Abstract
The management of bone fragility fracture requires the use of newer therapies such as denosumab, a human monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL). Unlike most medications for the treatment of osteoporosis, denosumab can be administered to patients with chronic kidney disease (CKD) regardless of its severity.
Despite its potent antiresorptive effect, phase III clinical trials (FREEDOM trial) have shown a surprisingly low incidence (4 out of 3886 participants) of severe hypocalcaemia (defined as adjusted serum calcium <1.90 mmol/L) following denosumab.
In the current study, Block et al. evaluated the pharmacokinetics and pharmacodynamics of denosumab in subjects with renal function ranging from normal to dialysis-dependent kidney failure. The study included 55 patients (12, 13, 13, 9 and 8 with normal renal function, mild CKD, moderate CKD, severe CKD and kidney failure, respectively) with normal predenosumab-adjusted serum calcium concentrations. The study reported that renal impairment does not significantly affect the pharmacokinetics of denosumab. In terms of major adverse events, five subjects (one with mild CKD, two with severe CKD and two with renal failure) developed hypocalcaemia: two of these required hospitalization for intravenous calcium treatment. None of the patients who developed hypocalcaemia were taking calcium or vitamin D supplementation. In comparison, none of the patients taking calcium or vitamin D supplements developed hypocalcaemia.
Limitations of the study were the small sample size and the fact that the study protocol was amended during the trial (calcium and vitamin D supplementation was introduced) and subjects with extremes of parathyroid hormone or 1,25-dihydroxyvitamin D concentration were excluded.
The authors conclude that adequate calcium and/or vitamin D supplementation should be recommended when patients with reduced kidney function commence denosumab.