OsteoporosisPhase 4NCT04177940
Denosumab (DMAB) Discontinuation And Switching In Glucocorticoid-Induced Osteoporosis (GIOP): A Pilot Study
A Phase 4 study testing DMAB Discontinuation and Switching in people with Osteoporosis, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
Investigators will test the hypothesis that an increase in bone turnover markers (e.g. carboxy-terminal collagen crosslinks (CTX) and P1NP) in patients currently taking chronic glucocorticoids will be attenuated more in those who switch from denosumab to "late" zoledronic acid (9 months after last denosumab dose)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteoporosis
- What is being tested?
- DMAB Discontinuation and Switching
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Aug 2020to 14 Jan 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women and men, age 18 years or older and able to provide informed consent (IC)
- ≥ 3 months of glucocorticoid use at > 7.5 mg /day (prednisone equivalent dose) and anticipated to remain on glucocorticoids for at least six months
- A baseline BMD T-score of ≤ -2.0 at the lumbar spine, total hip, or femoral neck; OR
- A BMD T-score ≤ -1.0 at the lumbar spine, total hip, or femoral neck and a history of an osteoporotic fracture.
Who cannot join
- • Patients with fewer than three lumbar vertebrae that could be evaluated on dual energy x-ray absorptiometry (DXA)
- Treatment with bisphosphonates in the preceding 2 years
- Greater than 24 months (>4 injections) of prior treatment with denosumab
- Women of childbearing potential, who are not currently using birth control, are pregnant, planning to become pregnant, or are breastfeeding. For women of childbearing potential: refusal to use 2 highly effective forms of contraception and to continue this practice for 7 months after last injection of study medication*
- Men planning to conceive in the next 12 months
- Unstable systemic medical condition
Show all 30Show fewer
- Uncontrolled hyperthyroidism
- Uncontrolled hypothyroidism
- History of Addison disease
- History of osteomalacia
- History of osteonecrosis of the jaw (ONJ)
- History of atypical femur fracture
- History of tooth extraction, jaw surgery, dental implants, or other dental surgery within the prior 6 months
- History of anorexia nervosa, bulimia (by history or physical) or obvious malnutrition.
- Invasive dental work(implants/surgery) planned in the next 2 years
- History of Paget's disease of bone
- Other bone diseases which affect bone metabolism
- Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9 nmol/L)]
- Hypercalcemia >10% above upper limit of normal (ULN)
- Elevated transaminases or total bilirubin ≥ 2.0 x ULN
- History of any solid organ or bone marrow transplant
- Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma or localized squamous cell carcinoma of the skin)
- Hypocalcemia <10% below lower limit of normal (LLN)
- Estimated glomerular filtration rate < 30 mL/minute/1.73 m^2
- Intolerance to calcium supplements, vitamin D supplements
- Contraindication to, or poorly tolerant of denosumab therapy (including hypersensitivity to the drug)
- Contraindication to, or poorly tolerant of zoledronic therapy (including hypersensitivity to the drug)
- Contraindication to, or poorly tolerant of alendronate (including hypersensitivity to the drug and sever gastro-intestinal intolerance to oral bisphosphonates)
- Recipient of an investigational drug within 4 weeks prior to study drug administration
- Not a good candidate for study participation in opinion of investigator
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Investigators will test the hypothesis that an increase in bone turnover markers (e.g. carboxy-terminal collagen crosslinks (CTX) and P1NP) in patients currently taking chronic glucocorticoids will be attenuated more in those who switch from denosumab to "late" zoledronic acid (9 months after last denosumab dose) compared to participants randomized to "early" zoledronic acid (6 months after last denosumab dose) or weekly alendronate (6 months after last denosumab dose).
Read the detailed description
This is an open-label, randomized, parallel-group pilot clinical trial in which Denosumab users will be assigned in a 1:1:1 allocation to one the following groups:
- Switch from Denosumab 60 mg administered subcutaneously (SC) to weekly oral alendronate (70 mg; started 6 months after last denosumab dose) OR
- Switch from Denosumab 60 mg administered subcutaneously (SC) to one "early" zoledronic acid infusion (5 mg; 6 months after last denosumab dose) OR
- Switch from Denosumab 60 mg administered subcutaneously (SC) to one "late" zoledronic acid infusion (5 mg; 9 months after last denosumab dose)
Participants will be advised to maintain adequate calcium and vitamin D intake per United States Department of Agriculture (USDA) and Department of Health and Human Services (DHHS) guidelines. All individuals will need ≥ 12 months of previous denosumab treatment (minimum of 2 doses) prior to switching to assigned randomization arm. The minimum number of doses (n = 2) is based on published data that the rebound in BMD might be less pronounced in patients receiving very limited denosumab. According to a systematic review of patients with multiple vertebral fractures following denosumab cessation, those with ≤2 years of denosumab treatment had fewer fractures compared with those with >2 years. Therefore, the maximum number of prior doses (n = 4) is based on higher incidence of rebound loss of bone mineral density (BMD), more rapid turnover, and potentially greater vertebral fractures after discontinuation of denosumab in patients who received more extensive treatment. Investigators will limit the trial to a more restricted use of denosumab duration (2-4 doses) to maintain greater homogeneity, given the somewhat smaller planned sample size. Users of denosumab will be sorted into two groups:
- Prevalent users: Defined as individuals with a minimum of one previous dose of denosumab, and up to 4 previous doses of denosumab (maximum). Prevalent users with one previous dose will receive a second dose of denosumab before proceeding to assigned randomization arm. Therefore, randomization will occur 2 weeks after screening visit if they had already 2-4 denosumab doses.
- New denosumab users: Defined as individuals who have not previously received denosumab. New users will receive two doses of denosumab before proceeding to assigned randomization arm.
- Conditions
- Osteoporosis
- Being tested
- DMAB Discontinuation and Switching
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DMAB Discontinuation and SwitchingDrug
Investigators will test the hypothesis that an increase in bone turnover markers (e.g. CTX and P1NP) in patients currently taking chronic glucocorticoids will be attenuated more in those who switch from denosumab to "late" zoledronic acid (9 months after last denosumab dose) compared to participants randomized to "early" zoledronic acid (6 months after last denosumab dose) or weekly alendronate (6 months after last denosumab dose
| Study group | Role | What they receive |
|---|---|---|
| Denosumab (DMAB) to Alendronate (ALN) | Active comparator | Switch from Denosumab 60 mg administered subcutaneously (SC) to weekly oral alendronate (70 mg; started 6 months after last denosumab dose) Receives: Drug: DMAB Discontinuation and Switching |
| DMAB to "Early" Zoledronic Acid (ZA) | Active comparator | Switch from Denosumab 60 mg administered subcutaneously (SC) to one "early" zoledronic acid infusion (5 mg; 6 months after last denosumab dose) Receives: Drug: DMAB Discontinuation and Switching |
| DMAB to "Late" ZA | Active comparator | Switch from Denosumab 60 mg administered subcutaneously (SC) to one "late" zoledronic acid infusion (5 mg; 9 months after last denosumab dose) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Difference in the Log-transformed CTX Values Between V4 vs. V6
Absolute difference in the log-transformed CTX Values between randomization (V4) and 6 months after randomization (V6)
Measured: from randomization (V4) through 6 months post randomization (V6)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2019
- Study start17 Aug 2020
- Primary completion22 Jul 2024
- Study completion14 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University, Vrije Universiteit Brussel, Amgen
- Responsible party
- Principal investigator, Kenneth Saag, MD, MSc, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04177940
- Sponsor's protocol ID
- IRB-300004179
- Other IDs
- Protocol Number: 20187528
- Status last verified
- Mar 2026
- First submitted
- 22 Nov 2019
- Last updated
- 23 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Denosumab (DMAB) Discontinuation And Switching In Glucocorticoid-Induced Osteoporosis (GIOP): A Pilot Study
- ClinicalTrials.gov ID
- NCT04177940
- Acronym / sponsor ID
- IRB-300004179
- Conditions
- Osteoporosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Maastricht University, Vrije Universiteit Brussel, Amgen
- Study start
- 17 Aug 2020 (actual)
- Primary completion
- 22 Jul 2024 (actual)
- Study completion
- 14 Jan 2025 (actual)
- First posted
- 26 Nov 2019 (actual)
- Results
- Posted 23 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigators will test the hypothesis that an increase in bone turnover markers (e.g. carboxy-terminal collagen crosslinks (CTX) and P1NP) in patients currently taking chronic glucocorticoids will be attenuated more in those who switch from denosumab to "late" zoledronic acid (9 months after last denosumab dose) compared to participants randomized to "early" zoledronic acid (6 months after last denosumab dose) or weekly alendronate (6 months after last denosumab dose).
Detailed description
This is an open-label, randomized, parallel-group pilot clinical trial in which Denosumab users will be assigned in a 1:1:1 allocation to one the following groups:
- Switch from Denosumab 60 mg administered subcutaneously (SC) to weekly oral alendronate (70 mg; started 6 months after last denosumab dose) OR
- Switch from Denosumab 60 mg administered subcutaneously (SC) to one "early" zoledronic acid infusion (5 mg; 6 months after last denosumab dose) OR
- Switch from Denosumab 60 mg administered subcutaneously (SC) to one "late" zoledronic acid infusion (5 mg; 9 months after last denosumab dose)
Participants will be advised to maintain adequate calcium and vitamin D intake per United States Department of Agriculture (USDA) and Department of Health and Human Services (DHHS) guidelines. All individuals will need ≥ 12 months of previous denosumab treatment (minimum of 2 doses) prior to switching to assigned randomization arm. The minimum number of doses (n = 2) is based on published data that the rebound in BMD might be less pronounced in patients receiving very limited denosumab. According to a systematic review of patients with multiple vertebral fractures following denosumab cessation, those with ≤2 years of denosumab treatment had fewer fractures compared with those with >2 years. Therefore, the maximum number of prior doses (n = 4) is based on higher incidence of rebound loss of bone mineral density (BMD), more rapid turnover, and potentially greater vertebral fractures after discontinuation of denosumab in patients who received more extensive treatment. Investigators will limit the trial to a more restricted use of denosumab duration (2-4 doses) to maintain greater homogeneity, given the somewhat smaller planned sample size. Users of denosumab will be sorted into two groups:
- Prevalent users: Defined as individuals with a minimum of one previous dose of denosumab, and up to 4 previous doses of denosumab (maximum). Prevalent users with one previous dose will receive a second dose of denosumab before proceeding to assigned randomization arm. Therefore, randomization will occur 2 weeks after screening visit if they had already 2-4 denosumab doses.
- New denosumab users: Defined as individuals who have not previously received denosumab. New users will receive two doses of denosumab before proceeding to assigned randomization arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Denosumab (DMAB) to Alendronate (ALN) | Active comparator | Drug: DMAB Discontinuation and SwitchingSwitch from Denosumab 60 mg administered subcutaneously (SC) to weekly oral alendronate (70 mg; started 6 months after last denosumab dose) |
| DMAB to "Early" Zoledronic Acid (ZA) | Active comparator | Drug: DMAB Discontinuation and SwitchingSwitch from Denosumab 60 mg administered subcutaneously (SC) to one "early" zoledronic acid infusion (5 mg; 6 months after last denosumab dose) |
| DMAB to "Late" ZA | Active comparator | –Switch from Denosumab 60 mg administered subcutaneously (SC) to one "late" zoledronic acid infusion (5 mg; 9 months after last denosumab dose) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Women and men, age 18 years or older and able to provide informed consent (IC)
- ≥ 3 months of glucocorticoid use at > 7.5 mg /day (prednisone equivalent dose) and anticipated to remain on glucocorticoids for at least six months
- A baseline BMD T-score of ≤ -2.0 at the lumbar spine, total hip, or femoral neck; OR
- A BMD T-score ≤ -1.0 at the lumbar spine, total hip, or femoral neck and a history of an osteoporotic fracture.
Key exclusion criteria (30 listed)
- • Patients with fewer than three lumbar vertebrae that could be evaluated on dual energy x-ray absorptiometry (DXA)
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 |
|---|---|---|
| DMAB Discontinuation and SwitchingInvestigators will test the hypothesis that an increase in bone turnover markers (e.g. CTX and P1NP) in patients currently taking chronic glucocorticoids will be attenuated more in those who switch from denosumab to "late" zoledronic acid (9 months after last denosumab dose) compared to participants randomized to "early" zoledronic acid (6 months after last denosumab dose) or weekly alendronate (6 months after last denosumab dose | Drug | DMAB to "Early" Zoledronic Acid (ZA), Denosumab (DMAB) to Alendronate (ALN) |
Primary outcome
Absolute Difference in the Log-transformed CTX Values Between V4 vs. V6
Time frame: from randomization (V4) through 6 months post randomization (V6)
Absolute difference in the log-transformed CTX Values between randomization (V4) and 6 months after randomization (V6)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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 DMAB Discontinuation and Switching in people with Osteoporosis, run by University of Alabama at Birmingham at 1 site in United States.
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 4 inclusion and 30 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 2026. 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 United States. 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?
Yes. Results are posted in the registry (first posted 23 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Absolute Difference in the Log-transformed CTX Values Between V4 vs. V6 (time frame: from randomization (V4) through 6 months post randomization (V6)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2026.