Zoledronate options after stopping denosumab in postmenopausal osteoporosis.

StrAtegies For Zoledronic Acid Post-dEnosumab Discontinuation in Postmenopausal oSTeoporosis

Phase 4 Interventional University Hospital, Toulouse · NCT06767150

This trial will test whether using a blood bone‑turnover marker to decide on extra zoledronate infusions better prevents spinal bone loss in postmenopausal women who stop denosumab.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment200 (estimated)
Ages18 Years and up
SexFemale
SponsorUniversity Hospital, Toulouse Academic / other
Drugs / interventionsdenosumab, romosozumab
Locations17 sites (Amiens and 16 other locations)
Trial IDNCT06767150 on ClinicalTrials.gov

What this trial studies

This is an open‑label, randomized superiority trial comparing two approaches after denosumab discontinuation: a single standardized zoledronate infusion versus a biomarker‑guided strategy that gives an additional zoledronate infusion if serum CrossLaps rises above 300 pg/mL. Eligible participants are postmenopausal women treated with denosumab for at least two years who meet stopping criteria after reaching therapeutic targets. Participants will be followed for one year with primary outcome of lumbar spine bone mineral density change and secondary outcomes including bone turnover markers and fracture events. The biomarker arm uses scheduled CrossLaps monitoring to trigger extra treatment, while the control arm receives one infusion with a possible rescue dose at month 12.

Who should consider this trial

Good fit: Postmenopausal women who have received denosumab for at least two years, are stopping because they reached treatment targets, and who had a prior severe fracture or a femoral/lumbar T‑score ≤ -2.5 before starting denosumab.

Not a fit: Patients with contraindications to bisphosphonates (for example significant kidney disease or prior zoledronate intolerance), those on other bone‑active medications, or those unable to attend the study sites are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, tailoring zoledronate infusions to CrossLaps levels could reduce post‑denosumab bone loss and lower the risk of rebound vertebral fractures.

How similar studies have performed: Some prior studies suggest bisphosphonates can blunt rebound bone loss after denosumab but evidence is limited and inconsistent, making this biomarker‑guided approach relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Women with post-menopausal osteoporosis
* And treated with denosumab for at least 2 years and reaching decision of denosumab withdrawal because of achieved therapeutic target defined as no fracture during treatment; no new risk factors; no BMD decrease \> 0.03 g/cm² at the spine or hip;
* And with a history of severe fracture or a femoral or lumbar T-score ≤ -2.5 prior denosumab initiation.

Exclusion Criteria:

* Dmab use for bone disease other than post-menopausal osteoporosis.
* Uncontrolled endocrine diseases. Liver failure.
* Use of medication affecting bone metabolism during the last year, including bisphosphonates, teriparatide, romosozumab, Selective Estrogen Receptor Modulators, breast cancer hormonotherapy, glucocorticoids over 5 mg/day.
* Contra-indication to bisphosphonates according to license recommendation including chronic kidney disease with GFR stage \> or = G3b. Prior intolerance to zoledronic acid.
* Subjects unable to give an informed consent or to fill the case report form. Subjects under law protection.
* Foreseeable poor compliance with the strategy, alcoholism, toxicomania.

Where this trial is running

Amiens and 16 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Postmenopausal OsteoporosisPostmenopausal osteoporosisstrategydenosumabzoledronatereboundwithdrawal
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.