Osteoporosis in Post-menopausal WomenPhase 4STRONG-HIPNCT07772609
Sequential Treatment With Romosozumab Followed by Denosumab vs. Zoledronic Acid for Gains in HIP BMD
A Phase 4 study testing Romosozumab, Zoledronic Acid 5 MG in 5 ML Injection and Calcium 500 mg and Vitamin D3 800 IU in people with Osteoporosis in Post-menopausal Women, run by Sahlgrenska University Hospital at 9 sites in Sweden.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 60 years and older, women only
- Conditions the study is for
- Osteoporosis in Post-menopausal Women
- What is being tested?
- Romosozumab, Zoledronic Acid 5 MG in 5 ML Injection and Calcium 500 mg and Vitamin D3 800 IU
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 216 participants
- Where
- 9 sitesSweden
- Study dates
- 11 Jan 2027to 31 Dec 2031
- Phase
- Phase 4
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 60 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The subject is a postmenopausal woman aged 60 years or older at screening.
- The subject has provided written informed consent before any trial-specific procedure is performed.
- 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.
- 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.
- Corrected plasma calcium or ionized calcium is within the local reference range before randomization.
- Serum 25-hydroxyvitamin D concentration ≥50 nmol/L before randomization.
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- 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.
- The subject is able and willing, in the investigator's judgment, to comply with the trial procedures and attend scheduled visits.
- For participants entering the extension, separate written extension consent is obtained before any extension-specific procedure is performed.
Who cannot join
- Severe osteoporosis, defined as total hip or lumbar spine T-score < -3.5 and/or prevalent grade 2 or grade 3 vertebral fracture.
- Previous myocardial infarction or stroke at any time before screening.
- 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.
- Use of intravenous bisphosphonate therapy or teriparatide within 3 years before randomization.
- Use of oral bisphosphonate or denosumab within 12 months before randomization.
- Any previous use of romosozumab.
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- Use of systemic estrogen, selective estrogen receptor modulator within 3 months.
- Use of oral glucocorticoids for more than 14 consecutive days during the 6 months before screening.
- Known metabolic bone disease other than postmenopausal osteoporosis, including but not limited to Pagets disease, osteomalacia, untreated hyperparathyroidism, osteogenesis imperfecta, or active renal osteodystrophy.
- Creatinine clearance below 35 mL/min, rapidly deteriorating renal function, or another renal condition that makes zoledronic acid unsafe.
- 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.
- Unexplained serum alkaline phosphatase >2 times the local upper limit of normal.
- 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.
- 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.
- Known hypersensitivity or contraindication to romosozumab, denosumab, zoledronic acid, calcium supplementation, or vitamin D supplementation that cannot be safely managed under the protocol.
- 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.
- 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.
- Any other medical, psychiatric, social or logistical condition that, in the investigators opinion, makes participation unsafe or would compromise protocol adherence or data reliability.
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
Sweden9 sites
Karolinska University Hospital Huddinge
Huddinge, Stockholm County, 14186
Bo Freyschuss, MD, PhD, +46 8123 800 00, bofreyschuss@outlook.com
Linköping University Hospital
Linköping, Östergötland County, 58185
Anna Spångeus, MD, PhD, +46 10 103 00 00, anna.spangeus@liu.se
Skåne Universitetssjukhus
Malmö, Skåne County, 20502
Kristina Åkesson, MD, PhD, +46 40 33 10 00, kristina.akesson@med.lu.se
Sahlgrenska University Hospital Mölndal
Mölndal, Västra Götaland County, 43180
Mattias Lorentzon, MD, PhD, +46313431979, mattias.lorentzon@medic.gu.se
Skaraborgs sjukhus
Skövde, Västra Götaland County, 54949
Eric Bertholds, MD, +46 500 43 10 00, eric.bertholds@vgregion.se
Sabbatsbergs sjukhus
Stockholm, Stockholm County, 11361
Kristina Ekstrand, MD, +468 123 380 00, kristina.ekstrand@regionstockholm.se
Sundsvalls sjukhus
Sundsvall, Västernorrland County, 856 43
Margareta Rödén, MD, +4660 18 10 00, margareta.berglund.roden@rvn.se
Norrlands universitetssjukhus
Umeå, Västerbotten County, 90185
Anna Ramnemark, MD, PhD, 090-785 00 00, anna.ramnemark@regionvasterbotten.se
Akademiska sjukhuset
Uppsala, Uppsala County, 751 85
Andreas Kindmark, MD, PhD, +46 18 611 00 00, andreas.kindmark@medsci.uu.se
About this study
Official title: 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.
Read more
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.
- Conditions
- Osteoporosis in Post-menopausal Women
- Being tested
- Romosozumab, Zoledronic Acid 5 MG in 5 ML Injection, Calcium 500 mg and Vitamin D3 800 IU, Denosumab
- Keywords
- Randomized controlled trial, Romosozumab, Denosumab, High resolution peripheral computed tomography, Bone mineral density, Zoledronic acid, Postmenopausal, Osteoporosis, Fracture risk
- 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 will be administered by subcutaneous injection once monthly for 3 consecutive months. Each monthly dose consists of two consecutive 105 mg injections.
Zoledronic Acid 5 MG in 5 ML InjectionDrug
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.
Calcium 500 mg and Vitamin D3 800 IUDietary supplement
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.
DenosumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Short-course Romosozumab Followed by Denosumab | Experimental | 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. Receives: Drug: Romosozumab; Dietary Supplement: Calcium 500 mg and Vitamin D3 800 IU; Drug: Denosumab |
| Zoledronic Acid | Active comparator | 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. Receives: Drug: Zoledronic Acid 5 MG in 5 ML Injection; Dietary Supplement: Calcium 500 mg and Vitamin D3 800 IU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in total hip bone mineral density
Percentage change from baseline to month 24 in total hip bone mineral density, measured by dual-energy X-ray absorptiometry.
Measured: 24 months
Secondary outcomes (10)
Percent change in lumbar spine bone mineral density at Months 6, 12 and 24.
Percentage change from baseline to months 6, 12 and 24 in lumbar spine bone mineral density, measured by dual-energy X-ray absorptiometry.
Measured: Baseline to 6, 12 and 24 months.
Percent Change From Baseline in Total Hip BMD at Months 6 and 12
Percentage change from baseline to month 6 and 12 total hip mineral density, measured by dual-energy X-ray absorptiometry.
Measured: Baseline to 6 and 12 months.
Incident vertebral fracture
Incident morphometric vertebral fracture by Genant grading on centrally read vertebral fracture assessment (VFA)
Measured: 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 to first clinical fragility fracture
Measured: Baseline to month 24, and for those entering the extension study, to months 36 and 48.
Occurrence of any fracture during follow-up.
Occurrence of any new morphometric vertebral fracture or clinical fragility fracture during follow-up.
Measured: 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
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.
Measured: Baseline and Months 1, 3, 6, 12, and 24
Percent Change From Baseline in Plasma Procollagen Type I N-Terminal Propeptide
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.
Measured: Baseline and Months 1, 3, 6, 12, and 24
EuroQol 5-Dimension 5-Level (EQ-5D-5L) Health-State Utility Index
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.
Measured: Baseline, Month 12, and Month 24
Model-Estimated Lifetime Number of Fractures
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.
Measured: Month 24
Budget Impact of the Sequential Treatment Strategy
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.
Measured: Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2026
- Study start11 Jan 2027 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoporosis in Post-menopausal WomenStudies of the same condition, open and under way.
- 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 216 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Uppsala University Hospital, Karolinska University Hospital, Norrlands University Hospital, Sundsvall Hospital, Skane University Hospital, Region Stockholm, Skaraborg Hospital, University Hospital, Linkoeping, Göteborg University
- Responsible party
- Principal investigator, Mattias Lorentzon, Sahlgrenska University Hospital
- Investigators
- Mattias Lorentzon, MD, PhD, Principal investigator, Sahlgrenska University Hospital Mölndal, Västra Götalandsregionen and University of Gothenburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07772609
- Sponsor's protocol ID
- 2026-527447-18-00
- Other IDs
- 2026-527447-18-00
- Acronym
- STRONG-HIP
- Status last verified
- Aug 2026
- First submitted
- 13 Aug 2026
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.