Whether surgical or conservative treatment is the best strategy for MRONJ is a matter of debate. In a retrospective multicenter study, the authors reported the superiority of surgical therapy over conservative therapy . Therefore, at the authors' institution, surgery is indicated for patients with MRONJ whose primary disease is stable, clinical symptoms are strong, and quality of life can be improved by surgery. MRONJ, whose primary disease is cancer, is no exception. Of course, there is a difference in backgrounds between patients with malignancy and osteoporosis as the primary disease of MRONJ. Patients with malignant tumors use higher doses of antiresorptive agents and are also more likely to have lowered immunocompetence due to anticancer drugs and poor general health. The malignancy may progress rapidly. Therefore, at the authors' institution, surgery is performed after close discussion of the primary disease with the primary physician. In addition, the authors discussed preoperative drug holidays with the primary care physician, and in principle, surgery is often performed without a drug holiday.
In 2009, the AAOMS position paper recommended a 3-month drug holiday for low-dose antiresorptive agents before invasive dental surgery. However, the recommendation was modified in 2011 to operate without a drug holiday even with low-dose antiresorptive agents . However, some reports suggest that a drug holiday should be considered in patients who have received oral antiresorptive agents for less than 4 years, and others advocate a short drug holiday [2, 7, 8]. Therefore, the drug holiday for antiresorptive agents before surgery is controversial. However, these discussions refer to oral, low-dose antiresorptive agents. Antiresorptive agents used for malignant tumors are mainly administered intravenously in high doses. Hayashida et al. reported that preoperative drug holidays did not improve surgical outcomes in MRONJ patients using low- or high-dose antiresorptive agents, but there are few reports on drug holidays for malignancies .
In this study, the authors examined the benefits of preoperative drug holidays specifically in MRONJ patients with malignancy as the primary disease. Although the preoperative drug holiday depended on the progression of the cancer, we considered 2-3 months to be the maximum in consideration of the postoperative healing period. Since sequester separation by a drug holiday may facilitate surgical operation and reduce surgical invasion, we investigated whether sequester separation was accelerated by a drug holiday and whether a drug holiday improves the cure rate. In this study, only about 10% of patients had sequester separation, and a drug holiday of more than 3 months had no effect on sequester separation. A longer drug holiday may promote sequester separation. However, too long antiresorptive agent drug holidays are unacceptable for cancer patients. Although sequester separation may reduce surgical invasiveness, it was thought to be less effective after about 3 months and ultimately not beneficial for the patient.
In addition, surgery with a drug holiday for MRONJ has no effect on the outcomes. Instead, it was thought to be dependent on systemic conditions such as steroid use and low nutrition due to low albumin levels. Considering these factors, MRONJ patients with cancer as the primary disease should be operated early without a drug holiday if their general condition is relatively good, clinical symptoms are strong, and quality of life is improved.
There are some limitations in the study. First, this is a retrospective analysis using a small number of patients; therefore, it is unclear whether the results obtained can be generalized. Second, this study was a cross-sectional study and did not longitudinally observe the effects of a drug holiday. However, as far as we know, this is the first study to investigate how a preoperative drug holiday affects sequester separation and treatment outcome in patients receiving high-dose antiresorptive agent therapy. We would like to increase the number of cases in the future and conduct a more detailed examination to confirm these results.