scholarly journals AB1017 ANTI RANK LIGAND IN ACUTE CHARCOT NEURO-OSTEOATHROPATHY OF THE FOOT: A PROMISING TREATMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1801.1-1801
Author(s):  
S. Carvès ◽  
J. Henry ◽  
M. Bourgeon Ghittori ◽  
R. Belkhir ◽  
G. Nocturne ◽  
...  
Keyword(s):  
Structural Damage ◽  
Human Monoclonal Antibody ◽  
Joint Destruction ◽  
Nuclear Factor ◽  
Rank Ligand ◽  
Osteoclastic Activity ◽  
Pet Ct ◽  
Receptor Activator ◽  
Standard Pressure

Background:Acute Charcot neuroarthropathy (CN) of the foot is a rare and severe complication of peripheral neuropathy leading to joint destruction. Usual treatment rely on standard pressure offloading and no pharmacological treatment is available. Inflammation and increased osteoclastic activity via receptor activator of nuclear factor (RANK) ligand are major features of acute CN.Objectives:To assess clinical, metabolic and radiographic effect of denosumab, a fully human monoclonal antibody against RANK ligand, in acute CN.Methods:In this open study, we included all consecutive patients with acute CN treated with denosumab 60 mg in our mixed rheumatology/diabetes clinic dedicated to diabetic foot. Diagnosis of acute CN was based on clinical presentation and supported by biology, radiography, magnetic resonance imaging (MRI). Baseline and follow-up assessment included clinical examination and emission tomography–computed tomography (PET-CT).Results:Seven patients with acute CN were treated with denosumab between 2017 and 2019 (age from 43 to 70 years). Five were diabetic. All patients received denosumab, because of failure of standard pressure offloading, with evolving joint destruction of midfoot. CN evolves since a median of 6 months (2 to 20) at denosumab initiation. All patients clinically improved after denosumab injection (table). After a mean follow-up of 16 months, only 1/7 patients had a new flare. In the 4 patients with available follow-up X-ray, structural damage remained stable. In all 3 patients with available PET-CT evolution, the maximum standardized uptake lean value (SUL max) decreased.Table 1.Baseline characteristics and follow up treatmentThree patients were retreated, with a mean interval of 6 months: One patients because of persistent clinical and biological inflammation (CRP 17 mg/L), one because of relapse due to intensive walking, and one due to an associated osteoporosis.No adverse event and hypocalcemia was observed.Conclusion:One to three injection of denosumab 60 mg was efficient in preventing flare and further bone destruction in a 16 months medium follow up. These results justify the conduction of a randomized control study to assess the efficacy of denosumab as the first-line pharmacological therapy in acute CN.References:[1]Molines L and al. Charcot’s foot: Newest findings on its pathophysiology, diagnosis and treatment. Diabetes Metab. Sept 2010;36(4):251-5.[2]Mabilleau G, and al. Increased osteoclastic activity in acute Charcot’s osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand. Diabetologia. juin 2008;51(6):1035-40.Disclosure of Interests:None declaredDisclosure of Interests:Sandrine Carvès: None declared, Julien Henry: None declared, Murielle BOURGEON GHITTORI: None declared, Rakiba Belkhir: None declared, Gaetane Nocturne: None declared, Florent Besson: None declared, Guillaume Cluzel: None declared, Maud Creze: None declared, Raphaèle Seror Consultant of: BMS UCB Pfizer Roche, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB

scholarly journals Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL), and Mammographic Density in Premenopausal Women

2018 ◽  
Vol 11 (12) ◽  
pp. 789-796 ◽  
Author(s):  
Adetunji T. Toriola ◽  
Catherine M. Appleton ◽  
Xiaoyu Zong ◽  
Jingqin Luo ◽  
Katherine Weilbaecher ◽  
...  
Keyword(s):  
Mammographic Density ◽  
Premenopausal Women ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Rank Ligand ◽  
Receptor Activator

scholarly journals Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Olivier Bourron ◽  
Franck Phan ◽  
Mamadou Hassimiou Diallo ◽  
David Hajage ◽  
Carole-Elodie Aubert ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Lower Limb ◽  
Arterial Calcification ◽  
Nuclear Factor ◽  
Calcification Score ◽  
Receptor Activator ◽  
Nuclear Factor Kb

Abstract Background Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. Methods Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model. Results At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (β coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p < 0.001), triglycerides (0.11, 0.03–0.20, p = 0.007), log(RANKL) (0.07, 0.02–0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15–0.57, p = 0.001), statin use (0.39, 0.06–0.72, p = 0.023) and duration of follow up (0.04, 0.01–0.06, p = 0.004). Conclusion In patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy. Trial registration NCT02431234

scholarly journals RANK (Receptor Activator of Nuclear Factor kappa B) and RANK Ligand Are Expressed in Giant Cell Tumors of Bone

2002 ◽  
Vol 117 (2) ◽  
pp. 210-216 ◽  
Author(s):  
Sophie Roux ◽  
Larbi Amazit ◽  
Geri Meduri ◽  
Anne Guiochon-Mantel ◽  
Edwin Milgrom ◽  
...  
Keyword(s):  
Giant Cell ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Rank Ligand ◽  
Giant Cell Tumors ◽  
Nuclear Factor Kappa ◽  
Receptor Activator ◽  
Tumors Of Bone

Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis

2011 ◽  
Vol 71 (1) ◽  
pp. 108-113 ◽  
Author(s):  
Maria J H Boumans ◽  
Rogier M Thurlings ◽  
Lorraine Yeo ◽  
Dagmar Scheel-Toellner ◽  
Koen Vos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Osteoclast Precursors ◽  
Receptor Activator ◽  
Hands And Feet

ObjectivesTo examine how rituximab may result in the inhibition of joint destruction in rheumatoid arthritis (RA) patients.MethodsTwenty-eight patients with active RA were treated with rituximab. Radiographs of hands and feet before and 1 year after therapy were assessed using the Sharp–van der Heijde score (SHS). Expression of bone destruction markers was evaluated by immunohistochemistry and immunofluorescence of synovial biopsies obtained before and 16 weeks after the initiation of treatment. Serum levels of osteoprotegerin, receptor activator of nuclear factor κB ligand (RANKL), osteocalcin and cross-linked N-telopeptides of type I collagen (NTx) were measured by ELISA before and 16 weeks post-treatment.ResultsAfter 1 year, the mean (SD) change in total SHS was 1.4 (10.0). Sixteen weeks after treatment there was a decrease of 99% in receptor activator of nuclear factor κB-positive osteoclast precursors (p=0.02) and a decrease of 37% (p=0.016) in RANKL expression in the synovium and a trend towards reduced synovial osteoprotegerin expression (25%, p=0.07). In serum, both osteoprotegerin (20%, p=0.001) and RANKL (40%, p<0.0001) levels were significantly reduced 16 weeks after treatment, but the osteoprotegerin/RANKL ratio increased (157%, p=0.006). A trend was found towards an increase of osteocalcin levels (p=0.053), while NTx concentrations did not change.ConclusionsRituximab treatment is associated with a decrease in synovial osteoclast precursors and RANKL expression and an increase in the osteoprotegerin/RANKL ratio in serum. These observations may partly explain the protective effect of rituximab on the progression of joint destruction in RA.

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