Zhen Chenxiao, Wang Shenghang, Yang Jiancheng, Zhang Gejing, Cai Chao, Wang Jianping, Wang Aifei, Xu Youjia, Fang Yanwen, Wei Min, Yin Dachuan, Luo Xinle, Gong Ming, Zhang Hao, Shang Peng
School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, China.
Research & Development Institute of Northwestern Polytechnical University, Shenzhen, 518057, China.
J Orthop Translat. 2025 Jan 10;50:144-157. doi: 10.1016/j.jot.2024.10.012. eCollection 2025 Jan.
Clinical studies, epidemiological investigations and animal experiments have demonstrated that iron overload lead to bone loss, especially postmenopausal osteoporosis. As a physiotherapy tool, electromagnetic fields already used in clinical treatment of osteoporosis and participates in bone remodeling by affecting the iron metabolism of organisms. As an electromagnetic field with constant magnetic flux density and direction, the mechanism of static magnetic field (SMF) regulating iron metabolism remains unclear. Therefore, the aim of this study was to investigate the effects of moderate static magnetic field (MMF) on iron metabolism and bone metabolism in postmenopausal osteoporosis and -deficient mouse models, and to elucidate the underlying mechanisms.
Firstly, the effects of MMF on bone metabolism and iron metabolism in 22 postmenopausal osteoporosis participants were evaluated by comparing the changes of bone mineral density (BMD) and serum ferritin before and after treatment. Secondly, 10-week-old male C57BL/6 and mice were randomly divided into four groups, namely GMF- group and MMF- group, GMF- group and MMF- group (n = 8/group). The MMF-treated mice were exposed daily to MMF, while the remaining group was exposed to geomagnetic field (GMF) for 8 weeks. BMD was scanned and bone tissues were collected for mechanical, structural and histological analysis. In addition, analysis of serum and tissue iron content evaluated the regulation of systemic iron metabolism by MMF. Finally, the effects of MMF on the differentiation of primary macrophages and primary osteoblasts were evaluated .
In clinical trial, MMF decreased serum ferritin levels in postmenopausal osteoporosis patients, which was negatively correlated with changes in lumbar BMD. , the results showed that -deficient mice were accompanied by iron overload, along with reduced lumbar vertebra bone mass and bone quality. MMF improved the bone mass, microstructure and biomechanical properties of lumbar vertebrae in mice. , MMF reduced the number and differentiation of osteoclasts in mice, and promoted primary osteoblast differentiation by activating Wnt/β-catenin signaling pathway. Further, MMF also reduced the iron ion conversion and enhanced the antioxidant system of mice. These data suggested that MMF could regulate iron metabolism and salvage bone loss caused by iron accumulation.
The clinical trial and laboratory results suggested that MMF intervention has a protective effect on bone loss caused by iron metabolism disorders.
Translational potential of this article: This study demonstrated the feasibility and potential effectiveness of MMF in the treatment of postmenopausal osteoporosis patients, demonstrating for the first time that MMF can reduce bone loss in mice with inherited iron metabolism abnormalities. It was suggested that MMF plays an important role in iron metabolism disorders or as an alternative therapy to ameliorate osteoporosis caused by iron accumulation.
临床研究、流行病学调查及动物实验均表明，铁过载会导致骨质流失，尤其是绝经后骨质疏松。作为一种物理治疗手段，电磁场已用于骨质疏松症的临床治疗，并通过影响机体的铁代谢参与骨重塑。作为一种磁通密度和方向恒定的电磁场，静磁场（SMF）调节铁代谢的机制尚不清楚。因此，本研究旨在探讨中度静磁场（MMF）对绝经后骨质疏松和缺铁小鼠模型铁代谢及骨代谢的影响，并阐明其潜在机制。
首先，通过比较22例绝经后骨质疏松患者治疗前后骨密度（BMD）和血清铁蛋白的变化，评估MMF对骨代谢和铁代谢的影响。其次，将10周龄雄性C57BL/6小鼠随机分为四组，即地磁场（GMF）组和MMF组、GMF组和MMF组（每组n = 8）。接受MMF治疗的小鼠每天暴露于MMF，其余组暴露于地磁场（GMF）8周。扫描BMD并收集骨组织进行力学、结构和组织学分析。此外，通过分析血清和组织铁含量评估MMF对全身铁代谢的调节作用。最后，评估MMF对原代巨噬细胞和原代成骨细胞分化的影响。
在临床试验中，MMF降低了绝经后骨质疏松患者的血清铁蛋白水平，这与腰椎BMD的变化呈负相关。结果表明，缺铁小鼠伴有铁过载，同时腰椎骨量和骨质降低。MMF改善了缺铁小鼠腰椎的骨量、微观结构和生物力学性能。此外，MMF减少了缺铁小鼠破骨细胞的数量和分化，并通过激活Wnt/β-连环蛋白信号通路促进原代成骨细胞分化。此外，MMF还减少了缺铁小鼠的铁离子转化并增强了其抗氧化系统。这些数据表明，MMF可以调节铁代谢并挽救由铁蓄积引起的骨质流失。
临床试验和实验室结果表明，MMF干预对铁代谢紊乱引起的骨质流失具有保护作用。
本文的转化潜力：本研究证明了MMF治疗绝经后骨质疏松患者的可行性和潜在有效性，首次证明MMF可以减少遗传性铁代谢异常小鼠的骨质流失。提示MMF在铁代谢紊乱中起重要作用，或作为改善铁蓄积引起的骨质疏松的替代疗法。
