Wang Dong, Shen Jiahui, Wang Yan, Cui Hongwei, Li Yanxin, Zhou Liyun, Li Guang, Wang Qiyu, Feng Xiaotian, Qin Mengran, Dong Benchao, Yang Peichuan, Li Yan, Ma Xinlong, Ma Jianxiong
College of Integrative Medicine of Tianjin University of traditional Chinese Medicine, Tianjin 301617,China; Graduate School of Tianjin University of traditional Chinese Medicine, Tianjin 301617, China.
Tianjin Hospital of Tianjin University (Tianjin Hospital), Tianjin 300211, China; Tianjin Orthopedic Institute, Tianjin 300050, China; Tianjin Key Laboratory of Orthopedic Biomechanics and Medical Engineering, Tianjin 300050, China.
Cell Signal. 2025 Mar;127:111598. doi: 10.1016/j.cellsig.2025.111598. Epub 2025 Jan 7.
Osteoporosis (OP) is a common disease in the elderly, characterized by decreased bone strength, reduced bone density, and increased fracture risk. There are two clinical types of osteoporosis: primary osteoporosis and secondary osteoporosis. The most common form is postmenopausal osteoporosis, which is caused by decreased estrogen production after menopause. Secondary osteoporosis, on the other hand, occurs when certain medications, diabetes, or nutritional deficiencies lead to a decrease in bone density. Ferroptosis, a new iron-dependent programmed cell death process, is critical in regulating the development of osteoporosis, but the underlying molecular mechanisms are complex. In the pathologic process of osteoporosis, several studies have found that ferroptosis may occur in osteocytes, osteoblasts, and osteoclasts, cell types closely related to bone metabolism. The imbalance of iron homeostasis in osteoblasts and excessive iron accumulation can promote lipid peroxidation through the Fenton reaction, which induces ferroptosis in osteoblasts and affects their role in regulating bone metabolism. Ferroptosis in osteoblasts inhibits bone formation and reduces the amount of new bone production. Osteoclast-associated ferroptosis abnormalities, on the other hand, may alter the homeostasis of bone resorption. In this paper, we start from the molecular mechanism of ferroptosis, and introduce the ways in which ferroptosis affects the physiological and pathological processes of the body. After that, the effects of ferroptosis on osteoblasts and osteoclasts will be discussed separately to elucidate the molecular mechanism between ferroptosis and osteoporosis, which will provide a new breakthrough for the prevention and treatment of osteoporosis and a more effective and better idea for the treatment strategy of osteoporosis.
骨质疏松症（OP）是老年人中的一种常见疾病，其特征为骨强度降低、骨密度减少以及骨折风险增加。骨质疏松症有两种临床类型：原发性骨质疏松症和继发性骨质疏松症。最常见的形式是绝经后骨质疏松症，它是由绝经后雌激素分泌减少引起的。另一方面，继发性骨质疏松症发生在某些药物、糖尿病或营养缺乏导致骨密度降低时。铁死亡是一种新的铁依赖性程序性细胞死亡过程，在调节骨质疏松症的发展中起关键作用，但其潜在的分子机制很复杂。在骨质疏松症的病理过程中，多项研究发现铁死亡可能发生在骨细胞、成骨细胞和破骨细胞中，这些细胞类型与骨代谢密切相关。成骨细胞中铁稳态的失衡和铁的过度积累可通过芬顿反应促进脂质过氧化，从而诱导成骨细胞发生铁死亡并影响其在调节骨代谢中的作用。成骨细胞中的铁死亡会抑制骨形成并减少新骨生成量。另一方面，破骨细胞相关的铁死亡异常可能会改变骨吸收的稳态。在本文中，我们从铁死亡的分子机制入手，介绍铁死亡影响机体生理和病理过程的方式。之后，将分别讨论铁死亡对成骨细胞和破骨细胞的影响，以阐明铁死亡与骨质疏松症之间的分子机制，这将为骨质疏松症的预防和治疗提供新的突破，并为骨质疏松症的治疗策略提供更有效、更好的思路。
