Postmenopausal OsteoporosisPhase 4NCT07406685
The Comparison of Ibandronate and Zoledronic Acid After Denosumab Discontinuation
A Phase 4 study testing Ibandronate IV and Zoledronic acid IV in people with Postmenopausal Osteoporosis and Postmenopausal Osteopenia, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 85 years, women only
- Conditions the study is for
- Postmenopausal Osteoporosis, Postmenopausal Osteopenia, Primary Osteoporosis
- What is being tested?
- Ibandronate IV and Zoledronic acid IV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteTaiwan
- Study dates
- 20 Aug 2026to 31 Oct 2030
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal women aged 50 to 85 years.
- BMD T-score ≤ -1.5 and > -3.0 at the lumbar spine or total hip.
- Regular treatment with denosumab administered every 6 months for at least 1 year and less than 3 years (3 to 5 doses).
- Physically and mentally capable of understanding and complying with the study protocol and follow-up.
- Signed informed consent.
Who cannot join
- History of fragility or osteoporotic fracture within the past 12 months.
- 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.
- Allergy to bisphosphonates.
- Secondary osteoporosis.
- Metabolic bone diseases.
- Any autoimmune disease.
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- Requirement for long-term use of medications known to affect bone metabolism (e.g., systemic glucocorticoids or hormone therapy).
- Primary or metastatic bone tumors.
- Cancer patients, except for in situ carcinoma and non-melanoma skin cancer, unless fully treated and in remission for five years.
- Hypocalcemia.
- Vitamin D deficiency (serum 25-hydroxyvitamin D < 25 ng/mL).
- Renal disease (eGFR < 35 mL/min/1.73 m²) or dialysis patients.
- Planned dental procedures (e.g., extractions, implants) within the next year.
- Smoking more than one pack per day (except for those who have quit for over ten years).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Fon-Yih Tsuang Clinical Associate Professor, Ph.D contact
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, 100
Fon-Yih Tsuang Clinical Associate Professor, Ph.D, 886-2312-3456 Ext. 265956 ext. 886-911138400, k880113a@gmail.com
About this study
Official title: 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.
Read the 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.
- Conditions
- Postmenopausal Osteoporosis, Postmenopausal Osteopenia, Primary Osteoporosis, Osteoporosis
- Being tested
- Ibandronate IV, Zoledronic acid IV
- Keywords
- Postmenopausal, Osteoporosis, Osteopenia, Denosumab, Ibandronate, Zoledronic acid, Discontinuation
- Medical subject headings
- Osteoporosis, Postmenopausal, Osteoporosis, Bone Diseases, Metabolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ibandronate IVDrug
Ibandronate 3mg/3months for 12 months
Zoledronic acid IVDrug
Zoledronic acid 5mg/1year for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Ibandronate group | Experimental | use Ibandronate 1 year and follow-up for 2 years Receives: Drug: Ibandronate IV |
| Zoledronic acid group | Active comparator | use Zoledronic acid 1 year and follow-up for 2 years Receives: Drug: Zoledronic acid IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage change in bone mineral density (BMD)
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.
Measured: Baseline to 24 months after treatment initiation.
Secondary outcomes (4)
Change in bone turnover makers (BTM) level
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.
Measured: Baseline to 24 months
Change in visual Analogue Scale (VAS) score
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.
Measured: Baseline to 24 months
Incidence of osteoporotic fractures
The occurrence and anatomical sites of osteoporotic fractures will be recorded throughout the study period.
Measured: During the intervention period, up to 24 months.
Incidence of adverse events (AEs) and serious adverse events (SAEs)
All AEs and SAEs will be recorded and evaluated throughout the study period to assess the safety of sequential therapy.
Measured: During the intervention period, up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2026
- Study start20 Aug 2026
- Primary completion31 Aug 2030 (estimated)
- Study completion31 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Postmenopausal OsteoporosisStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Taiwan University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07406685
- Sponsor's protocol ID
- 202601190MINA
- Status last verified
- Aug 2026
- First submitted
- 1 Feb 2026
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kumar S, Wang M, Kim AS, Center JR, McDonald MM, Girgis CM. Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures. J Bone Miner Res. 2025 Aug 24;40(9):1017-1034. doi: 10.1093/jbmr/zjaf037.
PubMed 40057981Ha J, Jung KY, Kim KJ, Ahn SH, Kim HJ, Chung YS. Effects of Sequential Anti-Resorptive Agents on Bone Mineral Density Following Denosumab Withdrawal: A Multicenter Real-World Study in Korea (MAXCARE Study). Endocrinol Metab (Seoul). 2025 Oct;40(5):748-758. doi: 10.3803/EnM.2024.2227. Epub 2025 Feb 11.
PubMed 39933434Ramchand SK, Tsai JN, Lee H, Sassana-Khadka G, Jordan M, Ryan S, Leder BZ. The comparison of alendronate and raloxifene after denosumab (CARD) study: A comparative efficacy trial. Osteoporos Int. 2024 Feb;35(2):255-263. doi: 10.1007/s00198-023-06932-2. Epub 2023 Oct 6.
PubMed 37798320Kendler D, Chines A, Clark P, Ebeling PR, McClung M, Rhee Y, Huang S, Stad RK. Bone Mineral Density After Transitioning From Denosumab to Alendronate. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e255-64. doi: 10.1210/clinem/dgz095.
PubMed 31665314Lee CC, Wang CY, Yen HK, Hung CC, Lai CY, Hu MH, Wang TM, Li CY, Fu SH. Zoledronate Sequential Therapy After Denosumab Discontinuation to Prevent Bone Mineral Density Reduction: A Randomized Clinical Trial. JAMA Netw Open. 2024 Nov 4;7(11):e2443899. doi: 10.1001/jamanetworkopen.2024.43899.
PubMed 39527056Tutaworn T, Nieves JW, Wang Z, Levin JE, Yoo JE, Lane JM. Bone loss after denosumab discontinuation is prevented by alendronate and zoledronic acid but not risedronate: a retrospective study. Osteoporos Int. 2023 Mar;34(3):573-584. doi: 10.1007/s00198-022-06648-9. Epub 2023 Jan 5.
PubMed 36602607Solling AS, Harslof T, Langdahl B. Treatment With Zoledronate Subsequent to Denosumab in Osteoporosis: A 2-Year Randomized Study. J Bone Miner Res. 2021 Jul;36(7):1245-1254. doi: 10.1002/jbmr.4305. Epub 2021 Apr 20.
PubMed 33813753Anastasilakis AD, Papapoulos SE, Polyzos SA, Appelman-Dijkstra NM, Makras P. Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial. J Bone Miner Res. 2019 Dec;34(12):2220-2228. doi: 10.1002/jbmr.3853. Epub 2019 Oct 14.
PubMed 31433518Burckhardt P, Faouzi M, Buclin T, Lamy O; The Swiss Denosumab Study Group. Fractures After Denosumab Discontinuation: A Retrospective Study of 797 Cases. J Bone Miner Res. 2021 Sep;36(9):1717-1728. doi: 10.1002/jbmr.4335. Epub 2021 May 19.
PubMed 34009703Cosman F, Huang S, McDermott M, Cummings SR. Multiple Vertebral Fractures After Denosumab Discontinuation: FREEDOM and FREEDOM Extension Trials Additional Post Hoc Analyses. J Bone Miner Res. 2022 Nov;37(11):2112-2120. doi: 10.1002/jbmr.4705. Epub 2022 Oct 12.
PubMed 36088628Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, Roux C, Torring O, Valter I, Wang AT, Brown JP. Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension. J Bone Miner Res. 2018 Feb;33(2):190-198. doi: 10.1002/jbmr.3337. Epub 2017 Nov 22.
PubMed 29105841Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O. Clinical Features of 24 Patients With Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases. J Bone Miner Res. 2017 Jun;32(6):1291-1296. doi: 10.1002/jbmr.3110. Epub 2017 Mar 13.
PubMed 28240371Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, Czerwinski E, Fahrleitner-Pammer A, Kendler DL, Lippuner K, Reginster JY, Roux C, Malouf J, Bradley MN, Daizadeh NS, Wang A, Dakin P, Pannacciulli N, Dempster DW, Papapoulos S. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017 Jul;5(7):513-523. doi: 10.1016/S2213-8587(17)30138-9. Epub 2017 May 22.
PubMed 28546097Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011 Apr;96(4):972-80. doi: 10.1210/jc.2010-1502. Epub 2011 Feb 2.
PubMed 21289258Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11.
PubMed 19671655