Early detection of medication-related osteonecrosis of the jaw (MRONJ) in patients with metastatic breast cancer using FDG-PET/CT scans.

Background: Patients with osseous metastatic breast cancer receive bone-modifying agents (BMAs) as part of their standard care. Medication-related osteonecrosis of the jaw (MRONJ) is one of the most important toxicities of this class of drugs. MRONJ heavily impacts patients' quality of life and represents a major medical burden necessitating a discontinuation of treatment. Currently, the diagnosis of MRONJ is established upon the manifestation of clinical symptoms like exposed necrotic jawbone, pain, swelling or signs indicative of infection of the jaw. The objective of this study was to assess the potential of imaging modalities, specifically FDG-PET/CT (positron emission tomography with computed tomography) in the early detection of MRONJ. Methods: This cohort study in Austria included all patients with metastatic breast cancer who were receiving denosumab and regular PET/CTs, diagnosed with MRONJ between 2000 and 2022 at the Department of Obstetrics and Gynecology Innsbruck. For each of the patients in the study cohort, two control patients with comparable clinical characteristics were matched to serve as a control group. Control patients with metastasized breast cancer did not develop MRONJ but did receive denosumab and regular FDG-PET/CTs. Imaging data were independently assessed by two experienced nuclear medicine physicians. Findings: Baseline characteristics were well balanced. Patients received 120 mg denosumab once per month subcutaneously without de-escalation of therapy. The median time to develop MRONJ was 23 months (range 5-71, lower Quartile (Q1), upper Quartile (Q3) 16, 40 months). Nuclear medicine physicians detected jaw alterations in 91% (19/21) of MRONJ cases (sensitivity, 95% CI: 70%-98.8%) and in 29% (12/42) of controls, corresponding to a specificity of 71% (30/42; 95% CI: 55%-84%). Median lead time of imaging by demonstrating lesion in the jaw was 238 days (range 11-1118, Q1, Q3 106,494) prior to MRONJ diagnosis. In 68% (13/19) of MRONJ cases the nuclear medicine physicians were able to predict the exact tooth location of MRONJ with a deviation of no more than two teeth. Interpretation: The high sensitivity and negative predictive value of imaging for early detection of MRONJ underscore its significance for clinical practice. Given that the majority of patients receive regular PET/CTs, our results provide an excellent opportunity for early intervention when MRONJ is detected with a considerable lead time. Funding: This study received no external funding.