Verifying the effectiveness of romosozumab re-administration on bone mineral density

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.