title: Compromised osseous healing of dental extraction sites in zoledronic acid-treated dogs.
abstract: The goal of this study was to document how treatment with high doses of zoledronic acid affects dental extraction healing. Our results, showing significantly compromised osseous healing within the socket as well as presence of exposed bone and development of a sequestrum in one animal, provide a building block toward understanding osteonecrosis of the jaw.
  
  
  OBJECTIVE
  The goal of this study was to document how treatment with a bisphosphonate affects the bone tissue following dental extraction.
  
  
  METHODS
  Skeletally mature female beagle dogs were either untreated controls (CON) or treated with intravenous zoledronic acid (ZOL). Following the extraction of the fourth premolars, healing was allowed for 4 or 8 weeks. Properties of the extraction site were assessed using microcomputed tomography (micro-CT) and dynamic histomorphometry.
  
  
  RESULTS
  The initial infilling of the extraction socket with bone was not affected by ZOL, but subsequent removal of this bone was significantly suppressed compared to CON. After 8 weeks of healing, the alveolar cortical bone adjacent to the extraction socket had a remodeling rate of ∼50% per year in CON animals while ZOL-treated animals had a rate of <1% per year. One ZOL-treated animal developed exposed bone post-extraction which eventually led to the formation of a sequestrum. Assessment of the sequestrum with micro-CT and histology showed that it had features consistent with those reported in humans with osteonecrosis of the jaw.
  
  
  CONCLUSIONS
  These results, showing significantly compromised post-extraction osseous healing as well as presence of exposed bone and development of a sequestrum in one ZOL animal, provide a building block toward understanding the pathophysiology of osteonecrosis of the jaw.
authors.affiliation: Department of Anatomy and Cell Biology, 635 Barnhill Drive, MS-5035, Indianapolis, IN 46202, USA. matallen@iupui.edu
authors.forename: M R
authors.initials: MR
authors.lastname: Allen
authors.forename: D J
authors.initials: DJ
authors.lastname: Kubek
authors.forename: D B
authors.initials: DB
authors.lastname: Burr
authors.forename: S L
authors.initials: SL
authors.lastname: Ruggiero
authors.forename: T-M G
authors.initials: TM
authors.lastname: Chu
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D004164:Diphosphonates / Q000009:adverse effects*; D004285:Dogs; D005260:Female; D007093:Imidazoles / Q000009:adverse effects*; D007571:Jaw Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging; D010020:Osteonecrosis / Q000139:chemically induced* / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed; D014081:Tooth Extraction; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
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