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OsteoporosisPhase 4DSTNCT03868033

Denosumab Sequential Therapy

A Phase 4 study testing Zoledronic Acid and Denosumab in people with Osteoporosis, run by National Taiwan University Hospital at 1 site in Taiwan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Denosumab is a potent anti-resorptive agent and is now widely used in the treatment of osteoporosis. Although denosumab has excellent effect to increase bone mass and prevent fracture in FREEDOM study with very low complications, even up to ten years, it's effect is reversible. Read more about this study

Who is it for?
Ages 50 to 80 years
Conditions the study is for
Osteoporosis
What is being tested?
Zoledronic Acid and Denosumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
101 participants
Where
1 siteTaiwan
Study dates
12 Apr 2019to 31 Dec 2023
Phase
Phase 4
Are there results?
None posted in the registry

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 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Postmenopausal women
  • Men >50-year-old
  • After Denosumab treatment ≥ 2 years due to osteoporosis

Who cannot join

  • Patientshadeverusedantiosteoporosismedications other than Dmab
  • Estimated glomerular filtration rate <35 ml/min.
  • Malignancy
  • Continuous steroid treatment, hormone therapy or other medical treatment affecting bone metabolism
  • Secondary osteoporosis
  • Metabolic bone diseases
Show all 9Show fewer
  • Contraindications to ZOL
  • Patients older than 80 years old
  • Hypocalcemia

Trial locations and contacts

1 site in 1 country.

Taiwan1 site

  • Department of Orthopedics, National Taiwan University Hospital

    Taipei, N/A = Not Applicable, 64041

Other trials in Taiwan

About this study

Official title: Department of Orthopedics, National Taiwan University Hospital

Denosumab is a potent anti-resorptive agent and is now widely used in the treatment of osteoporosis. Although denosumab has excellent effect to increase bone mass and prevent fracture in FREEDOM study with very low complications, even up to ten years, it's effect is reversible. After holding the drug, circulating denosumab levels fall rapidly, and bone resorption reaching twice baseline levels for about 6 months. How to prevent bone loss after denosumab therapy is an important issue, especially when considering the compliance, persistence, or other comorbidities of the patient. We want to verify if zoledronic acid could be used as a sequential therapy after denosumab to prevent rapid bone loss by randomized clinical trial.

Read the detailed description

Denosumab is a monoclonal antibody directed against the protein RANK-L, the principal regulator of osteoclast development. Thus, it acts as a potent anti-resorptive agent and is now widely used in the treatment of osteoporosis. Because it's easily to be used with very low risk of complications, patient has better compliance and persistence of denosumab than bisphosphonates. It's market share increasing very rapidly in Taiwan.

Although denosumab has excellent effect to increase bone mass and prevent fracture in FREEDOM study with very low complications, even up to ten years, it's effect is reversible. After holding the drug, circulating denosumab levels fall rapidly, and bone resorption reaching twice baseline levels for about 6 months. Over the first 12 months off therapy, all the bone density gained on treatment is lost4. According to previous meta-analysis study, although the persistence of denosumab therapy is better than bisphosphonates, only 62% patients keep the treatment after two years. We could image how low the persistence is after five-year or ten-year treatment in the real world.

How to prevent bone loss after denosumab therapy is an important issue, especially when considering the compliance, persistence, or other comorbidities of the patient. There is only one randomized controlled trial dealing with this problem, although the primary goal of the study is designed to compare the compliance and persistence1. After switching from denosumab to alendronate for one year, bone mineral density does not decrease rapidly, although there is mild elevation of bone turn over marker.

We want to verify if zoledronic acid could be used as a sequential therapy after denosumab to prevent rapid bone loss by randomized clinical trial.

Conditions
Osteoporosis
Keywords
Osteoporosis, Denosumab, Zoledronate, Bone mineral density
Medical subject headings
Osteoporosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Zoledronic AcidDrug

    Also called Aclasta

    Use Zoledronic acid as a sequential therapy after denosumab treatment for more than 2 years

  • DenosumabDrug

    Also called Prolia

    Continuous Denosumab treatment in arm 1 for two years or as a 2nd year treatment in arm 2 for one year

Study groups in NCT03868033
Study groupRoleWhat they receive
Continuous DenosumabExperimentalContinuous anti-resorptive therapy by Denosumab for 2 years
Receives: Drug: Denosumab
Zoledronic acid to DenosumabExperimentaltreat with Zoledronic acid for one year and then shift to Denosumab for another one year
Receives: Drug: Zoledronic Acid; Drug: Denosumab
Continuous Zoledronic acidExperimentalContinuous anti-resorptive therapy by Zoledronic acid for 2 years
Receives: Drug: Zoledronic Acid
Zoledronic acid to observationExperimentaltreat with Zoledronic acid for one year and then close follow up by bone turn over marker. resume another dose of Zoledronic acid if elevated CTX level above normal range
Receives: Drug: Zoledronic Acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes of lumbar spine, total hip and femoral neck bone mineral density

    Changes of lumbar spine, total hip and femoral neck bone mineral density from baseline

    Measured: baseline, 1 year, 2 year

Secondary outcomes (2)

  1. Change of bone turnover marker

    Changes of bone turnover marker, including C-terminal telopeptide of type I collagen (CTX) and propeptide of procollagen type I (P1NP)

    Measured: baseline, 6 months, 12 months, 15 months, 18 months, 24 months

  2. Clinical osteoporotic fracture

    Incidence of clinical osteoporotic fracture

    Measured: baseline, 1 year, 2 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Mar 2019
  2. Study start12 Apr 2019
  3. Primary completion1 Jul 2023
  4. Study completion31 Dec 2023

Resources

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
Single blind
Who is masked
Outcomes assessor
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03868033
Sponsor's protocol ID
201811067MIPC
Acronym
DST
Status last verified
Sep 2023
First submitted
6 Mar 2019
Last updated
23 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Yen HK, Chiang MH, Tsao SL, Liu JH, Tseng TH, Lin TC, Lee CC, Hung CC, Huang CC, Fu SH, Wang CY. The third-year results of denosumab sequential therapy trial: An extension of a randomized clinical trial. J Formos Med Assoc. 2026 Sep 25:S0929-6646(26)00914-9. doi: 10.1016/j.jfma.2026.09.029. Online ahead of print.

    PubMed 42786015

  • Yen HK, Lee CC, Wang CY, Lin TC, Fu SH, Huang CC, Hung CC, Groot OQ, Li CY. Therapeutic Strategies of Denosumab Sequential Therapy: A Four-Armed Randomized Controlled Trial. Clin Pharmacol Ther. 2026 Feb;119(2):480-489. doi: 10.1002/cpt.70088. Epub 2025 Oct 7.

    PubMed 41058078

  • 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.

    PubMed 39527056

  • Lee CC, Wang CY, Hung CC, Huang CC, Li CY, Chen HY, Chang YL, Tseng WJ, Wang TM, Yang RS, Wong TH, Fu SH. A Multi-Institutional Randomized Controlled Trial to Investigate Whether Zoledronate Prevents Bone Loss After Discontinuation of Denosumab: The Study Protocol of Denosumab Sequential Therapy (DST) Trial. Front Med (Lausanne). 2021 Sep 8;8:717168. doi: 10.3389/fmed.2021.717168. eCollection 2021.

    PubMed 34568375

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Zoledronic Acid and Denosumab in people with Osteoporosis, run by National Taiwan University Hospital at 1 site in Taiwan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes of lumbar spine, total hip and femoral neck bone mineral density (time frame: baseline, 1 year, 2 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03868033, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2024.

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