Romosozumab is a humanized monoclonal antibody that targets sclerostin and promotes bone formation while inhibiting bone resorption.¹ It is indicated for postmenopausal women with osteoporosis at high risk of fracture, or patients who have failed or are intolerant to other available osteoporosis therapies.¹ However, evidence for romosozumab in glucocorticoid-induced osteoporosis (GIOP), including vs. denosumab, remains limited.¹ At the EULAR 2026 Congress, Professor Mok, Chi-Chiu, from Tuen Mun Hospital, presented an extended observation at month 48 of a randomized controlled trial evaluating sequential romosozumab followed by denosumab vs. denosumab alone in long-term glucocorticoid (GC) users at high risk of fracture.¹

The study enrolled adults aged ≥18 years receiving oral prednisolone ≥5mg/day for ≥12 months with fragility fracture or high fracture risk and low bone density (T-score ≤-2.5 or Z-score ≤-3.0 at the hip, femoral neck, or spine).¹ Existing anti-osteoporotic treatments were discontinued, and all patients received calcium supplementation (1,200mg/day elemental calcium) and cholecalciferol (1,000IU/day).¹ Patients were randomized 1:1 to romosozumab 210mg subcutaneously (SC) every month (Q1M) for 12 doses followed by denosumab 60mg SC every 6 months (Q6M) through month 24, or denosumab 60mg SC Q6M for 4 doses.¹ Patients in both groups subsequently received denosumab 60mg Q6M for a further two years.¹ The month 48 extension assessed bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck, as well as trabecular bone score (TBS) and new or worsening fractures at month 48.¹

A total of 70 patients were randomized, with 63 completing the 24-month core study.¹ Of these, 54 patients entered the extension study, with 27 patients in each treatment group.¹ Mean age was 62.6±9.1years, 96% were women, the mean prednisolone dose was 6.6±3.5mg/day, and mean GC exposure was 10.7 years.¹ Approximately half of the patients had prior oral bisphosphonate exposure.¹ Baseline characteristics were generally comparable between treatment groups, although the romosozumab  group had numerically higher fracture risk and lower baseline BMD at some sites.¹

At month 48, sequential romosozumab-denosumab produced greater BMD gains than denosumab alone, particularly at the lumbar spine (+11.1% vs. +6.0%; p<0.01) and total hip (+6.6% vs. +3.5%; p<0.01).¹ A similar numerical pattern was seen at the femoral neck, where BMD increased by 5.7% and 3.4%, respectively.¹ Spinal TBS also demonstrated a significant within-group increase in the romosozumab-denosumab group (+3.7%; p=0.02), whereas the 1.8% increase with denosumab alone was not statistically significant (p=0.14).¹

Absolute BMD gains from baseline to month 48 were significantly greater with romosozumab-denosumab than denosumab alone at the spine (p=0.008) and total hip (p=0.01), but not the femoral neck (p=0.24).¹ Although the absolute change in TBS numerically favored romosozumab-denosumab, the between-group difference was not significant (p=0.06).¹ Exploratory analyses suggested greater BMD and TBS gains in spine and hip with sequential romosozumab-denosumab among patients without prior bisphosphonate exposure, although these findings should be interpreted cautiously given the small sample size.¹

Safety outcomes were comparable between treatment groups at month 48.¹ New or worsening vertebral fractures occurred in 22.2% of patients with  romosozumab-denosumab vs. 14.8% with denosumab alone, with no significant difference found between groups (p=0.73).¹ However, the fracture findings should be interpreted cautiously given the underpowered extension study.¹ Three new cardiovascular events (11.1%) were reported in each group.¹

In conclusion, sequential romosozumab-denosumab provided greater gains in spine and hip BMD and spinal TBS than denosumab alone at month 48 in chronic GC users at high fracture risk, suggesting benefits in both bone quantity and trabecular bone quality.¹ These findings support romosozumab-denosumab as a potential strategy to maximize BMD gains in patients receiving long-term GCs at high or very high fracture risk.¹