SIRTUIN-1 IN MEDICATION-RELATED OSTEONECROSIS OF THE JAW
Bojtor Bence
Rácz Károly Konzervatív Orvostudományi Tagozat
Dr. Fekete Andrea
2026-05-04 14:00:00
Anyagcsere betegségek
Dr. Lakatos Péter
Dr. Lakatos Péter András és Dr. Kósa János Pál
Dr. Pálinkás Márton
Dr. Vereb Tamás
Dr. Nagy György
Dr. Tőke Judit
Dr. Csupor Emőke
Medication-Related Osteonecrosis of the Jaw (MRONJ) is a relatively scarce, but substantial adverse drug reaction, primarily associated with antiresorptive drugs, such as bisphosphonates and denosumab. Its exact pathophysiology is still not entirely understood; however, there is increasing evidence that certain genetic factors, particularly the SIRT1 gene, are involved in the development of the disease.
In our studies, we have successfully identified SNP rs932658 in the promoter region of the SIRT1 gene to be associated with the risk of MRONJ development. Furthermore, rs932658 is also associated with the stage improvement of patients treated with adequate therapy. Our results suggest that the rs932658 allele A is a protective factor in MRONJ, as patients with this favorable genetic variant have less chance of developing MRONJ, as well as heal better once the disease has already occurred. These findings further confirm SIRT1 as a potentially important regulator in MRONJ, as well as more broadly, in bone biology. Elucidating the exact pathomechanism of MRONJ holds great significance as it may contribute to enhanced effectiveness in the prevention and treatment of this adverse drug reaction. Furthermore, the identification of SIRT1 and SIRT1-dependent molecular pathways as potentially important biological targets in MRONJ might aid the development of innovative MRONJ therapy. After further validation in populations with heterogeneous genetic backgrounds, our results can also aid the implementation of personalized medical care in the field of antiresorptive treatment. Early risk stratification systems supplemented by genetic testing might be useful to detect patients with an elevated chance of MRONJ development; thus, we might be able to manage and prevent MRONJ better, enabling physicians to treat the often malignant primary disease more effectively.
In conclusion, our findings strengthen the evidence that genetic factors, particularly variants of the SIRT1 gene, play a meaningful role in the susceptibility and clinical course of MRONJ. The identification of the rs932658 allele A as a protective allele not only provides novel insight into the disease pathogenesis but also raises the possibility of incorporating genetic information into routine patient management. Ultimately, these advances could contribute to safer antiresorptive therapies, improved patient outcomes, and the development of more effective, targeted interventions.
