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

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K21416
• Project/Area Number (Other): 18H06332 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0907:Oral science and related fields
• Research Institution: Showa University
• Principal Investigator: Isawa Motoki 昭和大学, 歯学部, 助教 (20827373)
• Project Period (FY): 2018-08-24 – 2021-03-31
• 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

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.

Free Research Field

小児歯科

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。