Romosozumab and Denosumab, Alone or Combined, in Postmenopausal Osteoporosis

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• 6-Month Percentage Change in PA Spine BMD [Time frame: 6 months]

Secondary outcome measures (4)

• 6-Month Percentage Change in femoral neck BMD [Time frame: 6 months]
• 6-Month Percentage Change in total hip BMD [Time frame: 6 months]
• Percentage Change in Serum CTX at 6 Months [Time frame: 6 months]
• Percentage Change in Serum P1NP at 6 Months [Time frame: 6 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• National Taiwan University Hospital Yunlin Branch — Douliu

Identifiers

NCT: NCT07283887 · 202509047MINA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗