Effect of pentoxifylline and α-tocopherol on medication-related osteonecrosis of the jaw in rats: Before and after dental extraction

Arch Oral Biol. 2022 May:137:105397. doi: 10.1016/j.archoralbio.2022.105397. Epub 2022 Mar 11.

Abstract

Objective: Evaluate the effect of pentoxifylline and α-tocopherol administration in the prevention or treatment of medication-related jaw osteonecrosis (MRONJ).

Methodology: Sixty Wistar rats were divided into three prevention (C-prev, BP-prev and BP/PT-prev) and three treatment groups (C-treat, BP-treat and BP/PT-treat), n = 10. The animals in the BP-prev, BP/PT-prev, BP-treat and BP/PT-treat groups received zoledronic acid (0.1 mg/kg) for 12 weeks, while the animals in the C-prev and C-treat groups received saline solution. At week 6, all animals underwent tooth extraction. Between week 5 and week 12, the BP/PT-prev group was treated with pentoxifylline (50 mg/kg/day) and α-tocopherol (80 mg/kg/day), with euthanasia at the end of week 12. The BP/PT-treat group received the same drug protocol, but it was performed between week 12 and week 16, with euthanasia at the end of week 16. Afterwards, the presence of osteonecrosis was evaluated by clinical analysis, radiographic and histological.

Results: BP/PT-treat group showed a reduction in the histological incidence of osteonecrosis by 50%, decrease the percentage of empty osteocyte gaps and the necrotic area, decrease the presence of bone sequestration and increase the number of osteocytes and alveolar blood flow (p < 0.05). However, BP/PT-prev group showed only a reduction in the necrotic area percentage when compared to BP-prev (p < 0.05).

Conclusions: Pentoxifylline and α-tocopherol administration before tooth extraction was not effective in preventing MRONJ. However, this drug protocol was able to reduce MRONJ manifestation when administrate after discontinuation of bisphosphonate, thus it can be considered as a viable strategy for the treatment of this pathological condition.

Keywords: Bisphosphonates; Oral surgery; Osteonecrosis; Phosphodiesterase inhibitors; Vitamin E.

MeSH terms

  • Animals
  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / pathology
  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / prevention & control
  • Bone Density Conservation Agents* / pharmacology
  • Diphosphonates
  • Osteonecrosis* / drug therapy
  • Pentoxifylline* / pharmacology
  • Pentoxifylline* / therapeutic use
  • Rats
  • Rats, Wistar
  • Tooth Extraction / methods
  • alpha-Tocopherol / pharmacology
  • alpha-Tocopherol / therapeutic use

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • alpha-Tocopherol
  • Pentoxifylline