Objective To observe the effects of different doses of calcium-sensing receptor inhibitors on the osteolysis and the expression inflammatory factor induced by wear particles, so as to investigate its effect of preventing aseptic loosening of artificial joints. Methods Forty C57BL/6J male mice aged 8-10 weeks were divided into control group,particle group, low dose group and high dose group according to the random number table, with 10 mice in each group.Wear particle-induced mouse calvaria osteolysis model were established in the particle group, low-dose group and high-dose group, then the control group was treated with sham operation. From the second day after operation, mice in low-dose group and high-dose group were given 0.2 mg/kg and 2.0 mg/kg NPS2390 intraperitoneally every other day.The control group and particle group were replaced by the same amount of normal saline. After 14 days, the skull specimens were taken and the skull bone mineral density, bone volume fraction, bone porosity, skull bone area, the number of osteoclast and the expression of the inflammatory factor tumor necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) were compared between the groups. Results In particle group, the number of osteoclasts, the bone porosity and the expression of inflammatory factor TNF-α and IL-1β were higher than that in control group,however,the bone mineral density,the bone volume fraction,and the bone area of the skull in particle group were lower than those of control group,the differences were statistically significant (P＜0.05). In low dose group, the bone mineral density was higher than that in particle group, the number of osteoclast and the expression of inflammatory factor TNF-α and IL-1β in low dose group were lower than those in the particle group, the differences were statistically significant (P＜0.05). The bone mineral density, bone volume fraction and bone area of the high-dose group were higher than those of the granule group, while the bone porosity, the number of osteoclasts, the expression of inflammatory factors TNF-α and IL-1β were lower than those of the granule group, the differences were statistically significant(P＜0.05).The bone mineral density and bone volume fraction of the high dose group were higher than those of the low dose group, and the number of osteoclasts and the expression of inflammatory factors TNF-α and IL-1β were lower than those of the low dose group,and the differences were statistically significant (P＜0.05).Conclusion The calcium-sensing receptor inhibitor (NPS2390) can effectively inhibit osteolysis and the expression of inflammatory induced by wear particles, and provides new ideas for prevention aseptic loosening of artificial joints.