Step-down Therapy After Long-term Osteoporosis Treatment: A Randomized Trial

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 4
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 50
Maximum Age: 85
Healthy Volunteers: f
View:

• 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.

Locations
Other Locations
Taiwan
National Taiwan University Hospital Yunlin Branch
RECRUITING
Douliu
Contact Information
Primary
Shau-Huai Fu, PhD
b90401045@gmail.com
+886972655734
Time Frame
Start Date: 2026-01-01
Estimated Completion Date: 2028-12-31
Participants
Target number of participants: 44
Treatments
Active_comparator: Control
Zoledronate is given 6 months after the final denosumab injection, with a second zoledronate infusion administered 18 months after the last denosumab dose.
Experimental: Denosumab De-escalation + Zoledronate
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.
Sponsors
Collaborators: National Taiwan University Hospital, Yun-Lin Branch
Leads: National Taiwan University Hospital

This content was sourced from clinicaltrials.gov