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

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

Interventions

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.

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.

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.

Sponsors & Collaborators

• Uppsala University Hospital

  collaborator OTHER

• Karolinska University Hospital

  collaborator OTHER

• Norrlands University Hospital

  collaborator OTHER

• Sundsvall Hospital

  collaborator OTHER

• Skane University Hospital

  collaborator OTHER

• Region Stockholm

  collaborator OTHER_GOV

• Skaraborg Hospital

  collaborator OTHER_GOV

• University Hospital, Linkoeping

  collaborator OTHER

• Göteborg University

  collaborator OTHER

• Sahlgrenska University Hospital

  lead OTHER

Principal Investigators

• Mattias Lorentzon, MD, PhD · Sahlgrenska University Hospital Mölndal, Västra Götalandsregionen and University of Gothenburg

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

60 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-01-11

Primary Completion

2029-12-31

Completion

2031-12-31

Countries

• Sweden

Study Locations