title: Increased human defensine levels hint at an inflammatory etiology of bisphosphonate-associated osteonecrosis of the jaw: an immunohistological study.
abstract: BACKGROUND
  Human β-defensins (hBD) are antimicrobial peptides that are an integral part of bone innate immunity. Recently, it could be shown that expression of hBD-1, -2 and -3 were upregulated in cases of osteomyelitis of the jaws. In order to gain insight into the possible impairment of hBD metabolism in bisphosphonate-associated osteonecrosis of the jaws (BONJ), the present exploratory study was designed so as to determine the qualitative and quantitative expression of afore mentioned hBDs in BONJ and infected osteoradionecrosis (ORN), both of which represent inflammatory bone diseases.
  
  
  METHODS
  Bone samples were collected from patients with BONJ (n = 20) and ORN (n = 20). Non-infected healthy bone samples (n = 20) were included as controls. Immunohistological staining in an autostainer was carried out by the (Strept-ABC)-method against hBD-1,-2,-3. Specific positive vs. negative cell reaction of osteocytes (labeling index) near the border of bony resection was determined and counted for quantitative analysis. Number of vital osteocytes vs. empty osteocytes lacunae was compared between groups.
  
  
  RESULTS
  hBD-1,-2 and -3 could be detected in BONJ as well as ORN and healthy bone samples. Immunoreactivity against hBD-2 and -3 was significantly higher in BONJ than in ORN and healthy jaw bone samples. Number of empty osteocyte lacunae was significantly higher in ORN compared with BONJ (P = 0.001).
  
  
  CONCLUSIONS
  Under the condition of BONJ an increased expression of hBD-1,-2,-3 is detectable, similarly to the recently described upregulation of defensins in chronically infected jaw bones. It remains still unclear how these findings may relate to the pathoetiology of these diseases and whether this is contributing to the development of BONJ and ORN or simply an after effect of the disease.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Erlangen, Germany. Philipp.Stockmann@uk-erlangen.de
authors.forename: Philipp
authors.initials: P
authors.lastname: Stockmann
authors.forename: Falk
authors.initials: F
authors.lastname: Wehrhan
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwarz-Furlan
authors.forename: Florian
authors.initials: F
authors.lastname: Stelzle
authors.forename: Susanne
authors.initials: S
authors.lastname: Trabert
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Neukam
authors.forename: Emeka
authors.initials: E
authors.lastname: Nkenke
mesh_terms: D004164:Diphosphonates / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007571:Jaw Diseases / Q000139:chemically induced* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D010020:Osteonecrosis / Q000139:chemically induced* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010025:Osteoradionecrosis / Q000473:pathology; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: D004164:Diphosphonates; D023083:beta-Defensins