Int J Biol Sci 2016; 12(4):347-358. doi:10.7150/ijbs.13269 This issue

Research Paper

Vitamin K2 Prevents Glucocorticoid-induced Osteonecrosis of the Femoral Head in Rats

Yue-Lei Zhang, Jun-Hui Yin, Hao Ding, Wei Zhang, Chang-Qing Zhang, You-Shui Gao

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China

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Zhang YL, Yin JH, Ding H, Zhang W, Zhang CQ, Gao YS. Vitamin K2 Prevents Glucocorticoid-induced Osteonecrosis of the Femoral Head in Rats. Int J Biol Sci 2016; 12(4):347-358. doi:10.7150/ijbs.13269. Available from

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Graphic abstract

Glucocorticoid medication is one of the most common causes of atraumatic osteonecrosis of the femoral head (ONFH), and vitamin K2 (VK2) has been shown to play an important and beneficial role in bone metabolism. In this study, we hypothesized that VK2 could decrease the incidence of glucocorticoid-induced ONFH in a rat model. Using in vitro studies, we investigated how bone marrow-derived stem cells in the presence of methylprednisolone proliferate and differentiate, specifically examining osteogenic-related proteins, including Runx2, alkaline phosphatase and osteocalcin. Using in vivo studies, we established glucocorticoid-induced ONFH in rats and investigated the preventive effect of VK2. We employed micro-CT scanning, angiography of the femoral head, and histological and immunohistochemical analyses, which demonstrated that VK2 yielded beneficial effects for subchondral bone trabecula. In conclusion, VK2 is an effective antagonist for glucocorticoid on osteogenic progenitors. The underlying mechanisms include acceleration of BMSC propagation and promotion of bone formation-associated protein expression, which combine and contribute to the prevention of glucocorticoid-induced ONFH in rats.

Keywords: Vitamin K2, Osteonecrosis of the femoral head, Glucocorticoid, Osteocalcin, Runx2