What is the role of Denosumab (denosumab) in Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)?

From the Guidelines

Denosumab is a viable treatment option for chronic kidney disease-mineral bone disorder (CKD-MBD), particularly for patients with advanced CKD or on dialysis who have secondary hyperparathyroidism and elevated fracture risk. The standard dosing is 60 mg subcutaneously every 6 months, with no dose adjustment required for kidney function. Before initiating denosumab, ensure adequate vitamin D and calcium levels to prevent hypocalcemia, which is a significant risk especially in CKD patients. Pre-treatment calcium levels should be normal, and patients should receive vitamin D supplementation (typically cholecalciferol 1000-2000 IU daily or calcitriol 0.25-0.5 mcg daily) along with calcium supplements (500-1000 mg elemental calcium daily). Monitor calcium levels closely, particularly 1-2 weeks after the first dose and after subsequent doses if hypocalcemia risk is high. Denosumab works by inhibiting RANKL (receptor activator of nuclear factor kappa-B ligand), thereby reducing osteoclast formation and bone resorption. Unlike bisphosphonates, denosumab is not cleared by the kidneys, making it advantageous in CKD. However, be aware that discontinuation can lead to rebound bone turnover and potential vertebral fractures, so long-term therapy planning is essential 1.

Some key points to consider when using denosumab in CKD-MBD include:

• The importance of monitoring calcium levels closely to prevent hypocalcemia
• The need for adequate vitamin D and calcium supplementation before initiating denosumab
• The potential for rebound bone turnover and vertebral fractures after discontinuation of denosumab
• The advantage of denosumab not being cleared by the kidneys, making it a viable option for patients with advanced CKD or on dialysis.

It is also important to consider the underlying bone phenotype and the potential risks and benefits of antiresorptive therapy, including denosumab, in patients with CKD-MBD 1.

In terms of specific patient populations, denosumab may be particularly beneficial for patients with advanced CKD or on dialysis who have secondary hyperparathyroidism and elevated fracture risk. However, the decision to use denosumab should be individualized based on the patient's specific clinical circumstances and the potential risks and benefits of therapy 1.

Overall, denosumab is a valuable treatment option for patients with CKD-MBD, particularly those with advanced CKD or on dialysis who have secondary hyperparathyroidism and elevated fracture risk. However, it is essential to carefully consider the potential risks and benefits of therapy and to monitor patients closely for adverse effects, particularly hypocalcemia.

From the Research

Role of Denosumab in CKD-MBD

• Denosumab is a medication that can improve bone health in patients with chronic kidney disease (CKD) by reducing bone turnover and increasing bone mineral density (BMD) 2, 3, 4.
• However, denosumab is associated with a risk of hypocalcemia, particularly in patients with advanced CKD or end-stage renal disease (ESRD) 2, 5, 6, 3.
• To minimize the risk of hypocalcemia, it is essential to optimize CKD-mineral and bone disorder (CKD-MBD) and 25-hydroxyvitamin D levels, provide calcium and vitamin D prophylaxis, and closely monitor calcium levels after denosumab injection 2, 5, 6.
• The efficacy and safety of denosumab in CKD patients may depend on the patient's bone turnover status, with higher bone turnover markers (BTMs) associated with greater improvements in BMD and increased risk of hypocalcemia 3.
• Denosumab may have varying effects on BMD improvement, with a stronger impact in the first year of treatment, and early monitoring of parathyroid hormone (PTH) levels is crucial 4.

Patient Selection and Monitoring

• Choosing the "right patient" for denosumab is essential, and clinicians should carefully assess the patient's risk of hypocalcemia and monitor their calcium levels closely 2, 5, 6.
• A clinical care pathway focused on the safe provision of denosumab in advanced CKD can reduce the risk of hypocalcemia and improve patient outcomes 5.
• Regular monitoring of BTMs, PTH levels, and vascular calcification can help assess the effectiveness and safety of denosumab in CKD patients 3, 4.

Future Research Directions

• Further studies are needed to fully understand the efficacy and safety of denosumab in CKD patients, particularly in terms of its effects on fracture risk and long-term outcomes 2, 4.
• Research on the optimal dosing and administration of denosumab in CKD patients, as well as the development of strategies to minimize the risk of hypocalcemia, is also necessary 5, 3.