Expression of the receptor activator of nuclear factor-kB ligand in peripheral blood mononuclear cells in patients with acute Charcot neuroarthropathy

Abstract

Introduction. The receptor activator of nuclear factor-kB (RANK), ligand (RANK-L) and osteoprotegerin (OPG) are implicated in the pathogenesis of acute Charcot neuroarthropathy (CN).Materials and Methods. This study aimed to investigate the expression of RANK-L and OPG in peripheral blood mononuclear cells (PBMC) from patients with acute CN.Results. We found that the expression of RANK-L was lower in patients with acute CN as compared with diabetic control subjects and healthy control participants; whereas OPG expression was not detected in patients and in both control groups. RANK-L expression at the onset of disease was inversely correlated with the index of polyunsaturation (PUI), a bone marrow MRS-derived measurable index that allows evaluation of disease activity in acute CN, and recovery time. Finally, the expression of RANK-L increased at the time of healing compared with the values found during the acute phase.Conclusions. In conclusion, our preliminary data provide a first step in applying analysis of RANK-L expression in peripheral blood cells to the diagnosis of acute CN. Based on our data we also suggest that analysis of RANK-L expression could be a complementary tool that can be employed to obtain quantitative parameters that may help clinicians to monitor disease activity in patients with acute CN.

Pathogenesis and potential relative risk factors of diabetic neuropathic osteoarthropathy

“…However, in acute DNOAP, the local inflammatory response related to increased pro-inflammatory cytokine secretion is not associated with a systemic inflammatory syndrome [ 40 ]. Bergamini et al [ 41 ] reported that the RANKL expression was significantly lower in the peripheral blood mononuclear cells of acute DNOAP patients than that in normal and diabetic controls and the RANKL expression increased at the time of healing compared with the values of acute phase. Their data suggested the existence of compensatory immunoregulatory mechanisms to potentially limit bone resorption during acute DNOAP.…”

Corneal confocal microscopy detects severe small fiber neuropathy in diabetic patients with Charcot neuroarthropathy

“…Pathways that have received the most attention in the pathogenesis of CN include the receptor activator of nuclear factor-jB, receptor activator of nuclear factor-jB ligand and osteoprotegerin 11 , and more recently, abnormalities in sclerostin, dickkopf-1, Wnt inhibitory factor-1 and Wnt ligand-1 12 . The role of these pathways is complex, with a recent study showing initial suppression of receptor activator of nuclear factor-jB ligand in peripheral blood mononuclear cells followed by increased levels in those with faster healing on magnetic resonance imaging 13 .…”

“…Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique, which allows high-resolution imaging of corneal nerves. We have pioneered its use to identify axonal loss in diabetic 21,22 and other peripheral neuropathies 23,24 , and have shown that it has a very high sensitivity and specificity for identifying diabetic autonomic neuropathy 13 . Furthermore, we have recently shown a rapid decline in corneal nerve fibers, with no change in neurophysiology or quantitative sensory testing, before the development of CN in a patient with diabetes; suggesting that small fiber neuropathy might be critical in the development of CN 25 .…”

Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy

“…A small study by Bergamini et al 28 in 2016 provided potentially conflicting data by demonstrating significantly decreased levels of RANKL in circulating peripheral blood monocytes from patients with acute CNA compared with controls. They found that increased levels of circulating RANKL coincided with clinical resolution and suggested that there is a local compensatory mechanism in acute CNA which limits bone remodelling.…”