Abstract:

The most common cause of implant failure in joint replacement is aseptic loosening due to particle-induced osteolysis. We investigated the effect of a single subcutaneous dose of zoledronic acid (ZA) 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. Osteoclast numbers were measured per high power field using TRAP-staining. The osteoid tissue area determined. Twenty-eight mice were used, seven per group. For statistical analysis one-way ANOVA and a Student’s t-test used. Bone resorption was 0.26mm2 ± 0.09mm2 in animals with particle implantation, 0.14mm2 ± 0.05 mm2 in animals with particle implantation and ZA treatment directly after surgery (p=0.0047), and 0.15 mm2 ± 0.05 mm2 in animals with particle implantation and ZA treatment on the fourth postoperative day (p=0.006). The osteoclast number was 8.7 ± 2.8 in animals without particle implantation and 20 ± 4 in animals with particle implantation, compared to 9.2 ± 2.5 in animals with particle implantation and ZA treatment directly after surgery (p=0.0001), and 10.3 ± 1.4 in animals with particle implantation and ZA treatment on the fourth postoperative day (p=0.0004). Net bone growth was significantly increased in animals with zoledronic acid treatment: 0.02 mm2 ± 0.03 mm2 in animals with particle implantation only (group 2), 0.25 mm2 ± 0.08 mm2 with particle implantation and zoledronic acid treatment directly after surgery (group 3; p=0.0018), and 0.21 mm2 ± 0.11 mm2 with particle implantation and zoledronic acid treatment on the fourth postoperative day (group 4; p=0.0042). In summary, using the murine calvarial osteolysis model, particle-induced bone resorption was markedly decreased by a single s.c. dose of ZA and Zoledronic acid is a potent anti-resorptive drug and may also stimulate bone apposition locally in the process of particulate-induced osteolysis.