Single or Repeat Zoledronate Versus Alendronate Following Denosumab (EUROpean Denosumab Effects Consolidation Study)

Study Overview
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Brief Summary
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A 24-month prospective, open-label, randomized, multicenter, multinational, non-inferiority pragmatic clinical trial evaluating zoledronate single or double infusion versus oral alendronate following denosumab

Detailed Description
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125 postmenopausal women treated with Dmab for 3 or more years who will reach osteopenia with denosumab will be randomized into three groups: i) zoledronate infusion (5mg) at 6 months after last Dmab dose (single Zol group) ii) zoledronate infusion (5mg) at 6 and 12 months after last Dmab dose (double Zol group) iii) alendronate 70mg orally weekly for 12 months (ALN group) All women will receive no further treatment during the 2nd year of the study. Participating centers: ECTS affiliated bone centers Endpoints: Primary: BMD changes at the lumbar spine at 12 months. Secondary: i) BMD changes at the lumbar spine at 24 months; ii) BMD changes at the non-dominant femoral neck and total hip at 12 and 24 months; iii) changes at levels of bone turnover markers throughout the study; iv) incident fractures: vertebral (clinical and morphometric identified on VFA scans) and non-vertebral; v) clinical parameters: height change, VAS for back pain, and use of analgesics

Official Title
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The Effectiveness of Single or Repeat Zoledronate Infusion Versus Oral Alendronate in Consolidating the Bone Accrual Achieved With Denosumab: a Study Organised by the European Calcified Tissue Society

Conditions
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Osteoporosis, Postmenopausal

Intervention / Treatment
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* Drug: Zoledronate or Alendronate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Postmenopausal women treated with denosumab for 3 or more years who will reach osteopenia Exclusion Criteria: a bone disease other than postmenopausal osteoporosis use of medications other than bisphosphonates or SERMS affecting bone metabolism during the last 12 months before entering the study creatinine clearance <60 mL/min/1.73 m2 liver failure any type of cancer uncontrolled endocrine diseases serum 25-hydroxy vitamin D (25-OHD) concentrations lower than 20 ng/mL (50 nmol/L)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| single Zol group<br>postmenopausal women treated with denosumab for 3 or more years who will reach osteopenia with denosumab and will receive a single zoledronate infusion (5mg) at 6 months after the last denosumab dose | Drug: Zoledronate or Alendronate<br>* infusion (for zoledronate) or oral digestion (for alendronate)<br>* Other names: Calcium and vitamin D supplementation;|
| double Zol group<br>postmenopausal women treated with denosumab for 3 or more years who will reach osteopenia with denosumab and will receive two zoledronate infusions (5mg) at 6 and 12 months after the last denosumab dose | Drug: Zoledronate or Alendronate<br>* infusion (for zoledronate) or oral digestion (for alendronate)<br>* Other names: Calcium and vitamin D supplementation;|
| ALN group<br>postmenopausal women treated with denosumab for 3 or more years who will reach osteopenia with denosumab and will receive alendronate 70mg orally weekly for 12 months | Drug: Zoledronate or Alendronate<br>* infusion (for zoledronate) or oral digestion (for alendronate)<br>* Other names: Calcium and vitamin D supplementation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lumbar spine BMD | BMD changes at the lumbar spine at 12 and 24 months | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| femoral neck BMD | BMD changes at the non-dominant femoral neck and total hip at 12 and 24 months | 24 months | 
| P1NP | bone turnover (formation) marker | baseline, 3 months, 6 months, 12 months, 18 months, 24 months | 
| CTx | bone turnover (resorption) marker | 24 months | 
| fracture | incident fractures: vertebral (clinical and morphometric identified on VFA scans) and non-vertebral | 24 months | 
| height | loss of height | 24 months |