The Role of Peripheral Nerves in Bone Remodelling and Pain in Diabetes

Bone fragility and of poorer quality as well as damage to the peripheral nervous system (diabetic peripheral neuropathy, DPN) are very important complications in patients with Diabetes. DPN can lead to physical disability and pain and ultimately Charcot neuro-osteoarthropathy (CN). Pain symptoms can be severe, decreasing greatly the quality of life of diabetic patients. We still know relatively little about how DPN affects bone and joints and its association with pain in these patients. Recently, significant progress has been made in our knowledge of the distribution and function of nerves in bone and our understanding of skeletal pain in several musculoskeletal conditions such as fractures, osteoarthritis and bone cancer. We also know more on how these nerves are involved in the control of bone remodelling. In contrast, the role of bone innervation has been less studied in the context of diabetes, despite evidence for a decreased density of nerve fibres in this condition which is positively correlated to the loss of bone. This presentation will summarise the recent research advances on the association of DPN with the development of bone pathology and how nerves regulate bone loss in diabetes. One aspect which has also been poorly explored is the role of neuropeptides and neurotrophins expressed by small sensory nerve fibres in the regulation of skeletal homeostasis and the development of chronic pain in diabetes. We have preliminary data suggesting that calcitonin-gene related peptide (CGRP) and nerve growth factor (NGF) measured in bone and serum of diabetic patients can contribute to inflammation and chronic pain in DPN and could indicate different stages of CN progression. This talk will also discuss the potential role of these neuropeptides and neurotrophins in bone turnover and pain in DPN and CN.