title: Differential modulation of zoledronate and etidronate in osseous healing of an extracted socket and tibia defect.
abstract: OBJECTIVE
  Osteonecrosis of the jaw has been increasing after dentoalveolar surgery in patients treated with an antiresorptive bisphosphonate (BP), especially strong zoledronate (ZA). The pathophysiology underlying why osteonecrosis occurs exclusively in the jaw bone remains unclear. This study investigated skeletal site-specific bone healing during the use of BPs to explore the preferential incidence of osteonecrosis of the jaw bone.
  
  
  METHODS
  Extraction of mandibular molar and creation of a tibia defect were performed in rats 2 weeks after weekly intravenous injections with the potent ZA and the weaker BP etidronate. Bone healing was evaluated radiographically and histologically 1 and 4 weeks after defect creation.
  
  
  RESULTS
  Bone healing at the extracted socket showed that resorption precedes bone formation, while it was the opposite at the tibia defect. ZA use potentially suppressed bone remodeling, which led to impaired healing at the extracted socket but full regeneration of the tibia defect. However, etidronate showed less suppression of bone remodeling and resulted in increased bone formation at the extracted socket and full regeneration of the tibia defect.
  
  
  CONCLUSIONS
  These results suggest that skeletal site-dependent differences in the bone healing process underlie BP-related preferential occurrence of osteonecrosis of the jaw bone.
authors.affiliation: Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Shin Saeng
authors.initials: SS
authors.lastname: Lim
authors.affiliation: Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Beomseok
authors.initials: B
authors.lastname: Lee
authors.affiliation: Dental Research Institute, Seoul National University, Seoul, Republic of Korea. Electronic address: ishwkim@snu.ac.kr.
authors.forename: In Sook
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Dental Research Institute, Seoul National University, Seoul, Republic of Korea; Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address: sjhwang@snu.ac.kr.
authors.forename: Soon Jung
authors.initials: SJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000473:pathology; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D012968:Etidronic Acid / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects* / Q000601:surgery; D014081:Tooth Extraction; D020390:Tooth Socket / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D012968:Etidronic Acid