Knee osteoarthritis is increasingly recognized as a whole-organ disease in which synovial inflammation and neurovascular alterations contribute substantially to pain and functional impairment. In recent years, genicular artery embolization (GAE) has emerged as a minimally invasive, image-guided intervention targeting pathological synovial hypervascularization in patients with symptomatic knee osteoarthritis refractory to conservative treatment. This narrative review summarizes the pathophysiological rationale underlying GAE, focusing on the role of synovitis, angiogenesis, and neurovascular coupling in osteoarthritic pain. We provide an overview of the anatomical and technical principles of the procedure and critically appraise the available clinical evidence, including observational studies and randomized sham-controlled trials. While early observational studies have consistently reported clinically meaningful pain reduction, randomized evidence remains heterogeneous and highlights a substantial placebo response. Current data suggest that GAE may benefit selected patients with mild-to-moderate disease and inflammatory phenotypes, whereas its role in advanced osteoarthritis remains limited. Finally, we discuss unresolved issues, including patient selection, choice of embolic agents, and long-term safety, and outline future research directions required to define the place of GAE in the therapeutic algorithm of knee osteoarthritis.

OBJECTIVE:To investigate the relative contribution of cartilage and synovial turnover to predict progression in patients with knee or hip osteoarthritis (OA). METHODS:A total of 449 patients with symptomatic knee or hip OA (mean age: 62 yr, 62% women) with a Kellgren-Lawrence (KL) score ≥2 from the prospective KHOALA cohort study were investigated. Progression was defined as a one-point increase in the KL scores from knee or hip radiographs and/or a joint replacement during 5 years follow-up. The association of baseline urinary CTX-II and serum Col 3-4, biochemical markers of cartilage and synovial turnover, respectively, with progression was assessed by multivariable discrete-time survival models. RESULTS:Increased baseline CTX-II levels were associated with an increased risk of knee and/or hip OA progression, patients with levels in the fourth quartile having an odds ratio (OR; 95%CI) of 2.57 (1.57-4.18) compared with subjects with levels in first quartile, after adjustment for demographical and OA clinical variables and KL scores. When analyses were restricted to patients with knee or hip OA progression only, similar findings were obtained with corresponding ORs (95% CI) of 2.36 (1.32-4.21) and 3.39 (1.42-8.11), respectively. There was no significant association of baseline Col 3-4 and the risk of knee or hip progression. CONCLUSIONS:Increased urinary CTX-II, but not Col 3-4, is independently associated with a higher risk of structural progression in patients with knee or hip OA. Cartilage turnover may play a more important role than synovial activity as assessed with Col 3-4 to mediate joint damage in established OA. TRIAL REGISTRATION:ClinicalTrials.gov, http://clinicaltrials.gov, NCT00481338.

Purpose:Dental evaluation is recommended before bisphosphonates (BPs) initiation because of the rare but serious risk of medication-related osteonecrosis of the jaw. In this context, the objective of this study was to assess the prevalence of the indication for dental care (DC) prior to BPs initiation for osteoporosis (OP). Methods:Monocentric retrospective study between January 2019 and August 2022. Inclusion criteria: patients requiring OP treatment with dental evaluation (panoramic dental X-ray (PD) and dental teleconsultation). Exclusion criteria: PD without tele-dental evaluation, BPs for other indications than OP, OP not treated with BPs. Collected data: demographic characteristics, medical history, bone status, conclusions of tele-dental expertise. Results:130 patients were included, mean age of 74.3 years (±12.2), 102 were women. DC was required for 95/130 patients (DC group). In the DC group, 77/95 required surgical DC, 35/77 completed the surgical DC, and 30/35 initiated BPs. 18/95 patients required non-surgical DC, 6/18 completed the DC, and 5/6 initiated BPs. BPs were initiated in 35/95 (36,8%) patients in the DC group and 29/35 (82,9%) in the non-DC group. Conclusion:The prevalence of DC required before BPs initiation in OP patients is high and have a negative impact on the effective implementation of OP treatment. These results emphasize the need for healthcare policies aimed at improving access to DC and the necessity for clear guidelines regarding DC management in the context of BPs therapy.

ObjectiveTo examine the course of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) in France on treatment with Janus kinase inhibitors (JAKis) using the MAJIK-SFR registry.MethodsProspective national multicentre observational study identifying patients with RA-ILD from the MAJIK-SFR registry. Pulmonary assessment data were collected at JAKi initiation and follow-up visits (6 months, 12 months and a median of 21 months postinclusion), including chest high-resolution CT (HRCT), pulmonary function tests (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)), acute exacerbations of ILD, respiratory infections and lung cancers.ResultsWe enrolled 42 patients (26 women, 62%) with RA-ILD with a mean age of 61±13 years and a mean disease duration of 16±10 years. Compared with the 778 RA patients without ILD from the MAJIK registry, RA-ILD patients were older, displayed more severe and active disease and had more prevalent comorbidities. Non-specific interstitial pneumonia and usual interstitial pneumonia accounted for 46% and 43% of the chest HRCT ILD patterns, respectively. No significant changes in FVC and DLCO were observed during the follow-up period. Chest HRCT lesions remained stable in 69% of patients. Progressive ILD was identified in 8 patients (19%). 16 (38%) respiratory tract infections were observed. Only one acute regressive exacerbation of ILD was noted, and no lung cancer was diagnosed. No deaths occurred. JAKi was discontinued in 17 patients including 8 for inefficacy on joint involvement and 5 for intolerance.ConclusionThe analysis indicates stability of RA-ILD in patients treated with JAKi. The tolerance profile of JAKi in this higher risk population did not reveal new safety signal.

AIMS:Thermogenic adipocytes are able to dissipate energy as heat from lipids and carbohydrates through enhanced uncoupled respiration, due to UCP1 activity. PPAR family of transcription factors plays an important role in adipocyte biology. The purpose of this work was to characterize the role of PPARα and pemafibrate in the control of thermogenic adipocyte formation and function. MATERIALS AND METHODS:We used human multipotent adipose-derived stem cells and primary cultures of stroma-vascular fraction cells, transfected with siRNA against PPARα, differentiated into white or beige adipocytes, by the treatment of rosiglitazone or pemafibrate. The expression of key marker genes of adipogenesis and thermogenesis was determined using RT-qPCR and Western blotting. An RNAseq analysis was also performed. KEY FINDINGS:We show that inhibition of PPARα mRNA increases UCP1 mRNA and protein expression in beige adipocytes induced by rosiglitazone. Knock-down of PPARα also increases stimulated glycerol release. Pemafibrate, described as a selective PPARα modulator, induces adipogenesis and the expression of UCP1 in the absence of PPARα expression. These effects are inhibited by a specific PPARγ antagonist highly suggesting that the pemafibrate effects in adipogenesis and beiging were mediated by PPARγ. SIGNIFICANCE:Conversion of white into thermogenic adipocytes is mainly due to the activation of PPARγ. Moreover, we show that PPARα seems to act as a hindrance for PPARγ-dependent beiging. Our data question the role of PPARα in human adipocyte browning and the specificity of pemafibrate in adipocytes.

ObjectivesTo compare two strategies—a hydrocortisone replacement strategy and a prednisone tapering strategy—for their success in glucocorticoid discontinuation in patients with rheumatoid arthritis (RA) with low disease activity (LDA).MethodsThe Strategies for glucocorticoid TApering in Rheumatoid arthritis (STAR) study was a double-blind, double-placebo randomised controlled trial including patients with RA receiving a stable dose of glucocorticoid 5 mg/day for ≥3 months and were in LDA for ≥3 months. Patients were randomly assigned in a 1:1 ratio to either replace prednisone with 20 mg/day of hydrocortisone for 3 months, then reduce to 10 mg/day for 3 months before discontinuation or to taper prednisone by 1 mg/day every month until complete discontinuation, contingent on maintaining LDA. The primary outcome was the percentage of patients achieving glucocorticoid discontinuation at 12 months. Other secondary outcomes were proportion of flares, need for additional glucocorticoid use, disease activity, patient-reported outcomes and the results of adrenocorticotropic hormone (ACTH) stimulation tests.ResultsOf the 102 patients randomised in the trial (mean age 62.4 years, 70.6% females), 53 had hydrocortisone replacement and 49 tapered prednisone. At 12 months, 29 patients (55%) in the hydrocortisone replacement group and 23 patients (47%) in the prednisone tapering group achieved glucocorticoid discontinuation (p=0.4). No difference was observed between groups in the secondary outcomes. No cases of acute adrenal insufficiency were observed; however, 17 patients still had an abnormal ACTH stimulation test at 12 months, with no differences between arms.ConclusionA hydrocortisone replacement strategy was not superior to a prednisone tapering strategy for achieving glucocorticoid discontinuation success in patients with RA in LDA.Trial registration numberNCT02997605.

Kaposi sarcoma (KS) is an angioproliferative neoplasm induced by human herpesvirus 8 (HHV8) targeting the cutaneous and lymphatic systems, with possible involvement of other organs such as lower limb bones.1 A 72-year-old male patient of Senegalese origin with a 10-year history of rheumatoid arthritis (RA) taking methotrexate (MTX) consulted regarding a 1-year history of chronic mechanical pain of the left heel.

Changes in autonomic (ANS) and enteric nervous systems (ENS) may be involved in pathogenesis of obesity. We hypothesized that baseline autonomic and enteric parameters may predict outcomes of diverse obesity therapies. We studied ANS and ENS physiology in 37 patients (8 male, 29 female, age 45 years, weight 129.7 kg) at 4 centers in patients undergoing medical (9: low-calorie diet) versus invasive (22: 16 sleeve, 6 bypass) and semi-invasive (6: 2 band, 2 high energy stimulation, 2 aspiration) weight loss therapies. Weight loss was reported as percent weight loss from baseline to latest values at 1 year and in some up to 5 years; classified as < or > /= 20

L’arthrose est la maladie articulaire la plus fréquente. Le mode de définition (clinique, radiologique) doit être précisé ainsi que l’articulation ciblée pour l’appréciation des donnés épidémiologique et des multiples facteurs de risque clairement identifiés ou encore discutés (non envisagés ici). En France, la prévalence de l’arthrose symptomatique de la hanche et du genou en population générale âgée de 45 à 75 ans s’établit à 1.9 % pour les hommes et 4,7 % chez les femmes. Son taux d’incidence augmente rapidement avec l’âge, de façon plus marquée chez les femmes que chez les hommes. Des facteurs de risque systémiques peuvent être en cause : âge, exe féminin, ethnie, génétique (30 à 65 % du risque), nutrition (Vitamines D,C,K), obésité et syndrome métabolique, densité et masse osseuse élevées. Des facteurs de risque locaux interviennent aussi tels que la morphologie articulaire (particulièrement l’effet came ), les troubles statiques (genu varum ), l’activité physique excessive, les traumatismes articulaires ou encore les déficits musculaires.Le facteur individuel majeur modifiable, dont la prévalence ne va faire qu’augmenter dans les années à venir est l’obésité. Il est donc impératif de mieux comprendre le lien reliant l’excès de poids à l’arthrose afin de mettre en place des politiques de santé adaptées.

Obesity is a complex disease highly related to diet and lifestyle and is associated with low amount of thermogenic adipocytes. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to fight overweight and associated comorbidities. Recent studies suggest a role for several fatty acids and their metabolites, called lipokines, in the control of thermogenesis. The purpose of this work was to analyze the role of several lipokines in the control of brown/brite adipocyte formation. We used a validated human adipocyte model, human multipotent adipose-derived stem cell model (hMADS). In the absence of rosiglitazone, hMADS cells differentiate into white adipocytes, but convert into brite adipocytes upon rosiglitazone or prostacyclin 2 (PGI2) treatment. Gene expression was quantified using RT-qPCR and protein levels were assessed by Western blotting. We show here that lipokines such as 12,13-diHOME, 12-HEPE, 15dPGJ2 and 15dPGJ3 were not able to induce browning of white hMADS adipocytes. However, both fatty acid esters of hydroxy fatty acids (FAHFAs), 9-PAHPA and 9-PAHSA potentiated brown key marker UCP1 mRNA levels. Interestingly, CTA2, the stable analog of thromboxane A2 (TXA2), but not its inactive metabolite TXB2, inhibited the rosiglitazone and PGI2-induced browning of hMADS adipocytes. These results pinpoint TXA2 as a lipokine inhibiting brown adipocyte formation that is antagonized by PGI2. Our data open new horizons in the development of potential therapies based on the control of thromboxane A2/prostacyclin balance to combat obesity and associated metabolic disorders.

INTRODUCTION:Bisphosphonate-related osteonecrosis of the jaw (BRONJ) have been characterized with the use of oral bisphosphonates in osteoporosis and zoledronate in oncology. Uncertainties remain, though, with the occurrence of BRONJ related to the use of zoledronate in osteoporosis.OBJECTIVES:We aimed to estimate the incidence and characterize the risk factors of zoledronate-associated BRONJ in osteoporosis as compared with oral bisphosphonates in real life setting.METHODS:Cases of BRONJ associated with zoledronate, alendronate or risedronate were extracted from the French pharmacovigilance database up to 2020. The incidence of BRONJ was estimated as their respective numbers related to cases of BRONJ in patients treated with bisphosphonates for osteoporosis, over the same period, according to the Medic'AM database.RESULTS:Between 2011 and 2020, BRONJ incidence with zoledronate was 9.6/100,000 patient-year (PY), significantly higher than with alendronate (5.1/100,000 PY, P<0.001), and risedronate (2.0/100,000 PY, P<0.001). The number of patients treated with bisphosphonates has steadily decreased by 44.5% over 10 years. Meanwhile, the incidence of BRONJ decreased (5.8/100,000 PY in 2011; 1.5/100,000 in 2020), although a rebound was observed in 2018, including 47.6% of BRONJ following denosumab. Apart from classical risk factors, recent dental cares stood out in more than 40% of BRONJ, and zoledronate had a shorter exposure time than oral bisphosphonates.CONCLUSIONS:In a real-life setting, our data confirm that zoledronate-associated BRONJ in osteoporosis is scarce, seeming slightly more common compared with oral bisphosphonates. We also raise awareness of dental care guidelines and greater vigilance when using bisphosphonates in patients with previous exposure to denosumab.

Oxytocin (OT), a neuropeptide best known for its role in emotional and social behaviors, has been linked to osteoarthritis (OA). This study aimed to investigate the serum OT level in hip and/or knee OA patients and to study its association with disease progression. Patients from the KHOALA cohort with symptomatic hip and/or knee OA (Kellgren and Lawrence (KL) scores of 2 and 3) and follow-up at 5 years were included in this analysis. The primary endpoint was structural radiological progression, which was defined as an increase of at least one KL point at 5 years. Logistic regression models were used to estimate the associations between OT levels and KL progression while controlling for gender, age, BMI, diabetes and leptin levels. Data from 174 hip OA patients and 332 knee OA patients were analyzed independently. No differences in OT levels were found between the 'progressors' and 'non-progressors' groups among the hip OA patients and knee OA patients, respectively. No statistically significant associations were found between the OT levels at baseline and KL progression at 5 years, the KL score at baseline or the clinical outcomes. Higher structural damage at baseline and severe structural progression of hip and knee osteoarthritis did not appear to be associated with a low serum OT level at baseline.