Osteoimmunology and bone microenvironment remodeling in osteoporosis: mechanisms and translational perspectives

Osteoporosis is traditionally viewed as a disorder of impaired bone remodeling characterized by an imbalance between osteoblast-mediated bone formation and osteoclast-driven bone resorption. However, emerging evidence has revealed that osteoporosis is also a disease of the bone marrow microenvironment, where immune cells, mesenchymal stem cells, osteocytes, and marrow adipocytes interact through complex inflammatory and metabolic networks. In this review, we summarize recent advances in osteoimmunology and the cellular crosstalk governing skeletal homeostasis. We discuss how immune cell subsets, cellular senescence, senescence-associated secretory phenotype (SASP), marrow adiposity, and osteocyte-derived signals contribute to osteoporosis pathogenesis. We further highlight key molecular pathways, including RANK/RANKL/OPG, Wnt/β-catenin, Hippo-YAP, and inflammatory signaling networks that coordinate communication between bone and immune cells. Finally, we review current and emerging therapeutic strategies targeting osteoimmune interactions, bone marrow remodeling, and precision medicine approaches. By integrating advances in immunology, bone biology, and translational research, this review provides an updated framework for understanding osteoporosis as a complex osteoimmune disorder and discusses future opportunities for therapeutic intervention.