| With the intensification of population aging in China, the prevalence of osteoporosis has significantly increased, and its core pathological mechanism is the disruption of bone metabolism balance. Growth differentiation factor 15 (GDF15, belonging to the TGF-β superfamily) affects bone metabolism through multiple mechanisms. It can not only inhibit osteoblast differentiation, down-regulate osteogenic genes such as ALP and RUNX2, and block the BMP2 signaling pathway, but also promote osteoclast differentiation, cooperates with RANKL to activate the NF-κB/MAPK pathway, and up-regulate osteoclast genes. It can also promote the expression of inflammatory factors and intensify bone resorption through pathways such as TLR/MyD88 and IL-6. However, high GDF15 inhibits hepcidin, resulting in iron overload, inhibits osteogenesis and enhances osteoclast. Meanwhile, as an SASP factor, it inhibits the differentiation of osteoblasts and enhances the activity of osteoclasts, resulting in bone destruction. The serum GDF15 level in patients with osteoporosis is elevated and negatively correlated with bone mineral density, which can be used as a diagnostic marker. In the future, it is necessary to deeply explore the molecular regulatory mechanisms such as the Smad/MAPK cross-pathway, as well as the synergistic effect of inflammation - ferroptosis - cellular senescence, and develop anti-GDF15 antibodies and targeted intervention strategies combined with anti-aging drugs, in order to provide a new direction for the diagnosis and treatment of osteoporosis. |