Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aminobisphosphonates are drugs used in the treatment of hypercalcemia, Paget's disease, osteoporosis, and malignancy. Some patients treated with aminobisphosphonates have a transient febrile reaction that may be caused by an increased serum concentration of proinflammatory cytokines. Aminobisphosphonates induce the production of certain proinflammatory cytokines in vitro, especially in cells of monocytic lineage. A unique feature of aminobisphosphonates is that they bind the Vgamma2Vdelta2 class of T cells, which are found only in primates, and stimulate cytokine production. The effects of aminobisphosphonates on other cells, including macrophages, are incompletely understood. We show in this study that treatment of murine macrophages with pamidronate, a second generation aminobisphosphonate, induces TNF-alpha production. Furthermore, pretreatment of murine macrophages with pamidronate before stimulation with IFN-gamma significantly augments IFN-gamma-dependent production of TNF-alpha. This pamidronate-mediated augmentation of TNF-alpha production results in sustained phosphorylation of the tyrosine residue at position 701 of STAT1 after IFN-gamma treatment. Our data suggest that this sustained phosphorylation results from inhibition of protein tyrosine phosphatase activity. We also show that pamidronate treatment increases TNF-alpha production in vivo in mice. Pamidronate-augmented TNF-alpha production by macrophages might be a useful strategy for cytokine-based anticancer therapy.
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PMID:Modulation of TNF-alpha gene expression by IFN-gamma and pamidronate in murine macrophages: regulation by STAT1-dependent pathways. 1569 6

Pamidronate (APD), a third-generation bisphosphonate, has proven to be useful in haemodialysis (HD) patients with ectopic calcifications and hypercalcaemia. Little is known about bisphosphonates clearance in patients undergoing HD. The authors' main objective was to study HD removal and clearance of APD. In total, 23 HD-requiring anuric end-stage renal disease (ESRD) adult individuals (12 men) aged 61.7 +/- 13 (mean +/- SD) years were admitted into the study. APD clearance and elimination were evaluated by (99m)Technetium APD (half-life 6 h). In total, 1 mg of labelled APD was injected via the arteriovenous graft prior to the start of HD. Blood samples were then drawn from the arterial (predialyser) and venous (postdialyser) lines of the extracorporeal circuit 2 h after the HD onset. In a subgroup of patients (n: 15) the dialysate was collected and quantified during the three initial HD hours. Venous APD concentrations (postdialyser) were 72 + 7% of arterial (predialyser) concentrations. Mean APD clearance was 69.3 + 16.6 mL/min, and mean APD extraction during dialysis session was 31.6 + 10.1%. In the present study involving HD-requiring anuric ESRD patients APD was successfully eliminated by HD. At the dose administered here none of the participants reported adverse events. APD is a potentially useful drug to be administered to HD-requiring ESRD patients, the understanding of its removal during HD as well as its dialytic clearance allows for a safer management of a drug that is usually eliminated by renal excretion.
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PMID:Elimination and clearance of pamidronate by haemodialysis. 1675 31

Osteochemonecrosis of the jaws is a well described side effect of bisphosphonate therapy. Bisphosphonates are non metabolised analogues of pyrophosphate that are capable of localizing to bone, slowing both rate of growth and rate of dissolution therefore reducing the rate of bone turnover. Although the exact mechanism is not clear but it has been established that bisphosphonates target osteoclast, inhibiting their function in several ways: There are two types of bisphosphonates. The first are oral preparations of bisphosphonates, which include Alendronate and Risedronate. They are indicated for the treatment of osteoporosis. They are considered as lower risk of osteochemonecrosis. The second are administered intravenously. Pamindronate is a first generation bisphosphonate; 90 mg administered intravenouly over 2-24 hours every 3-4 weeks. The next generation of intravenous bisphosphonate is Zoldronic acid, which is more effective than Pamidronate in controlling hypercalcaemia of bone and reducing the skeletal related events in patients with metastatic breast cancer, multiple myeloma, hypercalcaemia of malignancy, paget's disease and bone metastasis from prostate and lung cancer.
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PMID:Osteochemonecrosis of jaws and bisphosphonates. 1749 45

We describe the use of pamidronate to control marked hypercalcemia in an extremely premature infant with neonatal hyperparathyroidism that resulted from an inactivating mutation (R220W) of the calcium-sensing receptor. Despite improvement in bone mineralization and subsequent parathyroidectomy with normalization of the serum calcium level, the combination of chronic lung disease, osteomalacia, and poor thoracic cage growth ultimately proved fatal. Pamidronate therapy seems to be safe in the short-term and effective in helping control hypercalcemia even in the very premature infant, allowing for planned surgical intervention when it becomes feasible.
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PMID:Neonatal hyperparathyroidism and pamidronate therapy in an extremely premature infant. 1797 27

Secondary hyperparathyroidism and the associated metabolic abnormalities are common complications of chronic kidney disease. When these disorders cannot be managed by conventional measures, including phosphate restriction, phosphate binders, vitamin D therapy, and calcimimetics, tertiary hyperparathyroidism and the associated metabolic abnormalities may develop. In such cases parathyroidectomy is required. We report a case in which a patient with tertiary hyperparathyroidism and refractory hypercalcemia who was not a surgical candidate was managed with the bisphosphonate pamidronate. This patient had failed conventional measures to manage hypercalcemia and presented with mental status changes. Pamidronate therapy was associated with a sustained decrease in serum calcium concentration and improvement in clinical symptoms. This is the first case, to our knowledge, in which pamidronate was used in a patient refractory to all other reasonable medical management, including calcimimetics.
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PMID:Hypercalcemia associated with tertiary hyperparathyroidism managed conservatively with pamidronate in a hemodialysis patient. 1936 80

Idiopathic infantile hypercalcemia (IIH) is a rare disorder caused by CYP24A1 loss-of-function mutation, resulting in impaired degradation of 1,25-dihydroxyvitamin D3. Pamidronate, an intravenously administered bisphosphonate, which is a potent inhibitor of bone resorption, has been reported only once for treatment IIH. We present a case of a previously healthy 5-month-old boy with IIH, where calcemia peaked to 5 mmol/L. Treatment with methylprednisone and furosemide had only minor effects; therefore, 2 intravenous infusions of pamidronate (0.6 mg/kg per dose) corrected the serum calcium level to 2.95 mmol/L. Furthermore, CYP24A1 homozygous mutation p.R396W (c.1186c>t) was identified in this patient, confirming the clinical diagnosis of IIH. In conclusion, IIH has a favorable outcome once properly detected and appropriately treated. Pamidronate has a beneficial effect in those patients with IIH where glucocorticoids and furosemide fail to meet the expectations.  
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PMID:Intravenous pamidronate in the treatment of severe idiopathic infantile hypercalcemia. 2348 30

Multiple myeloma (MM) is a haematological malignancy characterised by the clonal proliferation of plasma cells in the bone marrow. More than 80% of patients with MM display evidence of myeloma bone disease (MBD), characterised by the formation of osteolytic lesions throughout the axial and appendicular skeleton. MBD significantly increases the risk of skeletal-related events such as pathologic fracture, spinal cord compression and hypercalcaemia. MBD is the result of MM plasma cells-mediated activation of osteoclast activity and suppression of osteoblast activity. Bisphosphonates (BP), pyrophosphate analogues with high bone affinity, are the only pharmacological agents currently recommended for the treatment and prevention of MBD and remain the standard of care. Pamidronate and zoledronic acid are the most commonly used BP to treat MBD. Although generally safe, frequent high doses of BP are associated with adverse events such as renal toxicity and osteonecrosis of the jaw. As such, optimal duration and dosing of BP therapy is required in order to minimise BP-associated adverse events. The following guidelines provide currently available evidence for the adoption of a tailored approach when using BP for the management of MBD.
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PMID:Bisphosphonate guidelines for treatment and prevention of myeloma bone disease. 2878 11

Hypercalcemia may follow hypocalcemia in the course of acute renal failure (also named now as acute kidney injury) secondary to rhabdomyolysis. The clinician should be aware of this calcium kinetics to avoid the complications of both hypocalcemia and hypercalcemia that may occur at few days interval during the recovery phase. We present herewith the case of a young gentleman who developed anuric ARF due to a strenuous exercise induced rhabdomyolysis. He was treated with supportive, corrective and dialysis measures. The progress was favourable with a diuretic phase. During the diuretic phase, he developed progressive hypercalcemia that reached up to 3.54 mEq/lwith constipation and drowsiness. Investigations showed besides stigmata of rhabdomyolysis and ARF, low initial levels of vitamin D metabolites. The calcemia eventually normalized with fluids, dialysis and a single dose of Pamidronate Sodium . The patient was discharged 3 weeks after admission with a recovered clinical condition, improved renal functions and normal calcemia. The biphasic kinetics of calcium in this setting is ocumented. We conclude that serum corrected calcium should be monitored in the context of ARF due to rhabdomyolysis.
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PMID:Calcium Kinetic in a patient with acute renal failure due to Rhabdomyolysis. A Case Report and Review of Literature. 2884 16

BACKGROUND Hypercalcemia is a common complication in the intensive care unit (ICU). It can be a result of diverse etiologies, such as malignancy. In this case, bisphosphonates can serve as an effective therapeutic option. However, bisphosphonates are not safe to use in patients with end stage renal disease. CASE REPORT We report a case of severe hypercalcemia possibly secondary to bone metastasis. The patient is known to have end-stage renal disease (ESRD) and undergoing dialysis 3 times a week. She had severe persistent hypercalcemia which did not resolve with regular measures or calcitonin. The literature was searched for the possibility of administering bisphosphonate as a treatment option. It was found that pamidronate pharmacokinetics can be safe and effective in end-stage renal disease patients. Therefore, Pamidronate was administered, showing effective results with regards to the level of calcium and no observed adverse effects. Re-dosing was required at an 8-week interval, with no adverse effects. CONCLUSIONS Pamidronate is a safe option to use in treating hypercalcemia in end-stage renal disease patients on dialysis. This can be especially beneficial in patients with sustained hypercalcemia secondary to malignancy.
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PMID:Use of Pamidronate to Treat Hypercalcemia in an Oncology Dialysis Patient: A Case Report. 3020 47

Objectives Vitamin A is essential for normal cellular physiology and is often taken as a dietary supplement. Hypervitaminosis A can lead to hypercalcemia by increasing osteoclasts and subsequent bone resporption. Dietary supplements including vitamin A are new popular treatment stategies for autism. Case presentation We report a five-year old boy with autism spectrum disorder presenting with severe abdominal pain and bilateral lower extremity pain, who was found to have persistent hypercalcemia due to hypervitaminosis A. The patient ingested over 700 times the recommended intake of Vitamin A per day for age. Retention of vitamin A in the liver and adipose tissue causes toxic levels of retinoids and hypercalcemia. Conclusions Acute treatment included intravenous rehydration, furosemide, and calcitonin. Pamidronate was the definitive treatment for hypercalcemia from hypervitaminosis A due to its osteoclast inhibition and long biologic half-life. Parents should be counseled on risks of toxicity and absence of evidence showing benefits of vitamin A therapy for autism.
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PMID:Hypercalcemia from hypervitaminosis A in a child with autism. 3265 63


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