Life‐threatening hypocalcaemia associated with denosumab in advanced chronic kidney disease

Killen, Jeremy; Yong, Kenneth; Luxton, Grant; Endre, Z. H.

doi:10.1111/imj.13097

Cited by 10 publications

(5 citation statements)

References 4 publications

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“…Stage 3B CKD is the likely explanation [18]. While CKD may predispose patients receiving denosumab to hypocalcemia [10, 19], it seems reasonable that it has a protective effect against hypophosphatemia, as is evidenced by our case as well as others [20, 21].…”

Section: Discussionsupporting

confidence: 58%

Severe, Symptomatic Hypocalcemia due to Denosumab Administration: Treatment and Clinical Course

Strickling

Wilkowski

2019

Case Rep Nephrol Dial

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Denosumab is a receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor used in the treatment of osteoporosis. Blockade of RANK ligand prevents osteoclastic resorption of bone, but in doing so impairs the parathyroid hormone (PTH)-driven maintenance of serum calcium. A subsequent elevation of PTH remains active at sites other than bone, potentially lowering serum phosphate by inhibiting proximal tubular reabsorption. We present 2 patients who developed severe, symptomatic hypocalcemia after administration of denosumab. These patients provide an opportunity to describe the clinical course and treatment, including the need to consider a continuous calcium infusion, of severe, symptomatic hypocalcemia caused by denosumab.

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Section: Discussionsupporting

confidence: 58%

Severe, Symptomatic Hypocalcemia due to Denosumab Administration: Treatment and Clinical Course

Strickling

Wilkowski

2019

Case Rep Nephrol Dial

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“…16 A pharmacokinetics and pharmacodynamics study of 55 patients with various degrees of renal impairment given denosumab reported an overall 15% incidence of hypocalcaemia, 17 which was highest in patients with moderate-to-severe CKD with no episodes in patients with normal kidney function. The association between hypocalcaemia, denosumab and advanced renal failure is supported by individual case reports in the nontransplant population [18][19][20][21][22][23][24] as well as a recent case series that found six of eight patients with CKD stage 5 and two of five patients with CKD stage 4 given denosumab developed severe hypocalcaemia. 25 In line with our findings, some patients required aggressive treatment with calcium and calcitriol to reverse the clinically significant hypocalcaemia.…”

Section: Discussionmentioning

confidence: 93%

Acute hypocalcaemia following denosumab in heart and lung transplant patients with osteoporosis

Shrosbree

Elder

Eisman

2018

Internal Medicine Journal

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“…This increased risk of hypocalcaemia likely results from CKD-induced secondary hyperparathyroidism [ 21 ]. Additionally, CKD causes a reduction in the activity of 1-α-hydroxylase and conversion of vitamin D to the active form (calcitriol), resulting in the reduced intestinal absorption of calcium [ 39 ]. Denosumab is a useful therapeutic option for patients with advanced cancer and renal insufficiency or CKD because, in contrast to zoledronic acid, it is not excreted by the kidneys and requires no dose adjustment for renal insufficiency [ 6 , 40 ].…”

Section: Main Textmentioning

confidence: 99%

Hypocalcaemia in patients with prostate cancer treated with a bisphosphonate or denosumab: prevention supports treatment completion

et al. 2018

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BackgroundMost patients with advanced prostate cancer develop bone metastases, which often result in painful and debilitating skeletal-related events. Inhibitors of bone resorption, such as bisphosphonates and denosumab, can each reduce the incidence of skeletal-related events and delay the progression of bone pain. However, these agents are associated with an increased risk of hypocalcaemia, which, although often mild and transient, can be serious and life-threatening. Here we provide practical advice on managing the risk of hypocalcaemia in patients with advanced prostate cancer who are receiving treatment with bone resorption inhibitors. Relevant references for this review were identified through searches of PubMed with the search terms ‘prostate cancer’, ‘bone-targeted agents’, ‘anti-resorptive agents’, ‘bisphosphonates’, ‘zoledronic acid’, ‘denosumab’, ‘hypocalcaemia’, and ‘hypocalcemia’. Additional references were suggested by the authors.Main textAmong patients with advanced cancer receiving a bisphosphonate or denosumab, hypocalcaemia occurs most frequently in those with prostate cancer, although it can occur in patients with any tumour type. Consistent with its greater ability to inhibit bone resorption, denosumab has shown superiority in the prevention of skeletal-related events in patients with bone metastases from solid tumours. Consequently, denosumab is more likely to induce hypocalcaemia than the bisphosphonates. Likewise, various bisphosphonates have differing potencies for the inhibition of bone resorption, and thus the risk of hypocalcaemia varies between different bisphosphonates. Other risk factors for the development of hypocalcaemia include the presence of osteoblastic metastases, vitamin D deficiency, and renal insufficiency. Hypocalcaemia can lead to treatment interruption, but it is both preventable and manageable. Serum calcium concentrations should be measured, and any pre-existing hypocalcaemia should be corrected, before starting treatment with inhibitors of bone resorption. Once treatment has started, concomitant administration of calcium and vitamin D supplements is essential. Calcium concentrations should be monitored during treatment with bisphosphonates or denosumab, particularly in patients at high risk of hypocalcaemia. If hypocalcaemia is diagnosed, patients should receive treatment with calcium and vitamin D.ConclusionWith preventative strategies and treatment, patients with prostate cancer who are at risk of, or who develop, hypocalcaemia should be able to continue to benefit from treatment with bisphosphonates or denosumab.

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Life‐threatening hypocalcaemia associated with denosumab in advanced chronic kidney disease

Cited by 10 publications

References 4 publications

Severe, Symptomatic Hypocalcemia due to Denosumab Administration: Treatment and Clinical Course

Severe, Symptomatic Hypocalcemia due to Denosumab Administration: Treatment and Clinical Course

Acute hypocalcaemia following denosumab in heart and lung transplant patients with osteoporosis

Hypocalcaemia in patients with prostate cancer treated with a bisphosphonate or denosumab: prevention supports treatment completion

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