Charcot Foot in Diabetes: Farewell to the Neurotrophic Theory

Abstract

Neuropathic osteoarthropathy is characterised by relatively painless swelling together with extensive damage in bones and joints, predominantly in the feet and ankles. The uncontrolled natural course of the condition leads to gross foot deformity, skin pressure ulceration, spreading infections, and sometimes amputation. Jean-Martin Charcot in 1883 described "Charcot foot" named after him in patients with tabes dorsalis insensitivity. Charcot believed that intrinsic bone weakness was the underlying condition, and was caused by neurogenic deficiencies in bone nutrition. His followers believed such dystrophy to be mediated by sympathetic denervation of the bone vasculature (neurotrophic, or neurovascular theory). Attempts to prove this theory were futile. A neurogenic circulatory disorder potentially relevant to bone nutrition could not be identified. Nowadays, Charcot foot is mostly seen in diabetic neuropathy, which has replaced syphilis as a frequent cause of peripheral nerve dysfunction. Recent studies in the diabetic Charcot foot and bone turnover indicate that the neurotrophic theory is a myth. The assumption of bone resorption due to sympathetic denervation proved to be false--sympathetic activity increases osteoclastic activity and thereby bone loss (sympathomimetic bone resorption). Except for the transient, inflammatory stage of the diabetic Charcot foot, there is no evidence of relevant osteoporosis or demineralisation of the foot skeleton in diabetes.

Outcomes of surgical treatment of diabetic foot osteomyelitis: a series of 185 patients with histopathological confirmation of bone involvement

“…These changes were not compatible with osteomyelitis, being, rather, typical of acute fractures. This point is consistent with a recent review of diabetic foot neuroarthropathy [24]. A study on bone histomorphology showed several pathological findings but did not describe in detail the type of inflammation seen in the 29 cases of osteomyelitis [25].…”

Bone Histomorphology May Be Unremarkable in Diabetes Mellitus

“…Short-term (< 12 months) histomorphological studies in diabetic rats and mice have shown that substitution of insulin deficiency reverses the negative effects that diabetes mellitus has on bone morphology and bone healing [9][10][11][12]21]. Epidemiologic and clinical studies in humans have confirmed that bone quality, in general, is not much affected by diabetes: bone mineral density is slightly reduced in long-standing type 1 diabetes, but normal or increased in type 2 diabetes [8,22]. Diabetic polyneuropathy does not seem to exert negative effects on bone quality and bone healing in diabetic patients; in essence, fracture healing in diabetic polyneuropathy is virtually not different from fracture healing in control subjects [23].…”

Marked loss of sympathetic nerve fibers in chronic Charcot foot of diabetic origin compared to ankle joint osteoarthritis

“…missing warm perception in 87% missing cold perception in 80% Vibration perception threshold n.a. 12 AE 1 Neuropathy symptom score [1][2][3][4][5][6][7][8][9][10] n.a. 6.0 AE 1.…”

“…5 In addition, a neurovascular theory suggests a disturbance of sympathetic vascular control leading to hyperemia and exaggerated bone resorption, 2 although this has been debated by others. 6 The exact sequence of events in the development of Charcot foot is unclear, but three etiological causes-neurotrophic, microtraumatic, and neurovascular-may accompany each other depending on the time point of investigation, that is, the duration of the disease and the stage of inflammation. In this context, recent investigations with magnetic resonance imaging (MRI) have demonstrated that an incipient stage of the disease exists, which might be quite different from more chronic stages with long-term inflammation.…”