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PubMed1979

Technetium-99m-labeled methylene diphosphonate and hydroxyethylidine diphosphonate--biologic and clinical comparison: concise communication.

The biologic and imaging characteristics of Tc-99m MDP and Tc-99m HEDP were compared in ten patients: Tc-99m MDP exhibited lower blood activity, lower 4-hr urinary excretion, and higher normal bone-to-background ratio. Assessment of overall image quality also favored Tc-99m MDP, indicating that the normal skeleton is better visualized with this agent. The total number of lesions seen (18) was not large enough to allow critical comparison of relative lesion-detecting efficacy. However, discrepancies between the two agents were observed, suggesting additional evaluation of the relative lesion-detecting efficacy of these two bone agents.

Adult↗
PubMed1983

Tc-99m hydroxymethylene diphosphonate and Tc-99m methylene diphosphonate: biological and clinical comparison: concise communication.

The biologic and imaging characteristics of Tc-99m HMDP and Tc-99m MDP were compared in ten patients. Tc-99m HMDP blood levels were marginally lower at 4 hr. There were no significant differences in 4-hr urinary clearance, normal bone-to-background ratio, or ratio of lesion to normal bone. Relative image quality comparison showed a slight preference for Tc-99m HMDP. Biologically Tc-99m HMDP compares favorably with Tc-99m MDP. Under the conditions of this study, Tc-99m HMDP image quality is at least comparable to that of Tc-99m MDP.

Aged↗
PubMedDate not supplied

[Experiences with cement-free implantation of the Zweymüller/Endler and Zweymüller total hip joint endoprosthesis. Indications, results, complications and modification of periarticular ossification by diphosphonate (ethylidene-1-hydroxy-1,1-diphosphonate)].

In the last six years the authors have implanted 340 hip joint prostheses of the Zweymüller/Endler or Zweymüller type in 285 patients from the lateral transgluteal approach. Approximately one-third of these patients (111) had previously undergone surgery on the hip joint in question. Intraoperative complications included four cases of elongation of the leg due to implantation of an over-long prosthesis shaft. Four of the shafts implanted were too small and in two cases subsequently loosened. In two patients a divulsion of the trochanter major occurred and there were two cases of cracking of the calcar femoris with involvement of the trochanter minor. There were also two cases of shaft divulsion at the level of the prosthesis tip. Postoperative complications included periarticular ossifications in 41 cases. There were 11 cases of phlebothrombosis and six of pneumonia. Superficial hematomas developed in the wound region in four cases. In addition, there were two cases of shaft and one of acetabular loosening, as well as three prosthesis dislocations. Between October and December 1987, a total of 232 of these patients were examined and the results rated according to Merl d'Aubigne's classification: 166 (71%) were classified as very good or good, 49 (21%) as satisfactory, and 17 (7%) as unsatisfactory. The most common postoperative complication was periarticular ossification, seen in 41 cases. Even though this is not a serious complication and the periarticular ossifications did not necessarily result in severe limitation of movement, a major functional loss as compared to the preoperative findings was seen in the patients with severe ossification (IIIrd degree) at the examination 12 months postoperatively. By giving EHDP, since November 1984, it has proved possible to reduce the incidence of periarticular ossifications from 28 to 12%. In the last 24 months even better results have been achieved by administration of EHDP unter function-scintigraphic control. According to the author's results the Zweymüller/Endler and Zweymüller systems satisfy the requirements for a cement-free total hip replacement since, on the one hand, intraoperative and postoperative complications are slight and, on the other, a good functional result is achieved. The Zweymüller prosthesis has proved particularly suitable for hip joints operated on previously.

Adult↗
PubMed1978

The effects of diphosphonates on the growth and glycolysis of connective-tissue cells in culture.

1. The effects of two diphosphonates (compounds containing a P-C-P bond), disodium dichloromethanediphosphonate and disodium 1-hydroxyethane-1,1-diphosphonate, on the metabolism of cultured rat calvaria cells, rabbit ear cartilage cells and rat skin fibroblasts were investigated. 2. The diphosphonates had no effect on the growth of cartilage cells and on the exponential growth of the calvaria cells and the fibroblasts. However, dichloromethanediphosphonate stopped the growth of the calvaria cells and the fibroblasts after the beginning of confluence, whereas the untreated cells were still growing to a certain extent. This inhibition was dose-dependent. After the drug was withdrawn, the cells recovered slowly. 1-Hydroxyethane-1,1-diphosphonate had no detectable effect on the growth of any of the cell types studied. Both diphosphonates decreased the cloning efficiency of calvaria cells and fibroblasts. 3. The K+ content of cartilage, calvaria and skin cells was diminished only by the highest (0.25 mM) concentration of dichloromethanediphosphonate. 4. Radioactive dichloromethanediphosphonate and 1-hydroxyethane-1,1-diphosphonate were taken up linearly with time for at least 48 h by calvaria cells and fibroblasts. The diphosphonate concentration in the cells depended on its concentration in the medium. 5. Both diphosphonates, in a dose-dependent fashion, markedly inhibited glycolysis, dichloromethanediphosphonate being more effective than 1-hydroxyethane-1,1-diphosphonate, at drug doses that had no effect on cell growth or cellular K+ content. Calvaria cells were much more sensitive than cartilage cells. When cartilage cells were cultured in an N2 atmosphere, these effects on glucose and lactate metabolism disappeared. 6. As increased acid production appears to be associated with resorption of bone, this decrease in lactate may explain why diphosphonates are effective inhibitors of bone resorption in vivo.

Animals↗
PubMed1976

The effect of several diphosphonates on acid phosphohydrolases and other lysosomal enzymes.

Diphosphonates are known to inhibit bone resorption in tissue culture and in experimental animals. This effect may be due to their ability to inhibit the dissolution of hydroxyapatite crystals, but other mechanisms may be important. Since lysosomal enzymes have implicated in the process of bone resorption, we have examined the effect of several phosphonates and of a polyphosphate (P20,2) on lysosomal hydrolases derived from rat liver and rat bone. Dichloromethylene diphosphonate strongly inhibited acid beta-glycerophosphatase (EC 3.1.3.2) and acid p-nitrophenyl phosphatase (EC 3.1.3.2) and to a lesser degree (in descending order) acid pyrophosphatase (EC 3.1.3.-), arylsulfatase A (EC 3.1.6.1), deoxyribonuclease II(EC 3.1.4.6) and phosphoprotein phosphatase (EC 3.1.3.16) of rat liver. Inhibition of acid p-nitrophenyl phosphatase and arylsulfatase A was competitive. Ethane-1-hydroxy-1, 1-diphosphonate did not inhibit any of these enzymes, except at high concentrations. Neither dichloromethylene diphosphonate nor ethane-1-hydroxy-1, 1-diphosphonate had any effect on beta-glucuronidase (EC 3.2.1.31), arylesterase (EC 3.1.1.2) and cathepsin D (EC 3.4.23.5). Of several other phosphonates tested only undec-10-ene-1-hydroxy-1, 1-diphosphonic acid inhibited acid p-nitrophenyl phosphatase strongly, the polyphosphate (P20, I) had little effect. Acid p-nitrophenyl phosphatase in rat calvaria extract behaved in the same way as the liver enzyme and was also strongly inhibited by dichloromethylene diphosphonate, but not by ethane-1-hydroxy-1, 1-diphosphonate. It is suggested that the inhibition of bone resorption by dichloromethylene diphosphonate might be due in part to a direct effect of this diphosphonate on lysosomal hydrolases.

Acid Phosphatase↗
PubMed1977

The effects of various diphosphonates on a rat model of cardiac calciphylaxis.

Seven diphosphonate analogs were treated for their effects on myocardial and cardiovascular degeneration and calcification in an experimental model of cardiac calciphylaxis. A single oral dose of dihydrotachysterol (DHT) administered to rats induced myocardial and vascular degeneration, focal myocarditis and vasculitis, and myocardial and vascular mineralization. The results demonstrated a considerable variation among the various diphosphonates in their ability to block the pathological changes observed in this model. Ethane-1-hydroxy-1,1-diphosphonate (EHDP) was the most effective diphosphonate in reducing myocardial and vascular degeneration and calcification, whereas diphosphonates such as ethane-1-amino-1,1-diphosphonate (EADP) and hydroxymethylene diphosphonate (HMDP) had little or no effect compared to saline controls. For those diphosphonates which were effective, e.g., EHDP, the tissue-protective effects were observed whether the rats were treated with drug prior to the administration of DHT, or whether drug treatment commenced after DHT administration. The results are discussed in terms of the known biological properties of the diphosphonate drugs.

Animals↗
PubMed1980

The effects of calcitonin and colchicine on the cellular response to diphosphonate.

The mechanism by which diphosphonates inhibit bone resorption remains speculative; however, the osteoclast appears to be selectively affected by the drug. This study examined the effects off diphosphonate on osteoclasis in bones treated concomitantly with agents which reduce the osteoclast ruffled border, calcitonin and colchicine. Dichloromethylene diphosphonate, calcitonin, and colchicine inhibited parathyroid-hormone-stimulated bone resorption, as indicated by a significantly reduced release of 45Ca from prelabelled long bones. Quantitative and qualitative histological analyses of osteoclasts indicated differences among effects resulting from agents. Only bones treated with diphosphonate demonstrated a majority of osteoclasts with degenerative appearance; colchicine-treated bones exhibited many spherulated cells with cytoplasmic blebs. The number of normal osteoclasts in calcitonin-treated bones was the same as in controls and decreased with diphosphonate and colchicine treatment. All inhibitory agents reduced the number of nuclei per osteoclast; furthermore, colchicine effected an additional significant reduction, as compared with diphosphonate and calcitonin. The number and frequency of abnormal osteoclasts was increased by diphosphonate, but unaffected by colchicine and calcitonin. The addition of calcitonin, but not colchicine, to diphosphonate-treated bones decreased the incidence of abnormal osteoclasts. Although both calcitonin and colchicine are known to reduce the osteoclast ruffled border, this study has shown differences between the morphological effects of the 2 agents which presumably reflect differences in their mode of action and their interaction with diphosphonate.

Animals↗
PubMed1991

[99mTc]diphosphonate uptake and hemodynamics in arthritis of the immature dog knee.

The relationship between [99mTc]diphosphonate uptake and bone hemodynamics was studied in canine carrageenan-induced juvenile chronic arthritis. Blood flow was determined with microspheres, plasma and red cell volumes were measured by labeled fibrinogen and red cells, and the microvascular volume and mean transit time of blood were calculated. Normal femoral epiphyses had lower central and higher subchondral blood flow and diphosphonate uptake values. Epiphyseal vascular volume was uniform, resulting in a greater transit time of blood centrally. In arthritis, blood flow and diphosphonate uptake were increased subchondrally and unaffected centrally, while epiphyseal vascular volume was increased throughout, leading to prolonged transit time centrally. The normal metaphyses had low blood flow and diphosphonate uptake values in cancellous bone and very high values in growth plates, but a large vascular volume throughout. The mean transit time therefore was low in growth plates and high in adjacent cancellous bone. Arthritis caused decreased blood flow and diphosphonate uptake in growth plates but increased vascular volume and transit time of blood. Diphosphonate uptake correlated positively with blood flow and plasma volume and negatively with red cell volume in a nonlinear fashion. Thus, changes in diphosphonate uptake and microvascular hemodynamics occur in both epiphyseal and metaphyseal bone in chronic synovitis of the immature knee. The [99mTc]diphosphonate bone scan seems to reflect blood flow, plasma volume, and red cell volume of bone.

Animals↗