Levels of Endothelial Nitric Oxide Synthase and Calcitonin Gene–related Peptide in the Charcot Foot: A Pilot Study

The pathogenesis of Charcot neuroarthropathy is unclear. To investigate the possibility that decreased levels of calcitonin gene–related peptide and endothelial nitric oxide synthase are involved in the process, we studied bone samples from healthy subjects (n = 4), subjects with diabetic neuropathy (n = 4), and subjects with Charcot neuroarthropathy (n = 4). A statistically significant difference was found in endothelial nitric oxide synthase expression between bone specimens in patients with diabetic neuropathy, Charcot neuroarthropathy, and normal bone (P = .008). A trend toward calcitonin gene–related peptide intensification was observed in normal bone as compared to diabetic neuropathy and Charcot neuroarthropathy bone specimens, but it did not reached statistical significance (P = .23). This pilot study suggests that abnormal calcitonin gene–related peptide and endothelial nitric oxide synthase activity may play a role in the development of Charcot neuroarthropathy. Level of Clinical Evidence: 4