Effect of continuous and intermittent sodium alendronate oral dosing on post-extraction alveoli healing in rats

Arch Oral Biol. 2021 Dec:132:105291. doi: 10.1016/j.archoralbio.2021.105291. Epub 2021 Oct 19.

Abstract

Objective: This study aimed to compare alveolar healing after tooth extraction in two experimental rat models using continuous or discontinuous dosing of sodium alendronate (ALN).

Design: Forty-eight male Wistar rats were divided into eight experimental groups (n = 6/group) and administered ALN (2.5, 5.0, or 7.5 mg/kg) by gavage, weekly, either intermittently or following a continuous regimen (2.5, 5.0, or 7.5 mg/kg) before tooth extraction. The positive control rats were administered zoledronic acid (ZA; 0.2 mg/kg, intravenous), whereas negative control rats received sterile saline (0.9% NaCl, gavage).

Results: Only the ZA-treated animals showed a larger radiolucent extraction site area compared to the saline group (p = 0.007). Small areas of bone tissue filling the alveoli were visualized in the 7.5 mg/kg continuous ALN group and compared with the saline group (p < 0.001). Increased amounts of empty osteocyte lacunae (p < 0.001) and osteoclasts with signs of apoptosis (p = 0.004) were observed in the continuous ALN groups (2.5, 5.0, and 7.5 mg/kg) compared with the saline group. Increased immunolabeling for TNF-α was observed in the 7.5 mg/kg discontinuous ALN group and all continuous ALN groups compared with the saline group (p < 0.001). The number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was higher in the two continuous ALN groups (5.0 and 7.5 mg/kg) than in the saline group (p < 0.001).

Conclusions: Continuous administration of ALN impaired post-extraction alveolar bone healing in rats; however, discontinuation of ALN administration before tooth extraction allowed for adequate post-dental extraction alveolar healing.

Keywords: Alendronate; Bisphosphonate-associated osteonecrosis; Bisphosphonates; Inflammation; Wound healing; Zoledronic acid.

MeSH terms

  • Alendronate* / pharmacology
  • Animals
  • Bone Density Conservation Agents*
  • Diphosphonates / pharmacology
  • Male
  • Rats
  • Rats, Wistar
  • Sodium
  • Tooth Extraction
  • Wound Healing

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Sodium
  • Alendronate