Osteoporosis International

, Volume 28, Issue 8, pp 2465–2473 | Cite as

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?

  • T. HasegawaEmail author
  • A. Kawakita
  • N. Ueda
  • R. Funahara
  • A. Tachibana
  • M. Kobayashi
  • E. Kondou
  • D. Takeda
  • Y. Kojima
  • S. Sato
  • S. Yanamoto
  • H. Komatsubara
  • M. Umeda
  • T. Kirita
  • H. Kurita
  • Y. Shibuya
  • T. Komori
  • Japanese Study Group of Cooperative Dentistry with Medicine (JCDM)
Original Article



Root amputation, extraction of a single tooth, bone loss or severe tooth mobility, and an unclosed wound were significantly associated with increased risk of developing medication-related osteonecrosis of the jaw (MRONJ). We recommend a minimally traumatic extraction technique, removal of any bone edges, and mucosal wound closure as standard procedures in patients receiving bisphosphonates.


Osteonecrosis of the jaws can occur following tooth extraction in patients receiving bisphosphonate drugs. Various strategies for minimizing the risk of MRONJ have been advanced, but no studies have comprehensively analyzed the efficacy of factors such as primary wound closure, demographics, and drug holidays in reducing its incidence. The purpose of this study was to retrospectively investigate the relationships between these various risk factors after tooth extraction in patients receiving oral bisphosphonate therapy.


Risk factors for MRONJ after tooth extraction were evaluated using univariate and multivariate analysis. All patients were investigated with regard to demographics; type and duration of oral bisphosphonate use; whether they underwent a discontinuation of oral bisphosphonates before tooth extraction (drug holiday), and the duration of such discontinuation; and whether any additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed.


We found that root amputation (OR = 6.64), extraction of a single tooth (OR = 3.70), bone loss or severe tooth mobility (OR = 3.60), and an unclosed wound (OR = 2.51) were significantly associated with increased risk of developing MRONJ.


We recommend a minimally traumatic extraction technique, removal of any bone edges, and mucosal wound closure as standard procedures in patients receiving bisphosphonates. We find no evidence supporting the efficacy of a pre-extraction short-term drug holiday from oral bisphosphonates in reducing the risk of MRONJ.


Antibiotics administration BRONJ Discontinuation Primary closure Surgical procedure 



We received no individual, institutional, or departmental funding from external sources.

Compliance with ethical standards

This study was approved by the institutional review board of Kobe University Graduate School of Medicine (authorization number 1900) and by the Institutional Review Boards of the respective hospitals.

Conflicts of interest



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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2017

Authors and Affiliations

  • T. Hasegawa
    • 1
    Email author
  • A. Kawakita
    • 2
  • N. Ueda
    • 3
  • R. Funahara
    • 1
  • A. Tachibana
    • 4
  • M. Kobayashi
    • 5
  • E. Kondou
    • 6
  • D. Takeda
    • 7
  • Y. Kojima
    • 8
  • S. Sato
    • 9
  • S. Yanamoto
    • 2
  • H. Komatsubara
    • 7
  • M. Umeda
    • 2
  • T. Kirita
    • 3
  • H. Kurita
    • 6
  • Y. Shibuya
    • 9
  • T. Komori
    • 1
  • Japanese Study Group of Cooperative Dentistry with Medicine (JCDM)
  1. 1.Department of Oral and Maxillofacial SurgeryKobe University Graduate School of MedicineKobeJapan
  2. 2.Department of Clinical Oral OncologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  3. 3.Department of Oral and Maxillofacial SurgeryNara Medical UniversityNaraJapan
  4. 4.Department of Oral and Maxillofacial SurgeryKakogawa Central City HospitalKakogawaJapan
  5. 5.Department of Oral and Maxillofacial SurgeryShin-Suma General HospitalKobeJapan
  6. 6.Department of Dentistry and Oral SurgeryShinshu University School of MedicineMatsumotoJapan
  7. 7.Department of Oral and Maxillofacial SurgeryKobe Central HospitalKobeJapan
  8. 8.Department of Dentistry and Oral SurgeryKansai Medical UniversityHirakataJapan
  9. 9.Department of Oral Maxillofacial SurgeryNagoya City University Graduate School of Medical SciencesNagoyaJapan

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