Osteoporosis is a common metabolic bone disease in patients with diabetes, which can develop simultane-ously with Type 2 diabetes (T2D) in postmenopausal women. Bisphosphonate (BP) is administered to pa-tients with both the conditions and may cause medication-related osteonecrosis of the jaws (MRONJ). It affects the differentiation and function of osteoclasts as well as thickness of cortical bone through bone mineralization. Therefore, this study aimed to investigate the effects of T2D on osteoclast differentiation and activity as well as cortical bone formation in postmenopausal patients with MRONJ. Tissue samples were collected from 10 patients diagnosed with T2D and Stage III MRONJ in the experimental group and from 10 patients without T2D in the control group. Histological examination was conducted, and expres-sion of dendritic cell-specific transmembrane protein (DC-STAMP) and tartrate resistant acid phosphatase (TRAP) was assessed. Cortical bone formation was analyzed using CBCT images. The number of TRAP-positive osteoclasts and DC-STAMP-positive mononuclear cells were significantly less in the experi-mental group (p < 0.05). Furthermore, the thickness and ratio of cortical bone were significantly greater in the experimental group (p < 0.05). In conclusion, T2D decreased the differentiation and function of osteo-clasts, and increased cortical bone formation in postmenopausal patients with MRONJ.

Objective: To evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. Methods: multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011-December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. Results: 243 patients were included, ninety-five (44.2%) used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients treated with denosumab without CDK4/6 inhibitors the incidence of MRONJ and mean time to the occurrence of MRONJ was 6.6% (8/120) and 16.8 months (SD 7.8) respectively. In patients treated with denosumab and CDK4/6 inhibitor 13.7% (13/95) and 15.4 month (SD 8.7) respectively. The difference in the incidence was not significant (p=0.085). Conclusion: it suggest that the incidence of MRONJ in patients with metastatic breast cancer treated with denosumab was higher and the onset of MRONJ occurred earlier in the presence of CDK4/6 inhibitors. Although the difference was not significant, given that the use of this combination is very common in routine clinical practice, it would be advisable to carry out larger prospective studies to clarify the risk of this association.