title: Short-term perioperative teriparatide therapy for the prevention of medication-related osteonecrosis of the jaw: A randomized, controlled preclinical study in rats.
abstract: OBJECTIVE
  Dentoalveolar procedures in patients receiving bisphosphonates and other antiresorptive agents are associated with an increased risk of medication-related osteonecrosis of the jaw (MRONJ). The aim of present study was to evaluate the effects of perioperative teriparatide (TPD) therapy in prevention of MRONJ.
  
  
  METHODS
  Two protocols of TPD therapy were studied. For protocol A, 25 TPD-treated (AT) and 25 control (AC) rats received 5 weekly injection of 0.06 mg/kg zoledronate. At the end of week 5, extraction of bilateral mandibular first molars was performed for all rats, and 4-week TPD (20 μg/kg/day) and saline therapy was started for AT and AC rats, respectively. For protocol B, 25 TPD-treated (BT) and 25 control (BC) rats received 5 weekly injection of 0.06 mg/kg zoledronate. One week later, 4-week TPD and saline therapy was started for BT and BC rats, respectively. Both groups underwent tooth extraction at the end of week 7 of the experiment. All rats were sacrificed 8 weeks after tooth extraction and assessed clinically for bone exposure/fistula, and histologically for density of osteocytes in newly formed bone and empty osteocyte lacunae in alveolar bone.
  
  
  RESULTS
  Incidence of bone exposure/fistula and mean numbers of osteocytes and empty lacunae per 25 mm2(at 400× magnification) were 20%, 15.36, and 2.63 in AT group; 78%, 5.78, and 6.81 in AC group; 14%, 16.94, and 2.08 in BT group; and 78%, 7.54, and 5.95 in BC group; respectively. The differences between AT and AC and between BT and BC were statistically significant (P < 0.001). However, no statistically significant difference between AT and BT and between AC and BC was found.
  
  
  CONCLUSIONS
  Four weeks of TPD therapy, beginning at the same day or 2 weeks before tooth extraction, had a potential role in prevention of ONJ.
authors.affiliation: Department of Oral and Maxillofacial Surgery (Head: Prof. Dr. M. Zandi), Hamadan University of Medical Sciences, Hamadan, Iran; Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Zandi
authors.affiliation: Department of Pathology, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Dehghan
authors.affiliation: Department of Oral and Maxillofacial Surgery (Head: Prof. Dr. M. Zandi), Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address: mohamadimofrad.amir@yahoo.com.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Mohammadi-Mofrad
authors.affiliation: Department of Biostatistics, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Payam
authors.initials: P
authors.lastname: Amini
authors.affiliation: Faculty of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Farshid
authors.initials: F
authors.lastname: Vahdatinia
mesh_terms: D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000517:prevention & control*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000009:adverse effects; D007093:Imidazoles / Q000009:adverse effects; D008297:Male; D059035:Perioperative Period; D051381:Rats; D017208:Rats, Wistar; D019379:Teriparatide / Q000627:therapeutic use*; D014081:Tooth Extraction / Q000009:adverse effects; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D019379:Teriparatide; D000077211:Zoledronic Acid
keywords: Bisphosphonate; Jaw; Osteonecrosis; Osteoporosis; Prevention; Teriparatide