ペントキシフィリン, トコフェロール, クロドロネート併用療法 (PENTOCLO療法) による放射線性下顎骨壊死の治療経験
Delanian et al. reported the efficacy of pentoxifylline-tocopherol-clodronate (PENTOCLO) treatment for osteoradionecrosis (ORN) of the mandible in 2011. Spontaneous sequestration and epithelialization of the mandibular lesion are induced by this method. We report a case of osteoradionecrosis of the...
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| Published in | 日本口腔外科学会雑誌 Vol. 66; no. 12; pp. 610 - 615 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
社団法人 日本口腔外科学会
20.12.2020
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0021-5163 2186-1579 |
| DOI | 10.5794/jjoms.66.610 |
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| Abstract | Delanian et al. reported the efficacy of pentoxifylline-tocopherol-clodronate (PENTOCLO) treatment for osteoradionecrosis (ORN) of the mandible in 2011. Spontaneous sequestration and epithelialization of the mandibular lesion are induced by this method. We report a case of osteoradionecrosis of the mandible which responded to treatment with PENTOCLO. A 60-year-old man was referred to our department with persistent mandibular ORN after definitive chemoradiotherapy for oropharyngeal carcinoma (T2N0M0). Periodontitis of the right second molar caused ORN, followed by pathological fracture. PENTOCLO treatment was started following 4-week antibiotic therapy. The sequestrum spontaneously separated with mucosal epithelialization two months after the treatment started. The second molar was removed at 11 months because of its increasing mobility. The extraction socket had epithelized and computed tomography (CT) showed that the pathological fracture had healed. No adverse events occurred during this treatment course. PENTOCLO may be an organpreserving treatment option for ORN of the mandible. |
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| AbstractList | Delanian et al. reported the efficacy of pentoxifylline-tocopherol-clodronate (PENTOCLO) treatment for osteoradionecrosis (ORN) of the mandible in 2011. Spontaneous sequestration and epithelialization of the mandibular lesion are induced by this method. We report a case of osteoradionecrosis of the mandible which responded to treatment with PENTOCLO. A 60-year-old man was referred to our department with persistent mandibular ORN after definitive chemoradiotherapy for oropharyngeal carcinoma (T2N0M0). Periodontitis of the right second molar caused ORN, followed by pathological fracture. PENTOCLO treatment was started following 4-week antibiotic therapy. The sequestrum spontaneously separated with mucosal epithelialization two months after the treatment started. The second molar was removed at 11 months because of its increasing mobility. The extraction socket had epithelized and computed tomography (CT) showed that the pathological fracture had healed. No adverse events occurred during this treatment course. PENTOCLO may be an organpreserving treatment option for ORN of the mandible. |
| Author | 廣田, 誠 南山, 周平 小栗, 千里 光永, 幸代 山隈, 優 光藤, 健司 |
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| References | 27) Oizumi T, Yamaguchi K, et al : A Strategy against the Osteonecrosis of the Jaw Associated with Nitrogen-Containing Bisphosphonates (N-BPs) : Attempts to Replace N-BPs with the Non-N-BP Etidronate. Biol Pharm Bull 39: 1549-1554, 2016. 11) Annane D, Bellissant E, et al : Corticosteroids in the treatment of severe sepsis and septic shock in adults. A systemic review. JAMA 301: 2362-2375, 2009. 18) Hamama S, Gilbert-Sirieix M, et al : Radiation-induced enteropathy: molecular basis of pentoxifylline-vitamin E anti-fibrotic effect involved TGF-β1 cascade inhibition. Radiother Oncol 105: 305-312, 2012. 7) Lapa C, Linz C, et al : Three-phase bone scintigraphy for imaging osteoradionecrosis of the jaw. Clin Nucl Mes 39: 21-25, 2014. 9) Robard L, Louis MY, et al : Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: Preliminary results. Eur Ann Otorthinolaryngol Head Neck Dis 131: 333-338, 2014. 24) Froom P, Elmalah I, et al : Clodronate in myelofibrosis: A case report. Am J Med Sci 323: 115-116, 2002. 16) Chiao TB and Lee AJ : Role of pentoxifylline and vitamin E in attenuation of radiation-induced fibrosis. Ann Pharmacother 39: 516-522, 2005. 29) Saarto T, Vehmanen L, et al : Ten-year follow-up of three years of oral adjuvant clodronate therapy shows significant prevention of osteoporosis in early-stage breast cancer. J Clin Oncol 26: 4289-4295, 2008. 23) Viniegra A and Goldberg H : Resolving macrophages counter osteolysis by anabolic actions on bone cells. J Dent Res 97: 1160-1169, 2018. 17) Berbee M, Fu Q, et al : Pentoxyfylline enhances the radioprotective properties of γ -tocotrienol: differential effects on the hematopoietic, gastrointestinal and vascular systems. Radiat Res 175: 297-306, 2011. 28) 米田俊之：ビスフォスフォネート製剤関連顎骨壊死の病態とそのマネージメント．日口外誌 56: 286-291, 2010. 25) Walter C, Klein M, et al : Influence of bisphosphonates on endothelial cells, fibroblasts, and osteogenic cells. Clin Oral Investig 14: 35-41, 2010. 6) Delanian S, Chatel C, et al : Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocoperol-clodronate combination (PENTOCLO) : A phase II trial. Int J Radiat Oncol Biol Phys 80: 832-839, 2011. 3) Suh JD, Blackwell KE, et al : Disease relapse after segmental resection and free flap reconstruction for mandibular osteoradionecrosis. Otolaryngol Head Neck Surg 142: 586-591, 2010. 22) Frith J and Rogers MJ : Antagonistic effects of different classes of bisphosphonates in osteoclasts and macrophages in vitro. J Bone Miner Res 18: 204-212, 2003. 19) Westbury CB and Yarnold JR : Radiation Fibrosis –Currrent clinical and therapeutic perspectives. Clin Oncol 24: 657-672, 2012. 26) Delanian S and Lefaix JL : Current management for late normal tissue injury: Radiation-induced fibrosis and necrosis. Semin Radiat Oncol 17: 99-107, 2007. 4) Marx R and Johnson R : Studies in the radiobiology of osteoradionecrosis and their clinical significance. Oral Surg Oral Med Oral Pathol 64: 379-390, 1987. 2) 青木伸二郎， 廣田, 誠， 他：放射線性下顎骨骨壊死に対する外科治療−広範囲切除前の段階的外科治療について−．口腔腫瘍 18: 7-15, 2006. 14) Okunieff P, Augutine E, et al : Pentoxifylline in the treatment of radiation-induced fibrosis. J Clin Oncol 22: 2207-2213, 2004. 21) Delanian S, Depondt J, et al : Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: A phase II trial. Head Neck 27: 114-123, 2005. 30) Rodan G and Fleisch A : Bisphosphonates: mechanism of action. J Clin Invest 97: 2692-2696, 1996. 8) Dissard A, Dang NP, et al : Efficacy of pentoxifylline-tocopherol-clodronate in mandibular osteoradionecrosis. Laryngoscope 130: 559-566, 2020. 12) de Kruif MD, Lemaire LC, et al : Prednisolone dose-dependently influences inflammation and coagulation during human endotoxemia. J Immunol 178: 1845-1851, 2007. 15) Berbee M, Fu Q, et al : Reduction of radiation-induced vascular nitrosative stress by the vitamin E analog γ -tocotrienol: evidence of a rolo for tetrahydrobiopterin. Int J Radiat Oncol Biol Phys 79: 884-891, 2011. 1) 楠川仁悟：放射線性下顎骨骨壊死の予防と治療．頭頸部癌 30: 434-438, 2004. 20) Delanian S, Porcher R, et al : Kinetics of response to long term treatment combining pentoxifylline, tocopherol in patients with superficial radiation-induced fibrosis. J Clin Oncol 23: 8570-8579, 2005. 5) Delanian S and Lefaix JL : The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol 73: 119-131, 2004. 13) Sliwa K, Woodiwiss A, et al : Therapy of ischemic cardiomyopathy with the immunomodulating agent pentoxifylline: results of a randomized study. Circulation 109: 750-755, 2004. 10) Huang CY, Hsieh RW, et al : Short- versus long-course antibiotics in osteomyelitis: A systematic review and meta-analysis. Int J Antimicrob Agents 53: 246-260, 2019. |
| References_xml | – reference: 26) Delanian S and Lefaix JL : Current management for late normal tissue injury: Radiation-induced fibrosis and necrosis. Semin Radiat Oncol 17: 99-107, 2007. – reference: 23) Viniegra A and Goldberg H : Resolving macrophages counter osteolysis by anabolic actions on bone cells. J Dent Res 97: 1160-1169, 2018. – reference: 19) Westbury CB and Yarnold JR : Radiation Fibrosis –Currrent clinical and therapeutic perspectives. Clin Oncol 24: 657-672, 2012. – reference: 24) Froom P, Elmalah I, et al : Clodronate in myelofibrosis: A case report. Am J Med Sci 323: 115-116, 2002. – reference: 3) Suh JD, Blackwell KE, et al : Disease relapse after segmental resection and free flap reconstruction for mandibular osteoradionecrosis. Otolaryngol Head Neck Surg 142: 586-591, 2010. – reference: 25) Walter C, Klein M, et al : Influence of bisphosphonates on endothelial cells, fibroblasts, and osteogenic cells. Clin Oral Investig 14: 35-41, 2010. – reference: 21) Delanian S, Depondt J, et al : Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: A phase II trial. Head Neck 27: 114-123, 2005. – reference: 16) Chiao TB and Lee AJ : Role of pentoxifylline and vitamin E in attenuation of radiation-induced fibrosis. Ann Pharmacother 39: 516-522, 2005. – reference: 28) 米田俊之：ビスフォスフォネート製剤関連顎骨壊死の病態とそのマネージメント．日口外誌 56: 286-291, 2010. – reference: 17) Berbee M, Fu Q, et al : Pentoxyfylline enhances the radioprotective properties of γ -tocotrienol: differential effects on the hematopoietic, gastrointestinal and vascular systems. Radiat Res 175: 297-306, 2011. – reference: 18) Hamama S, Gilbert-Sirieix M, et al : Radiation-induced enteropathy: molecular basis of pentoxifylline-vitamin E anti-fibrotic effect involved TGF-β1 cascade inhibition. Radiother Oncol 105: 305-312, 2012. – reference: 9) Robard L, Louis MY, et al : Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: Preliminary results. Eur Ann Otorthinolaryngol Head Neck Dis 131: 333-338, 2014. – reference: 29) Saarto T, Vehmanen L, et al : Ten-year follow-up of three years of oral adjuvant clodronate therapy shows significant prevention of osteoporosis in early-stage breast cancer. J Clin Oncol 26: 4289-4295, 2008. – reference: 14) Okunieff P, Augutine E, et al : Pentoxifylline in the treatment of radiation-induced fibrosis. J Clin Oncol 22: 2207-2213, 2004. – reference: 6) Delanian S, Chatel C, et al : Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocoperol-clodronate combination (PENTOCLO) : A phase II trial. Int J Radiat Oncol Biol Phys 80: 832-839, 2011. – reference: 15) Berbee M, Fu Q, et al : Reduction of radiation-induced vascular nitrosative stress by the vitamin E analog γ -tocotrienol: evidence of a rolo for tetrahydrobiopterin. Int J Radiat Oncol Biol Phys 79: 884-891, 2011. – reference: 7) Lapa C, Linz C, et al : Three-phase bone scintigraphy for imaging osteoradionecrosis of the jaw. Clin Nucl Mes 39: 21-25, 2014. – reference: 8) Dissard A, Dang NP, et al : Efficacy of pentoxifylline-tocopherol-clodronate in mandibular osteoradionecrosis. Laryngoscope 130: 559-566, 2020. – reference: 22) Frith J and Rogers MJ : Antagonistic effects of different classes of bisphosphonates in osteoclasts and macrophages in vitro. J Bone Miner Res 18: 204-212, 2003. – reference: 27) Oizumi T, Yamaguchi K, et al : A Strategy against the Osteonecrosis of the Jaw Associated with Nitrogen-Containing Bisphosphonates (N-BPs) : Attempts to Replace N-BPs with the Non-N-BP Etidronate. Biol Pharm Bull 39: 1549-1554, 2016. – reference: 5) Delanian S and Lefaix JL : The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol 73: 119-131, 2004. – reference: 10) Huang CY, Hsieh RW, et al : Short- versus long-course antibiotics in osteomyelitis: A systematic review and meta-analysis. Int J Antimicrob Agents 53: 246-260, 2019. – reference: 2) 青木伸二郎， 廣田, 誠， 他：放射線性下顎骨骨壊死に対する外科治療−広範囲切除前の段階的外科治療について−．口腔腫瘍 18: 7-15, 2006. – reference: 12) de Kruif MD, Lemaire LC, et al : Prednisolone dose-dependently influences inflammation and coagulation during human endotoxemia. J Immunol 178: 1845-1851, 2007. – reference: 20) Delanian S, Porcher R, et al : Kinetics of response to long term treatment combining pentoxifylline, tocopherol in patients with superficial radiation-induced fibrosis. J Clin Oncol 23: 8570-8579, 2005. – reference: 30) Rodan G and Fleisch A : Bisphosphonates: mechanism of action. J Clin Invest 97: 2692-2696, 1996. – reference: 11) Annane D, Bellissant E, et al : Corticosteroids in the treatment of severe sepsis and septic shock in adults. A systemic review. JAMA 301: 2362-2375, 2009. – reference: 4) Marx R and Johnson R : Studies in the radiobiology of osteoradionecrosis and their clinical significance. Oral Surg Oral Med Oral Pathol 64: 379-390, 1987. – reference: 13) Sliwa K, Woodiwiss A, et al : Therapy of ischemic cardiomyopathy with the immunomodulating agent pentoxifylline: results of a randomized study. Circulation 109: 750-755, 2004. – reference: 1) 楠川仁悟：放射線性下顎骨骨壊死の予防と治療．頭頸部癌 30: 434-438, 2004. |
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| Title | ペントキシフィリン, トコフェロール, クロドロネート併用療法 (PENTOCLO療法) による放射線性下顎骨壊死の治療経験 |
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