SEARCH · PubMed Health

Results for “Diphosphonates”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 181 records · Page 10Linked to original sources

PubMed1987

131I labeled diphosphonates for the palliative treatment of bone metastases--IV. Syntheses of benzylidenediphosphonates and their organ distribution in rats.

Palliative treatment of bone pain induced by disseminated bone metastases can be performed with osteotropic, beta(-)-emitting radionuclides. Newly developed 131I labeled benzylidenediphosphonic acid (BDP) derivatives show osteotropic characteristics which suggest that they might possibly be useful radiopharmaceuticals for that purpose. Six BDP derivatives were synthesized with H, OH or NH2 in the 4- and alpha-position. Syntheses were performed by the formal addition of 2 mol of phosphorous acid in the presence of PBr3 to 1 mol of the respective benzonitrile. Transformation of the 4-methoxy and 4-nitro substituents, which were stable during the diphosphonate formation, to 4-HO and 4-NH2 was achieved by hydrolytic ether cleavage in boiling HBr and catalytic hydrogenation with Pd/C, respectively. Transformation of the alpha-amino to alpha-hydroxy group was achieved by the action of NaNO2 in HCl. 4-Hydroxybenzylidenediphosphonic acid (9) was formed unexpectedly during the reaction of 4-hydroxybenzoic acid with H3PO3/PBr3. The addition of 2 mol of phosphorous acid to the benzoic acid was accompanied by an additional reduction at the alpha-carbon. The new BDP derivatives were analyzed by HPLC, NMR and elemental analysis. After labeling with 131I the BDP derivatives were tested in female Sprague-Dawley rats to obtain organ uptake and kinetic data. The various substituents showed an influence on the bone affinity and the uptake in other organs. Among the BDP derivatives tested alpha-amino-(3-[131I]iodo-4-hydroxybenzylidene)diphosphonate (4a) showed the best biological characteristics.

Animals↗

PubMed1991

Effects of amino-butylidene diphosphonate in hypercalcemia due to malignancy.

We studied the effect of a single 5 mg intravenous infusion of amino-butylidene diphosphonate (ABDP) in nine patients with hypercalcemia of malignancy, in whom serum calcium values were stable or rising after intravascular volume expansion. Serum calcium fell progressively in all patients and in seven reached the normal reference range by day 6 (p less than 0.001). The decrease in serum calcium was associated with a decrease in the fasting urinary calcium/creatinine ratio (p less than 0.05). Hypercalcemia recurred in seven of the patients by day 12, but two patients remained normocalcemic for 21 days. We conclude that ABDP is a highly potent diphosphonate and that a single intravenous infusion is capable of inhibiting tumour-mediated bone resorption for several days.

Adult↗

PubMed1978

Histological and histochemical investigations of the epiphyseal cartilage in rats after administration of heparin, coumarin as well as coumarin and diphosphonate (EHDP).

Heparin and coumarin (Marcumar) as well as coumarin combined with a diphosphonate (EHDP) were examined histologically and histochemically with regard to their effect on the structure of the epiphyseal cartilage in rats. Topo-optical reactions were used to assess the submicroscopic structural changes in the developing trabeculae of metaphysis. The zone of resting cartilage and the zone of young proliferation cartilage in epiphyseal plates revealed a reduced cell count due to the influence of anticoagulants. With regard to the matrix of the epiphyseal plate, it may be stated that its ultrastructure appeared partly regular and that, on the other hand, large areas of degeneration were detected in the connective-tissue. The negative effect of anticoagulants on the ground substance could not be reduced definitely by means of a diphosphonate (EHDP) in conjunction with Marcumar which was administered simultaneously.

Animals↗

PubMed1985

Dichloromethylene-diphosphonate in patients with prostatic carcinoma metastatic to the skeleton.

A total of 17 patients with multiple osteoblastic bone metastases owing to prostatic carcinoma was treated with 2-dichloromethylene-diphosphonate, a powerful inhibitor of bone resorption. The drug was given intravenously (300 mg.) for 2 weeks and then orally (3,200 mg.) or intramuscularly (100 mg.) for 4 to 11 weeks. A definite improvement in pain, assessed by daily consumption of analgesic drugs and by an analogic scale, was observed within 10 days in 16 of the 17 patients. Four patients confined to bed rest for pain were able to walk after 2 weeks and reversal of paralysis also was noted in 1 patient. Transient changes in serum calcium (decreasing) and alkaline phosphatase (increasing) were observed in most patients. In the 3 patients in whom it was performed, repeated bone scanning showed a partial regression of pathological areas in 2 and the complete disappearance of most pathological areas in 1. Our results suggest that 2-dichloromethylene-diphosphonate may represent an important supportive treatment in patients with bone metastases owing to prostatic carcinoma, providing sustained relief of pain and regression of bone destruction without undesirable side effects.

Adult↗

PubMed1980

Skeletal uptake of diphosphonate. Method for prediction of post-menopausal osteoporosis.

24-h whole-body retention (WBR) of diphosphonate (a sensitive indicator of skeletal metabolism) was measured in 37 oophorectomised women. 14 women had been prescribed oestrogen supplements and 3 of these had defaulted from therapy. For the study group there was a significant correlation between WBR and both the rate of bone loss as measured by photonabsorptiometry (r = 0.7, p ¿ 0.001) and urinary hydroxyproline (r = 0.53, p < 0.001). The oestrogen-treated group had significantly lower values for WBR and rate of bone loss than the untreated group (p < 0.01, p < 0.01 respectively) indicating suppressed skeletal metabolism. However, the highest values were found in those who had defaulted from oestrogen therapy suggesting a rebound period of accelerated skeletal metabolism and bone loss. There was a significant negative correlation between WBR and oestrogen dosage (r = 0.75, p < 0.02) suggesting that it may be possible to adjust the dosage for optimal skeletal metabolic activity. WBR of diphosphonate provides a simple and sensitive measure of skeletal metabolism which correlates well with conventional measurements of bone loss. WBR may be useful in the screening and identification of women who have increased bone turnover just after the menopause and who may subsequently be at risk of osteoporosis developing.

Aged↗

PubMed1995

Accumulation of technetium-99m methylene diphosphonate. Conditions affecting adsorption to hydroxyapatite.

Experiments were carried out to explore the mechanism of technetium-99m methylene diphosphonate (99mTc-MDP) adsorption with various calcium compounds including hydroxyapatite powder. 99mTc-MDP adsorption to hydroxyapatite was markedly inhibited by the addition of either pyrophosphate or methylene diphosphonate (MDP). Moreover, adsorbed 99mTc-MDP was partly removed by rinsing with pyrophosphate solution. Adsorption was pH-dependent and was inhibited by univalent cations, adenosine triphosphate solution, and guanosine triphosphate. Adsorption was most apparent to hydroxyapatite and calcium pyrophosphate and was less marked for the other calcium compounds tested. It is suggested that 99mTc-MDP adsorption is affected by the hydroxyapatite crystalline structure and environmental factors such as pH and the presence of phosphates, calcium compounds, and various cations.

Adsorption↗

PubMed1978

Increased concentration of 99mTc-methylene diphosphonate and 67Ga-citrate in extracranial bone metastases from pinealoma.

A rare case of extracranial bone metastases from pinealoma is reported. 99mTc-methylene diphosphonate and 67Ga-citrate scans were of great clinical value in confirming the presence of bone metastases. Bone lesions were positively delineated by both radionuclides, but the concentration of 67Ga-citrate was more extensive than that of 99mTc-methylene diphosphonate.

Bone Neoplasms↗

PubMed1986

Which diphosphonate for routine bone scintigraphy (MDP, HDP or DPD)?

Of 790 patients, 772 with proven cancerous disease have been studied without any selection using either MDP (three different kits), HDP (two types) or DPD. The groups were identical in age distribution, male/female ratio, body weight and verified percentage metastatic involvement. Technical conditions (Mo/Tc-generator used, dilution volume, total activity of the final product per vial, preparation/injection and injection/examination delays) were identical. Analogous scintigrams according to qualitative criteria (image quality, bone delineation, soft tissue fixation, metastatic/normal tissue contrast, aspecific uptake by non-target organs) and superior to MDP. Quantitative data were quite similar for all types of diphosphonates spine; metastatic/normal bone fixation ratio, bone/soft tissue ratio) have been evaluated. The results obtained showed that there was no criterion to demonstrate that HDP or DPD would be superior to MDP. Quantitative data were quite similar for all types of diphosphonates studied. Two out of the three MDPs were slightly superior to the other products with regard to detectability of metastatic lesions. Our results show, that in non-selected clinical routine work for bone scintigraphy HDP and DPD do not present any decisive qualitative or quantitative advantage in comparison to MDP.

Adolescent↗

PubMed1994

Benign myocardial uptake of hydroxymethylene diphosphonate.

During 'routine' bone scanning with diphosphonates, 10 elderly men were noted to show prominent myocardial uptake of Tc-hydroxymethylene diphosphonate (HDP) consistently, but no heart activity was seen with Tc-methylene disphosphonate (MDP). None had evidence of recent myocardial injury and the uptake persisted over a period of many months. In some, myocardial uptake defects were noted, analogous to 201Tl- and Tc-methoxyisobutyl isonitrile (MIBI) scans postinfarction. The condition appears to be essentially benign but its aetiology remains obscure. We have not been able to identify its cause; presumably atherosclerosis is one factor.

Aged↗

PubMed1983

The use of dichloromethylene diphosphonate for the management of hypercalcaemia in multiple myeloma.

We have assessed the effects of the diphosphonate, dichloromethylene diphosphonate (Cl2MDP), in 19 patients with hypercalcaemia and increased bone resorption due to myeloma. Cl2MDP (800-3200 mg daily by mouth or 300 mg daily by intravenous infusion) decreased plasma calcium and biochemical indices of increased bone resorption in 16 of 19 patients. This effect persisted for the duration of treatment (up to 14 weeks). Prolonged treatment was associated with a progressive rise in serum alkaline phosphatase and only a transient fall in hydroxyproline suggesting the stimulation of bone repair. Since myeloma is associated with significant morbidity and mortality due to progressive bone loss, these results suggest that long-term treatment of myeloma with Cl2MDP is worthy of further study.

Aged↗

PubMed1988

Treatment of hypercalcaemia in thyrotoxicosis with aminohydroxypropylidene diphosphonate.

Two patients had symptomatic hypercalcaemia accompanying thyrotoxicosis, despite initial treatment with volume repletion, beta blockade and antithyroid drugs. They were further managed with intravenous infusions of aminohydroxypropylidene diphosphonate resulting in rapid normalization of the serum calcium, with relief of symptoms. Aminohydroxypropylidene diphosphonate effectively suppressed the increased bone resorption of thyrotoxicosis without any undesirable adverse effects.

Adult↗

PubMed1980

99mTc-hydroxymethane diphosphonate: a new bone imaging agent with a low tin content.

A prospective double-blind comparison of 99mTc-hydroxymethane diphosphonate (HMDP) and 99mTc-methylene diphosphonate (MDP) as bone-seeking agents was performed with 102 patients. Densitometry showed that both cancellous/compact bone and cancellous bone/soft-tissue ratios were greater with HMDP (p less than 0.05); compact bone/soft-tissue and bone lesion/normal bone ratios were the same with both agents. Bone delineation, soft-tissue uptake, and overall image quality were the same with both agents. The HMDP formulation contained 78% fewer stannous ions and had a longer useful life after technetium labeling than MDP.

Adolescent↗

PubMed1985

Inhibition by diphosphonate compounds of calcification of porcine bioprosthetic heart valve cusps implanted subcutaneously in rats.

Calcification limits the long-term success of heart valve bioprostheses fabricated from glutaraldehyde cross-linked porcine aortic valves. The pathophysiology of calcification of bioprostheses has been studied experimentally with subcutaneous implants of the valve cusps in rats; in this preparation, the accumulation of calcific deposits is biochemically and morphologically identical to that occurring in clinical specimens. The objective of the present study was to determine whether mineralization of bioprosthetic valve cusps (BC) subcutaneously implanted in 3-week-old male rats could be inhibited through the use of diphosphonate compounds. Ethanehydroxydiphosphonate (EHDP), administered by daily subcutaneous injection (25 mg/kg/24 hr) for 21 days inhibited calcification (BC Ca++ = 154.9 +/- 4.1), but caused somatic growth retardation and disruption of epiphyseal development. However, local administration of EHDP by osmotic pump (5 mg/kg/24 hr) implanted in direct contact with the cuspal tissue for 14 days prevented BC calcification (BC CA++ = 4.3 +/- 0.7) without adverse effects. Furthermore, EHDP given by osmotic pump had a prolonged effect on reducing calcification, as demonstrated by implants harvested 21 days (BC CA++ = 12.2 +/- 6.4) after the drug supply was exhausted. Finally, BC preincubated in aminopropanehydroxydiphosphonate for 24 hr before 21 day implantation underwent less calcification (CA++ = 24.2 +/- 7.4) than control valves (BC CA++ 126.6 +/- 7.5) with no adverse effects. We conclude that diphosphonates inhibit BC calcification, and that adverse effects of systemic therapy can be avoided by local administration.

Animals↗

PubMed1979

Scintigraphic assessment of technetium 99m-diphosphonate uptake, vascularity and vessel permeability in human bone tumours.

Differences in the rate of uptake of 99Tcm-diphosphonate were found in 20 human bone tumours investigated. As some tumours have a slow rate of uptake it is suggested that the time used for routine scintigraphy at 3 hours is not always optimal and a further study should be performed in some cases. Various degrees of tumour vascularity and vessel permeability were found. The rate of diphosphonate uptake correlates with the vascularity, while it does not correlate with permeability which is generally increased as compared to normal bone.

Bone Neoplasms↗

PubMed1988

GFR-corrected 24-hour whole body retention of diphosphonate: an improved index of bone metabolism.

The 24-hour whole body retention of diphosphonate (WBR) depends on bone uptake and renal clearance of diphosphonate. To evaluate the influence of glomerular filtration we measured WBR, creatinine clearance (CrCl) and s-alkaline phosphatase (s-AP) in 91 normals and 79 patients with different calcium metabolic disorders. As presumed, a negative correlation between CrCl and WBR exists (r = -0.67, p less than 0.001). By defining CrCl = 100 ml/min as standard, we have introduced a new mathematical model which allows recalculation of the measured WBR to WBR at CrCl = 100 ml/min (WBR100): WBR100 = [(1-WBR) x 100/WBR x CrCl +1]-1 Whole body retention at a clearance of 100 ml/min is demonstrated to be independent of CrCl (r = 0.14, NS). Using this approach we estimate that deviations of CrCl below 70 ml/min and above 150 ml/min lead to more than 25% increase/decrease in WBR. Using s-alkaline phosphatase as a standard, it is shown that WBR overestimates bone formation when CrCl is low. This new model permits the interpretation of WBR measurements in terms of bone turnover in patients with low glomerular filtration rates.

Adult↗

PubMed1992

Role of technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis. A comparative study.

A comparative study of the parts played by technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis is presented. Nineteen patients were included in the study. All patients (11 men aged 19-70 years and eight women aged 18-72 years) had a history of back pain varying in duration from one to 15 weeks. A 99mTc diphosphonate bone scan was positive in 17 patients. The two patients with negative results had less than two weeks of back pain. The 67Ga citrate bone scan showed uptake in all patients.

Adult↗

PubMed1976

Accumulation of 99mTc-diphosphonate in four patients with hepatic neoplasm: case reports.

The accumulation of bone-seeking radiopharmaceuticals in extraosseous lesions has been reported in patients with myocardial infarctions, cerebral infarctions, and some soft-tissue tumors. While the precise mechanisms involved remain uncertain, the spectrum of abnormalities exhibiting such accumulation increases. In our laboratory, 99mTc-diphosphonate concentrated in four hepatic tumors (one cholangiocarcinoma and three metastases from colon carcinoma). This property of phosphate-related radiopharmaceuticals has not been reported previously. Awareness of the possibility of focal diphosphonate accumulation in the liver should help avoid confusion with right lower rib-cage metastasis or pleural effusion.

Adenocarcinoma↗

PubMed1987

Prevention of leaflet calcification of bioprosthetic heart valves with diphosphonate injection therapy. Experimental studies of optimal dosages and therapeutic durations.

Ethanehydroxydiphosphonate therapy was studied for prevention of calcification of bioprosthetic heart valve cusps (from glutaraldehyde-preserved porcine aortic valves) implanted subcutaneously in 3-week-old male rats. Animals received daily subcutaneous injections of the drug (1, 5, 10, 15, or 25 mg/kg/24 hr) for 21 days with maximal inhibition of bioprosthetic heart valve calcification at a dosage of 15 mg/kg/24 hr (calcium level of diphosphonate-treated bioprostheses 3.5 +/- 0.5 micrograms/ml; calcium level of control bioprostheses, 161.2 +/- 5.0 micrograms/mg), but with irreversibly diminished bone and somatic growth. A dosage optimum was observed at 10 mg/kg/24 hr with significant inhibition of bioprosthetic heart valve calcification (at 21 days, the calcium level was 16.4 +/- 3.6 micrograms/mg) and an absence of adverse effects on epiphyseal development and overall growth. Bioprosthetic heart valves retrieved from animal receiving ethanehydroxydiphosphonate (15 mg/kg/24 hr) for only the first week after implantation had significantly more calcification after 21 days than did bioprostheses from animals treated for 2 or 3 weeks. Bioprostheses explanted after 110 days from animals receiving the drug (15 mg/kg/24 hr) for the first 3 weeks had calcification equivalent to that of untreated control rats. Diphosphonate (15 mg/kg/24 hr) was most efficacious when initiated within 48 hours of bioprosthesis implantation, but was totally ineffective if administered after 1 week. It is concluded that ethanehydroxydiphosphonate optimally prevents bioprosthesis calcification without significant adverse effects on epiphyseal development and overall somatic growth at a dosage of 10 mg/kg/24 hr in rat subdermal implants, but it must be administered by continuous daily injections beginning within 48 hours of the implantation; this approach should be pursued in further long-term circulatory experimental studies because of its possible clinical relevance.

Animals↗