ARTHRITIS IN DIABETES: PATHOGENESIS OF CHARCOT ARTHROPATHY15 Jun 2018
Charcot neuroarthropathy is a rare but serious complication of peripheral neuropathy, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interconnected factors. These may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (NO and CGRP), which may affect the normal coupling of bone formation / resorption and increased levels of RANKL, potentiating osteoclastogenesis. Repetitive unrecognised trauma due to neuropathy increases levels of pro-inflammatory cytokines (IL1β, IL6, TNFα) which could also contribute to increased bone resorption, on a background of a system biased towards inflammation with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts (CD14). Increased blood glucose and loss of circulating RAGE, leading to increased non-enzymatic glycation of collagen and accumulation of AGEs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot arthropathy are still lacking.