Pathogenesis and potential relative risk factors of diabetic neuropathic osteoarthropathy

Abstract

Diabetic neuropathic osteoarthropathy (DNOAP) is an uncommon, but with considerable morbidity and mortality rates, complication of diabetes. The real pathogenesis is still unclear. The two popular theories are the neuro-vascular theory and neuro-traumatic theory. Most theories and pathways focused on the uncontrolled inflammations that resulted in the final common pathway, receptor activator of nuclear factor κβ ligand (RANKL)/osteoprotegerin (OPG) axis, for the decreased bone density in DNOAP with an osteoclast and osteoblast imbalance. However, the RANKL/OPG pathway does not explain all the changes, other pathways and factors also play roles. A lot of DNOAP potential relative risk factors were evaluated and reported in the literature, including age, gender, weight, duration and type of diabetes, bone mineral density, peripheral neuropathy and arterial disease, trauma history, and some others. However, most of them are still in debates. Future studies focus on the pathogenesis of DNOAP are still needed, especially for the genetic factors. And, the relationship between DNOAP and those potential relative risk factors are still need to further clarify.

Keywords: Charcot foot; Diabetic neuropathic osteoarthropathy; Pathogenesis; Receptor activator of nuclear factor κβ ligand (RANKL); Risk factor.

Fig. 1

The radiographic characters of DNOAP. The fracture type (a) and the dislocation type (b)

Fig. 2

The pathogenesis of DNOAP. DNOAP diabetic neuropathic osteoarthropathy, AGE advanced glycation end products, RAGE receptor for advanced glycation end products, PKC protein kinase C, PI phosphatidylinositol, NO nitric oxide. ROS reactive oxidant species, CGRP calcitonin gene-related peptide, BMD bone mineral density, oxPTM oxidative post-translational modification, IL interleukin, TNF tumor necrosis factor, FLS fibroblast-like synoviocytes, RANKL receptor activator of nuclear factor κβ ligand, OPG osteoprotegerin, MMPs matrix metalloproteinase, Dkk-1 dickkopf-1, Wnt-1 Wnt ligand-1