Therapeutic effect of fluvastatin on medication-related osteonecrosis of the jaw

J Periodontol. 2022 Jun;93(6):837-846. doi: 10.1002/JPER.21-0294. Epub 2021 Oct 26.

Abstract

Background: Refractory jaw osteonecrosis that occurs in osteoporotic or cancer patients treated with bisphosphonates is called medication-related osteonecrosis of the jaw but its underlying mechanism is unclear. Statins, therapeutic agents for dyslipidemia, lower blood low-density lipoprotein cholesterol. Fluvastatin promotes the healing of tooth extraction sockets and reduces the risk of developing medication-related osteonecrosis of the jaw-like lesions. We used a rat model to investigate whether injecting fluvastatin at extraction sites promoted the healing of medication-related osteonecrosis of the jaw-like lesions.

Methods: Upper first molars of rats administered zoledronate and dexamethasone for 2 weeks were extracted. Two weeks after tooth extraction, rats with medication-related osteonecrosis of the jaw-like lesions (bone exposure) were included in this study. A single injection of fluvastatin was administered in the vicinity of the medication-related osteonecrosis of the jaw-like onset site in rats.

Results: The distance between the edges of the epithelia, the length of the necrotic bone exposed toward the oral cavity, the area of the necrotic bone, and the necrotic bone ratio were significantly smaller in the fluvastatin-administered group compared with the saline group. A single application of fluvastatin near the site of medication-related osteonecrosis of the jaw onset showed a tendency to close the epithelium, reduce necrotic bone, and form new bone, even when symptoms had already developed.

Conclusion: This study suggests that a single topical administration of fluvastatin may be a novel treatment for medication-related osteonecrosis of the jaw.

Keywords: bisphosphonate; bisphosphonate-associated osteonecrosis of the jaw; hydroxymethylglutaryl-CoA reductase inhibitors; jaw diseases; osteoporosis; stomatognathic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / drug therapy
  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / etiology
  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / pathology
  • Bone Density Conservation Agents* / therapeutic use
  • Diphosphonates
  • Fluvastatin / therapeutic use
  • Humans
  • Rats
  • Tooth Extraction
  • Tooth Socket

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Fluvastatin