The effects of icariin on wound healing of extraction sites with administration of zoledronic and dexamethasone: A rat model study

J Oral Pathol Med. 2018 Feb;47(2):198-205. doi: 10.1111/jop.12659. Epub 2017 Dec 3.


Objective: This study was intended to investigate the effects of icariin on the healing of tooth extraction sites under the systemic administration of zoledronic and dexamethasone.

Method: Thirty female rats underwent bilateral ovariectomy and were randomly assigned to 5 groups: SS group received a weekly injection of saline, while ZD, ZD + LICA, ZD + MICA, and ZD + HICA groups received zoledronic with dexamethasone for 8 weeks. One week later, mandibular first molars were extracted in all groups. Then, 30, 60, and 120 mg/kg icariin were intragastrically given to ZD + LICA, ZD + MICA, and ZD + HICA groups daily for 10 weeks, while saline was given to SS group and ZD group. Blood samples and mandibles were harvested for examinations after 10 weeks.

Results: Significantly smaller wound area was noted in SS and ZD + HICA groups, but the incidence of bisphosphonate-related osteonecrosis of the jaws (BRONJ) was not significantly different. Groups injected with zoledronic and dexamethasone had higher C-terminal cross-linked telopeptide of type 1 collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP 5b), and the number of osteoclast cells, with less vascular endothelial growth factor (VEGF) and osteocalcin (OCN). In contrast, CTX-1, TRACP 5b, and the number of osteoclast cells declined after using icariin and promoted VEGF and OCN were noted and the effects were in a dosage-dependent manner.

Conclusion: Concurrent use of zoledronic and dexamethasone inhibits the expression of VEGF, OCN, and wound healing and increases the number of osteoclast cells, serum CTX-1, and TRACP-5b after discontinuation for 10 weeks. Icariin weakens those effects in a dose-dependent manner but does not influence the onset of BRONJ.

Keywords: bisphosphonate-induced osteonecrosis of the jaws (BRONJ); icariin; prevention; wound healing.

MeSH terms

  • Alveolar Bone Loss / drug therapy
  • Alveolar Bone Loss / pathology
  • Alveolar Bone Loss / prevention & control
  • Animals
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / drug therapy
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / pathology
  • Collagen Type I / blood
  • Collagen Type I / metabolism
  • Dexamethasone / administration & dosage*
  • Dexamethasone / pharmacology*
  • Diphosphonates / administration & dosage*
  • Diphosphonates / pharmacology*
  • Female
  • Flavonoids / administration & dosage*
  • Flavonoids / pharmacology*
  • Imidazoles / administration & dosage*
  • Imidazoles / pharmacology*
  • Immunohistochemistry
  • Mandible / pathology
  • Mandible / surgery
  • Models, Animal
  • Molar / surgery
  • Osteocalcin / drug effects
  • Osteocalcin / metabolism
  • Osteoclasts / pathology
  • Rats
  • Tartrate-Resistant Acid Phosphatase / blood
  • Tartrate-Resistant Acid Phosphatase / metabolism
  • Tooth Extraction / adverse effects*
  • Vascular Endothelial Growth Factor A / drug effects
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects*
  • Zoledronic Acid


  • Collagen Type I
  • Diphosphonates
  • Flavonoids
  • Imidazoles
  • Vascular Endothelial Growth Factor A
  • Osteocalcin
  • Zoledronic Acid
  • Dexamethasone
  • Tartrate-Resistant Acid Phosphatase
  • icariin