A Detailed Analysis of the Association between Urate Deposition and Erosions and Osteophytes in Gout

Pecherstorfer, Caroline; Simón, David; Unbehend, Sara; Ellmann, Hanna; Englbrecht, Matthias; Hartmann, F; Figueiredo, C.; Hueber, Axel J.; Haschka, Judith; Kocijan, Roland; Kleyer, Arnd; Schett, Georg; Rech, Juergen; Bayat, Sara

doi:10.1002/acr2.11172

Cited by 8 publications

(5 citation statements)

References 24 publications

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“…The body’s immune system identifies MSU crystals as foreign invaders, triggering the innate immune response and leading to inflammation through signal transmission. , These crystals, which are endogenous danger signals, are detected by pattern-recognition receptors (PRRs), including both intracellular receptors (NLRs) and membrane receptors (TLRs). Recognition of MSU crystals can activate TLRs and the NALP3 inflammasome signal transduction, which controls the secretion of IL1β.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory Properties of Tongfeng Li’an Granules in an Acute Gouty Arthritis Rat Model

Zhao,

Long,

Zhong

et al. 2024

ACS Omega

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Objectives: To examine the anti-inflammatory properties and underlying mechanisms of Tongfeng Li'an Granules (TFLA), a traditional medicine, in acute gouty arthritis using a rat model. Materials and Methods: We identified 55 major compounds in TFLA via ultrahigh-performance liquid chromatography connected to quadrupole time-of-flight mass spectrometry (UPLC-TQF-MS/MS). Databases were employed for the prediction of potential targets, followed by PPI network construction as well as GO and KEGG analyses. After networkpharmacology-based analysis, a rat gouty arthritis model was used to validate the anti-inflammatory mechanism of TFLA. Results: UPLC-TQF-MS/MS and network pharmacology analyses revealed 55 active ingredients and 160 targets of TFLA associated with gouty arthritis, forming an ingredient-target-disease network. The PPI network identified 20 core targets, including TLR2, TLR4, IL6, NFκB, etc. Functional enrichment analyses highlighted the Toll-like receptor signaling pathway as significantly enriched by multiple targets, validated in in vivo experiments. Animal experiments demonstrated that TFLA improved pathological changes in gouty joint synovium, with decreased ankle joint circumference, serum IL6, IL10, and TNFα levels, as well as reduced protein and mRNA expression of NLRP3, TLR2, and TLR4 in ankle joint synovial tissue observed in the middle-and high-dose TFLA and positive control groups compared to the model group (p < 0.05). Conclusion: This research elucidated the pharmacological mechanisms of TFLA against gouty arthritis, implicating various ingredients, targets, and signaling pathways. Animal experiments confirmed TFLA's efficacy in alleviating inflammation in acute gouty arthritis by modulating Toll-like receptor signaling and NLRP3 expression.

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Section: Discussionmentioning

confidence: 99%

Anti-inflammatory Properties of Tongfeng Li’an Granules in an Acute Gouty Arthritis Rat Model

Zhao,

Long,

Zhong

et al. 2024

ACS Omega

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“…Tophi are associated with bone erosions [ 7 , 17 ], with a strong correlation between tophus volume and bone erosion volume on DECT imaging [ 18 , 19 ]. The DECT findings presented here are consistent with this association and suggest that bones can begin to remodel (decreased erosion size, increased sclerosis or new bone formation) as MSU deposition resolves during pegloticase plus MTX co-therapy.…”

Section: Discussionmentioning

confidence: 99%

Dual-energy CT assessment of rapid monosodium urate depletion and bone erosion remodelling during pegloticase plus methotrexate co-therapy

et al. 2022

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Objectives Pegloticase rapidly lowers serum urate in uncontrolled/refractory gout patients, with ≥1 tophus resolution in 70% of pegloticase responders and 28% of non-responders. Dual-energy computed tomography (DECT) non-invasively detects monosodium urate (MSU) deposition, including subclinical deposition, quantifies MSU volumes, and depicts bone erosions. This report presents DECT findings in MIRROR open-label trial participants receiving pegloticase/methotrexate co-therapy. Methods Serial DECT scans were obtained during pegloticase (8 mg biweekly infusions)/oral methotrexate (15 mg/week) co-therapy. Bilateral hand/wrist, elbow, foot/ankle, and knee images were analysed with default post-processing settings. MSU volumes were quantified and bone erosions were identified and evaluated for remodelling (decreased size, sclerosis, new bone formation). DECT and physical examination findings were compared. Results Two patients underwent serial DECT. Patient 1 (44-year-old male) completed 52-weeks of pegloticase/methotrexate co-therapy (26 infusions). Baseline examination detected 4 tophus-affected joints while DECT identified 73 MSU-affected joints (total MSU volume: 128.76 cm3). At end-of-treatment, there were no clinically-affected joints and 4 joints with DECT-detected MSU deposition. MSU volume decreased by 99% and bone erosion remodelling was evident. Patient 2 (51-year-old male) had 10-weeks of therapy (5 infusions), discontinuing because of urate-lowering response loss. Baseline examination detected 7 tophus-affected joints while DECT identified 55 MSU-affected joints (total MSU volume: 59.20 cm3). At end-of-treatment, there were 5 clinically-affected joints and 42 joints with DECT-detected MSU deposition. MSU volume decreased by 58% and bone erosion remodelling was evident. Conclusion DECT detected subclinical MSU deposition and quantified changes over time. Rapid tophus resolution and bone erosion remodelling occurred during pegloticase/methotrexate co-therapy. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT03635957

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“…This method correlates well with reference standard CT measurement and has good inter-reader reproducibility. This scoring system may facilitate research examining the mechanisms, impact and treatment of structural bone lesions in gout, beyond bone erosion, which, with a few exceptions [1,14], has been the major focus of research to date [15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Development of a radiographic scoring system for new bone formation in gout

Son

Cai

Stewart

et al. 2021

Preprint

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Background Features of new bone formation (NBF) are common in tophaceous gout. The aim of this project was to develop a plain radiographic scoring system for NBF in gout. Methods Informed by a literature review, scoring systems were tested in 80 individual 1st and 5th metatarsophalangeal joints. Plain radiography scores were compared with computed tomography (CT) measurements of the same joints. The best-performing scoring system was then tested in paired sets of hand and foot radiographs obtained over two years from an additional 25 patients. Inter-reader reproducibility was assessed using intra-class correlation coefficients (ICC). NBF scores were correlated with plain radiographic erosion scores (using the gout-modified Sharp-van der Heijde system). Results Following a series of structured reviews of plain radiographs and scoring exercises, a semi-quantitative scoring system for sclerosis and spur was developed. In the individual joint analysis, the inter-observer ICC (95% CI) was 0.84 (0.76-0.89) for sclerosis and 0.81 (0.72-0.87) for spur. Plain radiographic sclerosis and spur scores correlated with CT measurements (R2 = 0.65-0.74, P < 0.001 for all analyses). For the hand and foot radiograph sets, the inter-observer ICC (95% CI) was 0.94 (0.90-0.98) for sclerosis score and 0.76 (0.65-0.84) for spur score. Sclerosis and spur scores correlated highly with plain radiographic erosion scores (R2 = 0.87 and 0.71 respectively), but not with change in erosion scores over two years (R2 = -0.04 – 0.15). Conclusion A semi-quantitative plain radiographic scoring method for assessment of NBF in gout is feasible, valid, and reproducible. This method may facilitate consistent measurement of NBF in gout.

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A Detailed Analysis of the Association between Urate Deposition and Erosions and Osteophytes in Gout

Cited by 8 publications

References 24 publications

Anti-inflammatory Properties of Tongfeng Li’an Granules in an Acute Gouty Arthritis Rat Model

Anti-inflammatory Properties of Tongfeng Li’an Granules in an Acute Gouty Arthritis Rat Model

Dual-energy CT assessment of rapid monosodium urate depletion and bone erosion remodelling during pegloticase plus methotrexate co-therapy

Development of a radiographic scoring system for new bone formation in gout

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