Incidence of antiresorptive agent-related osteonecrosis of the jaw: A multicenter retrospective epidemiological study in Hyogo Prefecture, Japan

Masanori Nashi; Hiromitsu Kishimoto; Masaki Kobayashi; Akira Tachibana; Motoo Suematsu; Shigeyoshi Fujiwara; Yoshiyuki Ota; Susumu Hashitani; Takeshi Shibatsuji; Tetsuya Nishida; Kazuma Fujimura; Shungo Furudoi; Yoshiki Ishida; Shoichiro Ishii; Tsuyoshi Fujita; Soichi Iwai; Takashi Shigeta; Takeshi Harada; Daisuke Miyai; Daisuke Takeda; Masaya Akashi; Kazuma Noguchi; Toshihiko Takenobu

doi:10.1016/j.jds.2022.10.030

Incidence of antiresorptive agent-related osteonecrosis of the jaw: A multicenter retrospective epidemiological study in Hyogo Prefecture, Japan

J Dent Sci. 2023 Jul;18(3):1156-1163. doi: 10.1016/j.jds.2022.10.030. Epub 2022 Nov 8.

Authors

Masanori Nashi¹, Hiromitsu Kishimoto², Masaki Kobayashi³, Akira Tachibana⁴, Motoo Suematsu⁵, Shigeyoshi Fujiwara⁶, Yoshiyuki Ota⁷, Susumu Hashitani⁸, Takeshi Shibatsuji⁹, Tetsuya Nishida¹⁰, Kazuma Fujimura¹¹, Shungo Furudoi¹², Yoshiki Ishida¹³, Shoichiro Ishii¹⁴, Tsuyoshi Fujita¹⁵, Soichi Iwai¹⁶, Takashi Shigeta¹⁷, Takeshi Harada¹⁸, Daisuke Miyai¹⁹, Daisuke Takeda²⁰, Masaya Akashi²⁰, Kazuma Noguchi², Toshihiko Takenobu¹

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
² Department of Dentistry and Oral Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
³ Department of Oral and Maxillofacial Surgery, Shinsuma General Hospital, Kobe, Hyogo, Japan.
⁴ Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital, Kakogawa, Hyogo, Japan.
⁵ Department of Dentistry and Oral Surgery, Meiwa General Hospital, Nishinomiya, Hyogo, Japan.
⁶ Department of Oral and Maxillofacial Surgery, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan.
⁷ Department of Oral and Maxillofacial Surgery, Itami City Hospital, Itami, Hyogo, Japan.
⁸ Department of Oral and Maxillofacial Surgery, Takarazuka City Hospital, Takarazuka, Hyogo, Japan.
⁹ Department of Oral and Maxillofacial Surgery, Tokiwa Hospital, Miki, Hyogo, Japan.
¹⁰ Department of Dentistry and Maxillo-facial Surgery, Kobe City Medical Center West Hospital, Kobe, Hyogo, Japan.
¹¹ Department of Oral and Maxillofacial Surgery, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Hyogo, Japan.
¹² Department of Oral Surgery, Konan Medical Center, Kobe, Hyogo, Japan.
¹³ Department of Oral and Maxillofacial Surgery, Hyogo Prefectural Awaji Medical Center, Sumoto, Hyogo, Japan.
¹⁴ Department of Oral and Maxillofacial Surgery, Kinki Central Hospital, Itami, Hyogo, Japan.
¹⁵ Department of Oral and Maxillofacial Surgery, Mitsubishi Kobe Hospital, Kobe, Hyogo, Japan.
¹⁶ Department of Dentistry and Oral and Maxillofacial Surgery, Nishinomiya Municipal Central Hospital, Nishinomiya, Hyogo, Japan.
¹⁷ Department of Oral Maxillofacial Surgery, Hyogo Cancer Center, Akashi, Hyogo, Japan.
¹⁸ Department of Oral and Maxillofacial Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan.
¹⁹ Department of Dentistry and Oral Surgery, Nishiwaki Municipal Hospital, Nishiwaki, Hyogo, Japan.
²⁰ Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.

Abstract

Background/purpose: The incidence of medication-related osteonecrosis of the jaw is increasing worldwide, mostly due to the use of antiresorptive agents (ARAs) such as bisphosphonate (BP) and denosumab (Dmab). However, the proportion of BP-related osteonecrosis of the jaw (BRONJ) and Dmab-related osteonecrosis of the jaw (DRONJ) among all ARA-related osteonecrosis of the jaw (ARONJ) cases is not clear; this hinders appropriate treatment, recurrence-prevention planning, and avoidance of unnecessary Dmab withdrawal. Moreover, the causative drug administered at each disease stage remains unknown. Therefore, we conducted a retrospective study of patients with ARONJ who visited oral and maxillofacial surgery departments at hospitals in Hyogo Prefecture, Japan, over 3 years to classify and compare patient characteristics with those having BRONJ and DRONJ. We sought to identify the proportion of DRONJ in ARONJ.

Materials and methods: After excluding stage 0 patients, 1021 patients were included (471 high-dose; 560 low-dose). ARA treatment for bone metastases of malignant tumors and multiple myeloma was considered high dose, while that for cancer treatment-induced bone loss and osteoporosis was low dose.

Results: Low doses of BP and Dmab accounted for >50% patients; the results differed from those in other countries. DRONJ accounted for 58% and 35% of high-dose and low-dose cases, respectively. Stage 3 ARONJ cases comprised 92 (19.5%) low-dose BRONJ, 39 (20.1%) high-dose BRONJ, 24 (30%) low-dose DRONJ, and 68 (24.5%) high-dose DRONJ. Eighty-nine patients who received switch therapy were divided into BRONJ or DRONJ, but there was no difference in the ratio of each stage compared to the non-switch therapy.

Conclusion: To the best of our knowledge, this is the first study to clarify the proportion of BRONJ and DRONJ cases, causative drug, and its doses by disease stages. DRONJ accounted for approximately 30% of the ARONJ, approximately 60% of which was due to high doses.

Keywords: Antiresorptive agent-related osteonecrosis jaw; Bisphosphonate; Denosumab; Switching therapy.