Osteoporosis
Conditions
Keywords
romosozumab, denosumab, combination therapy
Brief summary
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
DRUGDenosumab
After study entry, a single dose of denosumab will be administered for a six-month duration.
DRUGRomosozumab
After study entry, romosozumab will be administered monthly for six months.
Sponsors
National Taiwan University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-Month Percentage Change in PA Spine BMD | 6 months | Percentage change from baseline in PA spine BMD at 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6-Month Percentage Change in femoral neck BMD | 6 months | Percentage change from baseline in femoral neck BMD at 6 months |
| 6-Month Percentage Change in total hip BMD | 6 months | Percentage change from baseline in total hip BMD at 6 months |
| Percentage Change in Serum CTX at 6 Months | 6 months | Six-month percentage change in CTX from baseline. |
| Percentage Change in Serum P1NP at 6 Months | 6 months | Six-month percentage change in P1NP from baseline. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Bone Metabolism Markers | 6 months | Changes in OPG, RANKL, and Osteocalcin |
| Radiographic Changes at Hip and Spine | 6 months | X-ray Changes in Hip, Spine, and Pelvis |
| Incidence of Clinical Osteoporotic Fractures | 6 months | Clinical Osteoporotic Fracture Rate |
| Change in Quality of Life | 6 months | Change in Quality of Life, measured by EQ5D5L |
| Safety Outcome: Adverse Events | 6 months | any Adverse Events |
Countries
Taiwan
Contacts
Primary ContactShau-Huai Fu, PhD
Outcome results
None listed