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Denosumab for treatment of immobilization-related hypercalcaemia in a patient with advanced renal failure.

de Beus E, Boer WH - Clin Kidney J (2012)

Bottom Line: This did not result in a sufficient decrease in the serum calcium concentration nor was the decrease sustained.This resulted in rapid and sustained decrease in the serum calcium concentration.Furthermore, we summarize what is known about hypercalcaemia caused by immobilization.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Hypertension , University Medical Centre Utrecht , Utrecht , The Netherlands.

ABSTRACT
We describe the case of a young adult with immobilization-related hypercalcaemia and advanced renal insufficiency. Because of the uncertain safety profile of bisphosphonates in such patients, only a low dose of pamidronate was administered twice. This did not result in a sufficient decrease in the serum calcium concentration nor was the decrease sustained. We decided to administer a single dose of denosumab, a monoclonal antibody against the receptor activator of nuclear factor-κB ligand, a new antiresorptive agent registered for use in osteoporosis. This resulted in rapid and sustained decrease in the serum calcium concentration. Transient hypocalcaemia ensued with normalization after vitamin D supplementation. Furthermore, we summarize what is known about hypercalcaemia caused by immobilization.

No MeSH data available.


Related in: MedlinePlus

Time course of serum corrected calcium and phosphate level and administered medication.
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SFS116F1: Time course of serum corrected calcium and phosphate level and administered medication.

Mentions: A 19-year-old male was admitted to the intensive care unit of our hospital for meningococcal meningitis complicated by multi-organ failure including acute renal insufficiency. Amputation of the right lower leg had to be performed and there were significant neurological sequelae resulting in prolonged immobilization. During this admission, hypercalcaemia developed after 2 months with a maximum corrected serum calcium concentration of 3.4 mmol/L. The serum parathyroid hormone (PTH) concentration was below the detection limit (for laboratory values, see Table 1). The tentative diagnosis was immobilization-related hypercalcaemia. Despite renal impairment [estimated GFR (eGFR) of 18 mL/min/1.73 m2], a reduced dose of pamidronate (30 mg) was administered intravenously with near normalization of the serum calcium concentration (see Figure 1). Three months later, the serum calcium concentration had increased again (to 2.96 mmol/L) and the same dose of pamidronate was administered. The serum calcium concentration again decreased to a near-normal level (2.70 mmol/L). Renal function remained stable. The serum phosphate level was high, which is attributed to both impaired renal excretion and increased efflux from the bones. After a prolonged admission, the patient was discharged to a rehabilitation centre. Mobilization was limited to spending 4h in a chair per day. He had a persistent renal insufficiency with an eGFR of 24 mL/min/1.73 m². Unfortunately, 2 months later, the serum calcium concentration increased again to a corrected level of 3.9 mmol/L and the patient suffered from nausea and vomiting. He was readmitted to the hospital and hyper hydration was performed in combination with oral furosemide (dose 125 mg twice daily), and calcitonin was administered subcutaneously (dose 400 IU twice daily). The serum calcium concentration decreased to 2.74 mmol/L. At this time, further analysis showed that both the serum 25-OH-vitamin D and 1,25-di-OH-vitamin D concentrations were low. No PTH-related peptide was present. Urinary calcium excretion was high (9.4 mmol/24 h with a fractional calcium excretion of 9.8%). Other rare causes of hypercalcaemia were excluded: urinary metanephrines and the serum thyroid stimulating hormone, cortisol and aluminium concentrations and the free light chain kappa/lambda ratio were all normal. A chest X-ray showed no lymphadenopathy and there were no signs of skeletal metastasis on magnetic resonance imaging of the vertebrae and the left leg that was performed earlier. This analysis confirmed that immobilization was the cause of the hypercalcaemia. A few weeks later, the serum calcium concentration had increased again to 3.02 mmol/L. Because of the recurrent hypercalcaemia and lack of success of treatment with low-dose biphosphonate, we decided to treat the patient with a single subcutaneous dose of denosumab (60 mg). One week later, the serum calcium concentration had decreased from 3.02 to 1.9 mmol/L. The serum phosphate level had decreased in parallel (to 0.58 mmol/L) suggesting effective inhibition of bone resorption. Supplementation with both calciumcarbonate/colecalciferol and active vitamin D (alfacalcidol) was started after which the serum calcium concentration normalized. During the episode of hypocalcaemia, serum PTH concentration increased to 47.8 pmol/L. After 2 months, the serum calcium level rose to 2.66 mmol/L. At that time, all vitamin D and calcium-supplementation was stopped. During a 2-month follow-up since then, the patient's serum calcium concentration has remained within the normal range without further administration of denosumab.Table 1.


Denosumab for treatment of immobilization-related hypercalcaemia in a patient with advanced renal failure.

de Beus E, Boer WH - Clin Kidney J (2012)

Time course of serum corrected calcium and phosphate level and administered medication.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400549&req=5

SFS116F1: Time course of serum corrected calcium and phosphate level and administered medication.
Mentions: A 19-year-old male was admitted to the intensive care unit of our hospital for meningococcal meningitis complicated by multi-organ failure including acute renal insufficiency. Amputation of the right lower leg had to be performed and there were significant neurological sequelae resulting in prolonged immobilization. During this admission, hypercalcaemia developed after 2 months with a maximum corrected serum calcium concentration of 3.4 mmol/L. The serum parathyroid hormone (PTH) concentration was below the detection limit (for laboratory values, see Table 1). The tentative diagnosis was immobilization-related hypercalcaemia. Despite renal impairment [estimated GFR (eGFR) of 18 mL/min/1.73 m2], a reduced dose of pamidronate (30 mg) was administered intravenously with near normalization of the serum calcium concentration (see Figure 1). Three months later, the serum calcium concentration had increased again (to 2.96 mmol/L) and the same dose of pamidronate was administered. The serum calcium concentration again decreased to a near-normal level (2.70 mmol/L). Renal function remained stable. The serum phosphate level was high, which is attributed to both impaired renal excretion and increased efflux from the bones. After a prolonged admission, the patient was discharged to a rehabilitation centre. Mobilization was limited to spending 4h in a chair per day. He had a persistent renal insufficiency with an eGFR of 24 mL/min/1.73 m². Unfortunately, 2 months later, the serum calcium concentration increased again to a corrected level of 3.9 mmol/L and the patient suffered from nausea and vomiting. He was readmitted to the hospital and hyper hydration was performed in combination with oral furosemide (dose 125 mg twice daily), and calcitonin was administered subcutaneously (dose 400 IU twice daily). The serum calcium concentration decreased to 2.74 mmol/L. At this time, further analysis showed that both the serum 25-OH-vitamin D and 1,25-di-OH-vitamin D concentrations were low. No PTH-related peptide was present. Urinary calcium excretion was high (9.4 mmol/24 h with a fractional calcium excretion of 9.8%). Other rare causes of hypercalcaemia were excluded: urinary metanephrines and the serum thyroid stimulating hormone, cortisol and aluminium concentrations and the free light chain kappa/lambda ratio were all normal. A chest X-ray showed no lymphadenopathy and there were no signs of skeletal metastasis on magnetic resonance imaging of the vertebrae and the left leg that was performed earlier. This analysis confirmed that immobilization was the cause of the hypercalcaemia. A few weeks later, the serum calcium concentration had increased again to 3.02 mmol/L. Because of the recurrent hypercalcaemia and lack of success of treatment with low-dose biphosphonate, we decided to treat the patient with a single subcutaneous dose of denosumab (60 mg). One week later, the serum calcium concentration had decreased from 3.02 to 1.9 mmol/L. The serum phosphate level had decreased in parallel (to 0.58 mmol/L) suggesting effective inhibition of bone resorption. Supplementation with both calciumcarbonate/colecalciferol and active vitamin D (alfacalcidol) was started after which the serum calcium concentration normalized. During the episode of hypocalcaemia, serum PTH concentration increased to 47.8 pmol/L. After 2 months, the serum calcium level rose to 2.66 mmol/L. At that time, all vitamin D and calcium-supplementation was stopped. During a 2-month follow-up since then, the patient's serum calcium concentration has remained within the normal range without further administration of denosumab.Table 1.

Bottom Line: This did not result in a sufficient decrease in the serum calcium concentration nor was the decrease sustained.This resulted in rapid and sustained decrease in the serum calcium concentration.Furthermore, we summarize what is known about hypercalcaemia caused by immobilization.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Hypertension , University Medical Centre Utrecht , Utrecht , The Netherlands.

ABSTRACT
We describe the case of a young adult with immobilization-related hypercalcaemia and advanced renal insufficiency. Because of the uncertain safety profile of bisphosphonates in such patients, only a low dose of pamidronate was administered twice. This did not result in a sufficient decrease in the serum calcium concentration nor was the decrease sustained. We decided to administer a single dose of denosumab, a monoclonal antibody against the receptor activator of nuclear factor-κB ligand, a new antiresorptive agent registered for use in osteoporosis. This resulted in rapid and sustained decrease in the serum calcium concentration. Transient hypocalcaemia ensued with normalization after vitamin D supplementation. Furthermore, we summarize what is known about hypercalcaemia caused by immobilization.

No MeSH data available.


Related in: MedlinePlus