Melatonin alleviates sodium sulfite-induced osteoporosis in mice via suppression of the ferroptosis pathway.

Sodium sulfite (SS) is a common food additive that is widely absorbed and distributed throughout the body, but its excessive intake has been linked to adverse health effects. Here, we investigate the impact of chronic SS exposure on bone tissue and the underlying mechanisms. Using a mouse model, we demonstrate that prolonged SS exposure induces significant bone loss, which correlates with alterations in ferroptosis-related markers. In vitro, SS exposure activates ferroptosis, which is characterized by elevated reactive oxygen species levels and impaired osteogenic differentiation in MC3T3 cells. Notably, melatonin, a potent endogenous antioxidant, mitigates SS-induced oxidative stress, inhibits ferroptosis, restores osteoblast function, and alleviates bone loss in mice. These findings highlight ferroptosis as a critical contributor to SS-induced osteoporosis and identify melatonin as a promising therapeutic agent for its prevention and treatment.