Peripheral Neuropathy as a Component of Skeletal Disease in Diabetes

Abstract

Purpose of Review The goal of this review is to explore clinical associations between peripheral neuropathy and diabetic bone disease and to discuss how nerve dysfunction may contribute to dysregulation of bone metabolism, reduced bone quality, and fracture risk. Recent Findings Diabetic neuropathy can decrease peripheral sensation (sensory neuropathy), impair motor coordination (motor neuropathy), and increase postural hypotension (autonomic neuropathy). Together, this can impair overall balance and increase the risk for falls and fractures. In addition, the peripheral nervous system has the potential to regulate bone metabolism directly through the action of local neurotransmitters on bone cells and indirectly through neuroregulation of the skeletal vascular supply. Summary This review critically evaluates existing evidence for diabetic peripheral neuropathy as a risk factor or direct actor on bone disease. In addition, we address therapeutic and experimental considerations to guide patient care and future research evaluating the emerging relationship between diabetic neuropathy and bone health.

The Role of Bone Scintigraphy with SPECT/CT in the Characterization and Early Diagnosis of Stage 0 Charcot Neuroarthropathy

“…However, the pathology at this stage is not well understood although Magnetic Resonance Imaging (MRI) has proved helpful by identifying reactive, inflammatory bone marrow with or without microfracture before overt radiographic changes are apparent [ 4 , 8 ]. The previous use of three-phase bone scintigraphy in diabetes patients with neuropathy suggested increased blood flow to bone but the planar imaging has low anatomical resolution [ 9 ]. However, the introduction of hybrid Single Photon Emission Computed Tomography/ Computed Tomography (SPECT/CT) in nuclear medicine has improved the diagnostic potential of bone scintigraphy [ 10 ].…”

Neuroskeletal Effects of Chronic Bioelectric Nerve Stimulation in Health and Diabetes

“…In this study, we hypothesized that a neuroregenerative eStim paradigm may be sufficient to halt the progression of diabetic peripheral neuropathy (DPN), contributing to restoration of function. Considering correlations between neural and musculoskeletal health in diabetes (Melendez-Ramirez et al, 2010;Forbes and Cooper, 2013;Jaiswal et al, 2017;Beeve et al, 2019), we also hypothesized that eStim would provide a simultaneous benefit for innervated downstream organs, including muscle and bone, in both control and diabetic rats. To test this hypothesis, we utilized a fully implantable, wireless system for sciatic nerve stimulation that has previously been employed to promote nerve regeneration (MacEwan et al, 2018).…”

Bone Mineral Density in Diabetes Mellitus Foot Patients for Prediction of Diabetic Neuropathic Osteoarthropathic Fracture

“…[9,10] Current concepts suggest that osteopenic bones show more initial microfracture, and there is evidence that both neuropathy and diabetes are related with osteopenia. [11] Diabetic induced neuropathy causes bone dissolution and increases osteoclast activity by increasing the expression of receptor activator of nuclear transcription factor β ligand, which can lead to increased activation of nuclear transcription factor β. [12] This osteolysis pathway can further be enhanced by the presence of free radicals, hyperlipidemia, increased ambient glucose concentration and advanced glycation end-products present in diabetic patients.…”

“…Osteoporosis has also been hypothesized to have a role in DNOAP development, but it is still controversial [ 9 , 10 ]. Current concepts suggest that osteopenic bones show more initial microfracture, and there is evidence that both neuropathy and diabetes are related with osteopenia [ 11 ]. Diabetic induced neuropathy causes bone dissolution and increases osteoclast activity by increasing the expression of receptor activator of nuclear transcription factor β ligand, which can lead to increased activation of nuclear transcription factor β [ 12 ].…”