Disease relevance of Etidronic acid

• No side-effects were noted in patients treated with 5 mg of EHDP/kg body weight - day [1].
• We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity [2].
• CONCLUSION: This study demonstrated that a single 60-mg infusion of APD is safe and more effective than EHDP given at the dose of 7.5 mg/kg for 3 days in the treatment of cancer-related hypercalcemia [3].
• We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma [2].
• Use of etidronate (EHDP) in Paget's disease of bone [4].

Psychiatry related information on Etidronic acid

• Re-186 HEDP conditioning therapy in patients with advanced acute lymphoblastic leukemia before allogeneic bone marrow transplantation [5].

High impact information on Etidronic acid

• Using acridine orange as an indicator, we found that EHDP reduces proton accumulation by osteoclasts [6].
• Furthermore, [3H]leucine incorporation by the fibroblast, which does not resorb bone, is also diminished by EHDP, Cl2MDP and APD except when co-cultured with bisphosphonate-binding bone particles [6].
• However, inside-out plasma membrane vesicles from osteoclasts transport H+ normally in response to ATP in high concentrations of EHDP, Cl2MDP, or APD [6].
• Dichloromethylene diphosphonate (Cl2MDP, or clodronate disodium) is one of the most potent of the known diphosphonates as an inhibitor of bone resorption and differs from EHDP in that it does not inhibit skeletal mineralization [7].
• A semiquantitative technique employing (14C) ethane-1-hydroxy 1, -1-diphosphonate (EHDP) binding has been used to detect crystals, presumably hydroxyapatite, in human synovial fluid samples which were handled to prevent the formation of artifactual mineral phase [8].

Chemical compound and disease context of Etidronic acid

• This technique has been used to investigate the effects of retinyl acetate and EHDP on bone resorption [9].
• The in vivo effects of four bisphosphonates, including pamidronate, etidronic acid, and olpadronate, on bone tumor burden in mice intratibially inoculated with PC-3-GFP human prostate cancer cells were visualized by whole-body fluorescence imaging and X-ray [10].
• Rhenium-186 (tin)-labeled hydroxyethylidene diphosphonate (186Re-labeled HEDP) was evaluated in 27 men with progressive androgen-independent prostate cancer and bone metastases [11].
• Etidronate disodium (EHDP) therapy is often instituted emergently for treatment of hypercalcemia associated with malignancy, and a staging bone scan is part of the evaluation of the patient with extensive metastatic disease [12].
• High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone [13].

Biological context of Etidronic acid

• The plasma immunoreactive parathroid hormone levels were similar prepartum, at parturition, and 1 day postpartum in cows administered EHDP as in control cows [14].
• EHDP reduced bone resorption by about 50% and depressed bone mineralization by almost as much [15].
• Decreased intestinal absorption of Ca2+ occurs in response to treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) [16].
• The influence of 1-hydroxyethane-1,1-diphosphonate and dichloromethanediphosphonate on lysine hydroxylation and cross-link formation in rat bone, cartilage and skin collagen [17].
• EHDP, which alone had no effect on gene expression in the femur or vertebrae, inhibited the effect of L-T4 on mRNA markers in the femur [18].

Anatomical context of Etidronic acid

• Thus, the resorption-antagonizing capacities of EHDP, Cl2MDP and APD reflect metabolic inhibition, with selectivity for the osteoclast resulting from high affinity binding to bone mineral [6].
• Long-term EHDP treatment induced a moderate mineralization defect, as indicated by increased absolute osteoid volume and a high proportion of osteoid surfaces devoid of adjacent osteoblasts [19].
• We demonstrated that the expression of PTHrP decreased in the progression of bovine vascular smooth muscle cell (BVSMC) calcification and that inhibition of calcification by etidronate (EHDP) and levamisole restored PTHrP secretion, suggesting that the expression of PTHrP is associated with calcification [20].
• 1-Hydroxyethane-1,1-diphosphonate, on the other hand, decreased the incorporation of [3H]proline into the collagen of calvaria and osseous tibial shafts and showed no effect on the collagen synthesis of the cartilaginous tibial heads [21].
• The studies showed that dichloromethanediphosphonate, but not 1-hydroxyethane-1,1-diphosphonate, causes articular chondrocytes to increase net collagen biosynthesis, both when measured as 3H-labelled or as non-radioactive material, in a dose-related fashion [21].

Associations of Etidronic acid with other chemical compounds

• The retention of radioactivity in human, rat, and dog following a single injected dose of radiolabeled etidronate disodium (EHDP) is shown to follow power-law decay curves with similar slopes for times up to 4, 60, and 80 days, respectively [22].
• The diphosphonate compound ethane-hydroxy-1, 1-diphosphonate (EHDP) is an effective inhibitor of the calcification reaction induced by the subcutaneous injection of lead acetate in the mouse [23].
• The effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDPTM) on bone mineral metabolism was tested in 4 healthy young men during 20 weeks of continuous bed rest [24].
• Comparative studies in this area have suggested that, at therapeutic doses, pamidronate has a more pronounced calcium-lowering action than etidronate (etidronic acid) and clodronate (clodronic acid) and provides a longer period of normocalcaemic remission [25].
• In these in vitro processes, pyrophosphate is displaced faster than HEDP, while the HEDP reaction is accelerated by calcium ions [26].

Gene context of Etidronic acid

• T cells were incubated with interleukin-2 and further activated with 1 2-o-tetradecanoyl-phorbol 13-acetate and ionomycin, either in the presence or absence of EHDP [27].
• The concentration of soluble Fas ligand in activated T cell culture supernatants was actually increased by EHDP [27].
• Although the exact EHDP-regulated molecule that induces apoptosis of human osteoblasts is unknown at present, our study may explain part of the therapeutic action of bisphosphonates in RA complicated by bone loss [27].
• Based on area analysis, the bisphosphonates were effective for the range 10(-7)-10(-8) M, with ABP about two to five times more effective than EHDP or APD [28].
• This effect disappears after prolonged treatment so that EHDP, calcitonin and C12MDP have no effect after 7 weeks of daily treatment [23].

Analytical, diagnostic and therapeutic context of Etidronic acid

• Seven individuals had prolonged remissions after their initial course of therapy, nineteen responded to retreatment with 5 mg/kg of EHDP for 6 months of each year, while 14 patients required cycles of 20 mg/kg for 1 month of every 4 [29].
• Effect of the diphosphonate EHDP on bone mineral metabolism during prolonged bed rest [24].
• These tehcniques were utilized to assess the effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on crystallization of calcium oxalate in an aqueous salt solution in vitro [30].
• We report serial bone scintigraphy in a patient who received a single dose of EHDP for hypercalcemia [31].
• The right/left ratios of tibial uptake of 99mTc-diphosphonate (EHDP) and relative blood flow (based on microsphere distribution) were determined in control rats and rats with a ligated right femoral artery or a healing right tibial fracture [32].

References