MicroRNAs: emerging biomarkers and therapeutic targets of bone fragility in chronic kidney disease

Lay Summary Bone fragility is a very common complication in patients with chronic kidney disease. Incomplete understanding of the mechanisms and insufficient diagnostic tools lead to undertreatment of bone fragility. MicroRNAs may help to close this treatment gap, which is especially large in patients with advanced chronic kidney disease. MicroRNAs are key epigenetic regulators of bone homeostasis and show promise both as therapeutic targets and as biomarkers of bone diseases. However, more evidence is required before microRNAs are ready for clinical prime time. Bone fragility is highly prevalent, yet underdiagnosed in patients with chronic kidney disease. Incomplete understanding of the pathophysiology and limitations of current diagnostics contribute to therapeutic hesitation, if not nihilism. This narrative review addresses the question of whether microRNAs (miRNAs) may improve therapeutic decision making in osteoporosis and renal osteodystrophy. miRNAs are key epigenetic regulators of bone homeostasis and show promise as both therapeutic targets and as biomarkers, primarily of bone turnover. Experimental studies show that miRNAs are involved in several osteogenic pathways. Clinical studies exploring the usefulness of circulating miRNAs for fracture risk stratification and for guiding and monitoring therapy are few and, so far, provide inconclusive results. Likely, (pre)analytical heterogeneity contributes to these equivocal results. In conclusion, miRNAs are promising in metabolic bone disease, both as a diagnostic tool and as therapeutic targets, but not yet ready for clinical prime time.