MicroRNAs as potential biopredictors for premenopausal osteoporosis: a biochemical and molecular study

Abstract

Background: Circulating micro-RNAs have been proposed as a new type of biomarker in several diseases, particularly those related to bone health. They have shown great potential due to their feasibility and simplicity of measurement in all body fluids, especially urine, plasma, and serum.

Aim: This study aimed to evaluate the expression of a set of mRNAs, namely miR-21, miR-24, mir-100, miR-24a, miR-103-3p, and miR-142-3p. Their proposed roles in the progression of osteoporosis were identified using a real-time polymerase chain reaction (RT-PCR) analysis in premenopausal women. In addition, their correlations with osteocalcin (OC), bone-specific alkaline phosphatase (BAP), and deoxypyridinoline (DPD) bone markers were explored.

Methods: A total of 85 healthy premenopausal women aged 25-50 years old were included in this study. Based on a DXA scan (Z-score) analysis and calcaneus broadband ultrasound attenuation scores (c-BUAs), measured via quantitative ultrasound (QUS), the subjects were classified into three groups: normal group (n = 25), osteopenia (n = 30), and osteoporosis (n = 30). Real-time-PCR and immunoassay analyses were performed to determine miRNA expression levels and serum OC, s-BAP, and DPD, respectively, as biomarkers of bone health.

Results: Among the identified miRNAs, only miR-21, miR-24, and mir-100 were significantly upregulated and increased in the serum of patients with osteopenia and osteoporosis, and miR-24a, miR-103-3p, and miR-142-3p were downregulated and significantly decreased in osteoporosis. Both upregulated and downregulated miRNAs were significantly correlated with BMD, c-BUA, OC, s-BAP, and DPD.

Conclusion: A group of circulating miRNAs was shown to be closely correlated with the parameters BMD, c-BUA, OC, s-BAP, and DPD, which are traditionally used for bone-health measurements. They could be identified as non-invasive biomarkers in premenopausal patients with osteoporosis. More studies with large sample sizes are recommended to estimate the mechanistic role of miRNAs in osteoporosis pathogenesis and to provide evidence for the use of these miRNAs as a non-invasive method of diagnosing clinical osteoporosis, especially in premenopausal patients.

Keywords: BMD; MicroRNAs; Osteoporosis; QUS; Serum bone markers; c-BUA.