Bisphosphonate and the Eruption of Developing Teeth: Its Effects and Mechanism

Bisphosphonates have similar chemical structures to endogenous inorganic pyrophosphate which inhibits mineral deposition in biological tissues. Even though their clinical applications have been attempted, their molecular mechanism and cellular effects on dental hard tissue development remain to be elucidated. The present study was performed to investigate their effects on the development of the tooth and their mode of action. Alendronate, a synthetic derivative of bisphosphonates was subcutaneously daily injected in postnatal day 1 Sprague Dawley rats for successive 10 days. Animals were sacrificed at 3, 12 and 40 days after the final administration and light microscopy, RT-PCR and TUNEL were used for the analyses. Alendronate inhibited the teeth development and retarded their eruption. In the alendronate group, the mandibular first and second molars were under-developed, compared with those in the control group at day 3. Ameloblasts in the mandibular 1st molar were discontinuous in several parts. The development of the mandibular 2nd molar was deterred by the woven bone growing into the dental papilla. The third molar tooth germ did not appear. The TUNEL positive cells were rarely seen in the normally developing hard tissue cells. But in the alendronate group, the positive cells appeared frequently in layers of ameloblasts. Furthermore, the expression of alkaline phosphatase mRNA was downregulated in the alendronate group, suggesting that osteoblastic activity was decreased. These results suggested that bisphosphonates may act on dental hard tissue cells, preventing tooth development and eruption.