Background: Circular RNAs (circRNAs) are emerging as important regulators in human disease. The expression profile and mechanism of circRNAs in postmenopausal osteoporosis remains largely unknown. Bone morphogenetic protein 2 (BMP2) is known to play important role in inducing osteogenic differentiation. MiR-98 was reported to regulate osteogenic differentiation of human bone mesenchymal stromal cells by targeting BMP2. Aim: We aimed to analyze circRNA expression profiles in osteoporosis and explore the molecular mechanism of circRNA_0016624 and interaction between circRNA_0016624, miR-98 and BMP2 during osteogenic differentiation. Methods: RNA-seq and bioinformatics analysis was performed in postmenopausal osteoporosis patients to screen for differentially expressed circRNAs. MiRanda and TargetScan were used to detect miR-98 binding sites of circRNA_0016624 and the target relationship was confirmed by dual luciferase assay. Expression level of circRNA_0016624, miR-98 and BMP2 were measured by qRT-PCR or Western blot. ARS staining was used to observe the level of osteogenic differentiation after transfection. Results: There were 387 circRNAs were differentially expressed in osteoporosis (vertical bar fold change vertical bar > 2 and P-value < 0.01). circRNA_0016624 and BMP2 were down-regulated in osteoporosis. CircRNA_0016624 could sponge miR-98 and regulate miR-98 expression. Overexpression of circRNA_0016624 promoted the expression of BMP2 and prevented osteoporosis. Conclusion: circRNA_0016624 could sponge miR-98 and enhance BMP2 expression, thus circRNA_0016624 prevents osteoporosis and may provide a novel therapeutic strategy. (C) 2019 Elsevier Inc. All rights reserved.