Clinical value of hsa_circ_0003254 in postmenopausal osteoporosis and its role in the progression of osteoporosis

Objective Circular RNAs (circRNAs) are important regulators of human disease, yet their specific mechanistic role in postmenopausal osteoporosis (PMOP) remains unclear. This study aimed to investigate the expression pattern, diagnostic value, and biological function of hsa_circ_0003254.Methods This study enrolled 207 postmenopausal females grouped into osteopenia (OPn, n = 72), osteoporosis (OP, n = 85), and healthy controls (Health, n = 50). RT-qPCR was employed to detect expression differences of hsa_circ_0003254, receiver operating characteristic (ROC) analysis, and logistic regression were utilized to assess its diagnostic value. The functional role of hsa_circ_0003254 in osteogenesis was assessed by transfecting hBMSCs with pcDNA-circ or si-circ. Western blot analysis was performed to determine the protein levels of RUNX2, ALP, and OCN.Results Analysis of the clinical cohort revealed that the expression of hsa_circ_0003254 was significantly elevated in patients with OPn and OP compared to healthy controls. Its expression level showed a significant positive correlation with both the PINP and the CTX-1. ROC analysis confirmed the diagnostic efficacy of hsa_circ_0003254 for PMOP, distinguishing healthy controls from OP patients (AUC = 0.876) and differentiating OPn from OP patients (AUC = 0.934). Multivariate logistic regression analysis confirmed hsa_circ_0003254 as a risk factor for PMOP (OR = 18.507, p < 0.001). Functionally, Osteogenic induction downregulated hsa_circ_0003254. Overexpression suppressed ALP activity, cell viability, and osteogenic gene expression (ALP, RUNX2, OCN), while knockdown enhanced all these parameters.Conclusions Hsa_circ_0003254 may serve as a potential circulating biomarker for PMOP. Its elevated expression might participate in osteoporosis progression by regulating osteogenic differentiation.