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

Lancet. 2005 Dec 10;366(9502):2058-61. doi: 10.1016/S0140-6736(05)67029-8. Epub 2005 Aug 10.


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 TNFalpha and interleukin 1beta. This cascade then leads to increased expression of the nuclear transcription factor, NF-kappaB, 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.

Publication types

  • Review

MeSH terms

  • Arthropathy, Neurogenic / etiology*
  • Arthropathy, Neurogenic / physiopathology
  • Carrier Proteins / physiology*
  • Diabetic Foot / physiopathology*
  • Humans
  • Inflammation / complications*
  • Interleukin-1 / adverse effects
  • Interleukin-1 / physiology*
  • Membrane Glycoproteins / physiology*
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tumor Necrosis Factor-alpha / adverse effects
  • Tumor Necrosis Factor-alpha / physiology*


  • Carrier Proteins
  • Interleukin-1
  • Membrane Glycoproteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human
  • TNFSF11 protein, human
  • Tumor Necrosis Factor-alpha