Osteoimmunology: interactions of the bone and immune system

Osteoimmunology represents an emerging interdisciplinary domain that investigates the reciprocal crosstalk between the skeletal and immune compartments, which serves as the core immunological basis for the pathogenesis of diverse musculoskeletal disorders. This bidirectional communication is facilitated by a shared microenvironment and common molecular mediators. This review systematically synthesizes the regulatory effects of T cells, B cells, and macrophages on bone homeostasis. Their modulatory actions are predominantly executed via proinflammatory cytokines and canonical signaling cascades, with particular emphasis on the RANKL/RANK/OPG axis. In parallel, we highlight that bone lineage cells (e.g., osteoblasts and osteoclasts) are not merely passive targets of immune regulation. Instead, they actively participate in immune cell development and function by secreting cytokines. Together, these interactions form an integrated and dynamic regulatory balance. Under physiological conditions, this finely tuned bone-immune crosstalk maintains bone-immune homeostasis. Its disruption, however, contributes to the pathogenesis of typical musculoskeletal pathologies, including rheumatoid arthritis, osteoporosis, and tumor-associated bone metastasis. Adopting an integrated perspective, this review integrates the shared regulatory mechanisms and microenvironment-dependent features of osteoimmune interactions. It provides a theoretical framework for understanding osteoimmune imbalance in musculoskeletal disorders and for developing precise therapeutic strategies.