Moderate static magnetic field regulates iron metabolism and salvage bone loss caused by iron accumulation

Objective: 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 HAMP-deficient mouse models, and to elucidate the underlying mechanisms. Methods: 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 HAMP +/+ and HAMP- /- mice were randomly divided into four groups, namely GMF-HAMP+/+ group and MMF-HAMP+/+ group, GMF-HAMP-/- group and MMFHAMP-/- 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 vitro. Results: In clinical trial, MMF decreased serum ferritin levels in postmenopausal osteoporosis patients, which was negatively correlated with changes in lumbar BMD. In vivo, the results showed that HAMP-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 HAMP-/- mice. In vitro, MMF reduced the number and differentiation of osteoclasts in HAMP-/- mice, and promoted primary osteoblast differentiation by activating Wnt/beta-catenin signaling pathway. Further, MMF also reduced the iron ion conversion and enhanced the antioxidant system of HAMP- /- mice. These data suggested that MMF could regulate iron metabolism and salvage bone loss caused by iron accumulation. Conclusions: 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: 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.