Circulating miR-19b in Serum Exosomes: A Novel Biomarker for Estrogen-Associated Osteoporosis.

Introduction: Osteoporosis, a significant health concern among postmenopausal women, is influenced by estrogen deficiency, which affects bone metabolism. Current diagnostic methods, such as dual-energy X-ray absorptiometry (DXA), have limitations in sensitivity, necessitating the identification of novel biomarkers for early diagnosis. This study investigates the role of circulating exosomal miR-19b as a potential biomarker for estrogen-associated osteoporosis. Methods: We analyzed the expression of miR-19b in MC3T3-E1 preosteoblast cells treated with 10 pM estradiol and assessed its antagonistic effects using 10 nM anastrozole. Serum exosomes were isolated from premenopausal (PR-M) and postmenopausal (PT-M) women using microfluidics-based extracellular vesicle (EV) isolation. Exosomal miR-19b expression was quantified using qRT-PCR, and its correlation with age, estrogen levels, and osteoporosis risk was evaluated. Characterization of exosomes was performed using transmission electron microscopy (TEM) and tunable resistive pulse sensing (TRPS), while protein markers CD9, CD63, and β-actin were confirmed through Western blot analysis. Results: Our findings demonstrate that estrogen downregulates exosomal miR-19b expression, with a significant difference observed between the PR-M and PT-M groups. Receiver operating characteristic (ROC) analysis revealed that miR-19b effectively differentiates between these groups, with an area under the curve (AUC) of 0.9911. Pearson correlation analysis further confirmed the strong association between miR-19b expression, estrogen levels, and age. Additionally, miR-19b inhibition was found to regulate IGF-1 expression, influencing bone cell differentiation and osteoporosis progression. Conclusion: This study establishes exosomal miR-19b as a novel biomarker for estrogen-related osteoporosis, providing a foundation for early diagnosis and therapeutic targeting. Our findings highlight the potential of exosomal miRNAs in advancing precision medicine for osteoporosis management.