Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul;18(3):1156-1163.
doi: 10.1016/j.jds.2022.10.030. Epub 2022 Nov 8.

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

Masanori Nashi  1 , Hiromitsu Kishimoto  2 , Masaki Kobayashi  3 , Akira Tachibana  4 , Motoo Suematsu  5 , Shigeyoshi Fujiwara  6 , Yoshiyuki Ota  7 , Susumu Hashitani  8 , Takeshi Shibatsuji  9 , Tetsuya Nishida  10 , Kazuma Fujimura  11 , Shungo Furudoi  12 , Yoshiki Ishida  13 , Shoichiro Ishii  14 , Tsuyoshi Fujita  15 , Soichi Iwai  16 , Takashi Shigeta  17 , Takeshi Harada  18 , Daisuke Miyai  19 , Daisuke Takeda  20 , Masaya Akashi  20 , Kazuma Noguchi  2 , Toshihiko Takenobu  1
Affiliations

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

Masanori Nashi et al. J Dent Sci. 2023 Jul.

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.

PubMed Disclaimer

Conflict of interest statement

Hiromitsu Kishimoto received compensation from Asahi Kasei Pharma Corporation.

References

    1. Marx R.E. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic (1) J Oral Maxillofac Surg. 2003;61:1115–1117. - PubMed
    1. Qi W.X., Tang L.N., He A.N., Yao Y., Shen Z. Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials. Int J Clin Oncol. 2014;19:403–410. - PubMed
    1. Aoki K., Matsunaga S., Ito S., et al. Persistent bone resorption lacunae on necrotic bone distinguish bisphosphonate-related osteonecrosis of jaw from denosumab-related osteonecrosis. J Bone Miner Metabol. 2021;39:737–747. - PubMed
    1. Ruggiero S.L., Dodson T.B., Fantasia J., et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg. 2014;72:1938–1956. - PubMed
    1. Yoneda T., Hagino H., Sugimoto T., et al. Antiresorptive agent-related osteonecrosis of the jaw: position paper 2017 of the Japanese allied committee on osteonecrosis of the jaw. J Bone Miner Metabol. 2017;35:6–19. - PubMed

LinkOut - more resources