title: Teriparatide and the treatment of bisphosphonate-related osteonecrosis of the jaw: a rat model.
abstract: OBJECTIVE
  The objectives of this study were to establish a bisphosphonate-related osteonecrosis of the jaw (BRONJ) rat model and to analyse the effects of teriparatide (TP) on this model.
  
  
  METHODS
  Sprague-Dawley rats were divided into three groups: I-zoledronic acid (ZA, n = 10); II-ZA and teriparatide (ZA + TP, n = 10); III-control (n = 10). Osteonecrosis was induced by administering zoledronic acid to groups ZA and ZA + TP. A week after the injections, rats underwent extraction of the first left mandibular molar. Following a four week period, TP was administered to the ZA + TP group for 28 days. Upon killing, extraction sockets were examined clinically, radiologically and histopathologically.
  
  
  RESULTS
  Clinical examination revealed necrotic bone exposure in none of the animals. MicroCT (µCT) examination showed that bone mineral density of the newly formed bone in the extraction socket was lower in the ZA group than in the ZA + TP group (p < 0.05). Histopathological examination revealed that only the ZA and ZA + TP groups developed osteonecrosis, and the osteonecrotic bone area in the ZA group was larger than that in the ZA + TP group (p < 0.05). Tartrate-resistant acid phosphatase (TRAcP) enzyme histochemistry revealed that the number of detached and large osteoclasts were higher in the ZA group than in other groups, whereas the number of apoptotic osteoclasts in both ZA and ZA + TP groups were higher than in the control group (p < 0.05).
  
  
  CONCLUSIONS
  Our data indicate that bisphosphonate-related osteonecrosis of the jaw model used in the present study is an attractive model to investigate treatment modalities and that TP might be an effective treatment in BRONJ.
authors.affiliation: Department of Dentomaxillofacial Radiology, Faculty of Dentistry, Yeditepe University, Istanbul, Turkey.
authors.forename: N
authors.initials: N
authors.lastname: Ersan
authors.forename: L J
authors.initials: LJ
authors.lastname: van Ruijven
authors.forename: A L J J
authors.initials: AL
authors.lastname: Bronckers
authors.forename: V
authors.initials: V
authors.lastname: Olgaç
authors.forename: D
authors.initials: D
authors.lastname: Ilgüy
authors.forename: V
authors.initials: V
authors.lastname: Everts
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000473:pathology / Q000517:prevention & control*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007527:Isoenzymes / Q000032:analysis; D008963:Molar / Q000601:surgery; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase; D019379:Teriparatide / Q000008:administration & dosage / Q000627:therapeutic use*; D014081:Tooth Extraction; D020390:Tooth Socket / Q000187:drug effects / Q000473:pathology; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D007527:Isoenzymes; D019379:Teriparatide; D000077211:Zoledronic Acid; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Microcomputed tomography; bisphosphonate-associated osteonecrosis of the jaw; tartrate-resistant acid phosphatase; teriparatide; zoledronic acid