Journal of Foot and Ankle Surgery (Asia Pacific)

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VOLUME 10 , ISSUE S1 ( August, 2023 ) > List of Articles


Charcot Theories and Pathophysiology: A Narrative Review

Gautam Kumar, Dennis P Jose, Udit Agrawal, Inderjit Singh

Keywords : Charcot joint, Charcot neuroarthropathy, Neuropathy, Receptor activator of nuclear factor-kB ligand

Citation Information :

DOI: 10.5005/jp-journals-10040-1305

License: CC BY-NC 4.0

Published Online: 03-10-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Charcot neuropathic osteoarthropathy (CNO) is defined as relatively painless, progressive, noninfectious, and degenerative arthropathy involving soft tissues and one or more joints with an underlying neurological deficit. Major theories of pathophysiology include neurovascular theory (French theory), neurotraumatic theory (German theory), and neuro-osseous-inflammatory theory. As per the neurovascular theory, loss of sensation due to neuropathy acted as a barrier for feeling pain and discomfort in patients, which predisposed them to repeated trauma and microfractures. Charcot patients have been found to have increased blood flow, which increases venous pressure enhancing fluid filtration due to capillary leakage, which in turn leads to increased compartmental pressure and ischemia compromising the tendons and ligaments. The neurotraumatic theory states that insensate feet are predisposed to repetitive unrecognized trauma and abnormal loading of the joint. The forefoot act as a lever due to increased plantar pressure forcing the collapse of the midfoot. In neuro-osseous-inflammatory theory, emphasis is given to disturbances in the balance between pro and anti-inflammatory cytokines. Increased proinflammatory markers activate cytokine pathways centered on receptor activator of nuclear factor kB (NF-kB) ligand (RANKL). The ratio of RANKL/osteoprotegerin (OPG) is elevated. RANKL induces differentiation of osteoclast precursor to osteoclast and leads to osteolysis. Factors with significant CNO association include hyperglycemia, neuropathy, low bone mineral density (BMD), inflammation, and neuropathy.

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