Denosumab Treatment in CKD Patients at High Risk of Fracture

Capital Medical University

Status: Enrolling

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

Treatments: Drug: Non-denosumab; Drug: Denosumab

Study type: Interventional

Funder types: Other

Identifiers

NCT05692297

K2022-203-00

Details and patient eligibility

About

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.

Enrollment: 102 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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102 participants in 2 patient groups

Denosumab group

Experimental group

Description:

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.

Treatment:

Drug: Denosumab

Non-denosumab group

Active Comparator group

Description:

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.

Treatment:

Drug: Non-denosumab