Osteoporosis, Postmenopausal Osteopenia, Postmenopausal Osteoporosis, Primary Osteoporosis
Conditions
Keywords
Postmenopausal, Osteoporosis, Osteopenia, Denosumab, Ibandronate, Zoledronic acid, Discontinuation
Brief summary
This study is a prospective, multicenter, open-label, randomized non-inferiority trial comparing intravenous ibandronate and zoledronic acid as sequential therapy after denosumab discontinuation in postmenopausal women with osteoporosis. This trial primarily targets patients with short-term denosumab exposure (less than three years) and is conducted as a preliminary investigation. The findings are expected to provide foundational evidence to inform the design of future studies assessing sequential therapies following longer-term denosumab treatment.
Detailed description
Osteoporosis has been recognized by the World Health Organization (WHO) as the second most prevalent global epidemic disease, following coronary heart disease. Untreated osteoporosis may lead to a vicious cycle of recurrent fractures, resulting in disability and even mortality. In clinical practice, antiresorptive agents are commonly used as first-line therapy. Denosumab is widely preferred due to its convenient administration and potent suppression of bone turnover. However, its antiresorptive effect is reversible; discontinuation of denosumab is associated with rebound increases in bone turnover markers (BTMs) and rapid bone mineral density (BMD) loss. Therefore, subsequent antiresorptive therapy is required to prevent fracture occurrence. Zoledronic acid has been shown to effectively suppress post-denosumab rebound bone turnover and is currently considered the standard sequential treatment following denosumab discontinuation. The objective of this study is to demonstrate that ibandronate, when used as a sequential therapy after denosumab discontinuation, provides protection comparable to zoledronic acid in patients with short-term denosumab exposure (\< 3 years). This study aims to generate preliminary clinical evidence to support future trials and to offer an alternative post-denosumab treatment strategy in clinical practice. Participants will receive one year of ibandronate or zoledronic acid therapy, initiated 6 months (± 1 week) after the last dose of denosumab, followed by a total of two years of follow-up. Eligible participants will be randomized in a 1:1 ratio, with an estimated sample size of 26 patients per group.
Interventions
DRUGIbandronate IV
Ibandronate 3mg/3months for 12 months
DRUGZoledronic acid IV
Zoledronic acid 5mg/1year for 12 months
Sponsors
National Taiwan University Hospital
National Taiwan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Postmenopausal women aged 50 to 85 years. 2. BMD T-score ≤ -1.5 and \> -3.0 at the lumbar spine or total hip. 3. Regular treatment with denosumab administered every 6 months for at least 1 year and less than 3 years (3 to 5 doses). 4. Physically and mentally capable of understanding and complying with the study protocol and follow-up. 5. Signed informed consent.
Exclusion criteria
1. History of fragility or osteoporotic fracture within the past 12 months. 2. Current or prior treatment within the past 12 months with osteoporosis medications other than denosumab, including Romosozumab, Teriparatide, Alendronate, Ibandronate, Zoledronic acid, Risedronate and Raloxifene. 3. Allergy to bisphosphonates. 4. Secondary osteoporosis. 5. Metabolic bone diseases. 6. Any autoimmune disease. 7. Requirement for long-term use of medications known to affect bone metabolism (e.g., systemic glucocorticoids or hormone therapy). 8. Primary or metastatic bone tumors. 9. Cancer patients, except for in situ carcinoma and non-melanoma skin cancer, unless fully treated and in remission for five years. 10. Hypocalcemia. 11. Vitamin D deficiency (serum 25-hydroxyvitamin D \< 25 ng/mL). 12. Renal disease (eGFR \< 35 mL/min/1.73 m²) or dialysis patients. 13. Planned dental procedures (e.g., extractions, implants) within the next year. 14. Smoking more than one pack per day (except for those who have quit for over ten years).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in bone mineral density (BMD) | Baseline to 24 months after treatment initiation. | Change in BMD at the lumbar spine, femoral neck, and total hip measured by dual-energy X-ray absorptiometry (DXA) from baseline to 24 months. Baseline is defined as the time point 6 months after the last dose of denosumab, immediately prior to initiation of sequential therapy. BMD measurements will be performed at 6, 12, 18, and 24 months after treatment initiation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in bone turnover makers (BTM) level | Baseline to 24 months | Changes in serum bone turnover markers, including procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type I collagen (CTX), will be evaluated to assess bone metabolic activity following denosumab discontinuation and sequential therapy. Measurements will be obtained at baseline and at 3, 6, 9, 12, 18, and 24 months after treatment initiation. |
| Change in visual Analogue Scale (VAS) score | Baseline to 24 months | The Visual Analogue Scale (VAS) for pain will be used to assess participants' self-reported pain intensity. The VAS score ranges from 0 to 10, higher scores indicate worse pain intensity, and lower scores indicate less pain. Pain intensity of the lower back and lower extremities will be evaluated at baseline and every 6 months during follow-up. |
| Incidence of osteoporotic fractures | During the intervention period, up to 24 months. | The occurrence and anatomical sites of osteoporotic fractures will be recorded throughout the study period. |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | During the intervention period, up to 24 months. | All AEs and SAEs will be recorded and evaluated throughout the study period to assess the safety of sequential therapy. |
Countries
Taiwan
Contacts
CONTACTFon-Yih Tsuang Clinical Associate Professor, Ph.D
Outcome results
None listed