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Biological Effects of Anti-RANKL Antibody and Zoledronic Acid on Growth in Growing Mice

Research Project

Project/Area Number 19K21416
Project/Area Number (Other) 18H06332 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 0907:Oral science and related fields
Research InstitutionShowa University

Principal Investigator

Isawa Motoki  昭和大学, 歯学部, 助教 (20827373)

Project Period (FY) 2018-08-24 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords骨吸収抑制薬 / 抗RANKL抗体 / ビスホスホネート / 破骨細胞 / 成長 / デノスマブ / ゾレドロネート
Outline of Research at the Start

骨吸収抑制薬は骨密度を上昇させる作用をもつ。近年、この薬剤は小児の骨系統疾患である骨形成不全症やステロイド性骨粗鬆症の治療にも使用され始めている。しかし成長過程の小児に対する骨吸収抑制薬の影響について、詳細は不明である。本研究では、破骨細胞分化を阻害する抗RANKL 抗体と破骨細胞の骨吸収機能を阻害するビスホスホネートを用いて、骨吸収抑制薬がマウスの成長(身長・体重)や硬組織(骨・歯)に及ぼす影響を解析することを目的とする。成長における疾患発症時期が異なるため、治療時期特異的なモデルマウスを作成し、治療開始から成長後の影響を解明することにより患者のQOL を向上する一助となると期待できる。

Outline of Final Research Achievements

The anti-bone resorptive drugs denosumab, an anti-human-RANKL antibody, and zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, have recently been applied for treatment of pediatric patients with bone diseases, though details regarding their effects in growing children have yet to be fully elucidated. In the present study, we administered these anti-resorptive drugs to mice from the age of 1 week and continued once-weekly injections for a total of 7 times. Mice that received the antiRANKL antibody displayed normal growth and tooth eruption, though osteopetrotic bone volume gain in long and alveolar bones was noted, while there were nearly no osteoclasts and a normal of number osteoblasts observed. In contrast, ZOL significantly delayed body growth, tooth root formation, and tooth eruption, with increased osteoclast and decreased osteoblast numbers. These findings suggest regulation of tooth eruption via osteoblast differentiation by some types of anti-resorptive drugs.

Academic Significance and Societal Importance of the Research Achievements

骨吸収抑制薬は小児の骨関連疾患治療にも用いられているが、それが成長にいかなる影響を及ぼすかは不明であった。本研究によって、抗RANKL抗体製剤およびビスホスホネート製剤を用いて、若齢マウスの成長、骨および歯に及ぼす影響を解明することを目的とした。抗RANKL抗体はゾレドロネートよりも、成長や歯には変化が認められなかったため、小児への安全性が高いと推察される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Annual Research Report
  • Research Products

    (3 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Biological Effects of Anti-RANKL Antibody and Zoledronic Acid on Growth and Tooth Eruption in Growing Mice2019

    • Author(s)
      Isawa M, Karakawa, Sakai N, Nishina S, Kuritani M, Chatani M, Negishi-Koga T, Sato M, Inoue M, Shimada Y, Takami M
    • Journal Title

      Sci Rep

      Volume: 9(1) Issue: 1 Pages: 19895-19895

    • DOI

      10.1038/s41598-019-56151-1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 骨形成不全症のため歯科治療困難であった1例2018

    • Author(s)
      井澤基樹
    • Organizer
      日本小児歯科学会中部地方会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 下顎右側乳犬歯・第1乳臼歯部に発生した 歯牙腫の1例2018

    • Author(s)
      井澤基樹
    • Organizer
      日本小児口腔外科学会
    • Related Report
      2018 Annual Research Report

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Published: 2018-08-27   Modified: 2024-03-26  

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