OsteoporosisPhase 4OPTIMISTNCT06059222
The Optimised Use of Romozosumab Study
A Phase 4 study testing Romosozumab and Zoledronate in people with Osteoporosis, run by University of Aarhus at 1 site in Denmark.
Trial summary
OPTIMIST is a two-year, randomised, active controlled, open-label, multicentre intervention trial. OPTIMIST includes 3 treatment groups each comprising combinations of romosozumab (ROMO) and zoledronate (ZOL) treatment used in standard doses (210 mg monthly (sc) and 5 mg yearly (iv), respectively). 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?
- Romosozumab and Zoledronate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 1 siteDenmark
- Study dates
- 2 Oct 2023to 31 Aug 2032
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 (postmenopausal for at least two years)
- BMD T-score < -2.5 at lumbar spine, total hip, or femoral neck
- Osteoporotic fracture within the last 3 years at the spine, hip, pelvis, humerus or forearm after the age of 50 years.
Who cannot join
- Osteoporosis treatment including hormone replacement therapy within the last 5 years
- Metabolic bone disease
- Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, liver dysfunction (baseline phosphatase higher than twice upper limit), rheumatism, severe COPD (chronic obstructive pulmonary disease), hypopituitarism, Cushing's disease
- Ongoing treatment with glucocorticoids (systemic)
- Estimated glomerular filtration rate (eGFR) < 35 mL/min
- Contraindications for zoledronate according to the Supplementary protection certificates (SPC)
Show all 9Show fewer
- Contraindications for romosozumab according to the SPC
- For the subgroup with Jamshidi biopsies contraindications for local anaesthetics according to the SPC
- For the subgroup with Jamshidi biopsies contraindications for tetracycline or doxycykline according to the SPC
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Department of Endrocinology and Internal Medicine
Aarhus, 8000
Vivi Mäkinen, 78450000, vivmaa@rm.dk
About this study
OPTIMIST is a two-year, randomised, active controlled, open-label, multicentre intervention trial. OPTIMIST includes 3 treatment groups each comprising combinations of romosozumab (ROMO) and zoledronate (ZOL) treatment used in standard doses (210 mg monthly (sc) and 5 mg yearly (iv), respectively).
The study will investigate if it is possible to maximize the effect of romosozumab by giving it in 2 periods of 6 months interrupted by zoledronate for 12 months compared to romosozumab for 12 months uninterrupted followed by zoledronate for 12 months. The investigators will also evaluate if 6 months of romosozumab followed by 18 months of zoledronate is non-inferior to the standard regimen of romosozumab for 12 months followed by zoledronate for 12 months.
Read the detailed description
Recent clinical trials have demonstrated the benefit of bone anabolic treatment over no treatment or antiresorptive treatment in terms of increasing bone mineral density (BMD) and reducing fracture risk for patients with osteoporosis. However, the bone anabolic treatment is expensive and therefore restricted to a limited group of patients.
This study is based on the hypothesis that treatment with romosozumab for 6 months, zoledronate for 12 months, and romosozumab for 6 months results in larger gains in bone mineral density than treatment regimens based on romosozumab treatment for 6 or 12 months followed by zoledronate for a total of 24 months of treatment due to reappearance of the bone anabolic effect of romosozumab upon retreatment.
The OPTIMIST study is a two-year, randomised, active controlled, open-label, intervention trial. The study includes 270 postmenopausal women who will be randomised to 3 groups. Group 1 (n=90) will receive romosozumab for 12 months followed by zoledronate for 12 months. Group 2 (n=90) will receive romosozumab for 6 months followed by zoledronate for 12 months and romosozumab for 6 months. Group 3 (n=90 ) will receive romosozumab for 6 months followed by zoledronate for 18 months.
The investigational drugs in this study are romosozumab 210 mg/2,34 mL and zoledronate 5 mg/100 mL
This study will include 270 treatment naïve postmenopausal women. When inclusion and exclusion criteria have been reviewed, and the participant meets the requirements for study participation and continues to participate in the study, the patients will be randomized 1:1:1 Data will be registered in RedCAP (eCRF) and site monitoring assessed by the local Good Clinical Practice unit (GCP-unit).
The patients will be recruited from the outpatient clinics and the Dual-Energy X-ray Absorptiometry (DXA) units to which patients are referred from their general practitioner or fracture liaison services (FLS) at:
Department of Endocrinology, Odense University Hospital Department of Endocrinology and Internal Medicine, Aarhus University Hospital Department of Endocrinology, Køge Hospital Department of Endocrinology, Hvidovre Hospital Department of Endocrinology, Bispebjerg Hospital
During the intervention phase, there will be obtained fasting blood test, high-resolution peripheral quantitative computed tomography (HR-pQCT),Oral Glucose Tolerance Test (OGTT), DXA, Vertebral fracture assessment (VFA) and biochemistry at different time stamps. From 105 patients there will be obtained bone marrow aspirates and performed jamshidi bone biopsies.
The study will therefore show if it would be possible to treat twice as many patients for the same prize but also if the treatment for 12 months can be optimized. The knowledge about the optimal use of romosozumab will be included in an update of osteoporosis treatment guidelines. This will lead to optimized treatment of patients with severe osteoporosis.
- Conditions
- Osteoporosis
- Being tested
- Romosozumab, Zoledronate
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomosozumabDrug
Also called Evenity
Romosozumab 210 mg/2.34 ml from baseline to month 11
ZoledronateDrug
5 mg/100 ml at month 12
RomosozumabDrug
Also called Evenity
210 mg/2.34 ml from baseline to month 5 and from month 18 to month 23
ZoledronateDrug
5 mg/100 ml at month 6
RomosozumabDrug
Also called Evenity
210 mg/2.34 ml from baseline to month 5
ZoledronateDrug
5 mg/100 ml at month 5 and month 18
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - ROMO 12 months, ZOL 12 months | Active comparator | 90 patients 12 months of romosozumab (ROMO) followed by 12 months of zoledronate (ZOL) Receives: Drug: Romosozumab; Drug: Zoledronate |
| Group 2 - ROMO 6 months, ZOL 12 months, ROMO 6 months | Active comparator | 90 patients 6 months of romosozumab followed by 12 months of zoledronate and lastly 6 months of romosozumab. Receives: Drug: Romosozumab; Drug: Zoledronate |
| Group 3 - ROMO 6 months, ZOL 18 months | Active comparator | 90 patients 6 months of romosozumab followed by 18 months of zoledronate
. Receives: Drug: Romosozumab; Drug: Zoledronate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in total hip BMD
Change in total hip BMD
Measured: 24 months
Secondary outcomes (3)
Changes in femoral neck BMD
Change in femoral neck BMD
Measured: 24 months
Changes in trabecular bone volume fraction (bone volume/tissue volume, BV/TV) and cortical porosity measured by high-resolution peripheral quantitative computed tomography (HR-pQCT)
Mean percent change in trabecular bone volume fraction and cortical porosity measured by HR-pQCT at the radius and tibia
Measured: 24 months
Change in spine BMD
Change in spine BMD
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2023
- Study start2 Oct 2023
- Primary completion31 Aug 2030 (estimated)
- Study completion31 Aug 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by University of AarhusThe 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
- 270 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bente Langdahl, MD, Professor, DMSc, PhD,, Study director, Department of Endocrinology and Internal medicin, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06059222
- Sponsor's protocol ID
- CT-2023-505940-20-00
- Acronym
- OPTIMIST
- Status last verified
- Jul 2026
- First submitted
- 8 Sep 2023
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Optimised Use of Romozosumab Study
- ClinicalTrials.gov ID
- NCT06059222
- Acronym / sponsor ID
- OPTIMIST / CT-2023-505940-20-00
- Conditions
- Osteoporosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- 2 Oct 2023 (actual)
- Primary completion
- 31 Aug 2030 (estimated)
- Study completion
- 31 Aug 2032 (estimated)
- First posted
- 28 Sep 2023 (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.
OPTIMIST is a two-year, randomised, active controlled, open-label, multicentre intervention trial. OPTIMIST includes 3 treatment groups each comprising combinations of romosozumab (ROMO) and zoledronate (ZOL) treatment used in standard doses (210 mg monthly (sc) and 5 mg yearly (iv), respectively).
The study will investigate if it is possible to maximize the effect of romosozumab by giving it in 2 periods of 6 months interrupted by zoledronate for 12 months compared to romosozumab for 12 months uninterrupted followed by zoledronate for 12 months. The investigators will also evaluate if 6 months of romosozumab followed by 18 months of zoledronate is non-inferior to the standard regimen of romosozumab for 12 months followed by zoledronate for 12 months.
Detailed description
Recent clinical trials have demonstrated the benefit of bone anabolic treatment over no treatment or antiresorptive treatment in terms of increasing bone mineral density (BMD) and reducing fracture risk for patients with osteoporosis. However, the bone anabolic treatment is expensive and therefore restricted to a limited group of patients.
This study is based on the hypothesis that treatment with romosozumab for 6 months, zoledronate for 12 months, and romosozumab for 6 months results in larger gains in bone mineral density than treatment regimens based on romosozumab treatment for 6 or 12 months followed by zoledronate for a total of 24 months of treatment due to reappearance of the bone anabolic effect of romosozumab upon retreatment.
The OPTIMIST study is a two-year, randomised, active controlled, open-label, intervention trial. The study includes 270 postmenopausal women who will be randomised to 3 groups. Group 1 (n=90) will receive romosozumab for 12 months followed by zoledronate for 12 months. Group 2 (n=90) will receive romosozumab for 6 months followed by zoledronate for 12 months and romosozumab for 6 months. Group 3 (n=90 ) will receive romosozumab for 6 months followed by zoledronate for 18 months.
The investigational drugs in this study are romosozumab 210 mg/2,34 mL and zoledronate 5 mg/100 mL
This study will include 270 treatment naïve postmenopausal women. When inclusion and exclusion criteria have been reviewed, and the participant meets the requirements for study participation and continues to participate in the study, the patients will be randomized 1:1:1 Data will be registered in RedCAP (eCRF) and site monitoring assessed by the local Good Clinical Practice unit (GCP-unit).
The patients will be recruited from the outpatient clinics and the Dual-Energy X-ray Absorptiometry (DXA) units to which patients are referred from their general practitioner or fracture liaison services (FLS) at:
Department of Endocrinology, Odense University Hospital Department of Endocrinology and Internal Medicine, Aarhus University Hospital Department of Endocrinology, Køge Hospital Department of Endocrinology, Hvidovre Hospital Department of Endocrinology, Bispebjerg Hospital
During the intervention phase, there will be obtained fasting blood test, high-resolution peripheral quantitative computed tomography (HR-pQCT),Oral Glucose Tolerance Test (OGTT), DXA, Vertebral fracture assessment (VFA) and biochemistry at different time stamps. From 105 patients there will be obtained bone marrow aspirates and performed jamshidi bone biopsies.
The study will therefore show if it would be possible to treat twice as many patients for the same prize but also if the treatment for 12 months can be optimized. The knowledge about the optimal use of romosozumab will be included in an update of osteoporosis treatment guidelines. This will lead to optimized treatment of patients with severe osteoporosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 - ROMO 12 months, ZOL 12 months | Active comparator | Drug: Romosozumab, Drug: Zoledronate90 patients 12 months of romosozumab (ROMO) followed by 12 months of zoledronate (ZOL) |
| Group 2 - ROMO 6 months, ZOL 12 months, ROMO 6 months | Active comparator | Drug: Romosozumab, Drug: Zoledronate90 patients 6 months of romosozumab followed by 12 months of zoledronate and lastly 6 months of romosozumab. |
| Group 3 - ROMO 6 months, ZOL 18 months | Active comparator | Drug: Romosozumab, Drug: Zoledronate90 patients 6 months of romosozumab followed by 18 months of zoledronate . |
Who may qualify
- Ages
- 50 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Postmenopausal women (postmenopausal for at least two years)
- BMD T-score < -2.5 at lumbar spine, total hip, or femoral neck
- Osteoporotic fracture within the last 3 years at the spine, hip, pelvis, humerus or forearm after the age of 50 years.
Key exclusion criteria (9 listed)
- Osteoporosis treatment including hormone replacement therapy within the last 5 years
- Metabolic bone disease
- Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, liver dysfunction (baseline phosphatase higher than twice upper limit), rheumatism, severe COPD (chronic obstructive pulmonary disease), hypopituitarism, Cushing's disease
- Ongoing treatment with glucocorticoids (systemic)
- Estimated glomerular filtration rate (eGFR) < 35 mL/min
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 |
|---|---|---|
| RomosozumabAlso: EvenityRomosozumab 210 mg/2.34 ml from baseline to month 11 | Drug | Group 1 - ROMO 12 months, ZOL 12 months |
| Zoledronate5 mg/100 ml at month 12 | Drug | Group 1 - ROMO 12 months, ZOL 12 months |
| RomosozumabAlso: Evenity210 mg/2.34 ml from baseline to month 5 and from month 18 to month 23 | Drug | Group 2 - ROMO 6 months, ZOL 12 months, ROMO 6 months |
| Zoledronate5 mg/100 ml at month 6 | Drug | Group 2 - ROMO 6 months, ZOL 12 months, ROMO 6 months |
| RomosozumabAlso: Evenity210 mg/2.34 ml from baseline to month 5 | Drug | Group 3 - ROMO 6 months, ZOL 18 months |
| Zoledronate5 mg/100 ml at month 5 and month 18 | Drug | Group 3 - ROMO 6 months, ZOL 18 months |
Primary outcome
Change in total hip BMD
Time frame: 24 months
Change in total hip BMD
3 secondary outcomes
Changes in femoral neck BMD
Time frame: 24 months
Changes in trabecular bone volume fraction (bone volume/tissue volume, BV/TV) and cortical porosity measured by high-resolution peripheral quantitative computed tomography (HR-pQCT)
Time frame: 24 months
Change in spine BMD
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
- 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.
Bente Langdahl, MD, Professor, DMSc, PhD, study director
Department of Endocrinology and Internal medicin, Aarhus University Hospital
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 Romosozumab and Zoledronate in people with Osteoporosis, run by University of Aarhus at 1 site in Denmark.
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: looking for participants now, as of the sponsor's last update on 2 Jul 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 Denmark. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vivi Makinen, MD (78450000, vivmaa@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in total hip BMD (time frame: 24 months). 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 2 Jul 2026.