A sequential romosozumab-denosumab combination may improve lumbar BMD in glucocorticoid-induced osteoporosis

A sequential combination of 1 year of romosozumab plus 2 years of denosumab appeared superior to denosumab or bisphosphonates alone for 36 months in participants with glucocorticoid (GC)-induced osteoporosis. The findings come from a Japanese study involving patients starting glucocorticoid therapy for rheumatic diseases.

The efficacy of 12 months of romosozumab followed by 24 months of denosumab on bone mineral density (BMD) was assessed in an open-label, prospective Japanese study [1]. It included participants with rheumatic diseases who had not previously received GCs or osteoporosis treatment and who newly started prednisolone (≥15 mg/day). The participants were randomised to romosozumab-denosumab (n=11) or 36 months of either denosumab alone (n=14) or bisphosphonates alone (n=14).

The study cohort had a median age between 70.5 and 75 years and consisted predominately of women, all postmenopausal. GC dosages varied between 15 to 25 mg/day, and the median lumbar BMD was between 0.82 and 0.90 g/cm².

“The rate of BMD increase in the romosozumab-denosumab group was the greatest at all time points,” Dr Mai Kawazoe (Toho University School of Medicine, Japan) underlined. She further pointed out that lumbar spine BMD in the romosozumab-denosumab and denosumab monotherapy groups significantly increased from baseline over time. For the primary endpoint, changes in lumbar spine BMD at month 36, the median increases were 11.3% with romosozumab-denosumab, 9.4% with denosumab, and 2.1% with bisphosphonates. At the same time point, changes in total hip BMD demonstrated a similar pattern: romosozumab-denosumab 0.99%, denosumab 0.27%, and bisphosphonates -0.61%. For femoral neck BMD, a slight decline was seen at 6 months in the romosozumab-denosumab group, followed by improvement from month 12 onward.

In all groups, the bone formation marker P1NP serum levels decreased from month 3. The bone resorption marker TRACP-5b serum levels also declined across all arms. New vertebral fractures were observed in 9.1% (romosozumab-denosumab) and 14.3% (denosumab and bisphosphonates) of participants.

“We demonstrated the efficacy of romosozumab followed by denosumab, particularly in increasing BMD at the lumbar spine,” Dr Kawazoe concluded.

1. Kawazoe M, et al. Comparison of the efficacy of 12-month romosozumab followed by 24-month denosumab versus 36-month denosumab or risedronate for glucocorticoid-induced osteoporosis in patients with rheumatic diseases; a randomized prospective study. OP0049, EULAR 2025, 11–14 June, Barcelona, Spain.

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Posted on 18 June 20258 August 2025