Biphasic remodeling and trabecular-cortical uncoupling in the jawbone during antiresorptive therapy and...

Although antiresorptive therapy (ART) is crucial for managing oncology-related skeletal complications, it carries a risk of medication-related osteonecrosis of the jaw (MRONJ). Because conventional radiography relies on subjective interpretation, detecting early necrotic transition remains challenging. This study aimed to establish objective, quantitative imaging criteria for jawbone remodeling and MRONJ onset by evaluating 2D fractal dimension (FD) and 3D CBCT cortical thickness under zoledronic acid or denosumab therapy.

Panoramic radiographs and CBCT scans of cancer patients receiving zoledronic acid (ZA, n = 155) or denosumab (Dmab, n = 168), and healthy controls (n = 95) were analyzed. Longitudinal FD and contralateral and lesion-site cortical thicknesses were quantified to differentiate systemic remodeling from localized necrosis.

Systemic ART induced widespread jawbone osteosclerosis, characterized by significant longitudinal FD increases (ZA: P < 0.05; Dmab: P < 0.001) and contralateral cortical thickening (P < 0.05). Conversely, MRONJ onset triggered a distinct trabecular-cortical uncoupling: a paradoxical reduction in FD (osteolysis) at the necrotic site (P < 0.05) concurrent with reactive periosteal cortical thickening, most pronounced on the lingual aspect (P < 0.001). ZA induced diffuse sclerosis, whereas Dmab-induced changes were localized to the anterior mandible.

Jawbone trabecular and cortical compartments exhibit distinct remodeling patterns during ART and osteonecrosis. Combining quantitative assessments of these compartments provides an objective, non-invasive method for monitoring skeletal burden and detecting early necrotic transitions before clinical bone exposure occurs.