Clinical study evaluating the effect of bevacizumab on the severity of zoledronic acid-related osteonecrosis of the jaw in cancer patients

Bone. 2014 Jan:58:103-7. doi: 10.1016/j.bone.2013.10.002. Epub 2013 Oct 9.


This study aimed to evaluate the effect of bevacizumab (BVZ) on the severity of osteonecrosis of the jaw (ONJ) in a cohort of cancer patients treated with intravenous zoledronic acid (ZA). We reviewed 42 oncologic patients with ONJ between 2007 and 2010. Only patients with solids tumors and who had received ZA were included. Data analyses included age, sex, underlying disease, ZA and BVZ dosages, dental history and ONJ characteristics. Of the 42 ONJ patients treated with ZA, 10 also received BVZ. In the 10 ZA/BVZ patients, the mean duration of ZA treatment at the time of ONJ diagnosis was 12.4 months (±6.8), compared to 22.9 months (±4.8) in the 32 patients who received ZA only (p<0.05). Cox's model analysis of the delay to ONJ diagnosis confirmed the impact of BVZ on ONJ diagnosis. In the ZA/BVZ-treated group, 7 (70%) patients developed spontaneous osteonecrosis. Multiple logistic regression analysis showed that ZA/BVZ is associated with increased risk of developing spontaneous ONJ (OR 6.07; 95% CI, [1.3-28.2], p<0.05). And finally, the number of ONJ lesions was increased in the ZA/BVZ-treated group compared to the ZA group (p<0.01). Other clinical conditions as type of tumor (prostate, breast…), cancer severity or other chemotherapy drugs also could be involved in ONJ evolution. However, this study demonstrates for the first time the potential negative influence of BVZ on the incidence and severity of ONJ in patients receiving ZA. Within the study limits, our results suggest that combination ZA/BVZ treatment may possibly predispose to the development of spontaneous and earlier ONJ.

Keywords: Bevacizumab; Cancer; Jaw; Osteonecrosis; Zoledronic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / drug therapy*
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / pathology
  • Diphosphonates / adverse effects*
  • Diphosphonates / therapeutic use*
  • Female
  • Humans
  • Imidazoles / adverse effects*
  • Imidazoles / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Risk Factors
  • Treatment Outcome
  • Zoledronic Acid


  • Antibodies, Monoclonal, Humanized
  • Diphosphonates
  • Imidazoles
  • Bevacizumab
  • Zoledronic Acid