Medication-related osteonecrosis of the jaw after tooth extraction in cancer patients: a multicenter retrospective study

• Published in: Osteoporosis international Vol. 30; no. 1; pp. 231 - 239
• Main Authors: Hasegawa, T., Hayashida, S., Kondo, E., Takeda, Y., Miyamoto, H., Kawaoka, Y., Ueda, N., Iwata, E., Nakahara, H., Kobayashi, M., Soutome, S., Yamada, SI, Tojyo, I., Kojima, Y., Umeda, M., Fujita, S., Kurita, H., Shibuya, Y., Kirita, T., Komori, T.
• Format: Journal Article
• Language: English
• Published: London Springer London 01-01-2019; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Amputation; Bisphosphonate-Associated Osteonecrosis of the Jaw - etiology; Bisphosphonates; Bone cancer; Bone Density Conservation Agents - adverse effects; Cancer; Demography; Denosumab - adverse effects; Diphosphonates - adverse effects; Drug dosages; Endocrinology; Female; Humans; Immunosuppressive agents; Immunosuppressive Agents - adverse effects; Immunotherapy; Inflammation; Jaw; Male; Mandible; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Neoplasms - drug therapy; Original Article; Orthopedics; Osteonecrosis; Patients; Retrospective Studies; Rheumatology; Risk Factors; Targeted cancer therapy; Teeth; Tooth Extraction - adverse effects; Tooth Root - surgery; Bisphosphonate; Discontinuation; Drug holiday; Denosumab; MRONJ
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-018-4746-8

Summary
Root amputation, immunosuppressive therapy, mandibular tooth extraction, pre-existing inflammation, and longer duration of treatment with bone-modifying agents were significantly associated with an increased risk of medication-related osteonecrosis of the jaw. Hopeless teeth should be extracted without drug holiday before the development of inflammation in cancer patients receiving high-dose bone-modifying agents.
Introduction
No studies have comprehensively analyzed the influence of pre-existing inflammation, surgical procedure–related factors such as primary wound closure, demographic factors, and drug holiday on the incidence of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this study was to retrospectively investigate the relationships between these various factors and the development of MRONJ after tooth extraction in cancer patients receiving high-dose bone-modifying agents (BMAs) such as bisphosphonates or denosumab.
Methods
Risk factors for MRONJ after tooth extraction were evaluated with univariate and multivariate analyses. The following parameters were investigated in all patients: demographics, type and duration of BMA use, whether BMA use was discontinued before tooth extraction (drug holiday), the duration of such discontinuation, the presence of pre-existing inflammation, and whether additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed.
Results
We found that root amputation (OR = 22.62), immunosuppressive therapy (OR = 16.61), extraction of mandibular teeth (OR = 12.14), extraction of teeth with pre-existing inflammation, and longer duration (≥ 8 months) of high-dose BMA (OR = 7.85) were all significantly associated with MRONJ.
Conclusions
Tooth extraction should not necessarily be postponed in cancer patients receiving high-dose BMA. The effectiveness of a short-term drug holiday was not confirmed, as drug holidays had no significant impact on MRONJ incidence. Tooth extraction may be acceptable during high-dose BMA therapy until 8 months after initiation.