In treating many debilitating diseases, we are often faced with a difficult decision: how do we reconcile the potential benefits of treatment with the risks of adverse effects? Bisphosphonates (BPs) are widely used to treat bone cancers such as multiple myeloma and Paget’s disease of bone. Its role in inhibiting osteoclast activity has been shown to dramatically increase bone density and slow the course of aggressive bone malignancies. However, osteoclasts are needed for normal bone turnover and its inhibition by BP may lead to other devastating disorders such as osteonecrosis of the jaw.
Recently, there has been an increase in the use of BPs in children with acquired bone diseases such as osteogenesis imperfecta. Because of this, an area that requires further investigation is the effect of bisphosphonates on the developing dentition. During the process of eruption, both the roots of deciduous teeth and the alveolar cortex coronal to the crowns of erupting permanent teeth must undergo resorption by osteoclasts. Because BPs inhibit bone resorption, the physiologic process guiding tooth eruption may be affected. In fact, several studies have demonstrated that in high, repeated doses, BPs may result in developmental abnormalities such as ankylosis.
Under the guidance of Dr. Christine Hong at the UCLA School of Dentistry, our research team sought to determine whether a single, low dose of BP would cause any developmental abnormalities in the developing dentition. We found that administering a one-time, pediatric dose of BP substantially delayed the tooth eruption process. The first molars were delayed by roughly 44 days, while the second molars were delayed by 19 days. Interestingly, the eruption of third molars were not affected. This is likely due to the BPs working in a developmental, stage-dependent manner, in which the osteoclasts are disproportionately inhibited in areas of active resorption. Because the third molar buds were still in the early stages of formation, the osteoclasts were not suppressed. Additionally, we found that the dentition was surrounded by normal periodontium, with no ankylosis detected.
This study demonstrates that caution is advised in the administration of BP in children, even in minimal doses, as it may delay the eruption of the developing dentition. In clinical application, the dosage and the time of administration can be modulated to offset some of the adverse consequences related to delayed dental eruption. Practitioners will soon have to consider not only the dosage, but also the timing of the drug delivery to ensure that natural biological processes go undisturbed. We expect that future studies will further investigate the susceptibility of the deficient mineralization of enamel to caries and oral disease.
~Tim Yu, Los Angeles ’18