Denosumab associated with hypocalcemia requiring treatment in patients with advanced CKD
The risk of hypocalcemia requiring ED or hospital care in patients taking denosumab appeared to increase with worsening chronic kidney disease (CKD) stage, with dialysis dependence, and with CKD-mineral and bone disorder, an analysis found.
Denosumab use was associated with hypocalcemia requiring emergency treatment in patients with chronic kidney disease (CKD), a study found.
The study looked at female Medicare beneficiaries ages 65 years and older with CKD who started denosumab, oral bisphosphonates, or IV bisphosphonates for osteoporosis between 2012 to 2020. The goal of the study was to assess the risk for emergently treated hypocalcemia by stage of CKD and presence of progression and the presence of CKD-mineral and bone disorder (CKD-MBD). The study was published Nov. 19 by Annals of Internal Medicine.
Hospital and ED admissions for hypocalcemia were assessed in the first 12 treatment weeks. There were 361,453 patients treated with denosumab, 829,044 treated with oral bisphosphonates, and 160,413 treated with IV bisphosphonates. Compared with oral bisphosphonates, denosumab was associated with increased risk of emergently treated hypocalcemia within a week after administration, which peaked at week 2 but persisted for approximately 10 weeks. Risk for emergently treated hypocalcemia with denosumab versus oral bisphosphonates increased with worsening CKD stage (P<0.001); the greatest risk difference was seen among dialysis-dependent patients (3.01% vs. 0.00%; risk difference [RD], 3.01% [95% CI, 2.27% to 3.77%]) and patients with stage 4 and 5 CKD (0.57% vs. 0.03%; RD, 0.54% [95% CI, 0.41% to 0.68%]). Denosumab had a greater risk for emergently treated hypocalcemia versus bisphosphonates in those with CKD-MBD than those without.
The study authors noted the scarcity of data on the treatment of osteoporosis in patients with advanced CKD, despite osteoporosis and CKD being common comorbidities. They concluded that therapies like denosumab may not be effective in the management of osteoporosis in patients with advanced CKD and CKD-MBD.
“Diagnosis and management of skeletal fragility in these high-risk patients is complex, requiring careful patient selection, adequate supplementation with calcium and vitamin D, and frequent monitoring of serum calcium under supervision of a clinician with expert knowledge and experience treating CKD-MBD,” they wrote.