Precision Diagnostics in Bone Disease: The Potential of Circulating and Stem Cell-Associated miRNAs as Minimally Invasive Biomarkers.

Abstract

Stem cell-associated microRNAs (miRNAs) have emerged as pivotal regulators of osteogenesis, influencing lineage commitment, differentiation, and skeletal tissue homeostasis. Their dysregulation has been increasingly linked to a spectrum of osteogenic disorders, including osteoporosis, osteoarthritis, and impaired fracture healing. This narrative review synthesizes current evidence on the diagnostic potential of stem cell-associated miRNAs in bone-related pathologies. We highlight their roles in modulating osteoblast and osteoclast activity, maintaining mesenchymal stem cell fate, and orchestrating signaling pathways such as Wnt/β-catenin, bone morphogenetic protein, and Notch. Particular emphasis is placed on circulating miRNAs as minimally invasive biomarkers, offering prospects for early detection, disease stratification, and monitoring therapeutic response. Furthermore, we discuss methodological advances in miRNA profiling, challenges in clinical translation, and the need for standardized validation frameworks. By integrating molecular insights with translational perspectives, this review underscores the promise of stem cell-associated miRNAs as diagnostic tools in osteogenic disorders, while identifying critical gaps that must be addressed to enable their incorporation into precision medicine strategies.