Histopathological Effects of Teriparatide in Medication-Related Osteonecrosis of the Jaw: An Animal Study

J Oral Maxillofac Surg. 2016 Jan;74(1):68-78. doi: 10.1016/j.joms.2015.07.005. Epub 2015 Jul 14.

Abstract

Purpose: Osteonecrosis of the jaw after tooth extraction is a major complication in patients using bisphosphonates (BPs) for bone lesions, such as for the treatment of osteoporosis. The purpose of this study was to investigate the histopathologic effects of teriparatide (a synthetic parathyroid hormone) on rats developing osteonecrosis with BP use.

Materials and methods: Rats (n = 80) that had been injected intraperitoneally with zoledronic acid for 7 weeks were used. Maxillary first molar extractions and bone defects were established in the same region in the eighth week. Teriparatide was administered subcutaneously to prevent osteonecrosis. Animals were sacrificed and histopathologic changes were examined. Osteoblasts, osteoclasts, inflammatory phase of bone healing, and osteonecrotic areas were evaluated.

Results: The osteoclast numbers were larger in the experimental groups (teriparatide administered before and immediately after tooth extraction) than in the control group (administered zoledronic acid). The inflammatory phase of bone healing was more pronounced in the experimental group (teriparatide administered before tooth extraction) than in the control group. There were significant differences in osteoclast numbers and in the inflammatory phase of bone healing between the experimental and control groups (P < .05). The osteoblast numbers and osteonecrotic areas were similar in size between the experimental and control groups. There were no significant differences (P > .05).

Conclusions: BPs have negative effects on osteoclasts and the inflammatory phase of bone healing, whereas teriparatide was found to be effective in eliminating the negative effects of BPs. Teriparatide had positive effects in preventing osteonecrosis; therefore, teriparatide could be an effective agent for MRONJ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / pathology
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / prevention & control*
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Cell Count
  • Dexamethasone / administration & dosage
  • Dexamethasone / therapeutic use
  • Diphosphonates / administration & dosage
  • Diphosphonates / adverse effects
  • Disease Models, Animal
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects
  • Inflammation
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Male
  • Molar / surgery
  • Osteoblasts / drug effects
  • Osteoclasts / drug effects
  • Rats
  • Rats, Wistar
  • Teriparatide / administration & dosage
  • Teriparatide / therapeutic use*
  • Tooth Extraction
  • Wound Healing / drug effects
  • Zoledronic Acid

Substances

  • Anti-Inflammatory Agents
  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Teriparatide
  • Zoledronic Acid
  • Dexamethasone