Histological Evaluation of Bisphosphonates on Tooth Eruption and Development

Objectives: Bisphosphonates (BPs) are extensively used to treat adults with a variety of bone diseases due to their effects on preventing bone resorption. However, recent clinical applications in children have been introduced to treat some acquired and genetic bone disorders, most notably Osteogenesis Imperfecta. The effect of BPs on the developing dentition is not well understood. In this study, we evaluated the effect of a single dose of zoledronic acid (ZA), a potent BP, on the formation and eruption of molars in neonate rats.
Methods: 40 rats were given a single injection of either ZA or saline control 1 week after birth, and the eruption of their molars was observed clinically. Groups of rats were sacrificed at regular intervals and both maxilla and mandibles underwent MicroCT analysis, histological analysis, and bone density analysis.
Results: Eruption of 1st molars and 2nd molars in ZA-treated rats was significantly delayed, erupting at or around day 62 and day 41 respectively. The controls had molars that erupted normally at day 18 and day 22 respectively. Interestingly, 3rd molar eruption was not delayed in ZA-treated rats, erupting along with the controls at day 35. Histological analysis confirmed that the 1st and 2nd molars had already begun the eruption process at the time of ZA administration, while the 3rd molar tooth bud had not yet completed formation. Additionally, there was evidence of thicker and denser compact bone in the BP rats, but no sign of ankylosis in the histological specimens.
Conclusions: BP administration may affect tooth eruption and development in children. This inhibiting effect of BP appears to be in a developmental stage-dependent manner, with a preference for sites that are undergoing active eruption due to the increased bone turnover. The timing and dose of BP must be considered for the normal development and eruption of dentition in children.