Romosozumab and Denosumab Combination Therapy After Denosumab in Postmenopausal Osteoporosis

Transition from long-term denosumab (Dmab) to parathyroid hormone-analogs or romosozumab (Romo) might expose patients to the risk of the so-called rebound phenomenon. Adding Romo to Dmab might represent an option in patients experiencing a fracture while on Dmab. The aim of this study was to investigate the effects of the combination of Romo to Dmab in postmenopausal osteoporosis.

We did a 36-month combined retrospective and prospective study analyzed with prospective score matching. Postmenopausal women were divided into two groups: patients on Dmab who added Romo to Dmab (Dmab from baseline [M-24] to Romo initiation [M0] ➔ Dmab + Romo from M0 to M+12), and matched controls on Dmab continuing Dmab (Dmab from M-24 to M0 ➔ Dmab from M0 to M+12). Bone mineral density and bone turnover markers (CTX, P1nP) were assessed at follow-up time points.

A total of 50 women were included in the study: 25 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% confidence interval -5.2 to 11.8), indicating a nonsignificant trend toward greater improvement with combination therapy. Adding Romo to Dmab increased P1nP significantly between M0 and M+3 (+22.5 ng/mL, SE = 8.7; P = 0.028).

Ongoing treatment with Dmab did not blunt the anabolic response of Romo, indicating sustained modeling-based bone formation activity. Adding Romo in patients failing Dmab might be a valuable option.