Osteonecrosis development by tooth extraction in zoledronate treated mice is inhibited by active vitamin D analogues, anti-inflammatory agents or antibiotics

• Published in: Scientific reports 2022-01, Vol.12 (1), p.19-13, Article 19
• Main Authors: Soma, Tomoya, Iwasaki, Ryotaro, Sato, Yuiko, Kobayashi, Tami, Ito, Eri, Matsumoto, Tatsuaki, Kimura, Atsushi, Miyamoto, Kana, Matsumoto, Morio, Nakamura, Masaya, Morita, Mayu, Asoda, Seiji, Kawana, Hiromasa, Nakagawa, Taneaki, Miyamoto, Takeshi
• Format: Article
• Language: English
• Subjects: 692/308/1426; 692/699/317/821; Animals; Anti-Bacterial Agents - administration & dosage; Anti-inflammatory agents; Anti-Inflammatory Agents - administration & dosage; Antibiotics; Apoptosis; Apoptosis - drug effects; Bisphosphonate-Associated Osteonecrosis of the Jaw - blood; Bisphosphonate-Associated Osteonecrosis of the Jaw - etiology; Bisphosphonate-Associated Osteonecrosis of the Jaw - prevention & control; Bisphosphonates; Calcitriol; Cytokines; Cytokines - blood; Diphosphonates - adverse effects; Female; Humanities and Social Sciences; Humans; Inflammation; Jaw; Lipopolysaccharides; Mice; Mice, Inbred C57BL; multidisciplinary; Osteocytes - cytology; Osteocytes - drug effects; Osteonecrosis; Reagents; Science; Science (multidisciplinary); Teeth; Tooth Extraction - adverse effects; Tooth extractions; Vitamin D; Vitamin D - administration & dosage; Vitamin D - analogs & derivatives; Zoledronic acid; Zoledronic Acid - adverse effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-03966-6

Invasive dental treatment such as tooth extraction following treatment with strong anti-bone resorptive agents, including bisphosphonates and denosumab, reportedly promotes osteonecrosis of the jaw (ONJ) at the extraction site, but strategies to prevent ONJ remain unclear. Here we show that in mice, administration of either active vitamin D analogues, antibiotics or anti-inflammatory agents can prevent ONJ development induced by tooth extraction during treatment with the bisphosphonate zoledronate. Specifically, tooth extraction during treatment with zoledronate induced osteonecrosis in mice, but administration of either 1,25(OH) 2 D 3 or ED71, both active vitamin D analogues, significantly antagonized osteonecrosis development, even under continuous zoledronate treatment. 1,25(OH) 2 D 3 or ED71 administration also significantly inhibited osteocyte apoptosis induced by tooth extraction and bisphosphonate treatment. Administration of either active vitamin D analogue significantly inhibited elevation of serum inflammatory cytokine levels in mice in response to injection of lipopolysaccharide, an infection mimetic. Furthermore, administration of either anti-inflammatory or antibiotic reagents significantly blocked ONJ development following tooth extraction and zoledronate treatment. These findings suggest that administration of active vitamin D, anti-inflammatory agents or antibiotics could prevent ONJ development induced by tooth extraction in patients treated with zoledronate.