Romosozumab and Denosumab, Alone or Combined, in Postmenopausal Osteoporosis

Romosozumab and Denosumab, Alone or Combined, in Postmenopausal Osteoporosis: A Three-Arm Randomized Pilot Trial

Osteoporosis is a lifelong chronic condition requiring long-term management. Conventional first-line anti-resorptive therapies often yield slow BMD improvement and may plateau after years of treatment. Recent AACE/ACE guidelines recommend anabolic agents as initial therapy in patients with severe osteoporosis or very high fracture risk; however, even anabolic monotherapy may be insufficient, with many patients failing to reach a T-score ≥ -2.5. To address this unmet need, we propose a pilot study exploring cyclic treatment using romosozumab combined with denosumab, compared with standard denosumab monotherapy. In addition to monitoring biochemical bone markers and BMD, we will incorporate imaging feature extraction from X-rays and AI-based radiomic analysis to identify imaging biomarkers that may support precision treatment strategies.

This single-center, open-label, 6-month, randomized pilot trial will enroll 90 postmenopausal women with osteoporosis (T-score ≤ -2.5) at NTUH Yunlin Branch, randomized 1:1:1 into three arms: denosumab alone, romosozumab alone, or combined therapy. The primary endpoint is percent change in lumbar spine BMD at 6 months; secondary outcomes include hip and femoral neck BMD, bone turnover markers (CTX, P1NP), fracture incidence, and adverse events. Results will estimate effect size and synergy to inform future large-scale RCTs and clinical application.

Study Overview

• Status: Recruiting
• Conditions: Osteoporosis
• Intervention / Treatment: Drug: Denosumab; Drug: Romosozumab

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Shau-Huai Fu, PhD; Phone Number: +886972655734; Email: b90401045@gmail.com

Study Locations

• Taiwan
  • Taiwan
    • Douliu, Taiwan, Taiwan, 640
      • Recruiting
      • National Taiwan University Hospital Yunlin Branch
      • Contact: Shau-Huai Fu, PhD; Phone Number: 0972655734; Email: b90401045@gmail.com
      • Contact: Email: b90401045@gmail.com
      • Principal Investigator: Shau-Huai Fu, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Postmenopausal women over 50 years of age eligible for osteoporosis treatment, defined as having a bone mineral density (BMD) T-score ≤ -2.5 at the lumbar spine, total hip, or femoral neck, and who have never received osteoporosis medications (including both injectable and oral agents); or those who have used oral osteoporosis medications for no more than six months and have discontinued them for at least three months; or those who have previously received injectable osteoporosis drugs but have discontinued them for more than two years.

Exclusion Criteria:

• Age >80 years; continuous corticosteroid use; secondary osteoporosis; current use of medications affecting bone metabolism; ongoing hormone replacement therapy; metabolic bone disorders; active cancer; hypocalcemia; continued use of any osteoporosis treatment without an adequate washout period; contraindications to denosumab; and contraindications to romosozumab, such as a history of myocardial infarction or stroke within the past year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Denosumab; After study entry, a single dose of denosumab will be administered for a six-month duration.	Drug: Denosumab; After study entry, a single dose of denosumab will be administered for a six-month duration.
Active Comparator: Romosozumab; After study entry, romosozumab will be administered monthly for six months.	Drug: Romosozumab; After study entry, romosozumab will be administered monthly for six months.
Experimental: Romosozumab plus denosumab; After study entry, a single dose of denosumab will be administered. Romosozumab will be given monthly for six months.	Drug: Denosumab; After study entry, a single dose of denosumab will be administered for a six-month duration.; Drug: Romosozumab; After study entry, romosozumab will be administered monthly for six months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-Month Percentage Change in PA Spine BMD	Percentage change from baseline in PA spine BMD at 6 months	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-Month Percentage Change in femoral neck BMD	Percentage change from baseline in femoral neck BMD at 6 months	6 months
6-Month Percentage Change in total hip BMD	Percentage change from baseline in total hip BMD at 6 months	6 months
Percentage Change in Serum CTX at 6 Months	Six-month percentage change in CTX from baseline.	6 months
Percentage Change in Serum P1NP at 6 Months	Six-month percentage change in P1NP from baseline.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Bone Metabolism Markers	Changes in OPG, RANKL, and Osteocalcin	6 months
Radiographic Changes at Hip and Spine	X-ray Changes in Hip, Spine, and Pelvis	6 months
Incidence of Clinical Osteoporotic Fractures	Clinical Osteoporotic Fracture Rate	6 months
Change in Quality of Life	Change in Quality of Life, measured by EQ5D5L	6 months
Safety Outcome: Adverse Events	any Adverse Events	6 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: December 7, 2025
• First Submitted That Met QC Criteria: December 7, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 7, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: combination therapy; denosumab; romosozumab
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Nutritional and Metabolic Diseases; 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: 202509047MINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes