BIOMARKERS IN THE DIAGNOSIS AND PROGNOSIS OF MEDICATION-RELATED OSTEONECROSIS OF THE JAW: A LITERATURE REVIEW

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially serious complication mainly associated with the use of antiresorptive medications, such as bisphosphonates and denosumab, as well as certain antiangiogenic agents. Characterized by the presence of exposed bone or bone that can be probed through a fistula in the maxillofacial region in patients receiving related medication therapy and without a history of radiation therapy to the jaws, the condition has a multifactorial etiopathogenesis and represents a significant diagnostic and therapeutic challenge. Although diagnosis is predominantly based on medication history, clinical evaluation, and imaging examinations, different biomarkers have been investigated as complementary tools to estimate risk, assist in disease identification, and assess prognosis. Among the biomarkers studied are those related to bone metabolism and remodeling, such as C-terminal telopeptide of type I collagen (CTX), bone formation markers, inflammatory mediators, angiogenic factors, proteins, genes, and microRNAs. However, available evidence demonstrates heterogeneous results and does not yet support the use of a single biomarker as a definitive method for predicting the development of MRONJ or establishing its diagnosis. Recent studies using molecular and bioinformatic approaches have identified different genes, proteins, and microRNAs potentially related to the pathophysiology of the disease, while more recent clinical investigations suggest that immunonutritional markers, including albumin, hemoglobin, prognostic nutritional index, and HALP score, may be associated with treatment outcomes. Therefore, biomarkers represent a promising area for improving the diagnostic and prognostic assessment of MRONJ, although their clinical application still depends on validation through prospective studies, methodological standardization, and the establishment of reference values. Thus, this literature review aims to analyze the main scientific evidence regarding biomarkers investigated in medication-related osteonecrosis of the jaw, with emphasis on their diagnostic, predictive, and prognostic potential, as well as the current limitations to their incorporation into clinical practice.