The Study Of The Role Of Strontium Ranelate In Co-Cr-Mo Particles-induced Osteolysis

Objective：To evaluate the influence of strontium ranelate on experimentalCo-Cr-Mo particle-induced osteolysis and to explore the theoretical foundationtheoretical foundation for treating Aseptic loosening.Method：Co-Cr-Mo particles were implanted onto the calvaria of particle groupB, lower dose treatment group C, higher dose treatment group D. The other13micewere randomly selected as normal control group A. group A：saline; group B:Co-Cr-Mo particles＋saline; group C: Co-Cr-Mo particles＋saline＋low-dosestrontium ranelate; group D: Co-Cr-Mo particles＋saline＋high-dose strontiumranelate. After28days, three skulls per group were analyzed using histomorphometry.Five calvariae per group were prepareed for the assay of TNF-a and RANKLsecretion using quantitative ELISA. The expression of TNF-a, RANKL and OPGmRNA were evaluated using quantitative reverse transcription PCR.Results： As assessed by histomorphometry, Co-Cr-Mo particles inducedextensive bone resorption and an intense inflammatory reaction in group B, and groupC seemed less extensive than group B, but not at all in group D. Although Co-Cr-Moparticles could induce a significant increase of TNF-a and RANKL in group B,Strontium ranelate settled them down in group C and group D dose-dependently. OPGseemed not sensitive to Co-Cr-Mo particles or Strontium ranelate, but the ratio ofRANKL/OPG mRNA showed a parallel outcome with TNF-a and RANKL.Conclusions：Strontium ranelate in the osteolysis murine model ultimatelyattenuated osteolytic response to Co-Cr-Mo particles, suggesting a protective effect.This phenomenon was associated with a down-regulation of pro-resorptive cytokines–TNF-a and RANKL. It is hypothesized that excessive inflammatory response andosteolysis could be inhibited by Strontium ranelate, illustrated by the absence ofincrease of TNF-a and RANKL in higher dose treatment mice after Co-Cr-Moimplantation.