Severe Hypocalcemia Risk with Denosumab and CKD Patients Save

On 1-19-2024 the Food and Drug Administration (FDA) issued a Drug Safety Communication about the risk of severe hypocalcemia in chronic kidney disease (CKD) patients taking denosumab for osteoporosis, with an accentuated risk in older women who are dialysis-dependent.

This report is an update to their November 2022 investigation, the results of a related study being recently reported in JAMA.

A retrospective cohort study compared 1523 dialysis-dependent patients initiating denosumab against 1281 initiating oral bisphosphonates between 2013 and 2020. The primary endpoint was the cumulative incidence of severe hypocalcemia (ie, <7.5 mg/dL [1.88 mmol/L] or emergent care) at 12 weeks.

was 41.1% with denosumab, 60 mg, vs 2.0% with oral bisphosphonates (weighted risk difference, 39.1% [95% CI, 36.3%-41.9%]).

At 12 weeks they found that 607 of 1523 (41%) denosumab-treated patients and 23 of 1281 (2%) oral bisphosphonate–treated patients developed severe hypocalcemia. The 12-week weighted risk ratio was 20.7 [95% CI, 13.2-41.2]).

The rate of very severe hypocalcemia (serum calcium below 6.5 mg/dL [1.63 mmol/L] or emergent care) was also increased with denosumab (10.9%) vs oral bisphosphonates (0.4%).

The FDA warning now appears as a Boxed Warning in the Prolia product label. Hypocalcemia is usually seen between weeks 2-5 post injection (range: 2-10 wks). Pts may or may not be symptomatic or manifest findings of hypocalcemia - confusion; seizures; irregular heart rhythm; face twitching; uncontrolled muscle spasms; weakness, tingling, or numbness. CKD patients, especially those on dialysis should have serum calcium and renal function tests monitored.