The Comparison of Ibandronate and Zoledronic Acid After Denosumab Discontinuation

February 9, 2026 updated by: National Taiwan University Hospital

The Comparison of Ibandronate and Zoledronic Acid After Denosumab Discontinuation: A Randomized Non-inferiority Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Estimated)

52

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Fon-Yih Tsuang Clinical Associate Professor, Ph.D
  • Phone Number: 886-911138400 886-2312-3456 Ext. 265956
  • Email: k880113a@gmail.com

Study Locations

  • Taiwan
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
        • Contact:
          • Fon-Yih Tsuang Clinical Associate Professor, Ph.D
          • Phone Number: 886-911138400 886-2312-3456 Ext. 265956
          • Email: k880113a@gmail.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ibandronate group
use Ibandronate 1 year and follow-up for 2 years
Drug: Ibandronate IV
Ibandronate 3mg/3months for 12 months
Active Comparator: Zoledronic acid group
use Zoledronic acid 1 year and follow-up for 2 years
Drug: Zoledronic acid IV
Zoledronic acid 5mg/1year for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage change in bone mineral density (BMD)
Time Frame: 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.
Baseline to 24 months after treatment initiation.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in bone turnover makers (BTM) level
Time Frame: 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.
Baseline to 24 months
Change in visual Analogue Scale (VAS) score
Time Frame: 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.
Baseline to 24 months
Incidence of osteoporotic fractures
Time Frame: During the intervention period, up to 24 months.
The occurrence and anatomical sites of osteoporotic fractures will be recorded throughout the study period.
During the intervention period, up to 24 months.
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: 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.
During the intervention period, up to 24 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Collaborators

National Taiwan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 17, 2026

Primary Completion (Estimated)

March 17, 2030

Study Completion (Estimated)

September 17, 2030

Study Registration Dates

First Submitted

February 1, 2026

First Submitted That Met QC Criteria

February 9, 2026

First Posted (Actual)

February 12, 2026

Study Record Updates

Last Update Posted (Actual)

February 12, 2026

Last Update Submitted That Met QC Criteria

February 9, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202601190MINA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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