Risk factors for developing medication-related osteonecrosis of the jaw when preserving the tooth that can be a source of infection in cancer patients receiving high-dose antiresorptive agents: a retrospective study.

PURPOSE: To retrospectively investigate whether apical lesion, alveolar bone loss, probing pocket depth, or local infectious symptoms were associated with the onset of medication-related osteonecrosis of the jaw (MRONJ) in patients treated with high-dose antiresorptive agents who did not undergo tooth extraction. METHODS: The study included 92 patients receiving high-dose antiresorptive agent therapy who had teeth with apical lesion ≧ 3 mm, alveolar bone loss ≧ 1/2, probing pocket depth ≧ 4 mm, or local infection symptoms such as swelling, pain, and pus discharge, but did not undergo tooth extraction. Univariate and multivariate Cox regression analyses were performed to determine the relationship between each variable and MRONJ onset. RESULTS: MRONJ developed in 15 of 92 patients (35 of 404 teeth) from 74 to 1883 days (median, 383 days) after the first visit. Multiple Cox regression analysis revealed that a lower number of teeth, diabetes, increased leukocyte count, administration of antiresorptive agents for 180 days or more, local infection symptoms, apical lesion ≧ 3 mm, and probing pocket depth ≧ 4 mm were significantly correlated with the development of MRONJ. CONCLUSION: It is recommended that teeth with apical lesion ≧ 3 mm, probing pocket depth ≧ 4 mm, or local infection symptoms are extracted before or as early as possible after beginning of medication in cancer patients receiving high-dose antiresorptive agent therapy to prevent the development of MRONJ.

Risk factors for the development of medication-related osteonecrosis of the jaw and effects of tooth extraction with local infection.

Background/purpose: Tooth extraction has been avoided in patients receiving antiresorptive agent (ARA) therapy. This study aimed to investigate dental findings associated with medication-related osteonecrosis of the jaw (MRONJ) development in patients. Materials and methods: First, in patients treated with high-dose ARAs, the relationship between dental findings and MRONJ development was examined. Next, in patients with MRONJ undergoing surgery, the relationship between dental findings and MRONJ occurring at a site distant from the initial site was examined. Results: MRONJ occurred in 13 of 172 patients (80 of 3725 teeth) during observation. Multiple tooth loss, periodontal ligament space enlargement, alveolar bone loss, periapical osteosclerosis, and local infection symptoms were associated with MRONJ development. Tooth extraction significantly reduced MRONJ development. Regarding other-site recurrence, new MRONJ developed at other sites in 54 of 357 patients with MRONJ (171 of 5038 teeth). Multiple tooth loss, apical lesions, periodontal ligament space enlargement, and periapical osteosclerosis were significantly associated with MRONJ development. In patients with malignant tumors, tooth extraction significantly reduced the subsequent incidence of MRONJ, while in patients with osteoporosis, there was no difference in the incidence of MRONJ between patients with and without tooth extraction. Conclusion: MRONJ was more likely to develop from teeth with local infections. Extraction of teeth with local infection in patients with malignancy may be more effective than tooth preservation in preventing MRONJ.

Bone resection methods in medication-related osteonecrosis of the jaw in the mandible: An investigation of 206 patients undergoing surgical treatment.

Background /purpose: 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. Materials and methods: 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. Results: 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. Conclusion: 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.

Ineffectiveness of Antiresorptive Agent Drug Holidays in Osteoporosis Patients for Treatment of Medication-Related Osteonecrosis of the Jaw: Consideration from Immunohistological Observation of Osteoclast Suppression and Treatment Outcomes.

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.

Relationship between Drug Holidays of Antiresorptive Agents and Surgical Outcomes in Cancer Patients with Medication-Related Osteonecrosis of the Jaw.

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.