title: Bisphosphonate uptake in areas of tooth extraction or periapical disease.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Dental Student, University of Southern California, Herman Ostrow School of Dentistry, Los Angeles, CA.
authors.forename: Simon
authors.initials: S
authors.lastname: Cheong
authors.affiliation: Research Associate, Department of Chemistry, University of Southern California, Los Angeles, CA.
authors.forename: Shuting
authors.initials: S
authors.lastname: Sun
authors.affiliation: Dental Student, University of Michigan School of Dentistry, Ann Arbor, MI.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kang
authors.affiliation: Research Associate, Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA.
authors.forename: Olga
authors.initials: O
authors.lastname: Bezouglaia
authors.affiliation: Professor, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.affiliation: Professor, Department of Chemistry, University of Southern California, Los Angeles, CA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McKenna
authors.affiliation: Associate Professor, Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Aghaloo
authors.affiliation: Professor, Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles; Molecular Biology Institute, UCLA, Los Angeles, CA. Electronic address: taghaloo@dentistry.ucla.edu.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tetradis
mesh_terms: D000818:Animals; D004164:Diphosphonates / Q000009:adverse effects / Q000493:pharmacokinetics*; D019793:Fluorescein / Q000737:chemistry; D007093:Imidazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010483:Periapical Diseases / Q000378:metabolism*; D014081:Tooth Extraction; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D019793:Fluorescein