Bisphosphonate uptake in areas of tooth extraction or periapical disease

J Oral Maxillofac Surg. 2014 Dec;72(12):2461-8. doi: 10.1016/j.joms.2014.07.004. Epub 2014 Jul 12.


Purpose: Bisphosphonates (BPs) are widely used for the management of bone diseases such as osteoporosis and bone malignancy. However, osteonecrosis of the jaws (ONJ) is a serious complication of BP treatment. ONJ lesions mainly occur after extraction of teeth deemed unrestorable or around teeth with active periodontal or periapical disease. Because socket healing or dental disease shows higher bone turnover, the authors hypothesized that preferentially high BP accumulation would be observed in these areas.

Materials and methods: The authors tested the uptake of fluorescein-labeled zoledronic acid (5-FAM-ZOL) in sites of tooth extraction or experimental periapical disease in mice. Maxillary molars were extracted or the crowns of mandibular molars were drilled to induce pulp exposure. Animals were injected with 5-FAM-ZOL 200 μg/kg at various times after intervention and fluorescence was measured at healthy versus intervention sites. Fluorescein injections were used as controls. Data were analyzed by t test and mixed effects linear models were constructed because the animals had repeated measurements over time and at the 2 sites.

Results: A statistically significant (P≤.001 to .002) time-dependent uptake of 5-FAM-ZOL was detected in the areas of extraction socket and in the alveolar ridge around teeth with periapical disease compared with the healthy contralateral sites of the same animals. For the 2 conditions, the uptake reached a maximum 3 days after experimental intervention and decreased thereafter.

Conclusions: These data suggest that sites with increased bone turnover, such as extraction sites or areas of periapical inflammation, are exposed to higher BP doses than the remaining alveolar ridge and could explain, at least in part, the susceptibility of such areas to ONJ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diphosphonates / adverse effects
  • Diphosphonates / pharmacokinetics*
  • Fluorescein / chemistry
  • Imidazoles / adverse effects
  • Imidazoles / pharmacokinetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Periapical Diseases / metabolism*
  • Tooth Extraction*
  • Zoledronic Acid


  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid
  • Fluorescein