Denosumab Raises Hypocalcemia Risk in Chronic Kidney Disease

TOPLINE:
Denosumab treatment for osteoporosis raises the risk for hypocalcemia, which worsens with advancing stages of chronic kidney disease (CKD), in those with CKD–Mineral and Bone Disorder (CKD-MBD) and in those undergoing dialysis.
METHODOLOGY:
There is a paucity of data regarding treatments for osteoporosis in patients with advanced CKD, who often develop CKD-MBD, a clinical syndrome involving disturbances in calcium, vitamin D, phosphate, and parathyroid hormone.
Researchers assessed Medicare data from 2012 to 2020 to identify the risk for hypocalcemia according to CKD stage and the presence of CKD-MBD in female patients (age, ≥ 65 years) initiating first-line treatment for osteoporosis.
CKD stages were determined according to estimated glomerular filtration rates: Stage I (≥ 90 mL/min/1.73 m²), stage II (60 to < 90 mL/min/1.73 m²), stage III (30 to < 60 mL/min/1.73 m²), stage IV (15 to < 30 mL/min/1.73 m²), and stage V (< 15 mL/min/1.73 m²).
Hospital and emergency department admissions for hypocalcemia, indicating the need for urgent care, were evaluated during the initial 12 weeks of treatment.
TAKEAWAY:
Researchers included 361,453 patientsinitiating first-line treatment with denosumab, 829,044 with oral bisphosphonates, and 160,413 with IV bisphosphonates.
The prevalence of CKD-MBD was 42.8% in non–dialysis-dependent patients with CKD stages IV and V and 98.9% in dialysis-dependent patients.
At 12 weeks, hypocalcemia requiring emergent treatment was observed in 201 women (0.06%) receiving denosumab, 46 women (0.01%) receiving IV bisphosphonates, and 16 women (0.004%) receiving oral bisphosphonates.
The incidence of hypocalcemia requiring emergent treatment with denosumab peaked at 2 weeks and returned to its baseline level by around 10 weeks.
The risk for emergently treated hypocalcemia with denosumab vs oral bisphosphonates increased significantly with worsening CKD stage (P < .001), with a notably elevated risk in non–dialysis-dependent patients with CKD stages IV and V (risk ratio [RR], 17.5), dialysis-dependent patients (RR, 109.8), and those with CKD-MBD stages IV-V (RR, 59.0).
Compared with IV bisphosphonates, denosumab led to an increased risk for hypocalcemia across CKD stages.
IN PRACTICE:
“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,” the authors wrote.
SOURCE:
The study was led by Steven T. Bird, PhD, PharmD, Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland. It was published online in Annals of Internal Medicine.
LIMITATIONS:
The study population included only female Medicare beneficiaries, potentially affecting its applicability to men and non-Medicare populations. Researchers lacked access to clinical laboratory data for estimated glomerular filtration rates. This study did not account for cases of hypocalcemia treated in nonemergent care settings or undiagnosed instances among patients whose serum calcium levels were not regularly monitored.
DISCLOSURES:
This study received funding from the Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. One author declared employment with the Centers for Medicare & Medicaid Services, and another declared employment with the US Food and Drug Administration. Additional authors reported having ties with Acumen, LLC, a contractor on this study’s interagency agreement.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 
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