Les enjeux de la microarchitecture osseuse

Le diagnostic de l'ostéoporose (OP) postménopausique repose essentiellement sur la densitométrie osseuse. Evaluée par absorptiométrie à rayon X (DXA), la densité minérale osseuse (DMO) fournit une mesure fiable et non invasive de la quantité d'os présent. Si la DMO est considérée comme un bon estimateur de la résistance osseuse, elle ne fournit, cependant, qu'une information partielle sur la qualité de l'os. Dès la première définition de l'OP en 1993, il a été souligné que cette maladie, facteur de risque de fracture, était aussi conditionnée par d'autres facteurs parmi lesquels l'altération de la microarchitecture trabéculaire osseuse prend une grande place. Cette notion du rôle de la microarchitecture trabéculaire a été élargie en 2001 à celle du rôle de facteurs qualitatifs osseux. Un des enjeux majeurs actuels serait donc de mieux diagnostiquer l'OP et donc la possibilité de mieux définir le risque fracturaire en combinant différentes informations, indépendantes et complémentaires relatives à la résistance osseuse, faisant espérer une meilleure maîtrise de l'épidémiologie de la maladie. Dans ce sens, plusieurs études ont démontré l'intérêt d'associer l'analyse de la micro-architecture osseuse à la DMO pour une meilleure prédiction du risque fracturaire. L'objectif de cet article est de faire le point sur les enjeux de la microarchitecture osseuse et les différents outils de caractérisation (analyse morphologique, topologique, de texture) et les méthodes d'imagerie (imagerie par rayons X, scanner et IRM) de la microarchitecture trabéculaire osseuse

Cluster analysis in early axial spondyloarthritis predicts poor outcome in the presence of peripheral articular manifestations

Objectives To assess whether two cluster analysis-based axial SpA (axSpA) endotypes (A for purely axial; B for both axial and peripheral) are stable over time and are associated with different long-term disease outcomes. Methods K-means cluster analysis was performed at each visit (until 5 years) on 584 patients from the DESIR cohort, who completed all planned visits, and validated in 232 consecutive axSpA patients from the BeGiant cohort. Cluster stability overtime was assessed by kappa statistics. A generalized linear mixed-effect analysis was applied to compare outcomes between clusters. Classification and regression tree (CART) analysis was performed to determine a decision rule able to assign a given patient to a definite cluster at onset. Results Both endotypes remained remarkably stable over time. In the DESIR cohort, patients in cluster B showed higher disease activity, worse functional outcome and higher need for anti-rheumatic drugs than patients in cluster A. CART analysis yielded three main clinical features (arthritis, enthesitis and dactylitis) that accurately determined cluster assignment. These results could be replicated in the Be-GIANT cohort. Conclusion Cluster-based axSpA endotypes were reproducible in two different cohorts, stable over time and associated with different long-term outcome. The axSpA endotype with additional peripheral disease manifestations is associated with more severe disease and requires more intensive drug therap

Monocyte transcriptomes from patients with axial spondyloarthritis reveal dysregulated monocytopoiesis and a distinct inflammatory imprint

International audienceBackground: In patients with axial spondyloarthritis (axSpA), monocytes show a pre-activated phenotype. Gut inflammation is a trigger of monocyte activation and may also affect their development in the bone marrow (BM). As gut inflammation is commonly observed in axSpA patients, we performed a detailed analysis of monocyte transcriptomes of axSpA patients in two cohorts and searched for signs of activation and developmental adaptations as putative imprints of gut inflammation. Methods: Transcriptomes of blood CD14+ monocytes of HLA-B27+ axSpA patients and healthy controls (HC) were generated by microarrays from cohort 1 and by RNA-sequencing from cohort 2. Differentially expressed genes from both analyses were subjected to gene set enrichment analysis (GSEA) and to co-expression analysis in reference transcriptomes from BM cells, blood cells and activated monocytes. As serological markers of translocation, 1,3 beta-glycan, intestinal fatty acid binding protein, and lipopolysaccharide binding protein (LBP) were determined by LAL and ELISA. Results: Transcriptome analysis identified axSpA-specific monocyte signatures showing an imprint of LPS/cytokine-activated monocytes, late granulopoietic BM cells, blood neutrophils, and G-CSF-mobilized blood cells, which suggests LPS/TNF activation and more prominent BM adaptation promoting a neutrophil-like phenotype. GSEA mapped axSpA upregulated genes to inflammatory responses and TNFα signaling and downregulated probe-sets to metabolic pathways. Among translocation markers, LBP levels were significantly increased in axSpA patients vs. HC (p < 0.001). Stratified analysis by disease activity and stage identified an “active disease signature” (BASDAI ≥ 4) with an imprint of LPS/cytokine-activated monocytes and CD16+ monocyte subsets. The “AS signature” (vs. non-radiographic axSpA) showed a reinforced neutrophil-like phenotype due to deprivation of dendritic cell transcripts. Conclusions: The neutrophil-like phenotype of axSpA monocytes points towards a biased monocytopoiesis from granulocyte-monocyte progenitors. This shift in monocytopoiesis and the LPS/cytokine imprint as well as the elevated LBP levels are indicators of systemic inflammation, which may result from bacterial translocation. The BM adaptation is most prominent in AS patients while disease activity appears to be linked to activation and trafficking of monocytes

2022 French Society for Rheumatology (SFR) recommendations on the everyday management of patients with spondyloarthritis, including psoriatic arthritis

International audienceObjective: Update the French Society for Rheumatology (SFR) recommendations on the everyday management of patients with spondyloarthritis, including psoriatic arthritis.Methods: Following standardized procedures, a systematic literature review was done by four supervised rheumatology residents based on questions defined by a task force of 16 attending rheumatologists. The findings were reviewed during three working meetings that culminated in each recommendation receiving a grade and the level of agreement among experts being determined.Results: Five general principles and 15 recommendations were developed. They take into account pharmacological and non-pharmacological measures along with treatment methods based on the dominant phenotype present (axial, articular, enthesitis/dactylitis) and the extra-articular manifestations (psoriasis, inflammatory bowel disease, uveitis). NSAIDs are the first-line pharmacological treatment in the various presentations. Conventional synthetic disease modifying antirheumatic drugs (csDMARDs) are not indicated in the axial and isolated entheseal forms. If the response to conventional treatment is not adequate, targeted therapies (biologics, synthetics) should be considered; the indications depend on the clinical phenotype and presence of extra-articular manifestations.Conclusion: This update incorporates recent data (published since the prior update in 2018) and the predominant clinical phenotype concept. It aims to help physicians with the everyday management of patients affected by spondyloarthritis, including psoriatic arthritis

Erratum to ``2022 French Society for Rheumatology (SFR) Recommendations on the Everyday Management of Patients with Spondyloarthritis, Including Psoriatic Arthritis'' [Joint Bone Spine 2022;89:105344]

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Clinical presentation of patients suffering from recent onset chronic inflammatory back pain suggestive of spondyloarthritis: The DESIR cohort

International audienceOBJECTIVES:DESIR is a prospective longitudinal multicentric French cohort of patients with inflammatory back pain suggestive of spondyloarthritis, with a 10-year-follow-up. The purpose is to evaluate the performances of the different sets of classification criteria for axial spondyloarthritis, and to describe the frequency and characteristics of the clinical features of axial spondyloarthritis.METHODS:Demographic data and items allowing classification and indices calculation were collected, as well as biologic and imaging data. Baseline data are analyzed. The performance of the several classification criteria sets was evaluated (likelihood ratio) with the physician's diagnosis as external gold standard. For the clinical presentation of axial spondyloarthritis, a descriptive analysis was conducted.RESULTS:Seven hundred and eight patients are included. Ninety-two percent of them satisfy at least one set of classification criteria: mNY 26%, Amor 79%, ESSG 78%, ASAS 70%; physician's confidence level 6.8±2.7. 81 and 83% of patients fulfil modified (including MRI) Amor or ESSG criteria. Axial involvement is present in 100% of the cases. NSAIDs are taken by 90%, with an NSAID sore of 50±46. BASDAI over 40 is noted in 60% and elevated CRP in 30% of the cases. HLA-B27 is present in 58%. According to ASDAS CRP levels, 12.7% are in inactive disease, 63% in high disease activity; mean BASFI was 30. Peripheral involvement is present in 57%, with arthritis in 37% of these. Enthesitis is noted in 49% of the patients, and first symptom in 22.5%; anterior chest wall involvement is noted in 44.6%, and dactylitis in 13%. For extra articular manifestations, psoriasis is recorded in 16%, uveitis in 8.5% and IBD in 5.1%. Smoking is present in 36.3% and hypertension in 5.1% of the cases.CONCLUSION:These data represent the base of evaluation of the follow-up of this cohort, allowing future specific studies

Non–TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug

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