Siglec-15 on Osteoclasts Is Crucial for Bone Erosion in Serum-Transfer Arthritis

: Osteosarcoma of the jaws (OSJ) is a relatively rare disease, accounting for between 2% and 10% of all cases of osteosarcoma, it is morphologically and radiologically identical to the trunk and extremity variant, but distinct in several crucial aspects. : The lesion is characterized by sarcomatous cells which produces a variable amount of osteoid bone. It arises centrally within the bone and can be subdivided into osteoblastic, chondroblastic and fibroblastic subtype, depending on the predominant cell type. : Radiographically, these tumors display a spectrum of bone changes from well-demarcated borders to lytic bone destruction with indefinite margins and variable cortical bone erosion or, in some cases, images of sclerotic bone. Therapeutic options for OSJ include surgery, chemotherapy and radiotherapy, which are employed according to age of the patient, histological classification and localization of the tumor. Today there is no a general consensus in the treatment guidelines for the OSJ though surgery represents the key of the treatment. The main prognostic factor deeply influencing the patient's prognosis remains the complete tumor resection with negative surgical margins. : The aim of the present review is to describe the state of the art regarding diagnostic and surgical treatment aspects of the primary osteosarcoma of the jaws.

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OP0182 PROTEOGLYCAN LOSS IN ARTICULAR CARTILAGE IS ASSOCIATED WITH JOINT INFLAMMATION SEVERITY IN PSORIATIC ARTHRITIS – A COMPOSITIONAL MAGNETIC RESONANCE IMAGING STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5557 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 113.2-113

Author(s):

P. Sewerin ◽

D. Abrar ◽

S. Nebelung ◽

M. Frenken ◽

T. Ulrich ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Bone Erosion ◽

Joint Inflammation ◽

Resonance Imaging ◽

Research Support ◽

Weighted Image ◽

The Third ◽

Deutschland Gmbh ◽

Pip Joint ◽

Flexor Tenosynovitis

Background:Even though cartilage loss is a known feature of psoriatic arthritis (PsA), little is known about its role in the pathogenesis of PsA. Using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) as a non-invasive marker of the tissue’s proteoglycan content, such early (i.e. pre-morphological) changes have been associated with inflammation in rheumatoid arthritis (RA). Yet, this association has not been studied before in PsA.Objectives:Is the severity of local joint inflammation associated to local proteoglycan loss in PsA patients?Methods:Metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of 17 patients with active PsA were evaluated by high-resolution clinical standard morphological and dGEMRIC sequences using a 3T MRI scanner (Magnetom Skyra, Siemens) and a dedicated 16-channel hand coil. Images were analyzed by two independent raters for dGEMRIC indices, PsA MRI scores (PsAMRIS) and total cartilage thickness (TCT). Kendall-Tau correlation coefficients (τ) were calculated.Results:We found significant negative correlations between dGEMRIC indices and total PsAMRIS (τ = -0.5, p= 0.012), synovitis (τ = -0.56, p= 0.006), flexor tenosynovitis (τ = -0.4, p= 0.049), and periarticular inflammation (τ = -0.72, p< 0.001). Significant positive correlations were found between TCT and dGEMRIC indices in all joint levels (τ = 0.43, p<0.001). No significant correlations were determined between dGEMRIC indices and bone erosion, bone edema or bone proliferation.Conclusion:In PsA, proteoglycan loss as assessed by dGEMRIC is associated with periarticular inflammation, synovitis, and flexor tenosynovitis, but not with bone erosion or proliferation, thereby highlighting the need for effective anti-inflammatory treatment regimes. Beyond morphology, advanced MRI techniques may be used to assess cartilage composition in PsA and to identify early changes in cartilage as an imaging biomarker with potential application in detection and monitoring of PsA.Figure 1Right hand of a 26-year-old male with psoriatic arthritis Coronal STIR image (A) of digits 1-5, transversal fat-saturated (fs) T2-weighted image of digits 2-4 (B) and the corresponding transversal fs contrast-enhanced T1-weighted image (C) at the distal portion of the proximal phalanges. Horizontal white bar in (A) indicates level of transversal slices (B) & (C). Sagittal fs Proton Density-weighted image of the third digit (D). A: Increased signal at the collateral ligaments and synovitis of the proximal interphalangeal (PIP) joint of the third digit (white arrow). Periarticular inflammation around the PIP joint and the body of the proximal phalanx of the third digit (arrowhead). B & C: Extensive flexor tenosynovitis (asterix) and periarticular inflammation in the subcutaneous tissues (arrowhead) alongside thickened flexor tendon pulleys (arrow). D & E: Representative sagittal T1-weighted images of the MCP, PIP and DIP joint of the 3rd digit. Following iv contrast administration and appropriate delay of 40 min, A gives the morphological T1 map, while B gives the corresponding parameter map with dGEMRIC values [ms] overlaid. Note the significant decrease in dGEMRIC indices of the PIP joint as compared to the MCP joint.Disclosure of Interests:Philipp Sewerin Grant/research support from: AbbVie Deutschland GmbH & Co. KGBristol-Myers Squibb Celgene GmbHLilly Deutschland GmbHNovartis Pharma GmbH Pfizer Deutschland GmbHRheumazentrum Rhein-Ruhr, Consultant of: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Speakers bureau: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Daniel Abrar: None declared, Sven Nebelung: None declared, Miriam Frenken: None declared, Tim Ulrich: None declared, Karl Ludger Radke: None declared, Gerald Antoch: None declared, Stefan Vordenbäumen: None declared, Ralph Brinks: None declared, Matthias Schneider Grant/research support from: GSK, UCB, Abbvie, Consultant of: Abbvie, Alexion, Astra Zeneca, BMS, Boehringer Ingelheim, Gilead, Lilly, Sanofi, UCB, Speakers bureau: Abbvie, Astra Zeneca, BMS, Chugai, GSK, Lilly, Pfizer, Sanofi, Benedikt Ostendorf: None declared, Christoph Schleich: None declared

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AB0587 ASSESSING THE CHARACTERISTICS AND MANAGEMENT OF KNEE OSTEOARTHRITIS PATIENTS WITH HYPERTENSION BY CLINICIAN SPECIALITY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.549 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1330.2-1331

Author(s):

D. Baldock ◽

E. Baynton ◽

C. F. Ng

Keyword(s):

Knee Osteoarthritis ◽

Sports Medicine ◽

Primary Care Physicians ◽

Bone Erosion ◽

Holistic Treatment ◽

Knee Oa ◽

Patient Demographics ◽

Medical Chart Review ◽

Complex Patients ◽

Minimum Number

Background:Though the pathogenesis of knee osteoarthritis (OA) is complex, patients with OA frequently have other comorbidities, including hypertension, which eludes to other considerations needed when deciding appropriate treatment management.Objectives:This study aims to examine the profiles of knee OA patients with hypertension vs. those without any comorbidities, and to elucidate key differences between these patient groups as potential areas of consideration.Methods:A multi-center, online medical chart review study of patients with OA was conducted between May – July 2020 among US rheumatologists (rheums), orthopedic surgeons (orthos), primary care physicians with a focus in sports medicine (SM PCPs), and pain specialists. Physicians recruited were screened for duration of practice in their specialty (3-50 years) and caseload (>=35 knee OA patients personally managed, at least 10 being moderate-severe). Patient charts were recorded for the next 5 eligible patients seen during the screening period. Respondents abstracted patient demographics and treatments used. Descriptive statistics were used to analyse the data.Results:260 physicians were recruited and collectively reported 796 knee OA patients; 559 were reported to experience hypertension whilst 237 were reported as not experiencing any comorbidities.Reported hypertension patients were significantly older (mean 67 vs 59 years old, respectively; p≤0.01) and weighed more (mean 82kg vs 77kg, respectively; p≤0.01) than patients without comorbidities; they were also significantly more likely to be previous smokers compared to those without comorbidities (23% vs 8%, respectively; p≤0.01). With regards to current knee OA severity, both orthos and SM PCPs reported a significantly higher proportion of hypertension patients that were deemed ‘severe’ (physician opinion) vs patients without comorbidities (orthos: 50% vs 32%, respectively; SM PCPs: 42% vs 23%, respectively; p≤0.01).Rheums and pain specialists reported greater mild opioid usage amongst hypertension patients compared to those without comorbidities (rheums: 28% vs 10%, respectively (p≤0.05); pain specialists: 40% vs 9%, respectively; (p≤0.01)); orthos and SM PCPs stated significantly greater use of corticosteroid injections amongst their reported hypertension patients vs those without comorbidities (orthos: 60% vs 41%, respectively; SM PCPs: 40% vs 19%, respectively; p≤0.01). Hypertension patients reported by orthos and SM PCPs are more likely to be considered for total knee replacement (TKR) surgery compared to those without comorbidities (orthos: 59% vs 32%, respectively; SM PCPs: 37% vs 19%, respectively; p≤0.01). Conversely, hypertension patients reported by rheums are less likely to be considered for TKR vs those without comorbidities (41% vs 18%, respectively; p≤0.05).Reported hypertension patients had a significantly higher mean Visual Analogue Scale for Pain (VAS) score than patients without comorbidities (6.6 vs 5.9, respectively; p≤0.01). A significantly higher proportion of patients with hypertension demonstrate radiographic evidence of bone erosion compared to those without comorbidities (69% vs 56%, respectively; p≤0.01).Conclusion:From the sample surveyed, knee OA patients with hypertension may require a more specific and holistic treatment approach that takes into account their CV status and managing physician specialty. Further investigation using comparator cohort is warranted.References:[1]Ipsos Osteoarthritis Therapy Monitor (May – July 2020, 260 specialists reporting on 769 knee OA patients seen in consultation, data collected online. Participating physicians were primary treaters and saw a minimum number of 35 knee OA patients). Data © Ipsos 2021, all rights reserved.[2]Ipsos Osteoarthritis Therapy Monitor (May – July 2020, 260 specialists reporting on 769 knee OA patients seen in consultation, data collected online. Participating physicians were primary treaters and saw a minimum number of 35 knee OA patients). Data © Ipsos 2021, all rights reserved.Disclosure of Interests:None declared.

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AB0576 BONE EROSION IN PSORIATIC ARTHRITIS ASSOCIATED WITH PSORIASIS DURATION, SKIN, NAIL AND JOINT DISEASE SEVERITY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2796 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1325.2-1326

Author(s):

M. Chamurlieva ◽

E. Loginova ◽

T. Korotaeva ◽

Y. Korsakova ◽

E. Gubar ◽

...

Keyword(s):

Clinical Practice ◽

Psoriatic Arthritis ◽

Disease Severity ◽

Bone Erosion ◽

Joint Disease ◽

Practice Research ◽

Forest Plot ◽

Clinical Practice Research Datalink ◽

Increased Risk ◽

Nail Disease

Background:Psoriatic arthritis (PsA) is heterogeneous in its clinical presentation and disease course, but many patients (pts) develop a destructive form of arthritis. Psoriasis (PsO) precedes arthritis by an average of 7 years. [1]. Theory of transition from PsO to PsA has been proposed recently [2]. But association between skin disease severity and joint disease are still unclear.Objectives:to evaluate association between bone erosion, PsO duration, skin and nail disease severity in PsA pts based on data from clinical practice (RU-PsART cohort).Methods:737 (M/F=350/387) PsA pts fulfilling the CASPAR criteria were included. Mean age 47.4±12.7 years (yrs), PsA duration 55[17;120] mos., PsO duration 165[74.5;292] mos., mean DAPSA 23.3[14;36.9] mos., HAQ-DI - 0.98 [0.5;1.38], CRP - 7.4 [2.1;18] mg/l. All pts underwent standard clinical examination (tender joins count (TJC)/68, swelling joints count (SJC)/66, CRP (mg/l), DAPSA, dactylitis, enthesitis by LEI + Plantar Facia (PF), HAQ-DI. Mild disease was defined as body surface area (BSA)≤10%, moderate to severe as BSA>10%. The presence/absent of nail PsO was evaluated. X-ray of feet and hand were done in 622 out of 737 pts. The one-factor model of logistic regression was used to identify a group of features that are associated with achievement MDA. M±SD, Me [Q25; Q75], Min-Max, %, t-test, Pierson-χ2, Manna-Whitney tests, ORs with 95% CI were performed. All p<0.05 were considered to indicate statistical significance.Results:PsO precedes of PsA by an average of 9.2 years. BSA≤10% was found in 615 out of 672 pts (91.5%), BSA>10% - in 57 out of 672 pts (8.5%). Nail PsO were seen in 230 out of 737 (31.2%). Bone erosion was found in 237 out of 622 of pts (38.1%). Among these pts nail PsO were seen in 67 out of 237 pts (28.3%). Enthesitis found in 236 out of 737 pts (42.1%), dactylitis – in 197 out 731 pts (27%), axial PsA – in 315 out of 731 pts (43.1%). Bone erosion significantly associated with PsO duration more than 5 yrs., skin and nail PsO severity, high PsA activity by DAPSA, axial manifestation and duration of PsA > 36 mos. (Figure 1).Figure 1Forest plot of factors associated with bone erosion in PsA pts.Conclusion:In our cohort the majority of PsA pts had mild PsO preceded PsA on average of 9.2 yrs. Bone erosion was found in 30% of PsA pts which associated with PsO duration, skin and nail disease severity as well as with PsA activity. Early diagnosis and therapeutic intervention within a “window of opportunity” are very important for improving outcomes and prevent structural damage in PsA.References:[1]Tillett W, et al. Interval between onset of psoriasis and psoriatic arthritis comparing the UK Clinical Practice Research Datalink with a hospital-based cohort. Rheumatol. 2017; 56, 2109–2113[2]Scher JU, et al. Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition. Nat Rev Rheumatol. 2019;15(3):153-166. doi: 10.1038/s41584-019-0175-0. PMID: 30742092.Disclosure of Interests:None declared.

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The Role of Collagen Triple Helix Repeat-Containing 1 Protein (CTHRC1) in Rheumatoid Arthritis

International Journal of Molecular Sciences ◽

10.3390/ijms22052426 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2426

Author(s):

Askhat Myngbay ◽

Limara Manarbek ◽

Steve Ludbrook ◽

Jeannette Kunz

Keyword(s):

Rheumatoid Arthritis ◽

Drug Targets ◽

Triple Helix ◽

Cancer Metastasis ◽

Bone Erosion ◽

Cartilage Destruction ◽

Patient Treatment ◽

Collagen Triple Helix ◽

Potential Biomarker

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.

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AB0042 CYTOKINE NETWORK ELUCIDATED BY THE QUANTIFICATION OF MULTIPLE CYTOKINES IN THE SERUM SEQUENTIALLY SAMPLED FROM RA PATIENTS WHO WERE TREATED WITH BIOLOGIC DMARDS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5109 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1323.2-1324

Author(s):

K. Sato ◽

S. Mamada ◽

C. Hayashi ◽

T. Nagashima ◽

S. Minota

Keyword(s):

Bone Erosion ◽

Feedback System ◽

Serum Levels ◽

Type I Interferons ◽

Type I ◽

Serum Samples ◽

Cytokine Network ◽

Biologic Dmards ◽

Type I Ifns ◽

Before And After

Background:Biologic disease modifying anti-rheumatic drugs (DMARDs) have demonstrated that proinflammatory cytokines such as interleukin (IL-) 6 and tumor necrosis factor (TNF) play important roles in the pathogenesis of rheumatoid arthritis (RA). Other cytokines, such as type I interferons (IFNs), are also implicated in its pathogenesis (ref 1). However, the complete picture of the cytokine network involved in RA remains to be elucidated.Objectives:By quantifying sets of cytokines in the serum of RA patients before and after treatment with various biologic DMARDs, we sought to determine the effects of drugs on (A) type I IFNs, (B) soluble IL-6 receptors, and (C) other cytokines.Methods:52 patients with RA were treated with various biologic DMARDs (tocilizumab (TOC): 16, abatacept (ABT): 15, and TNF inhibitors (TNFi): 21). Serum samples were obtained (1) before, (2) approximately 4 weeks after (3) and approximately 12 weeks after the initiation of treatment. A suspension bead-array system was used for analysis; Bio-Plex Human Cytokine 17-plex Assay kits and Express Custom Panels (Bio-Rad), including IFN-β, IFN-α2, soluble IL-6 receptor α (sIL6Rα) and gp130 were used.Results:(1) As expected, the disease activity score 28-joiny count (DAS28) using the erythrocyte sedimentation rate (ESR) significantly decreased in all three groups (TOC, ABT and TNFi) by 12 weeks.(2) IFN-α2 was barely detected in the serum samples. IFN-β seemed to increase slightly in the ABT group, but the increase was not statistically significant.(3) The levels of sIL6Rα did not change substantially. Those of gp130 decreased slightly but significantly in the TOC group by 12 weeks.(4) The levels of IL-6 decreased significantly in the ABT group by 12 weeks. Those in the TNFi group decreased significantly at 4 weeks but not 12 weeks (Fig. 1A).(5) The levels of IL-7 decreased significantly only in the TOC group (Fig. 1B).Conclusion:(1) The biologic DMARDs tested in this study did not significantly affect the serum levels of type I IFNs in this study.(2) The decrease in gp130 in the TOC group may imply that gp130 is induced by IL-6, although whether this level of decrease has physiological significance is open to question.(3) Serum IL-6 was significantly decreased in the TNFi group at 4 weeks but not 12 weeks. TNF has been reported to induce IL-6 (ref 2), but negative feedback loop(s) may be present. Such a feedback system might make the discontinuation of TNFi difficult, even if patients are in remission.(4) IL-7 may be a target of IL-6. A higher level of IL-7 has been reported to be present in the joints of RA patients compared with osteoarthrosis and it is a cytokine implicated in the differentiation of osteoclasts (ref 3). This may partly explain the effect of TOC on preventing bone erosion in RA.References:[1]Ann Rheum Dis. 2007; 66: 1008–14[2]Rheumatology 2007; 46: 920-6[3]Rheumatology 2008; 47: 753-9Acknowledgments:We thank all the members of the Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University. We are also grateful to the patients involved in this study.Disclosure of Interests:Kojiro Sato Grant/research support from: Abbie, Pfizer, Chugai, Astellas, Mitsubishi-Tanabe, Ono, Takeda, Sachiko Mamada: None declared, Chiyomi Hayashi: None declared, Takao Nagashima: None declared, Seiji Minota: None declared

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