Mandibular necrosis in beagle dogs treated with bisphosphonates

David Burr, Matthew Allen

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Objectives - To test the effect of bisphosphonate (BP) treatment for up to 3 years on bone necrosis and osteocyte death in the mandible using a canine model. Materials and Methods - Dogs were treated with clinical doses of oral alendronate (ALN, 0.2 or 1.0 mg kg day) for 1 or 3 years. In a separate study, dogs were treated with i.v. zoledronate (ZOL) at 0.06 mg kg day for 6 months. En bloc staining was used to identify necrotic areas in the mandible; viable osteocytes were identified using lactate dehydrogenase. Results - None of the treatments was associated with exposed bone, but 17-25% of dogs treated for 1 year and 25-33% of dogs treated for 3 years with ALN showed pockets of dead bone. Necrotic areas had no viable osteocytes and were void of patent canaliculi. No control animals demonstrated necrotic bone. ZOL treatment for 6 months was associated with osteocyte death greater than that seen in animals treated with ALN or saline. It is not clear whether osteocyte death occurs because of direct toxic effects of BPs, or because suppressed remodelling fails to renew areas that naturally undergo cell death. Necrotic areas are also associated with bone other than the mandible, e.g. the rib, which normally undergo high rates of remodelling. Conclusions - Reduced remodelling rate using BPs may contribute to the pathogenesis of bone matrix necrosis. The development of an animal model that mimics important aspects of BP-related osteonecrosis of the jaw is important to understanding the pathogenesis of osteonecrosis.

Original languageEnglish
Pages (from-to)221-228
Number of pages8
JournalOrthodontics and Craniofacial Research
Volume12
Issue number3
DOIs
StatePublished - Aug 2009

Fingerprint

Osteocytes
Diphosphonates
zoledronic acid
Necrosis
Dogs
Osteonecrosis
Mandible
Bone and Bones
Bisphosphonate-Associated Osteonecrosis of the Jaw
Alendronate
Bone Matrix
Poisons
Ribs
L-Lactate Dehydrogenase
Canidae
Cell Death
Animal Models
Staining and Labeling

Keywords

  • Bisphosphonates
  • Mandible
  • Osteocytes
  • Osteonecrosis

ASJC Scopus subject areas

  • Orthodontics
  • Oral Surgery
  • Otorhinolaryngology
  • Surgery

Cite this

Mandibular necrosis in beagle dogs treated with bisphosphonates. / Burr, David; Allen, Matthew.

In: Orthodontics and Craniofacial Research, Vol. 12, No. 3, 08.2009, p. 221-228.

Research output: Contribution to journalArticle

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