Background and Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive therapy. Although several local and systemic risk factors have been documented, the role of metabolic biomarkers and their relationship with clinical characteristics remains insufficiently investigated. The aim of the present study was to evaluate the relationships between antiresorptive therapy, serum vitamin D levels, demographic characteristics, and lesion location in patients diagnosed with MRONJ. Materials and Methods: This retrospective study included 72 patients diagnosed with MRONJ, divided into three groups according to the antiresorptive therapy administered: zoledronic acid (n = 30), denosumab (n = 22), and oral bisphosphonates (n = 20). Clinical and demographic data, including age, sex, smoking status, serum vitamin D levels, number of extracted teeth, lesion location (mandibular versus maxillary), and associated comorbidities, were obtained from medical records. Statistical analysis was performed using Welch’s ANOVA, Welch’s t-test, chi-square, Fisher’s exact, and Pearson and Spearman correlation analyses. Results: No significant differences in serum vitamin D levels were observed among the three antiresorptive therapy groups. However, patients with mandibular MRONJ had significantly lower serum vitamin D levels than those with maxillary involvement (p = 0.046). Lower serum vitamin D levels were independently associated with mandibular MRONJ after multivariable adjustment. Female sex and thyroid disease were more frequent in the oral bisphosphonate group. Additionally, patient age was moderately positively correlated with the number of extracted teeth (r = 0.440, p < 0.001). Conclusions: This retrospective study identified a possible association between lower serum vitamin D levels and mandibular MRONJ. Given the observational design of the study, these findings should be interpreted with caution and require confirmation in larger prospective studies.

The anti-apoptotic Bcl-2 protein family, frequently upregulated in a wide range of cancers, contributes to tumor persistence and therapeutic resistance, making these proteins attractive targets for structure-based inhibitor development. Betulinic acid-derived hybrids represent promising scaffolds for apoptosis-oriented anticancer drug discovery due to their reported antiproliferative and pro-apoptotic properties. In this study, a virtual library of 152 betulinic acid-derived hybrids was screened against Bcl-2 and Bcl-XL. This molecular docking study using AutoDock Vina identified BA–Celastrol and BA–Proanthocyanidin B2 as top-ranked ligands, with docking scores ranging from −13.00 to −8.7 kcal/mol. Both compounds were further analyzed by 100 ns molecular dynamics simulation runs, which revealed system-dependent ligand behavior rather than uniform preservation of the initial docked pose across all complexes. BA–Celastrol showed a more compact internal ligand conformation in the ligand property and RMSF analyses, whereas BA–Proanthocyanidin B2 showed greater intramolecular flexibility and conformational adaptability. Ligand displacement relative to the protein differed between targets, with BA–Proanthocyanidin B2 showing a more retained profile in the Bcl-XL model and BA–Celastrol showing more moderate positional behavior in the Bcl-2 model. MM-GBSA calculations resulted in free energy values ranging from −4.95 to −31.82 kcal/mol, indicating protein-dependent energetic differences across the investigated systems. Based on docking performance, molecular dynamics stability, and energetic data, both hybrids were ranked as computational candidates for further exploration against Bcl-2 family targets. The present findings, although confined to computational analysis, underscore the need for prioritizing betulinic acid-based hybrids for subsequent experimental evaluation.

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) may differ in clinical presentation and severity according to the indication for antiresorptive therapy. This study compared patients with MRONJ treated for an oncologic indication or osteoporosis and evaluated factors associated with advanced disease, defined as American Association of Oral and Maxillofacial Surgeons (AAOMS) stages II and III. Methods: This retrospective observational study included 119 patients with MRONJ, comprising 73 patients with an oncologic indication and 46 treated for osteoporosis. Demographic, clinical, treatment-related, and selected biochemical data were collected from medical records. MRONJ severity was classified according to the AAOMS staging system. Between-group differences were assessed using non-parametric and categorical tests, and multivariable logistic regression was used to examine associations with advanced MRONJ after adjustment for selected covariates. Results: Patients with an oncologic indication were younger and had a shorter duration of antiresorptive therapy than those treated for osteoporosis. The distribution of AAOMS stages differed between groups (p = 0.001). Stage III disease was more frequent in the oncologic group than in the osteoporosis group (32.9% vs. 8.7%), whereas stage II frequencies were similar (43.8% vs. 41.3%). Advanced MRONJ was also more frequent in the oncologic group (76.7% vs. 50.0%; p = 0.003). In the multivariable model, older age (OR, 1.16; 95% CI, 1.06–1.27; p = 0.001) and diabetes mellitus (OR, 8.88; 95% CI, 2.29–34.50; p = 0.002) were associated with higher odds of advanced MRONJ. Compared with oncologic patients, those treated for osteoporosis had lower adjusted odds of advanced disease (OR, 0.14; 95% CI, 0.05–0.44; p < 0.001). No statistically significant association between recorded treatment duration and advanced MRONJ was detected in the sensitivity analysis. Conclusions: MRONJ severity differed between patients treated for an oncologic indication and those treated for osteoporosis, with the difference particularly pronounced for stage III disease. These findings should be interpreted in the context of differences in antiresorptive treatment regimens and do not establish an independent causal effect of treatment indication.