Understanding the intricate interplay between sensory nerves and bone tissue cells is of paramount significance in the field of bone biology and clinical medicine. The regulatory role of sensory nerves in bone homeostasis offers a novel perspective for the development of targeted therapeutic interventions for a spectrum of bone-related diseases, including osteoarthritis, osteoporosis, and intervertebral disc degeneration. By elucidating the mechanisms through which sensory nerves and their neuropeptides influence the differentiation and function of bone tissue cells, this review aims to shed light on emerging therapeutic targets that harness the neuro-skeletal axis for the treatment and management of debilitating bone disorders. Moreover, a comprehensive understanding of sensory nerve-mediated bone regulation may pave the way for the development of innovative strategies to promote bone health and mitigate the burden of skeletal pathologies in clinical practice. •Sensory nerves and neuropeptides exert significant influence on MSCs, osteoclasts, osteoblasts, chondrocytes, and NPCs.•The regulatory role of sensory nerves and neuropeptides in conditions like OA, OP, and IVDD presents promising therapeutic opportunities.•Innovative approaches for enhancing skeletal health involve modulating sensory nerve activity, including specific neuropeptides.•Targeted therapies leveraging the neuro-skeletal axis can improve bone health and alleviate skeletal pathologies.