From the Guidelines
For patients on Prolia (denosumab) injections, calcium levels should be checked before each dose, which is typically administered every 6 months, and also within 2 weeks after the initial dose in patients at high risk for hypocalcemia, such as those with severe renal impairment or parathyroid disorders, as recommended by recent guidelines 1.
Monitoring Schedule
The monitoring schedule should include:
- Serum calcium levels before each dose
- Serum phosphorus, magnesium, and vitamin D levels regularly
- Correction of any pre-existing hypocalcemia before starting Prolia
- Ensuring adequate vitamin D levels before starting Prolia
- Advising patients to take calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) supplements throughout treatment
Importance of Monitoring
This monitoring schedule is crucial because Prolia works by inhibiting osteoclast activity, which can reduce calcium release from bone into the bloodstream, potentially leading to hypocalcemia, especially in the first weeks after administration, as noted in studies on denosumab and bone metabolism 1.
Symptoms of Hypocalcemia
Patients should be aware of the symptoms of hypocalcemia, which include:
- Paresthesias
- Muscle stiffness
- Tetany
- Seizures in severe cases
Additional Considerations
It is essential to note that denosumab may be administered to patients with impaired renal function or even patients on hemodialysis; however, the risk for severe hypocalcemia and hypophosphatemia is greater, and the dose, schedule, and safety of denosumab have not yet been defined, as discussed in the context of bone metastases treatment 1.
From the FDA Drug Label
In patients without advanced chronic kidney disease who are predisposed to hypocalcemia and disturbances of mineral metabolism (e. g. history of hypoparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, excision of small intestine, treatment with other calcium-lowering drugs), assess serum calcium and mineral levels (phosphorus and magnesium) 10 to14 days after Prolia injection Monitor serum calcium weekly for the first month after Prolia administration and monthly thereafter
Checking Calcium Levels:
- For patients without advanced chronic kidney disease, check serum calcium and mineral levels 10 to 14 days after Prolia injection.
- For patients with advanced chronic kidney disease, monitor serum calcium weekly for the first month after Prolia administration and monthly thereafter. 2
From the Research
Monitoring Calcium Levels in Patients on Prolia Injections
- Patients on Prolia (denosumab) injections are at risk of developing hypocalcemia, a known side-effect of denosumab treatment 3.
- The frequency of checking calcium levels in these patients is crucial, especially in those with underlying conditions such as vitamin D deficiency or chronic kidney disease.
- A study suggests that patients with a baseline serum calcium level of less than 9.3 mg/dL are at a higher risk of developing hypocalcemia 4.
- Another study recommends that patients with chronic kidney disease (CKD) should have their calcium levels monitored closely, as they are at a higher risk of developing hypocalcemia 5.
- A population-based cohort study found that the incidence of hypocalcemia in denosumab users was low, but increased substantially in those with estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 6.
- The study also found that only one-third of denosumab users had their serum calcium checked within 180 days after their prescription, highlighting the need for regular monitoring 6.
Risk Factors for Hypocalcemia
- Age ≥65 years 4
- Grade 1 or higher serum alkaline phosphatase elevation 4
- Adjusted serum calcium level of less than 9.3 mg/dL at baseline 4
- Co-administration of cytotoxic agents 4
- Lower baseline serum calcium and 25 hydroxyvitamin D 5
- Both low and high bone turnover 5