Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model

PLoS One. 2015 Oct 6;10(10):e0139793. doi: 10.1371/journal.pone.0139793. eCollection 2015.

Abstract

We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 μg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthroplasty, Replacement / adverse effects*
  • Bone Density / drug effects
  • Disease Models, Animal
  • Femur / drug effects
  • Femur / surgery
  • Male
  • Osteogenesis / drug effects
  • Osteolysis / etiology
  • Osteolysis / prevention & control*
  • Parathyroid Hormone / administration & dosage
  • Parathyroid Hormone / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Parathyroid Hormone

Grants and funding

This work is supported by the National Natural Science Foundation of China (81101377, 81171687, 81371954, 81201414), the Zhejiang Provincial Natural Science Foundation of China (Y2100161, Y2090283) and the Scientific Research Fund of Zhejiang Provincial Education Department (Y201018936), and the Fund of Health Department of Zhejiang Province (2012RCA032). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.