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At least 613 records · Page 34Linked to original sources
PubMed1990

Effect of ethane-I-hydroxy-I, I-diphosphonate on arterial calcinosis induced by hypervitaminosis D: a morphologic investigation.

The present study was undertaken to examine changes in vascular ultrastructure of rats subjected to hypervitaminosis D with or without treatment with ethane-I-hydroxy-I, I-diphosphonate (EHDP). Five groups of rats were studied. Untreated rats were given 0.9% NaCl i.p. Sham-treated rats were given vehicle (corn oil). Treated rats were given ergocalciferol (75,000 IU i.p.) dissolved in vehicle with or without EHDP (5 mM/100 g body-weight i.p.). Rats which had been given ergocalciferol without EHDP developed hypercalcemia and demonstrated significant arterial calcinosis. A similar degree of calcinosis was not observed in rats given ergocalciferol with EHDP. EHDP appeared to inhibit arterial calcinosis; however, it did not affect plasma calcium levels. This suggests that EHDP might delay calcium influx into the cell and thereby prevent calcium overload. Our findings support the suggestion that EHDP therapy can be an effective treatment for the inhibition of dystrophic arterial calcinosis.

Animals↗
PubMed1990

Interactions of tubulin with guanylyl-(beta-gamma-methylene)diphosphonate. Formation and assembly of a stoichiometric complex.

Complete replacement of the nucleotide on the exchangeable binding site of purified calf brain tubulin by the non-hydrolyzable GTP-analogue guanylyl-(beta,gamma-methylene)diphosphonate (GMPPCP) has been achieved by treatment of tubulin-GDP with phosphodiesterase-free alkaline phosphatase. GMPPCP binds to tubulin with a low affinity relative to GTP or GDP. Binding of the analogue is linked to magnesium ion concentration and, like the binding of other guanine nucleotides, is promoted by high concentrations of glycerol. The complex of pure tubulin and GMPPCP readily assembles at 37 degrees C into microtubules or curled ribbons of protofilaments, depending on buffer composition. Assemblies are cold-reversible at 0-2 degrees C, and multiple reversible assemblies can be observed during repeated heating/cooling cycles.

Animals↗
PubMed1989

[Inhibition of prednisolone osteopathy by diphosphonate (EHDP) in an animal experiment].

The application of a low dose of prednisolone (0.4 mg per kg body weigh and day) in young hamsters leads to a loss of bone mass. This effect is inhibited by the administration of the diphosphonate EHDP (6.2 mg per kg body weight and day). The total volume of the limb bones is increased. The application of a high dose of prednisolone (40 mg per kg body weight and day) induces a severe osteopathy. These pathological bone changes couldn't be prevented by EHDP, but there was a significant shift of the investigated parameters into the direction of normalization.

Animals↗
PubMed1989

Renal uptake of technetium-99m methylene diphosphonate following therapeutic radiation for vertebral metastases.

Radionuclide bone scans in two patients with breast cancer and concurrent chemotherapy treatment revealed increased band-like uptake of [99mTc]methylene diphosphonate along the medial upper renal cortex corresponding to the portions of the kidneys included within the radiation field. The latency of onset of abnormal uptake was 5 to 9 mo following completion of radiation in one patient, peaked near 13 to 14 mo for both patients, and returned to baseline after 20 to 27 mo. Transient serum creatinine level elevations were also detected. These findings suggest that transient subclinical renal impairment may occur and be detected on bone scans following inadvertent inclusion of renal cortex in radiation fields.

Breast Neoplasms↗
PubMed1989

Reversible pulmonary uptake and hypertrophic pulmonary osteoarthropathic distribution of technetium-99m methylene diphosphonate in a case of Pneumocystis carinii pneumonia.

Diffuse pulmonary deposition of [99mTc]methylene diphosphonate (MDP) as well as abnormalities characteristic of hypertrophic pulmonary osteoarthropathy have been observed in a patient with Pneumocystis carinii pneumonia (PCP). The findings of the bone scan together with those in the corresponding scintigraphy, and roentgenograms of the chest and skeletal structures are presented. Parallel reversal of [67Ga]citrate and [99mTc]MDP pulmonary uptake with specific treatment for and clinical resolution of PCP implies a causal relationship.

Adult↗
PubMedDate not supplied

[The influence of diphosphonic analogues of inorganic pyrophosphate on reactions catalyzed by DNA-dependent RNA-polymerase II].

Diphosphonic analogues of inorganic pyrophosphate were studied for their influence both on RNA pyrophosphorolysis and pyrophosphate exchange, catalyzed by purified DNA-dependent RNA-polymerase II from calf thymus. Methylene-, oxyethylene-and aminomethylenediphosphonic acids are shown to compete with PPi for incorporation into nucleoside triphosphate. They activate RNA pyrophosphorolysis in the concentration of 2 mM, but to a less extent than PPi does.

Animals↗
PubMed1986

[Morphologic and metabolic studies on the effect of ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on the epiphyseal plate and metaphysis of the rat].

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) has been widely used in recent clinical and laboratory investigations. The author examined epiphyseal and metaphyseal morphology as well as cartilage matrix and calcium metabolism during EHDP administration and after drug discontinuation by 35S, 45Ca and 3H-thymidine autoradiographic study. The effect of low-dose EHDP was limited to osteoclast dysfunction of the metaphysis with resultant widening of trabeculae. High dose administration of EHDP induces a variety of disorders with a manifestation of marked widening of the epiphyseal growth plate. This process is probably derived from a reduction in matrix calcification that relates an inhibition of chondrocyte metabolism with a resultant decreased rate of chondroitin sulfate turnover. Furthermore, high dose EHDP causes a metaphysis which exhibits rickets+-like changes with little calcification and a decrease in the normal rate of osteoprogenitor cell differentiation to osteoblasts and osteocytes.

Animals↗
PubMed1986

[Long-term experience using EHDP (ethylidene-1-hydroxy-1,1-diphosphonate) in the treatment of Paget's disease].

12 patients with symptomatic Paget's disease of bone were treated with the diphosphonate EHDP during a 6 month period and underwent a follow up of 12 months. 6 patients received a daily dose of 5 mg/kg, 6 patients a daily dose of 10 mg/kg. All patients reported a remarkable improvement of their clinical symptoms. The decline of the serum-alkaline-phosphatase level served as an objective criterium for reduced bone turn-over metabolism. After three months of treatment with the high dose of EHDP the serum level of the alkaline phosphatase was reduced to 52% of the initial value. After 6 months of therapy a similar good result was achieved with the lower dose of EHDP. The serum alkaline-phosphatase level remained low up to 12 months after cessation of therapy in both groups of patients. So far similar long periods of remission have not been achieved by calcitonin, which is considered to be the standard therapy of Paget's disease. Another advantage of EHDP over calcitonin is the oral route of application. If a fast initial effect is desired, a daily dose of 10 mg/kg of EHDP should be used over a period of 3 months instead of the usually recommended dose of 5 mg/kg.

Alkaline Phosphatase↗
PubMed1987

High doses of the diphosphonate EHDP for the prevention of heterotopic ossification. An experimental and clinical study.

The effect of Ethane-1-Hydroxyl-1, 1-Diphosphonate (EHDP) on experimental and clinical heterotopic ossification was studied. Demineralized cortical bone matrix was implanted in the abdominal wall of three groups of adult male rats. Two groups received injections amounting to 5 and 20 mg/kg/day of EHDP, respectively, and a control group received placebo. The lower dose of EHDP had no effect on bone formation, whereas the higher dose resulted in a marked reduction in ash content and 45Ca uptake in the implants. Inhibitory effects on heterotopic bone and serum alkaline phosphatase activity were observed when treating with high doses (50 mg/kg/day) a paraplegic patient following resection of para-articular ossifications around the hips. The effect of EHDP on bone formation is interpreted as reflecting a dose-dependent interference with the deposition of hydroxyapatite crystals in the bone matrix.

Adult↗
PubMed1988

Comparative study of the effects of radiation, indomethacin, prednisolone, and ethane-1-hydroxy-1,1-diphosphonate (EHDP) in the prevention of ectopic bone formation.

Forty male New Zealand white rabbits were treated with immobilization and forcible manipulation of the right knee known to cause ectopic bone formation in the quadriceps muscle. The animals were also treated with either: A) A total radiation dose of 1840 rad (18.4 Gy); B) A 0.5 mg/kg/day oral dose of prednisolone; C) 10 mg/kg/day of indomethacin, given in two oral doses; D) Ethane-1-hydroxy-1,1-diphosphonate (EHDP) given in a 20-mg/kg/day oral dose; or E) with the vehicle given alone as a control. The experimental period was four weeks, and the amount of ectopic bone was determined by planimetry of serial transverse sections of the femur. The degree of knee stiffness was recorded during the experiment. The amount (mean +/- SEM) of ectopic bone was 1.412 +/- 0.264 cm3 in controls; it was insignificantly higher in the EHDP-treated group, but significantly lower (p less than 0.01) in rabbits treated with radiation (0.390 +/- 0.094 cm3), prednisolone (0.181 +/- 0.076 cm3), and indomethacin (0.314 +/- 0.112 cm3). In control animals and those given EHDP, the treatment invariably led to almost complete stiffness of the right knee. The rabbits treated with prednisolone and indomethacin offered the least resistance to the manipulations, and the group treated with radiation showed intermediate stiffness. Semiquantitative histologic evaluation demonstrated less inflammation in the group treated with prednisolone than in the control group.

Animals↗
PubMed1979

Complexing of reduced technetium and tin(II) by chelating phosphate compounds. II. In vitro stability of pyrophosphate and ethane-1, hydroxy-1, diphosphonate (EHDP) complexes.

The in vitro stability of 99mTc- and 113Sn-pyrophosphate and ethane-1, hydroxy-1, diphosphonate (EHDP) complexes was studied by varying the mode of preparation. The 1-hr distribution in the rat was used as an indicator for complex formation or destruction. A maximum of bone uptake and urinary excretion and a minimum of soft tissue concentration was obtained if there was an excess of phosphate in relation to tin(II) in the equilibrium. Formation of tin(II) colloid was favoured in the presence of an excess of tin(II) in the equilibrium, 99mTc colloid occurred with some delay. After dilution in neutral normal saline the chelates were more or less destroyed, as shown by a 113Sn(II) colloid formation whereas the 99mTc-phosphate complexes were transformed into a 99mTc kidney agent. At pH 11 the 113Sn(II)-phosphate complexes proved to be stable, the 99mTc-phosphate complexes were also transformed into the 99mTc kidney agent. Oxidation of all tin(II) in the equilibrium by hydrogen peroxide did not change the distribution patterns of 113Sn, 99mTc was oxidized to pertechnetate. In general complexes between tin(II) and chelating phosphate compounds proved to be more stable than those with reduced technetium. EHDP was found to form stronger complexes with tin(II) and reduced technetium than pyrophosphate.

Animals↗
PubMed1985

[EHDP (ethylidene-1-hydroxy-1,1-diphosphonate) in the treatment of polyosseous Paget disease].

13 patients with polyosseous Paget's disease were treated for a mean period of 7 months with disodium etidronate (EHDP, ethylidene-1-hydroxy-1,1-diphosphonate); the average daily dosage was 5 mg/kg body weight. Subjectively, all patients reported a considerable improvement, in particular with regard to pain. Objectively, a significant decrease in plasma alkaline phosphatase activity and in urinary hydroxyproline excretion was observed. Bone scintigraphy showed a decreased activity of bone lesions after therapy, but no clear-cut regression was found radiologically. No serious side-effects were observed during treatment with EHDP and oral administration of the drug proved to be advantageous.

Aged↗
PubMed1985

Role of 99mTc methylene diphosphonate bone imaging in the management of lymphoma.

The role of modern techniques of 99mTc methylene diphosphonate bone imaging in the management of lymphoma patients was assessed by comparing results of 107 bone scans in 16 patients with Hodgkin's disease, and 45 patients with non-Hodgkin's lymphoma to simultaneous radiologic, clinical, and histopathologic features as well as to subsequent disease course. The sensitivity and specificity were both greater than or equal to 0.96 in both Hodgkin's disease and non-Hodgkin's lymphoma and the overall accuracy by site was 98%. The scan proved to be useful in the definition and follow-up of skeletal lymphomatous disease in both symptomatic and asymptomatic patients, and defined abnormalities which were not predicted by either serum alkaline phosphatase activity or the presence of bone marrow involvement. In no patient, however, did the bone scan result by itself alter either initial staging or estimates of extent of disease at the time of relapse. Bone scanning, therefore, cannot be recommended as a screening procedure in patients with lymphoma; rather, this test is best reserved for the definition and follow-up of skeletal metastases in patients with active, concomitant, extraosseous disease.

Bone Neoplasms↗
PubMed1977

Appearance of a gastric ulcer during diphosphonate therapy in a woman with CRST syndrome.

A 46-year-old woman with the CRST variant of scleroderma (calcinosis, Raynaud's phenomenon, sclerodactyly, and telangiectasis) was treated with a diphosphonate (disodium etidronate) in an effort to reduce her dystrophic calcifications or retard their progression. After 18 months of therapy, no improvement in her calcinosis was noted. In addition, she developed bloody diarrhea, epigastric burning, and weight loss during the last two months of Therapy. Upper gastrointestinal series revealed a gastric ulcer. Endoscopy with biopsy proved it to be benign. Gastric ulcerations has been seen in animals given disodium etidronate but only at much higher doses than are currently recommended for humans. Although a cause and effect relationship cannot be established with certainty in this patient, it is suggested since she was not receiving other ulcerogenic drugs chronically. This information may be important to other investigators of disodium etidronate.

Calcinosis↗
PubMed1978

[32P] diphosphonate dose determination in patients with bone metastases from prostatic carcinoma.

In an initial safety study, phosphorus-32 (as diphosphonate) was administered intravenously to five patients with painful bone metastases from prostatic carcinoma; two patients received 9 mCi and three were given 3 mCi. Hematological, biochemical, ECG, x-ray, bone-scan data, and clinical observation, were followed for 2 mo. At both dose levels, bone-marrow depression was noted. One of the patients, who received 9 mCi, had only a slight dip in the levels of circulating white blood cells and platelets. The other 9-mCi patient was the only one with discrete metastases by bone scan; he had bone-marrow depression, from which he recovered, and was the only one of the five who had relief of bone pain.

Adenocarcinoma↗
PubMedDate not supplied

The diagnostic value of 99m Tc-diphosphonate bone imaging in transient osteoporosis of the hip.

We present topographic and quantitative studies of 99m Tc-diphosphonate bone scans from 46 patients and 25 control subjects in which we found transient osteoporosis of the hip (TOH) (12 cases--2 bilateral), early aseptic osteonecrosis of the femoral head (19 cases--2 bilateral), early coxitis (11 cases), and stress fracture of the femoral neck (4 cases). Active TOH was characterized by intense, homogeneous increased uptake of the entire femoral head, extending to the acetabulum and the neck, and sometimes to the shaft. The scintigram of TOH differed greatly from that in the other hip disorders studied. Bone scintigraphy can help to diagnose the cause of pain in a hip before definite roentgenographic signs appear.

Adult↗
PubMed1983

Treatment of Paget's disease of bone with ethane-1, hydroxy-1,1 diphosphonate (EHDP) at a low dosage (5 mg/kg/day).

Paget's disease of bone in 51 patients was treated with ethane-1, hydroxy-1,1 diphosphonate (EHDP) for six months at a dosage of 5 mg/kg/day. Clinically, the analgesic effect on bone pain is clear, with parallel reduction in radioisotope uptake observed by quantitative bone scintigraphy. There is also a reduction of about 70% of the excess level of serum alkaline phosphatase and total 24-hour urinary hydroxyproline. Histologically, there is a significant reduction in both the osteoclastic resorption surfaces and the number of osteoclasts. In contrast to that obtained by calcitonin, these clinical, biologic, and histologic changes continue for at least one year beyond the end of the treatment. That is the main characteristic of this treatment, of which the clinical and biologic tolerance is admittedly very satisfactory. Accumulation of osteoid tissue, which is indicative of a mineralization defect, does not appear at low dosages under the prescribed conditions. EHDP (5 mg/kg/day) can be regarded as effective treatment for some patients with Paget's disease of bone.

Adult↗