Factors affecting development of medication-related osteonecrosis of the jaw in cancer patients receiving high-dose bisphosphonate or denosumab therapy: Is tooth extraction a risk factor?

PLoS One. 2018 Jul 26;13(7):e0201343. doi: 10.1371/journal.pone.0201343. eCollection 2018.


Methods for preventing medication-related osteonecrosis of the jaw (MRONJ) in cancer patients who have received high-dose bisphosphonate (BP) or denosumab (Dmab) have not yet been established. Tooth extraction after starting medication has been believed to be a major risk factor for MRONJ, and therefore this procedure tends to be avoided. This study investigated the risk factors for MRONJ, with a special reference to the correlation between tooth extraction and development of MRONJ. One hundred and thirty-five cancer patients who were administrated high-dose BP or Dmab were enrolled in the study. Demographic factors, general condition, treatment factors, and dental findings were examined retrospectively using medical records and panoramic X-ray findings. The cumulative occurrence rate of MRONJ was calculated using the Kaplan-Meier method, and the correlation between these variables and development of MRONJ was analyzed by univariate and multivariate Cox regression analysis. MRONJ developed in 18 of 135 patients. The 1-, 2-, and 3-year cumulative occurrence rates were 8.6%, 21.5%, and 29.2%, respectively. The duration of medication before first visit to the dental unit and the presence of a tooth with clinical symptoms were significantly correlated with the development of MRONJ. The rate of MRONJ occurrence in patients who had teeth with clinical symptoms, but who did not undergo tooth extraction, became higher 2 years later than that in patients who underwent extraction of teeth with symptoms, although not significant. Early dental examination and effective preventative care to avoid infection/inflammation are important for preventing MRONJ.

MeSH terms

  • Aged
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / etiology*
  • Bone Density Conservation Agents / adverse effects*
  • Bone Density Conservation Agents / therapeutic use
  • Denosumab / adverse effects*
  • Denosumab / therapeutic use
  • Diphosphonates / adverse effects*
  • Diphosphonates / therapeutic use
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Risk Factors
  • Tooth Extraction / adverse effects*


  • Bone Density Conservation Agents
  • Diphosphonates
  • Denosumab

Grants and funding

The authors received no specific funding for this work.