• The bone-blood axis represents a bidirectional regulatory network between skeletal and hematopoietic systems, crucial for maintaining bone mass and hematopoietic function.
• Core signaling pathways (Wnt/β-catenin, Notch, RANK/RANKL/OPG, Hippo-YAP) mediate the crosstalk, with immune cells acting as key bridges.
• Metabolic products like lactate and 2-hydroxyglutarate serve as intercellular signaling molecules linking metabolism and epigenetics in bone remodeling and hematopoietic fate.
• Targeting the bone-blood axis (e.g., with denosumab or enasidenib) offers promising therapeutic strategies for cross-system diseases such as osteoporosis and leukemia.