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

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...

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Bibliographic Details
Published in:Scientific reports 2019-12, Vol.9 (1), p.19895-11, Article 19895
Main Authors: Isawa, Motoki, Karakawa, Akiko, Sakai, Nobuhiro, Nishina, Saki, Kuritani, Miku, Chatani, Masahiro, Negishi-Koga, Takako, Sato, Masashi, Inoue, Mitsuko, Shimada, Yukie, Takami, Masamichi
Format: Article
Language:English
Subjects:
13/1
631/136/818
64/60
692/308/3187
Animals
Animals, Newborn
Antibodies - pharmacology
Biological effects
Bone diseases
Humanities and Social Sciences
Humans
Long bone
Mice
Monoclonal antibodies
multidisciplinary
Osteoblastogenesis
Osteoblasts
Osteoblasts - metabolism
Osteoblasts - pathology
Osteoclasts
Osteoclasts - metabolism
Osteoclasts - pathology
Osteopetrosis - drug therapy
Osteopetrosis - metabolism
RANK Ligand - antagonists & inhibitors
RANK Ligand - metabolism
Rats
Science
Science (multidisciplinary)
Teeth
Tooth Eruption - drug effects
TRANCE protein
Zoledronic acid
Zoledronic Acid - pharmacology
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Summary: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 anti-RANKL 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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-56151-1