The brain-bone axis: investigating the interaction between the central nervous system and skeletal homeostasis

The brain serves as the core component of the central nervous system and plays a pivotal role in regulating the functions of various essential organs throughout the body. The skeletal system serves as the fundamental supportive and protective framework of the human body, and is extensively innervated by nerves. Currently, a large body of epidemiological and experimental evidence confirms the close interplay between bones and the brain, but the underlying mechanisms remain unclear. This review is anchored on the concept of the brain-bone axis, aiming to gain a deeper understanding of the physiological and pathological interactions between these two organs. A comprehensive analysis of the potential foundations and mechanisms underlying the intricate association between the brain and the skeleton is offered. In summary, the brain can influence skeletal homeostasis through modulation of the neuromolecules, extracellular vesicles, and brain-marrow neural circuit, conversely the skeleton can influence the brain in its development, function, and pathology by physical exercise, massage therapy, and skeletal trauma. Simultaneously, the strategies for the treatment of skeletal and neurological disorders were organized, in which Traditional Chinese Medicine appears to offer new perspectives for the prevention and disease management, ultimately aiming to furnish patients with more effective therapeutic methods.