BACKGROUND Postmenopausal osteoporosis, a common disease among elderly women, is linked to estrogen deficiency, mechanical loading, and genotype. Circular RNAs (circRNAs) are formed through reverse splicing of the splice donor at the 3' end and the splice accepter at the 5' end in pre-mRNA and have been shown to be involved in the development of multiple diseases. Based on their high sequence conservation and stability, circRNAs may be useful biomarkers in different diseases. However, the roles of circRNAs in postmenopausal osteoporosis remain incompletely understood. MATERIAL AND METHODS Fifty-three postmenopausal women were assigned to either the postmenopausal osteoporosis group (n=28) or the control group (n=25). Reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis was performed to determine the differential expression of circRNAs between the 2 groups. Receiver-operating characteristic (ROC) curve analysis was conducted to evaluate the clinical diagnostic value of circRNA. Prediction of the binding sites between circRNA and miRNAs was conducted using miRanda and RNAhybrid. The function of the circRNA in osteoclastogenesis was determined by circRNA overexpression followed by tartrate-resistant acid phosphatase staining and RT-qPCR analysis. RESULTS Among 4 circRNAs previously identified by RNA-sequencing analysis as differentially expressed in patients with postmenopausal osteoporosis, only hsa_circ_0021739 showed a significant difference in expression between the groups and was downregulated in patients with postmenopausal osteoporosis. The hsa_circ_0021739 expression level was determined to be correlated with the lumbar vertebra, femur, and forearm T-scores. Overexpression of hsa_circ_0021739 decreased the level of hsa-miR-502-5p and inhibited the differentiation of osteoclasts. CONCLUSIONS The circRNA hsa_circ_0021739 is a potential blood biomarker for postmenopausal osteoporosis. In addition, hsa-miR-502-5p is a likely target of hsa_circ_0021739, which acts to regulate the differentiation of osteoclasts.