OsteoporosisPhase 4NCT05361408
A Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis (ZOOM Study)
A Phase 4 study testing Zoledronic acid, once and Zoledronic acid, twice in people with Osteoporosis, run by Yonsei University at 1 site in South Korea.
Trial summary
Denosumab(Dmab) is a monoclonal antibody that inhibits the receptor-activator of nuclear factor kappa-B ligand. It improves bone density and reduces fractures by inhibiting osteoclast recruitment and differentiation. Read more about this study
- Who is it for?
- Ages 50 years and older, women only
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Zoledronic acid, once and Zoledronic acid, twice
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteSouth Korea
- Study dates
- 11 Feb 2022to 13 Feb 2024
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal women (defined as no menstruation for more than 48 weeks prior to screening and no other pathological or physiological causes. If in doubt, a serum follicle-stimulating hormone (FSH) test may be performed at screening)
- Patients diagnosed with osteoporosis, osteoporotic fractures, received at least two doses of denosumab, and who have osteopenia in follow-up DXA
Who cannot join
- Secondary osteoporosis (Systemic glucocorticoid use, aromatase inhibitor, thyrotoxicosis, hypeparathyroidism, etc)
- Active cancer treatment
- Inflammatory bowel disease
- History of medication related osteonecrosis of jaw(MRONJ)
- low-energy fracture within the last 12months
- Estimated glomerular filtration rate (eGFR) < 35 mL/min
Show all 9Show fewer
- Hepatic dysfunction (aspartate transaminase (AST)/alanine transferase (ALT) > 3 x upper normal limit)
- Contraindication for zoledronic acid according to the SPC
- Allergic to zoledronic acid
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Yonsei University Health System, Severance Hospital
Seoul
About this study
Official title: A Single Center, Open-label, Parallel, Phase IV Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis
Denosumab(Dmab) is a monoclonal antibody that inhibits the receptor-activator of nuclear factor kappa-B ligand. It improves bone density and reduces fractures by inhibiting osteoclast recruitment and differentiation. Although the FREEDOM trial showed Dmab increase bone mineral density for ten years, the effect was reversible. When Dmab is discontinued, the rebound phenomenon, the bone mineral density returns to the pre-treatment value, and multiple vertebral fractures may occur. Recently, a guideline to administer bisphosphonates sequentially when Dmab is discontinued has been published. In several studies, Zoledronic acid prevented bone loss after denosumab discontinuation with a single administration in Dmab short-term(less than 2.5years) users, but in Dmab long-term(more than 2.5years) users, zoledronic acid did not fully prevent loss of BMD. Our study tried to evaluate that ZOL administration twice for six months apart in long-term Dmab users is not inferior to a single administration of ZOL in Dmab short-term users.
Read the detailed description
Background Dmab is an osteoporosis treatment that improves bone density and lowers the risk of fractures. However, in a recent study, it is known that cases in which bone density decreases and multiple vertebral fractures occur when Dmab is discontinued. Therefore, the guideline recommends using zoledronic acid sequentially when discontinuing Dmab. However, the effect of preserving bone mineral density in patients who discontinue Dmab after using a long period is still not known.
Aim To investigate the difference in lumbar bone mineral density between the two groups when zoledronic acid was administered differently according to the administration period after discontinuation of denosumab in postmenopausal osteoporosis patients.
Methods A prospective, single-center, open-label, parallel, intervention study in 114 patients investigating the difference in bone mineral density between the short-term denosumab group and long-term denosumab group when zoledronic acid was administered differently. Each group is classified into a short-term group when used for less than 2.5 years and a long-term group when used for more than 2.5 years according to the maintenance period of the denosumab. The short-term group administrates zoledronic acid once six months after the last denosumab injection, and the long-term group administrates zoledronic acid six months and 12 months after the last denosumab injection, respectively. In the long-term group, if the side effect is severe after the first zoledronic acid administration and additional administration is difficult, it can be replaced with risedronic acid and maintained for another six months. The patients will be monitored with DXA at baseline and 12 months. Bone turnover marker (b-crosslap(CTx), P1NP) will be monitored at 6 and 12 months after the infusion of the first zoledronic acid. Whole spine x-rays are taken at baseline and 12 months after the zoledronic acid injection to check for vertebral fractures.
Perspectives Osteoporosis is a disease that requires continuous management in old age. In order to prevent fractures, the order and maintenance of drug administration should be decided from a long-term perspective. Denosumab is a potent inhibitor of bone resorption which can be used in patients with high risk and very high fracture risk. But since it is reversible, additional treatment must be continued to maintain bone mass when the drug is discontinued. This study will show if two injections of zoledronic acid six months apart in long-term denosumab patients can effectively prevent bone loss compared to a single administration of zoledronic acid in the short-term denosumab group.
- Conditions
- Osteoporosis
- Being tested
- Zoledronic acid, once, Zoledronic acid, twice
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic acid, onceDrug
Also called Zoledronate
Intravenous infusion of 5mg zoledronic acid, once
Zoledronic acid, twiceDrug
Also called Zoledronate
Intravenous infusion of 5mg zoledronic acid for 6month interval, twice
| Study group | Role | What they receive |
|---|---|---|
| Denosumab short-term user | Active comparator | Denosumab injection less than 5 times Receives: Drug: Zoledronic acid, once |
| Denosumab long-term user | Active comparator | Denosumab injection more than 5 times Receives: Drug: Zoledronic acid, twice |
What is being measured
The primary outcome is the main question the study is designed to answer.
BMD lumbar spine
Change in lumbar spine BMD from baseline to one year after the zoledronic acid infusion
Measured: One year
Secondary outcomes (3)
BMD Femoral neck and total hip
Changes in femoral neck and total hip BMD from baseline to one year after the zoledronic acid infusion
Measured: One year
Bone turnover marker
Changes in p-CTX and P1NP From Baseline to Six and twelve months After the Zoledronic Acid Infusion.
Measured: One year
Vertebral fracture
Morphometric Vertebral Fractures Assessed by whole spine x-ray
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2022
- Study start11 Feb 2022
- Primary completion13 Feb 2024
- Study completion13 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05361408
- Sponsor's protocol ID
- 4-2021-1023
- Status last verified
- Mar 2025
- First submitted
- 29 Apr 2022
- Last updated
- 7 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tsourdi E, Zillikens MC, Meier C, Body JJ, Gonzalez Rodriguez E, Anastasilakis AD, Abrahamsen B, McCloskey E, Hofbauer LC, Guanabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Pepe J, Palermo A, Langdahl B. Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS. J Clin Endocrinol Metab. 2020 Oct 26:dgaa756. doi: 10.1210/clinem/dgaa756. Online ahead of print.
PubMed 33103722Solling 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 33813753
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center, Open-label, Parallel, Phase IV Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis
- ClinicalTrials.gov ID
- NCT05361408
- Acronym / sponsor ID
- 4-2021-1023
- Conditions
- Osteoporosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 11 Feb 2022 (actual)
- Primary completion
- 13 Feb 2024 (actual)
- Study completion
- 13 Feb 2024 (actual)
- First posted
- 4 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Denosumab(Dmab) is a monoclonal antibody that inhibits the receptor-activator of nuclear factor kappa-B ligand. It improves bone density and reduces fractures by inhibiting osteoclast recruitment and differentiation. Although the FREEDOM trial showed Dmab increase bone mineral density for ten years, the effect was reversible. When Dmab is discontinued, the rebound phenomenon, the bone mineral density returns to the pre-treatment value, and multiple vertebral fractures may occur. Recently, a guideline to administer bisphosphonates sequentially when Dmab is discontinued has been published. In several studies, Zoledronic acid prevented bone loss after denosumab discontinuation with a single administration in Dmab short-term(less than 2.5years) users, but in Dmab long-term(more than 2.5years) users, zoledronic acid did not fully prevent loss of BMD. Our study tried to evaluate that ZOL administration twice for six months apart in long-term Dmab users is not inferior to a single administration of ZOL in Dmab short-term users.
Detailed description
Background Dmab is an osteoporosis treatment that improves bone density and lowers the risk of fractures. However, in a recent study, it is known that cases in which bone density decreases and multiple vertebral fractures occur when Dmab is discontinued. Therefore, the guideline recommends using zoledronic acid sequentially when discontinuing Dmab. However, the effect of preserving bone mineral density in patients who discontinue Dmab after using a long period is still not known.
Aim To investigate the difference in lumbar bone mineral density between the two groups when zoledronic acid was administered differently according to the administration period after discontinuation of denosumab in postmenopausal osteoporosis patients.
Methods A prospective, single-center, open-label, parallel, intervention study in 114 patients investigating the difference in bone mineral density between the short-term denosumab group and long-term denosumab group when zoledronic acid was administered differently. Each group is classified into a short-term group when used for less than 2.5 years and a long-term group when used for more than 2.5 years according to the maintenance period of the denosumab. The short-term group administrates zoledronic acid once six months after the last denosumab injection, and the long-term group administrates zoledronic acid six months and 12 months after the last denosumab injection, respectively. In the long-term group, if the side effect is severe after the first zoledronic acid administration and additional administration is difficult, it can be replaced with risedronic acid and maintained for another six months. The patients will be monitored with DXA at baseline and 12 months. Bone turnover marker (b-crosslap(CTx), P1NP) will be monitored at 6 and 12 months after the infusion of the first zoledronic acid. Whole spine x-rays are taken at baseline and 12 months after the zoledronic acid injection to check for vertebral fractures.
Perspectives Osteoporosis is a disease that requires continuous management in old age. In order to prevent fractures, the order and maintenance of drug administration should be decided from a long-term perspective. Denosumab is a potent inhibitor of bone resorption which can be used in patients with high risk and very high fracture risk. But since it is reversible, additional treatment must be continued to maintain bone mass when the drug is discontinued. This study will show if two injections of zoledronic acid six months apart in long-term denosumab patients can effectively prevent bone loss compared to a single administration of zoledronic acid in the short-term denosumab group.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab short-term user | Active comparator | Drug: Zoledronic acid, onceDenosumab injection less than 5 times |
| Denosumab long-term user | Active comparator | Drug: Zoledronic acid, twiceDenosumab injection more than 5 times |
Who may qualify
- Ages
- 50 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Postmenopausal women (defined as no menstruation for more than 48 weeks prior to screening and no other pathological or physiological causes. If in doubt, a serum follicle-stimulating hormone (FSH) test may be performed at screening)
- Patients diagnosed with osteoporosis, osteoporotic fractures, received at least two doses of denosumab, and who have osteopenia in follow-up DXA
Key exclusion criteria (9 listed)
- Secondary osteoporosis (Systemic glucocorticoid use, aromatase inhibitor, thyrotoxicosis, hypeparathyroidism, etc)
- Active cancer treatment
- Inflammatory bowel disease
- History of medication related osteonecrosis of jaw(MRONJ)
- low-energy fracture within the last 12months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zoledronic acid, onceAlso: ZoledronateIntravenous infusion of 5mg zoledronic acid, once | Drug | Denosumab short-term user |
| Zoledronic acid, twiceAlso: ZoledronateIntravenous infusion of 5mg zoledronic acid for 6month interval, twice | Drug | Denosumab long-term user |
Primary outcome
BMD lumbar spine
Time frame: One year
Change in lumbar spine BMD from baseline to one year after the zoledronic acid infusion
3 secondary outcomes
BMD Femoral neck and total hip
Time frame: One year
Bone turnover marker
Time frame: One year
Vertebral fracture
Time frame: One year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2025.
- Background: PubMed 33103722Tsourdi E, Zillikens MC, Meier C, Body JJ, Gonzalez Rodriguez E, Anastasilakis AD, Abrahamsen B, McCloskey E, Hofbauer LC, Guanabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Pepe J, Palermo A, Langdahl B. Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS. J Clin Endocrinol Metab. 2020 Oct 26:dgaa756. doi: 10.1210/clinem/dgaa756. Online ahead of print.
- Background: PubMed 33813753Solling 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Zoledronic acid, once and Zoledronic acid, twice in people with Osteoporosis, run by Yonsei University at 1 site in South Korea.
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 2 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 7 Mar 2025. 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 South Korea. 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?
BMD lumbar spine (time frame: One 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 NCT05361408, which also lists 2 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 7 Mar 2025.