BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is characterized by lipid accumulation in hepatocytes and is closely associated with oxidative stress. Increasing clinical evidence indicates that MAFLD is linked to bone metabolic disorders, including osteoporosis. Recent studies indicate that the expression profiles of liver circular RNAs (circRNAs) are altered in MAFLD. However, the effects of these changes on bone metabolism remain poorly understood. AIM: To investigate the effects and mechanism of differently expressed circRNAs secreted by the liver on osteogenic differentiation in MAFLD. METHODS: RNA sequencing was performed to identify highly expressed circRNAs in the liver, validated by quantitative real-time reverse transcription polymerase chain reaction, and localized using fluorescence RESULTS: CircSOD2 was significantly upregulated in liver tissues and primary hepatocytes from subjects with MAFLD. CircSOD2 was induced by oxidative stress and attenuated by antioxidants in the mouse model. In addition, circSOD2 was delivered from hepatocytes to bone marrow mesenchymal stem cells (BMSCs). Furthermore, circSOD2 inhibited the osteogenic differentiation of BMSCs and CONCLUSION: This study provides a novel mechanism underlying the liver-bone crosstalk, demonstrating that circSOD2 upregulation in hepatocytes, induced by oxidative stress, inhibits osteogenic differentiation of BMSCs by sponging miR-29b. These findings offer a better understanding of the relationship between MAFLD and osteoporosis.