Alendronate prevents glucocorticoid-induced osteonecrosis of the femoral head in rats

作者:Yin, Junhui; Weng, Shiyang; Chen, Yixuan; Zhang, Wen; Gao, Youshui*
来源:International Journal of Clinical and Experimental Medicine, 2017, 10(7): 10133-10142.

摘要

Objective: Osteonecrosis of the femoral head (ONFH) frequently results in collapse and subsequent degenerative joint disease of the hip. Bisphosphonates (BPs) therapy has been reported to retard osteoporosis; however, the effect of BPs on the prevention of glucocorticoid-induced ONFH remains controversial. Methods: In the current study, we investigated the state of MC3T3-E1 in vitro, in the presence of dexamethasone (DEX) with or without alendronate (ALN) treatment and detected osteogenesis-associated proteins, namely osteopontin (OPN) and osteocalcin (OCN). In in vivo studies, we investigated the preventive effect of ALN on methylprednisolone (MP)-induced ONFH in rats. We employed micro-CT scanning, angiography, and histologic and immunohistochemical analysis to demonstrate ALN's effect on the subchondral trabeculae of the femoral head. Results: In in vitro study, we observed that high-dose DEX clearly inhibited osteogenic differentiation of MC3T3-E1. OPN and OCN expression levels in MC3T3E1 were downregulated by DEX; however, the suppressive effect could be reserved when ALN was supplemented. The mineralization of MC3T3-E1 was improved significantly in the DEX+ALN group compared to that of DEX solely. In in vivo study, the parameters of micro-structure of trabecular bone were greatly ameliorated by ALN. Moreover, angiography of the femoral head revealed a protective role of ALN on osseous circulation. Combined effects of ALN contributed to decreased incidence of MP-induced ONFH in rats. Conclusion: ALN counteracts the suppressive effect of DEX on MC3T3-E1 cells, which benefits the trabecular bone and microcirculation of the femoral head in rats and can prevent glucocorticoid-induced ONFH.