Sequential Treatment With Romosozumab Followed by Denosumab vs. Zoledronic Acid for Gains in HIP BMD (STRONG-HIP)

August 18, 2026 updated by: Mattias Lorentzon, Sahlgrenska University Hospital

Short-course Romosozumab Followed by Denosumab Versus Zoledronic Acid: A Multicentre Randomized Active-controlled Trial in Postmenopausal Women at High Fracture Risk

Osteoporosis is associated with a high risk of fractures, disability, loss of independence, and excess mortality. Zoledronic acid is an established first-line treatment in Sweden, but many patients at high fracture risk remain at substantial residual fracture risk. Short-course treatment with romosozumab followed by denosumab produces large increases in bone mineral density, but has not been directly compared with zoledronic acid.

STRONG-HIP is a multicentre, randomized, active-controlled phase 4 trial in 216 postmenopausal women aged 60 years or older with osteoporosis and high fracture risk. Participants are randomized 1:1 to receive romosozumab 210 mg monthly for 3 months followed by denosumab 60 mg every 6 months, or zoledronic acid 5 mg intravenously at baseline and Month 12.

The primary objective is to determine whether the romosozumab-denosumab sequence produces a greater percentage increase in total hip bone mineral density from baseline to Month 24 than zoledronic acid. Secondary outcomes include total hip and lumbar spine BMD at earlier time points, vertebral and clinical fractures, bone turnover markers, safety, health-related quality of life, and health-economic outcomes. A mechanistic substudy will assess bone microarchitecture and estimated strength using HR-pQCT.

Participants are followed for 24 months in the main study and may enter an optional extension with follow-up to Month 48 to assess the durability of treatment effects.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
216

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Sweden
    • Skåne County
      • Malmö, Skåne County, Sweden, 20502
    • Stockholm County
      • Huddinge, Stockholm County, Sweden, 14186
        • Karolinska University Hospital Huddinge
        • Contact:
      • Stockholm, Stockholm County, Sweden, 11361
    • Uppsala County
      • Uppsala, Uppsala County, Sweden, 751 85
    • Västerbotten County
    • Västernorrland County
      • Sundsvall, Västernorrland County, Sweden, 856 43
    • Västra Götaland County
      • Mölndal, Västra Götaland County, Sweden, 43180
      • Skövde, Västra Götaland County, Sweden, 54949
    • Östergötland County
      • Linköping, Östergötland County, Sweden, 58185
        • Linköping University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. The subject is a postmenopausal woman aged 60 years or older at screening.
  2. The subject has provided written informed consent before any trial-specific procedure is performed.
  3. The subject has osteoporosis at screening defined as a T-score of -2.5 or lower at the total hip or lumbar spine (L1-L4) on central reader confirmed bone densitometry by DXA.
  4. The subject is at high fracture risk, defined by at least one of the following: a previous low-trauma fracture after age 50 years (excluding skull, face, fingers and toes); FRAX probability at or above the age-specific Swedish intervention threshold (using Nordic and Nordic borne calculations, as appropriate) in use at screening.
  5. Corrected plasma calcium or ionized calcium is within the local reference range before randomization.
  6. Serum 25-hydroxyvitamin D concentration ≥50 nmol/L before randomization.
  7. Adequate renal function for zoledronic acid treatment, defined as creatinine clearance ≥35 mL/min calculated using the clinical trial center specified calculation procedure (e.g. the Cockcroft-Gault equation) before randomization.
  8. The subject is able and willing, in the investigator's judgment, to comply with the trial procedures and attend scheduled visits.
  9. For participants entering the extension, separate written extension consent is obtained before any extension-specific procedure is performed.

Exclusion Criteria:

  1. Severe osteoporosis, defined as total hip or lumbar spine T-score < -3.5 and/or prevalent grade 2 or grade 3 vertebral fracture.
  2. Previous myocardial infarction or stroke at any time before screening.
  3. Transient ischemic attack, unstable angina, coronary or major peripheral revascularization within 12 months before screening, decompensated heart failure, uncontrolled clinically relevant arrhythmia, or any cardiovascular condition that in the investigator's judgment confers unacceptably high risk of a major adverse cardiovascular event during study participation.
  4. Use of intravenous bisphosphonate therapy or teriparatide within 3 years before randomization.
  5. Use of oral bisphosphonate or denosumab within 12 months before randomization.
  6. Any previous use of romosozumab.
  7. Use of systemic estrogen, selective estrogen receptor modulator within 3 months.
  8. Use of oral glucocorticoids for more than 14 consecutive days during the 6 months before screening.
  9. Known metabolic bone disease other than postmenopausal osteoporosis, including but not limited to Pagets disease, osteomalacia, untreated hyperparathyroidism, osteogenesis imperfecta, or active renal osteodystrophy.
  10. Creatinine clearance below 35 mL/min, rapidly deteriorating renal function, or another renal condition that makes zoledronic acid unsafe.
  11. Hypocalcaemia (ionized calcium <1.15 mmol/l or total albumin corrected calcium of <2.15 mmol/l) or vitamin D 25-OH-vit-D <50nmol/l, not corrected before randomization.
  12. Unexplained serum alkaline phosphatase >2 times the local upper limit of normal.
  13. Malignancy within the last 5 years, except adequately treated basal-cell carcinoma of the skin, squamous-cell carcinoma in situ of the skin, or cervical carcinoma in situ.
  14. Current osteonecrosis of the jaw, unhealed oral or jaw lesions, active dental or jaw infection, or planned invasive dental extraction/implant procedure that has not been completed and healed before randomization, if considered by the investigator to represent a contraindication or unacceptable risk for treatment with romosozumab, denosumab or zoledronic acid.
  15. Known hypersensitivity or contraindication to romosozumab, denosumab, zoledronic acid, calcium supplementation, or vitamin D supplementation that cannot be safely managed under the protocol.
  16. Inability to undergo protocol DXA/VFA reliably, for example because of body habitus exceeding scanner limits, inability to position safely, or interfering hardware or artefacts that prevent valid endpoint assessment.
  17. Current participation, or recent participation within 30 days or five half-lives (whichever is longer), in another interventional clinical trial that could affect safety or data interpretation.
  18. Any other medical, psychiatric, social or logistical condition that, in the investigators opinion, makes participation unsafe or would compromise protocol adherence or data reliability.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Short-course Romosozumab Followed by Denosumab
Participants will receive romosozumab 210 mg by subcutaneous injection at Baseline and Months 1 and 2, followed by denosumab 60 mg by subcutaneous injection at Months 3, 9, 15, and 21. Participants entering the optional extension will continue denosumab at Months 27, 33, 39, and 45, unless contraindicated or clinically inappropriate. All participants will receive daily calcium and vitamin D supplementation throughout the study.
Drug: Romosozumab
Romosozumab 210 mg will be administered by subcutaneous injection once monthly for 3 consecutive months. Each monthly dose consists of two consecutive 105 mg injections.
Other Names:
  • Evenity
Dietary supplement: Calcium 500 mg and Vitamin D3 800 IU
Calcium and vitamin D supplementation, using 500 mg elemental calcium plus 20 micrograms cholecalciferol daily for 24 months. Participants entering the optional extension will receive daily calcium and vitamin D supplementation throughout the study.
Drug: Denosumab
Denosumab 60 mg by subcutaneous injection at Months 3, 9, 15, and 21. Participants entering the optional extension will continue denosumab at Months 27, 33, 39, and 45 unless contraindicated or clinically inappropriate.
Active Comparator: Zoledronic Acid
Participants will receive zoledronic acid 5 mg by intravenous infusion at Baseline and Month 12. Participants entering the optional extension will receive additional infusions at Months 24 and 36, unless contraindicated or clinically inappropriate. All participants will receive daily calcium and vitamin D supplementation throughout the study.
Dietary supplement: Calcium 500 mg and Vitamin D3 800 IU
Calcium and vitamin D supplementation, using 500 mg elemental calcium plus 20 micrograms cholecalciferol daily for 24 months. Participants entering the optional extension will receive daily calcium and vitamin D supplementation throughout the study.
Drug: Zoledronic Acid 5 MG in 5 ML Injection
Zoledronic acid 5 mg intravenously at Baseline and Month 12, with additional doses at Months 24 and 36 in the extension unless contraindicated or clinically inappropriate.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent change in total hip bone mineral density
Time Frame: 24 months
Percentage change from baseline to month 24 in total hip bone mineral density, measured by dual-energy X-ray absorptiometry.
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent change in lumbar spine bone mineral density at Months 6, 12 and 24.
Time Frame: Baseline to 6, 12 and 24 months.
Percentage change from baseline to months 6, 12 and 24 in lumbar spine bone mineral density, measured by dual-energy X-ray absorptiometry.
Baseline to 6, 12 and 24 months.
Percent Change From Baseline in Total Hip BMD at Months 6 and 12
Time Frame: Baseline to 6 and 12 months.
Percentage change from baseline to month 6 and 12 total hip mineral density, measured by dual-energy X-ray absorptiometry.
Baseline to 6 and 12 months.
Incident vertebral fracture
Time Frame: From baseline to months 12, 24 in the main study. For those entering the extension study, from baseline to months 36 and 48.
Incident morphometric vertebral fracture by Genant grading on centrally read vertebral fracture assessment (VFA)
From baseline to months 12, 24 in the main study. For those entering the extension study, from baseline to months 36 and 48.
First clinical fragility fracture
Time Frame: Baseline to month 24, and for those entering the extension study, to months 36 and 48.
Time to first clinical fragility fracture
Baseline to month 24, and for those entering the extension study, to months 36 and 48.
Occurrence of any fracture during follow-up.
Time Frame: Baseline to Month 24, and for those entering the extension study, to Months 36 and 48.
Occurrence of any new morphometric vertebral fracture or clinical fragility fracture during follow-up.
Baseline to Month 24, and for those entering the extension study, to Months 36 and 48.
Percent Change From Baseline in plasma C-Terminal Telopeptide of Type I Collagen
Time Frame: Baseline and Months 1, 3, 6, 12, and 24
Percent change from baseline in plasma C-terminal telopeptide of type I collagen (CTX), a marker of bone resorption. Samples will be collected before study-drug administration at treatment visits and analysed centrally. Treatment-group differences over time will be assessed using a longitudinal repeated-measures model.
Baseline and Months 1, 3, 6, 12, and 24
Percent Change From Baseline in Plasma Procollagen Type I N-Terminal Propeptide
Time Frame: Baseline and Months 1, 3, 6, 12, and 24
Percent change from baseline in Plasma Procollagen Type I N-Terminal Propeptide, a marker of bone formation. Samples will be collected before study-drug administration at treatment visits and analysed centrally. Treatment-group differences over time will be assessed using a longitudinal repeated-measures model.
Baseline and Months 1, 3, 6, 12, and 24
EuroQol 5-Dimension 5-Level (EQ-5D-5L) Health-State Utility Index
Time Frame: Baseline, Month 12, and Month 24
The EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire will be converted to a health-state utility index using the prespecified Swedish value set. Index values range from -0.31 to 1.00, where 1.00 represents full health and higher values indicate better health-related quality of life. Between-group changes from baseline will be evaluated at Months 12 and 24.
Baseline, Month 12, and Month 24
Model-Estimated Lifetime Number of Fractures
Time Frame: Month 24
Expected lifetime numbers of hip, vertebral, and other osteoporotic fractures will be estimated for each treatment strategy using a lifetime decision-analytic osteoporosis model informed by the randomized Month-24 total hip BMD treatment difference and Swedish epidemiological data.
Month 24
Budget Impact of the Sequential Treatment Strategy
Time Frame: Month 24
Estimated net financial impact over a prespecified 5-year implementation horizon of introducing the sequential treatment strategy in Swedish clinical practice, based on the eligible population, expected uptake, treatment costs, and projected fracture-related cost offsets.
Month 24

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Model-Predicted Fracture Risk Reduction Based on Total Hip BMD
Time Frame: Month 24
Fracture-specific relative and absolute risk reductions will be estimated from the adjusted randomized between-group difference in percent change from baseline in total hip BMD at Month 24. The treatment difference will be translated into expected fracture-risk reductions using prespecified validated meta-regression models underpinning the FDA-qualified total hip BMD surrogate endpoint. Estimates may include hip, vertebral, nonvertebral, and all clinical fractures, according to the available validated models.
Month 24
Incremental Cost per Quality-Adjusted Life-Year (QALY) Gained
Time Frame: Month 24
Incremental cost per quality-adjusted life-year gained for the sequential treatment strategy compared with zoledronic acid, estimated from a Swedish healthcare perspective using a lifetime health-economic model. The model will use treatment effects derived from the randomized Month-24 total hip BMD difference together with Swedish epidemiological, cost, mortality, and utility inputs.
Month 24
Model-Estimated Lifetime Healthcare Costs
Time Frame: Month 24
Discounted lifetime healthcare costs per participant, including treatment, administration, monitoring, adverse-event management, and fracture-related healthcare costs, estimated from a Swedish healthcare perspective using a lifetime health-economic model based on treatment effects and other study data available at Month 24.
Month 24
Model-Estimated Quality-Adjusted Life-Years
Time Frame: Month 24
Discounted lifetime quality-adjusted life-years (QALYs) per participant estimated using EQ-5D-5L and prespecified fracture-state utility inputs in a lifetime health-economic model based on treatment effects and other study data available at Month 24.
Month 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sahlgrenska University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Karolinska University Hospital
Göteborg University
Sundsvall Hospital
Region Stockholm
University Hospital, Linkoeping
Skane University Hospital
Uppsala University Hospital
Skaraborg Hospital
Norrlands University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mattias Lorentzon, MD, PhD, Sahlgrenska University Hospital Mölndal, Västra Götalandsregionen and University of Gothenburg

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 11, 2027

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 13, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 19, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 19, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2026-527447-18-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data underlying the published results may be made available to qualified researchers upon reasonable request. Supporting documents may include the study protocol, statistical analysis plan, and a redacted clinical study report.

IPD Sharing Time Frame

Beginning after publication of the primary study results and available for a period determined by applicable institutional and data-retention policies.

IPD Sharing Access Criteria

De-identified individual participant data and supporting study documents may be made available to qualified researchers upon reasonable request after publication of the primary results, subject to scientific review, applicable ethical and data-protection requirements, and a data-use agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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