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Background: The indication of denosumab for osteoporosis was expanded from second-line to first-line therapy in 2019. The aim of this study was to evaluate the efficacy of denosumab as both first- and second-line therapy in postmenopausal women with osteoporosis and osteopenia with risk factors by using the Fracture Risk Assessment Tool (FRAX). Methods: We conducted a medication use evaluation of denosumab in 98 patients who had been treated three or more times for osteoporosis or osteopenia at Chungnam National University Hospital from July 1st, 2017 to January 31st, 2020. Risk factors were identified using quantitative Ngram analyses of FRAX estimations. Patient information, including menopause status and results of bone mineral density tests (Tscore), was obtained from electronic medical records. Results: Age, body mass index (BMI), prior medication use, and T-score were identified as risk factors and were included as variables in the evaluation of denosumab use. Since no significant differences were detected between groups, denosumab is likely effective regardless of age or BMI. In addition, no significant difference was detected in T-scores following denosumab treatment, between groups who took bisphosphonates and selective estrogen receptor modulators (SERMs) with denosumab as first-line therapy for postmenopausal osteoporosis. Denosumab may, therefore, be effective as second-line therapy. Conclusion: Efficacy of denosumab was evaluated in postmenopausal women with osteoporosis. Denosumab may be used as first- and second-line therapy regardless of age, BMI, and prior use of bisphosphonates and SERMs.