PEARL: Denosumab carries risk of hypocalcemia particularly in those with low serum calcium, abnormal mineral metabolism, hypovitaminosis D, or advanced renal disease

The body increases serum calcium levels primarily through the release of bone stores.

Denosumab works by inhibiting the RANK ligand (RANKL). RANKL works to activate osteoclasts which are involved in bone resorption (bone breakdown).

Patients at risk for hypocalcemia are those with:

• low serum calcium (ionized or corrected for albumin)
• abnormal mineral metabolism (hypoparathyroidism, hypothyroidism, etc)
• hypovitaminosis D.

Patients who have advanced renal disease (eGFR <30) have low metabolically active vitamin D and are reliant on bone resorption to maintain serum calcium level. This makes patients with renal disease especially prone to hypocalcemia with the use of denosumab.