Para médicos · reumatologia
Resumos de artigos, podcasts e newsletters sobre Osteoartrite, para atualização médica.
A newsletter aborda o manejo do risco cardiovascular na artrite reumatoide e a eficácia de terapias sequenciais com romosozumabe e denosumabe para prevenir a perda óssea em usuários de corticoides. Além disso, discute o uso de doses reduzidas de rituximabe em AR soropositiva e a correlação entre sinovite e progressão radiográfica na osteoartrite de mãos.
A newsletter discute como a obesidade atenua a resposta aos inibidores de JAK na artrite reumatoide, enfatizando que o IMC elevado é um modificador de efeito clínico relevante. O conteúdo também aborda a alta prevalência de critérios de fibromialgia em pacientes pós-COVID, a conduta expectante na artrite por parvovírus B19 e a associação genética entre regulação tireoidiana e deposição de cristais de pirofosfato de cálcio.
A newsletter analisa um estudo populacional que revela alta prevalência de edema ósseo sacroilíaco em indivíduos saudáveis, alertando para a necessidade de contexto clínico no diagnóstico de espondiloartrites. Além disso, discute as divergências entre diretrizes globais para esclerose sistêmica e apresenta avanços em novas terapias biológicas para o lúpus.
A newsletter discute as novas diretrizes do ACR 2025 para o lúpus eritematoso sistêmico, enfatizando a importância da ultrassonografia para identificar sinovites frequentemente subestimadas no exame clínico. O conteúdo detalha o desempenho de terapias como anifrolumabe e belimumabe em diferentes perfis de pacientes, além de abordar a aprovação do anacinra e casos de fraturas por insuficiência na artrite reumatoide.
This study aimed to investigate the relationship between cognitive performance and the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA), emphasizing the role of plasma metabolites and proteins. Using National Health and Nutrition Examination Survey 2011 to 2014 data, cognitive functions of participants aged >60 years were evaluated, examining their correlation with OA and RA. Covariates, including demographics and health-related factors, were included. Genetic causality was determined using Mendelian randomization with single-nucleotide polymorphisms from the UK Biobank and other datasets. Linkage disequilibrium score regression and colocalization analyses were performed to validate genetic correlations and identify shared genetic variants. Cognitive performance was assessed in 387 and 237 OA and RA patients, respectively, compared with 1569 controls. OA patients had significantly lower Consortium to Establish a Registry for Alzheimer's Disease-4 cognitive scores (odds ratio [OR]: 0.962, P = .001), while RA patients had lower digit symbol substitution test scores (OR: 0.980, P = .001). Mendelian randomization revealed a negative causal association between cognitive performance and OA (OR: 0.767, P = .001) and RA (OR: 0.712, P = .006). Plasma components, including bone sialoprotein 2, NKP44, and the metabolite X-11478, were causally linked to cognitive performance. Mediation analysis identified mediators, including FGR and 6CKine. Linkage disequilibrium score regression revealed a genetic correlation between cognitive performance and OA and RA, with colocalization analysis identifying shared genetic factors. GDF5 and TRAIP were associated with OA, and EHMT2 with RA. Cognitive factors, influenced by plasma components, may influence OA and RA onset. This relationship highlights the need for integrated interventions targeting cognitive function and joint health.
A newsletter destaca os avanços do EULAR 2026, com ênfase no estudo INDIGO sobre o obexelimabe na doença relacionada à IgG4 e no papel do metotrexato na redução da progressão para artrite reumatoide em pacientes ACPA-negativos. Além disso, discute a importância da padronização na fisioterapia para osteoartrite e o uso combinado de biomarcadores e ultrassom para triagem de doença pulmonar intersticial.
Background Osteoarthritis is a leading cause of pain and disability, yet the biological processes linking peripheral joint pathology with central pain mechanisms and wider symptom burden remain poorly defined. Methods We performed an integrated metabolomic and inflammatory analysis of cerebrospinal fluid and serum obtained from patients with osteoarthritis (n = 81) and healthy pain-free controls (n = 70). Proton nuclear magnetic resonance spectroscopy was used for metabolomic profiling, alongside targeted protein assays for inflammatory mediators. Orthogonal partial least squares discriminant analysis was applied to assess separation between groups and to determine diagnostic accuracy. Associations between metabolites and clinical outcomes, including pain intensity, disability and sleep disturbance, were examined, with adjustment for age and BMI. Results Clear separation between osteoarthritis and healthy pain-free control participants was observed in both biofluids, with classification accuracies of 87% for serum and 89% for cerebrospinal fluid. Reduced serum histidine, glutamine, albumin (lysyl) and lysine distinguished osteoarthritis from healthy controls. In cerebrospinal fluid, osteoarthritis was characterised by higher lactate and glutamate and lower glucose and glutamine compared to controls. Combining metabolomic data with inflammatory proteins increased diagnostic accuracy to 90% and remained significant after matching for age and BMI. Reductions in serum histidine and glutamine were consistent across subgroups, including stratification by pain severity. These metabolites correlated inversely with pain intensity, disability, sleep disturbance and overall symptom impact, and were more markedly altered in women, who also reported greater symptom burden. Conclusions Osteoarthritis is associated with a distinct pattern of peripheral and central metabolic disturbance. Histidine and glutamine emerge as promising biomarkers related to pain and clinical severity, highlighting metabolic pathways as potential targets for improved stratification and intervention in osteoarthritis pain.
Background Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease affecting synovial joints and extra-articular systems. Public recognition of early symptoms, complications, and misconceptions is important for timely help-seeking. Objective To assess public awareness of RA articular symptoms and extra-articular complications in Jordan, identify misconceptions, evaluate intended healthcare-seeking behavior, determine predictors of awareness, and examine questionnaire psychometric performance. Methods A cross-sectional online survey using nonprobability, quota-based recruitment through social media and messaging-application advertisements was conducted among adults across all Jordanian governorates between February 10 and March 24, 2026. The cleaned analytic sample included 2332 respondents. Awareness was assessed using six symptom items and five complication items, with scores transformed to a 0–100 scale. Adequate awareness was defined as correct identification of at least 6 of 11 awareness items. Misconception burden was calculated from four items. Multivariable regression identified predictors of awareness and appropriate intended action. Internal consistency and exploratory factor analysis evaluated questionnaire performance. Results The mean total awareness score was 54.4 (SD, 33.5), and 56.3% of respondents had adequate awareness. Symptom awareness was slightly higher than complication awareness (mean scores, 56.9 vs. 51.4). Joint pain (73.1%), subcutaneous nodules (68.2%), and joint deformity (64.3%) were most recognized, whereas eye inflammation (29.7%), morning stiffness (45.5%), and small-joint swelling (46.5%) were less frequently identified. Misconceptions were common: 46.7% believed RA is not serious, 34.9% endorsed herbal cure beliefs, and 30.5% confused RA with osteoarthritis. Only 40.4% selected an appropriate intended action. Prior awareness of RA, knowing someone with RA, and higher education were the strongest predictors of awareness. Symptom and complication subscales showed good internal consistency (Cronbach’s alpha, 0.806 and 0.799), and exploratory factor analysis supported a dominant general awareness factor. Conclusion
Summary This expert position statement reframes arthroplasty and spinal fusion complications under the unified endpoint of implant fixation failure, defined as loss of mechanical integrity of the bone–implant unit over time. It synthesizes mechanistic and clinical evidence and provides evidence-informed recommendations for peri-operative bone health optimization. Background Osteoporosis is traditionally conceptualized as causing fragility fractures. However, compromised bone quality also affects the integrity of bone–implant constructs, influencing whether implants maintain fixation, interfaces remain stable, and fusion constructs consolidate. Objective To synthesize mechanistic, translational, and clinical evidence on how osteoporosis and osteoporosis pharmacotherapies influence implant fixation failure across arthroplasty and spinal fusion, and to provide evidence-informed clinical recommendations for peri-operative bone health assessment and optimization within a unified construct-level framework. Methods A position statement was developed following a structured literature search. Evidence was synthesized narratively by defining implant fixation failure as a construct-level outcome encompassing periprosthetic fracture, loosening, subsidence, pseudarthrosis, and junctional failure. Recommendations were categorized by strength (strong or conditional) and certainty of evidence (high, moderate, or low). Results Low bone mineral density (BMD) is associated with implant fixation failure across arthroplasty and spinal fusion. In arthroplasty, randomized trials demonstrate preservation of periprosthetic BMD with bisphosphonates, while registry analyses suggest improved implant survival. In spinal fusion, antiresorptive and anabolic therapies influence fixation-related parameters, with anabolic agents showing the most consistent evidence for enhanced fusion mass and earlier union. Much of the literature relies on radiographic or biomechanical endpoints rather than definitive outcomes. Conclusions Viewing arthroplasty and spinal fusion complications through a shared construct-level perspective provides a coherent link between osteoporosis and reconstructive durability. Systematic peri-operative bone health optimization may improve construct longevity, although more definitive outcome-driven trials are needed. Closer integration
Shoulder rehabilitation is prolonged, feedback-dependent, and frequently limited by adherence, particularly after surgery. Virtual reality (VR) and related immersive or semi-immersive technologies may support rehabilitation by combining motion tracking, visual feedback, graded repetition, and gamified engagement. This narrative review summarizes current evidence on VR and digitally assisted shoulder and upper-limb rehabilitation and critically evaluates the extent to which these data can inform post-arthroplasty pathways. A narrative review was performed using PubMed/MEDLINE, PubMed Central, and targeted cross-checking in Scopus, Web of Science, and the Directory of Open Access Journals up to May 2026. Search domains combined shoulder and upper-limb terms, virtual reality, augmented reality, mixed reality, extended reality, and exergaming terms, rehabilitation and telerehabilitation terms, and postoperative shoulder surgery or arthroplasty terms. Priority was given to systematic reviews, randomized or controlled studies, validation studies, feasibility studies, and clinician-perspective studies relevant to shoulder biomechanics and rehabilitation implementation. The available literature supports three main conclusions. First, consumer-grade immersive systems can provide reliable within-system shoulder motion monitoring, although absolute agreement across devices remains imperfect. Second, VR, exergaming, and digitally assisted rehabilitation have shown feasibility, high acceptability, and potential benefits for adherence, pain, range of motion, and patient-reported function in rotator cuff repair, adhesive capsulitis, subacromial impingement, and other shoulder disorders. Third, evidence directly specific to anatomic or reverse shoulder arthroplasty rehabilitation remains limited; therefore, extrapolation from rotator cuff repair, conservative shoulder disorders, and digital home-based arthroplasty rehabilitation should be made cautiously. Rehabilitation clinicians support supervised or hybrid use rather than autonomous unsupervised replacement of conventional care. VR should be interpreted as an adjunct to clinician-led rehabilitation, not as a stand-alone substitute. Its most plausible current roles are improving engagement, enabling structured repetition, supporting within-system
BACKGROUND: Virtual reality (VR) had gained traction as an innovative approach for post-total knee arthroplasty (TKA) rehabilitation in patients with knee osteoarthritis (KOA). However, evidence of its comparative efficacy against conventional methods remained fragmented. This study synthesized data from randomized controlled trials (RCTs) to evaluate VR's impact on pain, functional recovery, and quality of life in KOA patients post-TKA. METHODS: A systematic search was performed across PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (inception to December 2024). RCTs comparing VR-based rehabilitation with standard care in KOA patients post-TKA were included. Data on pain (Visual Analogue Scale [VAS], Numerical Pain Rating Scale [NPRS]), functional outcomes (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], Timed Up and Go [TUG], Range of Motion [ROM]), and quality of life (Short Form-36 [SF-36], EuroQol Five-Dimensional Questionnaire [EQ-5D]) were extracted. Risk of bias was assessed using the Cochrane Collaboration tool. Meta-analyses were conducted using RevMan 5.3, with mean differences (MD) or standardized MD and 95% confidence intervals (CI) calculated for continuous outcomes. Heterogeneity was quantified via the I² statistic. RESULTS: Ten RCTs (588 participants) were analyzed. VR interventions demonstrated transient advantages in WOMAC scores at one month (SMD: -1.40; 95% CI: -2.37 to -0.43; P 70%) was observed, which was attributed to variability in VR modalities, session duration, and rehabilitation settings. CONCLUSION: VR-based rehabilitation provided short-term improvements in functional mobility and joint flexibility for KOA patients post-TKA, but its long-term benefits remained uncertain. Methodological limitations, including high heterogeneity and inadequate blinding, necessitated cautious interpretation of the findings. Future trials should adopt standardized protocols, integrate gender-stratified analyses, and prioritize long-term follow-ups to optimize VR's clinical utility.
A newsletter apresenta os principais destaques do congresso EULAR 2026, abordando desde a eficácia da manutenção do alopurinol na gota até novos alvos terapêuticos para a Síndrome de Sjögren. Além das atualizações clínicas, explora como fatores psicossociais e a satisfação conjugal influenciam diretamente o prognóstico e a saúde mental de pacientes com doenças reumáticas crônicas.
A newsletter apresenta os resultados do estudo REPLENISH, que valida o secuquinumabe como uma nova opção biológica para a polimialgia reumática, dobrando as taxas de remissão sustentada. São discutidos também novos insights do EULAR 2026, incluindo a distinção entre entesófitos inflamatórios e mecânicos, o valor prognóstico do fator reumatoide na GEPA e o potencial das fibras dietéticas em melhorar a resposta clínica ao metotrexato na artrite reumatoide.
Objective To identify autoantibodies in presymptomatic individuals that associate with the onset of rheumatoid arthritis (RA) and to distinguish early RA from osteoarthritis (OA), particularly in individuals lacking classic RA serologic markers. Methods We analyzed serum and plasma from three cohorts: presymptomatic individuals who later developed RA (n = 518), a subset of these at RA diagnosis (n = 241), matched population controls (n = 530), and patients with OA (n = 287). Bead‐based multiplex flow immunoassay detected IgG autoantibodies against joint‐related peptides relevant in arthritis models. Principal component analysis was used to identify subgroups and univariable regression analyses to characterize the performance of autoantibodies with significance for patients with RA negative for anti–cyclic citrullinated peptide (anti‐CCP) and rheumatoid factor (RF), that is, the seronegative RA diagnosis (SeNe) test. Multivariable logistic regression identified autoantibodies with the strongest discriminative power between cases and controls. Results Autoantibody profiles revealed three distinct presymptomatic subgroups, suggesting early immune heterogeneity. The SeNe test was associated with symptom onset within 2.5 years in 13% of anti‐CCP and RF‐negative individuals. Specificity for RA versus OA was 97% (95% confidence interval, 95%–99%). An improved version (SeNe 2.0) identified 16% of anti‐CCP and RF‐negative presymptomatic individuals with 98% specificity versus population controls. Two of five SeNe 2.0 autoantibodies were associated with the presymptomatic state in the multivariable model, including RF and anti‐CCP. Conclusion These novel biomarkers can identify presymptomatic, seronegative individuals at high risk of RA onset and support their recruitment into trials for personalized prevention. Additionally, they distinguish early seronegative RA from OA with high specificity. image
A newsletter analisa a busca por biomarcadores para a nefrite lúpica, destacando que, apesar de candidatos promissores como a IL-16 e o CD163 urinários, a biópsia renal ainda é o padrão-ouro indispensável. O conteúdo também aborda benefícios da combinação leflunomida e hidroxicloroquina no tratamento de Sjögren e a confiabilidade do PHQ-8 no rastreio de depressão em pacientes com dor crônica, sem viés de sobreposição somática.
Objective Musculoskeletal complications represent a significant burden in diabetes, yet the distinct presentation between Type 1 (T1DM) and Type 2 Diabetes Mellitus (T2DM) remains under-characterized. This study aimed to evaluate and quantify the burden of rheumatic manifestations and subclinical enthesopathy in these two distinct clinical phenotypes. Methods We conducted a cross-sectional analysis of 65 patients (21 T1DM, 44 T2DM). A comprehensive rheumatological evaluation assessed adhesive capsulitis (defined as painful restriction of active and passive motion in ≥ 2 planes), knee osteoarthritis (per American College of Rheumatology clinical classification criteria), cheiroarthropathy, and soft tissue rheumatism. High-resolution musculoskeletal ultrasound evaluated five bilateral entheseal sites using the Glasgow Ultrasound Enthesitis Scoring System (GUESS). Effect sizes (Cohen’s d) and 95% Confidence Intervals (CI) were calculated to assess the magnitude of intergroup differences. Results The T2DM phenotype was characterized by older age and higher BMI compared to T1DM. T2DM patients exhibited a markedly higher prevalence of adhesive capsulitis, knee osteoarthritis, and anserine bursitis. Ultrasound revealed a substantially higher enthesopathy burden in the T2DM group, with a mean GUESS score of 6.8 ± 2.1 compared to 1.1 ± 0.2 in T1DM. The effect size for the difference in enthesopathy scores (Cohen’s d = 3.29) exceeded the effect size for the age difference (d = 2.79), suggesting that the observed structural burden may not be fully explained by age alone. Available HbA1c data showed similarly suboptimal glycemic control in both groups. Conclusion T2DM was associated with a higher burden of structural entheseal abnormalities and higher GUESS scores compared with T1DM. These findings may reflect the combined influence of obesity, metabolic factors, and age. Interpretation should consider baseline demographic differences between groups and the broad clinical definitions employed.
A newsletter discute o uso de canabinoides na osteoartrite, destacando que o CBD tópico apresenta melhores sinais de eficácia que a via oral, embora ainda faltem evidências robustas para prescrição rotineira. O conteúdo também aborda novos protocolos de ultrassom para coluna vertebral, o potencial terapêutico da liraglutida e os marcadores de gravidade em uma coorte de 10 anos de Doença de Still.
OBJECTIVE: To enable interventions aimed at preventing onset of frequent knee osteoarthritis (OA) symptoms and their sequelae, effective screening methods are required. Conventional radiographs are accessible and inexpensive; consequently, they have the potential to identify those at high risk of developing symptoms. Thus, we aimed to determine whether radiographic severity is prognostic of frequent symptoms at 12-and 48-month follow-up visits. METHODS: We studied knees from participants of the Osteoarthritis Initiative without frequent symptoms at the baseline visit. Posteroanterior semi-flexed knee radiographs were obtained at the baseline visit and scored for Kellgren-Lawrence (KL) grade (0-4). Frequent knee symptoms were defined by self-report at baseline, month 12, and month 48 follow-up visits. We used knee-based logistic regression, using generalized estimating equations to account for correlation between knees within person, to assess if baseline KL grade was associated with incident frequent symptoms (at 12 and 48 months). RESULTS: The study included 5,653 knees (3,407 participants). The incidence of frequent symptoms at 12 months by baseline KL grades were: 12.4% (KL0), 15.6% (KL1), 18.6% (KL2), 24.7% (KL3), and 37.2% (KL4). Relative to KL0, the odds (and 95% confidence interval) of frequent knee symptoms at 12 months were elevated for KL1 (OR=1.30, (1.05-1.61)), KL2 (OR=1.61, (1.32-1.96)), KL3 (OR=2.31, (1.82-2.92)), and KL4 (OR=4.18, (2.69-6.48)). 48-month results were similar. CONCLUSION: s: Radiographic OA severity should be considered a potential prognostic biomarker to identify individuals at high risk of developing knee symptoms.
Objective To explore the association between periarticular subchondral bone mineral density (sBMD) and the presence and progression of osteoarthritis (OA) knee pain. Methods Participants were recruited from the Osteoarthritis Initiative (OAI). Tibial sBMD at medial and lateral compartments was measured by dual-energy x-ray absorptiometry at 30 or 36 months (baseline) and reassessed at 48 months. Knee pain was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale (range 0-20, with a higher score indicating greater pain) through month 108. Baseline knee pain was categorized as low/no or high (pain score < 5 vs ≥ 5). Pain progression was defined as an increase in WOMAC pain score of ≥ 2 in at least 3 of the 6 follow-up visits. Logistic regression with generalized estimating equations was used to assess associations between sBMD (per SD increase) and knee pain, accounting for within-participant correlation between knees. Results Of 594 participants (mean age 64.1 years; 50.5% male; 1137 knees), 31.6% of knees exhibited higher pain at baseline, and 37.4% demonstrated pain progression during follow-up. Higher medial sBMD and medial-to-lateral sBMD ratio were associated with the progression of knee pain (medial sBMD: odds ratio [OR] 1.50; 95% CI 1.25-1.81; P < 0.001; medial-to-lateral ratio: OR 1.29; 95% CI 1.11-1.49; P = 0.001). Medial-to-lateral sBMD ratio was also associated with the presence of knee pain (OR 1.21; 95% CI 1.05-1.40; P = 0.01). Conclusion Higher medial-to-lateral sBMD ratio was associated with both the presence and progression of knee pain, suggesting that relative subchondral bone distribution may better capture biomechanical loading imbalance related to symptomatic OA than absolute sBMD alone.
Background Molecular endotyping may facilitate the successful development of personalized treatments of knee osteoarthritis (KOA). The aim of this exploratory and hypothesis-generating study was to develop a clinically actionable tool for predicting molecular endotypes of KOA using blood-based biomarkers, and to explore the potential for differential treatment effects across biomarker-based endotypes in prior phase II-III KOA drug trials. Methods Fourteen biomarkers from 226 KOA participants from IMI-APPROACH were assessed for a multinomial logistic regression model to predict structural damage, inflammation, and low tissue turnover endotypes. An optimized panel of six serum biomarkers (C2M, C3M, N-MID, PRO-C2, PRO-C4, sCTX-I) was identified quantitatively by testing all biomarker combinations in models adjusting for age, sex, and BMI. These biomarkers were used for endotype predictions in KOA participants from the randomized placebo-controlled trials MIV-711 (n = 244) (NCT02705625), salmon calcitonin (n = 947) (NCT00486434), and UBX0101 (n = 175) (NCT04129944). Results The structural damage endotype showed the greatest numerical 26-week reduction in NRS knee pain when treated with MIV-711 (-6.46%; 95% CI: -16.23%, 3.31%). Notably, only the structural damage endotype had a significant two-year reduction in WOMAC pain when treated with salmon calcitonin (-6.19%; 95% CI: -10.55%, -1.83%). Considering the subset treated with salmon calcitonin with the top 20% highest probability of belonging to the structural damage endotype, a 9–15% reduction in standard deviation of the two-year change in WOMAC pain was observed. Enriching the trial for this subset with lower outcome variability could have led to an 18–28% reduction in the needed sample size. Conclusions This exploratory study suggests the feasibility of predicting KOA endotypes using a minimal panel of tissue-turnover biomarkers. The observed treatment effects of anti-bone resorptive treatments and reduced outcome
OBJECTIVE: While osteoarthritis (OA) and rheumatoid arthritis (RA) can necessitate total knee arthroplasty (TKA), the mechanisms and radiographic patterns of joint space narrowing (JSN) differ. Deep learning (DL) enables compartment-specific measurement of minimum joint space width (mJSW). This study compared JSN patterns between patients with RA and OA undergoing TKA and evaluated associations between mJSW and RA disease activity. METHODS: In this retrospective study, 409 RA patients undergoing TKA (2000-2021) were age- and sex-matched with OA patients. A validated DL model quantified medial and lateral mJSW from AP knee radiographs at two time points: early (>2 years before TKA) and late (≤2 years before TKA). The rate of JSN was calculated in 302 patients with paired radiographs. Mixed-effects models adjusted for BMI and alignment. RA disease activity, serology, and medications were recorded. RESULTS: RA demonstrated narrower lateral mJSW than OA at the late time point (5.6 vs. 7.0 mm, P<0.01), with comparable medial values. RA exhibited uniform bicompartmental JSN, whereas OA patients showed medial narrowing. RA had a faster mean lateral ΔmJSW (0.11 mm/year; P = 0.01), while OA had a faster mean medial ΔmJSW (0.21 mm/year; P<0.001). Longer RA duration and higher inflammatory markers were negatively associated with lateral mJSW. Seronegative RA showed faster lateral ΔmJSW in the surgical knee than seropositive patients (0.12 vs 0.06 mm/year; P = 0.03). CONCLUSION: Patients with RA demonstrated diffuse, symmetric cartilage loss contrasting with medialpredominant narrowing in patients with OA. Automated DL-based measurement enables scalable, compartment-specific assessment of compartment-specific patterns of joint degeneration.
Chronic pain is the hall-mark symptom of osteoarthritis (OA) and although several therapies are available, a sizeable number of patients do not gain adequate pain relief from these therapies. Predicting those patients who will not respond to current therapies remains a challenge. Although psychosocial, sensitivity, inflammation and genetic factors have been identified as pain mechanisms that predict response to pain therapy, none of these is a sufficiently strong predictor alone. An emerging approach to this challenge is the use of machine-learning algorithms that integrate several pain mechanisms, which are superior to previous prediction models. Importantly, these machine-learning algorithms identify networks of pain mechanisms that could be targeted therapeutically. From these models, a new mechanistic framework is proposed, in which pain in OA can be viewed either as a simpler joint disease with inflammation or as a complex pain problem that involves multiple factors. The latter is associated with a higher risk of poor response to standard OA pain therapy. Understanding the complexity of pain in OA and predicting those who are at risk of not responding to standard OA pain therapy are essential for improving the management of pain in OA.
A newsletter discute a necessidade de ajustar os pontos de corte dos índices CDAI e SDAI para a realidade brasileira, visando uma identificação mais precisa da remissão na artrite reumatoide e evitando o sobretratamento. Além disso, revisa as diretrizes de rastreio para doença pulmonar intersticial associada à AR e destaca o potencial condroprotetor da metformina em pacientes diabéticos com osteoartrite.
Objective Identification of osteoarthritis (OA)–specific synovial inflammatory pathways and their temporal relevance is critical for therapeutic targeting. We compared mononuclear inflammatory/immune cell responses following joint injury that does or does not lead to OA to define bona fide OA‐associated cellular events. Methods We undertook detailed temporal flow cytometric and messenger RNA (mRNA) expression analysis in mice after sham or destabilization of the medial meniscus (DMM) surgery. This was compared with patients with meniscal injury and OA, evaluating the role of synovial monocytes/macrophages versus lymphocytes in catabolic metalloproteinase secretion in vitro. We determined the effect of transient or delayed systemic T cell depletion on DMM‐induced OA pathology. Results OA‐inducing/DMM and non–OA‐inducing/sham surgery had an identical synovial monocyte/macrophage number, activation, and polarization. The number and activation of synovial (not splenic or peripheral blood) CD4 + and CD8 + lymphocytes were increased from one day after DMM versus sham and showed a persistent cyclical elevation throughout OA onset and progression. There was a temporal imbalance in synovial Th17/Treg and Th1/Th2 lymphocytes during DMM‐induced OA initiation and progression. We confirmed early postinjury and late OA CD3/CD8 T cell responses in synovial tissues from patients, identified an association between CD8 and early postinjury symptoms, and defined a significant role for CD3 + T cells in synovial metalloproteinase secretion. Anti‐CD3 cell depletion studies in mice provided an initial approach to testing this hypothesis, offering preliminary evidence that early postinjury T cell responses may be associated with long‐term OA pathology. Conclusion We identify a hitherto unappreciated pathophysiologic role of acute T cell activation after joint injury in long‐term posttraumatic OA risk, providing a novel diagnostic and therapeutic target.
The psoriatic arthritis phenotype has evolved over the past several decades. The original description of 5 clinical patterns has been expanded into 6 domains including peripheral arthritis (which includes 3 of the patterns described by Moll and Wright namely distal, oligoarticular and polyarticular), axial disease, dactylitis, enthesitis, skin and nails. In this article we review the evolution of the PsA phenotype, from the Moll and Wright subtypes described in 1973 and how they might have changed, evolution of our understanding of axial PsA, consider race and geographic differences in disease expression, role of obesity and sex on the PsA phenotype, effect of co-expression of PsA and FM as well as OA on the phenotype, and consider difficult to treat PsA.
Osteoarthritis is fundamentally a whole-joint disease, and a critical pathological feature is the limited capacity of articular cartilage for self-regeneration, leading to accelerated joint degeneration once breakdown begins. Current therapeutic strategies are primarily palliative, and conventional marrow stimulation procedures such as microfracture often yield suboptimal, short-lived outcomes. Stem cell-based biologic augmentation using mesenchymal stem cells has emerged as a promising approach through direct chondrocyte differentiation, paracrine stimulation, and immunomodulation. Umbilical cord-derived mesenchymal stem cells offer robust proliferative capacity, enhanced biological potency, and lower immunogenicity than adult mesenchymal stem cells, and can be obtained with minimal ethical concerns. Clinical trials of human umbilical cord blood-derived mesenchymal stem cells combined with hyaluronic acid hydrogel (CARTISTEM®) have demonstrated excellent safety, improved patient-reported outcomes, and durable hyaline-like cartilage regeneration. Emerging evidence further suggests that combining high tibial osteotomy with human umbilical cord blood-derived mesenchymal stem cells-based cartilage regeneration for medial compartment osteoarthritis with varus malalignment creates a synergistic biological and mechanical environment that promotes structural cartilage repair. In conclusion, surgically transplanted human umbilical cord blood-derived mesenchymal stem cells show therapeutic potential in arthritic knees, although the role of intra-articular injections and the optimal indications for combined high tibial osteotomy remain to be clarified.
Background This study aimed to estimate the global, regional, and national Osteoarthritis (OA) burden and trends in older adults from 1990 to 2021, with a particular focus on the contribution of high body mass index (BMI) to the OA burden. Methods Using 2021 Global Burden of Disease Study data, we estimated the incidence, DALYs, and trends of OA in older adults across 204 countries and territories from 1990 to 2021. Spearman’s correlation analysis was applied to investigate relationships between age-standardized rates and the sociodemographic index (SDI). We quantified the BMI-attributable contribution to the OA burden. The Bayesian Age-Period-Cohort (BAPC) model was applied to project the global OA trend in older adults up to 2040. Results From 1990 to 2021, global OA cases in older adults increased by 148.65%. Age-standardized incidence and DALY rates increased annually by 0.08% and 0.31%, respectively. East and Southeast Asia exhibited the fastest increase in age-standardized DALY rates. The OA burden peaked in the 65–69-year age group, with women compared with men experiencing a higher burden. Knee OA imposed the heaviest burden, followed by hand OA, with regional variations across four anatomical sites. The OA burden, including specific sites, positively correlated with the SDI. The attributable proportion of OA burden due to high BMI increased by 21.39%, with the knee OA burden from high BMI exceeding the hip OA burden. The BAPC model predicted that OA burden will continue to rise in the future. Conclusions OA in older adults is a major global challenge, with knee OA being the most burdensome. High BMI, a modifiable risk factor, contributes significantly to OA, particularly in the knees. To reduce the OA burden, public health strategies should prioritize obesity
Objective The aim of this single-blind randomized clinical trial was to compare the effectiveness of extracorporeal shock wave therapy (ESWT) and high-intensity laser therapy (HILT) on clinical parameters in knee osteoarthritis. Patients and methods A total of 60 patients aged between 40 and 75 years, diagnosed with primary knee osteoarthritis and admitted to the Department of Physical Medicine and Rehabilitation, Gaziantep University, were included in the study. Sixty patients were randomized into two groups using the envelope method. Group 1 received ESWT (3 sessions/week, total of 6 sessions), and Group 2 received HILT (5 sessions/week, total of 10 sessions) for a duration of 2 weeks. A standardized home exercise program was applied to all patients. Patients were evaluated before treatment, after treatment, and at the 6th week post-treatment using the Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lequesne algofunctional knee index. Statistical analyses were performed using SPSS 22.0 (IBM Corp., Armonk, NY, USA), including t-test, chi-square, ANOVA, and Pearson correlation; significance was set at p < 0.05. Results In both groups, compared to pre-treatment values, significant improvements were observed in VAS (p < 0.001), WOMAC pain, stiffness, and physical function (p < 0.001), as well as Lequesne index scores (p < 0.001) after treatment and at the 6th week post-treatment. No significant differences were found between the groups in intergroup comparisons. Conclusion Both ESWT and HILT are effective and safe treatment methods for reducing pain, disease severity, and improving physical function in knee osteoarthritis. Our findings support broader clinical use of both treatments, though further comprehensive studies are required. Key Points • In both the ESWT and laser groups, significant improvements were observed in VAS,
Objectives To evaluate the long-term efficacy and safety of iguratimod (IGU) in patients with knee osteoarthritis (KOA). Methods This retrospective study included patients diagnosed with KOA at Beijing Jishuitan Hospital between July 2023 and January 2024. All participants received IGU monotherapy at a dose of 25 mg twice daily for 3 months and were subsequently followed for a total duration of 12 months. Clinical data, including demographic characteristics, laboratory tests, and imaging assessments, were systematically collected and analyzed. Pain intensity, global disease assessment, physical function, and adverse events were evaluated at baseline, 3 months, and 12 months. Results A total of 62 patients were included in the analysis, of whom 77.4% were female. The mean age was 58.56 ± 8.57 years, and disease duration ranged from less than 1 year to more than 10 years. At baseline, the mean Visual Analogue Scale (VAS) score was 6.08 ± 1.56, and the mean Patient Global Assessment (PGA) score was 3.94 ± 1.34. Significant reductions in both scores were observed at 3 and 12 months. The VAS score decreased to 2.39 ± 1.64 at 3 months and 2.65 ± 1.70 at 12 months, while the PGA score declined to 1.39 ± 1.07 and 1.53 ± 1.21, respectively (all p < 0.001). The median total functional score improved markedly from 6.00 (IQR: 5.00) at baseline to 1.00 (IQR: 3.00) at 3 months and 1.00 (IQR: 2.00) at 12 months (p < 0.001). At 3 months, 51.6% of patients achieved a squat test score of 0, and 66.1% achieved a stair climbing test score of 1; these functional gains were maintained at 12 months (p < 0.001). Similar improvements were observed across additional functional domains. At both follow-up time points, 58.1% of patients reported no restriction in the chair rise
Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Beyond structural injury to cartilage, synovium, and subchondral bone, OA is increasingly recognized as an immunometabolic disorder characterized by low-grade inflammation and dysregulated innate and adaptive immune responses. Nutritional biomarkers-derived from macro- and micronutrient status and metabolite signatures-can shape the OA inflammatory microenvironment by modulating macrophage polarization, T-cell subset balance, cytokine networks, and key signaling programs (e.g., NF-kappaB, JAK/STAT, NLRP3 inflammasome, and oxidative stress pathways), thereby influencing tissue catabolism and pain sensitization. This review reorganizes the literature around how clinically measurable nutritional biomarkers map onto immune-cell programs and core OA pathological processes, and critically appraises evidence strength and translational readiness. Most biomarker–OA links are supported primarily by mechanistic rationale and observational associations, while longitudinal and interventional validation remains limited and heterogeneous; key gaps include standardized assays and cutoffs, phenotype- and joint site–stratified prospective cohorts, and externally validated models demonstrating incremental prognostic utility beyond established clinical and imaging predictors.
Aims This review critically evaluates the therapeutic role of cannabis and its derivatives in managing osteoarthritic pain, with a focus on clinical evidence and efficacy of various pharmacological dose and forms. Methods A literature search was conducted using Medline, EMBASE, CINAHL and COCHRANE databases with the key terms “cannabis”, “cannabidiol”, “CBD”, “osteoarthritis” and “human”. Inclusion criteria were limited to studies published in English with full-text access from year 2020 onwards; animal-based laboratory research, narrative surveys, and questionnaire-based studies were excluded. Results Out of 517 search results, 19 were included in this review. Initial clinical studies using different CBD formulations and dosages suggest potential benefits for relieving OA symptoms, with topical CBD showing the most encouraging results and an acceptable safety profile. Nonetheless, the overall strength of the evidence is constrained by considerable variability in CBD dosing and product types, as well as the absence of robust comparisons with standard analgesic treatments, making it challenging to determine the true therapeutic value of CBMPs for OA symptom management. Conclusion Although cannabinoids provide a strong biological basis as a potentially useful adjunct for managing osteoarthritis-related pain, the current body of evidence does not yet justify their routine clinical use. Challenges such as variability in product quality, absence of consistent prescribing guidelines and regulatory barriers further hinder their integration into practice. Robust, well-designed clinical trials with standardised dosing and formulation protocols are needed to determine the most effective and safe therapeutic approach.
Background Knee osteoarthritis (OA) causes significant chronic pain and disability. Current non-operative treatments are largely symptom-modifying. While intra-articular mesenchymal stem cell (MSC) therapies are promising, randomized controlled trials (RCTs) report inconsistent results due to heterogeneity in cell sources, preparations, and techniques. Methods We searched PubMed, Scopus, Cochrane Library, and Google Scholar through December 10, 2025. Peer-reviewed RCTs evaluating intra-articular stem cell–based therapies for knee OA were included. Primary analyses compared MSCs versus controls across pain, function, structure, and safety. Subgroup and sensitivity analyses explored heterogeneity by preparation, source, comparator, follow-up, age, and injection guidance. Results Twenty-eight RCTs were included. MSC therapies significantly improved pain: ΔVAS (MD -1.67; p = 0.007), post-treatment VAS (MD –3.55; p = 0.01), and KOOS pain (MD 15.37; p = 0.03). Functional gains occurred in KOOS ADL (MD 12.84; p = 0.04), KOOS sports (MD 11.76; p < 0.001), and KOOS symptoms (MD 15.16; p = 0.02). WOMAC, KOOS quality of life, and Lequesne Index showed no significant differences. Benefits were more consistent with culture-expanded preparations, bone marrow sources, saline controls, and ultrasound guidance. ΔVAS remained significant after excluding short follow-up studies; ΔVAS and KOOS pain remained significant in older cohorts. MRI-based WORMS scores were non-significant, indicating no consistent structural benefit. Safety analyses revealed higher rates of injection-site pain (RR 2.04; p = 0.0005), joint swelling (RR 3.39; p = 0.0003), and other adverse events (RR 1.26; p = 0.01). Serious complications (e.g., infection) were uncommon and non-significant. Conclusion Current evidence suggests stem cell–based therapies serve a primarily symptom-modifying rather than structure-modifying role. Higher frequencies of local reactions must be weighed against symptomatic benefits. Larger, standardized trials are needed to identify optimal preparations and patient profiles
Objective To analyze unselected routine care patients with all rheumatic diagnoses for positive anxiety, depression, and/or fibromyalgia screening within a single MDHAQ (multidimensional health assessment questionnaire), and for pain and RAPID3 (routine assessment of patient index data) in patients with positive vs negative screens. Methods Each rheumatology patient with any diagnosis at Rush University is given an MDHAQ at each encounter to provide comprehensive medical history information, completed by most patients in 5-10 minutes and scored by a professional in <30 seconds. Frequencies of positive MDHAQ anxiety, depression, and fibromyalgia screening indices were computed in patients with 15 rheumatic diagnoses in 5 categories: inflammatory, connective tissue, non-inflammatory, bone mineral disorders, and primary fibromyalgia. Median pain 0-10 visual numeric scale (VNS) and 0-30 RAPID3 scores were compared in patients with positive vs negative screens. Results In 1,337 study patients (excluding primary fibromyalgia), 30% had positive screens for anxiety, 24% for depression, and 25% for (non-primary) fibromyalgia, and 44% any of these 3 multimorbidity screens. Positive screens in different rheumatic diagnosis categories ranged from 17%-39% for anxiety, 9%-33% for depression, 7%-31% for (non-primary) fibromyalgia, and 30%-52% for any multimorbidity screen. Median pain was 7.0/10 vs 4.0/10 and median (RAPID3) 17.0/30 vs 8.2/30 in patients with any of 3 positive vs all negative screens (p< 0.001). Conclusion Positive anxiety, depression, and/or fibromyalgia screens in 44% of routine care patients who have significantly higher pain scores agree with extensive research findings, suggesting inclusion of pragmatic screening for clinical decisions at all routine encounters.
A newsletter destaca que adolescentes com vasculite por IgA apresentam maior risco de púrpura persistente e proteinúria, exigindo vigilância renal redobrada. Na espondiloartrite axial, o uso de upadacitinibe mostrou-se superior à troca por outro anti-TNF ou anti-IL-17 após falha terapêutica inicial. O conteúdo também aborda o diagnóstico de eritema ab igne e a identificação de dano miocárdico subclínico no lúpus através de técnicas avançadas de imagem.
Objective This study aimed to investigate alterations in the spatial distribution of urate crystals in the osteoarthritic synovium of patients with different levels of serum uric acid (SUA). Additionally, we examined the association between SUA levels and the severity of synovitis and pain in anteromedial osteoarthritis (AMOA) of the knee. Methods Patients who underwent knee arthroplasty due to AMOA were prospectively enrolled. Blood, synovial fluid, and synovium samples were collected and UA levels were quantified. The degree of synovitis was evaluated histologically, and the levels of inflammatory cytokines in the synovial fluid were measured. The spatial distribution of urate crystals in the synovium was determined using Gomori methenamine silver staining, and the pain subscale of the Western Ontario McMaster Universities Osteoarthritis Index was used to evaluate knee pain. The relationships among SUA, degree of synovitis, and knee pain were assessed using Spearman rank correlation and multivariable analyses. Results The pattern of urate crystal deposition in the osteoarthritic synovium was significantly altered in populations with different SUA levels. The capillary wall, sublining layer, and lining cells were sequentially affected. SUA level was the only risk factor for high‐grade synovitis and severe pain in the multivariate analysis. SUA level was also positively correlated with UA level in the synovial fluid and synovium, Krenn histologic score of the synovium, knee pain, and inflammatory cytokine level in the synovial fluid. Conclusion Spatial urate crystal distribution in the synovium was altered when SUA levels were elevated. Elevated SUA levels were also associated with aggravated synovitis and pain.
Objective We employed global genetic deletion of CD14 and intra‐articular CD14 blockade across multiple murine osteoarthritis (OA) models that vary in severity of pathology and rate of progression to test the hypothesis that CD14 inhibition attenuates synovial inflammation and associated pain during disease progression. Methods Human OA synovial fluid samples were evaluated for associations between soluble CD14 (sCD14) levels with knee hyperalgesia and inflammation. Next, the effect of CD14 deficiency on OA progression was assessed across mild to severe murine surgical models of post‐traumatic OA (PTOA), in which pain behavior and a high‐dimensional transcriptomic and proteomic analysis of CD14‐dependent synovial inflammation were performed. In a therapeutic approach, local delivery of a CD14 blocking antibody was administered, and the effects on OA histopathology and pain were evaluated across surgical and nonsurgical murine models of PTOA. Results Increased sCD14 within human synovial fluid correlates with joint effusion volume and knee hyperalgesia. Further, targeting CD14 protects against increased evoked pain behaviors and OA‐driven mobility impairments across murine models that differ in severity and across male and female cohorts. Using flow cytometry, single‐cell transcriptomics, and spatial proteomics, we further show that CD14 deficiency modulates the synovial and fat pad inflammatory landscape post injury, reducing myeloid populations and modulating local fibroblast populations. Lastly, across surgical and nonsurgical PTOA models, which incorporated risk factors of sex and obesity, we reveal that local delivery of a CD14 blockade protects against OA‐associated pain and mobility loss. Conclusion Our results strongly support that targeting synovial and fat pad inflammation through blockade of CD14 can safely ameliorate OA pain and disability after a predisposing injury. image
Numerous bone erosions were identified in the MCP and wrist joints of healthy individuals. Relatively well-defined erosions measuring ≥0.5 mm3 were frequently observed in specific carpal bones, particularly the capitate and lunate. Additionally, erosions smaller than 0.5 mm3 showed a positive correlation with age, suggesting that numerous small cortical bone defects may represent age-related physiological changes. These findings provide important context when interpreting erosive changes associated with joint diseases in clinical practice.
Objective To explore whether biologic levels of specific per‐ and polyfluoroalkyl substances (PFAS) and a mixture of PFAS—reflecting the overall effect and accounting for correlations among PFAS—relate to incident hand osteoarthritis (HOA) and progression. Methods Among a case‐cohort sample from the Osteoarthritis Initiative (n = 1,878), we examined associations of eight PFAS in serum with odds of developing over the subsequent 4 years (1) symptomatic HOA and (2) an increased number of joints with radiographic osteoarthritis (Kellgren‐Lawrence ≥2; yes/no). We used weighted logistic regression to assess single PFAS (continuous and quartiles) and quantile g‐computation to assess the PFAS mixture in relation to our primary outcomes. Results Participants were primarily female (58%) and on average aged 62 years and overweight (mean body mass index = 28.6 kg/m 2 ). Participants with higher perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA; continuous variables) had greater odds of incident symptomatic HOA (odds ratio [OR] [95% confidence interval (CI)] per interquartile range increment: PFDA 1.12 [1.05–1.20]; PFNA 1.07 [1.00–1.13]), but associations were not monotonic when these PFAS were represented in quartiles. Participants with higher perfluorohexane sulfonic acid had lower odds of incident HOA (eg, OR 0.94 [95% CI 0.88–1.00] per interquartile range increment). We observed no other consistent associations between PFAS and either outcome. Conclusion We observed possible associations of PFDA and PFNA serum concentrations with symptomatic HOA incidence, but we otherwise found no consistent evidence that greater PFAS concentrations relate to a greater chance of developing HOA incidence or progression.
Objective To evaluate the relation of colchicine use to the risk of total joint arthroplasty (TJA) in individuals with gout, the most common form of arthritis for which colchicine is prescribed. Methods This new‐user design, time‐stratified, population‐based cohort study used a UK primary care database (2000–2021). We identified participants with gout who were newly prescribed colchicine after their gout diagnosis. Each colchicine initiator was propensity score matched with a noninitiator using one‐year cohort accrual blocks. The effect of colchicine on the risk of TJA was assessed using Cox proportional hazard regression. Analyses were repeated and limited to participants with both gout and knee/hip osteoarthritis (OA). Results We identified 31,478 colchicine initiators who were propensity score matched to an equal number of noninitiators (mean age 60 years, mean body mass index 30), with a median follow‐up time of 4.5 years. Colchicine initiators had a 12% lower risk of TJA than noninitiators (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.81–0.96), which remained similar after additional adjustment for confounders (HR 0.89, 95% CI 0.82–0.97). Colchicine initiators with gout had a 23% lower risk of TJA among those with knee/hip OA (HR 0.77, 95% CI 0.64–0.92) compared with noninitiators (HR 0.77, 95% CI 0.64–0.92). Conclusion In this large population‐based cohort of people with gout, colchicine initiation was associated with a modestly lower risk of TJA. Colchicine may offer a long‐term benefit in reducing the risk of joint arthroplasty in individuals with gout and knee or hip OA.
Objective Pain is the hallmark symptom of osteoarthritis (OA), and its biologic drivers remain poorly understood. Although the role of innate immunity in OA has been extensively studied, the involvement of adaptive immunity, in particular Treg cells, is not well understood. Methods We performed omics profiling of peripheral blood from 46 patients with knee OA with similar radiographic stage, including deep immunophenotyping, cytokine profiling, transcriptomics, and T cell receptor analysis on sorted CD4+ Treg cells and Teff cells. Results We identified an immunologic signature associated with OA‐related pain. Cytokines promoting Treg expansion and activation (with increases of sIL2‐RA, sTNFR1, and sTNFR2) were correlated with the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscore, suggesting a potential Treg dysfunction. Nineteen T cell subsets were correlated with WOMAC pain. Notably, we found a negative correlation of cell subsets associated with Treg expansion and activation (FoxP3+CTLA4+, CD4+CD57+, Treg CD95+, and CD4 Treg CD45RA−). Differential gene expression analysis between patients with low and high WOMAC pain intensity (threshold ≥40/100) revealed an upregulation of inflammasome‐related genes such as IL1RL1 , IL31RA , IFITM3 , NLRP3 , and IFNG in Treg cells. Functional enrichment analysis highlighted an overrepresentation of innate immune response, interleukin‐8, and interferon activation and pro‐inflammatory genes in the Treg cells of patients with high pain intensity. Conclusion Collectively, our systems immunology approach highlights potential associations between Treg dysfunctionality and OA‐related pain, providing new hypotheses into the adaptive immune system's contribution to OA‐related pain.
Articular cartilage is crucial for joint function; however, it has limited regenerative capacity when damaged, a hallmark of many rheumatic diseases. Non-invasive imaging is essential for early diagnosis, therapeutic monitoring and prognostication. MRI remains the reference standard, offering detailed assessment of both morphological and compositional cartilage changes. Technological advances, including high-resolution and compositional MRI techniques such as T2 mapping, T1ρ, delayed gadolinium-enhanced MRI of cartilage, sodium imaging, diffusion imaging and ultra-short echo-time imaging, enable early detection of matrix alterations that precede structural breakdown. CT arthrography, although it involves radiation, serves as a valuable alternative when MRI is contra-indicated, offering high performance in the detection and evaluation of cartilage surface lesions. Emerging modalities, such as ultrasonography and PET, offer additional functional insights but are currently limited in scope. Artificial intelligence is poised to transform cartilage imaging through accelerated acquisition, automated segmentation, improved interpretation and enhanced efficiency, with growing clinical adoption. Advanced cartilage imaging will probably have an increasingly important role in clinical rheumatology, particularly for the optimization of individualized management of cartilage pathology.
Articular cartilage is crucial for joint function; however, it has limited regenerative capacity when damaged, a hallmark of many rheumatic diseases. Non-invasive imaging is essential for early diagnosis, therapeutic monitoring and prognostication. MRI remains the reference standard, offering detailed assessment of both morphological and compositional cartilage changes. Technological advances, including high-resolution and compositional MRI techniques such as T2 mapping, T1ρ, delayed gadolinium-enhanced MRI of cartilage, sodium imaging, diffusion imaging and ultra-short echo-time imaging, enable early detection of matrix alterations that precede structural breakdown. CT arthrography, although it involves radiation, serves as a valuable alternative when MRI is contra-indicated, offering high performance in the detection and evaluation of cartilage surface lesions. Emerging modalities, such as ultrasonography and PET, offer additional functional insights but are currently limited in scope. Artificial intelligence is poised to transform cartilage imaging through accelerated acquisition, automated segmentation, improved interpretation and enhanced efficiency, with growing clinical adoption. Advanced cartilage imaging will probably have an increasingly important role in clinical rheumatology, particularly for the optimization of individualized management of cartilage pathology.
A newsletter analisa uma meta-análise que indica benefícios significativos da metformina na redução da dor e melhora funcional em pacientes com osteoartrite de joelho. Outro destaque é a discussão sobre o mimetismo clínico entre a artrite reumatoide soronegativa e a doença por depósito de pirofosfato de cálcio (CPPD), especialmente em pacientes idosos. O conteúdo também revisa os principais avanços terapêuticos de 2025 em doenças como lúpus, esclerose sistêmica e IgG4-RD.
Objectives Femoroacetabular impingement (FAI) and synovitis have been recognized as essential factors for developing osteoarthritis (OA) in the hip joints. However, little is known about altered synovial cellular compositions, their associated transcriptomic profiles, and cell‐cell interactions in FAI and hip OA. Methods Synovial samples from a sex‐matched cohort of FAI and hip OA patients (n = 6/condition) were analyzed using integrative single‐cell RNA sequencing and spatial transcriptomics. Results Compared to FAI, epiregulin (EREG)‐enriched lining synovial fibroblast‐like synoviocytes (FLS) were significantly increased in hip OA. EREG + FLS are pro‐inflammatory due to elevated expression of CXCL1 , IL8 , and MMPs . Pseudotime analysis predicts that EREG + FLS are derived from DPP4 + PI16 + sublining FLS, likely regulated by NFIX and REL, as well as ELK3 and ETV6 transcription factors under FAI or OA conditions, respectively. Importantly, the only putative cell‐cell interaction is fibroblast growth factor 2 (FGF2) – syndecan 4 (SDC4) communication between COL1A1 + IGFBP5 + fibrotic macrophages (MΦ) and EREG + FLS. This interaction may induce expression of IL6, IL8, and MMP1 in hip OA synovium. The gene ontology (GO) analysis of activated genes downstream of FGF2‐SDC4 signaling revealed that inflammation and angiogenesis were upregulated in hip OA, while positive gene transcription and skeletal muscle differentiation were dominant in FAI. Moreover, we also found that EREG + CCL20 + MMP3 hi lining FLS along with most MΦ and monocyte populations are unique to hip OA patients compared to knee OA and RA patients. Conclusion The findings of this study offer a groundwork in tailoring novel targets and therapies for FAI and hip OA patients.
Dry needling (DN) targeting myofascial trigger points (MTrPs) has been proposed as a treatment for knee disorders, including knee osteoarthritis (KOA) and patellofemoral pain syndrome (PFPS). This meta-analysis evaluated the effectiveness of DN in improving pain and function in patients with knee disorders. This meta-analysis was conducted in accordance with PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420261294603). Systematic searches were performed in PubMed, Embase, Web of Science, Cochrane CENTRAL, CNKI, Wanfang, and VIP databases from inception to December 2025 for randomized controlled trials (RCTs) comparing DN targeting MTrPs with sham DN, no intervention, or other active treatments for knee disorders. Primary outcomes were pain intensity measured by the Visual Analog Scale (VAS) and Numeric Pain Rating Scale (NPRS). Secondary outcomes included functional status assessed by the WOMAC functional subscale and the Kujala Patellofemoral Score. Weighted mean differences (WMDs) were calculated using random-effects models. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and certainty of evidence was evaluated using the GRADE framework. Twenty RCTs (n = 1,234; mean age range: 22-69 years) met the inclusion criteria. Compared with controls, DN significantly reduced knee pain across all pain measures: NPRS (WMD = -1.00, 95% CI: -1.25 to -0.76; I² = 0.0%), VAS (WMD = -1.19, 95% CI: -1.73 to -0.66; I² = 80.4%), and WOMAC Pain subscale (WMD = -1.76, 95% CI: -2.57 to -0.95; I² = 67.6%), with an overall pooled pain reduction of WMD = -1.25 (95% CI: -1.58 to -0.92; I² = 74.7%). DN also significantly improved knee function as measured by the WOMAC functional subscale (WMD = -6.59, 95% CI: -8.88 to -4.29; I² = 61.6%) and the Kujala Patellofemoral Score (WMD = 6.39, 95% CI: 4.64 to 8.14; I² = 30.1%). Pre-specified sensitivity analyses using standardized mean differences confirmed the robustness of these
Hand osteoarthritis is a leading cause of pain, disability, and reduced quality of life in older adults. Joint protection programs are recommended as a core component of self-management, but traditional delivery is limited by barriers to access. Digital programs can overcome these challenges for some people, but their reach and effectiveness depend on usability. We conducted a mixed methods usability study of a remotely delivered joint protection program designed for people with hand osteoarthritis. Twenty-three participants took part, recruited through purposeful sampling to ensure inclusion of groups often underrepresented in research. Usability was assessed using predefined task completion, browser-based eye-tracking, participant ratings, and think-aloud protocols, with iterative refinements applied between participants. Routine navigation tasks, such as navigating between different modules, accessing interactive activities, and viewing short videos, were consistently completed with high success. More complex interactive tasks, including drag-and-drop activities, scenario-based modules, and toggling videos to full screen, initially posed challenges. Over successive iterations, however, usability improved markedly, with later participants achieving near-perfect performance. Qualitative analysis revealed that participants valued clear language, short and focused videos, interactive elements, and the ability to proceed at their own pace, while raising concerns about excessive clicking, unclear instructions, and variation in age representation. Iterative refinements, including platform adjustments, clearer instructions and an introductory video, addressed these issues and contributed to improved performance. This study demonstrates that a remotely delivered, technology-enabled joint protection program for hand osteoarthritis is usable, accessible, and engaging across a diverse sample. Beyond refining the program itself, the study introduces a practical framework for iterative, equity-informed usability testing that can inform the design of future digital health interventions.
Immune cell senescence is an important intermediary linking organismal ageing, chronic low-grade inflammation, and disordered bone metabolism. With advancing age, immune cells undergo systemic functional remodeling and exhibit a series of characteristic alterations, including reduced proliferative capacity, skewed differentiation, abnormal migration and homing, impaired phagocytic and clearance functions, and changes in their secretory profile. These changes persistently disrupt the osteoimmune microenvironment and ultimately promote enhanced bone resorption, suppressed bone formation, and deterioration of bone quality. This Review centers on the immunological basis of bone homeostasis and systematically summarizes the major biological features of immune cell senescence, with a particular focus on the key cellular mechanisms through which it drives chronic bone disease. It further analyses its pathological manifestations and disease-specific differences in osteoporosis, osteoarthritis, rheumatoid arthritis, and diabetes-related bone disease. Current evidence indicates that the contribution of immune cell senescence varies across different diseases: its pathogenic association appears to be relatively more direct in osteoporosis and rheumatoid arthritis, whereas in osteoarthritis and diabetes-related bone disease it more often acts as a contributor to inflammatory amplification and microenvironmental deterioration. At present, intervention strategies targeting immune cell senescence mainly focus on modulation of macrophage polarization, immune-mediated clearance of senescent cells, restoration of adaptive immune homeostasis, and MSC-related improvement of the local microenvironment, but overall these approaches remain at the preclinical or early translational stage. Future studies should integrate single-cell sequencing, spatial transcriptomics, and multi-omics approaches to define local immune cell senescence landscapes and establish robust biomarker systems, thereby promoting the transition from mechanistic research to precision intervention in chronic bone diseases.
Osteoarthritis (OA) is a common degenerative disease characterized by the deterioration of articular cartilage, affecting approximately 240 million people worldwide. Low-grade inflammation-particularly the imbalance in macrophage polarization-is a critical factor in osteoarthritis progression. M1-type macrophages exacerbate cartilage destruction by secreting pro-inflammatory factors and matrix-degrading enzymes, while M2-type macrophages promote repair through anti-inflammatory factors. While macrophage polarization changes in OA have been reported, the macrophage subpopulation communication architecture and dominant ligand-receptor axes across dynamic state transitions remain unclear-and that this is what our integrated framework aims to address. This study leverages single-cell transcriptomic data, including 6 normal samples and 12 OA samples, to systematically analyze the interaction patterns and key ligand-receptor pairs of M1/M2 macrophages during OA progression. Methods include cell subset annotation, GSVA functional enrichment, pseudotemporal trajectory analysis, and hdWGCNA network construction. This study provides single-cell-level evidence for the inflammatory mechanisms of OA. Cell-cell communication analysis revealed strong bidirectional interactions between M1 and M2 macrophages. Integrative analysis of macrophage subpopulations, pseudotime, hdWGCNA, and cell-cell communication analysis identified SEMA4A as the only overlapping key gene. The SEMA4 signaling pathway exhibited active communication among macrophage subpopulations, with M1 macrophages acting as dominant signal senders. Ligand-receptor analysis showed that SEMA4A-PLXNB2 was the predominant interaction pair with the highest communication probability. This study identified a dynamic "increase-then-decrease" expression pattern of SEMA4A along the macrophage pseudotime trajectory, suggesting its involvement in macrophage differentiation and state transitions. Ligand-receptor analysis revealed SEMA4A-PLXNB2 as the dominant interaction signaling pathway among macrophage subpopulations, with M1 macrophages acting as central hubs in sending and receiving signals. Together with previous evidence that SEMA4A forms a positive feedback loop with NF-κB and amplifies IL-6/TNF-α production, thereby promoting cartilage catabolism and tissue remodeling,
Osteoarthritis (OA) is increasingly recognized as a chronic low-grade inflammatory joint disorder characterized by progressive cartilage degeneration, synovial inflammation, subchondral bone remodeling, and disrupted intercellular communication. Growing evidence indicates that exosomal non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, are key regulators of the OA microenvironment. By mediating intercellular signal transfer among chondrocytes, synovial fibroblasts, macrophages, osteoblasts, and osteoclasts, exosomal ncRNAs influence inflammatory mediator production, immune cell polarization, extracellular matrix metabolism, and osteochondral homeostasis. These regulatory effects are closely associated with major signaling pathways, including NF-κB, PI3K/AKT/mTOR, MAPK, and inflammasome-related cascades. Beyond their mechanistic roles in disease progression, exosomal ncRNAs also show strong potential as minimally invasive biomarkers for OA diagnosis and staging, as well as therapeutic agents or delivery vehicles for targeted intervention. This review focuses on the mechanisms of exosomal ncRNAs in modulating the osteoarthritis inflammation microenvironment, highlighting the potential of exosomal ncRNAs in osteoarthritis diagnosis and the prospects for their use in osteoarthritis medicine.
Knee osteoarthritis (OA) is a disabling joint condition that leads to extreme morbidityand quality of life impairment, particularly among older adults. This study aimed to investigate the socio-demographic factors and comorbid conditions influencing the severity of symptoms of knee OA using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Data were derived from 622 patients across 9 months from the major healthcare facilities of Dhaka. This study found age, sex, educational status, obesity, diabetes mellitus, and cardiovascular disease (CVD) were predictors for the severity of symptoms of OA of the knee. Female participants were more prone to have severe symptoms compared to males, and those who were more than 70-years-old were at greater risk of severe symptoms. Low educational status, obesity, diabetes mellitus, and CVD were also predictors for severe OA of the knee. Age (p < 0.001), obesity (p < 0.001), and diabetes (p < 0.001) were the best predictors of severity of symptoms based on the multinomial logistic regression analysis. The findings from the study highlighted the associated factors of knee OA and the need for integral healthcare measures that address both the socio-economic and the physical determinants. Focused interventions need to be employed, particularly for high-risk groups such as the elderly, women, and the comorbid, to minimize the incidence of OA of the knee and maximize the outcomes for patients in settings such as that of Bangladesh, where resources may not be available.
Abstract This systematic review and meta-analysis aimed to assess the clinical outcomes of biologic therapies, which include platelet-rich plasma and cell-based therapies (e.g., adipose-derived mesenchymal stem cells), on pain, physical function, and disease progression in patients with knee osteoarthritis (OA), focusing on studies with a follow-up of at least 12 months. We searched for randomized controlled trials (RCTs) posted at some stage in January 2000–May 2025. Eligible research protected the ones in adults with Kellgren–Lawrence grades I–III OA who underwent at least 12 months of follow-up. The bias risk was assessed, and the evidence certainty was evaluated. Random-effects models were used for pooled analyses. Fourteen RCTs were included. Compared with control treatments, biologic therapies significantly reduced pain and improved physical function. Potential structural benefits, including cartilage thickness preservation and favourable biochemical changes, were noted. However, substantial heterogeneity in study design and intervention protocols, along with potential publication bias, reduced the certainty of evidence to a very low level. Biologic therapies may be associated with improvements in pain and physical function at ≥12 months of follow-up, with preliminary indications of structural benefit. Nevertheless, high-quality multicenter RCTs with extended follow-up are warranted.
Background Knee osteoarthritis (KOA) is closely associated with an imbalance in macrophage M1/M2 polarization within its inflammatory microenvironment. Platelet-rich plasma (PRP) has demonstrated therapeutic efficacy in KOA. Moreover, microRNAs (miRNAs) also play a protective or destructive role in the pathogenesis of KOA. This study aims to elucidate the molecular mechanisms by which PRP-related miRNAs ameliorate the inflammatory microenvironment to alleviate KOA. Methods An in vivo KOA rat model was established via intra-articular injection with monosodium iodoacetate (MIA). Safranin O-fast green staining and hematoxylin and eosin (HE) staining were used to assess cartilage degeneration and synovial inflammation, respectively. Macrophage phenotype was analyzed by immunohistochemistry (IHC) and immunofluorescence (IF). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression of inflammatory cytokines. Chondrocyte anabolic and catabolic status was evaluated using IF and western blotting (WB). Bioinformatics analysis was employed to screen for differentially expressed miRNAs in PRP and Dual-luciferase reporter assay was conducted to verify that mRNA is a direct target for miRNA. Furthermore, we explored the biological functions of miRNA and mRNA by transfecting mimics and siRNA. Results In vitro , PRP inhibited M1-type macrophage polarization while promoting M2-type polarization, leading to suppressed pro-inflammatory cytokine release and enhanced anti-inflammatory cytokine release, collectively reducing cartilage degeneration. We identified microRNA let-7a-5p using bioinformatic approaches and subsequently investigated its molecular mechanisms. Similar to PRP, let-7a-5p was found to regulate macrophage polarization, the release of inflammatory cytokine, and cartilage degeneration. Furthermore, we identified and experimentally validated MAPK8 as a target gene of let-7a-5p. Conclusion PRP reshapes macrophage polarization by regulating the let-7a-5p/MAPK8 axis, thereby improving the inflammatory microenvironment of KOA and providing a potential new therapeutic target for KOA management.
Case reports (CRs) are essential in physiotherapy, yet reporting remains heterogeneous and insufficiently standardised. The 2013 CAse REport (CARE) guideline improves transparency but lacks physiotherapy-specific detail. This study aimed to develop a consensus-driven extension of the CARE reporting guideline to support structured reporting of physiotherapy CRs, encompassing physiotherapy-specific assessments and interventions. An e-Delphi consensus process study following the ACcurate COnsensus Reporting Document (ACCORD) guidelines. Online. Forty-four international experts in physiotherapy practice, research and education, along with six core committee members. Experts objectively scored items for relevance (5-point Likert scale) and provided open-ended responses for each item of the drafts. Scores and responses were analysed to facilitate iterative refinement of the Physiotherapy CAse REport (PhyCARE) reporting guidelines. Consensus was predetermined at over 70% agreement. Round 1 had the majority of items achieving ≥70% agreement, except two items that did not meet the threshold were revised and replaced with an alternative. Five new items addressing physiotherapy-specific reporting needs were added, and 10 items were relocated. In round 2, all 35 items across 13 domains achieved 84%-100% agreement. The nomenclature of one domain was revised to 'Outcomes and Follow-up'. Following two e-Delphi rounds, consensus was achieved, and suggestions from online meeting, piloting led to item rephrasing, after which the PhyCARE guidelines were finalised. The PhyCARE guidelines have the potential to provide a physiotherapy-specific extension of CARE to support structured, transparent and reproducible reporting of physiotherapy CRs.
To investigate the age-associated prevalence patterns of sacroiliac joint (SIJ) variations, evaluate their association with structural damage in axial spondyloarthritis (axSpA) patients, and compare their prevalence and morphological spectrum with European data. This retrospective study analyzed high-resolution CT scans from 806 adults. Six predefined SIJ morphotypes were evaluated. Age-associated prevalence was modeled using generalized additive models (GAM) and Bayesian additive regression trees (BART) to capture non-linear dependencies. The association between SIJ variations and structural damage severity (Innsbruck CT grade) in axSpA patients was assessed with multivariable cumulative-link mixed models. European data were derived from a random-effects meta-analysis. SIJ variation prevalence showed a strong, monotonic increase with age (OR = 1.26/year, 95% CI 1.15–1.38), accelerating after 60 years and being more common in women (73.5% vs. 25.2%, P < 0.001). Critically, the presence of any SIJ variant was significantly associated with higher odds of severe structural damage in axSpA patients (OR = 2.23, 95% CI: 1.56–3.19, P < 0.001). BART modeling provided superior net benefit for risk prediction versus GAM, facilitating exploratory risk stratification. While overall prevalence was similar to European data (44.4% vs. 41.0%, P = 0.236), morphological distributions differed significantly: semicircular defects (11.2% vs. 4.8%) and crescent-shaped plates (12.4% vs. 3.6%) were more prevalent in our cohort. SIJ variations are strongly associated with age, suggesting a degenerative component, and constitute a relevant risk marker for severe structural damage in axSpA. The BART model effectively supports exploratory risk assessment. Our cohort shares a similar prevalence but demonstrates a distinct morphological spectrum compared to European populations.
Purpose Gait affects knee loading. Modifying gait could reduce load and protect against cartilage loss. Our objective is to look for modifiable gait parameters and determine their relation with worsening cartilage damage. Methods We studied participants from the Multicenter Osteoarthritis Study (MOST) age 45‐90 with, or at risk for, knee osteoarthritis (OA). Gait assessment used inertial measurement units (APDM) on the pelvis and ankles during a 20‐meter walk. Knee magnetic resonance imaging (MRI) images were acquired at baseline and 2 years later. Cartilage damage worsening was assessed using MRI Osteoarthritis Knee Scores (MOAKS) in 14 knee subregions. We examined change (yes/no) in each subregion. We used ensemble machine learning to discriminate subregions with and without cartilage damage. Predictors tested included gait variables, radiographic OA, baseline cartilage damage, age, sex, height, weight, depressive symptoms, and race/clinic site. Data were split 70% training and 30% test sets. We identified the 10 variables that, across 100 repetitions, most frequently contributed to risk of damage. We used G‐computation to evaluate causal risk differences of worsening cartilage damage for each variable. Results We studied 1703 participants (mean age 61.4 [SD: 9.4] years, 56% female). At 2 years, 46% had worse cartilage damage in at least one knee subregion. Of gait variables, longer step length was associated with increased risk of damage, especially in knees with more baseline damage. Conclusion Longer step length was associated with worse cartilage damage over 2 years. Interventions to shorten step length might reduce risk of worsening cartilage damage.
Caliper and tape-based IMD measurements offer similar reliability, but averaging multiple trials improves precision. RABD-IMD methods demonstrate moderate construct validity, supporting their use in clinical assessment of CMC1 OA. Standardized, repeatable IMD assessments may enhance monitoring and care planning in thumb CMC1 OA. Key Points In persons with carpometacarpal osteoarthritis: • Caliper and tape intermetacarpal distance measures of thumb radial and palmar abduction demonstrate excellent test-rest reliability and acceptable precision. • Averaging two or three intermetacarpal distance measurements is recommended over a single measure due to superior precision. • Radial abduction (via the intermetacarpal distance) is strongly associated with self-reported disability and may be more clinically meaningful than palmar abduction.
Abstract Objectives This study aimed to evaluate periprosthetic fracture management following unlinked total elbow arthroplasty based on a retrospective case series analysis. Methods Medical records of 13 patients with periprosthetic fractures who underwent unlinked Kudo total elbow arthroplasty at our institution between 2013 and 2022 were retrospectively reviewed. Post-operative assessment included elbow range of motion, radiographic evaluation and the Mayo elbow performance score. Results Among the 13 patients, 11 were managed surgically, and two received conservative treatment. Seven patients with component loosening and insufficient bone stock underwent revision to a linked total elbow arthroplasty. Three patients with isolated ulnar loosening but preserved bone stock underwent revision with a long-stemmed unlinked ulnar component. One patient was treated with internal fixation. At the latest follow-up, the mean total arc of elbow motion was 91°. The mean Mayo elbow performance score was 85. All cases of aseptic loosening were treated without using strut bone allografts. Conclusions Unlinked Kudo total elbow arthroplasty is an effective option for primary TEA, considering the possibility of future periprosthetic fractures, as revision procedures are more straightforward than those for linked total elbow arthroplasty. When loosening is observed, early intervention is advised to reduce the risk of periprosthetic fracture.
To evaluate the capacity of the RA MRI Score (RAMRIS) in distinguishing rheumatoid arthritis (RA) and hand osteoarthritis (HOA). Patients with RA and HOA were retrospectively matched in pairs. Inflammatory and degenerative changes in MRI scans of the hands were quantified and compared using RAMRIS, focusing on bone marrow edema (BME), erosion, synovitis, and tenosynovitis. CRP, ESR, and autoantibodies (RF and ACPA) and clinical scores (DAS-28, FFbH, and pain level), smoking status, and medication use were assessed additionally. Overall, 100 RA and 100 HOA patients with confirmed diagnosis were included. Age, pain severity, and functional impairment did not differ between groups. RAMRIS revealed significantly higher synovitis subscores in RA compared to HOA (p<0.001), while no significant differences were found for BME (p = 0.076), erosion (p = 0.366), or tenosynovitis (p = 0.129). Higher RAMRIS scores were observed at the level of individual joints in RA. The mean erosion-subscore was found to be higher in RA males than in RA females, though this was not observed in all joints. In HOA, men exhibited a mean erosion score that was higher than that of women. Smoking status had limited association with RAMRIS findings, but RA non-smokers exhibited greater inflammatory burden than HOA non-smokers in multiple joints. RA exhibited significantly higher synovitis subscores, indicative of active inflammation and leading to overall higher RAMRIS scores, compared to HOA. However, HOA demonstrated high RAMRIS scores for synovitis, tenosynovitis, erosions, and BME. MRI may assist in distinguishing RA from HOA; however, its interpretation must be integrated into the clinical context.
Abstract Objectives Promotion of physical activity (PA) in individuals with rheumatic and musculoskeletal diseases (RMDs) is essential for disease management, yet evidence on social, environmental, and system-level determinants remains limited. This study aimed to quantify the prevalence of these determinants and compare them across four European nations. Method A cross-country survey was developed based on a scoping review and semi-structured stakeholder interviews. The survey comprised 27 items across social, environmental, and system domains. Participants rated each item as a facilitator, barrier, or neutral, using a scale from − 10 (barrier) to + 10 (facilitator). Responses were analyzed to assess cross-country differences in demographic characteristics, PA behavior, and determinant ratings. Results A total of 734 individuals with RMDs participated (41.1% RA, 40.7% axSpA, and 18.1% OA) from France (30.5%), Switzerland (34.4%), the Netherlands (17.3%), and Turkey (17.7%). Significant between-country differences were identified in PA behaviors and demographics ( p < 0.05). Overall determinant scores did not differ significantly ( p = 0.101). Key facilitators varied across countries: “knowledge and fitness to perform exercises” was prominent in Switzerland; “scheduled exercises” in the Netherlands and France; and “health professionals” in France and Turkey. Common barriers included “weather conditions”—particularly in Turkey and the Netherlands—“costs of memberships or sport facilities,” especially in France, and work-related duties in Turkey and the Netherlands. Conclusions Despite comparable overall scores, the relevance of social, environmental, and system-level determinants of PA varied across countries These findings highlight the importance of country-specific contextual factors for understanding PA participation and for designing tailored, effective PA promotion strategies in people with RMDs. Key Points • This study provides novel cross-country insights by comparing contextual determinants across four European countries on how cultural norms
Abstract The renin–angiotensin system (RAS), traditionally regarded as a hormonal cascade regulating cardiovascular and renal homeostasis, is increasingly recognized as a locally active, tissue-specific network within joint structures. Accumulating evidence indicates that synovial tissue, synovial fluid, and articular cartilage harbor a functionally active joint-local renin-angiotensin system that operates partially autonomously from the systemic RAS circulation and is implicated in the pathogenesis of both arthritis (RA) and osteoarthritis (OA). This narrative review integrates human, animal, and in vitro evidence to examine the dual-axis organization of the joint RAS, comprising a pathogenic angiotensin-converting enzyme (ACE)/Angiotensin II (Ang II)/ Angiotensin II type 1 receptor (AT1R) axis and a counter-regulatory ACE2/Angiotensin-(1–7) (Ang-(1–7))/Mas receptor-Mas related G protein-coupled receptor D (Mas–MrgD) axis, and to explore how imbalance between these pathways may differentially influence inflammatory and degenerative joint diseases. In RA, experimental and translational studies suggest that enhanced activity of the classical axis within synovial tissue is associated with synovial inflammation, fibroblast-like synoviocyte survival, angiogenesis, and bone erosion through pathways involving nuclear factor kappa B (NF-kB), mitogen-activated protein kinase (MAPK), and receptor activator of nuclear factor kB ligand (RANKL)/Wingless-related integration site (Wnt) signaling pathway. In OA, available data indicate that chondrocyte expression of AT1R/Angiotensin II type 2 receptor (AT2R), together with cytokine-induced receptor upregulation, may sensitize cartilage to Ang II-mediated effects, contributing to matrix metalloproteinase-13 (MMP-13)–mediated matrix degradation and activation of interleukin-6 (IL-6)/janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. Genetic studies support disease-specific patterns, with the ACE insertion/deletion polymorphism showing a more consistent association with RA susceptibility than with knee OA, although findings vary across populations and do not consistently correlate with disease severity. From a therapeutic perspective, modulation of the joint-local