| Objective To establish an experimental rabbit model of steroid-induced avascular necrosis of the femoral head, to observe the preventive effect of alendronate sodium and zoledronic acid on steroid-induced avascular necrosis of the femoral head, and to compare the effect of the two drugs. Methods Ninety healthy 28-week adult New Zealand rabbits, with an average weight of 3.8±0.3kg, with no restriction of gender, were randomly divided into 3 groups: positive control group (Group A), alendronate sodium group (Group B), and zoledronic acid group (Group C). Each group had 30 rabbits. All the animals were treated with an intravenous injection of 10μg/kg lipopolysaccharide for one time. After 24 hours, all the animals were treated with muscle injection of 20 mg/kg methylprednisone for 3 times, with an interval of 24 hours. Rabbits in alendronate sodium group were administered with 150 μg/kg alendronate sodium via subcutaneous injection per day, lasting for 45 days. Rabbits in zoledronic acid group were treated with 100μg/kg zoledronic acid via ear intravenous injection for once per 4 weeks, total for 2 times. Six weeks later, the bilateral femoral heads of rabbits were collected and split into halves along the sagittal plane. One half was paraffin embedded, sliced, and stained with HE. Avascular necrosis of the femoral head was evaluated by calculating empty lacuna rate. The other half was cut into two equal parts. Total RNA of the femoral head bone tissue was extracted from one half. OPG and RANKL mRNA expression levels were detected using real-time quantitative polymerase chain reaction (RTQ-PCR), and the ratio of OPG/RANKL mRNA was calculated. Total protein of the femoral head bone tissue was extracted from the other half, and the expression levels of OPG and RANKL were detected using Western blotting. Then the ratio of OPG/RANKL was calculated. Results The mortality of rabbits in positive control group, alendronate sodium group, and zoledronic acid group was 16.67% (5/30), 13.33% (4/30), and 10% (3/30), respectively. The empty lacuna rate in these 3 groups was 26.33 1.17, 20.85 1.47, and 18.55 2.43, respectively. The avascular necrosis rate of the femoral head in the 3 groups was 76.0% (19/25), 30.77% (8/26), and 7.41% (2/27), respectively. The level of OPG mRNA expression in the 3 groups was 0.85 0.086, 1.22 0.085, and 1.62 0.097, respectively, while the level of RANKL mRNA expression was 3.23 0.78, 2.84 0.95, and 1.43 0.93, respectively. The level of OPG protein expression in the 3 groups was 0.48 0.09, 0.54 0.09, and 0.74 0.08, respectively, while the level of RANKL protein expression was 1.51 0.10, 1.23 0.08, and 0.63 0.08, respectively. The rate of avascular necrosis of the femoral head in Group B and C was lower than that in Group A, while the rate in Group C was lower than that in Group B, and the difference was significant (P<0.05). The levels of both OPG mRNA expression and protein expression in Group B were lower than those in Group C, while the levels of both RANKL mRNA expression and protein expression were higher than those in Group C, and the ration of OPG/RANKL in Group B was lower than that in Group C. The difference was significant (P<0.05). Conclusion Alendronate sodium and zoledronic acid can effectively prevent the occurrence of steroid-induced avascular necrosis of the femoral head in rabbits. The mechanism is related to the regulation of RANKL/RANK/OPG system in the bone tissue of the femoral head. Zoledronic acid is more effective than alendronate sodium. |