Safety and efficacy of denosumab in osteoporotic hemodialysed patients

Abstract

Our pilot experience highlights the safety and efficacy of denosumab in the treatment of osteoporosis in HD patients, potentially supporting its use to reduce the burden of fractures in this patient population.

Contrasting PTH Response of Denosumab Use in Dialysis Patients: A Report of 2 Cases

“…Our patients' response to denosumab (decrease Ca level and increase iPTH level) was similar to several studies reported in ESRD patients [7,8,10,[15][16][17]. The transient surge of iPTH level in Patient 2 is most likely caused by a compensatory mechanism.…”

“…Patient's dialysate calcium bath was increased from 2.5 to 3.5 mEq/L and calcitriol 1 mcg daily treatment was initiated for hypocalcemia [15]. A retrospective study by Festuccia et al showed improvement in bone metabolism with denosumab in 12 hemodialysis patients without significant safety concerns over 24 months [8]. They observed a decrease in average serum Ca: 9 mg/dL at baseline, 8.1 mg/dL at 3 months, 9.4 mg/dL at 6 months, 9 mg/dL at 9 months, 9.8 mg/dL at 12 months, 8.9 mg/dL at 15 months, 9.2 mg/dL at 18 months, 9.3 mg/dL at 21 months, and 9.1 mg/dL at 24 months.…”

“…The U.S. Food and Drug Administration approved denosumab as an antiresorptive therapy in patients with osteoporosis and renal impairment [4]. Denosumab-associated severe hypocalcemia is a common adverse effect in the general population as well as patients with advanced CKD [5][6][7][8][9]. As a result, an increase in iPTH level is also commonly seen in order to compensate for a decrease in calcium [10,11].…”

Bone health in chronic kidney disease‐mineral and bone disorder: a clinical case seminar and update

“…Of concern, however, precipitating profound and prolonged hypocalcaemia resulting in seizures, cardiac arrhythmias and laryngospasm post‐denosumab administration in patients with CKD have been reported . Although there are no standardised and proven clinical recommendations to prevent this complication, evidence from small studies and expert opinion has recommended adequate vitamin D stores prior to the commencement of denosumab, with careful monitoring and supplementation of calcium as required post‐dose, especially within the first few weeks following its administration . Anecdotally, some centres now avoid the use of denosumab in patients with CKD stages 4–5.…”

“…[55][56][57][58] Although there are no standardised and proven clinical recommendations to prevent this complication, evidence from small studies and expert opinion has recommended adequate vitamin D stores prior to the commencement of denosumab, with careful monitoring and supplementation of calcium as required post-dose, especially within the first few weeks following its administration. [58][59][60][61] Anecdotally, some centres now avoid the use of denosumab in patients with CKD stages 4-5. Thus, although its non-renal pharmacokinetics are appealing for use in CKD, its role is yet to be fully defined for these patients, and risk of hypocalcaemia in patients with CKD remains a concern.…”