Effect of rifampicin on the risk of steroid-induced osteonecrosis of the femoral head.
OBJECTIVE
To investigate the effects and possible mechanism of rifampicin on steroid-induced osteonecrosis of the femoral head (ONFH).


METHODS
Bone marrow stromal cells (BMSC) separated from male rats were cultured in vitro without any treatment (Group mA), exposed to dexamethasone (Group mB), treated with rifampicin (Group mC), and exposed to dexamethasone and rifampicin simultaneously (Group mD) respectively (n = 5 in each group). After 7 days, P-glycoprotein (P-gp) activity and adipogenesis of the BMSC were evaluated. In an in vivo experiment, 80 rats were randomly divided into 4 groups (n= 20 in each group). Group A received intragastric saline for 5 weeks. Group B received intragastric saline for one week, followed by subcutaneous methylprednisolone and saline for 4 weeks. Group C received intragastric rifampicin for 5 weeks. Group D received intragastric rifampicin for one week, followed by subcutaneous methylprednisolone and rifampicin for 4 weeks. At the end of the experiment, all rats underwent analysis of P-gp activity of BMSC, P-gp expression in the femoral heads, MRI and histomorphometry of the femoral heads.


RESULTS
In vitro, the P-gp activity of BMSC increased and lipid accumulation decreased significantly in Group mD, compared to Group mB. In vivo, P-gp activity and P-gp expression in Group D increased compared to Group B. The mean area of MRI abnormal signal, adipocytic variables and apoptotic cells in Group D decreased, mean percentage of the whole epiphysis made up by the epiphyseal ossification center and trabecular structure variables improved compared to those in Group B. The incidence of ONFH was lower in Group D (50%) than in Group B (80%).


CONCLUSIONS
Rifampicin may decrease the risk of steroid-induced ONFH by enhancing P-gp activity, thus preventing steroid-induced BMSC adipogenesis.
Zhongshan Hospital of Fudan University, Shanghai, China.
Ning
N
Han
Zuo-qin
ZQ
Yan
Chang-an
CA
Guo
Feng
F
Shen
Jun
J
Liu
Yu-xing
YX
Shi
Zhi-yong
ZY
Zhang
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005270:Femur Head / Q000378:metabolism / Q000473:pathology; D005271:Femur Head Necrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000633:toxicity; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008775:Methylprednisolone / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use*; D012306:Risk; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D003907:Dexamethasone; D012293:Rifampin; D008775:Methylprednisolone