Circulating miRNAs in bone health and disease

microRNAs have evolved as important regulators of multiple biological pathways essential for bone homeostasis, and microRNA research has furthered our understanding of the mechanisms underlying bone health and disease. This knowledge, together with the finding that active or passive release of microRNAs from cells into the extracellular space enables minimal-invasive detection in biofluids (circulating miRNAs), motivated researchers to explore microRNAs as biomarkers in several pathologic conditions, including bone diseases. Thus, exploratory studies in cohorts representing different types of bone diseases have been performed. In this review, we first summarize important molecular basics of microRNA function and release and provide recommendations for best (pre-)analytical practices and documentation standards for circulating microRNA research required for generating high quality data and ensuring reproducibility of results. Secondly, we review how the genesis of bone-derived circulating microRNAs via release from osteoblasts and osteoclasts could contribute to the communication between these cells. Lastly, we summarize evidence from clinical research studies that have investigated the clinical utility of microRNAs as biomarkers in musculoskeletal disorders. While previous reviews have mainly focused on diagnosis of primary osteoporosis, we have also included studies exploring the utility of circulating microRNAs in monitoring anti-osteoporotic treatment and for diagnosis of other types of bone diseases, such as diabetic osteopathy, bone degradation in inflammatory diseases, and monogenetic bone diseases.

Automated summary

microRNAs play crucial roles in regulating biological pathways essential for bone homeostasis, and their release into extracellular space has enabled researchers to explore them as biomarkers in various pathologic conditions, including bone diseases. Studies have shown promising potential for the clinical utility of microRNAs as biomarkers in musculoskeletal disorders beyond just primary osteoporosis diagnosis.