title: Early effects of parathyroid hormone on bisphosphonate/steroid-associated compromised osseous wound healing.
abstract: CONCLUSIONS
  Administration of intermittent parathyroid hormone (PTH) promoted healing of tibial osseous defects and tooth extraction wounds and prevented the development of necrotic lesions in rats on a combined bisphosphonate and steroid regimen.
  
  
  BACKGROUND
  Osteonecrosis of the jaw (ONJ) has emerged in association with antiresorptive therapies. The pathophysiology of ONJ is unknown and no established cure currently exists. Our objective was to determine the effect of intermittent PTH administration on early osseous healing in the jaw and long bones of rats receiving bisphosphonate and steroid treatment.
  
  
  METHODS
  Ovariectomized rats received the combination therapy of alendronate and dexamethasone (ALN/DEX) for 12 weeks. Osseous wounds were created in the jaw and tibia. PTH was administered intermittently and healing at 2 weeks post-op was compared between the jaw and tibia by microcomputed tomography and histomorphometric analyses.
  
  
  RESULTS
  ALN/DEX treatment was associated with necrotic open wounds in the jaw but had no negative effects on healing and promoted bone fill in tibial defects. PTH therapy prevented the development of necrotic lesions in the jaw and promoted healing of the tibial defects. PTH therapy was associated with the promotion of osteocyte survival in osseous wounds both in the jaw and tibia.
  
  
  CONCLUSIONS
  Wound healing was impaired in the jaw in rats on a combined bisphosphonate and steroid regimen, and PTH therapy rescued necrotic lesions. These findings suggest that PTH therapy could be utilized to prevent ONJ from occurring in patients on combination antiresorptive and steroid therapy.
authors.affiliation: Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, 1011 North University Ave., Ann Arbor, MI, 48109, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kuroshima
authors.forename: P
authors.initials: P
authors.lastname: Entezami
authors.forename: L K
authors.initials: LK
authors.lastname: McCauley
authors.forename: J
authors.initials: J
authors.lastname: Yamashita
mesh_terms: D019386:Alendronate / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology / Q000517:prevention & control*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use / Q000633:toxicity; D001861:Bone Regeneration / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000627:therapeutic use / Q000633:toxicity; D004334:Drug Administration Schedule; D004341:Drug Evaluation / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use / Q000633:toxicity; D010011:Osteocytes / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy / Q000503:physiopathology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000293:injuries / Q000502:physiology; D014081:Tooth Extraction; D020390:Tooth Socket / Q000187:drug effects / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; D010281:Parathyroid Hormone; D003907:Dexamethasone; D019386:Alendronate