Magnesium and vitamin C supplementation attenuates steroid-associated osteonecrosis in a rat model
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AbstractMagnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biolo-gical effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in re-levant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C(VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. InSAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markerswere measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluatedby micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteo-blastogenesis and osteoclastogenesis. The mechanisms were testedin vitro. Histological evaluation showed SAONlesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytesand osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the boneformation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFαexpression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantlyincreased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks afterSAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improvedthe trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiationpotential of marrow cells.In vitrostudy showed promoting osteoblast differentiation effect of VC, and anti-inflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supple-mentation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic mi-nerals for preventing SAON.
Acceptance Date31/01/2020
All Author(s) ListLizhen Zheng, Jiali Wang, Jiankun Xu, Xiaotian Zhang, BaoYi Liu, Le Huang, Ri Zhang, Haiyue Zu, Xuan He, Jie Mi, Qianqian Pang, Xinluan Wang, Yechun Ruan, Dewei Zhao, LIng Qin
Journal nameBiomaterials
Year2020
Month4
Volume Number238
PublisherElsevier
Article number119828
ISSN0142-9612
eISSN1878-5905
LanguagesEnglish-United States
KeywordsCorticosteroids, Osteonecrosis, Magnesium, Vitamin C, Preclinical studies
