Risk for emergently treated hypocalcemia with denosumab increases with worsening CKD

Individuals with worsening chronic kidney disease (CKD) are at greater risk for emergently treated hypocalcemia with denosumab, and the highest risk is observed among dialysis-dependent (DD) patients and those with CKD–mineral and bone disorder (CKD-MBD), reveals a study.

This target trial emulation used Medicare fee-for-service data with prescription drug coverage from 2012 to 2020 and identified female patients aged ≥65 years initiating denosumab, oral bisphosphonates, or intravenous (IV) bisphosphonates for osteoporosis.

The researchers assessed hospital and emergency department admissions for hypocalcemia in the first 12 treatment weeks. They then calculated the inverse probability of treatment weighted cumulative incidence and weighted risk differences (RDs).

Of the patients identified, 361,453 were treated with denosumab, 829,044 with oral bisphosphonates, and 160,413 with IV bisphosphonates.

The risk for emergently treated hypocalcemia with denosumab, compared with oral bisphosphonates, increased with worsening CKD stage (p<0.001). The highest risk was noted in DD patients (3.01 percent vs 0.00 percent; RD, 3.01 percent, 95 percent confidence interval [CI], 2.27–3.77) and non-DD patients with CKD stages 4 and 5 (0.57 percent vs 0.03 percent; RD, 0.54 percent, 95 percent CI, 0.41–0.68).

Among patients with CKD stages 4 and 5 (both DD and non-DD), denosumab use showed a higher risk for emergently treated hypocalcemia, compared with oral bisphosphonates, in those with CKD-MBD (1.53 percent vs 0.02 percent; RD, 1.51 percent, 95 percent CI, 1.21–1.78) than in those without (0.22 percent vs 0.03 percent; RD, 0.19 percent, 95 percent CI, 0.08–0.31).

Denosumab also demonstrated an elevated risk when compared with IV bisphosphonates.

The study was limited by its inclusion of only Medicare populations and women.