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Drug holiday clinical relevance verification for antiresorptive agents in medication-related osteonecrosis cases of the jaw

  • Saki HayashidaEmail author
  • Souichi Yanamoto
  • Shigeyuki Fujita
  • Takumi Hasegawa
  • Takahide Komori
  • Yuka Kojima
  • Hironori Miyamoto
  • Yasuyuki Shibuya
  • Nobuhiro Ueda
  • Tadaaki Kirita
  • Hirokazu Nakahara
  • Mitsuyo Shinohara
  • Eiji Kondo
  • Hiroshi Kurita
  • Masahiro Umeda
Original Article
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Abstract

Treatment strategies of medication-related osteonecrosis of the jaw (MRONJ) are controversial. Recently, surgical treatment has been reported as superior to nonsurgical treatment, but the contribution discontinued antiresorptive agent use during MRONJ treatment remains unclear. This study aimed to evaluate the efficacy of drug holidays and treatment strategies in MRONJ cases. Four-hundred and twenty-seven patients with MRONJ treated at nine hospitals from 2009 to 2017 were included in this multicenter retrospective study. Multivariate Cox regression analysis showed that the primary disease (osteoporosis or malignant tumor), diabetes, serum albumin, and treatment method (surgical or nonsurgical) were significantly correlated with the cure rate. The cumulative 1-year cure rates in the surgical and nonsurgical treatment groups were 64.7% and 18.2%, respectively. However, discontinuing antiresorptive agents did not influence the treatment outcome in the cohort overall, or in 230 patients after performing propensity score matching among the discontinuation and continuation groups. When stratifying by treatment method, antiresorptive agent discontinuation significantly increased the cure rate in patients with osteoporosis who underwent nonsurgical treatment. In patients with malignant tumors undergoing nonsurgical therapy, discontinuing the antiresorptive agent was associated with a better treatment outcome, but not with statistical significance. In contrast, drug holidays showed no effect on improving outcomes in patients with both osteoporosis and malignant tumors who underwent surgical therapy. Thus, regardless of the primary disease, discontinuing antiresorptive agents during treatment for MRONJ may not be necessary and may be helpful in some cases. Future prospective trials should examine this question further.

Keywords

Discontinuing medication Medication-related osteonecrosis of the jaws Propensity score Treatment outcome 

Notes

Acknowledgements

We thank Editage (www.editage.jp) for their English language editing services.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

All authors have no conflicts of interest.

Ethical approval

Ethical approval statement of Institutional Review Board of Nagasaki University Hospital was obtained and committee's reference number was No. 16020827-2.

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Copyright information

© The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Saki Hayashida
    • 1
    Email author
  • Souichi Yanamoto
    • 1
  • Shigeyuki Fujita
    • 2
  • Takumi Hasegawa
    • 3
  • Takahide Komori
    • 3
  • Yuka Kojima
    • 4
  • Hironori Miyamoto
    • 5
  • Yasuyuki Shibuya
    • 5
  • Nobuhiro Ueda
    • 6
  • Tadaaki Kirita
    • 6
  • Hirokazu Nakahara
    • 7
  • Mitsuyo Shinohara
    • 8
  • Eiji Kondo
    • 9
  • Hiroshi Kurita
    • 9
  • Masahiro Umeda
    • 1
  1. 1.Department of Clinical Oral OncologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  2. 2.Department of Oral and Maxillofacial SurgeryWakayama Medical UniversityWakayamaJapan
  3. 3.Department of Oral and Maxillofacial SurgeryKobe University Graduate School of MedicineKobeJapan
  4. 4.Department of Dentistry and Oral SurgeryKansai Medical UniversityOsakaJapan
  5. 5.Department of Oral and Maxillofacial SurgeryNagoya City University Graduate School of Medical SciencesNagoyaJapan
  6. 6.Department of Oral and Maxillofacial SurgeryNara Medical UniversityKashiharaJapan
  7. 7.Department of Dentistry and Oral SurgeryOsaka City University Graduate School of MedicineOsakaJapan
  8. 8.Faculty of Medicine, Department of Oral and Maxillofacial SurgeryJuntendo UniversityTokyoJapan
  9. 9.Department of Dentistry and Oral SurgeryShinshu UniversityMatsumotoJapan

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