Osteoporosis is a metabolic bone disease characterized by a decrease in the amount of bone tissue per unit volume and changes in bone microstructure, often resulting in bone fragility and increased susceptibility to fracture. Iron plays an important role in the normal physiological activities of human body, and its abnormal metabolism is one of the risk factors of osteoporosis. Iron overload, as an abnormality of iron metabolism, has been reported to be associated with osteoporosis in recent years. However, the mechanism of iron overload involved in the process of osteoporosis is not fully understood. In this review, we summarize what we have learned about iron overload-associated bone loss from clinical studies and animal models. Starting from the three signaling pathways of Wnt/β-catenin, BMP/SMADs, PI3K/AKT/mTOR, the mechanism of iron overload affecting the process of osteoporosis was explored, we got the conclusion that iron overload accelerates the process of osteoporosis by inhibiting normal wnt signaling, suppressing the BMP-2/SMADs pathway, down-regulating the PI3K/AKT/mTOR pathway to inhibit bone formation, and destroying the bone strength and load-bearing capacity, which providing a new direction for clinical treatment.