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BACKGROUND: Interferon-γ (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1) play an important role in bone immunity and are closely related to the occurrence of osteoporosis. However, few studies have reported the diagnostic value of IFN-γ and MCP-1 in osteoporosis. OBJECTIVE: To explore the predictive value of peripheral blood IFN-γ and McP-1 in postmenopausal osteoporosis. METHODS: A total of 71 subjects were collected from the Outpatient department of the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from December 2019 to January 2021 according to the prospective case-control principle, who were divided into osteoporosis group (n=35) and control group (n=36). Baseline data and levels of IFN-γ and MCP-1 were compared between the two groups. Risk factors were analyzed by binary logistics regression analysis. The correlation between the levels of IFN-γ and MCP-1 and bone mineral density and bone mineral content were analyzed. Receiver operating characteristic curve (ROC) was used to evaluate the predictive efficacy of IFN-γ and MCP-1 in postmenopausal osteoporosis. RESULTS AND CONCLUSION: There were no significant differences in age, height, body mass, body mass index and menopause time between the two groups (P > 0.05), but significant differences existed in T value, lumbar bone mineral density, lumbar bone mineral content, overall bone mineral density and overall bone mineral content between the two groups (P < 0.05). The level of IFN-γ in the osteoporosis group was significantly lower than that in the control group (P < 0.05), while the level of MCP-1 was significantly higher than that in the control group (P < 0.05). Univariate and multivariate logistic regression analyses showed that IFN-γ and MCP-1 were independent risk factors for postmenopausal osteoporosis. Receiver operating characteristic curve further confirmed that IFN-γ and MCP-1 had good predictive value for postmenopausal osteoporosis (IFN-γ AUC=0.7992, MCP-1 AUC=0.8001). The critical predictive values (IFN-γ < 1 456 ng/L, sensitivity 100%, specificity 50%; MCP-1 > 365.9 ng/L, sensitivity 85.29%, specificity 67.57%) were determined. Indeed, IFN-γ value < 1456 ng/L and MCP-1 value > 365.9 ng/L suggest that there may be bone loss in postmenopausal women. [ABSTRACT FROM AUTHOR]