Denosumab Treatment in CKD Patients at High Risk of Fracture

Study Overview
=================
Brief Summary
-----------------
Objective: To verify the efficacy and safety of denosumab in the prevention and treatment of CKD-MBD in CKD patients with high risk of fracture. Methods: A cohort of CKD patients with high risk of fracture was established and followed up for long periods (≥24 months). Patients with CKD3b-5D stage and fracture risk assessment tool (FRAX) scores at high risk or very high risk of fracture were enrolled. A multicenter, prospective, open-label, randomised controlled, interventional study was conducted. The patients were divided into two groups. The patients in the denosumab group received subcutaneous injection of denosumab 60mg once every 6 months, and the patients in the non-denosumab group received conventional treatment. Bone metabolic markers (serum calcium, phosphorus, vitamin D, parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase 5b, osteocalcin, total N-terminal propeptide of type I collagen, etc.), bone mineral density (dual-energy X-ray, quantitative CT), and vascular calcification score were regularly monitored. All adverse events (all-cause death, cardiovascular death, cardiac events, fracture, hospitalization, emergency department visits, etc.) were recorded during the follow-up period. Bone mineral density and clinical parameters were compared between the two groups.

Official Title
-----------------
Denosumab Treatment in Patients With Chronic Kidney Disease (CKD) at High Risk of Fracture: A Prospective, Randomised Controlled Study

Conditions
-----------------
Chronic Kidney Diseases, Fracture, Bone Density, Low, End Stage Renal Disease

Intervention / Treatment
-----------------
* Drug: Denosumab
* Drug: Non-denosumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥18 years old; Stage 3b-5D chronic kidney disease; The 10-year probability of hip fracture assessed by fracture risk assessment tool (FRAX) was >5%; Voluntarily signed informed consent. Exclusion Criteria: Age < 18 or ≥100 years; Premenopausal women; Denosumab was absolutely contraindicated; Had received denosumab or bisphosphonates therapy; Tertiary hyperparathyroidism; Patients with malignant tumor; Patients at risk for osteonecrosis of the jaw; Estimated follow-up time ≤12 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab group<br>Fifty-one patients were randomly assigned to the denosumab group, which received subcutaneous injection of denosumab 60mg once every 6 months. Serum calcium, phosphorus, alkaline phosphatase, iPTH, tPINP, 25(OH)VitD, DXA and qCT were measured before medication. Serum calcium, phosphorus and iPTH were examined at day 1, 7 and 14, alkaline phosphatase, tPINP and 25(OH)VitD at day 7 and 14, and electrocardiogram at day 1 and 7 after treatment. Intravenous calcium supplementation was required if muscle spasms and QT prolongation occurred. Six months after medication, subcutaneous injections of denosumab 60mg were repeated. The protocol was repeated every 6 months, totally 24 months. Bone mineral density, clinical parameters and adverse events were evaluated at 24 months. | Drug: Denosumab<br>* The patients in the denosumab group received subcutaneous injection of denosumab 60mg once every 6 months for 24 months.<br>|
| Active Comparator: Non-denosumab group<br>The other 51 patients did not use denosumab and used other medications, such as diphosphonates, active vitamin D and/or active vitamin D analogue, calcimimetics, calcitonin, estrogen receptor agonists, etc. At the same time, calcium and vitamin D were supplemented. The baseline serum calcium, phosphorus, alkaline phosphatase, iPTH, tPINP, 25(OH)VitD, DXA, and qCT were measured. The above parameters were rechecked every 6 months, and the medications was recorded, totally 24 months. | Drug: Non-denosumab<br>* Taken other medications, such as diphosphonates, active vitamin D and/or active vitamin D analogue, calcimimetics, calcitonin, estrogen receptor agonists, etc.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of bone mineral density (BMD) decline at the lumbar spine | Rate of BMD decline =[(BMD24-BMD Baseline)÷BMD baseline]*100% | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of fresh fractures, cardiovascular cerebrovascular adverse events and all-cause mortality | Fresh fractures were new non-traumatic fractures during follow-up. Cardiovascular cerebrovascular adverse events were Acute myocardial infarction, heart failure, shock, cardiac arrest, stroke, and lower limb arterial occlusion occurred during follow-up. All-cause mortality was death from any cause during follow-up. | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Denosumab, Chronic Kidney Diseases, Treatment, Fracture