BİFOSFONAT KULLANAN HASTALARDA İLACA BAĞLI OLARAK ÇENELERDE GÖRÜLEN OSTEONEKROZUN ETYOPATOGENEZİNDE OTOFAJİ, APOPTOZ VE NEKROZUN ROLÜ

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a multifactorial disease involving inflammation, cellular stress, and various cell death mechanisms, in addition to suppressed bone turnover. This study aimed to compare the protein and gene expression levels of Caspase-3, Beclin-1, and MLKL in saliva and gingival tissue samples from patients with bisphosphonate-related MRONJ and healthy controls. This cross-sectional, controlled, analytical study included 17 patients with MRONJ and 15 systemically healthy controls. Saliva and gingival tissue samples were obtained from all participants. Protein levels were measured using enzyme-linked immunosorbent assays, while CASP3, BECN1, and MLKL gene expression levels were evaluated using quantitative real-time polymerase chain reaction. Inflammation in gingival tissue was scored semiquantitatively, while additional histomorphological features were assessed descriptively. Caspase-3, Beclin-1, and MLKL protein levels were significantly higher in the MRONJ group in both saliva and gingival tissue, and these differences remained significant after adjustment for multiple comparisons (all p<0.001). At the gene expression level, only salivary MLKL expression was significantly increased in the MRONJ group, with a 3.01-fold change (adjusted p=0.027). No significant between-group differences were observed in salivary CASP3 or BECN1 expression or in the expression of any of the three genes in gingival tissue. Histopathological inflammation scores were significantly higher in the MRONJ group (p=0.042). Additional epithelial, connective tissue, vascular, microbial, and cell-death-related histomorphological findings showed heterogeneous distributions and were interpreted descriptively. No significant associations were found between biomarker levels and disease stage, history of zoledronic acid-containing treatment, or duration of antiresorptive therapy. These findings indicate that MRONJ is associated with a biomarker profile reflecting cellular stress and cell death, particularly at the protein level. Although saliva offers the advantage of non-invasive collection, these biomarkers require validation in larger, independent patient cohorts before they can be considered for clinical use.