Effect of antiresorptive drugs on bony turnover in the jaw: denosumab compared with bisphosphonates

Br J Oral Maxillofac Surg. 2014 Apr;52(4):308-13. doi: 10.1016/j.bjoms.2014.01.021. Epub 2014 Feb 26.

Abstract

Osteonecrosis of the jaw as a result of treatment with receptor activators of nuclear factor kappa-B ligand (RANKL) inhibitors (denosumab) is a new type of bony necrosis, the exact pathogenesis of which is unknown. Our aim was to find out whether the turnover of bone in the jaw is increased after denosumab has been given compared with other skeletal sites, and if that turnover might have a role in denosumab-related osteonecrosis of the jaw (DRONJ). Bone scintigraphic images of 45 female patients with breast cancer and bone metastases were analysed retrospectively, and divided into 3 groups: those given denosumab, those given a bisphosphonate, and a control group (n=15 in each). All patients had bone scintigraphy before treatment (T0) and during the course of treatment after 12 (T1) and 24 (T2) months. The data were analysed quantitatively using 6 preset bony regions of interest. There was similar turnover of bone in the mandible compared with other skeletal sites (such as the femur), while the maxilla showed significantly higher turnover. None of the bony regions investigated showed any significant changes after the bisphosphonate had been given. There was a tendency to increase bone turnover in those patients taking denosumab. The bone turnover of the jawbone is not overtly changed either by a bisphosphonate or denosumab, so it seems unlikely that oversuppression of bony turnover in the jawbones plays an important part either in the pathogenesis of DRONJ or in the bisphosphonate-related osteonecrosis of the jaw (BRONJ).

Keywords: BRONJ; Bisphosphonate; Bone scan; Bone scintigraphy; Bone turnover; Denosumab; ONJ; Osteonecrosis of the jaw; Pathogenesis; RANKL-inhibitor; Xgeva.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / etiology
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / metabolism
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / secondary
  • Bone Remodeling / drug effects*
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / drug therapy
  • Carcinoma / diagnostic imaging
  • Carcinoma / drug therapy
  • Carcinoma / secondary
  • Denosumab
  • Diphosphonates / therapeutic use*
  • Female
  • Femur / diagnostic imaging
  • Femur / drug effects
  • Femur / metabolism
  • Frontal Bone / diagnostic imaging
  • Frontal Bone / drug effects
  • Frontal Bone / metabolism
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Imidazoles / therapeutic use
  • Jaw Diseases / chemically induced
  • Jaw Diseases / metabolism
  • Mandible / diagnostic imaging
  • Mandible / drug effects*
  • Mandible / metabolism
  • Maxilla / diagnostic imaging
  • Maxilla / drug effects*
  • Maxilla / metabolism
  • Middle Aged
  • Osteonecrosis / chemically induced
  • Osteonecrosis / metabolism
  • RANK Ligand / antagonists & inhibitors*
  • Radionuclide Imaging
  • Retrospective Studies
  • Zoledronic Acid

Substances

  • Antibodies, Monoclonal, Humanized
  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • RANK Ligand
  • TNFSF11 protein, human
  • Denosumab
  • Zoledronic Acid