Impact of Actinomyces naeslundii on bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats with periodontitis

J Craniomaxillofac Surg. 2015 Oct;43(8):1662-9. doi: 10.1016/j.jcms.2015.07.001. Epub 2015 Jul 14.


Bisphosphonates-related osteonecrosis of the jaws (BRONJ) is a severe complication of BPs therapy with unknown pathogenesis. This study aimed to evaluate the impact of Actinomyces naeslundii (A. naeslundii) on the progression of BRONJ in ovariectomized (OVX) rat model with periodontal diseases. Sixty rats were randomly assigned into four groups. All rats underwent bilateral ovariectomy. Six weeks after surgery, animals with periodontitis induced by ligature placement were administrated with normal saline (NS), NS &A. naeslundii inoculation, zolecdronic acid (ZA) and ZA &A. naeslundii inoculation for 12 weeks, respectively. Loads of total bacteria and A. naeslundii in the mouth were assessed by real time PCR. After sacrifice, the mandibles were harvested for micro-computed tomography (micro-CT) and histological examination. Real-time PCR demonstrated that A. naeslundii was not routinely found in the rats and ZA treatment did not promote its accumulation. Micro-CT examination disclosed that ligature placement induced significant alveolar bone loss, which was greatly attenuated by ZA treatment and aggravated by A. naeslundii. Histological assessment demonstrated that ZA treatment increased the risk of developing BRONJ-like disease but this condition was not worsen with the presence of A. naeslundii. Our study suggested that oral A. naeslundii inoculation aggravated periodontal disease but not BRONJ in our animal model.

Keywords: Actinomyces naeslundii; Bisphosphonates-related osteonecrosis of the jaws; ovariectomy; periodontal diseases; rat.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinomyces / physiology*
  • Actinomycosis / microbiology*
  • Alveolar Bone Loss / diagnostic imaging
  • Alveolar Bone Loss / microbiology
  • Animals
  • Bacterial Load
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / diagnostic imaging
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / microbiology*
  • Bone Density / drug effects
  • Bone Density Conservation Agents / administration & dosage
  • Cancellous Bone / diagnostic imaging
  • Diphosphonates / administration & dosage
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Imidazoles / administration & dosage
  • Mandibular Diseases / diagnostic imaging
  • Mandibular Diseases / microbiology
  • Ovariectomy / methods*
  • Periodontitis / diagnostic imaging
  • Periodontitis / microbiology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • X-Ray Microtomography / methods
  • Zoledronic Acid


  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid