Host inflammatory response and clinical parameters around implants in a rat model using systemic alendronate and zoledronate acid drug administrations

Sci Rep. 2022 Mar 15;12(1):4431. doi: 10.1038/s41598-022-08308-8.


Implant outcomes in comparison to a natural tooth in a rat model using systemic alendronate and zoledronate acid drug administrations were assessed. Fifty-four Sprague-Dawley rats were randomly allocated into two experimental groups (drug application of zoledronic acid; 0.04 mg/kg intravenously once a week and alendronic acid; 0.2 mg/kg subcutaneously five times a week) and one control group with 18 animals in each group. Drug delivery was conducted for a period of 4 months. After 4 weeks either a zirconia or a titanium implant was immediately inserted in the socket of the first molar of the upper jaw. In vivo investigations included host inflammatory parameters and the implant survival and success rates for up to 3 months. Material incompatibilities against titanium and zirconia nanoparticles were evaluated in vitro after stimulation of rat spleen cells. In vivo, IL-6 release around titanium implants demonstrated significantly higher values in the control group (p = 0.02) when compared to the zoledronic acid group. Around the natural tooth without drug administration, the control group showed higher IL-6 values compared with the alendronic acid group (p = 0.01). In vitro, only lipopolysaccharide and not the implant's nanoparticles stimulated significant IL-6 and TNFα production. In terms of the primary aim of in vivo and in vitro IL-6 and TNFα measurements, no implant material was superior to the other. No significant in vitro stimulation of rat spleen cells was detected with respect to titanium oxide and zirconium oxide nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate* / pharmacology
  • Animals
  • Dental Implants*
  • Inflammation*
  • Interleukin-6
  • Metal Nanoparticles
  • Osseointegration / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Titanium
  • Tumor Necrosis Factor-alpha
  • Zirconium
  • Zoledronic Acid* / pharmacology


  • Dental Implants
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Zoledronic Acid
  • Zirconium
  • Titanium
  • Alendronate