Romosozumab Versus Denosumab in Glucocorticoid-induced Osteoporosis: an Extended Observation of a Randomized Controlled Trial at 48 Months

Romosozumab Versus Denosumab in Patients With Glucocorticoid-induced Osteoporosis: a 2-year Extension Study of a Randomized Controlled Trial

The investigators conducted an open-label randomized controlled trial (RCT) in chronic glucocorticoid (GC) users with moderate/high risk of fracture to compare the efficacy and tolerability of romosozumab (ROMO) for 12 months followed by denosumab (DEN) for 12 more months vs DEN for 24 months throughout. Superiority of ROMO/DEN to DEN/DEN in raising the spine bone mineral density (BMD) was demonstrated at month 12 and month 24. The present study was to report the further BMD changes at 48 months (2 year extension) for those participants who were maintained on DEN treatment.

Study Overview

• Status: Completed
• Conditions: Osteoporosis; Glucocorticoids Toxicity
• Intervention / Treatment: Drug: Romosozumab; Drug: Denosumab

Detailed Description

The investigators conducted a pilot open-label 24-month randomized controlled trial (RCT) comparing the efficacy of romosozumab (ROMO) with denosumab (DEN) in moderate/high risk adult patients using long-term GCs (defined as a daily prednisolone dose of ≥5mg/day for ≥12 months). All patients had moderate to high risk of osteoporotic fracture as evidenced by at least one of the following: (1) a personal history of fragility/vertebral fracture; (2) dual energy X-ray absorptiometry (DXA) T score ≤-2.5 [age ≥40 years] or Z scores ≤-3.0 [age <40 years] at spine, hip or femoral neck; or (3) high risk of 10-year FRAX-estimated major fracture).

Of the 70 patients enrolled, 63 completed the study. At month 12, the spine bone mineral density (BMD) increased significantly in both the ROMO and DEN groups. The spine BMD gain from month 0-12 was significantly greater in ROMO-treated patients (p<0.001). Although the hip BMD at month 12 also increased significantly in the ROMO and DEN groups, the BMD gain was not significantly different between the groups. At month 24, the spine BMD continued to increase in both the ROMO and DEN groups, and the BMD gain remained significantly greater in ROMO-treated patients.

As there are no long-term data on the sequential use of ROMO and DEN in patients with GIOP, the current 2-year extension study is planned to observe the BMD changes at the spine and the hip of patients in the two treatment groups at month 48.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • Department of Medicine, Tuen Mun Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. patients who are continued on 6-monthly subcutaneous injection of DEN in either the ROMO or DEN arms after month 24 in our original RCT
2. Those who are willing to have a repeat DXA assessment at the end of 4 years.

Exclusion Criteria:

1. patients who refuse to be maintained on denosumab after month 24;
2. patients who are maintained on other anti-osteoporotic drugs after month 24; and
3. patients in whom prednisolone is planned to be tapered or discontinued after month 24.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Romosozumab/denosumab; Romosozumab for 12 months, then denosumab for 36 months	Drug: Romosozumab; osteoporosis treatment; Other Names: Evenity (brand names); Drug: Denosumab; osteoporosis treatment; Other Names: Prolia (brand name)
Active Comparator: Denosumab/denosumab; Densoumab for 48 months	Drug: Denosumab; osteoporosis treatment; Other Names: Prolia (brand name)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in BMD at the lumbar spine	spine BMD	24 more months after RCT completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in BMD at non-dominant hip and femoral neck	hip and femoral neck BMD	24 more months after RCT completion

Collaborators and Investigators

• Sponsor: Tuen Mun Hospital
• Investigators: Principal Investigator: Chi Chiu Mok, MD, FRCP, Tuen Mun Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2024
• Primary Completion (Actual): December 15, 2025
• Study Completion (Actual): April 30, 2026

Study Registration Dates

• First Submitted: June 9, 2024
• First Submitted That Met QC Criteria: June 21, 2024
• First Posted (Actual): June 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: outcome; osteoporosis; fracture; glucocorticoids; romosozumab; denosoumab
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Wounds and Injuries; Metabolic Diseases; Bone Diseases, Metabolic; Nutritional and Metabolic Diseases; Fractures, Bone; Osteoporosis; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Denosumab; romosozumab
• Other Study ID Numbers: CIRB-2024-224-3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No