PAD Refills

November 2023

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When should serum calcium be checked in people initiating or taking denosumab (Prolia®) for fracture risk reduction?

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Previous PAD Refills newsletters

Conclusion: Health Canada recommends that serum calcium be checked:

  • before initiating treatment with denosumab
  • before each subsequent dose
  • anytime during treatment if symptoms of hypocalcemia are suspected
  • within 14 days after each dose if risk factors for hypocalcemia

The BC Provincial Academic Detailing (PAD) service is now delivering the 2023 topic Medications for osteoporosis: an update.1 This topic looks at the evidence for bisphosphonates, denosumab, raloxifene, teriparatide and romosozumab.

A common question we receive is: When should calcium be checked in people initiating or taking denosumab (Prolia®)? 

Denosumab, a subcutaneous injection given once every 6 months, requires serum calcium monitoring and is contraindicated in people with hypocalcemia. This is a relevant clinical consideration when weighing the choice to initiate denosumab because a subsequent decision to discontinue it is complicated by an increased risk of rebound vertebral fractures.1 Osteoporosis Canada explains: “It is important to communicate the need for commitment to long-term therapy and the need to transition to alternative antiresorptive therapy if discontinuing denosumab”.2

Denosumab (Prolia®): monitoring for hypocalcemia3-10
All patients check serum calcium
  • Before initiating treatment (investigate & correct hypocalcemia before initiating)
  • Before each subsequent dose
  • Anytime during treatment, if symptoms of hypocalcemia are present
Patients with risk factors for hypocalcemia additional monitoring recommendations
  • Check serum calcium within 14 days after each dose
  • Examples of risk factors for hypocalcemia:
    • CrCl <30 mL/min, dialysis*
    • History of hypocalcemia
    • Hypoparathyroidism, thyroid or parathyroid surgery
    • Malabsorption syndromes, excision of small intestine
Patient education prevention & monitoring of hypocalcemia
  • Ensure adequate calcium and vitamin D intake during denosumab treatment to reduce the risk of hypocalcemia. In denosumab clinical trials, patients were instructed to take at least 1000 mg of calcium and 400 IU of vitamin D daily.
  • Report any symptoms of hypocalcemia during treatment such as: muscle spasms, muscle twitching or cramps or numbness or tingling in fingers, toes or around mouth.
*Consultation with nephrology for patients with chronic kidney disease (CKD) may be warranted prior to initiating denosumab to assess for any relevant mineral and bone disorders (CKD-MBD). Kidney function is an important risk factor for denosumab-associated hypocalcemia therefore treatment and monitoring may need to be individualized. The risk of denosumab-associated hypocalcemia increases as eGFR declines: eGFR 30ꟷ60 mL/min: < 1% of people; eGFR 15ꟷ30 mL/min: 4% of people; eGFR <15 mL/min, dialysis: 24ꟷ42% of people.

1BC Provincial Academic Detailing Service 2023 Medications for osteoporosis: an update; 2Osteoporosis Canada CMAJ 2023;195:E1333-E1348 (PMID:37816527); 3Health Canada Drug Product Database (Prolia); 4US FDA Approved Drugs (Prolia); 5COWAN J Bone Mineral Res 2023;38:650-58 (PMID:36970786); 6THONGRAYOON Osteoporos Int 2018;29:1737-45 (PMID:29713798); 7BLOCK J Bone Miner Res 2012;27:1471-79 (PMID:22461041); 8TSVETOV Osteoporos Int 2020;31:655-65 (PMID:31838550); 9JALLEH Case Rep Nephrol 2018;7384763 (PMID:30519493); 10US Food and Drug Administration Prolia (denosumab) Medication Guide