Denosumab (Prolia) and Renal Function
Denosumab is preferred over bisphosphonates in patients with impaired renal function as it does not require dose adjustment for renal impairment and has fewer adverse events related to renal toxicity. 1
Advantages of Denosumab in Renal Impairment
- Unlike bisphosphonates (such as zoledronic acid), denosumab does not require monitoring of renal function or dose adjustments for patients with impaired renal function 1, 2
- Denosumab is the agent of choice in patients with renal impairment (creatinine clearance <60 ml/min) 1
- Recent data comparing denosumab with zoledronic acid demonstrates fewer adverse events related to renal toxicity with denosumab 1
- Denosumab has been shown to be effective at reducing fracture risk without an increase in adverse events among patients with impaired kidney function 3
Pre-Treatment Assessment
- Serum calcium must be measured before starting denosumab, as hypocalcemia is more common with denosumab (13%) than with zoledronic acid (6%) 2, 4
- Vitamin D levels should be evaluated before starting therapy to ensure adequate levels 2
- A comprehensive dental examination is mandatory before initiating denosumab to reduce the risk of osteonecrosis of the jaw 2
Monitoring During Treatment
- Regular monitoring of serum calcium is necessary, especially after the first few doses, to detect hypocalcemia 2, 5
- Vitamin D status should be evaluated intermittently during treatment 2
- Oral health should be closely monitored throughout treatment to detect early signs of osteonecrosis of the jaw 2
- Unlike bisphosphonates, serum creatinine does not need to be monitored before each dose of denosumab 1
Risk of Hypocalcemia
- Hypocalcemia risk is higher in patients with renal impairment receiving denosumab 4, 5
- In a study of patients with severe renal insufficiency (creatinine clearance <30 mL/min), 45% experienced hypocalcemia of any grade after denosumab administration 6
- Low baseline calcium, low estimated glomerular filtration rate (eGFR), and high bone turnover markers increase the risk of hypocalcemia 5
- Hypocalcemia typically occurs within 7 days after the first dose of denosumab 5
Prevention of Hypocalcemia
- Calcium supplementation (500-1000 mg/day) is required during denosumab treatment 2
- Vitamin D supplementation should be administered alongside calcium 2
- Hypocalcemia must be corrected before starting denosumab 2
- Pretreatment with antiresorptive agents may reduce the risk of hypocalcemia 5
Long-Term Considerations
- Denosumab should not be stopped abruptly given its reversible mechanism of action 1
- If denosumab is discontinued for more than 6 months, bisphosphonate treatment is recommended to suppress rebound osteolysis 1
- In a recent study of patients with decreased kidney function (eGFR 9-50 mL/min) treated with denosumab for an average of 5.3 years, 21% had biochemical hypocalcemia, 7% developed symptoms of hypocalcemia, and 4% required hospitalization 7
Special Considerations
- Patients with CKD on immunosuppressive medications have an increased risk of infection with denosumab 8
- Higher doses of steroids (>2.5 mg/day) are significantly associated with increased side effects in CKD patients on denosumab 8
- Close monitoring is essential for patients with severe renal impairment receiving denosumab 6