Effects of P-Glycoprotein on Steroid-Induced Osteonecrosis of the Femoral Head

Abstract

P-glycoprotein (P-gp) activity may play an important role in steroid-induced osteonecrosis of the femoral head (ONF); however, the precise mechanism of its pathogenesis remains unknown. Therefore, we investigated the effects of increased P-gp activity on steroid-induced ONF using a rat model. Rats (n = 60) were treated with either a pharmacological stimulant of P-gp, rifampicin (group A); a suppressant, verapamil (group B); or normal saline (group C) administered in conjunction with methylprednisolone, an inducer of ONF. P-gp activity in bone marrow cells and expression in the femoral head significantly increased in group A (P < 0.05) but decreased in group B (P < 0.05). Likewise, the serum osteocalcin level, trabecular thickness and number, osteoclast and osteoblast numbers, and mean percentage of the epiphyseal ossification center were significantly increased in group A (P < 0.01) but decreased in group B (P < 0.01). In contrast, however, adipocytic variables, trabecular separation, and apoptotic cells decreased in group A (P < 0.01) but increased in group B (P < 0.01). The ONF incidence in group A (50%) and group B (100%) was significantly different from that in the control group C (80%, P < 0.05). Taken together, our findings suggested that enhanced P-gp activity was able to decrease the risk of steroid-induced ONF, possibly by inhibiting adipogenesis and apoptosis in the femoral head.