International Journal of Clinical Oral and Maxillofacial Surgery

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Exacerbation of Denosumab-Related Osteonecrosis of the Jaw After Discontinuation of Denosumab: A Case Report

Received: Oct. 08, 2022    Accepted: Oct. 28, 2022    Published: Dec. 08, 2022
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Abstract

Denosumab, a bone antiresorptive agent, is used to treat patients with osteoporosis or bone metastasis. It has been reported that denosumab, like bisphosphonates, causes osteonecrosis of the jaw (ONJ). Some clinical case reports have shown that the discontinuation of denosumab ameliorates ONJ. Herein, the authors present a case in which denosumab cessation exacerbated osteonecrosis in a patient who suffered from denosumab-related osteonecrosis of the jaw (DRONJ). A 56-year-old female patient was referred to us with swelling and pain in the left buccal region. The patient had metastatic breast cancer (cT3N1M1, stage IV) and had been treated with a triplet regimen of paclitaxel, capecitabine, and bevacizumab. In addition, denosumab (Ranmark®, 120 mg) had been subcutaneously injected for 3 years. She had no history of bisphosphonate use or radiotherapy in the head and neck region. Her left mandibular second molar was extracted at a dental clinic with only slight pain. Clinical examination revealed swelling and pain in the left buccal region, bone exposure in the intraoral left mandibular region with pus discharge, limited mouth opening, and subcutaneous abscess formation with fever. After the cessation of denosumab, image inspection revealed a spreading radiolucent lesion and extensive periosteal reaction in the bilateral mandible. It should be noted that DRONJ may worsen despite denosumab holidays.

DOI 10.11648/j.ijcoms.20220802.12
Published in International Journal of Clinical Oral and Maxillofacial Surgery ( Volume 8, Issue 2, December 2022 )
Page(s) 21-24
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This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Denosumab-Related Osteonecrosis of the Jaw, Denosumab, Discontinuation, Exacerbation

References
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[2] Keaveny TM, McClung MR, Genant HK, et al. Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab. Journal of Bone and Mineral Research. Vol. 29, No. 1, 2014, pp. 158-165.
[3] Poole KE, Treece GM, Gee AH, et al. Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis. Journal of Bone and Mineral Research. Vol. 30, No. 1, 2015, pp. 46-54.
[4] Zebaze R, Libanati C, McClung MR, et al. Denosumab Reduces Cortical Porosity of the Proximal Femoral Shaft in Postmenopausal Women With Osteoporosis. Journal of Bone and Mineral Research. Vol. 31, No. 10, 2016, pp. 1827-1834.
[5] Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. Journal of Bone and Mineral Research. Vol. 30, No. 1, 2015, pp. 3-23.
[6] Lo JC, O'Ryan FS, Gordon NP, et al. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. Journal of Oral and Maxillofacial Surgery. Vol. 8, No. 2, 2010, pp. 243-253.
[7] Papapoulos S, Chapurlat R, Libanati C, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. Journal of Bone and Mineral Research. Vol. 27, No. 3, 2012, pp. 694-701.
[8] Pozzi S, Vallet S, Mukherjee S, et al. High-dose zoledronic acid impacts bone remodeling with effects on osteoblastic lineage and bone mechanical properties. Clinical Cancer Research. Vol. 15, No. 18, 2009, pp. 5829-5839.
[9] O'Halloran M, Boyd NM, Smith A. Denosumab and osteonecrosis of the jaws - the pharmacology, pathogenesis and a report of two cases. Australian Dental Journal. Vol. 59, No. 4, 2014, pp. 516-519.
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[11] Ohga N, Yamazaki Y, Tsuboi K, Kitagawa Y. Healing of osteonecrosis of the jaw (ONJ) after discontinuation of denosumab in a patient with bone metastases of colorectal cancer: a case report and hypothesis. Quintessence International. Vol. 46, No. 7, 2015, pp. 621-626.
[12] Diz P, López-Cedrún JL, Arenaz J, Scully C. Denosumab-related osteonecrosis of the jaw. Journal of the American Dental Association. Vol. 143, No. 9, 2012, pp. 981-984.
[13] Vyas S, Hameed S, Murugaraj V. Denosumab-associated osteonecrosis of the jaw--a case report. Dental Update. Vol. 41, No. 5, 2014, pp. 449-450.
[14] Saad F, Brown JE, Van Poznak C, et al. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Annals of Oncology. Vol. 23, No. 5, 2012, pp. 1341-1347.
[15] Owosho AA, Blanchard A, Levi L, et al. Osteonecrosis of the jaw in patients treated with denosumab for metastatic tumors to the bone: A series of thirteen patients. Journal of Cranio-Maxillofacial Surgery. Vol. 44, No. 3, 2016, pp. 265-270.
[16] Hoefert S, Yuan A, Munz A, et al. Clinical course and therapeutic outcomes of operatively and non-operatively managed patients with denosumab-related osteonecrosis of the jaw (DRONJ). Journal of Cranio-Maxillofacial Surgery. Vol. 45, No. 4, 2017, pp. 570-578.
[17] Aljohani S, Gaudin R, Weiser J, et al. Osteonecrosis of the jaw in patients treated with denosumab: A multicenter case series. Journal of Cranio-Maxillofacial Surgery. Vol. 46, No. 9, 2018, pp. 1515-1525.
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  • APA Style

    Masahiko Okubo, Tsuyoshi Sato. (2022). Exacerbation of Denosumab-Related Osteonecrosis of the Jaw After Discontinuation of Denosumab: A Case Report. International Journal of Clinical Oral and Maxillofacial Surgery, 8(2), 21-24. https://doi.org/10.11648/j.ijcoms.20220802.12

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    ACS Style

    Masahiko Okubo; Tsuyoshi Sato. Exacerbation of Denosumab-Related Osteonecrosis of the Jaw After Discontinuation of Denosumab: A Case Report. Int. J. Clin. Oral Maxillofac. Surg. 2022, 8(2), 21-24. doi: 10.11648/j.ijcoms.20220802.12

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    AMA Style

    Masahiko Okubo, Tsuyoshi Sato. Exacerbation of Denosumab-Related Osteonecrosis of the Jaw After Discontinuation of Denosumab: A Case Report. Int J Clin Oral Maxillofac Surg. 2022;8(2):21-24. doi: 10.11648/j.ijcoms.20220802.12

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  • @article{10.11648/j.ijcoms.20220802.12,
      author = {Masahiko Okubo and Tsuyoshi Sato},
      title = {Exacerbation of Denosumab-Related Osteonecrosis of the Jaw After Discontinuation of Denosumab: A Case Report},
      journal = {International Journal of Clinical Oral and Maxillofacial Surgery},
      volume = {8},
      number = {2},
      pages = {21-24},
      doi = {10.11648/j.ijcoms.20220802.12},
      url = {https://doi.org/10.11648/j.ijcoms.20220802.12},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.ijcoms.20220802.12},
      abstract = {Denosumab, a bone antiresorptive agent, is used to treat patients with osteoporosis or bone metastasis. It has been reported that denosumab, like bisphosphonates, causes osteonecrosis of the jaw (ONJ). Some clinical case reports have shown that the discontinuation of denosumab ameliorates ONJ. Herein, the authors present a case in which denosumab cessation exacerbated osteonecrosis in a patient who suffered from denosumab-related osteonecrosis of the jaw (DRONJ). A 56-year-old female patient was referred to us with swelling and pain in the left buccal region. The patient had metastatic breast cancer (cT3N1M1, stage IV) and had been treated with a triplet regimen of paclitaxel, capecitabine, and bevacizumab. In addition, denosumab (Ranmark®, 120 mg) had been subcutaneously injected for 3 years. She had no history of bisphosphonate use or radiotherapy in the head and neck region. Her left mandibular second molar was extracted at a dental clinic with only slight pain. Clinical examination revealed swelling and pain in the left buccal region, bone exposure in the intraoral left mandibular region with pus discharge, limited mouth opening, and subcutaneous abscess formation with fever. After the cessation of denosumab, image inspection revealed a spreading radiolucent lesion and extensive periosteal reaction in the bilateral mandible. It should be noted that DRONJ may worsen despite denosumab holidays.},
     year = {2022}
    }
    

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    AU  - Masahiko Okubo
    AU  - Tsuyoshi Sato
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    AB  - Denosumab, a bone antiresorptive agent, is used to treat patients with osteoporosis or bone metastasis. It has been reported that denosumab, like bisphosphonates, causes osteonecrosis of the jaw (ONJ). Some clinical case reports have shown that the discontinuation of denosumab ameliorates ONJ. Herein, the authors present a case in which denosumab cessation exacerbated osteonecrosis in a patient who suffered from denosumab-related osteonecrosis of the jaw (DRONJ). A 56-year-old female patient was referred to us with swelling and pain in the left buccal region. The patient had metastatic breast cancer (cT3N1M1, stage IV) and had been treated with a triplet regimen of paclitaxel, capecitabine, and bevacizumab. In addition, denosumab (Ranmark®, 120 mg) had been subcutaneously injected for 3 years. She had no history of bisphosphonate use or radiotherapy in the head and neck region. Her left mandibular second molar was extracted at a dental clinic with only slight pain. Clinical examination revealed swelling and pain in the left buccal region, bone exposure in the intraoral left mandibular region with pus discharge, limited mouth opening, and subcutaneous abscess formation with fever. After the cessation of denosumab, image inspection revealed a spreading radiolucent lesion and extensive periosteal reaction in the bilateral mandible. It should be noted that DRONJ may worsen despite denosumab holidays.
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Author Information
  • Department of Oral and Maxillofacial Surgery, Saitama Medical University, Saitama, Japan

  • Department of Oral and Maxillofacial Surgery, Saitama Medical University, Saitama, Japan

  • Section