Study Evaluating Denosumab on Bone and Vascular Metabolism in Osteoporotic Chronic Kidney Disease

Study Overview
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Brief Summary
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Aim of this study is to evaluate in a population of old osteoporotic chronic kidney disease females the effect of denosumab: on bone mineral density (femoral T-score) at 24 months on bone mineral density evolution (femoral T-score) after 24 months of follow-up on bone mineral density evolution (lumbar T-score) after 24 months of follow-up on coronary and abdominal aorta calcification scores evolution after 24 months of follow-up on parameters of bone remodelling (OPG, RANKL, sclerostin, DKK-1), of mineral and calcium metabolism (FGF23 Ct, Klotho, PTH, 25(OH) vitamin D3, phosphorus, calcium, bone alklaline phosphatase, osteocalcin, CTX), of inflammation (CRP) after 24 months of follow-up on cardiovascular morbidity (cardiovascular events) and mortality after 24 months of follow-up the tolerance after 24 months of follow-up

Detailed Description
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Aim of this study is to evaluate in a population of old osteoporotic chronic kidney disease females the effect of denosumab: on bone mineral density (femoral T-score) (by bone densitometry) at 24 months on bone mineral density evolution (femoral T-score) (by bone densitometry) after 24 months of follow-up on bone mineral density evolution (lumbar T-score) (by bone densitometry) after 24 months of follow-up on coronary and abdominal aorta calcification scores evolution (by multiple detector computed tomography and plain abdominal X-ray) after 24 months of follow-up on parameters of bone remodelling (OPG, RANKL, sclerostin, DKK-1), of mineral and calcium metabolism (FGF23 Ct, Klotho, PTH, 25(OH) vitamin D3, phosphorus, calcium, bone alklaline phosphatase, osteocalcin, CTX), of inflammation (CRP) after 24 months of follow-up on cardiovascular morbidity (cardiovascular events) and mortality after 24 months of follow-up the tolerance after 24 months of follow-up

Official Title
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Randomized Controlled Study Evaluating the Effect of a Biotherapy Treatment (Anti-RANKL Ligand Antibody: Denosumab) on Bone and Vascular Metabolism in Osteoporotic Chronic Kidney Disease

Conditions
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Female With Osteoporosis and Chronic Kidney Disease

Intervention / Treatment
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* Drug: Denosumab
* Drug: NaCl (placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient of 65 years or older Chronic kidney disease stage 5 patient, hemodialyzed with extracorporeal treatment for at least 3 months Patient with osteoporosis (history of bone fracture or T-scoring < -2.5 SD) PTH levels in the serum in agreement with the KDIGO guidelines, in the absence of treatment with Cinacalcet. Exclusion Criteria: Cinacalcet treatment Calcium parameters (PTH, 25(OH) vitamin D3, Calcium) outside the KDIGO guidelines Suspicion of lower bone remodeling Hypersensibility to active substance or one of excipients of denosumab Patient with a cancer or myeloma Patient with severe heaptic cytolysis Patients with severe teeth problems Patient positive for HIV Patient involved in another biomedical research Vulnerable patients (protected by the law, under guardianship, deprived of freedom)

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 95 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab<br>Denosumab 60 mg, subcutaneous injection every 6 months for 24 months | Drug: Denosumab<br>* Patients will receive a subcutaneous injection of Denosumab every 6 months for the duration of the study. In addition, they will receive vitamin D and calcium (which is the normal treatment) for the duration of the study.<br>|
| Placebo Comparator: Placebo<br>NaCl 0.9% (1 mL), subcutaneous injection every 6 months for 24 months | Drug: NaCl (placebo)<br>* Patients will receive a subcutaneous injection of NaCl every 6 months for the duration of the study. In addition, they will receive vitamin D and calcium (which is the normal treatment) for the duration of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative variation of femoral bone mineral density after 24 months of follow-up (T-score evaluated by osteodensitometry) |  | 24 months after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative variation of lumbar bone mineral density after 24 months of follow-up (T-score evaluated by osteodensitometry) |  | 24 months after inclusion | 
| Relative variation of coronary calcification scores after 24 months of follow-up |  | 24 months after inclusion | 
| Relative variation of abdominal aorta calcification scores after 24 months of follow-up |  | 24 months after inclusion | 
| Variation of calcium at 6, 12, 18 and 24 months of follow-up |  | 6, 12, 18 and 24 months after inclusion | 
| Variation of phosphorus at 6, 12, 18 et 24 months of follow-up |  | 6, 12, 18 and 24 months after inclusion | 
| Morbi-mortality at 24 months of follow-up |  | 24 months after inclusion | 
| Adverse events occuring during the entire study |  | 24 months after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoporosis, chronic kidney disease, anti-RANK ligand antibody, bone mineral density, vascular calcifications