The standard treatment for medication-related osteonecrosis of the jaw (MRONJ) is surgery. However, reports on the appropriate extent of bone resection are few. We aimed to examine the relationship between the extent of bone resection and postoperative outcomes in patients with mandibular MRONJ. The clinical and imaging findings and treatment outcomes of 206 patients (258 surgeries) with mandibular MRONJ undergoing surgery were reviewed. Imaging findings were evaluated using computed tomography (CT) to sequestrum, osteolysis, periosteal reaction, and mixed-type osteosclerosis, and determine the extent of resection. In some cases, samples were taken from within the bone, and real-time polymerase chain reaction was used to confirm the presence of bacteria and fungi. The three-year cumulative cure rate was 81.7%. Patients with malignant tumors showing no osteolysis and undergoing sequestrum removal or marginal mandibulectomy had significantly worse prognosis than those with osteoporosis showing osteolysis and undergoing segmental mandibulectomy. Furthermore, patients with residual osteolysis, periosteal reactions, and mixed-type osteosclerosis on CT were more likely to develop recurrence. Eleven patients showed no osteolysis on CT images. Patients with cancer administered with high-dose denosumab had significantly poorer prognosis. Bacteria and fungi were also detected in samples obtained from gap-type periosteal reaction and mixed-type osteosclerosis. Surgery for MRONJ requires resection of the infected bone. Aside from the osteolysis area, the gap-/irregular-type periosteal reaction and mixed-type osteosclerosis must also be included in the resection area. Methods for determining the extent of bone resection in MRONJ without osteolysis are a future challenge.

It is controversial as to whether the withdrawal of antiresorptive (AR) agents is necessary while treating medication-related osteonecrosis of the jaw (MRONJ). In this study, we investigated whether a drug holiday promoted sequestrum separation and improved the surgical outcomes of MRONJ patients with malignant tumors, who were undergoing high-dose AR therapy. In total, we included 103 MRONJ patients with malignant tumors as their primary disease who underwent surgery at Nagasaki University Hospital or Kansai Medical University Hospital from January 2009 to December 2020. We recorded the patients’ age, sex, primary disease, MRONJ stage, type and administration period of the AR agent, presence of diabetes, corticosteroid use, drug holiday period, white blood cell count, serum albumin, serum creatinine, outcomes, and computed tomography findings. The relationships between a drug holiday and sequestrum separation, and between a drug holiday and outcome, were analyzed. Drug holidays of 60, 90, and 120 days were not significant factors of sequestrum separation and did not influence patients’ surgical outcomes as per the univariate and multivariate analyses. MRONJ patients with cancer as their primary disease should be operated upon immediately and without drug holidays if their general condition permits surgery.

In patients with osteoporosis receiving antiresorptive agents (ARs), it has been widely practiced to withdraw ARs for several months before tooth extraction and during treatment if medication-related osteonecrosis of the jaw (MRONJ) develops. This study examined the effects of drug holidays on recovery from osteoclast suppression and the treatment outcomes. The relationship between the period of the drug holidays and treatment outcomes was examined retrospectively in 166 osteoporosis patients with MRONJ who received ARs. Histological examinations using hematoxylin and eosin staining and cathepsin K stains were performed to observe the recovery from osteoclast suppression in 43 patients in whom living bone was observed in the resection margins of the surgical specimens. Three-month AR drug holidays were not significantly correlated with the treatment outcomes of the 139 patients who underwent surgical treatment and the 27 who underwent conservative treatment. Of the 43 patients who underwent histological investigations, 16 had drug holidays from 7 to 678 days. Osteoclast suppression was observed in almost all patients, except in one without a drug holiday and one with a 261-day drug holiday. These findings suggest that AR drug holidays for approximately 3 months neither recover osteoclast suppression nor affect treatment outcomes.

Surgical treatment has recently been recommended as a standard therapy for medication-related osteonecrosis of the jaw (MRONJ). However, no established methods exist for determining the extent of bone resection. We aimed to compare preoperative computed tomography (CT) and magnetic resonance imaging (MRI) findings with the histopathological findings of resection materials in patients with MRONJ undergoing surgery. This was a retrospective, observational study. We analyzed the preoperative CT and MRI findings, histopathological characteristics of the resected materials, and treatment outcomes of 14 patients with MRONJ who underwent segmental mandibulectomy at Department of Oral and Maxillofacial Surgery, Nagasaki University Hospital. Areas showing osteolysis, gap-type or irregular-type periosteal reactions, and mixed-type osteosclerosis on CT were histologically confirmed to contain osteomyelitis or necrotic bone. On MRI, MRONJ lesions exhibited low signal intensity on T1-weighted images (T1WI) and variable signal intensities on T2-weighted images (T2WI). The extent of MRONJ lesions was difficult to delineate using T1WI and T2WI. In contrast, high signal intensity on short tau inversion recovery (STIR) images accurately reflected the extent of histologically confirmed osteomyelitis. Osteomyelitis is present in areas with osteolysis, gap-type or irregular-type periosteal reactions, mixed-type osteosclerosis on CT, and high STIR signal intensity on MRI features. These findings may serve as reliable references for determining the extent of bone resection during surgery.

Local infections, such as periodontal disease or apical lesions, and invasive dental procedures, such as tooth extraction, are thought to trigger medication-related osteonecrosis of the jaw (MRONJ) development. However, some cases of MRONJ develop without any obvious odontogenic triggers. We conducted a retrospective study to clarify the characteristics of non-odontogenic MRONJ. We retrospectively reviewed data of 229 patients with mandibular MRONJ who underwent surgery. Based on imaging findings, we classified MRONJ as odontogenic MRONJ involving a dental infection and non-odontogenic MRONJ with no dental involvement. Clinical and imaging findings and treatment outcomes of both types of MRONJ were compared. Overall, 193 patients were classified as having odontogenic MRONJ and 36 as having non-odontogenic MRONJ. Non-odontogenic MRONJ was slightly more common among patients with malignancies who received denosumab; however, the difference was not significant. Univariate and multivariate analyses showed that patients with MRONJ with non-odontogenic triggers had significantly poorer treatment outcomes than their counterparts. Non-odontogenic MRONJ exists without the involvement of odontogenic infection as a cause of MRONJ. Compared with that in odontogenic MRONJ, the treatment outcome in non-odontogenic MRONJ is poor. Further studies are required to clarify the true nature of non-odontogenic MRONJ.