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 1,279 records · Page 71Linked to original sources
PubMed1975

Technetium-99m-labeled stannous imidodiphosphate, a new radiodiagnostic agent for bone scanning: comparison with other 99mTc complexes.

Imidodiphosphate (IDP) is an analog of pyrophosphate and diphosphonate, with a P-N-P bond instead of P-O-P or P-C-P. We have labeled IDP with 99mTc quantitatively (98%) using stannous ions as the reducing/complexing agent in a freeze-dried kit form. Radiobioassay of this compound was carried out in rabbits and the results were compared with those of eight other Tc-labeled bone-imaging agents, using the performance of simultaneously administered 85Sr as a reference standard. The 99mTc-IDP concentrated 20% higher in the bone, and its soft-tissue and blood levels were lower than with 85Sr. By comparison, the concentrations in the bone of the other 99mTc agents were 20% less than that of 85Sr. Regarding blood levels, Tc-IDP performed worse than the Tc-diphosphonate but better than the pyrophosphate and the other technetium complexes. Scintillation camera images of 99mTc-IDP in both rabbits and dogs showed excellent details of the skeleton. In a preliminary human study, images with 99mTc-IDP were somewhat inferior to those comparably procured with 99Tc-methylene diphosphonate, but count rates with the IDP complex were about twice those with the MDP compound. Because of its better bone uptake, however, it is suggested that 99mTc-IDP may be clinically useful in spite of its relatively slow blood clearance.

Adult↗
PubMed1994

[The effect of contaminants on characteristics of 99mTC radiopharmaceuticals].

The influence of 99Tc, oxygen and cupric ions on labeling yield of eight radiopharmaceuticals was examined. The results obtained for commercial and experimental preparations were compared. The latter were formulated so that the content of 99Tc was 4 times, hydrogen peroxide 5 times and copper 50 times higher than in commercial preparations. It was found that these impurities did not affect labeling of 99mTc(Sn)tetracyclin, 99mTc(Sn)dimercaptosuccinate and 99mTc(Sn)diethylida. Long-living 99Tc did not affect any preparations. Oxygen influenced in lesser extent 99mTc(Sn) DTPA, 99mTc(Sn)pyrophosphate and 99Tc(Sn) dicarboxy-propane diphosphonate but strongly 99mTc(Sn) phytate 99mTc(Sn)methylene diphosphonate. Copper influenced only 99mTc(Sn)-methylene diphosphonate. Therefore this preparation was examined in broader range of copper concentrations. According to the results of radiochemical and biodistribution analyses it was concluded that under the experimental conditions the effect of oxygen and copper resulted in an increased content of free 99mTc-pertechnetate in the examined preparations.

Animals↗
PubMed1993

Uptake and biodistribution of technetium-99m-MD32P during rat tibial bone repair.

The present study was carried out in order to test the hypothesis that intravenously injected Tc-MDP separates into its technetium and methylene diphosphonate components in the bone, and that the technetium is preferentially taken-up by the newly-formed osteoid, while the methylene diphosphonate is taken up by the forming mineral. Uptake of Tc-MDP was studied in a rat model of primary bone formation following tibial bone marrow ablation. Each of five radiopharmaceuticals (99mTCO4, 99mTc-MDP, Tc-MD32P, 99mTc-MD32P or MD32P) was injected and their uptake was followed in the whole bone as well as in the organic and inorganic phases of the bone. Irrespective of the radionuclides injected, 99mTc was always taken-up preferentially by the organic phase, while the 32P was preferentially taken-up by the inorganic phase. When 99mTcO4 was injected, it was not taken up by the bone at all. These results indicate that the increased incorporation of 99mTc, when administered as 99mTc-MDP during bone healing, reflects an enhancement in the formation of the organic matrix and not of the calcification process. The study also suggests that the 99mTc-MDP dissociates into its technetium and methylene diphosphonate moieties, which are then adsorbed onto the organic and inorganic phases respectively.

Animals↗
PubMed1993

Extracellular protein secretion of cultured normal and Pagetic osteoblasts.

Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) has been used to map the extracellular secretory activity of normal osteoblasts. The proteins osteonectin, bone sialoprotein, and both the C-telopeptide of collagen I together with collagen I have now been positionally identified. In addition the secretory differences which exist between normal and Pagetic osteoblasts have been mapped with the Pagetic osteoblasts shown to consistently secrete an altered 30 kDa C-telopeptide of collagen type I. The use of the diphosphonate Pamidronate in the treatment of Paget's disease of bone has beneficial effects with suppression of the bone isoenzyme marker alkaline phosphatase. It has been reported that diphosphonates directly inhibit human osteoblast secretory function as well as osteoclast metabolism. The effects of Pamidronate on the secretory activity of normal and Pagetic osteoblast cultures was also investigated. The extracellular protein secretion of normal and Pagetic osteoblasts was not affected by Pamidronate treatment as assessed by 2-D PAGE. This technique allows a comprehensive multiparameter assessment of extracellular secretory activity in normal and diseased states. The findings show that the Pagetic osteoblasts cultured in vitro are functionally abnormal and they support the hypothesis that the underlying problem in Paget's disease is characterised by disorder of osteoblast and osteoclast interactions.

Aged↗
PubMed1987

Chemically modified collagen: a natural biomaterial for tissue replacement.

Glutaraldehyde crosslinking of native or reconstituted collagen fibrils and tissues rich in collagen significantly reduces biodegradation. Other aldehydes are less efficient than glutaraldehyde in generating chemically, biologically, and thermally stable crosslinks. Tissues crosslinked with glutaraldehyde retain many of the viscoelastic properties of the native collagen fibrillar network which render them suitable for bioprostheses. Implants of collagenous materials crosslinked with glutaraldehyde are subject long-term to calcification, biodegradation, and low-grade immune reactions. We have attempted to overcome these problems by enhancing crosslinking through bridging of activated carboxyl groups with diamines and using glutaraldehyde to crosslink the epsilon-NH2 groups in collagen and the unreacted amines introduced by aliphatic diamines. This crosslinking reduces tissue degradation and nearly eliminates humoral antibody induction. Covalent binding of diphosphonates, specifically 3-amino-1-hydroxypropane-1, 1-diphosphonic acid (3-APD), and chondroitin sulfate to collagen or to the crosslink-enhanced collagen network reduces its potential for calcification. Platelet aggregation is also reduced by glutaraldehyde crosslinking and nearly eliminated by the covalent binding of chondroitin sulfate to collagen. The cytotoxicity of residual glutaraldehyde--leaching through the interstices of the collagen fibrils or the tissue matrix--and of reactive aldehydes associated with the bound polymeric glutaraldehyde can be minimized by neutralization and thorough rinsing after crosslinking and storage in a nontoxic bacteriostatic solution.

Adenosine Diphosphate↗
PubMed1990

Effects of bisphosphonates on isolated rat osteoclasts as examined by reflected light microscopy.

The bisphosphonates 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP), 3-amino-1,1-hydroxypropane-1,1-diphosphonic acid (APD), and 1-hydroxyethane-1,1-diphosphonic acid (EHDP) were compared for their ability to inhibit the osteoclastic resorption of bone in culture. This was achieved by measuring the effect of bisphosphonate concentration on the number of resorption pits formed and the total area of resorption. During this analysis, a new application of reflected polarized light microscopy was developed that has advantages over other microscopy techniques, including scanning electron microscopy (SEM), as applied to the analysis of resorbed bone surfaces. 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. Similar data were obtained by counting the number of resorption pits but with EC50 10 times higher. At lower concentrations (10(-9) M), bisphosphonates may enhance the formation of resorption pits. APD was found to be more toxic (10 times) than ABP or EHDP to osteoclasts and mononuclear cells, but toxic concentrations were at least 10(2) times higher than the resorption EC50. These data plus immunofluorescence, SEM, and transient incubation experiments show that it is the bisphosphonate-bone complex that directly inhibits the excavation of resorption pits by mature osteoclasts. The mechanism of action does not appear to require inhibition of osteoclast differentiation or toxic elimination of osteoclasts. Bisphosphonates, however, subtly affect the cytoskeleton of osteoclasts.

Alendronate↗
PubMed1984

Detection of malignant soft tissue tumors in bone imaging.

A total of 2530 consecutive bone scans were examined to evaluate the number and the type of soft tissue neoplasms detected with bone-seeking phosphonates. Sixty-eight primary or secondary soft tissue neoplasms of 63 patients accumulated 99mTc -methylene diphosphonate and 2 accumulated 99mTc -diphosphonate, and one metastasis was seen as a nonactive 'cold' focus in the urinary bladder. The localization of tumors was: 19 in the lung, 15 in the liver, 11 in the kidney, 10 in the peritoneal cavity or ascites, 5 in the large bowel, 4 in the vascular or lymphatic system, 3 in the connective tissue or muscles, 2 in the ovary, 1 in the urinary bladder, and 1 in the brain. Our results differ in many respects from those reported in the literature. The causes of the differences are discussed.

Abdominal Neoplasms↗
PubMed1983

A clinical comparison of 99mTc-DPD and two 99mTc-MDP agents.

Two hundred and fifty-seven patients were studied with bone-seeking radiopharmaceuticals. They were randomly divided into three groups. Two groups were injected with two different 99mTc-methylene diphosphonates from two manufacturers (MDP 1 and MDP 2) and the third group with 99mTc-dicarboxypropane diphosphonate (DPD). DPD was found to be superior with respect to blood clearance, femur to soft tissue ratio and subjectively assessed image quality. There seemed to be no marked differences between the bone-seeking agents in the visualisation of pathological foci. The image quality seemed to be better in the MDP 2 group than in the MDP 1 group but they were similar in other respects. The femur to soft tissue ratio decreased with increasing age in the DPD group but not in the MDP groups. With all agents worsening of scan quality with increasing age was noted and the image quality was better with men than with women. When short incubation times of radiopharmaceuticals were used before injection, the bone to soft tissue ratio was lower and the scan quality was poorer than with incubation times longer than 20 min.

Adult↗
PubMed1977

Aggregation of calcium oxalate crystals: effect of urine and various inhibitors.

The influence of various factors on aggregation of calcium oxalate crystals in vitro was determined. Aggregation was assessed by filtering the crystal suspension and measuring the flow rate through a filter. 10% urine completely inhibited aggregation. Orthophosphate and magnesium at concentrations occuring in urine had no effect. Citrate had no effect at 10(-4) M ,but did inhibit at 10(-3) M. The latter effect is probably due to calcium binding. Pyrophosphate and disodium dichioromethylene diphosphonate (C12MDP) inhibited strongly at 10(-4) M, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at 10(-5) M, whereas pentanemonophosphonate had no effect. Uromucoid also did not show any inhibitory activity. Studies by means of heat inactivation, ultrafiltration and fractionation on DEAE-cellulose and gel-filtration indicated that the inhibitory activity was heterogenous and that the major part was larger than 10 000 daltons.

Calcium↗
PubMed1979

Liver scanning for amyloid.

Subsequent liver scans with both 99mTc-colloid and 99mTc-diphosphonate in a patient with biopsy proven liver amyloidosis are described. The colloid liver scans demonstrated the variable pattern which can be obtained at different stages of the disease, whereas, the absence of Tc-diphosphonate uptake, by the infiltrated liver, did not confirm previous suggestions about the amyloid seeking properties of this material.

Aged↗
PubMed1980

The clinical comparison of skeletal imaging agents.

99-MTc-methylene diophosphonate from two manufacturers was compared with 99mTc-ethane hydroxy diphosphonate in a randomised trial to assess the relative blood clearances and the subsequent image quality. The 99mTc-methylene diphosphonate preparations were found to be superior with respect to both blood clearance and subjectively assessed image quality, particularly when the interval between injection and scanning was three hours. Bone/soft tissue ratios did not mirror the highly significant qualitative comparisons of image quality.

Aged↗
PubMed1990

The scintigraphy of sacroiliac joints. A comparison of 99mTc-DPD and 99mTc-MDP.

The accumulation of 99mTc-methylene diphosphonate (99mTc-MDP) and 99mTc-dicarboxypropane diphosphonate (99mTc-DPD) in sacroiliac (si) joints was evaluated as a function of imaging time in 22 control patients and 5 patients with sacroiliitis. The controls were injected with either 99mTc-DPD or 99mTc-MDP (12 and 10 patients, respectively) and the patients with sacroiliitis with both agents within 5 days. Both the anterior and posterior views of the si joints were taken. The sacroiliac joint-to-sacrum (SI/S) ratio was calculated with the region of interest method. No statistically significant differences between these bone-seeking agents were found in the SI/S ratios of the control or the diseased patients. A clear overlap of indices (mean +/- SD) was found between the control patients and the patients with sacroiliitis. When the inflamed si joint was divided into three small adjacent areas and the SI/S ratios calculated for these areas, a statistically significant (P less than 0.001) increase in the SI/S ratio was noticed when compared with the SI/S ratio of the whole joint. Comparison of control patients and patients with sacroiliitis showed the most significant differences in the anterior views as well as in the P value: P less than 0.001 in all patients injected with 99mTc-DPD and in most patients injected with 99mTc-MDP. In the posterior views, the significance was less marked. In every case, the inflamed part of the si joint was visible in the anterior views. The background subtraction had the greatest effect on the SI/S ratio of anterior images, but in the posterior views no significance was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Idiopathic infantile arterial calcification: a surviving patient with renal artery stenosis.

Idiopathic infantile arterial calcification (IIAC) is a rare hereditary, fatal disease. Death occurs usually within the first 28 months of life. IIAC is characterized by calcifications along the internal elastic membrane and proliferation of the intimal layer of muscular arteries. Specific therapy consists of administration of diphosphonates, but its effectiveness has been a matter of controversy. We report a case treated with diphosphonates which has had an unusual outcome.

Arteries↗
PubMed1990

Clodronate in hypercalcemia of malignancy.

Of the many compounds belonging to the diphosphonate family, clodronate has been widely used in hypercalcemia and osteolysis of malignancy. All published reports indicate that clodronate can normalize plasma calcium in the majority of hypercalcemic, rehydrated cancer patients in whom increased bone resorption is the prevailing disturbed calcium flux. In these patients, clodronate, given intravenously either as a single infusion or as repeated daily administrations, can normalize serum calcium, usually 3-5 days after the onset of therapy. In these good responders, long-term maintenance treatment should be individually adjusted since relapse appears to depend upon the type of tumor, the extent of malignancy and the administration of anticancer therapy. In a subset of well-rehydrated hypercalcemic patients in whom increased tubular calcium reabsorption represents the prevailing disturbed calcium flux, the acute effect of clodronate on plasma calcium is incomplete, despite the normalization of bone resorption. This type of therapeutic response can be experimentally reproduced in diphosphonate-treated animals receiving a constant infusion of parathyroid hormone-related peptide, a peptide isolated from lung, kidney and breast carcinomas. This indicates that, in addition to antiosteolytic drugs, such as clodronate, patients with hypercalcemia of malignancy would benefit from the development of agents that can selectively reduce the renal tubular reabsorption of calcium. In patients displaying a good response to clodronate, the fall in plasma calcium is accompanied by an increase in the calcium-regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3. This homeostatic reaction probably explains why hypocalcemia rarely occurs in clodronate-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Therapy of malignancy-associated hypercalcemia: 1983.

Hypercalcemia is common among patients with cancer and may be due to secretion by tumors of a humoral, calcemic, bone-resorbing factor or, alternatively, to skeletal metastases. In each case, hypercalcemia ultimately results from osteoclastic bone resorption. Therapy should be aimed at (1) reducing or eliminating tumor burden, (2) increasing renal calcium clearance, and (3) inhibiting osteoclastic bone resorption. Hydration with saline infusion and augmentation of calciuresis with furosemide should be the initial modes of therapy in most patients. Oral phosphorus should be used in hypophosphatemic patients. Glucocorticoids, calcitonin, and prostaglandin synthetase inhibitors may be effective in reducing bone resorption in selected patients. Mithramycin reliably induces a fall in serum calcium but long-term use is usually complicated by toxicity. A new class of drugs that inhibit osteoclastic bone resorption, the diphosphonates, is being employed in clinical trials in patients with malignancy-associated hypercalcemia. Results have been particularly promising with dichloromethylene diphosphonate.

Administration, Oral↗
PubMed2003

Gelatin sheet incorporating basic fibroblast growth factor enhances sternal healing after harvesting bilateral internal thoracic arteries.

OBJECTIVE: We previously reported that a gelatin sheet incorporating basic fibroblast growth factor accelerated sternal healing after bilateral internal thoracic artery removal in normal and diabetic rats. The aim of this study was to evaluate the effects of this therapeutic modality on sternal healing in a large-animal model before performing a clinical trial. METHODS: After median sternotomy and bilateral internal thoracic artery removal in a pedicled fashion, 14 beagle dogs received either a gelatin sheet incorporating basic fibroblast growth factor (100 mug per sheet) on the posterior table of the sternum (FGF group, n = 7) or did not receive a gelatin sheet (control, n = 7). We compared sternal healing 4 weeks after surgical intervention between the groups. RESULTS: Scintigraphic images obtained by using technetium 99 methylene diphosphonate bone scanning were assessed visually, and the impulse rate was quantified 30 and 60 minutes after injection of technetium 99 methylene diphosphonate to evaluate the sternal perfusion. Sternal uptake was significantly increased in the FGF group (30 minutes: 221% +/- 30% vs 180% +/- 36%; 60 minutes: 267% +/- 26% vs 197% +/- 42%; P <.01). Apparent sternal dehiscence, as assessed radiographically, was observed only in the control animals. Histologically, complete healing of the sternum with marked angiogenesis was observed in the FGF group, whereas poor healing with limited angiogenesis was seen in the control animals. Both bone mineral content (134 +/- 49 vs 52 +/- 32 mg, P <.01) and bone mineral density (133 +/- 53 vs 66 +/- 32 mg/mm(2), P <.05) along the incision line of the sternum, as assessed by means of dual-energy x-ray absorptometry, were higher in the FGF group. CONCLUSIONS: A gelatin sheet incorporating basic fibroblast growth factor enhances sternal perfusion and accelerates sternal bone healing in large animals.23

Animals↗
PubMed1987

The effect of some urinary stone inhibitors on membrane interaction potentials of stone crystals.

The effect of stone growth inhibitors (citrate, pyrophosphate, ethane diphosphonate, methane diphosphonate, chondroitin sulfate A, chondroitin sulfate C, heparin and ribonucleic acid) on crystal-membrane interactions of whewellite, weddellite, apatite, brushite, struvite, uric acid, monosodium urate and quartz (control) stones was quantitated. As a model for the initial retention of microcrystals by kidney epithelial membranes, crystal-induced membranolysis of red blood cells served as a measure of crystal-membrane interactions. The inhibitors induced changes in hemolytic potential from approximately 320 per cent enhancement to 80 per cent inhibition. No inhibitor behaved the same way for all crystals studied. However, some crystals showed consistent trends in altered hemolytic potential in the presence of inhibitors. These crystals included weddellite and sodium urate, which were inhibited consistently, and apatite and quartz, which were enhanced consistently. Whewellite, uric acid, brushite and struvite exhibited mixed patterns in the altered hemolytic potentials owing to the inhibitors.

Calcium Oxalate↗
PubMed1999

Thermodynamic studies on anion binding to apotransferrin and to recombinant transferrin N-lobe half molecules.

Equilibrium constants for the binding of anions to apotransferrin, to the recombinant N-lobe half transferrin molecule (Tf/2N), and to a series of mutants of Tf/2N have been determined by difference UV titrations of samples in 0.1 M Hepes buffer at pH 7.4 and 25 degrees C. The anions included in this study are phosphate, sulfate, bicarbonate, pyrophosphate, methylenediphosphonic acid, and ethylenediphosphonic acid. There are no significant differences between anion binding to Tf/2N and anion binding to the N-lobe of apotransferrin. The binding of simple anions like phosphate appears to be essentially equivalent for the two apotransferrin binding sites. The binding of pyrophosphate and the diphosphonates is inequivalent, and the studies on the recombinant Tf/2N show that the stronger binding is associated with the N-terminal site. Anion binding constants for phosphate, pyrophosphate, and the diphosphonates with the N-lobe mutants K206A, K296A, and R124A have been determined. Anion binding tends to be weakest for the K296A mutant, but the variation in log K values among the three mutants is surprisingly small. It appears that the side chains of K206, K296, and R124 all make comparable contributions to anion binding. There are significant variations in the intensities of the peaks in the difference UV spectra that are generated by the titrations of the mutant apoproteins with these anions. These differences appear to be related more to variations in the molar extinction coefficients of the anion-protein complexes rather than to differences in binding constants.

Anions↗