Factors affecting development of medication-related osteonecrosis of the jaw in cancer patients receiving high-dose bisphosphonate or denosumab therapy: Is tooth extraction a risk factor?

Sakiko Soutome,Saki Hayashida,Madoka Funahara,Souichi Yanamoto,Yuka Kojima,Yuki Sakamoto,Masahiro Umeda,Jonathan H Sherman

doi:10.1371/journal.pone.0201343

Abstract

Methods for preventing medication-related osteonecrosis of the jaw (MRONJ) in cancer patients who have received high-dose bisphosphonate (BP) or denosumab (Dmab) have not yet been established. Tooth extraction after starting medication has been believed to be a major risk factor for MRONJ, and therefore this procedure tends to be avoided. This study investigated the risk factors for MRONJ, with a special reference to the correlation between tooth extraction and development of MRONJ. One hundred and thirty-five cancer patients who were administrated high-dose BP or Dmab were enrolled in the study. Demographic factors, general condition, treatment factors, and dental findings were examined retrospectively using medical records and panoramic X-ray findings. The cumulative occurrence rate of MRONJ was calculated using the Kaplan–Meier method, and the correlation between these variables and development of MRONJ was analyzed by univariate and multivariate Cox regression analysis. MRONJ developed in 18 of 135 patients. The 1-, 2-, and 3-year cumulative occurrence rates were 8.6%, 21.5%, and 29.2%, respectively. The duration of medication before first visit to the dental unit and the presence of a tooth with clinical symptoms were significantly correlated with the development of MRONJ. The rate of MRONJ occurrence in patients who had teeth with clinical symptoms, but who did not undergo tooth extraction, became higher 2 years later than that in patients who underwent extraction of teeth with symptoms, although not significant. Early dental examination and effective preventative care to avoid infection/inflammation are important for preventing MRONJ.

Highlights

Bisphosphonate (BP) and denosumab (Dmab) are bone-modifying agents (BMA) used for managing osteoporosis, skeletal-related events in association with bone metastases from solid tumors, and multiple myeloma
Since BP-associated osteonecrosis of the jaw was first described by Marx in 2003 [1], case reports of medication-related osteonecrosis of the jaw (MRONJ) have increased
Patients with MRONJ have tended to be treated with surgical therapy [2,3,4,5,6,7,8,9] rather than with conservative therapy [10,11,12], since some systematic reviews have shown that surgery is superior to conservative therapy [13,14,15]

Summary

Introduction

Bisphosphonate (BP) and denosumab (Dmab) are bone-modifying agents (BMA) used for managing osteoporosis, skeletal-related events in association with bone metastases from solid tumors, and multiple myeloma. Since BP-associated osteonecrosis of the jaw was first described by Marx in 2003 [1], case reports of medication-related osteonecrosis of the jaw (MRONJ) have increased. Patients with MRONJ have tended to be treated with surgical therapy [2,3,4,5,6,7,8,9] rather than with conservative therapy [10,11,12], since some systematic reviews have shown that surgery is superior to conservative therapy [13,14,15]. Some authors have stated that dentoalveolar surgery, including tooth extraction, is a major risk factor for development of MRONJ [17,18,19]. Some investigators have advocated that, rather than tooth extraction per se, pre-existing inflammatory dental disease, such as periodontal disease or periapical pathology, is a risk factor for MRONJ [21]

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