Zou Lingling, Chen Guiquan, Rong Yi, Tang Cai, Lv Xingmin, Fan Yundong
School of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou City, Sichuan, China.
J Orthop Surg Res. 2025 Feb 20;20(1):186. doi: 10.1186/s13018-025-05588-4.
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.
骨质疏松症是一种代谢性骨病，其特征是单位体积骨组织量减少和骨微结构改变，常导致骨脆性增加和骨折易感性升高。铁在人体正常生理活动中起重要作用，其代谢异常是骨质疏松症的危险因素之一。铁过载作为铁代谢异常，近年来已被报道与骨质疏松症相关。然而，铁过载参与骨质疏松症过程的机制尚未完全明确。在本综述中，我们总结了从临床研究和动物模型中了解到的关于铁过载相关骨质流失的情况。从Wnt/β-连环蛋白、BMP/SMADs、PI3K/AKT/mTOR这三条信号通路入手，探讨了铁过载影响骨质疏松症过程的机制，得出铁过载通过抑制正常Wnt信号、抑制BMP-2/SMADs通路、下调PI3K/AKT/mTOR通路来抑制骨形成，破坏骨强度和承重能力，从而加速骨质疏松症进程的结论，为临床治疗提供了新方向。
