title: Preexisting Periapical Inflammatory Condition Exacerbates Tooth Extraction-induced Bisphosphonate-related Osteonecrosis of the Jaw Lesions in Mice.
abstract: BACKGROUND
  Surgical interventions such as tooth extraction increase the chances of developing osteonecrosis of the jaw in patients receiving bisphosphonates (BPs) for the treatment of bone-related diseases. Tooth extraction is often performed to eliminate preexisting pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related osteonecrosis of the jaw (BRONJ) development after tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction-induced BRONJ development in mice.
  
  
  METHODS
  Periapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BPs. The same tooth was extracted, and after an 3 additional weeks, the mice were harvested for histologic, histomorphometric, and histochemical staining analyses.
  
  
  RESULTS
  Pulp exposure induced periapical radiolucency as shown by increased inflammatory cells, tartrate-resistant acid phosphatase-positive osteoclasts, and bone resorption. When BPs were administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and tartrate-resistant acid phosphatase-positive osteoclasts. Although tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as shown by the presence of more bone necrosis.
  
  
  CONCLUSIONS
  Our study demonstrates that a preexisting pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development after tooth extraction. Our study further provides a clinical implication wherein periapical periodontitis should be controlled before performing tooth extraction in BP users in order to reduce the risk of developing BRONJ.
authors.affiliation: Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California.
authors.forename: Minju
authors.initials: M
authors.lastname: Song
authors.affiliation: Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alshaikh
authors.affiliation: Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California.
authors.forename: Terresa
authors.initials: T
authors.lastname: Kim
authors.affiliation: Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California.
authors.forename: Sol
authors.initials: S
authors.lastname: Kim
authors.affiliation: Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California.
authors.forename: Michelle
authors.initials: M
authors.lastname: Dang
authors.affiliation: Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California.
authors.forename: Shebli
authors.initials: S
authors.lastname: Mehrazarin
authors.affiliation: Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Ki-Hyuk
authors.initials: KH
authors.lastname: Shin
authors.affiliation: Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Mo
authors.initials: M
authors.lastname: Kang
authors.affiliation: Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California; David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: No-Hee
authors.initials: NH
authors.lastname: Park
authors.affiliation: Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California. Electronic address: rkim@dentistry.ucla.edu.
authors.forename: Reuben H
authors.initials: RH
authors.lastname: Kim
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000473:pathology*; D001862:Bone Resorption / Q000178:diet therapy / Q000209:etiology / Q000473:pathology; D004164:Diphosphonates / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000473:pathology; D008437:Maxilla / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008963:Molar / Q000187:drug effects / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D010483:Periapical Diseases / Q000150:complications / Q000473:pathology; D010485:Periapical Periodontitis / Q000473:pathology*; D019227:Tooth Apex / Q000187:drug effects / Q000473:pathology; D014081:Tooth Extraction / Q000009:adverse effects*
chemical_list: D004164:Diphosphonates
keywords: Bisphosphonate; bisphosphonate-related osteonecrosis of the jaw; inflammation; periapical periodontitis; tooth extraction