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; N Ueda; S I Yamada; S Kato; E Iwata; S Hayashida; Y Kojima; M Shinohara; I Tojo; H Nakahara; T Yamaguchi; T Kirita; H Kurita; Y Shibuya; S Soutome; M Akashi; Japanese Study Group of Co-operative Dentistry with Medicine (JCDM)

doi: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

Osteoporos Int. 2021 Nov;32(11):2323-2333. doi: 10.1007/s00198-021-05995-3. Epub 2021 May 17.

Authors

T Hasegawa¹, N Ueda², S I Yamada³, S Kato⁴, E Iwata^{5

6}, S Hayashida⁷, Y Kojima⁸, M Shinohara⁹, I Tojo¹⁰, H Nakahara¹¹, T Yamaguchi¹², T Kirita², H Kurita³, Y Shibuya⁴, S Soutome¹³, M Akashi⁵; Japanese Study Group of Co-operative Dentistry with Medicine (JCDM)

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. hasetaku@med.kobe-u.ac.jp.
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, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
⁶ Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital, Kakogawa, Japan.
⁷ Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
⁸ Department of Dentistry and Oral Surgery, Kansai Medical University, Hirakata, Japan.
⁹ Department of Oral and Maxillofacial Surgery, Juntendo University School of Medicine, Tokyo, Japan.
¹⁰ Department of Oral and Maxillofacial Surgery, Wakayama Medical University, Wakayama, Japan.
¹¹ Department of Oral and Maxillofacial Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
¹² Department of Preventive Dentistry, Research Field in Dentistry, Medical and Dental Sciences Area, Kagoshima University, Kagoshima, Japan.
¹³ Department of Oral Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

PMID: 33997909
DOI: 10.1007/s00198-021-05995-3

Abstract

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 of this 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.

Keywords: Denosumab; Denosumab-related osteonecrosis of the jaw; Discontinuation; Drug holiday; Medication-related osteonecrosis of the jaw.

Publication types

Multicenter Study

MeSH terms

Bisphosphonate-Associated Osteonecrosis of the Jaw* / epidemiology
Bisphosphonate-Associated Osteonecrosis of the Jaw* / etiology
Bone Density Conservation Agents* / adverse effects
Denosumab / adverse effects
Diphosphonates
Female
Humans
Male
Neoplasms* / complications
Neoplasms* / drug therapy
Osteonecrosis* / chemically induced
Osteonecrosis* / epidemiology
Pharmaceutical Preparations*
Retrospective Studies
Tooth Extraction / adverse effects

Substances

Bone Density Conservation Agents
Diphosphonates
Pharmaceutical Preparations
Denosumab