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

NCT07772609 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2026-527447-18-00
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 9

Brief 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. 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.

Conditions

Osteoporosis in Post-menopausal Women

Keywords

Randomized controlled trial; Romosozumab; Denosumab; High resolution peripheral computed tomography; Bone mineral density; Zoledronic acid; Postmenopausal; Osteoporosis; Fracture risk

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Secondary Outcomes (10)

• Percent change in lumbar spine bone mineral density at Months 6, 12 and 24.

  Baseline to 6, 12 and 24 months.

• Percent Change From Baseline in Total Hip BMD at Months 6 and 12

  Baseline to 6 and 12 months.

• Incident vertebral fracture

  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

  Baseline to month 24, and for those entering the extension study, to months 36 and 48.

• Occurrence of any fracture during follow-up.

  Baseline to Month 24, and for those entering the extension study, to Months 36 and 48.

Other Outcomes (4)

• Model-Predicted Fracture Risk Reduction Based on Total Hip BMD

  Month 24

• Incremental Cost per Quality-Adjusted Life-Year (QALY) Gained

  Month 24

• Model-Estimated Lifetime Healthcare Costs

  Month 24

Study Arms (2)

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.

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.

Drug: Zoledronic Acid 5 MG in 5 ML Injection; Dietary Supplement: Calcium 500 mg and Vitamin D3 800 IU

Interventions

Romosozumab DRUG

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.

Also known as: Evenity

Short-course Romosozumab Followed by Denosumab

Zoledronic Acid 5 MG in 5 ML Injection DRUG

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.

Zoledronic Acid

Calcium 500 mg and Vitamin D3 800 IU DIETARY_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.

Short-course Romosozumab Followed by Denosumab; Zoledronic Acid

Denosumab DRUG

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.

Short-course Romosozumab Followed by Denosumab

Eligibility Criteria

• Age: 60 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sahlgrenska University Hospital: lead
• Uppsala University Hospital: collaborator
• Karolinska University Hospital: collaborator
• Norrlands University Hospital: collaborator
• Sundsvall Hospital: collaborator
• Region Stockholm: collaborator
• Skaraborg Hospital: collaborator
• Göteborg University: collaborator
• Skane University Hospital: collaborator
• University Hospital, Linkoeping: collaborator

Study Sites (9)

Skåne Universitetssjukhus

Malmö, Skåne County, 20502, Sweden

Location

Karolinska University Hospital Huddinge

Huddinge, Stockholm County, 14186, Sweden

Location

Sabbatsbergs sjukhus

Stockholm, Stockholm County, 11361, Sweden

Location

Akademiska sjukhuset

Uppsala, Uppsala County, 751 85, Sweden

Location

Norrlands universitetssjukhus

Umeå, Västerbotten County, 90185, Sweden

Location

Sundsvalls sjukhus

Sundsvall, Västernorrland County, 856 43, Sweden

Location

Sahlgrenska University Hospital Mölndal

Mölndal, Västra Götaland County, 43180, Sweden

Location

Skaraborgs sjukhus

Skövde, Västra Götaland County, 54949, Sweden

Location

Linköping University Hospital

Linköping, Östergötland County, 58185, Sweden

Location

MeSH Terms

Conditions

Osteoporosis

Interventions

romosozumab; Zoledronic Acid; Injections; Calcium; Cholecalciferol; Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Administration Routes; Drug Therapy; Therapeutics; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mattias Lorentzon, MD, PhD

  Sahlgrenska University Hospital Mölndal, Västra Götalandsregionen and University of Gothenburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mattias Lorentzon, MD, PhD

CONTACT

+46313431979; mattias.lorentzon@medic.gu.se

Lena Silberberg, BSc

CONTACT

+46313421000; lena.silberberg@vgregion.se

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant in Geriatric Medicine and Professor of Geriatric Medicine

Study Record Dates

• First Submitted: August 13, 2026
• First Posted: August 19, 2026
• Study Start (Estimated): January 11, 2027
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2031
• Last Updated: August 19, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Beginning after publication of the primary study results and available for a period determined by applicable institutional and data-retention policies.
• 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.

Locations

SE (9)