The Comparison of Ibandronate and Zoledronic Acid After Denosumab Discontinuation

National Taiwan University

Status and phase: Not yet enrolling; Phase 4

Conditions: Osteoporosis; Postmenopausal Osteoporosis; Postmenopausal Osteopenia; Primary Osteoporosis

Treatments: Drug: Zoledronic acid IV; Drug: Ibandronate IV

Study type: Interventional

Funder types: Other

Identifiers

NCT07406685

202601190MINA

Details and patient eligibility

About

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.

Full 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.

Enrollment: 52 estimated patients

Sex: Female

Ages: 50 to 85 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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52 participants in 2 patient groups

Ibandronate group

Experimental group

Description:

use Ibandronate 1 year and follow-up for 2 years

Treatment:

Drug: Ibandronate IV

Zoledronic acid group

Active Comparator group

Description:

use Zoledronic acid 1 year and follow-up for 2 years

Treatment:

Drug: Zoledronic acid IV