Efficacy of sequential romosozumab-denosumab therapy in patients on hemodialysis: association with bone mineral density improvement and TRACP-5b rebound.

Osteoporosis treatment in patients undergoing maintenance dialysis remains to be established. Sequential romosozumab-to-denosumab therapy improved bone mineral density and suppressed bone turnover. Shorter transition periods were associated with reduced TRACP-5b rebound, highlighting the importance of transition management and suggesting this approach as a promising option for this high-risk population.

Purpose

Patients on dialysis have a higher risk of fractures than the general population. However, osteoporosis treatment in patients on dialysis has not been established. We aimed to evaluate the efficacy of sequential therapy with romosozumab followed by denosumab and examine the clinical impact of the transition period between these agents.

Methods

In this retrospective multicenter cohort study, 34 patients on maintenance dialysis received romosozumab for 12 months followed by denosumab for 12 months. Endpoints included lumbar spine and femoral neck bone mineral density and bone turnover marker levels. The transition period between the two agents was analyzed in relation to rebound of tartrate-resistant acid phosphatase 5b level.

Results

Sequential therapy improved bone mineral density (lumbar spine: 0.797-0.997 g/cm²; femoral neck: 0.490-0.537 g/cm² p < 0.001) and the corresponding T-scores (lumbar spine: -2.1 to -0.9; femoral neck: -3.0 to -2.7; p < 0.001). Bone turnover marker levels also improved, including a marked decrease in tartrate-resistant acid phosphatase 5b levels. However, as both agents may induce hypocalcemia, we implemented an internal protocol involving strict monitoring of parathyroid hormone and serum calcium levels. Consequently, some patients required a longer interval before transitioning from romosozumab to denosumab. A longer transition period was associated with greater rebound of tartrate-resistant acid phosphatase 5b level, particularly when the interval exceeded 4 months.

Conclusion

The sequential therapy was associated with significant improvements in bone mineral density and bone turnover marker levels among patients on dialysis. Timely transition between agents appears critical to maintain suppression of bone resorption.