Charcot neuroarthropathy: From the laboratory to the bedside

BACKGROUND: The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. INTRODUCTION: The present review provides a concise account of the advances made over the last twenty-five years in understanding the pathogenesis and management of Charcot neuroarthropathy (CN). METHODS: An overview of the widely known pathogenetic mechanisms underpinning CN are brought into focus, particularly the role of RANKL/RANK/OPG system and advanced glycation end production in the pathogenesis of CN. Furthermore, other potential triggering factors, namely nitric oxide, endothelial dysfunction, macro calcifications and body weight that influence CN are also discussed. RESULTS: The wide range of diagnostic tools available to clinicians for an accurate staging of this pathology is examined, particularly radiological and nuclear medicine imaging. Additionally, the difficult differential diagnosis between osteomyelitis and CN is also elucidated. CONCLUSIONS: The review concludes with the comprehensive summary of the major promising therapeutic strategies, including conservative treatment involving orthopedic devices, pharmacological approach, and the most common surgical techniques currently employed in the diagnosis and treatment of this acute disease.