Denosumab-Related Osteonecrosis of the Jaw After Tooth Extraction and Effects of a Short Drug Holiday in Cancer Patients

Jul 7, 2026

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Denosumab-related osteonecrosis of the jaw (DRONJ) risk after tooth extraction in cancer patients receiving oncologic doses of denosumab is driven by several factors: pre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer denosumab treatment duration, and female sex. A short drug holiday before extraction does not reduce complication risk. Multicenter retrospective analyses evaluated demographic and clinical variables to identify predictors of DRONJ and support immediate extraction strategies for inflamed teeth.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

Abstract

Summary

Introduction

Methods

Results

Conclusions

Background and Rationale

Bone-modifying agents and MRONJ/DRONJ

Tooth extraction as a major trigger

Osteoporosis International [https://doi.org/10.1007/s00198-021-05995-3](https://doi.org/10.1007/s00198-021-05995-3) Denosumab-related osteonecrosis of the jaw after tooth extraction and the effects of a short drug holiday in cancer patients: a multicenter retrospective study T. Hasegawa 1 & N. Ueda 2 & SI. Yamada 3 & S. Kato 4 & E. Iwata 1,5 & S. Hayashida 6 & Y. Kojima 7 & M. Shinohara 8 & I. Tojo 9 & H. Nakahara 10 & T. Yamaguchi 11 & T. Kirita 2 & H. Kurita 3 & Y. Shibuya 4 & S. Soutome 12 & M. Akashi 1 & Japanese Study Group of Co-operative Dentistry with Medicine (JCDM) Received: 2 February 2021 /Accepted: 5 May 2021 \# International Osteoporosis Foundation and National Osteoporosis Foundation 2021 Abstract Summary Pre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer duration of denosumab therapy, and female sex were significantly associated with an increased risk of denosumab-related osteonecrosis of the jaw after tooth extraction in patients with cancer on oncologic doses of denosumab. A short drug holiday did not protect against this complication. Introduction This study retrospectively investigated the relationship between various risk factors, including brief discontinuation of denosumab, and development of denosumab-related osteonecrosis of the jaw (DRONJ) after tooth extraction in patients with cancer who were receiving oncologic doses ofthis agent. Methods Data were collected on demographic characteristics, duration of denosumab therapy, whether or not denosumab was discontinued before tooth extraction (drug holiday), duration of discontinuation, presence of pre-existing inflammation, and whether or not additional surgical procedures were performed. Risk factors for DRONJ after tooth extraction were evaluated by univariate and multivariate analyses. Results A total of 136 dental extractions were performed in 72 patients (31 men, 41 women) with cancer who were receiving oncologic doses of denosumab. Post-extraction DRONJ was diagnosed in 39 teeth (28.7%) in 25 patients. Tooth extraction was significantly associated with development of DRONJ only in patients with pre-existing inflammation (odds ratio [OR] 243.77), those on corticosteroid therapy (OR 73.50), those with periapical periodontitis (OR 14.13), those who had been taking oncologic doses of denosumab for a longer period (OR 4.69), and in women (OR 1.04) . There was no significant difference in the occurrence of DRONJ between patients who had a drug holiday before tooth extraction and those who did not. Conclusions These findings suggest that inflamed teeth should be extracted immediately in patients with cancer who are receiving oncologic doses of denosumab. Drug holidays have no significant impact on the risk of DRONJ. * T. Hasegawa [hasetaku@med.kobe-u.ac.jp](hasetaku@med.kobe-u.ac.jp) 1 Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan 2 Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Japan 3 Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Japan 4 Department of Oral and Maxillofacial Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 5 Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital, Kakogawa, Japan 6 Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan 7 Department of Dentistry and Oral Surgery, Kansai Medical University, Hirakata, Japan 8 Department of Oral and Maxillofacial Surgery, Juntendo University School of Medicine, Tokyo, Japan 9 Department of Oral and Maxillofacial Surgery, Wakayama Medical University, Wakayama, Japan 10 Department of Oral and Maxillofacial Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan 11 Department of Preventive Dentistry, Research F

FAQs

Which factors are significantly associated with higher DRONJ risk after tooth extraction in cancer patients on denosumab?

Pre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer denosumab treatment duration, and female sex were significantly associated with increased DRONJ risk after tooth extraction.

Does a short drug holiday before tooth extraction lower the risk of denosumab-related osteonecrosis of the jaw?

No. The occurrence of DRONJ did not differ significantly between patients who had a drug holiday before tooth extraction and those who did not.

How strong is the association between tooth extraction and DRONJ development?

Tooth extraction was significantly associated with DRONJ particularly in subgroups with pre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer denosumab exposure, and in women, with the strongest association in those with pre-existing inflammation.

Jul 7, 2026

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