Denosumab and osteonecrosis of the jaws - the pharmacology, pathogenesis and a report of two cases

Aust Dent J. 2014 Dec;59(4):516-9. doi: 10.1111/adj.12217. Epub 2014 Sep 27.

Abstract

Denosumab (Amgen, Thousand Oaks, California, USA) is a new bone antiresorptive agent used in patients with osteoporosis or metastatic cancer to the bones. As with the bisphosphonates that are used as antiresorptive medications, denosumab has been associated with osteonecrosis of the jaws (ONJ). Over the past two years there has been an increase in the literature describing ONJ in patients receiving agents such as denosumab. Due to promising study results that demonstrate the effectiveness of denosumab in avoiding skeletal complications related to osteoporosis and metastatic bone disease, more patients will receive denosumab in the future. It is reported that this has the potential to become a comparable challenge to bisphosphonate related osteonecrosis of the jaws (BRONJ) for clinicians. This article describes the management of two patients that developed ONJ while receiving denosumab, reviews the incidence of ONJ associated with denosumab, and contrasts the pharmacokinetics of denosumab and the bisphosphonates. The importance of avoiding interventional dental treatment until denosumab has been withdrawn for six months cannot be overstated.

Keywords: Bisphosphonates; bisphosphonate related osteonecrosis of the jaws; denosumab; denosumab associated osteonecrosis of the jaws; necrosis of the jaws.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / diagnosis
  • Denosumab
  • Diphosphonates / pharmacokinetics
  • Female
  • Humans
  • Jaw Diseases / chemically induced*
  • Male
  • Middle Aged
  • Osteonecrosis / chemically induced*
  • RANK Ligand / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal, Humanized
  • Diphosphonates
  • RANK Ligand
  • Denosumab