ビスホスホネート投与患者の抜歯後BRONJ発生に関する多施設共同前向き研究
Tooth extraction is reported as the main trigger of bisphosphonate (BP) -related osteonecrosis of the jaw (BRONJ). A method to prevent BRONJ has not been scientifically proven. The American Association of Oral and Maxillofacial Surgeons (AAOMS) differs from the International Task Force on Osteonecro...
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| Published in | 日本口腔外科学会雑誌 Vol. 68; no. 4; pp. 168 - 183 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
公益社団法人 日本口腔外科学会
20.04.2022
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0021-5163 2186-1579 |
| DOI | 10.5794/jjoms.68.168 |
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| Abstract | Tooth extraction is reported as the main trigger of bisphosphonate (BP) -related osteonecrosis of the jaw (BRONJ). A method to prevent BRONJ has not been scientifically proven. The American Association of Oral and Maxillofacial Surgeons (AAOMS) differs from the International Task Force on Osteonecrosis of the Jaw with regard to the prevention of BRONJ via prophylactic withdrawal before tooth extraction. We performed a multicenter prospective study regarding the development of BRONJ after tooth extraction in BP-treated patients for the purpose of determining factors associated with the frequency of BRONJ. We extracted teeth from patients with a history of current or prior treatment with BP preparations; teeth were extracted using a common treatment protocol. The presence or absence of BRONJ and adverse events were evaluated. A total of 1,323 cases were targeted for this study; 2,371 teeth were extracted. The overall incidence of BRONJ was 1.74%; in the prophylactic withdrawal group it was 1.73%, whereas in the prophylactic non-withdrawal group it was 1.75%. Factors associated with the onset of BRONJ were sex, preparation adaptation classification, oral hygiene state, site of tooth extraction, and Denosumab usage. From analysis that considered the effect of confounding using the propensity score, prophylactic BP withdrawal did not result in a reduction of BRONJ (onset odds ratio with withdrawal: 1.13, 95%CI 0.36-3.57). |
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| AbstractList | Tooth extraction is reported as the main trigger of bisphosphonate (BP) -related osteonecrosis of the jaw (BRONJ). A method to prevent BRONJ has not been scientifically proven. The American Association of Oral and Maxillofacial Surgeons (AAOMS) differs from the International Task Force on Osteonecrosis of the Jaw with regard to the prevention of BRONJ via prophylactic withdrawal before tooth extraction. We performed a multicenter prospective study regarding the development of BRONJ after tooth extraction in BP-treated patients for the purpose of determining factors associated with the frequency of BRONJ. We extracted teeth from patients with a history of current or prior treatment with BP preparations; teeth were extracted using a common treatment protocol. The presence or absence of BRONJ and adverse events were evaluated. A total of 1,323 cases were targeted for this study; 2,371 teeth were extracted. The overall incidence of BRONJ was 1.74%; in the prophylactic withdrawal group it was 1.73%, whereas in the prophylactic non-withdrawal group it was 1.75%. Factors associated with the onset of BRONJ were sex, preparation adaptation classification, oral hygiene state, site of tooth extraction, and Denosumab usage. From analysis that considered the effect of confounding using the propensity score, prophylactic BP withdrawal did not result in a reduction of BRONJ (onset odds ratio with withdrawal: 1.13, 95%CI 0.36-3.57). |
| Author | 川口, 泰 西方, 聡 鈴木, 豊典 阿部, 貴洋 藤盛, 真樹 三澤, 肇 針谷, 靖史 末次, 博 工藤, 章裕 北田, 秀昭 嶋﨑, 康相 榊原, 典幸 鳥谷部, 純行 中嶋, 頼俊 野島, 正寛 浅香, 雄一郎 岡田, 益彦 谷村, 晶広 角, 伸博 太子, 芳仁 杉浦, 千尋 宮手, 浩樹 柴山, 尚大 宮澤, 政義 小林, 一三 笠原, 和恵 山下, 徹郎 牧野, 修治郎 佐藤, 雄治 道念, 正樹 |
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| References | 3) Yoneda T, Hagino H, et al : Bisphosphonate-related osteonecrosis of the jaw: position paper from the Allied Task Force Committee of Japanese Society for Bone and Mineral Research, Japan Osteoporosis Society, Japanese Society of Periodontology, Japanese Society for Oral and Maxillofacial Radiology, and Japanese Society of Oral and Maxillofacial Surgeons. J Bone miner Metab 28: 365-383, 2010. 7) Ruggiero SL, Dodson TB, et al : American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw-- 2014 update. J Oral Maxillofac Surg 72: 1938-1956, 2014. 12) Assael LA : Oral bisphosphonates as a cause of bisphosphonate-related osteonecrosis of the jaw: clinical findings, assessment of risk, and preventive strategies. J Oral Maxillofac Surg 67: 35-43, 2009. 18) Van den Wyngaert T, Huizing MT, et al : Bisphosphonates and osteonecrosis of the jaw: cause and effect or a post hoc fallacy? Ann Oncol 17: 1197-1204, 2006. 24) Patntirapong S, Poolgesom M : Alteration of macrophage viability, differentiation, and function by bisphosphonates. Oral Dis 24: 1294-1302, 2018. 21) Bone HG, Hosking D, et al : Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350: 1189-1199, 2004. 25) Weitzmann MN : Do γδ T cells predict osteonecrosis of the Jaw? J Bone Miner Res 28: 732-727, 2013. 14) Soutome S, Hayashida S, et al : Factors affecting development of medication-related osteonecrosis of the jaw in cancer patients receiving high-dose bisphosphonate or denosumab therapy: Is tooth extraction a risk factor? PLoS One 13: e0201343, 2018. 8) Khan AA, Morison A, et al : Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res 30: 3-23, 2015. 37) Taguchi A, Shiraki M, et al : Impact of Osteonecrosis of the Jaw on Osteoporosis Treatment in Japan: Results of a Questionnaire-Based Survey by the Adequate Treatment of Osteoporosis (A-TOP) Research Group. Calcif Tissue Int 97: 542-550, 2015. 20) Chiu WY, Chien JY, et al : The risk of osteonecrosis of the jaws in Taiwanese osteoporotic patients treated with oral alendronate or raloxifene. J Clin Endocrinol Metab 99: 2729-2735, 2014. 32) Ikesue H, Doi K, et al : Switching from zoledronic acid to denosumab increases the risk for developing medication-related osteonecrosis of the jaw in patients with bone metastases. Cancer Chemother Pharmacol 87: 871-877, 2021. 28) Otto S, Tröltzsch M, et al : Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: A trigger for BRONJ development? J Craniomaxillofac Surg 43: 847-854, 2015. 31) Higuchi T, Soga Y, et al : Replacing zoledronic acid with denosumab is a risk factor for developing osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol 125: 547-551, 2018. 36) Matthias Z, Charlotte W, et al : Microbial diversity in infections of patients with medication-related osteonecrosis of the jaw. Clin Oral Investig 23: 2143-2151, 2019. 13) Mavrokokki T, Cheng A, et al : Natute and Frequency of Bisphosphonate-Associated Osteonecrosis of the Jaw in Australia. J Oral Maxillofac Surg 65: 415-423, 2007. 26) Taguchi A, Shiraki M, et al : Lack of cooperation between physicians and dentists during osteoporosis treatment may increase fractures and osteonecrosis of the jaw. Curr Med Res Opin 32: 1261-1268, 2016. 35) Hasegawa T, Kawakita A, et al : A multicenter retrospective study of the risk factors associated with medication-related osteonecrosis of the jaw after tooth extraction in patients receiving oral bisphosphonate therapy: can primary wound closure and a drug holiday really prevent MRONJ? Osteoporos Int 28: 2465-2473, 2017. 4) 米田俊之， 萩野 浩， 他：ビスフォスフォネート関連顎骨壊死に対するポジションペーパー (改訂追補2012年版) http://jsbmr.umin.jp/guide/pdf/bronjpositionpaper2012.pdf. 参照年月日2013年4月1日 5) 米田俊之， 萩野 浩， 他：骨吸収抑制薬関連顎骨壊死の病態と管理:顎骨壊死検討委員会ポジションペーパー2016. https://www.jsoms.or.jp/medical/wp-content/uploads/2015/08/position_paper2016.pdf. 参照年月日2019年12月5日 34) Saia G, Blandamura S, et al : Occurrence of bisphosphonate-related osteonecrosis of the jaw after surgical tooth extraction. J Oral Maxillofac Surg 68: 797-804, 2010. 15) Soutome S, Otsuru M, et al : Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients. Sci Rep 11: 17226, 2021. 19) 井本しおん：骨粗鬆症治療薬ビスホスホネートの新たな役割−抗腫瘍効果の可能性−．神戸常盤紀要 6: 9-19, 2013. 22) Allen MR : Medication-Related Osteonecrosis of the Jaw: Basic and Translational Science Updates. Oral Maxillofac Clin North Am 27: 497-508, 2015. 27) Ripamonti CI, Maniezzo M, et al : Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumor patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol 20: 137-145, 2009. 6) Filleul O, Crompot E, et al : Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases. J Cancer Res Clin Oncol 136: 1117-1124, 2010. 29) 森川貴迪， 柴原孝彦：BRONJ・ARONJ・MRONJの現状と課題．日歯医師会誌 69: 977-986, 2017. 23) Shudo A, Kishimoto H, et al : Long-term oral bisphosphonates delay healing after tooth extraction: a single institutional prospective study. Osteoporos Int 29: 2315-2321, 2018. 2) 日本口腔外科学会：BRONJ 治療に関する実態調査．https://www.jsoms.or.jp/medical/wp-content/uploads/2016/06/bronj_jsoms_201512.pdf. 参照年月日2017年8月10日 17) Hellstein JW, Adler RA, et al : Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 142: 1243-1251, 2011. 10) Vahtsevanos K, Kyrgidis A, et al : Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol 27: 5356-5362, 2009. 33) Mozzati M, Arata V, et al : Tooth extraction in osteoporotic patients taking oral bisphosphonates. Osteoporos Int 24: 1707-1712, 2013. 38) Black DM and Rosen CL : Postmenopausal Osteoporosis. N Engl J Med 374: 2096, 2016. 1) Marx RE : Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws : a growing epidemic. J Oral Maxillofac Surg 61: 1115-1117, 2003. 16) Saad F, Brown JE, et al : Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded activetrolled phase Ⅲ trials in cancer patients with bone metastases. Ann Oncol 23: 1341-1347, 2012. 30) Voss P J, Steybe D, et al : Osteonecrosis of the jaw in patients transitioning from bisphosphonates to denosumab treatment for osteoporosis. Odontology 106: 469-480, 2018. 9) O'Leary TJ, Drake RB, et al : The plaque control record. J Periodontol 43: 38, 1972. 11) Hoff AO, Toth BB, et al : Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 23: 826-836, 2008. |
| References_xml | – reference: 24) Patntirapong S, Poolgesom M : Alteration of macrophage viability, differentiation, and function by bisphosphonates. Oral Dis 24: 1294-1302, 2018. – reference: 8) Khan AA, Morison A, et al : Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res 30: 3-23, 2015. – reference: 17) Hellstein JW, Adler RA, et al : Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 142: 1243-1251, 2011. – reference: 33) Mozzati M, Arata V, et al : Tooth extraction in osteoporotic patients taking oral bisphosphonates. Osteoporos Int 24: 1707-1712, 2013. – reference: 23) Shudo A, Kishimoto H, et al : Long-term oral bisphosphonates delay healing after tooth extraction: a single institutional prospective study. Osteoporos Int 29: 2315-2321, 2018. – reference: 19) 井本しおん：骨粗鬆症治療薬ビスホスホネートの新たな役割−抗腫瘍効果の可能性−．神戸常盤紀要 6: 9-19, 2013. – reference: 27) Ripamonti CI, Maniezzo M, et al : Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumor patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol 20: 137-145, 2009. – reference: 25) Weitzmann MN : Do γδ T cells predict osteonecrosis of the Jaw? J Bone Miner Res 28: 732-727, 2013. – reference: 3) Yoneda T, Hagino H, et al : Bisphosphonate-related osteonecrosis of the jaw: position paper from the Allied Task Force Committee of Japanese Society for Bone and Mineral Research, Japan Osteoporosis Society, Japanese Society of Periodontology, Japanese Society for Oral and Maxillofacial Radiology, and Japanese Society of Oral and Maxillofacial Surgeons. J Bone miner Metab 28: 365-383, 2010. – reference: 4) 米田俊之， 萩野 浩， 他：ビスフォスフォネート関連顎骨壊死に対するポジションペーパー (改訂追補2012年版) http://jsbmr.umin.jp/guide/pdf/bronjpositionpaper2012.pdf. 参照年月日2013年4月1日． – reference: 20) Chiu WY, Chien JY, et al : The risk of osteonecrosis of the jaws in Taiwanese osteoporotic patients treated with oral alendronate or raloxifene. J Clin Endocrinol Metab 99: 2729-2735, 2014. – reference: 28) Otto S, Tröltzsch M, et al : Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: A trigger for BRONJ development? J Craniomaxillofac Surg 43: 847-854, 2015. – reference: 37) Taguchi A, Shiraki M, et al : Impact of Osteonecrosis of the Jaw on Osteoporosis Treatment in Japan: Results of a Questionnaire-Based Survey by the Adequate Treatment of Osteoporosis (A-TOP) Research Group. Calcif Tissue Int 97: 542-550, 2015. – reference: 6) Filleul O, Crompot E, et al : Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases. J Cancer Res Clin Oncol 136: 1117-1124, 2010. – reference: 38) Black DM and Rosen CL : Postmenopausal Osteoporosis. N Engl J Med 374: 2096, 2016. – reference: 12) Assael LA : Oral bisphosphonates as a cause of bisphosphonate-related osteonecrosis of the jaw: clinical findings, assessment of risk, and preventive strategies. J Oral Maxillofac Surg 67: 35-43, 2009. – reference: 1) Marx RE : Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws : a growing epidemic. J Oral Maxillofac Surg 61: 1115-1117, 2003. – reference: 18) Van den Wyngaert T, Huizing MT, et al : Bisphosphonates and osteonecrosis of the jaw: cause and effect or a post hoc fallacy? Ann Oncol 17: 1197-1204, 2006. – reference: 34) Saia G, Blandamura S, et al : Occurrence of bisphosphonate-related osteonecrosis of the jaw after surgical tooth extraction. J Oral Maxillofac Surg 68: 797-804, 2010. – reference: 15) Soutome S, Otsuru M, et al : Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients. Sci Rep 11: 17226, 2021. – reference: 29) 森川貴迪， 柴原孝彦：BRONJ・ARONJ・MRONJの現状と課題．日歯医師会誌 69: 977-986, 2017. – reference: 14) Soutome S, Hayashida S, et al : Factors affecting development of medication-related osteonecrosis of the jaw in cancer patients receiving high-dose bisphosphonate or denosumab therapy: Is tooth extraction a risk factor? PLoS One 13: e0201343, 2018. – reference: 16) Saad F, Brown JE, et al : Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded activetrolled phase Ⅲ trials in cancer patients with bone metastases. Ann Oncol 23: 1341-1347, 2012. – reference: 5) 米田俊之， 萩野 浩， 他：骨吸収抑制薬関連顎骨壊死の病態と管理:顎骨壊死検討委員会ポジションペーパー2016. https://www.jsoms.or.jp/medical/wp-content/uploads/2015/08/position_paper2016.pdf. 参照年月日2019年12月5日． – reference: 9) O'Leary TJ, Drake RB, et al : The plaque control record. J Periodontol 43: 38, 1972. – reference: 31) Higuchi T, Soga Y, et al : Replacing zoledronic acid with denosumab is a risk factor for developing osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol 125: 547-551, 2018. – reference: 32) Ikesue H, Doi K, et al : Switching from zoledronic acid to denosumab increases the risk for developing medication-related osteonecrosis of the jaw in patients with bone metastases. Cancer Chemother Pharmacol 87: 871-877, 2021. – reference: 36) Matthias Z, Charlotte W, et al : Microbial diversity in infections of patients with medication-related osteonecrosis of the jaw. Clin Oral Investig 23: 2143-2151, 2019. – reference: 7) Ruggiero SL, Dodson TB, et al : American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw-- 2014 update. J Oral Maxillofac Surg 72: 1938-1956, 2014. – reference: 21) Bone HG, Hosking D, et al : Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350: 1189-1199, 2004. – reference: 11) Hoff AO, Toth BB, et al : Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 23: 826-836, 2008. – reference: 22) Allen MR : Medication-Related Osteonecrosis of the Jaw: Basic and Translational Science Updates. 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Odontology 106: 469-480, 2018. – reference: 35) Hasegawa T, Kawakita A, et al : A multicenter retrospective study of the risk factors associated with medication-related osteonecrosis of the jaw after tooth extraction in patients receiving oral bisphosphonate therapy: can primary wound closure and a drug holiday really prevent MRONJ? Osteoporos Int 28: 2465-2473, 2017. |
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| Snippet | Tooth extraction is reported as the main trigger of bisphosphonate (BP) -related osteonecrosis of the jaw (BRONJ). A method to prevent BRONJ has not been... |
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| SubjectTerms | BP製剤 (ビスホスホネート製剤) BP関連顎骨壊死 薬剤関連顎骨壊死 顎骨壊死 |
| Title | ビスホスホネート投与患者の抜歯後BRONJ発生に関する多施設共同前向き研究 |
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