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.

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.