Calcified Tissue International

, Volume 86, Issue 6, pp 502–510

Administration of the Bisphosphonate Zoledronic Acid During Tooth Development Inhibits Tooth Eruption and Formation and Induces Dental Abnormalities in Rats


    • Department of Histology and Cell BiologyMatsumoto Dental University
  • Tadashi Ninomiya
    • Division of Hard Tissue Research, Institute for Oral ScienceMatsumoto Dental University
  • Akihiro Hosoya
    • Department of Histology and Cell BiologyMatsumoto Dental University
  • Hiroaki Nakamura
    • Department of Histology and Cell BiologyMatsumoto Dental University

DOI: 10.1007/s00223-010-9366-z

Cite this article as:
Hiraga, T., Ninomiya, T., Hosoya, A. et al. Calcif Tissue Int (2010) 86: 502. doi:10.1007/s00223-010-9366-z


Bisphosphonates (BPs) are potent inhibitors of osteoclastic bone resorption and widely used for the treatment of osteoporosis and metastatic bone diseases. Recently, BPs have also been shown to benefit children with primary and secondary osteoporosis, including osteogenesis imperfecta; however, their long-term safety has not been established yet. Clinical and experimental studies have demonstrated that BPs delay or inhibit tooth eruption. The failure of tooth eruption causes several dental abnormalities. In this study, to determine the effects of BPs on tooth formation, the BP zoledronic acid (ZOL) was injected into 7- and 14-day-old rats, and the development of the mandibular teeth was examined. X-ray analysis demonstrated that ZOL inhibited the eruption of both incisors and molars and their formation, especially in the molar roots. Histological examination showed that, in ZOL-treated animals, alveolar bone remained unresorbed around tooth crowns, which injured ameloblasts and enamel matrix, leading to defects of the enamel. Furthermore, haphazard proliferation of odontogenic epithelium and mesenchyme associated with primitive tooth structures, which resembles human odontomas, was induced at the basal end of incisors but not around the molars. Tooth ankylosis to alveolar bone was occasionally observed in molars. These results suggest that administration of BPs during tooth development has the potential to inhibit tooth eruption and formation and to induce several types of dental abnormalities, which may be attributed to the altered osteoclastic activities.


BisphosphonateZoledronic acidTooth eruptionDental abnormalityOdontoma

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© Springer Science+Business Media, LLC 2010