Tooth extraction in mice administered zoledronate increases inflammatory cytokine levels and promotes osteonecrosis of t
- PDF / 7,473,581 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 57 Downloads / 162 Views
ORIGINAL ARTICLE
Tooth extraction in mice administered zoledronate increases inflammatory cytokine levels and promotes osteonecrosis of the jaw Tomoya Soma1 · Ryotaro Iwasaki1 · Yuiko Sato2,3 · Tami Kobayashi2,4 · Satoshi Nakamura2 · Yosuke Kaneko2 · Eri Ito5 · Hiroyuki Okada6 · Hisato Watanabe6 · Kana Miyamoto2,8 · Morio Matsumoto2 · Masaya Nakamura2 · Seiji Asoda1 · Hiromasa Kawana1,7 · Taneaki Nakagawa1 · Takeshi Miyamoto2,3,4,8 Received: 6 May 2020 / Accepted: 26 October 2020 © The Japanese Society Bone and Mineral Research 2020
Abstract Introduction Osteonecrosis of the jaw (ONJ) occurring after invasive dental treatment often adversely affects patients’ activities of daily living. Long-term administration of strong anti-bone resorptive agents such as bisphosphonates prior to invasive dental treatment is considered an ONJ risk factor; however, pathological mechanisms underlying ONJ development remain unclear. Materials and Methods We developed an ONJ mouse model in which a tooth is extracted during treatment with the bisphosphonate zoledronate. Results We observed induction of apoptosis in osteocytes, resulting in formation of empty lacunae in jaw bones at sites of tooth extraction but not in other bones of the same mice. We also observed elevated levels of inflammatory cytokines such as TNFα, IL-6 and IL-1 in jaw bone at the extraction site relative to other sites in zoledronate-treated mice. We also report that treatment in vitro with either zoledronate or an extract from Porphyromonas gingivalis, an oral bacteria, promotes expression of inflammatory cytokines in osteoclast progenitor cells. We demonstrate that gene-targeting of either TNFα, IL-6 or IL-1 or treatment with etanercept, a TNFα inhibitor, or a neutralizing antibody against IL-6 can antagonize ONJ development caused by combined tooth extraction and zoledronate treatment. Conclusions Taken together, the cytokine storm induced by invasive dental treatment under bisphosphonate treatment promotes ONJ development due to elevated levels of inflammatory cytokine-producing cells. Our work identifies novel targets potentially useful to prevent ONJ. Keywords Osteoclast · Osteocyte · Bisphosphonate · Cytokine · Inflammation
Introduction In 2003, Marx first reported osteonecrosis in jaw bones of patients taking intravenous bisphosphonates following tooth extraction [1]. Such osteonecrosis of the jaw (ONJ) due to invasive dental treatment such as tooth extraction or placement of dental implants is rare, but when present is challenging to treat and disrupts normal activities of daily living in Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00774-020-01174-2) contains supplementary material, which is available to authorized users. * Takeshi Miyamoto [email protected]; [email protected]‑u.ac.jp Extended author information available on the last page of the article
patients [2, 3]. ONJ is more common in patients with poor oral hygiene, diabetes mellitus or steroid usage, and thus infectious
Data Loading...
