title: Histopathological Effects of Teriparatide in Medication-Related Osteonecrosis of the Jaw: An Animal Study.
abstract: OBJECTIVE
  Osteonecrosis of the jaw after tooth extraction is a major complication in patients using bisphosphonates (BPs) for bone lesions, such as for the treatment of osteoporosis. The purpose of this study was to investigate the histopathologic effects of teriparatide (a synthetic parathyroid hormone) on rats developing osteonecrosis with BP use.
  
  
  METHODS
  Rats (n = 80) that had been injected intraperitoneally with zoledronic acid for 7 weeks were used. Maxillary first molar extractions and bone defects were established in the same region in the eighth week. Teriparatide was administered subcutaneously to prevent osteonecrosis. Animals were sacrificed and histopathologic changes were examined. Osteoblasts, osteoclasts, inflammatory phase of bone healing, and osteonecrotic areas were evaluated.
  
  
  RESULTS
  The osteoclast numbers were larger in the experimental groups (teriparatide administered before and immediately after tooth extraction) than in the control group (administered zoledronic acid). The inflammatory phase of bone healing was more pronounced in the experimental group (teriparatide administered before tooth extraction) than in the control group. There were significant differences in osteoclast numbers and in the inflammatory phase of bone healing between the experimental and control groups (P < .05). The osteoblast numbers and osteonecrotic areas were similar in size between the experimental and control groups. There were no significant differences (P > .05).
  
  
  CONCLUSIONS
  BPs have negative effects on osteoclasts and the inflammatory phase of bone healing, whereas teriparatide was found to be effective in eliminating the negative effects of BPs. Teriparatide had positive effects in preventing osteonecrosis; therefore, teriparatide could be an effective agent for MRONJ.
authors.affiliation: Assistant Professor, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Adiyaman University, Adiyaman, Turkey. Electronic address: aydink.ruzgar@gmail.com.
authors.forename: Aydin
authors.initials: A
authors.lastname: Keskinruzgar
authors.affiliation: Assistant Professor, Department of Pathology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Bozdag
authors.affiliation: Associate Professor, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Gaziantep University, Gaziantep, Turkey.
authors.forename: Mutan Hamdi
authors.initials: MH
authors.lastname: Aras
authors.affiliation: Associate Professor, Department of Medical Physiology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.
authors.forename: Tuncer
authors.initials: T
authors.lastname: Demir
authors.affiliation: Assistant Professor, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Inonu University, Malatya, Turkey.
authors.forename: Umit
authors.initials: U
authors.lastname: Yolcu
authors.affiliation: Professor, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Gazi University, Ankara, Turkey.
authors.forename: Sedat
authors.initials: S
authors.lastname: Cetiner
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000473:pathology / Q000517:prevention & control*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002452:Cell Count; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D007249:Inflammation; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008963:Molar / Q000601:surgery; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019379:Teriparatide / Q000008:administration & dosage / Q000627:therapeutic use*; D014081:Tooth Extraction; D014945:Wound Healing / Q000187:drug effects; D000077211:Zoledronic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D019379:Teriparatide; D000077211:Zoledronic Acid; D003907:Dexamethasone