Autonomic Nervous System in Bone Remodeling: From Mechanisms to Novel Therapies in Orthopedic Diseases

Recent literature has increasingly demonstrated the significant function of autonomic nerves in regulating physiological and pathological changes associated with the skeletal system. Extensive studies have been conducted to understand the contribution of the autonomic nervous system (ANS) to skeletal metabolic homeostasis and resistance to aseptic inflammation, specifically from the viewpoint of skeletal neurobiology. There have been plenty of studies on how the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS), the two main branches of the ANS, regulate bone remodeling, which is the process of bone formation and resorption. The following studies have revealed critical neurological pathways that induce significant alterations in bone cell biology and uncover the intricate linkages between the ANS and the skeletal system. Furthermore, inspired by the connection between the ANS and bone remodeling, neuromodulation has been utilized as a therapeutic method for patients with orthopedic diseases: by directly influencing the ANS, it is possible to alter the excitability of nerve fibers and the release of neurotransmitters, which can lead to anti-inflammatory and analgesic effects, thereby directly or indirectly impacting bone formation and bone resorption. Our work aims to review the most recent findings on the impact of the ANS on bone remodeling, enhance the current understanding of the interaction between nerves and bones, and explore potential neuromodulation methods that could be used to treat orthopedic conditions, thereby drawing attention to the significant role of the ANS in the skeletal system.