MedDataX Logo

StrAtegies For Zoledronic Acid Post-dEnosumab Discontinuation in Postmenopausal oSTeoporosis

NCT ID: NCT06767150

Last Updated: 2025-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-02

Study Completion Date

2030-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Denosumab (Dmab) is a treatment for postmenopausal osteoporosis. However, its withdrawal is associated with a rebound phenomenon associated with an unexpected increased risk of vertebral fractures. Defining the optimal strategy for Dmab withdrawal is critically needed. Investigator propose an open-label randomized superiority strategy trial to compare the 1-year lumbar densitometric efficacy of biomarkers-driven zoledronate (ZOL) infusion vs standardized ZOL treatment to mitigate rebound phenomenon.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Denosumab (Dmab) is a potent and validated treatment for postmenopausal osteoporosis. However, its withdrawal, especially after reaching therapeutic target, is associated with a rebound phenomenon characterized by: (i) an increase in bone turnover markers levels usually within first 6 months off-treatment, (ii) a decrease in BMD, and (iii) an unexpected increased risk of (multiple) vertebral fractures. Although current experts' recommendations propose a post-Dmab bisphosphonates therapy (such as ZOL) to mitigate rebound phenomenon, the optimal strategy is still matter of debate. Data suggesting a protective effect with bisphosphonates (1 infusion of ZOL or weekly alendronate) are scarce, with discrepancies, and highlight that a substantial proportion of patients experiences rebound-related bone loss despite bisphosphonate therapy. Crosslaps, a bone turnover maker, are available for daily clinical practice and reflect the antiresorptive activity of anti-resorptive drugs such as bisphosphonates. Investigator hypothesize that monitoring crosslaps levels, can help to identify patients requiring more intensive bisphosphonate (additional ZOL infusion) therapy to control the post-Dmab rebound phenomenon.

Investigator propose to compare 2 strategies for Dmab withdrawal in postmenopausal osteoporosis: a standard treatment control group treated with a single ZOL infusion versus a biomarker-guided ZOL group with an additional ZOL infusion in case of insufficient inhibition of bone resorption according to crosslaps.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Postmenopausal Osteoporosis

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Postmenopausal osteoporosis strategy denosumab zoledronate rebound withdrawal

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Intensive biomarkers-guided arm

A second infusion when crosslaps levels reach 300 pg/mL, no later than month-12

Group Type EXPERIMENTAL

a second infusion of ZOL when crosslaps levels reach 300 pg/mL

Intervention Type DRUG

a first infusion of ZOL 5 mg, 6 months after denosumab withdrawal (= study start) and a second infusion when crosslaps levels reach 300 pg/mL, no later than month-12

Standard treatment arm

Potentially a rescue second infusion at month-12, in case unfavourable outcome (incident osteoporotic fractures) or high risk of unfavourable outcome

Group Type ACTIVE_COMPARATOR

a rescue second infusion at month-12 (standard traitment)

Intervention Type DRUG

a first infusion of ZOL 5 mg, 6 months after denosumab withdrawal (= study start), and potentially a rescue second infusion at month-12, in case unfavourable outcome (incident osteoporotic fractures) or high risk of unfavourable outcome

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

a second infusion of ZOL when crosslaps levels reach 300 pg/mL

a first infusion of ZOL 5 mg, 6 months after denosumab withdrawal (= study start) and a second infusion when crosslaps levels reach 300 pg/mL, no later than month-12

Intervention Type DRUG

a rescue second infusion at month-12 (standard traitment)

a first infusion of ZOL 5 mg, 6 months after denosumab withdrawal (= study start), and potentially a rescue second infusion at month-12, in case unfavourable outcome (incident osteoporotic fractures) or high risk of unfavourable outcome

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University Hospital, Toulouse

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Amiens Hospital

Amiens, , France

Site Status RECRUITING

Bordeaux Hospital

Bordeaux, , France

Site Status RECRUITING

Cahors Hospital

Cahors, , France

Site Status RECRUITING

Dax Hospital

Dax, , France

Site Status RECRUITING

Le Mans Hospital

Le Mans, , France

Site Status RECRUITING

Lille Hospital

Lille, , France

Site Status NOT_YET_RECRUITING

Limoges Hospital

Limoges, , France

Site Status RECRUITING

Marseille Hsopital

Marseille, , France

Site Status RECRUITING

Montpellier Hospital

Montpellier, , France

Site Status RECRUITING

Nice Hospital

Nice, , France

Site Status RECRUITING

Orléans Hospital

Orléans, , France

Site Status RECRUITING

Cochin Hospital

Paris, , France

Site Status RECRUITING

Lariboisiere Hospital

Paris, , France

Site Status RECRUITING

Poitiers Hospital

Poitiers, , France

Site Status RECRUITING

Rennes Hospital

Rennes, , France

Site Status RECRUITING

Saint Etienne Hospital

Saint-Etienne, , France

Site Status RECRUITING

Toulouse Hospital

Toulouse, , France

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

France

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Yannick DEGBOE, MD

Role: CONTACT

Phone: 05 61 77 73 75

Email: [email protected]

Charline DAGUZAN

Role: CONTACT

Phone: 05 61 77 84 90

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Vincent GOEB

Role: primary

Nadia MEHSEN

Role: primary

Slim LASSOUED

Role: primary

Emilie SHIPLEY

Role: primary

Guillaume DIREZ

Role: primary

Bernard CORTET

Role: primary

Anna BILLO

Role: primary

Sophie TRIJAU

Role: primary

Paulina SZAFORS

Role: primary

Veronique BREUIL

Role: primary

Eric LESPESSAILLES

Role: primary

Karine BRIOT

Role: primary

Thomas FUNCK-BRENTANO

Role: primary

Guillaume LARID

Role: primary

François ROBIN

Role: primary

Thierry THOMAS

Role: primary

Yannick DEGBOE

Role: primary

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

RC31/23/0370

Identifier Type: -

Identifier Source: org_study_id