Use of pamidronate in the management of acute cancer-related hypercalcemia in children

Young, Guy; Shende, Ashok

doi:10.1002/(sici)1096-911x(199802)30:2<117::aid-mpo9>3.0.co;2-l

Cited by 43 publications

(19 citation statements)

References 16 publications

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“…Bisphosphonates have been reported to be highly effective for the treatment of hypercalcemia complicated in malignancies with long duration of action by reducing osteoclast viability and inhibiting osteoclast-mediated resorption of bone. 3,[31][32][33] As a first cohort study, we retrospectively confirmed that hypercalcemia resolved quickly in the patients treated with bisphosphonate compared with the patients who were not treated with bisphosphonate. Most of the patients treated with bisphosphonate developed hypocalcemia and almost the half of them required calcium supplementation.…”

Section: Discussionmentioning

confidence: 72%

Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19

et al. 2006

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Hypercalcemia is relatively rare but clinically important complication in childhood leukemic patients. To clarify the clinical characteristics, mechanisms of hypercalcemia, response to management for hypercalcemia, incidence of t(17;19) and final outcome of childhood acute lymphoblastic leukemia (ALL) accompanied by hypercalcemia, clinical data of 22 cases of childhood ALL accompanied by hypercalcemia (412 mg/dl) reported in Japan from 1990 to 2005 were retrospectively analyzed. Eleven patients were 10 years and older. Twenty patients had low white blood cell count (o20 Â 10 9 /l), 15 showed hemoglobinX8 g/dl and 14 showed platelet count X100 Â 10 9 /l. Parathyroid hormone-related peptide (PTHrP)-mediated hypercalcemia was confirmed in 11 of the 16 patients in whom elevated-serum level or positive immunohistochemistry of PTHrP was observed. Hypercalcemia and accompanying renal insufficiency resolved quickly, particularly in patients treated with bisphosphonate. t(17;19) or add(19)(p13) was detected in five patients among 17 patients in whom karyotypic data were available, and the presence of E2A-HLF was confirmed in these five patients. All five patients with t(17;19)-ALL relapsed very early. Excluding the t(17;19)-ALL patients, the final outcome of ALL accompanied by hypercalcemia was similar to that of all childhood ALL patients, indicating that the development of hypercalcemia itself is not a poor prognostic factor.

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Section: Discussionmentioning

confidence: 72%

Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19

et al. 2006

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“…This latter effect may explain more recent reports that the application of -3 fatty acids to hippocampal slices can decrease membrane excitability and block low frequency stimulation-induced longterm depression (LTD, Refs. [15][16][17]. Overall these reports suggest a multifaceted role for -3 EFAs involving both direct and indirect actions on neural function and suggest the hypothesis that -3 fatty acids may affect protein kinase activity.…”

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confidence: 57%

Protein Kinase Inhibition by ω-3 Fatty Acids

Mirnikjoo

Brown

Kim

et al. 2001

Journal of Biological Chemistry

153

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Recent data suggest that -3 fatty acids may be effective in epilepsy, cardiovascular disorders, arthritis, and as mood stabilizers for bipolar disorder; however, the mechanism of action of these compounds is unknown. Based on earlier studies implicating -3 fatty acids as inhibitors of protein kinase C activity in intact cells, we hypothesized that -3 fatty acids may act through direct inhibition of second messenger-regulated kinases and sought to determine whether the -3 double bond might uniquely confer pharmacologic efficacy and potency for fatty acids of this type. In our studies we observed that -3 fatty acids inhibited the in vitro activities of cAMPdependent protein kinase, protein kinase C, Ca 2؉ /calmodulin-dependent protein kinase II, and the mitogenactivated protein kinase (MAPK). Our results with a series of long-chain fatty acid structural homologs suggest an important role for the -3 double bond in conferring inhibitory efficacy. To assess whether -3 fatty acids were capable of inhibiting protein kinases in living neurons, we evaluated their effect on signal transduction pathways in the hippocampus. We found that -3 fatty acids could prevent serotonin receptor-induced MAPK activation in hippocampal slice preparations. In addition, we evaluated the effect of -3 fatty acids on hippocampal long-term potentiation, a form of synaptic plasticity known to be dependent on protein kinase activation. We observed that -3 fatty acids blocked long-term potentiation induction without inhibiting basal synaptic transmission. Overall, our results from both in vitro and live cell preparations suggest that inhibition of second messenger-regulated protein kinases is one locus of action of -3 fatty acids.

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“…Experience with bisphosphonates in the pediatric population is limited. Bisphosphonates have been used in pediatric patients in the management of primary or secondary osteoporosis [8,9], idiopathic osteoporosis [10], juvenile chronic arthritis [11], osteogenesis imperfecta [12,13,14,15,16], hypercalcemia related to subcutaneous fat necrosis [17], liver transplantation [18,19], bone marrow transplantation [20], malignancy [21,22], immobilization [23,24], renal disease [25], and hyperparathyroidism [26] as well as a few other medical conditions [27,28,29,30,31,32]. Many of these studies were case reports and the remainder had relatively small population sizes.…”

Section: Introductionmentioning

confidence: 99%

Pamidronate treatment of pediatric fracture patients on chronic steroid therapy

et al. 2005

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Pediatric nephrology and rheumatology patients with steroid-induced osteopenia are at risk of skeletal fracture. Bisphosphonate therapy has not been routinely advocated as a primary or secondary intervention for steroid-associated fractures in this population. This case control study evaluates the role of pamidronate therapy as a secondary fracture intervention. Children with symptomatic pathological fractures of the axial spine or ribs were treated with pamidronate 1 mg/kg/dose (n=17) IV at 60-day intervals for 1 yr (n=15) or 2 yr (n=2). Bone mineral density of L1-L4 (BMD) was assessed prior to treatment and at six-month intervals, and compared to 17 disease-age-gender-steroid dose-matched control patients. Alkaline phosphatase, calcium, phosphate, PTH, renal biochemistry, and 24-hr urine collections for CrCl, N-telopeptide/creatinine ratio, phosphate excretion, and calcium excretion were obtained every two months in the pamidronate population. Pamidronate caused a first exposure transient flu-like illness lasting <24 h in three patients and one patient had a new pathological fracture. No adverse events of hypocalcemia, allergic reaction or thrombophlebitis were noted. All patients reported improvement of skeletal pain. Despite ongoing steroid treatment, pamidronate significantly increased L1-L4 BMD Z-scores (mean+/-SE) relative to baseline (pamidronate vs control: 0-6 months: 0.27+/-0.14 vs -0.82+/-0.31; 0-12 months: 0.63+/-0.17 vs -0.46+/-0.27; 0-18 months: 0.55+/-0.32 vs 0.17+/-0.27; 0-24 months: 0.15+/-0.21 vs -0.23+/-0.22; 0-30 or 36 months: 0.77+/-0.71 vs -0.68+/-0.25) with repeated measures ANOVA assessment (F=11.27, p=0.0057). This study supports the safety and efficacy of pamidronate in steroid-induced fractures in pediatric nephrology and rheumatology patients.

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Use of pamidronate in the management of acute cancer-related hypercalcemia in children

Cited by 43 publications

References 16 publications

Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19

Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19

Protein Kinase Inhibition by ω-3 Fatty Acids

Pamidronate treatment of pediatric fracture patients on chronic steroid therapy

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