Step-down Therapy After Long-term Osteoporosis Treatment

NCT07281586 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 202412063MINE
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Maintaining bone mineral density (BMD) after discontinuing denosumab (Prolia) is a major clinical challenge, as rapid bone loss commonly occurs when treatment is stopped, especially after more than three years of use. Standard sequential therapy with bisphosphonates such as zoledronic acid (Aclasta) often fails to fully prevent BMD decline, and most bone loss occurs within the first year, making effective suppression of the rebound effect essential. This study investigates whether a de-escalation strategy-using half-dose denosumab (30 mg every six months) combined with sequential zoledronic acid-can better preserve lumbar spine BMD after long-term denosumab therapy. Eligible participants include postmenopausal women and men ≥50 years old with osteoporosis or osteopenia-related fractures who have received ≥3 years of denosumab. The open-label trial applies stratified randomization based on denosumab duration (\<4 years vs. ≥4 years), assigning 22 participants to each group. Control group: standard therapy with one zoledronic acid infusion at the end of denosumab's effect and a second infusion one year later. Intervention group: half-dose denosumab plus zoledronic acid at study entry, a second half-dose denosumab injection at six months, and a second zoledronic acid infusion at twelve months. The study aims to determine whether this combined tapering-plus-bisphosphonate approach more effectively prevents lumbar spine BMD loss compared with conventional sequential therapy.

Conditions

Osteoporosis

Keywords

long-term denosumab; zoledronate; half-dose denosumab; de-escalation strategy

Outcome Measures

Primary Outcomes (1)

• Change in Lumbar Spine BMD Over 2 Years

  Change in Lumbar Spine BMD Over 2 Years

  2 Years

Secondary Outcomes (5)

• Change in Total hip BMD Over 2 Years

  2 Years

• Change in Femoral Neck BMD Over 2 Years

  2 Years

• Change in C-terminal telopeptide Over 2 Years

  2 Years

• Change in Procollagen Type I N-Propeptide Over 2 Years

  2 Years

• Incidence of clinical osteoporotic fracture

  2 years

Study Arms (2)

Control

ACTIVE COMPARATOR

Zoledronate is given 6 months after the final denosumab injection, with a second zoledronate infusion administered 18 months after the last denosumab dose.

Drug: zoledronate

Denosumab De-escalation + Zoledronate

EXPERIMENTAL

Half-dose denosumab plus zoledronic acid at 6 months after the last denosumab dose, followed by a second half-dose denosumab injection at 12 months and a second zoledronic acid infusion at 18 months after the final denosumab dose.

Drug: zoledronate; Drug: Denosumab De-escalation

Interventions

zoledronate DRUG

In the control arm, participants will receive zoledronate at trial entry, with a second dose administered at the start of the second year

Control

Denosumab De-escalation DRUG

In the intervention arm, participants will receive a half-dose of denosumab at trial entry, followed by a second half-dose 6 months later during the first year.

Denosumab De-escalation + Zoledronate

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women aged ≥50 and ≤85 years with osteoporosis- or osteopenia-related fractures who have received denosumab (Prolia) continuously for at least 3 years, with no dosing interval exceeding 9 months; and men aged ≥50 and ≤85 years with osteoporosis- or osteopenia-related fractures who have received continuous denosumab (Prolia) therapy for at least 3 years, with dosing intervals not exceeding 9 months.

You may not qualify if:

• Secondary osteoporosis Metabolic bone diseases Active or prior malignancy Ongoing systemic glucocorticoid therapy Current use of hormone replacement therapy Use of any medications that affect bone metabolism Estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.73 m² Known hypersensitivity to zoledronic acid Hypocalcemia Any other contraindications to zoledronic acid use

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• National Taiwan University Hospital, Yun-Lin Branch: collaborator

Study Sites (1)

National Taiwan University Hospital Yunlin Branch

Douliu, Taiwan, 640, Taiwan

RECRUITING

MeSH Terms

Conditions

Osteoporosis

Interventions

Zoledronic Acid

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

Central Study Contacts

Shau-Huai Fu, PhD

CONTACT

+886972655734; b90401045@gmail.com

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: SPONSOR

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: December 15, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 15, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)