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.

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.

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.