Step-down therapy to preserve spine bone density after long-term denosumab

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

This test sees if switching to half-dose denosumab every six months plus a zoledronic acid infusion better preserves lumbar spine bone density in men and postmenopausal women aged 50–85 who have used denosumab for at least three years.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 50 Years to 85 Years
• Sex: All
• Sponsor: National Taiwan University Hospital (Academic / other)
• Drugs / interventions: denosumab
• Locations: 1 site (Douliu, Taiwan)
• Trial ID: NCT07281586 on ClinicalTrials.gov

What this trial studies

This open-label Phase 4 trial randomizes 44 participants, stratified by prior denosumab duration (<4 years vs ≥4 years), to test a de-escalation strategy of half-dose denosumab (30 mg every six months) combined with sequential zoledronic acid versus standard sequential zoledronic acid. Enrollment includes postmenopausal women and men aged 50–85 with osteoporosis or osteopenia-related fractures who have received continuous denosumab for ≥3 years. The primary focus is preservation of lumbar spine bone mineral density, with particular attention to the first year after changing therapy when rebound bone loss is greatest. The trial is single-center and open-label, with bone density and safety monitoring over the follow-up period.

Who should consider this trial

Good fit: Postmenopausal women and men aged 50–85 with osteoporosis or osteopenia-related fractures who have received continuous denosumab for at least three years without dosing gaps over nine months are the intended participants.

Not a fit: Patients with secondary metabolic bone disease, active or prior malignancy, ongoing systemic glucocorticoid use, current bone-active medications, significant renal impairment (eGFR <50 mL/min/1.73 m²), hypocalcemia, or known hypersensitivity to zoledronic acid are ineligible and unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could reduce the rapid bone loss and short-term fracture risk that commonly follow stopping long-term denosumab.

How similar studies have performed: Sequential bisphosphonate transitions after denosumab have shown mixed results in preventing rebound bone loss, and the half-dose denosumab de-escalation combined with zoledronic acid is a relatively new approach with limited prior evidence.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Where this trial is running

Douliu, Taiwan

• National Taiwan University Hospital Yunlin Branch — Douliu, Taiwan, Taiwan (Recruiting)

Study contacts

• Study coordinator: Shau-Huai Fu, PhD

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