Skip to main content

Severe Hypocalcemia Risk with Denosumab and CKD Patients

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.


If you are a health practitioner, you may to comment.

Due to the nature of these comment forums, only health practitioners are allowed to comment at this time.

The author has no conflicts of interest to disclose related to this subject