The Comparison of Ibandronate and Zoledronic Acid After Denosumab Discontinuation

NCT07406685 | Not Yet Recruiting Phase 4

• 1 other identifier: 202601190MINA
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Postmenopausal Osteoporosis; Postmenopausal Osteopenia; Primary Osteoporosis; Osteoporosis

Keywords

Postmenopausal; Osteoporosis; Osteopenia; Denosumab; Ibandronate; Zoledronic acid; Discontinuation

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 24 months after treatment initiation.

Secondary Outcomes (4)

• Change in bone turnover makers (BTM) level

  Baseline to 24 months

• Change in visual Analogue Scale (VAS) score

  Baseline to 24 months

• Incidence of osteoporotic fractures

  During the intervention period, up to 24 months.

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  During the intervention period, up to 24 months.

Study Arms (2)

Ibandronate group

EXPERIMENTAL

use Ibandronate 1 year and follow-up for 2 years

Drug: Ibandronate IV

Zoledronic acid group

ACTIVE COMPARATOR

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

Drug: Zoledronic acid IV

Interventions

Ibandronate IV DRUG

Ibandronate 3mg/3months for 12 months

Ibandronate group

Zoledronic acid IV DRUG

Zoledronic acid 5mg/1year for 12 months

Zoledronic acid group

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• National Taiwan University: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (21)

• 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.

  PMID: 40057981 RESULT

• Ha 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.

  PMID: 39933434 RESULT

• Ramchand 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.

  PMID: 37798320 RESULT

• Kendler 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.

  PMID: 31665314 RESULT

• Lee 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.

  PMID: 39527056 RESULT

• Tutaworn 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.

  PMID: 36602607 RESULT

• Solling 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.

  PMID: 33813753 RESULT

• Anastasilakis 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.

  PMID: 31433518 RESULT

• Burckhardt 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.

  PMID: 34009703 RESULT

• Cosman 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.

  PMID: 36088628 RESULT

• Cummings 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.

  PMID: 29105841 RESULT

• Anastasilakis 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.

  PMID: 28240371 RESULT

• Bone 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.

  PMID: 28546097 RESULT

• Bone 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.

  PMID: 21289258 RESULT

• Cummings 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.

  PMID: 19671655 RESULT

• Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.

  PMID: 18539106 RESULT

• Black DM, Bauer DC, Vittinghoff E, Lui LY, Grauer A, Marin F, Khosla S, de Papp A, Mitlak B, Cauley JA, McCulloch CE, Eastell R, Bouxsein ML; Foundation for the National Institutes of Health Bone Quality Project. Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials. Lancet Diabetes Endocrinol. 2020 Aug;8(8):672-682. doi: 10.1016/S2213-8587(20)30159-5.

  PMID: 32707115 RESULT

• Fogelman I, Blake GM. Different approaches to bone densitometry. J Nucl Med. 2000 Dec;41(12):2015-25.

  PMID: 11138687 RESULT

• LeBoff MS, Greenspan SL, Insogna KL, Lewiecki EM, Saag KG, Singer AJ, Siris ES. The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2022 Oct;33(10):2049-2102. doi: 10.1007/s00198-021-05900-y. Epub 2022 Apr 28.

  PMID: 35478046 RESULT

• Gullberg B, Johnell O, Kanis JA. World-wide projections for hip fracture. Osteoporos Int. 1997;7(5):407-13. doi: 10.1007/pl00004148.

  PMID: 9425497 RESULT

• Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992 Nov;2(6):285-9. doi: 10.1007/BF01623184.

  PMID: 1421796 RESULT

Related Links

• National Institute of Arthritis and Musculoskeletal and Skin Diseases. (2022.12) Osteoporosis. National Institutes of Health(NIH).
• 中華民國骨質疏鬆症學會(2025 年 10 月 30 日)。2025 台灣成人骨質疏鬆防治之共識及指引。

MeSH Terms

Conditions

Osteoporosis, Postmenopausal; Osteoporosis; Bone Diseases, Metabolic

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Fon-Yih Tsuang Clinical Associate Professor, Ph.D

CONTACT

886-2312-3456 Ext. 265956; k880113a@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2026
• First Posted: February 12, 2026
• Study Start: March 17, 2026
• Primary Completion (Estimated): March 17, 2030
• Study Completion (Estimated): September 17, 2030
• Last Updated: February 12, 2026

Record last verified: 2026-01

Locations

TW (1)