title: Differential impairment of vascularization and angiogenesis in bisphosphonate-associated osteonecrosis of the jaw-related mucoperiosteal tissue.
abstract: OBJECTIVE
  Impaired vascularization in the etiopathology of aminobisphosphonate-associated osteonecrosis of the jaw (BONJ) is assumed, but evidence is lacking. This immunohistochemical study differentiated vascularization and angiogenesis in BONJ-adjacent mucoperiosteal tissue.
  
  
  METHODS
  Twenty BONJ (after zoledronate treatment) and 20 control mucoperiosteal tissue samples were processed with an autostaining-based alkaline phosphatase-antialkaline phosphatase staining kit. Vascularization was assessed by CD31 staining and angiogenesis-related neovessels by CD105 staining. The ratio of stained capillary area to total area of visible field was assessed. Statistics included Bonferroni adjustment.
  
  
  RESULTS
  CD31-stained microvessels were detected in each section and CD105-stained neovessels in each control. BONJ-adjacent mucoperiosteal tissue showed significantly fewer CD105-positive vessels in capillary areas (P < .05) than control samples. CD31-stained capillary area was not significantly reduced in mucoperiosteal BONJ-samples.
  
  
  CONCLUSIONS
  Angiogenesis is impaired in BONJ-related mucoperiosteal tissue, but vascularization remains unaffected. Vessel remodeling and neovessel formation is delayed in BONJ, resulting in impaired tissue regeneration of bisphosphonate-exposed oral mucosa.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Erlangen, Germany. falk.wehrhan@uk-erlangen.de
authors.forename: Falk
authors.initials: F
authors.lastname: Wehrhan
authors.forename: Phillip
authors.initials: P
authors.lastname: Stockmann
authors.forename: Emeka
authors.initials: E
authors.lastname: Nkenke
authors.forename: Karl A
authors.initials: KA
authors.lastname: Schlegel
authors.forename: Arndt
authors.initials: A
authors.lastname: Guentsch
authors.forename: Theresia
authors.initials: T
authors.lastname: Wehrhan
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Neukam
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis; D000539:Alveolar Process / Q000098:blood supply* / Q000187:drug effects; D015703:Antigens, CD / Q000032:analysis; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D004396:Coloring Agents; D003238:Connective Tissue / Q000098:blood supply / Q000187:drug effects; D004164:Diphosphonates / Q000009:adverse effects*; D000071063:Endoglin; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007093:Imidazoles / Q000009:adverse effects; D007150:Immunohistochemistry; D007571:Jaw Diseases / Q000139:chemically induced* / Q000473:pathology; D009061:Mouth Mucosa / Q000098:blood supply / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010020:Osteonecrosis / Q000139:chemically induced* / Q000473:pathology; D010521:Periosteum / Q000098:blood supply / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D000077211:Zoledronic Acid
chemical_list: D015703:Antigens, CD; D050071:Bone Density Conservation Agents; D004396:Coloring Agents; D004164:Diphosphonates; C064206:ENG protein, human; D000071063:Endoglin; D007093:Imidazoles; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase