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.

Charcot Foot, a Rare and Severe Complication of Diabetes Mellitus

“…10The mechanism of appearance of Charcot foot is one still debated, besides the conventional theories -the neurovascular (Charcot), or the neurotraumatic (Volkmann and Virchow), other pathophysiological mechanisms such as inflammatory cytokines, their reactions, calcitonin, genes polymorphisms, interleukins or vitamin D3 levels have been recently highlighted. (11,12,13) The neurovascular theory is based on the opening of arterio-venous shunts, secondary to lesions of trophic or vasomotors nerves. This opening of the shunts results in an additional vascular contribution with the increase of the quantity of monocytes and osteoclasts that will cause bone resorption.…”

“…Thus, bone destruction occurs by accentuating osteoclastogenesis, a destruction that will potentiate the inflammatory response with entry into a vicious circle. (12,16) Hyperglycemia causes the growth of the nonenzymatic process and the formation of Amadori products. These are combined with other proteins and amino compounds resulting in advanced glycation end products (AGEs).…”

Role of bisphosphonates in the management of acute Charcot foot

“…This pro-inflammatory state can be triggered by repeated microtrauma. Hyperglycemia in DM can lead to increased PKC activity and formation of AGEs along with decreased phosphatidylinositol 3 kinase activity[ 8 ]. This, in turn, results in an excessive production of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6.…”

“…Recent advancements in the understanding of the pathophysiology of CF has shed light on factors like inflammatory cytokines and their interaction with receptor activator of nuclear factor kappa-B (RANK), its ligand (RANKL), and osteoprotegerin (OPG)[ 6 ]. Long-standing hyperglycemia, with its complications ranging from neuropathy to formation of advanced glycation end products (AGEs)[ 7 ] and protein kinase C (PKC) activation[ 8 ], is the major culprit. Calcitonin gene-related peptide (CGRP)[ 9 ], Wnt/beta-catenin pathway[ 10 ], and OPG gene polymorphisms[ 11 ] are new players in the field.…”

The successful complex treatment diabetic neuroosteoarthropathy of the middle part of the foot in the stage of purulent complications

“…лечение с обязательной иммобилизацией стопы и голеностопного сустава в индивидуальной ортопедической обуви или в разгрузочной повязке [6,7]. Другие предлагают ортопедическую коррекцию деформаций с использованием внутреннего остеосинтеза или аппаратов внешней фиксации [8][9][10][11].…”