Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss

Bingyang Dai; Xu Li; Jiankun Xu; Yuwei Zhu; Le Huang; Wenxue Tong; Hao Yao; Dick Ho-Kiu Chow; Ling Qin

doi:10.1016/j.bioactmat.2021.01.027

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss

Bioact Mater. 2021 Feb 3;6(8):2511-2522. doi: 10.1016/j.bioactmat.2021.01.027. eCollection 2021 Aug.

Authors

Bingyang Dai¹, Xu Li¹, Jiankun Xu¹, Yuwei Zhu², Le Huang¹, Wenxue Tong¹, Hao Yao¹, Dick Ho-Kiu Chow¹, Ling Qin¹

Affiliations

¹ Musculoskeletal Research Laboratory of Department of Orthopedics & Traumatology and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
² Department of Chemistry, The Chinese University of Hong Kong, New Territories, Hong Kong, China.

Abstract

Introduction: Magnesium (Mg) has a prophylactic potential against the onset of hyperlipidemia. Similar to statin, Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an association with increased bone mass. The combination of statin with Mg ions (Mg²⁺) may be able to alleviate the high-fat diet (HFD)-induced bone loss and reduce the side-effects of statin. This study aimed to explore the feasibility of combined Mg²⁺ with simvastatin (SIM) for treating HFD-induced bone loss in mice and the involving mechanisms.

Materials and methods: C57BL/6 male mice were fed with a HFD or a normal-fat diet (NFD). Mice were intraperitoneally injected SIM and/or orally received water with additional Mg²⁺ until sacrificed. Enzyme-linked immunosorbent assay was performed to measure cytokines and cholesterol in serum and liver lysates. Bone mineral density (BMD) and microarchitecture were assessed by micro-computed tomography (μCT) in different groups. The adipogenesis in palmitate pre-treated HepG2 cells was performed under various treatments.

Results: μCT analysis showed that the trabecular bone mass was significantly lower in the HFD-fed group than that in NFD-fed group since week 8. The cortical thickness in HFD-fed group had a significant decrease at week 24, as compared with NFD-fed group. The combination of Mg²⁺ and SIM significantly attenuated the trabecular bone loss in HFD-fed mice via arresting the osteoclast formation and bone resorption. Besides, such combination also reduced the hepatocytic synthesis of cholesterol and inhibited matrix metallopeptidase 13 (Mmp13) mRNA expression in pre-osteoclasts.

Conclusions: The combination of Mg²⁺ and SIM shows a synergistic effect on attenuating the HFD-induced bone loss. Our current formulation may be a cost-effective alternative treatment to be indicated for obesity-related bone loss.

Keywords: Bone loss; Cholesterol; Magnesium; Obesity; Simvastatin; Trabecular bone.