Bone metabolic dynamics and histopathological analysis of teriparatide administration to ARONJ

• Project/Area Number: 18K17167
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Nagasaki University (2019-2021); Shinshu University (2018)
• Principal Investigator: Morishita Kota 長崎大学, 病院(歯学系), 助教 (50779519)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2020: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ARONJ / テリパラチド / 顎骨壊死

Outline of Final Research Achievements

The purpose of this study is to clarify the mechanism by which teriparatide acts on the bone tissue of ARONJ. Multicenter clinical studies have suggested that intermittent administration of teriparatide is clinically effective. In addition, for the purpose of investigating the effect of teriparatide on bone, teriparatide was administered to the inflamed skull of mouse to examine the amount of bone resorption and osteoclast activity. It was confirmed that the number of cells increased, but the amount of bone resorption subsequently decreased.
Histopathological analysis of osteoclasts confirmed that withdrawal of the bisphosphonate for about 6 months had little effect on the jaw.

Academic Significance and Societal Importance of the Research Achievements

2003年にビスホスホネート製剤で顎骨壊死が起こることが報告されて以降、同様の顎骨壊死の報告が散見され、現在では広く知られている。骨吸収抑制薬関連顎骨壊死(ARONJ)は確立された治療法がないため一度発症すると治療に難渋することが多い。また、手術療法の治癒率が高いとする報告が多い一方、全身状態を考慮して手術を回避せざるを得ない症例も多数見受けられる。本研究では、遺伝子組換えヒト副甲状腺ホルモン製剤であるテリパラチドがARONJに対して臨床的に有効であることが示唆された。このことより、テリパラチド療法は手術が困難なARONJ症例において、治療法の選択肢の1つとなりうると考えられる。

Research Products

• [Journal Article] Duration of drug holiday of oral bisphosphonate and osteoclast morphology in osteoporosis patients with medication-related osteonecrosis of the jaw (2022)
  • Author(s): Morishita Kota、Otsuru Mitsunobu、Soutome Sakiko、Hayashida Saki、Murata Maho、Nakamura Wataru、Umeda Masahiro
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: - Issue: 4 Pages: 467-471
  • DOI: 10.1016/j.ajoms.2021.12.010
  • Peer Reviewed
• [Journal Article] Treatment outcomes of adjunctive teriparatide therapy for medication-related osteonecrosis of the jaw (MRONJ): A multicenter retrospective analysis in Japan (2020)
  • Author(s): Morishita Kota、Yamada Shin-ichi、Kawakita Akiko、Hashidume Masao、Tachibana Akira、Takeuchi Noritami、Ohbayashi Yumiko、Kanno Takahiro、Yoshiga Daigo、Narai Takashi、Sasaki Noboru、Shinohara Hisayuki、Uzawa Narikazu、Miyake Minoru、Tominaga Kazuhiro、Kodani Isamu、Umeda Masahiro、Kurita Hiroshi
  • Journal Title: Journal of Orthopaedic Science Volume: - Issue: 6 Pages: 1079-1083
  • DOI: 10.1016/j.jos.2020.01.012
  • Peer Reviewed
• [Presentation] 骨吸収抑制薬の投与期間および休薬期間と破骨細胞の形態異常との関連について (2019)
  • Author(s): 森下廣太，林田 咲，川北晃子，村田真穂 ， 柳本惣市，澤田俊輔，兒島由佳，梅田正博
  • Organizer: 第64回公益社団法人日本口腔外科学会総会・学術大会
• [Presentation] 骨吸収抑制剤関連顎骨壊死(ARONJ)に対するテリパラチドの治療効果に関する多施設共同後ろ向き観察研究． (2018)
  • Author(s): 森下廣太，山田慎一，川北晃子，梅田正博，橘 進彰，竹内憲民，鵜澤成一，三宅 実，吉松英樹，関根浄治，吉賀大午，冨永和宏，奈良井 節，小谷 勇，佐々木 昇，篠原久幸，栗田 浩．
  • Organizer: 第72回日本口腔科学会学術集会
• [Presentation] Successful treatment outcomes of adjunctive teriparatide therapy in ARONJ patients. (2018)
  • Author(s): Morishita K, Yamada S, Kawakita A, Hayashida S, Tachibana A, Takeuchi N, Uzawa N, Ohbayashi Y, Miyake M, Yoshino A, Sekine J, Yoshiga D, Tominaga K, Narai T, Kodani I, Sasaki N, Shinohara H, Kurita H.
  • Organizer: 2018 IADR/PER General Session.
  • Int'l Joint Research
• [Presentation] ARONJ患者に対するテリパラチド療法の治療効果に関する多施設共同後向き観察研究． (2018)
  • Author(s): 森下廣太，川北晃子，橘 進彰，竹内憲民，大林由美子，管野貴浩，吉賀大午，奈良井 節，佐々木 昇，篠原久幸．
  • Organizer: 第63回公益社団法人日本口腔外科学会総会・学術大会