Objective <p>Postmenopausal osteoporosis (PMOP) is a bone disorder in postmenopausal women and a significant risk factor for fragility fractures. This study aims to explore the role of miR-106a-5p in the pathogenesis of PMOP and its potential as a diagnostic biomarker.</p> Methods <p>220 postmenopausal women were recruited. The levels of miR-106a-5p, PTEN, and osteogenic-related genes were quantified using qRT-PCR. The relative protein of PTEN was detected using Western blotting. ROC curve and Pearson correlation were employed to evaluate the diagnostic value and relationships between variables. To model iron accumulation, hFOB1.19 osteoblasts were treated with ferric ammonium citrate (FAC). Cell proliferation and apoptosis were assessed using the CCK-8 and flow cytometry. The target relationship was verified using dual-luciferase assays.</p> Results <p>miR-106a-5p levels were reduced, while PTEN levels were increased in PMOP. miR-106a-5p was positively correlated with bone mineral density and negatively correlated with ferritin. In the FAC-treated cells, miR-106a-5p decreased, and PTEN increased. Dual-luciferase assays confirmed that miR-106a-5p targets PTEN. Successful transfection was confirmed by observing the corresponding changes in miR-106a-5p and PTEN expression. Up-regulated miR-106a-5p increased the PTEN protein level, mRNA expression of RUNX2, OPN, and OCN, promoted cell proliferation, and decreased cell apoptosis under iron accumulation conditions. These effects were reversed by the upregulation of PTEN.</p> Conclusion <p>miR-106a-5p has the potential to diagnose osteoporosis in postmenopausal women and is linked to ferritin levels. miR-106a-5p plays a protective role in PMOP by regulating PTEN under conditions of iron accumulation, suggesting its potential as a promising biomarker for PMOP.</p>