Charcot neuro‐osteoarthropathy

Abstract The classical neurotraumatic and neurotrophic theories for the pathogenesis of the acute Charcot neuro‐osteoarthropathy (CN) in diabetes, do not address certain key features of the disease. These features include the facts that the condition usually affects just one side, that it is self‐limiting, and that it is also very uncommon. Similarly, it is not known to what extent the condition may depend, as suggested by Jean‐Martin Charcot, on pre‐morbid osteopenia. Recent advances in understanding the mechanisms underlying the pathogenesis of osteopenia and osteoporosis and the central role of the RANKL/OPG signalling system have, however, suggested the possible involvement of other factors in the evolution of the disease. Specifically, it has been suggested that acute CN may be triggered in a susceptible individual by any event that leads to localized inflammation in the affected foot. This local inflammation leads to a vicious cycle in which there is increasing inflammation, increasing expression of RANKL, and increasing bone breakdown. The likely central role for the RANKL/OPG pathway suggests new possibilities for future treatments. Copyright © 2008 John Wiley & Sons, Ltd.