Background <p>Medication-related osteonecrosis of the jaw (MRONJ) can present with subtle trabecular alterations before overt radiographic or clinical signs become evident. This study evaluated the ability of fractal analysis on cone-beam computed tomography (CBCT) and panoramic radiographs (OPGs) to detect such early changes, and compared the diagnostic performance of the two imaging modalities.</p> Methods <p>This retrospective analysis included MRONJ patients with a history of intravenous zoledronic acid therapy and age- and sex-matched healthy controls, all of whom had both CBCT and OPG examinations. Fractal dimension (FD) values were calculated from 8 standardized regions of interest (ROIs) on CBCT and 6 on OPG images using ImageJ^® software. Group differences were assessed, and correlations with sex and medication duration were analyzed.</p> Results <p>A total of 54 patients (26 MRONJ, 28 controls) met the inclusion criteria and were included in the analysis. CBCT revealed significantly lower FD values in MRONJ patients compared to healthy controls, with reductions ranging from 0.02 to 0.05 in various ROIs (<i>p</i> &lt; 0.05), indicating trabecular bone alterations. OPG images, in contrast, failed to demonstrate statistically significant group differences. A significant negative correlation between FD values and medication duration was found in the mandibular corpus, tuberosity, and mental foramen regions on CBCT, but not on OPG. Sex-related differences were detected in certain ROIs, but were inconsistent across sites.</p> Conclusions <p>CBCT-based fractal analysis demonstrated markedly greater sensitivity than OPG in detecting both localized and widespread trabecular changes in MRONJ, including alterations invisible to conventional imaging. These results underscore CBCT fractal analysis as a promising noninvasive tool for early detection and monitoring of MRONJ-related bone changes.</p>