Objective:To explore the mechanism of alendronate on the formation of osteoclast from osteoclast precursors(OCPs) induced by wear debris,and provide more evidences for bisphosphonate on the treatment of aseptic loosening of prosthesis. Methods:OCPs were induced from hematopoietic stem cells in the presence of macrophage colony stimulating factor(M-CSF), and then OCPs were induced into osteoclast cells in the presence of M-CSF and receptor activator of NF-κB ligand(RANKL), and then polyethylene(103/ml) and different concentration alendronate(0.4 -滋g/ml,2.0 -滋g/ml,10.0 -滋g/ml,50.0 -滋g/ml) were added to the culture medium. After cultured for 4 days,the cells were stained with TRAP. Multinucleated( ≥ 3 nuclei) TRAP-positive cells were counted as osteoclasts, and the expression of TRAP mRNA were determined by RT-PCR. Results:The number of TRAP+ osteoclasts and the expression of TRAP mRNA from the polyethylene group were significantly higher than those in control group(P < 0.05), which in alendronate groups were all lower than those in the polyethylene group,and the number of TRAP+ osteoclasts and the expression of TRAP were decreased with the concentration increase of alendronate(P < 0.05). Conclusion:Bisphosphonate can inhibit the formation of osteoclast from osteoclast precursors induced by wear debris.