Osteoporosis, related fracture/fragility, and osteoarthritis are age-related pathologies that, over recent years, have seen increasing incidence and prevalence due to population ageing. The diagnostic approaches to these pathologies suffer from limited sensitivity and specificity, also in monitoring the disease progression or treatment. For this reason, new biomarkers are desirable for improving the management of osteoporosis and osteoarthritis patients. The non-coding RNAs, called miRNAs, are key post-transcriptional factors in bone homeostasis, and promising circulating biomarkers for pathological conditions in which to perform a biopsy can be problematic. In fact, miRNAs can easily be detected in biological fluids (i.e., blood, serum, plasma) using methods with elevated sensitivity and specificity (RT-qPCR, microarray, and NGS). However, the analytical phases required for miRNAs' evaluation still present some practical issues that limit their use in clinical practice. This review reveals miRNAs' potential as circulating biomarkers for evaluating predisposition, diagnosis, and prognosis of osteoporosis (postmenopausal or idiopathic), bone fracture/fragility, and osteoarthritis, with a focus on pre-analytical, analytical, and post-analytical protocols used for their validation and thus on their clinical applicability. These evidences may support the definition of early diagnostic tools based on circulating miRNAs for bone diseases and osteoarthritis as well as for monitoring the effects of specific treatments.
Keywords: biomarkers; circulating miRNAs; extra-analytical variability; fracture risk; miRNA signature; osteoarthritis; osteoporosis; sensitivity and specificity.