Step-down Therapy After Long-term Osteoporosis Treatment

Sponsor
National Taiwan University Hospital
Study ID
NCT07281586
Phase
PHASE4
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
50 Years - 85 Years
Healthy Volunteers
Not accepted

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
  • zoledronate — DRUG
    In the intervention arm, participants will receive zoledronate at trial entry, with a second dose administered at the start of the second year.
  • 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.

Study Details

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.

Key Dates

Start date
Jan 1, 2026
Status verified
Nov 2025
Primary completion
Dec 31, 2028
Completion
Dec 31, 2028

Study Design

Enrollment
44 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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.

Primary Outcome Measure

Change in Lumbar Spine BMD Over 2 Years [ Time Frame: 2 Years ]

Central Contacts

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