La Barbera G, Ciodaro F, Luppino G
… +10 more, Li Pomi F, Loteta S, Miceli G, Cusmano C, Chirico V, Alibrandi A, Chimenz R, Visalli C, Borgia F, Conti G
Joint Bone Spine
· 2026 May · PMID 41183588
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OBJECTIVE: The incudomalleal and incudostapedial articulations are synovial joints that may be involved in the inflammatory process in patients with juvenile idiophathic arthritis (JIA). The aim of the study was to asses...OBJECTIVE: The incudomalleal and incudostapedial articulations are synovial joints that may be involved in the inflammatory process in patients with juvenile idiophathic arthritis (JIA). The aim of the study was to assess the frequency of hearing impairment and associated risk factors in JIA patients. METHODS: We performed a cohort study on 45 patients with three JIA subtype (oligoarticular, polyarticular and psoriatic) aged between 3 and 18years. The control group consisted of 30 healthy sex and age-matched children. Subjects underwent audiological exams and clinical-rheumatologic evaluations, including joint count (Juvenile Arthritis Disease Activity Score=cJADAS10) and inflammatory markers. RESULTS: Audiological impairment was detected in 16/45 (35.5%) patients with JIA. Hypoacusis was found in a significant number of ears in JIA patients (16/90=17.8%; P<0.05) compared with to control group ears. Hypoacusis was frequently observed in patients with psoriasis (6/16 ears). Abnormal findings in tympanometry were observed in five types of As (with a shallow peak), four with type B (flat pattern), and in two with type C (with a negative pressure). The stapedius reflex was absent in only one patient (3%). JIA patients with hypoacusis had a significantly greater cJADAS10 (P<0.001) and Childhood Health Assessment Questionnaire (CHAQ) (P<0.001), a functional and quality of life assessment tool, than JIA patients with normal audiometry. CONCLUSION: Hearing impairment and/or abnormal tympanograms suggest ear involvement in patients with JIA. This may be considered a complication of the disease and/or a marker of JIA activity, according cJADAS10, and could represent a valuable criterion to select the best therapeutic strategy. Therefore, JIA patients should perform an Ear, Nose and Throat (ENT) evaluation to allow early detection of auditory system involvement to prevent the impact of hearing loss.
Geoffroy M, Beissat M, Kanagaratnam L
… +2 more, Ackah Miezan S, Salmon JH
Joint Bone Spine
· 2026 May · PMID 41183587
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OBJECTIVES: The primary objective of the study was to demonstrate the superiority of platelet-rich plasma injections in treating facet joint syndrome, compared to corticosteroid injections. Secondary objectives were to a...OBJECTIVES: The primary objective of the study was to demonstrate the superiority of platelet-rich plasma injections in treating facet joint syndrome, compared to corticosteroid injections. Secondary objectives were to assess the efficacy of PRP compared to CTC on pain, functional impact, tolerance, and healthcare utilization following the initial infiltrative management. METHODS: Patients were randomized (1:1) to receive intra-articular injections into the painful facet joints with either PRP or CTC under radiographic guidance. The primary outcome measure was a 50% improvement in the NRS (from 0 to 10) for spontaneous lumbar pain at 6months. STUDY DESIGN: Superiority, controlled, randomized (1:1), prospective, double-blind study. RESULTS: A total of 76 patients were included, at 6months, 6 patients in the PRP group and 5 in the CTC group showed a 50% improvement in spontaneous NRS. No statistically significant differences were found in pain at 3, 6, or 12months. Regarding functional evaluation, a statistically significant difference was observed in the PRP group at 3months according to the ODI. No significant differences were found between groups in terms of satisfaction. Four patients experienced transient adverse effects, only 1 in the PRP group. CONCLUSION: In patients with facet joint syndrome, PRP injections did not demonstrate superiority over CTC injections in terms of pain relief or clinically significant functional improvement at 6months. These results do not support the use of PRP injections for facet joint syndrome.
Michou L, Brown JP, Champagne L
… +5 more, Vallée M, Fournier F, Gagnon E, Droit A, Morin SN
Joint Bone Spine
· 2026 Mar · PMID 41135865
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OBJECTIVES: We performed next generation sequencing in two affected-sibling pairs of atypical femur fractures (AFF) and in unrelated cases of AFF to identify genetic variants of bisphosphonates (BP)-associated AFF. METHO...OBJECTIVES: We performed next generation sequencing in two affected-sibling pairs of atypical femur fractures (AFF) and in unrelated cases of AFF to identify genetic variants of bisphosphonates (BP)-associated AFF. METHODS: A whole exome sequencing (WES) was performed in two sisters with BP-associated AFF and their healthy brother naïve to BP treatment (family A). After bioinformatic filtering, the intrafamilial segregation was analysed. Then, we performed targeted sequencing of 62 genes, including 36 genes containing variants predicted to be damaging and segregating with the phenotype in both sisters of the family A, and 26 candidate genes for osteogenesis imperfecta (OI), hypophosphatasia and the mevalonate pathway. The targeted sequencing was performed on the family A, and on 47 unrelated participants and another affected sibling pair (family B) from the Quebec AFF Registry. 100 healthy controls recruited in same geographic area than patients were genotyped for rare variants. RESULTS: Sixty-three rare and deleterious variants were detected by the WES and shared by the two affected sisters of the family A. Among those variants, a rare likely pathogenic variant (p.Leu3fs) of the WNT1 gene, already linked to OI and early onset osteoporosis, was also shared by a third individual, an unrelated case with BP-associated AFF. The pair of siblings of family B carried a novel variant (p.Glu1323fs) in the COL1A2 gene, linked to OI. One unrelated case had a novel variant in the FDFT1 gene, involved in the mevalonate pathway. These rare variants were not found in 100 healthy controls. CONCLUSION: Some BP-associated AFFs may occur in the setting of clinically undiagnosed underlying genetic disorders predisposing to osteoporosis and fractures, such as OI.
Joint Bone Spine
· 2026 May · PMID 41130316
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Gout, one of the most prevalent inflammatory arthropathies, arises from hyperuricemia and is increasingly recognized as a condition extending beyond the joints. Hyperuricemia, the core risk factor for gout, is also an in...Gout, one of the most prevalent inflammatory arthropathies, arises from hyperuricemia and is increasingly recognized as a condition extending beyond the joints. Hyperuricemia, the core risk factor for gout, is also an independent risk factor for cardiovascular disease (CVD), complications, and mortality. Multiple conditions that predispose to gout and hyperuricemia, including obesity, metabolic syndrome, type 2 diabetes, hypertension, and chronic kidney disease (CKD), also elevate the risk of atherosclerosis, the central contributor to CVD and the leading cause of mortality in Western societies. The association between gout and atherosclerosis highlights the need for deeper understanding of causal links between these conditions. Because evidence remains insufficient to support urate-lowering therapies for improving cardiovascular outcomes, attention has shifted to other mechanisms connecting gout and atherosclerosis. Given the lack of convincing data for clinically significant monosodium urate crystal (MSUc) deposition in atherosclerotic plaques, this review focuses on the hypothesis that expansion of local articular to systemic inflammation, driven by macrophage activation by MSUc, is the primary mechanism accelerating atherosclerosis in gout. Mechanistically, we explore how epigenetic regulators normally restrain MSU-induced local inflammation, thereby protecting against atherosclerosis. We further discuss how aging-related somatic mutations in genes involved in clonal hematopoiesis of indeterminate potential (CHIP) disrupt this protection, resulting in heightened systemic inflammation and atherosclerosis in patients with gout.
Shao YJ, Kuo TT, Liao YJ
… +5 more, Chen YT, Chen IC, Kao CM, Chen YJ, Chen YM
Joint Bone Spine
· 2026 Mar · PMID 41110687
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OBJECTIVES: Janus kinase (JAK) inhibitors are effective treatments for autoimmune rheumatic diseases (AIRDs). However, concomitant use of JAK inhibitors with CYP enzyme inhibitors or OAT3 inhibitors can lead to drug-drug...OBJECTIVES: Janus kinase (JAK) inhibitors are effective treatments for autoimmune rheumatic diseases (AIRDs). However, concomitant use of JAK inhibitors with CYP enzyme inhibitors or OAT3 inhibitors can lead to drug-drug interactions. This study aimed to evaluate the impact of the concomitant use of CYP and OAT3 inhibitors on discontinuation of treatment and infectious complications in patients treated with JAK inhibitors. METHODS: Using the National Health Insurance Research Database, this retrospective cohort study included patients with rheumatoid arthritis, psoriatic arthritis and atopic dermatitis treated with JAK inhibitors in 2021-2023. The risks of discontinuation of treatment and infectious complications were evaluated using Cox proportional hazards models, adjusted for age, gender, other infectious and concomitant use of steroids or methotrexate. RESULTS: Among 7591 patients, concomitant use of strong CYP3A4, or CYP2C19 inhibitors increased the risk of treatment discontinuation for tofacitinib and baricitinib from 41% to 144%. The risk of overall infectious complications also increased when tofacitinib was used concomitantly with strong CYP2C19 inhibitors. The risk of pneumonia was further increased by concomitant use of strong CYP2C19 inhibitors with all JAK inhibitors and CYP3A4 inhibitors with tofacitinib. The risk of urinary tract infection was increased by concomitant use of strong CYP2C19 inhibitors when used with tofacitinib, or baricitinib. CONCLUSIONS: Concomitant use of strong CYP3A4, and CYP2C19 inhibitors with JAK inhibitors significantly increases the risk of discontinuation of treatment and infectious complications in patients with AIRDs. Careful consideration of drug-drug interactions is necessary when prescribing JAK inhibitors to optimize treatment persistence and minimize adverse events.
Juge PA, Debray MP, Pensec VD
… +25 more, Richez C, Avouac J, Wemeau-Stervinou L, Flipo RM, Nunes H, Saidenberg-Kermanac'h N, Gottenberg JE, Jouneau S, Constantin A, Cottin V, Marotte H, Soubrier M, Fautrel B, Nocturne G, Richette P, Berenbaum F, Zylberman-Yona H, Gorenne I, Bancal C, Borie R, Ebstein E, Forien M, Ottaviani S, Crestani B, Dieudé P
Joint Bone Spine
· 2026 Mar · PMID 41110685
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OBJECTIVES: To describe the baseline characteristics of patients enrolled in the TRANSLATE2 cohort (NCT04227535), a national, multicenter, prospective case-control study designed to investigate the genetic and non-geneti...OBJECTIVES: To describe the baseline characteristics of patients enrolled in the TRANSLATE2 cohort (NCT04227535), a national, multicenter, prospective case-control study designed to investigate the genetic and non-genetic determinants of interstitial lung disease (ILD) in rheumatoid arthritis (RA). METHODS: Cases with RA-ILD and RA controls without ILD were consecutively included in TRANSLATE2 with a 5-year prospective follow-up. All participants fulfilled the ACR/EULAR 2010 classification criteria for RA. ILD presence or absence was confirmed for every participant by chest high-resolution computed tomography (HRCT). Baseline demographic and clinical data were collected. Blood samples were collected at enrollment for centralized biobanking of DNA, RNA, and serum to support future genetic and biomarker studies. For ILD cases, chest HRCT scans were centrally reviewed to determine HRCT pattern. For the current study, associations with ILD were tested using univariable and multivariable logistic regression models. RESULTS: Among the 506 patients included (275 RA-ILD, 231 RA-noILD), RA-ILD cases were more frequently male (48.4% vs. 29.9%), older at enrollment (66.6 [9.9] vs. 58.5 [13.2] years) and older at RA onset (52.2 [14.7] vs. 45.8 [14.3] years). ILD was independently associated with male sex (OR 1.82; 95% CI 1.06, 3.14) and older age at RA onset (OR per 10 years 1.28; 95% CI 1.10,1.50). For ILD cases, the most frequent HRCT patterns were definite for usual interstitial pneumonia (39.3%) and non-specific interstitial pneumonia (17.8%). At enrollment, respiratory symptoms were observed in 67.3% with a mean forced vital capacity % predicted of 87.6% (21.7) and a mean diffusing capacity of the lung for carbon monoxide % predicted of 58.4% (18.8). CONCLUSION: The TRANSLATE2 cohort provides a comprehensive and deeply phenotyped dataset that offers a unique opportunity to investigate the genetic architecture, risk factors, and natural history of RA-ILD.
Joint Bone Spine
· 2026 Mar · PMID 41062019
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The skeleton is able to secrete hormones and mediate endocrine functions. Particularly, the fibroblast growth factor 23 (FGF23) has received considerable attention for its unique phosphaturic properties, raising the bone...The skeleton is able to secrete hormones and mediate endocrine functions. Particularly, the fibroblast growth factor 23 (FGF23) has received considerable attention for its unique phosphaturic properties, raising the bone to the status of an essential endocrine regulator. Excess in circulating levels of FGF23, not so surprisingly, then associated to mineral imbalance, in hereditary/acquired mineral and skeletal disorders. A key player, FGF23 excess precedes mineral and skeletal disturbances. However, unexpected effects have been described in the recent years. Various demonstrations have been made that FGF23 is directly regulated by non-mineral stress, including: inflammation, iron deficiency, and glycolysis. In turn, an emerging body of research shows association and causality between FGF23 and the cardiovascular system at large, from the iron metabolism to erythropoiesis, and to the cardiac muscle. This review summarizes canonical and novel effects of FGF23. FGF23 cleavage generates C-terminal peptides that also mediate biological functions. In aggregate, FGF23 measurements should be considered for larger application, as its excess can precede hypophosphatemia, explain hypophosphatemia or resistance to phosphate loading, and possibly predict cardiovascular progression in a wide range of uremic and non-uremic conditions.
Joint Bone Spine
· 2026 Mar · PMID 41038311
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OBJECTIVES: The inpatient epidemiology, morbidity, mortality, and healthcare expenditures associated with systemic sclerosis (SSc) remain poorly characterized. This study utilizes a national inpatient database to provide...OBJECTIVES: The inpatient epidemiology, morbidity, mortality, and healthcare expenditures associated with systemic sclerosis (SSc) remain poorly characterized. This study utilizes a national inpatient database to provide a comprehensive assessment of these parameters. METHODS: We identified adult patients with SSc from the 2021 National Inpatient Sample (NIS) using ICD-10-CM codes. The NIS, the largest publicly available all-payer inpatient healthcare database in the U.S., represents data from over 4000 non-federal acute care hospitals. A matched comparator group without SSc was created to serve as comparators. Extracted data included demographics, primary admission diagnoses, length of stay (LOS), in-hospital mortality and morbidity, comorbidities, and healthcare expenditures. Multivariable analyses were adjusted for age, sex, race/ethnicity, Charlson Comorbidity Index, payer type, median income, and hospital characteristics. RESULTS: The inpatient prevalence of SSc was 86.7 per 100,000 admissions. The most common primary diagnoses among SSc hospitalizations were sepsis (22.7%), heart failure with hypertension (14.4%), and COVID-19 (11.5%). The cohort was predominantly female (84.2%) with a mean age of 63.5 years. Compared to non-SSc admissions, SSc hospitalizations were associated with significantly longer LOS (mean difference 0.7 days; 95% CI: 0.5-0.9) and greater healthcare costs, including an adjusted mean increase of $3277 in hospital costs (95% CI: $2051-$4504) and $11,801 in total charges (95% CI: $6485-$17,116). SSc was also associated with increased odds of in-hospital mortality (adjusted OR 1.42; 95% CI: 1.26-1.61), shock (aOR 1.30; 95% CI: 1.17-1.44), systemic inflammatory response syndrome (aOR 1.32; 95% CI: 1.01-1.74), and acute respiratory distress syndrome (aOR 1.45; 95% CI: 1.12-1.87). Multivariate analysis also revealed that patients with SSc had significantly higher odds of several comorbid conditions, including pulmonary hypertension, interstitial lung disease, osteoporosis, Sjögren's syndrome, and hypertension. CONCLUSIONS: The inpatient prevalence of SSc exceeds its general population prevalence, indicating a high need for hospital-level care. Hospitalizations among patients with SSc are associated with worse clinical outcomes and significantly greater healthcare expenditures.
Bailly F, Granger B, Foltz V
… +4 more, Kab S, Petit A, Tubach F, Fautrel B
Joint Bone Spine
· 2026 Mar · PMID 41033646
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OBJECTIVE: Musculoskeletal pain (MP) is a leading cause of disability worldwide, affecting individual well-being and public health. However, in the literature, the prevalence of MP varies considerably because of methodol...OBJECTIVE: Musculoskeletal pain (MP) is a leading cause of disability worldwide, affecting individual well-being and public health. However, in the literature, the prevalence of MP varies considerably because of methodological inconsistencies, selection biases, and differences in case definitions. This study aimed to estimate the population-based prevalence of MP in France and identify key demographic, socioeconomic, and occupational factors associated with MP. METHODS: This cross-sectional study used baseline data for the CONSTANCES cohort study, a large, population-based epidemiological study with participants representative of the French adult population (18-69years old). Inverse probability weighting was used to correct for selection bias and to improve the generalizability of prevalence estimates. MP was assessed with the Nordic Musculoskeletal Questionnaire, with significant pain defined as lasting>30days in the past 12months. Multivariate logistic regression models were used to identify factors associated with low back pain, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 193,436 participants, 46.2% reported pain in at least one anatomical site. The most affected areas were the low back (26.6% adjusted prevalence), shoulder (21.4%), neck (19.0%), and knee (19.1%). Odds of low back pain was associated with female sex (OR: 1.39 [95% CI: 1.32-1.47]), older age, obesity, depression (1.71 [1.62-1.80]), and comorbidity burden (1.20 [1.15-1.25]). Odds of low back pain was associated with moderate or high occupational physical activity (OR: 1.33 [1.20-1.50] and 1.69 [1.48-1.93]) but was inversely associated with very active leisure-time physical activity (0.82 [0.70-0.96]). Education level but not household income was a significant socioeconomic factor associated with MP. CONCLUSION: MP imposes a substantial burden on the French population, particularly among individuals with physically demanding jobs and low education levels. These findings highlight the paradox of physical activity associated with MP.
Joint Bone Spine
· 2026 Jan · PMID 41022173
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Spondyloarthritis (SpA) encompasses a group of immune-mediated, inflammatory diseases, most notably axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). As the global population ages, so does the population liv...Spondyloarthritis (SpA) encompasses a group of immune-mediated, inflammatory diseases, most notably axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). As the global population ages, so does the population living with these conditions. Age-related immune changes - including chronic low-grade inflammation and the accumulation of senescent T cells - are increasingly recognised as contributors to disease pathophysiology in these individuals. People over the age of 50 often present with a distinct clinical phenotype, including more peripheral arthritis, dactylitis, and psoriasis. A subset may also present with pitting oedema and polymyalgic symptoms, sometimes associated with underlying malignancy. Imaging in older adults can be challenging, as structural and inflammatory changes such as bone marrow oedema and erosions may be seen in asymptomatic individuals without SpA, increasing the risk of misdiagnosis. Age-related comorbidities - including frailty, sarcopenia, falls, fractures, and dementia - occur more frequently in older individuals with SpA, further complicating diagnosis and treatment. Despite this, therapeutic responses appear similar to those in younger populations, particularly with tumour necrosis factor inhibitors (TNFi). Nonetheless, clinicians must be cautious of increased risks of serious infection and heart failure in this age group. Important questions remain about the long-term safety of disease-modifying antirheumatic drugs (DMARDs) in older patients and the efficacy and tolerability of newer biologic or synthetic agents targeting interleukin-17 (IL-17), IL-12/23 and Janus Kinases (JAK) pathways. A better understanding of SpA in older age is critical to delivering effective, individualised care to this growing population.
Robert C, Perrot L, Zelus A
… +5 more, Letavernier E, Courbon G, Lafforgue P, Robert T, Balandraud N
Joint Bone Spine
· 2026 Jan · PMID 41022172
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Calcium pyrophosphate deposition (CPPD) disease is a common crystal arthropathy in the elderly, but its early-onset forms are rare. While secondary hypomagnesemia is a recognized contributor to CCPD, inherited renal magn...Calcium pyrophosphate deposition (CPPD) disease is a common crystal arthropathy in the elderly, but its early-onset forms are rare. While secondary hypomagnesemia is a recognized contributor to CCPD, inherited renal magnesium-wasting syndromes remain underdiagnosed. Here we performed a whole exome sequencing (ES) in order to detect pathogenic variants in a 58-year-old male patient with early and severe, refractory CPPD disease. We conducted a comprehensive clinical, biochemical, radiological, and genetic evaluation of the patient. ES was performed and filtered for rare, likely pathogenic variants following ACMG/AMP criteria. Cascade genetic testing was performed in family members. Hypomagnesemia with inappropriate renal magnesium loss was found. Radiographs revealed diffuse chondrocalcinosis ES identified a novel heterozygous Cyclin and CBS Domain Divalent Metal Cation Transport Mediator (CNNM2) missense variant (c.319G>C; p.Gly107Arg), absent from population databases and predicted deleterious (REVEL 0.82). This variant affects a highly conserved residue in the extracellular β-barrel domain. Family screening revealed two additional carriers with isolated hypomagnesemia, consistent with autosomal dominant inheritance. CNNM2 encodes a basolateral magnesium transporter in the tubule. This is the first reported case of CPPD linked to a CNNM2 variant through persistent hypomagnesemia. Its variants have been linked to renal hypomagnesemia, neurological comorbidities, but no link to CPPD has been described. This expands the phenotypic spectrum of CNNM2-related disorders and highlights the relevance of genetic testing in CPPD cases with unexplained hypomagnesemia. Building on published functional studies and domain-level protein modeling, we propose a simplified three-tier classification scheme that organizes CNNM2 variants into clinically meaningful categories.
Joint Bone Spine
· 2026 Mar · PMID 41016585
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PURPOSE: Vaccine preventable diseases, especially respiratory infections, occur at higher frequency in patients with rheumatic diseases who are immunosuppressed. The focus of this review is to highlight vaccinations that...PURPOSE: Vaccine preventable diseases, especially respiratory infections, occur at higher frequency in patients with rheumatic diseases who are immunosuppressed. The focus of this review is to highlight vaccinations that patients with rheumatic diseases should optimally receive, with a focus on efficacy and safety of vaccines. MAIN FINDINGS: In general, vaccines are effective in reducing the burden of infection. However, due to underlying immunosuppression, their efficacy is most likely reduced compared to the general population. This is even true of the novel vaccines, mRNA and subunit vaccines. Emerging evidence, particularly for withholding methotrexate for 1-2 weeks post vaccination can improve immunogenicity without significantly increasing the risk of disease flare. Administration of live vaccines continue to provide clinicians a challenge especially in the setting of recent measles outbreaks. Assessing underlying degree of immunosuppression and following national guidelines can help clinicians vaccinate these patients safely. If this is not possible, then measles immunoglobulin can be administered. PRINCIPLE CONCLUSIONS: Vaccination is an important part of infection reduction strategies for the rheumatologist to consider during a consultation as the number of vaccines available for infective conditions increases. High dose prednisolone, B cell depleting therapies, and methotrexate have the most evidence for reduced vaccine responses and where feasible, attempts should be made to vaccinate when immunosuppression is thought to be lower.