TOPLINE:

In postmenopausal women with severe osteoporosis already receiving denosumab, adding romosozumab resulted in increased bone mineral density (BMD) at the lumbar spine and sustained bone formation activity.

METHODOLOGY:

• Researchers in Italy conducted a hybrid retrospective-prospective observational study to assess whether adding romosozumab to ongoing denosumab treatment improved bone-related outcomes in women with postmenopausal osteoporosis.
• They involved 50 postmenopausal women with severe osteoporosis. Women were divided into either a combination group receiving denosumab and romosozumab or a propensity score-matched group that received denosumab alone (n = 25 for both; mean age, 73.5 and 74.1 years, respectively).
• The combination group received denosumab for 24 months and continued denosumab with added romosozumab for 12 months, with subcutaneous 60 mg denosumab given first and 210 mg romosozumab given within 7 days.
• Outcomes included BMD at the lumbar spine, femoral neck, and total hip, and the bone turnover markers C-terminal telopeptide (CTX) and procollagen 1 intact N-terminal peptide (P1NP).
• Initiation of romosozumab served as the baseline for the combination group. Retrospective assessments were conducted 24 and 12 months before baseline and prospective assessments at 6 and 12 months after baseline.

TAKEAWAY:

• From baseline to 12 months, the combination group showed a 6.1% increase in lumbar spine BMD (P = .028). An overall improvement of 11.6% occurred from 24 months before to 12 months after baseline (P = .010).
• In the denosumab-alone group, BMD changes from baseline to 12 months were small and not significant at the lumbar spine, femoral neck, and total hip.
• At 12 months after baseline, the between-group difference of 3.2% in lumbar spine BMD showed a favorable trend toward combination therapy (P = .074), with no significant differences in BMD at the femoral neck or total hip.
• P1NP levels increased by 22.5 ng/mL in the combination group 3 months after baseline (P = .028), with a significant difference between groups at month 3 (P = .033). CTX levels remained suppressed and unchanged from baseline to 12 months.

IN PRACTICE:

“The findings support the combination of romosozumab and denosumab in patients with severe osteoporosis treated with long-term denosumab in whom the response to treatment is not deemed adequate,” the authors of the study wrote.

SOURCE:

This study was led by Giovanni Adami, MD, Rheumatology Unit, University of Verona in Verona, Italy. It was published online on December 1, 2025, in Arthritis & Rheumatology.

LIMITATIONS:

The study was underpowered due to its small sample size, and randomization was not feasible for ethical reasons. Fracture outcomes were not assessed, and larger cohorts were needed to evaluate this endpoint. Residual confounding remained possible because BMI and renal function were not included in the propensity score matching.

DISCLOSURES:

Several authors reported receiving advisory board honoraria, consultancy fees, speaker fees, and/or personal fees from multiple pharmaceutical and healthcare companies including Amgen, which manufactures denosumab and romosozumab.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.