Pentosidine as a biomarker for bone fragility: Molecular mechanisms, clinical relevance, and detection strategies

Fractures pose a significant public health challenge due to their association with poor health outcomes and increased healthcare costs. While bone mineral density (BMD) remains a fundamental element of fracture risk assessment, it fails to fully capture bone quality, including strength and microstructural integrity. Advanced glycation end products, particularly pentosidine, have emerged as critical determinants of bone fragility by altering collagen cross-linking and mechanical properties. This manuscript reviews current evidence on pentosidine as a biomarker for bone quality and fracture risk. Pentosidine, a stable advanced glycation end product, accumulates in bone collagen through nonenzymatic cross-linking, impairing bone toughness and increasing fracture susceptibility. Elevated pentosidine levels correlate with age, diabetes, and chronic kidney disease, conditions strongly linked to increased fracture risk. Clinical studies demonstrate that serum, plasma, and urinary pentosidine levels independently predict fracture risk, even in the absence of significant BMD changes. Advances in detection technologies, including liquid chromatography and enzyme-linked immunosorbent assay, have improved pentosidine quantification, though challenges remain in establishing bone-specific biomarkers. Future research should focus on refining detection strategies and validating pentosidine as a clinical tool for fracture risk assessment, particularly in high-risk populations.