Romosozumab and Denosumab Combination Therapy After Denosumab in Postmenopausal Osteoporosis

Background Transition from long‐term denosumab to PTH‐analogs or romosozumab might expose patients to the risk of the so‐called rebound phenomenon. Adding romosozumab to denosumab might represent an option in patients experiencing a fracture while on denosumab. The aim of this study was to investigate the effects of the combination of romosozumab to denosumab in post‐menopausal osteoporosis. Methods We did a 36‐month combined retrospective and prospective study analyzed with prospective score matching. Post‐menopausal women were divided into two groups: patients on denosumab who added romosozumab to denosumab (Dmab from M‐24 to M0 ➔ Dmab+Romo from M0 to M+12), and matched controls on denosumab continuing denosumab (Dmab from M‐24 to M0 ➔ Dmab from M0 to M+12). Bone mineral density (BMD) and bone turnover markers (CTX, P1nP) were assessed at follow‐up time points. Results A total of 50 women were included in the study. Twenty‐five patients in the Dmab ➔ Dmab+Romo group and 25 matched controls in the Dmab ➔ Dmab group. The between‐group difference at M+12 was 3.3% (95% CI ‐5.2‐11.8), indicating a non‐significant trend toward greater improvement with combination therapy. Adding romosozumab to denosumab increased P1nP significantly between M0 and M+3 (+22.5 ng/mL SE 8.7, p 0.028). Conclusion Ongoing treatment with denosumab did not blunt the anabolic response of romosozumab, indicating sustained modeling‐based bone formation activity. Adding romosozumab in patients failing denosumab might be a valuable option. image