Hypocalcemia Post Denosumab in Patients with Chronic Kidney Disease Stage 4-5

Dave, Vatsa; Chiang, Cherie; Booth, Jane; Mount, Peter F.

doi:10.1159/000380960

Cited by 110 publications

(88 citation statements)

References 20 publications

(43 reference statements)

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“…However, it may occur frequently in patients with a stage 4-5 chronic kidney disease, where the use of BPs is formally contraindicated [73]. Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) is highly recommended in patients with severe renal insufficiency (CHK stage 5).…”

Section: Denosumabmentioning

confidence: 99%

Safety issues and adverse reactions with osteoporosis management

Rossini¹,

Adami²,

Adami³

et al. 2016

Expert Opinion on Drug Safety

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The safety profile of most available drugs for the treatment of osteoporosis is well defined and the most serious adverse events are either rare or predictable. Osteoporosis treatment is a favorable choice in patients at moderate-high risk of fracture, while in patients at low risk pharmacological prevention should involve consideration of the balance between the beneficial effects of treatment, the probability of adverse effects and costs.

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Section: Denosumabmentioning

confidence: 99%

Safety issues and adverse reactions with osteoporosis management

Rossini¹,

Adami²,

Adami³

et al. 2016

Expert Opinion on Drug Safety

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show abstract

“…Post-denosumab hypocalcemia occurred in 5.2% of the cancer patients (1), but such an event was rarely reported in osteoporosis patients (2). Recently, severe hypocalcemia because of a lower dose of denosumab for osteoporosis has been reported in chronic kidney disease (CKD) patients (3,4). We describe the first case of rheumatoid arthritis (RA) and CKD associated with severe hypocalcemia and prolonged QT interval after the administration of a lower dose of denosumab.…”

mentioning

confidence: 99%

Severe hypocalcemia and prolonged QT interval due to denosumab in an elderly woman with rheumatoid arthritis and chronic kidney disease

Oiwa

Mokuda

2016

Eur J Rheumatol

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Denosumab has been approved for the prevention of skeletal-related events of bone metastases (120 mg at every 4 weeks) and for the treatment of osteoporosis (60 mg at every 6 months). Post-denosumab hypocalcemia occurred in 5.2% of the cancer patients (1), but such an event was rarely reported in osteoporosis patients (2). Recently, severe hypocalcemia because of a lower dose of denosumab for osteoporosis has been reported in chronic kidney disease (CKD) patients (3, 4). We describe the first case of rheumatoid arthritis (RA) and CKD associated with severe hypocalcemia and prolonged QT interval after the administration of a lower dose of denosumab.A 73-year-old woman with a 10-year history of RA visited us for follow-up assessment. She denied having tetany or paresthesia but had noticed lightheadedness for a month. On conducting laboratory tests, her level of corrected calcium (cCa) was 6.7 mg/dL (Table 1). She had decreased estimated glomerular filtration rate (eGFR), consistent with moderate CKD through the equation from age and creatinine (5). Her electrocardiogram showed a corrected QT interval of 0.50 s (Figure 1). Seven months ago, the subcutaneous administration of 60-mg denosumab (Pralia, Daiichi Sankyo; Tokyo, Japan) was started for glucocorticoid-induced osteoporosis and for the multiple compression fracture of the spine (after obtaining informed consent from the patient), and the second dose was administered 4 weeks previously. She had undergone surgery for a thoracoabdominal aortic aneurysm 4 months previously. Since the surgery, her weight reduced by 6.5 kg. Her medication included prednisolone (4 mg daily), trichlormethiazide, furosemide, carvedilol, and olmesartan; subcutaneous abatacept was also administered. She had not taken any nutritional supplement during denosumab therapy. Denosumab was considered to be responsible for hypocalcemia. Following intravenous calcium gluconate administration, the level of cCa increased to 7.2 mg/dL. Two days after therapy with alfacalcidol and calcium, the level was restored to 8.9 mg/dL with the normalization of the QT interval; the level of intact PTH was elevated at 251 ng/mL (normal range, 10-65 ng/mL). Additional tests at the presentation showed a low level of 25-hydroxyvitamin D (6 ng/mL).In a randomized-controlled trial of denosumab for post-menopausal osteoporosis, hypocalcemia (cCa <8.0 mg/dL) was not reported for 3 years among the 3886 women administered with denosumab (2). Women having a level of 25-hydroxyvitamin D of <12 ng/mL were not included in the study, and all the subjects received calcium and vitamin D. Therefore, screening and supplementation of vitamin D deficiency may have played a role in the safety profile. Recently, the effect of 60-mg denosumab on serum calcium in CKD patients was investigated (3). Hypocalcemia (cCa <7.5 mg/dL) did not occur in 13 patients with an eGFR of 30-49 mL/min ) who were initially included and did not receive supplementation showed hypocalcemia, whereas seven patients with severe CKD receiving supplementation d...

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“…Yet several cases of hypocalcaemia in patients receiving denosumab in the setting of renal disease have been reported 1 9 12. Denosumab blocks PTH-dependent osteoclastic activity, which is one of the main driving mechanisms for maintaining calcium homeostasis in kidney disease 9. Moreover, patients with impaired renal function have potential vitamin D deficiency due to reduced 1-alpha hydroxylase activity, which increases the risk of hypocalcaemia further 13.…”

Section: Discussionmentioning

confidence: 99%

Denosumab causing severe, refractory hypocalcaemia in a patient with chronic kidney disease

et al. 2018

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Denosumab is a fully human monoclonal antibody that is being increasingly used for the treatment of osteoporosis and prevention of skeletal-related events (SREs) in bone metastases from primary tumours. It has improved efficacy, better tolerability and convenient administration via subcutaneous route, in comparison with bisphosphonates; however, it has been reported to cause severe hypocalcaemia in certain high-risk individuals. We report the case of a 71-year-old man with a history of haemodialysis-dependent end-stage renal disease who developed severe hypocalcaemia with electrocardiographic changes after being started on denosumab for prevention of SREs from a recently diagnosed metastatic prostate cancer. He was admitted to the hospital for close monitoring and received multiple doses of intravenous calcium gluconate, along with haemodialysis with high calcium bath. We aim to highlight the risk of severe, life-threatening hypocalcaemia associated with denosumab and to recognise patients at risk of developing this serious adverse effect, so that prompt treatment and preventive strategies can be implemented.

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Hypocalcemia Post Denosumab in Patients with Chronic Kidney Disease Stage 4-5

Cited by 110 publications

References 20 publications

Safety issues and adverse reactions with osteoporosis management

Safety issues and adverse reactions with osteoporosis management

Severe hypocalcemia and prolonged QT interval due to denosumab in an elderly woman with rheumatoid arthritis and chronic kidney disease

Denosumab causing severe, refractory hypocalcaemia in a patient with chronic kidney disease

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