Nashi Masanori, Kishimoto Hiromitsu, Kobayashi Masaki, Tachibana Akira, Suematsu Motoo, Fujiwara Shigeyoshi, Ota Yoshiyuki, Hashitani Susumu, Shibatsuji Takeshi, Nishida Tetsuya, Fujimura Kazuma, Furudoi Shungo, Ishida Yoshiki, Ishii Shoichiro, Fujita Tsuyoshi, Iwai Soichi, Shigeta Takashi, Harada Takeshi, Miyai Daisuke, Takeda Daisuke, Akashi Masaya, Noguchi Kazuma, Takenobu Toshihiko
Department of Oral and Maxillofacial Surgery, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
Department of Dentistry and Oral Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
J Dent Sci. 2023 Jul;18(3):1156-1163. doi: 10.1016/j.jds.2022.10.030. Epub 2022 Nov 8.
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.
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.
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.
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.
背景/目的：在全球范围内，药物相关性颌骨坏死的发病率正在上升，这主要归因于抗吸收剂（ARA）的使用，如双膦酸盐（BP）和地诺单抗（Dmab）。然而，在所有与ARA相关的颌骨坏死（ARONJ）病例中，BP相关性颌骨坏死（BRONJ）和Dmab相关性颌骨坏死（DRONJ）的比例尚不清楚；这妨碍了适当的治疗、预防复发的规划以及避免不必要地停用Dmab。此外，每个疾病阶段所使用的致病药物仍不明确。因此，我们对日本兵库县各医院口腔颌面外科就诊的ARONJ患者进行了一项回顾性研究，为期3年，以对患者特征进行分类，并与BRONJ和DRONJ患者的特征进行比较。我们试图确定DRONJ在ARONJ中的比例。
排除0期患者后，纳入1021例患者（471例高剂量；560例低剂量）。用于恶性肿瘤和多发性骨髓瘤骨转移的ARA治疗被视为高剂量，而用于癌症治疗引起的骨质流失和骨质疏松症的治疗则为低剂量。
低剂量的BP和Dmab占患者的比例超过50%；这一结果与其他国家不同。DRONJ分别占高剂量和低剂量病例的58%和35%。3期ARONJ病例包括92例（19.5%）低剂量BRONJ、39例（20.1%）高剂量BRONJ、24例（30%）低剂量DRONJ和68例（24.5%）高剂量DRONJ。89例接受转换治疗的患者被分为BRONJ或DRONJ，但与未接受转换治疗的患者相比，各阶段的比例没有差异。
据我们所知，这是第一项按疾病阶段明确BRONJ和DRONJ病例比例、致病药物及其剂量的研究。DRONJ约占ARONJ的30%，其中约60%是由高剂量引起的。
