Molecular mechanisms and therapeutic implications of the sympathetic nervous system in bone-related disorders: a brain-bone axis perspective

The global aging crisis has increased the prevalence of skeletal disorders, necessitating innovative therapeutic strategies. This review employs the brain-bone axis (BBA) framework to examine the role of the sympathetic nervous system (SNS) in bone metabolism. The research systematically elucidates the molecular mechanisms by which the SNS mediates signaling pathways through neurofibers and neurotransmitters, such as norepinephrine, dopamine, neuropeptide Y, and leptin, regulating interactions between bone-related cells to maintain skeletal homeostasis. It also identifies the pathological associations between the dysregulation of these pathways and the progression of bone-related conditions, such as osteoporosis, osteoarthritis, and intervertebral disc degeneration. By integrating current evidence, we identify novel therapeutic targets within the BBA and propose neuro-centric intervention strategies to mitigate skeletal diseases. This review deepens the understanding of neuro-skeletal interactions and lays a foundation for innovative treatments for bone-related pathologies.