurrence of postauricular mastoid fistula with a labyrinthine fistula have been documented.

Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease that affects 23 million people worldwide. It is a clinically heterogeneous disorder characterized by the attack of inflammatory chemicals on the synovial tissue that lines joints. It is advantageous to develop effective, targeted treatments and identify specific diagnostic biomarkers for RA before extensive joint degradation, bone erosion, and cartilage destruction. Current modes of RA treatments have alleviated and notably halted the progression of RA. Despite this, not many patients reach low disease activity status after treatment, and a significant number of patients fail to respond to medication due to drug non-specificity. While the reasons for these rates remain unknown, the cellular and molecular signatures present in the synovial tissue for RA patients likely play a role in the varied treatment response. Thus, a drug that particularly targets specific genes and networks may have a significant effect in halting the progression of RA. This study evaluates and proposes potential drug targets through in silico mathematical modeling of various pathways of interest in RA. To understand how drugs interact with genes, we built a mathematical model with 30 two-gene and three-gene network interactions and analyzed the effect of 92 different perturbations to rate constants. We determined that inhibition of the LCK-CD4, VAV1-CD4, and MLT-ROR pathways could potentially serve as drug targets. We also found that increased activity of the DEC2-IL1β and the NF-kB-interleukin pathway and the decreased activity of the TNF-α-REV-ERB pathway could serve as diagnostic biomarkers.

Methyl gallate (MG) is a plant-derived phenolic compound known to present remarkable anti-inflammatory effect in different experimental models such as paw oedema, pleurisy, zymosan-induced arthritis and colitis. Herein we investigated the effect of MG in the mice model of antigen-induced arthritis (AIA), a model with complex inflammatory response, driven primally by immune process and that cause bone and cartilage erosion similarly found in rheumatoid arthritis. Arthritis was induced by i.a injection of albumin methylated from bovine serum (mBSA) in C57BL/6 male mice previously immunized. The dose-response analysis of MG (0.7-70 mg/kg; p.o) showed that maximum inhibition was reached with the dose of 7 mg/kg on paw oedema and cell infiltration induced by AIA at 7 h. Treatment with MG (7mg/kg; p.o) or with the reference drug, dexamethasone (Dexa,10 mg/kg, ip) reduced AIA oedema formation, leukocyte infiltration, release of extracellular DNA and cytokine production 7 and 24 h (acute response). Mice treated daily with MG for seven days showed no significant weight loss or liver and kidney toxicity contrary to Dexa that induced some degree of toxicity. Prolonged treatment with MG inhibited the late inflammatory response (28 days) reducing oedema formation, cell infiltration, synovial hyperplasia, pannus formation and cartilage degradation as observed in histopathological analyses. Ultimately, MG reduced bone resorption as evidenced by a decrease in tartrate-resistant acid phosphate (TRAP)-positive cells number in femur histology. Altogether, we demonstrate that MG ameliorates the inflammatory reaction driven primarily by the immune process, suggesting a potential therapeutic application in arthritis treatment.

Purpose of review Allergic fungal rhinosinusitis (AFRS) is a debilitating condition for children. Despite there being several reviews on this topic in the adult population, there is a paucity of reviews of AFRS in the pediatric literature. This article reviews the recent evidence of pediatric AFRS with the aim to optimize outcomes of pediatric patients with this condition. Recent findings AFRS is clinically characterized by nasal polyposis, a type I hypersensitivity to fungal epitopes, very thick eosinophilic mucin, and peripheral eosinophilia. Pediatric AFRS has similar clinical characteristics to that in adults but is thought to have a more aggressive nature, with higher serum immunoglobulin E and more frequently bone erosion and malformation of facial bones. Diagnosis of pediatric AFRS is made by using the Bent and Kuhn's criteria developed for adult AFRS. The mainstay of treatment is surgery followed by postoperative corticosteroids. Adjunctive therapies, including topical/oral antifungal agents, allergen immunotherapy and biologics may improve outcomes in pediatric AFRS, but to date the current evidence is limited. Summary To optimize the outcome of pediatric AFRS, adequate and early diagnosis and treatment are essential. Appropriate and comprehensive endoscopic sinus surgery to open the sinuses, remove the fungal burden of disease and improve access of the sinuses to postoperative topical corticosteroid remains the standard of care.

ObjectivesDenosumab is used for osteoporosis because it inhibits osteoclast maturation and suppresses bone resorption. Although denosumab is expected to inhibit the bone erosion in RA, its therapeutic efficacy is not well established. The aim of this study was to estimate the effects of denosumab on RA through a meta-analysis.MethodsA systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Web of Science and Scopus were searched for original studies providing information on BMD, joint destruction and disease activity in denosumab-treated RA. A random-effects model was used in the meta-analysis.ResultsOf the 367 studies identified, 18 met the selection criteria. The BMDs of the lumbar spine, total hip and femoral neck at 12 months after denosumab treatment increased by 5.27% (95% CI: 4.37, 6.18), 2.82% (2.46, 3.18) and 3.07% (2.66, 3.48), respectively. In the sensitivity analysis, age and sex tended to influence the effect of denosumab therapy on the rate of variation of BMD, but not glucocorticoid use. The changes in the modified total sharp, erosion and joint space narrowing scores at 12 months after denosumab treatment were significantly smaller with denosumab than with placebo, although the DAS did not change after denosumab treatment.ConclusionAlthough denosumab has an inhibitory effect on the bone resorption in RA, its effects might be influenced by the age and sex of RA patients, but not by glucocorticoid use.

Background:. Psoriatic arthritis (PsA) is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology. Dickkopf-1 (Dkk-1) is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation. The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients. Methods:. Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 69 patients with PsA and 60 controls, including 39 rheumatoid arthritis (RA) patients, and 21 healthy controls (HCs). Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA. The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed. Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA. Results:. Dkk-1 was elevated in 68.1% (47/69) of the patients with PsA, 46.2% (18/39) of RA patients, and 9.5% (2/21) of HCs. Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs. The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4. Elevated Dkk-1 level (odds ratio = 4.440, 95% confidence interval: 1.246–15.817, P = 0.021) was identified as the risk factor for bone erosion in PsA. Conclusions:. The serum level of Dkk-1 is abnormally elevated in PsA patients. The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.

Chikungunya virus (CHIKV) was introduced to the Americas in 2013, causing two million infections across over thirty countries. CHIKV causes a chronic debilitating arthritis in one fourth of infected individuals and currently evidence-based targeted therapies for the treatment of CHIKV arthritis are lacking. Multiple mouse models of chikungunya have been developed to study acute CHIKV infection. In humans, post-CHIKV arthritis may persist for months to years after viremia from a CHIKV infection has resolved. Therefore, the development of a mouse model of post-acute arthritis of chikungunya may facilitate the study of potential novel therapeutics for this arthritis. In this article we describe the development of a wild-type immunocompetent C57BL/6 mouse model for post-acute arthritis of chikungunya, including a histologic inflammation scoring system, as well as suggestions for how this mouse model may be used to examine the efficacy of novel therapies for CHIKV arthritis.

Rheumatoid arthritis is an autoimmune disease that causes chronic inflammation of synovial joints, often resulting in irreversible structural damage. The activity of the disease is evaluated by clinical examinations, laboratory tests, and patient self-assessment. The long-term course of the disease is assessed with radiographs of hands and feet. The evaluation of the X-ray images performed by trained medical staff requires several minutes per patient. We demonstrate that deep convolutional neural networks can be leveraged for a fully automated, fast, and reproducible scoring of X-ray images of patients with rheumatoid arthritis. A comparison of the predictions of different human experts and our deep learning system shows that there is no significant difference in the performance of human experts and our deep learning model.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory arthropathy characterized by excessive synovial hyperplasia and progressive joint destruction. Pro-inflammatory cytokines pla...

Bony erosion and dural ectasia rarely occur in the posterior part of the vertebral body in ankylosing spondylitis (AS). Because of the compression of nerve tissue that adheres to the inflamed dura mater, a range of neurologic symptoms may develop. Few studies have investigated therapies for this condition, and surgical intervention might alleviate the neurologic dysfunction. Here, we report an uncommon case of lumbar spinal cord herniation secondary to anterior dural ectasia in a patient with AS. The patient had a 31-year history of AS and presented with progressive numbness and weakness of his left leg that had lasted for nearly 1 month. Magnetic resonance imaging (MRI) revealed a dural defect in the posterior aspect of the L1 and L2 vertebral bodies, with displacement of the nerve tissue adjacent to the lytic lesion. The patient declined surgery and was prescribed oral meloxicam. The neurological symptoms of the left leg remained stable during 2 years of follow-up. The dural enhancement on MRI resolved, although the erosion-like lesion in the vertebral bodies persisted. This unusual case supports the central role of inflammation in anterior dural ectasia of patients with AS. Anti-inflammatory treatment may be an alternative therapy for patients who decline surgery.

Introduction This study aimed to determine the effects of denosumab treatment on the joint destruction of Japanese females with rheumatoid arthritis (RA) and anti-cyclic citrullinated peptide (CCP) antibodies. Materials and methods This retrospective longitudinal study included 56 patients treated with denosumab and 50 patients treated with bisphosphonate. All participants were positive for anti-CCP antibodies. All patients also had a history of osteoporosis treatment with bisphosphonate, which was either continued or switched to 60 mg of subcutaneous denosumab injection every 6 months. To assess the progression of joint destruction, hand and foot radiographs were taken, and changes in modified total Sharp score (mTSS), erosion score (ERO), and joint space narrowing score (JSN) were evaluated at 12 months and 24 months. The changes in BMD of the lumbar spine and hip were also assessed at 12 months. Results At 12 months, there were significant differences in the change of ERO (p = 0.015) and mTSS (p = 0.01). Similarly, there were significant differences in the change of ERO (p = 0.013) and mTSS (p = 0.003) at 24 months. In contrast, no significant difference was observed in the changes of JSN and clinical parameters. There were significant differences in the changes in BMD in the femoral neck (p = 0.011) and total hip (p = 0.012). Conclusion Denosumab treatment might be effective for the inhibition of bone erosion progression in the patients with RA, and it potentially contributes to the treatment of osteoporosis and prevention of destructive arthritis in patients with switching treatment from bisphosphonate.

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.

Background The currently available scoring methods for enthesitis are often measures of pain but not of inflammation at entheseal sites. The Outcome Measures in Rheumatology Clinical Trials (OMERACT) psoriatic arthritis (PsA) magnetic resonance imaging (MRI) scoring system (PsAMRIS) assesses inflammation and damage in PsA and was particularly developed for the hands. The ACHILLES trial used clinical measures for heel enthesitis in combination with MRI scoring based on PsAMRIS. Methods Patients (age ≥ 18 years) with spondyloarthritis (SpA) and PsA were included in the trial if they presented with clinical and MRI-positive heel enthesitis. MRI of the affected heel was performed at three time points: screening, Week 24 and Week 52. Inflammatory MRI findings (tendinitis, bursitis and bone marrow oedema [BME]) in the area of the Achilles tendon and/or plantar aponeurosis, periarticular inflammation of the ankle joint and heel erosion were assessed qualitatively (absent/present). In addition, BME and bone erosion were quantitatively assessed based on PsAMRIS, where their proportion was compared to the volume of the affected bone. Mean scores of BME and bone erosion quantification were calculated, and the mean composite score (based on PsAMRIS) was calculated based on the individual score of each subject for periarticular inflammation, BME and bone erosion and further extended for bursitis and tendinitis. Modifications to PsAMRIS were introduced by categorising oedema length as ≤/> 0.5 cm and locating bone erosion. Conclusions In ACHILLES, MRI was used to assess and evaluate heel enthesitis. Due to the lack of a validated scoring system for heel enthesitis at the time of ACHILLES initiation, this trial applied quantitative scoring based on PsAMRIS, with specific adaptations for the heel. Trial registration National Clinical Trial Registry, NCT02771210. Registered 13 May 2016.

Objectives 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). Methods 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. Results 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. Conclusion 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.

Ultrasound can be used to objectively diagnose and evaluate disease activity in patients with rheumatoid arthritis (RA). We aimed to determine the value of a new automated hand ultrasound (AHUS) scanning device and a simplified 3-joint ultrasound scoring system (US3) in detecting synovitis in RA. We compared AHUS and traditional ultrasound (US) scanning in detecting synovial hyperplasia (SH), joint effusion, bone erosion and power Doppler (PD) synovitis in 49 patients. In addition, we compared the value of US3 (in which 3 proximal interphalangeal [PIP] and/or metacarpophalangeal [MCP] joints with the highest scores for swelling and tenderness were evaluated) with the 22-joint ultrasound scoring system (US22) in 26 patients. Almost perfect κ coefficients (0.86-0.937) were obtained between AHUS and traditional US in detecting SH, joint effusion, bone erosion and PD synovitis (p0.001). The intra-class correlation coefficient (ICC) between AHUS and traditional US was 0.955-0.995. Of the US3 findings in AHUS, SH synovitis and PD synovitis were positively correlated with DAS28-CRP (adjusted R

Septic arthritis is a medical emergency associated with high morbidity and mortality, yet hardly any novel advances exist for its clinical management. Despite septic arthritis being a global health burden, experimental data uncovering its etiopathogenesis remain scarce. In particular, any interplay between septic arthritis and preceding joint diseases are unknown as is the contribution of the synovial membrane to the onset of inflammation. Using C57BL/6 mice as a model to study sepsis, we discovered that Group A Streptococcus (GAS) – an important pathogen causing septic arthritis - was able to invade the articular microenvironment. Bacterial invasion resulted in the infiltration of immune cells and detrimental inflammation. In vitro infected fibroblast-like synoviocytes induced the expression of chemokines (Ccl2, Cxcl2), inflammatory cytokines (Tnf, Il6), and integrin ligands (ICAM-1, VCAM-1). Apart from orchestrating immune cell attraction and retention, synoviocytes also upregulated mediators impacting on bone remodeling (Rankl) and cartilage integrity (Mmp13). Using collagen-induced arthritis in DBA/1 × B10.Q F1 mice, we could show that an inflammatory joint disease exacerbated subsequent septic arthritis which was associated with an excessive release of cytokines and eicosanoids. Importantly, the severity of joint inflammation controlled the extent of bone erosions during septic arthritis. In order to ameliorate septic arthritis, our results suggest that targeting synoviocytes might be a promising approach when treating patients with inflammatory joint disease for sepsis.

Bone remodelling is a complex mechanism regulated by osteoclasts and osteoblasts and perturbation of this process leads to the onset of diseases, which may be characterised by altered bone erosion or formation. In this review, we will describe some bone formation-related disorders as sclerosteosis, van Buchem disease, hypophosphatasia and Camurati–Engelmann disease. In the past decades, the research focused on these rare disorders offered the opportunity to understand important pathways regulating bone formation. Thus, the identification of the molecular defects behind the etiopathology of these diseases will open the way for new therapeutic approaches applicable also to the management of more common bone diseases including osteoporosis.

Rheumatoid arthritis (RA) is a common autoimmune disease with characteristics of synovial inflammation, pannus formation, cartilage destruction, and bone erosion. Further, the inflammation is linked to increased oxygen consumption, resulting in hypoxia within the inflammatory area. Hypoxia-inducible factor (HIF) was reported to be associated with adaptation to the hypoxic microenvironment in the RA synovium. Here, we have briefly summarized the structure and expression of HIF. Moreover, the function of HIF in inflammation, angiogenesis, cartilage damage, and immune cells of RA has been discussed.

Objective: To explore the role of musculoskeletal ultrasound (MSUS) in the differential diagnosis of gouty arthritis (GA) and rheumatoid arthritis (RA) and to analyze the ultrasound imaging features of the two diseases. Methods: A retrospective study was carried out. A total of 66 patients who had been admitted to The First Medical Center of Chinese PLA General Hospital from May 2018 to March 2019 were enrolled. Among them, 34 patients were diagnosed with RA and were included in the RA group; 32 patients were diagnosed with gouty arthritis and were included in the GA group. The imaging features of musculoskeletal ultrasound were compared between the two groups of patients. Results: A total of 34 patients were included in the RA group, including 17 males and 17 females. A total of 32 patients were included in the GA group, including 14 males and 18 females. There were no significant differences in gender composition, age, and duration of disease between the two groups (P>0.05). In the RA group, there were joint bone erosions with a clear boundary in seven cases and with a blurred boundary in 27 cases; synovial hyperplasia was observed in 27 cases, and point-like hyperechoic masses were observed in four cases. In the GA group, there were joint bone erosions with a clear boundary in 27 cases and with a blurred boundary in five cases; synovial hyperplasia was observed in four cases, tophus was observed in 23 cases, point-like hyperechoic masses were observed in 27 cases, and the tram-track sign was observed in 23 cases. The differences in bone erosion boundaries (c2=26.854, P

Adenoid cystic carcinoma is the most common type of malignancy seen in the lacrimal glands and is generally characterized by invasive malignant appearance with irregular margins and associated bone erosion or destruction. The authors report an unusual patient with a large expansile, well-circumscribed lacrimal adenoid cystic carcinoma with adjacent bone remodeling, radiologically mimicking a benign lesion.

Background: External auditory canal (EAC) cholesteatoma (EACC) is rare and its treatment for different lesions has not yet been standardized.Objective: This study aimed to explore the clinical feat...

Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS), which regulates the cardiovascular system. The RAS is reportedly also involved in bone metabolism. The upregulation of RAS components has been shown in arthritic synovial tissues, suggesting the potential involvement of Ang II in arthritis. Accordingly, in the present study, we investigated the role of Ang II in bone erosion and systemic bone loss in arthritis. Ang II was infused by osmotic pumps in tumor necrosis factor-transgenic (TNFtg) mice. Ang II infusion did not significantly affect the severity of clinical and histological inflammation, whereas bone erosion in the inflamed joints was significantly augmented. Ang II administration did not affect the bone mass of the tibia or vertebra. To suppress endogenous Ang II, Ang II type 1 receptor (AT1R)-deficient mice were crossed with TNFtg mice. Genetic deletion of AT1R did not significantly affect inflammation, bone erosion, or systemic bone loss. These results suggest that excessive systemic activation of the RAS can be a risk factor for progressive joint destruction. Our findings indicate an important implication for the pathogenesis of inflammatory bone destruction and for the clinical use of RAS inhibitors in patients with rheumatoid arthritis.

Atrophic rhinitis (AR) is a condition characterized by extensive atrophy of the nasal mucosa, bone erosion, and consequent cavity enlargement. It can be a primitive AR (PAR) or a secondary AR (SAR). The role of imaging in the diagnostic and follow-up processes of AR, especially during diagnosis, is to support strong clinical suspicion. In fact, it is justified only based on strong clinical and endoscopic evidence and thus imaging has the aim of diagnostic validation.

To investigate the efficacy of two tight-control treatment strategies aimed at simplified disease activity score [SDAI] remission (SDAI ≤ 3.3) compared to DAS28 remission (DAS282.6) on progression of bone erosions in early rheumatoid arthritis (ERA) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT).This was an open-label study in which 80 early RA patients were randomized to receive 1-year of tight-control treatment. Group 1 (n = 37) aimed at SDAI ≤ 3.3 and group 2 (n = 43) aimed at DAS28-CRP2.6. The number and size of bone erosions, as well as the bone mineral density (BMD) surrounding bone erosion at the second metacarpophalangeal joint (MCP2), were measured at baseline and 12 months.After 12 months, images were analyzed in 63 patients. Changes in clinical parameters, number and size of bone erosions as well as the BMD surrounding bone erosion between the two treatment groups were similar. Therefore, a post-hoc analysis including all 63 patients was performed to elucidate the independent predictors of erosion progression and repair. Multivariate analysis revealed that not achieving sustained SDAI remission at month 6, 9 and 12 (p = 0.034) and rheumatoid factor16U (p = 0.021) were independent predictors associated with an increase in erosion volume. Logistic regression analysis showed that achieving sustained SDAI remission (p = 0.043) was associated with partial erosion repair.Although more stringent treatment target did not notably affect clinical treatment outcome and erosion progression at 1 year, achieving sustained SDAI remission was found to be associated with partial erosion repair.

Studies have demonstrated mixed results after humeral head replacement (HHR) for osteoarthritis at short- and medium-term follow-up intervals. The purpose of this study was to investigate the long-term outcomes (minimum 10 years) of HHR for the treatment of osteoarthritis.This study included 44 shoulders in 42 patients who had been followed up for a minimum of 10 years, at a mean clinical follow-up of 17 years (range, 10-30 years). Of this group, 31 shoulders had radiographic follow-up beyond 5 years, at a mean of 11.1 years (range, 5-21 years).Patients experienced significant pain relief postoperatively that was maintained during the long-term follow-up (P .01), with a subgroup of 11 patients reporting persistent moderate or severe pain. Patients maintained increases in shoulder abduction (.01), external rotation (.01) and modified Neer scores (.01). Ten of 44 (22.7%) shoulders underwent revision surgery, predominantly for glenoid arthrosis (n = 9). In the 25 shoulders with 5 years of radiographic follow-up, Kaplan-Meier survival analysis demonstrated moderate to severe glenoid erosion in 50% at 5 years, which increased to 59% at 15 years and 88% at 20 years.HHR remains a successful operation for osteoarthritis at long-term follow-up. However, there is a substantive subgroup with continuing pain and a high rate of glenoid bone erosion after 10 years. Surgeons should carefully consider patients' needs and desires when judging the indications for HHR.

Objective To integrate the available data published on peripheral giant cell granuloma (PGCG) into a comprehensive analysis of its clinical/radiological features. Materials and methods An electronic search was undertaken in January 2018 in 5 databases, looking for publications reporting cases of PGCGs. Probability of recurrence was calculated for some variables. Results A total of 165 publications were included, 2824 lesions identified. PGCGs were slightly more prevalent in women and more prevalent in mandibles, usually asymptomatic, and presenting erosion of the subjacent bone in almost one-third of cases. Additional curettage (2.8%) or peripheral osteotomy (0%) after excision presented lower recurrence rates in comparison with excision alone (16%). Excision followed by curettage decreases the probability of recurrence by 85% in comparison with excision alone. Other factors (age, lesion size, follow-up, gender, location, clinical symptoms, bone erosion) seem to do not influence the probability of recurrence. Conclusions As surgical excision alone shows a considerable recurrence rate, excision followed by an additional therapy-curettage or peripheral osteotomy-should be the first choice of treatment of PGCG.