The decrease of particle-induced osteolysis after a single dose of bisphosphonate.

Abstract

The most common cause of implant failure in joint replacement is aseptic loosening due to particle-induced osteolysis. Bisphosphonates have been shown to be effective against particle-induced osteolysis when administered daily. We investigated the effect of a single subcutaneous dose of a more potent third generation bisphosphonate on particle-induced osteolysis. We utilized the murine calvaria osteolysis model in C57BL/J6 mice. Bone resorption was measured as resorption within the midline suture using Giemsa staining. Twenty-eight mice were used, seven per group. Seven animals were treated with a single dose of zoledronic acid (ZA) directly after surgery and seven animals were treated four days postoperatively. For statistical analysis one-way ANOVA and a Student's t-test were used. Bone resorption was 0.26+/-0.09 mm(2) in animals with particle implantation, 0.14+/-0.05 mm(2) in animals with particle implantation and ZA treatment directly after surgery (p = 0.0047), and 0.15+/-0.05 mm(2) in animals with particle implantation and ZA treatment on the fourth postoperative day (p = 0.006). In conclusion, particle-induced bone resorption was markedly decreased by a single s.c. dose of a third generation bisphosphonate. This important new finding holds great promise, because single dose treatment of particle-induced osteolysis may reduce side effects compared to repeated application of bisphosphonates.