Background/Purpose: To compare the efficacy and safety of romozosumab (ROMO) and denosumab (DEN) in high-risk patients treated with glucocorticoids (GCs).

Methods: Adult patients (≥18 years) who were receiving prednisolone ≥5mg/day for ≥12 months and had moderate/high risk of osteoporotic fracture (history of fracture, DEXA T score ≤-2.5 [age ≥40 years] or Z scores ≤-3.0 [age < 40 years] or high 10-year major fracture risk by FRAX) were included. Participants were randomized to receive either ROMO (210mg SC monthly) or DEN (60mg SC every 6 months) for 12 months, followed by DEN for 2 more 6-month doses in both arms. The primary efficacy end point was the change in bone mineral density (BMD) at the lumbar spine from baseline to month 12.Secondary end points included BMD change at the non-dominant hip and femoral neck at month 12, change in bone turnover markers, new vertebral fractures, change in BMD at the hip and spine at month 24 and adverse events (AEs).

Results: 70 patients were recruited and 63(90%) completed the study (age 62.6±9.1 years; 96% women; 35 each assigned to ROMO or DEN).The mean prednisolone dose at entry was 6.6±3.5mg/day. Osteoporosis at spine/hip/femoral neck and a history of fragility fracture was present in 34(48.6%) and 35(50%) patients, respectively. Oral bisphosphonates were being used in 33(47%) patients prior to first dose of the study drugs. While the baseline demographics and osteoporosis risk factors were not significantly different between the two groups, ROMO-treated patients had lower hip/femoral neck BMD and serum vitamin D3 levels than those treated with DEN. At month 12, a significant increase in spine BMD was observed in both the ROMO (+7.3±4.5%; p< 0.001) and DEN (+2.3±3.1%; p< 0.001) groups of patients. The inter-group difference in spine BMD at month 12 was statistically significant after adjustment for baseline BMD values, age, sex, osteoporosis risk factors and the cumulative prednisolone doses in 12 months (p < 0.001).The corresponding increase in hip BMD were +1.6%±3.3% (p=0.01) in the ROMO group and +1.6%±2.6% (p=0.003) in the DEN group. No significant inter-group difference in hip BMD was observed after adjustment for the same factors. The increase in femoral neck BMD from baseline to 12m was not significant in both groups. In DEN-treated patients, both serum CTX (-34.7±54.8%; p=0.002) and P1NP (-35.1±43.3%; p< 0.001) dropped significantly from baseline to 12m.However, in the ROMO group, a non-significant drop in CTX (-18.1±76.9%; p=0.18) but increase in P1NP (+1.7±70.3%; p=0.89) was observed. Only one new vertebral fracture developed in the ROMO group at 12m.The commonest AE was self-limiting injection site pain/redness, which was significantly more common in ROMO-treated patients. Post-injection musculoskeletal pain was reported in 2 and 3 patients in the ROMO and DEN group of patients, respectively. Mild hypocalcemia and hypercalcemia were observed in 2 DEN-treated patients. No serious AEs were reported. Complete 24-month data are pending in September 2023.

Conclusion: Romosozumab was superior to denosumab in raising the spine BMD at month 12 in chronic GC users with high fracture risk. Romosozumab may offer a new treatment option for GIOP in high-risk patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/romosozumab-versus-denosumab-in-high-risk-patients-treated-with-glucocorticoids-interim-12-month-results-from-a-pilot-randomized-controlled-trial/