Upon completing romosozumab therapy for osteoporosis, sequential treatment with other agents is required. However, for patients at high fracture risk despite such therapy, re-administration of romosozumab might be a potent subsequent option to prevent additional fractures. Currently, there is insufficient real-world clinical data verifying the efficacy of romosozumab re-administration. This study evaluated its efficacy. We enrolled 72 osteoporosis patients who remained at high risk of fractures after a 12-mo course of romosozumab, followed by sequential therapy either with bisphosphonates, denosumab, or teriparatide. Patients were re-administered another 12-mo romosozumab to assess changes in bone mineral density (BMD) and the percentages of patients achieving a T-score > -2.5 at the completion. Our result exhibited that BMD at the lumbar spine and femoral neck increased significantly through the re-administration phase (p < .001). The percentage of patients achieving a T-score > -2.5 in the lumbar spine, total hip and femoral neck increased significantly compared to before initial romosozumab therapy, with the greatest improvement seen after re-administration (all p < .001). Bone formation markers increased significantly (p < .001) during re-administration, while resorption markers showed no significant change (p = .408). The impact of prior sequential therapy was also evaluated. BMD increased significantly at all sites for patients who received bisphosphonates as sequential therapy (p < .05). After denosumab therapy, significant BMD increases were observed only in the lumbar spine (p < .01), while the total hip and femoral neck showed no significant change. After teriparatide therapy, BMD temporarily decreased during the sequential period but increased significantly after romosozumab re-administration, especially in the lumbar spine and femoral neck (both p < .001). In conclusion, romosozumab re-administration is an effective treatment. Furthermore, its efficacy varies depending on the sequential therapy used, with the highest effectiveness seen in the order of teriparatide, bisphosphonates, and denosumab.
Keywords: bone mineral density; bone turnover maker; osteoporosis; re-administration; romosozumab; sequential therapy.
The impact of romosozumab re-administration after the initial romosozumab followed by sequential therapy was verified in this study. Bone mineral density of the lumbar spine and femoral neck increased significantly with re-administration. The highest percentage of patients achieving a T-score > −2.5 throughout the observation was observed after the re-administration. When evaluating the efficacy of re-treatment classified with sequential therapy type, the highest effectiveness was seen with teriparatide, followed by bisphosphonates, and denosumab. However, bone mineral density temporarily decreased during the sequential teriparatide therapy, suggesting the choice of sequential therapy has a minimal overall impact in the entire medication period.
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