Objective To investigate the expression levels of osteoprotegerin (OPG) and receptor activator of NF-κB l igand (RANKL) mRNAs in bone tissues of the femoral head of the patients suffering glucocorticoid-induced osteonecrosisof the femoral head (ONFH), and to discuss the relationship between OPG/RANKL and ONFH. Methods Between March2007 and March 2008, bone tissues of the femoral head were collected as the experimental material from 35 patients suffering ONFH (experimental group) and from 21 patients suffering fracture of femoral neck (control group). The ratio of men to women in both groups was 4 ∶ 3, whose age was 41-70 years old (55.34 on average in the experimental group and 55.33 on average in the control group). The experimental group received over 3 weeks’ glucocorticoid treatment or more than 1 week’ s high-dose glucocorticoid treatment in recent 2 years, while the control group never received more than 1 week’s hormone treatment. In the two groups, the microstructure of bone tissues of the femoral head was detected by HE staining and the bone tissue total RNA was extracted, and then the expression levels of OPG mRNA and RANKL mRNA were examined by realtime quantitative PCR (RTQ-PCR) for each sample. Results HE staining: bone trabeculae and bone units were replaced by interrupted bone fragments, which were surrounded by many inflammatory granulation tissues and few osteocytes were seen in bone lacunae in the experimental group. In the control group, bone trabeculae and bone units were made by complete lamellar bones which surrounded blood vessels and osteocytes were seen in lacunae. RTQ-PCR testing: in the experimental group, OPG mRNA and RANKL mRNA were 1.35 ± 0.42 and 4.36 ± 1.35, respectively, while in the control group they were 1.78 ± 0.63 and 3.49 ± 1.02, respectively. The expression level of OPG mRNA in the experimental group was significantly lower than that in the control group, and the expression level of RANKL mRNA of the former was significantly higher than the latter. The OPG mRNA/ RANKL mRNA ratio in the xperiment group (0.34 ± 0.16) was significantly lower than that in the control group (0.54 ± 0.20), and there was significant difference (P lt; 0.05). Conclusion The glucocorticoid-induced ONFH may be related to the expression levels of OPG mRNA/RANKL mRNA in bone tissues.