Osteocalcin and C-terminal telopeptide of type I collagen in serum and saliva: A cross-sectional pilot study on correlations and implications for MRONJ risk stratification in women on antiresorptive medications.

Abstract

Background: Medication-related osteonecrosis of the jaw (MRONJ) lacks reliable biomarkers for early detection in patients receiving antiresorptive therapy. The objective is to evaluate serum and salivary C-terminal telopeptide of type I collagen (CTX) and osteocalcin (OC) as tools to differentiate healthy controls, MRONJ at-risk patients, and those with MRONJ clinically present.

Materials and methods: Cross-sectional pilot study of 30 females categorized into controls (n=10), MRONJ at-risk (n=9), and MRONJ clinically present (n=11). Serum and unstimulated saliva were analyzed by ELISA. Statistical analyses included ANCOVA with age as covariate, Dunn post-hoc test with Bonferroni correction, and bootstrapped ROC curves (1,000 iterations).

Results: After age adjustment, serum OC was a significant independent predictor of group status (p=0.002), as was salivary OC (p=0.045). Post-hoc analysis showed serum OC was significantly higher in the MRONJ at-risk group versus controls (Bonferroni-adjusted p=0.030) and MRONJ clinically present (adj p=0.012). Serum CTX did not reach significance after Bonferroni correction (p=0.183). Serum OC achieved the highest discriminatory performance (AUC=0.88, 95% CI: 0.70-1.00; 100% sensitivity at <4,801 pg/mL). No significant associations were found between biomarkers and medication duration or trigger type.

Conclusions: Serum OC is a promising adjunctive biomarker for MRONJ risk stratification, maintaining diagnostic significance after age adjustment. Serum-salivary correlations suggest noninvasive monitoring potential, though serum remains the more reliable measurement medium. While the proposed cutoff (<4,801 pg/mL) serves as a valuable preliminary reference, it remains exploratory and warrants external validation in larger prospective cohorts prior to clinical application.