The potential role of strontium ranelate in treating particle-induced osteolysis

Acta Biomater. 2015 Jul:20:147-154. doi: 10.1016/j.actbio.2015.03.034. Epub 2015 Apr 1.

Abstract

Ultra high molecular weight polyethylene (UHMWPE) wear-particle-induced osteolysis is one of the major issues affecting the long-term survival of total joint prostheses. Currently, there are no effective therapeutic options to prevent osteolysis from occurring. The aim of this study was to evaluate the role of strontium ranelate (SR) in reducing the risk of particle-induced osteolysis. Forty-eight C57BL/6J ultra-high molecular weight polyethylene (UHMWPE) particle-induced murine calvarial osteolysis models were used. The mice were randomized into four groups as: sham (Group 1), UHMWPE particles (Group 2), and SR with UHMWPE particles (Group 3 and Group 4). Groups 1 to 3 were sacrificed at two weeks and group 4 was sacrificed at the fourth week. The skulls were then analyzed with a high-resolution micro-CT. Histological evaluation was then conducted and osteoclast numbers were analyzed for comparison. Based on the micro-CT, percentage bone volume and trabecular thickness were found to be significantly higher in Group 4 than in Group 2 (p<0.001). Osteoclast numbers in SR treated groups (Group 3 and Group 4) were reduced when compared to groups that did not receive SR treatment (Group 2). These results indicated that SR treatment helps to increase bone volume percentage and trabecular thickness and also suppresses osteoclast proliferation. It is suggested that oral SR treatment could serve as an alternative therapy for preventing particle-induced osteolysis.

Keywords: Murine calvarial model; Particle-induced osteolysis; Strontium ranelate; Wear debris.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cell Count
  • Disease Models, Animal
  • Female
  • Mice, Inbred C57BL
  • Osteoclasts / drug effects
  • Osteoclasts / pathology
  • Osteolysis / chemically induced*
  • Osteolysis / drug therapy*
  • Osteolysis / pathology
  • Particle Size
  • Polyethylenes / adverse effects*
  • Skull / diagnostic imaging
  • Skull / drug effects
  • Skull / pathology
  • Thiophenes / pharmacology
  • Thiophenes / therapeutic use*
  • X-Ray Microtomography

Substances

  • Polyethylenes
  • Thiophenes
  • ultra-high molecular weight polyethylene
  • strontium ranelate