Physiology and pharmacology of nonbisphosphonate drugs implicated in osteonecrosis of the jaw

J Can Dent Assoc. 2012:78:c85.


Patients undergoing cancer chemotherapy are living longer and with better quality of life, and they require dental care both during and after their treatments. Bisphosphonates have been associated with drug-related osteonecrosis of the jaw (ONJ) since the discoveries of Marx in 2003 and Ruggiero and Woo in 2008. Recent literature has indicated a similar association with nonbisphosphonate drugs used in cancer therapy. Denosumab, an osteoclast inhibitor with applications in orthopedics and oncology, causes ONJ at a rate comparable to that for intravenously administered bisphosphonates. Case reports and drug agency records have indicated a correlation between ONJ and the neoangiogenesis inhibitors bevacizumab and sunitinib, which are used to treat many common cancers. The pharmacologic mechanisms of these 3 drugs appear distinct, yet a common effect on bone metabolism may occur in susceptible hosts. This review explores the mechanisms of these drugs that could lead to ONJ, according to current scientific understanding. The American Academy of Oral and Maxillofacial Surgeons has provided detailed recommendations for the management of bisphosphonate-related ONJ, which we suggest should also be applied in the management of patients with exposure to denosumab, bevacizumab and sunitinib.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / pharmacology
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Bevacizumab
  • Bone Density Conservation Agents / adverse effects*
  • Bone Density Conservation Agents / pharmacology
  • Denosumab
  • Humans
  • Indoles / adverse effects
  • Indoles / pharmacology
  • Jaw Diseases / chemically induced*
  • Osteonecrosis / chemically induced*
  • Pyrroles / adverse effects
  • Pyrroles / pharmacology
  • RANK Ligand / antagonists & inhibitors
  • Sunitinib


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Bone Density Conservation Agents
  • Indoles
  • Pyrroles
  • RANK Ligand
  • Bevacizumab
  • Denosumab
  • Sunitinib