The Clinical Potential of Circulating miRNAs as Biomarkers: Present and Future Applications for Diagnosis and Prognosis of Age-Associated Bone Diseases

Abstract

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.

Potential diagnostic value of miRNAs in peripheral blood for osteosarcoma: A meta-analysis

“…Fourth, peripheral blood miRNAs not only showed high specificity in OS, but also played a key role in the occurrence and development of other malignant tumors. Fifth, in recent years, the profile of microRNA biomarkers has been widely used in different clinical environments due to its stability, such as early detection of disease, prediction of disease, monitoring of disease progression, and response to treatment [65] . However, it seems very unlikely that microRNA would become the mainstay of diagnosis in OS patients, but it could be useful for the preliminary investigation to triage, especially in young patients with bone pain and/or indeterminate radiology findings.…”

Dysregulation of MicroRNAs in Hypertrophy and Ossification of Ligamentum Flavum: New Advances, Challenges, and Potential Directions

“…Generally, being integrated into microparticles (exosomes, microvesicles, and apoptotic bodies), or combined with specific proteins and lipoproteins make miRNAs highly stable and detectable in biological fluids (i.e., blood, serum, and plasma) (Hackl et al, 2016;Bottani et al, 2020). Furthermore, ample studies illustrated that a certain miRNA expression possessed tissue and pathology specificity in different kinds of diseases (Bartel, 2004).…”

“…Based on current evidence, a hypothetical map was depicted to briefly elaborate the potential interrelation among epigenetic regulations, genetic background, and environmental factors, and the biological importance of miRNAs in the pathomechanism of OLF/HLF (Figure 1). Besides involvement of mechanistic studies, miRNAs also possess potential applications as diagnostic biomarkers because specific miRNAs seem to have a disturbed expression in several cells and body compartments in patients with bone-related disorders (Bottani et al, 2020). Furthermore, miRNAs have a distinct advantage as novel therapeutic targets with the possibility of avoiding undesirable side effects, which may provide a novel sight into tailored therapies for HLF/OLF (Gao et al, 2020).…”

Measurements Methods for the Development of MicroRNA-Based Tests for Cancer Diagnosis

“…Several reports show that miRNAs are sensitive to physiological or pathological changes, specific to the pathology of interest, and they represent a reliable indicator of the presence of disease before clinical symptoms appear [ 53 ]. Moreover miRNAs have shown great potential as diagnostic biomarkers for neurodegenerative disorders [ 54 , 55 , 56 ], cardiovascular diseases [ 57 ], endometriosis [ 58 ], cancer (see [ 59 , 60 , 61 , 62 , 63 , 64 ] among others), and several other diseases.…”