Journal
JOURNAL OF BONE AND MINERAL RESEARCH
Volume 27, Issue 7, Pages 1471-1479Publisher
WILEY
DOI: 10.1002/jbmr.1613
Keywords
CHRONIC KIDNEY DISEASE; BONE; PHARMACOKINETICS; CALCIUM; VITAMIN D
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Funding
- Amgen Inc.
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This 16-week study evaluated pharmacokinetics and pharmacodynamics of denosumab in 55 subjects with renal function ranging from normal to dialysis-dependent kidney failure. Participants received a single 60-mg subcutaneous dose of denosumab. Kidney function groups were based on calculations using the Cockcroft-Gault equation and U.S. Food and Drug Administration (FDA) guidance in place when the study was designed. Renal function did not have a significant effect on denosumab pharmacokinetics or pharmacodynamics. These findings suggest denosumab dose adjustment based on glomerular filtration rate is not required. Rapid decreases in serum C-telopeptide in all groups were sustained throughout the study. The most common adverse events were hypocalcemia (15%), pain in extremity (15%), and nausea (11%). Most adverse events were mild to moderate in severity. Calcium and vitamin D supplementation was not initially required by the study protocol, but was added during the trial. No subject who received adequate calcium and vitamin D supplementation became hypocalcemic. Seven subjects had nadir serum calcium concentrations between 7.5 and <8.0?mg/dL (1.9 and <2.0?mmol/L), and 5 subjects (4 with advanced renal disease) had nadir serum calcium <7.5?mg/dL (<1.9?mmol/L). Two subjects (1 symptomatic, 1 asymptomatic) were hospitalized for intravenous calcium gluconate treatment. At the recommended dose, denosumab is a useful therapeutic option for patients with impaired renal function. Supplementation of calcium and vitamin D is strongly recommended when patients initiate denosumab therapy, particularly in patients with reduced renal function. (c) 2012 American Society for Bone and Mineral Research.
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