The role of proinflammatory cytokines in the cause of neuropathic osteoarthropathy (acute Charcot foot) in diabetes

The pathogenesis of the acute Charcot foot of diabetes remains unclear. All patients with this condition have evidence of peripheral neuropathy, with loss of protective sensation and abnormal foot biomechanics. However, the acute Charcot foot is also characterised by a pronounced inflammatory reacti...

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Bibliographic Details
Published in:The Lancet (British edition) 2005-12, Vol.366 (9502), p.2058-2061
Main Authors: Jeffcoate, William J, Game, Fran, Cavanagh, Peter R
Format: Article
Language:English
Subjects:
Arthropathy, Neurogenic - etiology
Arthropathy, Neurogenic - physiopathology
Biological and medical sciences
Biomechanics
Carrier Proteins - physiology
Cytokines
Diabetes
Diabetes. Impaired glucose tolerance
Diabetic Foot - physiopathology
Diseases of the osteoarticular system
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
General aspects
Humans
Hypotheses
Inflammation - complications
Inflammatory diseases
Interleukin-1 - adverse effects
Interleukin-1 - physiology
Medical sciences
Membrane Glycoproteins - physiology
Miscellaneous. Osteoarticular involvement in other diseases
Peptides
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Tumor Necrosis Factor-alpha - adverse effects
Tumor Necrosis Factor-alpha - physiology
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Summary:The pathogenesis of the acute Charcot foot of diabetes remains unclear. All patients with this condition have evidence of peripheral neuropathy, with loss of protective sensation and abnormal foot biomechanics. However, the acute Charcot foot is also characterised by a pronounced inflammatory reaction and the pathogenic significance of this inflammation has received little attention. We suggest that an initial insult—which may or may not be detected—is sufficient to trigger an inflammatory cascade through increased expression of proinflammatory cytokines, including TNFα and interleukin 1β. This cascade then leads to increased expression of the nuclear transcription factor, NF-κB, which results in increased osteoclastogenesis. Osteoclasts cause progressive bone lysis, leading to further fracture, which in turn potentiates the inflammatory process. The potential role of proinflammatory cytokines suggests the possibility of new treatments for this sometimes devastating complication of diabetes.
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(05)67029-8