Strontium ranelate reduces the progression of titanium particle-induced osteolysis by increasing the ratio of osteoprotegerin to receptor activator of nuclear factor-κB ligand in vivo

Geng,Tianxiang; Sun,Shouxuan; Chen,Xi; Wang,Bolun; Guo,Haohui; Zhang,Shuai; Jin,Qunhua

doi:10.3892/mmr.2017.8292

Strontium ranelate reduces the progression of titanium particle-induced osteolysis by increasing the ratio of osteoprotegerin to receptor activator of nuclear factor-κB ligand in vivo

Authors:
- Tianxiang Geng
- Shouxuan Sun
- Xi Chen
- Bolun Wang
- Haohui Guo
- Shuai Zhang
- Qunhua Jin
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Affiliations: Department of Orthopedic Surgery, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Orthopedic Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
Published online on: December 18, 2017 https://doi.org/10.3892/mmr.2017.8292
Pages: 3829-3836

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Abstract

The present study aimed to investigate the effects of strontium ranelate (SR), an anti‑osteoporotic drug, on osteolysis in an experimental mouse model of aseptic loosening. A total of 45 female C57BL/6J mice each received implantation of one titanium alloy pin into the tibia, followed by intraarticular injection of titanium particles. One week following surgery, mice were randomly divided into three groups: Control group (no additional treatment), SR625 group (treated with SR at a dose of 625 mg/kg/day), and SR1800 group (treated with SR at a dose of 1,800 mg/kg/day). SR was administered via oral gavage once every day for 12 weeks. Micro‑computed tomography scanning and hematoxylin/eosin staining were used to assess osteolysis around the prosthesis. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction analysis were used to measure the expression of receptor activator of nuclear factor‑κB ligand (RANKL) and osteoprotegerin (OPG). Compared with the control, the SR625 and SR1800 groups exhibited a significantly increased pulling force of the titanium alloy pin. Bone volume and the bone surface/volume ratio in the periprosthetic tissue were significantly increased in the SR‑treated groups. Significant differences were observed between the SR1800 group and control group with respect to trabecular thickness and trabecular number. Mechanistically, SR downregulated the expression of RANKL and upregulated the expression of OPG in the periprosthetic tissue. In addition, SR was observed to inhibit wear particle‑associated osteolysis in a dose‑dependent manner. In conclusion, the present data illustrated that SR inhibited titanium particle‑induced osteolysis in vivo.

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