{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:14:09Z","timestamp":1788790449841,"version":"build-2803163510"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\u00bb Chronic Charcot arthropathy results from the convergence of genetic predisposition (OPG\/RANKL\/RANK polymorphisms), metabolic disturbances (AGEs, vitamin D deficiency affecting 84.2% of patients), and inflammatory dysregulation (RANKL\/OPG axis, IL-17 family cytokines), explaining why only 0.08-1% of diabetic neuropathy patients develop this devastating complication.<\/jats:p>\n                  <jats:p>\u00bb The receptor activator of nuclear factor kappa-B ligand (RANKL)\/receptor activator of nuclear factor kappa-B (RANK)\/osteoprotegerin (OPG) axis dysregulation drives excessive osteoclastogenesis and bone resorption in the acute phase, while impaired Wnt\/\u03b2-catenin signaling and advanced glycation end products-modified collagen compromise healing quality in the chronic phase, resulting in malunion and permanent deformity.<\/jats:p>\n                  <jats:p>\u00bb Magnetic resonance imaging is the best non-invasive imaging modality for differentiating chronic Charcot from osteomyelitis (single bone involvement beneath ulcer, sinus tract, and abscess favor infection; periarticular distribution favors Charcot), though bone biopsy remains the gold standard when diagnostic uncertainty persists.<\/jats:p>\n                  <jats:p>\u00bb Current management relies primarily on mechanical interventions (accommodative footwear, bracing, surgical reconstruction for unbraceable deformities), but emerging molecular therapies targeting RANKL (denosumab), pro-inflammatory cytokines (IL-17 inhibitors), and Wnt pathway (romosozumab) show promise for disease modification.<\/jats:p>\n                  <jats:p>\u00bb Integrated risk stratification models combining genetic risk scores, serum biomarkers (RANKL\/OPG ratio, vitamin D levels), and clinical factors can identify high-risk individuals (AUC 0.89), enabling targeted preventive interventions including vitamin D supplementation, prophylactic off-loading, and potentially pharmacological prevention.<\/jats:p>","DOI":"10.2106\/jbjs.oa.25.00261","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T20:00:07Z","timestamp":1773864007000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Decoding Chronic Charcot Arthropathy: Molecular Mechanisms, Predictive Biomarkers, and Emerging Therapies"],"prefix":"10.2106","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6463-0752","authenticated-orcid":false,"given":"Osama","family":"Embaby","sequence":"first","affiliation":[{"name":"Department of Trauma and Orthopaedics, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9977-014X","authenticated-orcid":false,"given":"Afdhal Bin","family":"Asmadi","sequence":"additional","affiliation":[{"name":"Birmingham Heartlands Hospital, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiman Binte","family":"Asmadi","sequence":"additional","affiliation":[{"name":"Mansoura University Hospitals, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2943-3048","authenticated-orcid":false,"given":"Mohamed","family":"Elalfy","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,1]]},"reference":[{"key":"R1-20260318","doi-asserted-by":"crossref","first-page":"1344359","DOI":"10.3389\/fcdhc.2024.1344359","article-title":"Charcot neuro-osteoarthropathy: a review of key concepts and an evidence-based surgical management algorithm","volume":"5","author":"Argyropoulos","year":"2024","journal-title":"Front Clin Diabetes Healthc."},{"key":"R2-20260318","first-page":"100239","article-title":"An overview of Charcot's neuroarthropathy","volume":"22","author":"Dardari","year":"2020","journal-title":"J Clin Transl 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