Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Diphosphonates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,405 records · Page 78Linked to original sources
PubMedDate not supplied

[A new approach to the creation of heart valve xenograft bioprostheses resistant to calcification].

The calcium binding activity of xenograft tissue in stages of modification with papain, diphosphonates, and heparin was studied on a model of accelerated calcification in subcutaneous implantation of cusps of pig's aortic bioprostheses to 42 rats. In immobilization of 3-amino-1-oxypropylidendiphosphonic acid and xydiphon the amount of calcium in the implants reduced 50 times as compared to the control. The first stage of ion-covalent heparin immobilization--treatment with albumin--increased the calcium-binding activity of the biomaterial, but subsequent heparinization reduced again the calcium content in the cusp tissue to the level attained in the stage of diphosphonate immobilization. The results of the chemical analysis correlated with the findings of morphological examination. Besides, the new method of treatment made it possible to increase the strength of the biological tissue by 20%. This method of storage of bioprostheses is promising for clinical approbation.

Animals↗
PubMedDate not supplied

Serial bone scintigrams demonstrating obstructive uropathy and nephropathy due to transitional cell carcinoma of the urinary bladder.

Serial 99mTc diphosphonate bone scintigraphic studies of two patients with transitional cell carcinoma of the urinary bladder demonstrated gradually progressive renal dysfunction. The abnormalities in the last bone scan of each patient were compatible with the findings of the concurrent 131I hippuran and 99mTc-DTPA studies, and were presumably secondary to obstruction of the ureteral orifices by tumor in the urinary bladder. Progressive renal dysfunction may be reliably demonstrated by serial 99mTc diphosphonate bone scintigraphy.

Aged↗
PubMed1989

Mechanisms of inhibition of calcification.

Mineralization processes in the body are controlled by physicochemical and cellular regulation of hydroxyapatite (HA) nucleators and inhibitors. The chemical mechanism of action of HA inhibitors has been studied in vitro using solution pH-stat techniques or Types I and II collagen gel diffusion systems. Three biologically relevant systems are used with these methodologies: (1) transformation of amorphous calcium phosphate (ACP) to crystalline HA; (2) direct formation of HA; and (3) growth of HA crystals. Several different mechanisms have been identified for HA inhibition. Condensed phosphates (containing P-O-P linkages) and diphosphonates (containing P-C-P linkages) bind strongly to the surface of forming HA nuclei and crystals and poison growth sites at concentrations as low as 10(-6) M, blocking HA formation. From this in vitro work, diphosphonates have been developed for the treatment of Paget's disease. Proteoglycans, found in cartilage, delay HA formation by a steric effect whereby large volumes of solution become unavailable for HA formation and growth as these enormous macromolecules tumble about. Mg ions enter the structure of forming HA nuclei by replacing Ca, resulting in a distorted atomic structure that slows subsequent growth to HA. Al ions delay HA formation, not by entering the structure of forming HA nuclei, but by adsorbing on the surface of growing HA crystals. Serum proteins slow the transformation of ACP to HA by adsorbing on the ACP surface, which decreases its dissolution rate. Metal-citrate complexes can inhibit HA formation and growth at concentrations as low as 10(-5) to 10(-6) M. Phosphorylated molecules such as acidic proline-rich phosphoproteins and statherins found in saliva suppress HA crystal growth on tooth surfaces by adsorbing on active surface sites. Future research in this field lies in the study of interactions of HA inhibitors found together in calcifying tissues.

Aluminum↗
PubMed1989

Bone scanning in metabolic and endocrine bone disease.

99mTc diphosphonate bone scanning has proved to be a sensitive, though nonspecific, way of detecting a wide variety of metabolic bone disorders. Classic scan appearances of generalized increased tracer uptake throughout the skeleton are found in many types of metabolic bone disease, and whole-body retention measurements can be used to detect early forms of disease. Focal disease identified on bone scanning such as pseudofractures and brown tumors are clearly identified on the 99mTc diphosphonate bone scan, with isotope scan changes preceding radiological changes by up to 18 months. The use of whole-body retention measurements will further increase sensitivity of detection in patients with metabolic bone disease.

Bone Diseases↗
PubMed1987

Influence of disodium etidronate on Paget's disease of bone.

The use of agents that decrease bone resorption, notably the calcitonins, diphosphonates and mithramycin, has been shown to result in symptomatic and/or biochemical improvement in patients with Paget's disease of bone (osteitis deformans). The effects of short-term (6 months), low-dose (5 mg/kg body mass/d) etidronate disodium, a diphosphonate compound at present subject to registration in this country, on the clinical and laboratory manifestations of this disorder were examined. Marked symptomatic improvement was noted in 70% of patients, while biochemical parameters of bone turnover, namely serum alkaline phosphatase level (44%) and urine hydroxyproline excretion (56%), decreased significantly (P less than 0.001). A technetium-99m bone scan revealed an impressive reduction in uptake of isotope in 50% of patients. The drug was well tolerated and no adverse reactions (clinical, biochemical or haematological) were evident. It is concluded that short-term low-dose etidronate disodium affords a convenient and effective therapeutic alternative in patients with symptomatic Paget's disease.

Adult↗
PubMedDate not supplied

The effects of anticalcification treatments on bioprosthetic heart valves implanted in sheep.

Several preimplantation processes have been shown to inhibit the calcification of pieces of porcine aortic valves and of bovine parietal pericardium implanted subcutaneously in rats. To investigate the effectiveness of these processes in modifying the calcification of bioprosthetic valves implanted in an intracardiac position, mitral and tricuspid valve replacements were performed in young sheep. Bioprosthetic valves treated with the following preimplantation processes were studied: 1) surfactants, including sodium dodecyl sulfate, polysorbate-80, Triton X-100 and N-lauryl sarcosine; 2) covalently bound aminohydroxypropane diphosphonic acid; 3) toluidine blue; and 4) incorporation of polyacrylamide into valvular tissues. Quantitative calcium analyses showed that only the surfactants substantially reduced calcification of bioprostheses implanted in intracardiac positions. This effect was evident only in porcine aortic valvular bioprostheses, and not in pericardial bioprostheses. Triton X-100 and N-lauryl sarcosine not only reduced calcification but also induced alterations that decreased the durability of the valves. Toluidine blue decreased calcification to a degree that was statistically significant but not biologically important, while polyacrylamide incorporation and diphosphonate binding increased calcification. Thus, data regarding anticalcification treatments obtained from subcutaneous implantation studies in small animal models should be interpreted cautiously and validated by studies with intracardiac valvular implantation in large animals.

Animals↗
PubMed1987

Nuclear scintigraphic evaluation of third metacarpal and metatarsal bone fractures in three horses.

Nuclear scintigraphy was used to evaluate healing of third metacarpal bone (MC III) fractures in 2 horses (horses 1 and 2) and a third metatarsal bone fracture in 1 horse (horse 3) after stabilization of each fracture with 2 broad dynamic compression plates. In horse 1, the fracture had uniform uptake of 99mTc methylene diphosphonate on days 1, 15, and 30 after surgery. The fracture healed, and the horse was discharged from the clinic on day 52. In horse 2, a 6-cm photopenic region (ie, area of low radioactivity) was seen over the diaphysis of MC III on day 3. The region persisted and became more distinct by day 32. The diaphysis of MC III sequestered, and horse 2 was euthanatized on day 44. In horse 3, vascularity was seen bridging the fracture on day 5, with a 3-cm photopenic region over the dorsal diaphysis of the third metatarsal bone. By days 18 and 32, uptake of 99mTc methylene diphosphonate in the region had increased, indicating vascularization of the site. the fracture healed, and horse 3 was discharged from the clinic on day 47. Our findings indicated that serial nuclear scintigraphy can be used to evaluate fracture vascularization after surgery in horses.

Animals↗
PubMed1987

[Quantitative histological study of the bone mass and cellular activity after 120-days decubitus. Trial of preventive protocols].

Bone biopsies of iliac crests, performed at the beginning and the end of a decubitus period of 120 days, were studied in 20 healthy volunteers men. The purpose of this experiment is to simulate the bony alterations of astronauts. The bony mass of all bed-ridden patients remained constant. In strictly immobilized patients, the rate of bony mineralization is decreased and the osteoclastic resorption activity is stimulated. In bed-ridden patients subjected to preventive physical exercises, the bony formation and resorption are increased. When prevention is administered with the use of a diphosphonate, the osteoid and osteoclastic parameters are decreased. When both types of prevention are administered, the osteoid parameters and the resorption activity are decreased but less markedly than in patients treated with diphosphonate alone.

Adult↗
PubMed1987

Magnetic resonance imaging in the early diagnosis of ischemic necrosis of the femoral head. Preliminary results.

Magnetic resonance imaging (MRI) was performed on the hips of 25 patients with suspected ischemic necrosis of the femoral head. Twenty-six femoral heads manifested MRI changes of ischemic necrosis: diminished bone marrow signal in a ringlike, focal, or diffuse pattern. Plain radiographs were normal in 13 of 26 MRI-positive hips; six were asymptomatic. MRI was more effective in detecting early cases than conventional 99mTc-diphosphonate or 99mTc-sulfur colloid (SC) bone scanning. There were no false-negative MRI examinations, but diphosphonate scans were negative in nine hips with normal radiography and abnormal MRI. Sulfur colloid scans were normal in only two hips with positive MRI, but SC scan results were often equivocal because isotope deficits were bilaterally symmetric. The results of this preliminary investigation imply that MRI has extraordinary sensitivity for the detection of early ischemic necrosis. Unlike radionuclide scanning, MRI shows the exact location and extent of femoral head necrosis. Because MRI is expensive, it should be used in a cost-effective manner. Therefore, MRI is best suited for the diagnosis of early cases where less expensive tests are negative or equivocal and as a precursor to more costly interventional procedures, such as core biopsy study or decompression.

Adult↗
PubMed1985

[Treatment of Paget's disease with low dose sodium etidronate (5mg/kg/day). Occurrence of reversible transient suspected leukopenia].

27 patients with Paget's disease, from 51 to 80 years of age, were treated with etidronate disodium at a dose of 5 mg/kg/day. 70 percent of patients had multiple bone involvement. Six patients had previously been treated with diphosphonates, and nine had previously received synthetic pork or salmon calcitonin. The following parameters were studied: the serum alkaline phosphatase, urinary hydroxyproline, a self-assessment scale to evaluate pain and a scale to assess improvement in functional capacity. From the first month of treatment, significant improvement in pain indices was noted and over the following two months there was an associated significant regression in parameters of bone resorption and formation. The clinical and laboratory improvement brought about with diphosphonates persisted three months after cessation of therapy in 88 percent of cases. Gastrointestinal tolerance of the drug was excellent, but three cases of transitory leukopenia occurred which resolved spontaneously, requiring in two cases cessation of therapy. Even though it is impossible to correlate with certainty this previously undescribed finding to therapy with etidronate disodium, we believe that at a dose of 5 mg/kg/day, the drug provides rapid, effective, long term treatment in Paget's disease, but that regular hematologic surveillance should be performed.

Aged↗
PubMed1979

Activation of thymocyte glucocorticoid receptors to the steroid binding form. The roles of reduction agents, ATP, and heat-stable factors.

The specific glucocorticoid binding capacity in cytosol preparations of rat thymocytes decays with a half-life of 4 h at 0 degrees C or 20 min at 25 degrees C. Phosphatase inhibitors (molybdate, fluoride, glucose 1-phosphate) added alone do not prevent this inactivation. Dithiothreitol (2 mM) has a large stabilizing effect on the binding capacity at 0 degrees C but only a small effect at 25 degrees C. Addition of 10 mM molybdate plus 2 mM dithiothreitol totally prevents inactivation for at least 8 h at 25 degrees C as well as at 0 degrees C. Fluoride (100 mM) also retards the inactivation if added with dithiothreitol. Addition of dithiothreitol at 25 degrees C to inactivated cytosol receptors results in partial activation of the binding capacity. Addition of dithiothreitol to receptors inactivated at 25 degrees C in the presence of molybdate allows total reactivation of the binding capacity to the maximum zero time value. If binding capacity is inactivated by preincubation of the cytosol at 25 degrees C, addition of ATP with dithiothreitol enhances the activation observed with only dithiothreitol. This ATP stimulated activation is optimal at 1 to 3 mM. ATP (10 mM) is required when molybdate is added to prevent simultaneous inactivation. ADP, GTP, CTP, and UTP have some activating capacity but the effects of all nucleotides are inhibited by the ATP analog, adenyl-5'-yl (beta, gamma-methylene)diphosphonate. ATP-dependent activation can also be prevented with 50 mM EDTA, and addition of magnesium partially overcomes the EDTA inhibition. Dithiothreitol activation of thymocyte glucocorticoid binding capacity can also be enhanced by addition of a heat-stable preparation from thymocytes, L cells, or liver. Sephadex G-25 chromatography, assay of ATP, and inhibition of the activation with adenyl-5'-yl (beta, gamma-methylene)diphosphonate suggest that these preparations contain varying amounts of endogenous reducing equivalents and ATP as well as a larger heat stable factor. Maximum activation is obtained by adding dithiothreitol, ATP, molybdate, and the larger heat-stable factor. These results suggest that stabilization and activation of glucocorticoid binding capacity in thymocytes requires phosphorylation as well as reduction of the receptor itself or of some other component required for the steroid binding reaction.

Adenosine Triphosphate↗
PubMed1979

Complexes of technetium with pyrophosphate, etidronate, and medronate.

The reduction of [99Tc]pertechnetate was studied as a function of pH in complexing media of pyrophosphate, methylene diphosphonate (MDP), and ethane-1, hydroxy-1, and 1-diphosphonate (HEDP). Tast (sampled d-c) and normal-pulse polarography were used to study the reduction of pertechnetate, and normal-pulse polarography (sweeping in the anodic direction) to study the reoxidation of the products. Below pH 6 TcO4-was reduced to Tc(III), which could be reoxidized to Tc(IV). Above pH 10, TcO4-was reduced in two steps to Tc(V) and Tc(IV), each of which could be reoxidized to TcO4-. Between pH 6 and 10 the results differed according to the ligand present. In pyrophosphate and MDP, TcO4- was reduced in two steps to Tc(IV) and Tc(III); Tc(III) could be reoxidized in two steps to Tc(IV) and TcO4-. In HEDP, on the other hand, TcO4- was reduced in two steps to Tc(V) and Tc(III), and could be reoxidized to Tc(IV) and TcO4-. Additional waves were observed; they apparently led to unstable products.

Diphosphates↗
PubMed1977

Rapid miniaturized chromatographic quality-control procedures for Tc-99m radiopharmaceuticals.

Our laboratory has adopted a complete miniaturized charomatography system for Tc-99m radiopharmaceuticals in order to improve upon the commercial systems currently available. Three distinct, separate, chromatographic procedures are used to determine the labeling efficiencies of Tc-99m-labeled sulfur colloid, MAA, stannous chloride, phytate, DMSA, DTPA, pyrophosphate, diphosphonate, methylene diphosphonate, polyphosphate, and glucoheptonate. The chromatographic systems include Whatman 31 ET paper and acetone, Gelman ITLC-SG and 0.9% sodium chloride, and Gelman ITLC-SA and acetone. The chromatographic strips are miniaturized (1 X 6 cm), colored-coded, marked, and numbered. All the chromatographic quality-control procedures are simple, rapid, and can easily be incorporated into the routine quality-control program of any nuclear medicine facility.

Chromatography↗
PubMed1984

Effect of the high femoral osteotomy upon the vascularity and blood supply of the hip joint.

This investigation was done to study the effects of high femoral osteotomy upon the vascularity and blood supply of the hip and to further our knowledge of its physiologic basis. We have used established methods of study, including bone scans, microangiography, isotope clearance and perosseous venography, and based upon the results of these studies, we have reached certain conclusions. First, high femoral osteotomy increases the blood flow and vascularity in the hip joint, the femoral head and neck and the great trochanter. Second, bone scanning techniques using 99mTc labeled diphosphonate have shown increased uptake in the femoral head and neck after high femoral osteotomy. The localization was done using a Digital Gamma III computer, and the activity on the osteotomy side at two weeks was 3.5 times as great as on the control side. By 16 weeks postoperatively, there was still two times as much activity on the osteotomy side. Third, microangiography showed increased vascularity both at the osteotomy site and in the femoral head and neck and the greater trochanter on that side. Such an increase in vascularity first became evident two weeks after osteotomy and persisted during the four month period studied. Fourth, the results of the 99mTc diphosphonate clearance study showed a 25 per cent increase in femoral head blood flow on the operative side. Fifth, perosseous venography of the femoral head and neck showed a marked increase in venous drainage through the osteotomy site in the immediate postosteotomy stage.

Animals↗
PubMed1981

[Treatment of hypercalcemias].

Apart from the search for specific oncological treatments, interesting investigations are currently in progress into methods designed to increase bone resistance against tumoral aggression. Several substances are under study. Here the discussion will chiefly centre on the diphosphonates, their mechanism of action and indication in bone oncology. It has been seen that tumoral hypercalcemias (with or without bone metastases) essentially derive from disturbance of the balance between the huge mineral stores of the bone and the small extracellular space. It has also been learned that osteolysis inhibition is the major step in their treatment, while therapies designed to eliminate the calcium excess through the kidney (saline solutions, furosemide, ethacrinic acid, dialysis) or bind it with chelators (EDTA) can have only transitory effects. Tumoral osteolysis may be inhibited by drugs acting on bone and/or tumoral cells (mithramycin, calcitonin, corticosteroids etc.) or by the diphosphonates. At present the latter are the treatment of choice for tumoral hypercalcemias.

Adrenal Cortex Hormones↗
PubMed1981

Circulatory and vascular changes in the hip following innominate osteotomy: an experimental study.

The circulatory and vascular changes in the hip following Salter-type innominate osteotomy were studied in 35 dogs to determine the effects of innominate osteotomy on the blood supply of the hip joint. Microangiography, bone scanning, and isotope clearance were employed four months after the innominate osteotomy. Microangiography showed increased vascularity at the osteotomy site, in the ipsilateral side acetabulum, and in the femoral head in 65% of the dogs. Bone scanning with 99mTc diphosphonate showed increased activity at the osteotomy site, in the acetabulum, and in the femoral head and neck in 75% of the dogs. The 99mTc diphosphonate clearance studies showed that the blood supply to the femoral head was increased by almost 30% after innominate osteotomy in 50% of the dogs studied. These observations indicate that innominate osteotomy could increase the vascularity and blood supply of the hip by increasing the collateral circulation in the process of healing of the osteotomy. The physiologic basis of the joint to innominate osteotomy constitutes a rational basis for recommending the operation for the treatment of selected cases of congenital hip dislocation, Legg-Perthes disease of the femoral head, and degenerative osteoarthritis of the hip with or without acetabular dysplasia.

Acetabulum↗
PubMed1981

[Distribution in rats after intravenous injection of 88Y compounds (author's transl)].

88Y was given to rats in form of citrate, diphosphonate or chloride to determine its accumulation in various organs. The activity in the bones was high but not as high as that of calcium. The application of methylene-diphosphonate showed high enrichment in the liver because of intravital colloid formation. Elimination by the kidneys depends on the type of the 88Y compound applied.

Animals↗
PubMed1995

Axillary lymph node uptake of technetium-99m-MDP.

UNLABELLED: We sought to determine the frequency and significance of axillary lymph node visualization on bone scans performed with diphosphonates. METHODS: Consecutive 99mTc-methylene diphosphonate (99mTc-MDP) bone scans (2435) were inspected for axillary soft-tissue uptake. In positive cases, the results of physical examination, correlative imaging studies and serial bone scans were recorded, as was the site of venipuncture. RESULTS: Forty-eight studies (2%) showed axillary uptake ipsilateral to the injection site. Extravasation of tracer, documented by focal activity near the injection site, was present in every case. There was no association with axillary adenopathy, mass, induration or radiographically visible calcification. On some images, foci adjacent to the axilla were superimposed on the rib, scapula, or humerus. The bone-to-background ratio was frequently reduced; repeat imaging after 1-2 hr usually improved osseous detail. CONCLUSION: Ipsilateral axillary lymph node visualization due to extravasation of 99mTc-MDP is frequently associated with additional foci superimposed on osseous structures simulating pathology. Delayed skeletal uptake is common in such cases and necessitates a greater time interval between injection and imaging.

Axilla↗