Charcot's foot: newest findings on its pathophysiology, diagnosis and treatment.

Charcot neuro-osteoarthropathy (CNO) is one of the more devastating complications affecting diabetic patients with peripheral and/or autonomic neuropathy. The acute phase of the disease is often misdiagnosed, and can rapidly lead to deformity and amputation. The rapid progression towards foot deformation calls for early detection and intervention. Classical neurotraumatic and neurotrophic theories fail to explain all of the features of the condition, although recent advances that have clarified the mechanisms underlying the pathophysiology may make up for this lack. In particular, new data have emerged on the central role of the RANK/RANK-ligand (RANK-L)/osteoprotegerin (OPG) system in the pathogenesis of osteopenia. Also, it is now recognized that the acute phase of CNO can be triggered by any factor leading to local inflammation of the foot, especially in predisposed patients. As the cornerstone of treatment remains any method that avoids weight-bearing on the foot, the primary importance of the RANK/RANK-L/OPG signalling pathway is that it opens up the field to new treatment strategies for the future.