StrAtegies For Zoledronic Acid Post-dEnosumab Discontinuation in Postmenopausal oSTeoporosis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: a second infusion of ZOL when crosslaps levels reach 300 pg/mL, a rescue second infusion at month-12 (standard traitment).
- Who it may be relevant to
- Registry conditions: Postmenopausal Osteoporosis. Basic parameters: from 18 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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
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.
Interventions
- Drug 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 - 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
Primary outcome measures
- Maintain lumbar bone mineral density (BMD) after 1 year of ZOL [Time frame: 1 year after inclusion]
Secondary outcome measures (7)
- Maintain hip bone mineral density (BMD) after 1 year of ZOL [Time frame: 1 year after inclusion]
- the changes in hip and lumbar BMD from baseline [Time frame: Day 0, 1 year after inclusion, 2 year after inclusion]
- the changes from baseline in bone turnover markers [Time frame: 1 year after inclusion, 2 year after inclusion]
- morphometric vertebral fractures [Time frame: 1 year after inclusion, 2 year after inclusion]
- Patients requiring a second ZOL [Time frame: 1 year after inclusion, 2 year after inclusion]
- Relation between biomarker values and densitometry evolution [Time frame: 3, 6, 9, 12 months after inclusion]
- Relation between biomarker values and appearance of new vertebral fracture [Time frame: 3, 6, 9, 12 months after inclusion]
Eligibility 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
France · 17 centers
- Amiens Hospital — Amiens
- Bordeaux Hospital — Bordeaux
- Cahors Hospital — Cahors
- Dax Hospital — Dax
- Le Mans Hospital — Le Mans
- Lille Hospital — Lille
- Limoges Hospital — Limoges
- Marseille Hsopital — Marseille
- … and 9 more centers
Identifiers
NCT: NCT06767150 · RC31/23/0370