Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy.
Bone & joint research
The British Editorial Society of Bone & Joint Surgery
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Johnson-Lynn, S., McCaskie, A., Coll, A., & Robinson, A. (2018). Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy.. Bone & joint research, 7 (5), 373-378. https://doi.org/10.1302/2046-3758.75.bjr-2017-0334.r1
Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an 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 interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (cD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation end-products (AGLeps), leading to increased non-enzymatic glycation of collagen and accumulation of AGLeps 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 neuroarthropathy are still lacking.
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External DOI: https://doi.org/10.1302/2046-3758.75.bjr-2017-0334.r1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277302
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Licence URL: https://creativecommons.org/licenses/by-nc/4.0/