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 577 records · Page 32Linked to original sources
PubMed1977

The effects of ethylene-1-hydroxy-1, 1-diphosphonate on the developing mandibular condyle -- a light microscopic study.

The effects of high doses of ethylene-1-hydroxy-1, 1-diphosphonate (EHDP), a potential mineralization inhibitor, were studied in the developing mandibular condyle of the rat. The animals were given one injection of EHDP/day for four consecutive days. One group of animals received 30 mg and another group 50 mg EHDP/day. Animals from each group were killed either the day after or three days after the last EHDP-injection. EHDP-administration resulted in a failure of mineralization of the cartilage and osteoid, a widening of the hypertrophic zone, an appearance of cells in lacunae at the cartilage-methphyseal junction and in an inhibited capillary invasion. There was little evidence of a resumed mineralization in rats left to survive for three days after the last EHDP-injection. The results indicate additional effects of EHDP besides an inhibition of calcium phosphate crystallization, and also that EHDP may be a useful tool in the study of mechanisms of cellular hypertrophy and capillary invasion in mineralizing cartilage.

Animals↗
PubMedDate not supplied

Preparation and characteristics of dichloromethylene diphosphonate-containing liposomes.

Dichloromethylene diphosphonate (DMDP), encapsulated in liposomes and administered intravenously in mice, will eliminate all macrophages in spleen and liver. DMDP can be incorporated in liposomes to a maximum of 15 mM, if less than 12 mM is encapsulated not all macrophages will be eliminated (since the animals could not be injected with more liposomes). To determine DMDP content of the liposomes before in vivo administration, an in vitro test system was developed. This method is based on the competition for calcium binding by either DMDP or murexide. Murexide is a metallochromatic indicator which gives a distinct wavelength shift after binding of calcium. The decrease in absorbance at 510 nm of the murexide-calcium complex, due to the addition of DMDP, was used as a reliable (s.d. 5 per cent) value for measurement of DMDP concentrations. The possible use of this system in the study of calcium binding and transport over artificial biomembranes is discussed.

Alkaloids↗
PubMed1976

Whole-body autoradiography of 99Tcm-labelled ethylene-1-hydroxy-1, 1-diphosphonate (EHDP) in young rats.

The distribution of 99Tcm after intraperitoneal injection of 99Tcm-labelled ethylene-1-hydroxy-1, 1-diphosphonate (EHDP) in young albino rats was investigated by whole-body autoradiography. The distribution was characterized by a rapid and high uptake in bone and dentine, a rapid but moderate uptake in the urinary system and a slow and slight uptake in liver and spleen.

Alveolar Process↗
PubMed1987

Efficacy of aminohydroxypropylidene diphosphonate in the treatment of malignancy-associated hypercalcaemia.

Two patients with symptomatic malignancy-associated hypercalcaemia were treated with intravenously-administered aminohydroxypropylidene diphosphonate (APD). Both patients demonstrated dramatic falls in serum calcium concentration, and in urinary calcium and hydroxyproline excretion that were consistent with a reduction in the rate of bone resorption. Normocalcaemia occurred by day 5 and persisted for approximately three weeks after treatment. No significant side-effects were encountered. It was concluded that APD is a promising new agent in the management of hypercalcaemia that is associated with malignant disease and warrants further investigation.

Adenosine Diphosphate↗
PubMed1999

Increased renal retention of 99mTc-methylene diphosphonate after nephron-sparing surgery.

UNLABELLED: Nephron-sparing surgery has become established as an effective treatment for localized renal cell carcinoma when preservation of renal function is necessary. The surgery usually requires temporary renal artery occlusion and may induce ischemic renal damage. In this study, we retrospectively evaluated renal activity on bone scintigraphy after nephron-sparing surgery. METHODS: Eleven patients who underwent nephron-sparing surgery for renal cell carcinoma and had a normal contralateral kidney were studied. A total of 12 bone scintigraphy images with 99mTc-labeled methylene diphosphonate were obtained within 1 y after surgery in these patients to assess skeletal metastasis. Activity in the spared renal parenchyma was compared visually with that in the contralateral normal kidney. RESULTS: The tumor was successfully resected in every patient, and no clinically significant complications occurred. Activity in the spared renal parenchyma was elevated in six of seven examinations performed within 21 d after surgery. In three examinations, the increase in renal activity was heterogeneous, being relatively prominent near the surgical margin. Increased renal activity was not observed on five examinations performed 3 mo or more after surgery. CONCLUSION: Renal retention of bone-seeking agents is elevated in the early period after nephron-sparing surgery, probably as a result of ischemic insult during the surgical procedure. Bone scintigraphy may aid in evaluating the presence and degree of ischemic damage of the spared renal parenchyma.

Adult↗
PubMed1999

Rhenium-186-labeled hydroxyethylidene diphosphonate dosimetry and dosing guidelines for the palliation of skeletal metastases from androgen-independent prostate cancer.

Rhenium-186 (tin)-labeled hydroxyethylidene diphosphonate (186Re-labeled HEDP) was evaluated in 27 men with progressive androgen-independent prostate cancer and bone metastases. Administered activities ranged from 1251 to 4336 MBq (33.8-117.2 mCi). The primary objectives were to assess tumor targeting, normal organ dosimetry, and safety. Antitumor effects were assessed by posttherapy changes in prostate-specific antigen and, when present, palliation of pain. Whole-body kinetics, blood and kidney clearance, skeletal dose, marrow dose, and urinary excretion of the isotope were assessed. Targeting of skeletal disease was observed over the period of quantification (4-168 h). Radiation doses to whole body, bladder, and kidney were well tolerated. The dose-limiting toxicity was myelosuppression (grade III) at 4107 MBq (111 mCi) and grade II at 296 MBq (80 mCi). Probe clearance (whole body) and urinary excretion measurements were highly correlated. Of the six patients treated at the highest dosage schedules (three at 1510 MBq/m2 and three at 1665 MBq/m2), three showed a posttherapy decline in prostate-specific antigen of 50% or more. The declines were not sustained. The determination of total activity retained at 24 h, as well as an estimate of marrow dose, correlated with the amount of myelosuppression observed. These results suggest that a single 24-h measurement of retained activity would allow individualized dosing and an improved therapeutic index relative to fixed dosing schema. Repetitive dosing is required to increase palliation.

Androgens↗
PubMed2000

Short- and long-term effects of 186Re-1,1-hydroxyethylidene diphosphonate in the treatment of painful bone metastases.

UNLABELLED: This study evaluates the short- and long-term therapeutic efficacy of 186Re-1,1-hydroxyethylidene diphosphonate (HEDP) in the palliation of painful bone metastases and the influence of variables before therapy in determining the characteristics of pain palliation. METHODS: Sixty patients with painful bone metastases from different tumor types were treated with 1406 MBq 186Re-HEDP. After treatment, the patients were followed up clinically at weekly intervals for the first month and monthly thereafter up to 1 y, until death or pain relapse. Pain response was graded as complete, partial, minimal, or absent using the Wisconsin test scoring system. Duration of pain relief, performance status, tumor markers, serum alkaline phosphatase levels, hematologic toxicity, and metastatic bone progression were also evaluated. RESULTS: Overall, 80% of individuals experienced prompt relief of pain, with 31% complete, 34% partial, and 15% minimal responses. Transient World Health Organization grade 1-2 hematologic toxicity was apparent, with a decrease in the mean platelet (32%) and mean leukocyte (18%) counts at 3 and 4 wk, respectively. The degree of pain response did not correlate with any pretreatment variable. The duration of pain relief ranged from 3 wk to 12 mo and correlated positively with the degree of response (P = 0.02) and negatively with pretreatment scintigraphic scores and alkaline phosphatase levels (P = 0.02). CONCLUSION: 186Re-HEDP is effective for fast palliation of painful bone metastases from various tumors. The effect tends to last longer if patients are treated early in the course of their disease.

Aged↗
PubMed2000

Different patterns of global and regional skeletal uptake of 99mTc-methylene diphosphonate with age: relevance to the pathogenesis of bone loss.

UNLABELLED: Bone turnover changes with age have been shown by both histomorphometric and scintimetric methods; fewer studies have been performed on the regional differences of bone remodeling in the aging skeleton. To noninvasively investigate this issue, we evaluated the age-related patterns of global and regional bone uptake of 99mTc-methylene diphosphonate (MDP) in a large sample of healthy women. METHODS: In a group of 84 healthy women (33 pre- and 51 postmenopausal), the uptake of 99mTcMDP was semiquantitatively measured in 5 regions of interest. Total-body digital scans (TBDSs) were acquired at 5 min and at 4 h. Five regions of interest were drawn on the skeleton as a whole, on the lumbar spine, on the iliac wing, on the femoral neck, and on the femoral diaphysis of the 4-h TBDS. Regional skeletal uptake of the lumbar spine (LS-RSU), of the iliac wing (IL-RSU), of the femoral neck (FN-RSU), and of the femoral diaphysis (FD-RSU) was calculated as percentage injected dose retained in these skeletal segments at 4 h. RESULTS: As expected, in postmenopausal women the global skeletal uptake (GSU) values were higher than those in premenopausal women (40.7 +/- 5.9 percentage injected dose [%ID] versus 35.1 +/- 4.2 %ID; P < 0.0001). GSU correlated positively with age (r = 0.70; P < 0.001), but the addition of years since menopause to the regression model did not ameliorate the regression. On the other hand, LS-RSU (r = -0.55; P < 0.0001), IL-RSU (r = -0.45; P < 0.0001), and FN-RSU (r = -0.22; P < 0.005) decreased significantly, whereas FD-RSU increased significantly (r = 0.39; P < 0.001) with age; the same regressions were not influenced significantly by the addition of menopausal duration to the regression model. The strongest correlation among the different RSUs was that found between LS-RSU and IL-RSU (r = 0.63; P < 0.001). Moreover, the linear regression coefficients of the various RSUs with age were all significantly different from each other (P < 0.001). CONCLUSION: Our data show that the GSU of 99mTc-MDP increases with age, whereas different skeletal segments display a variable degree of turnover activation at different ages. This could ultimately induce the different rates of bone loss of different skeletal segments at various ages and, consequently, their variable propensity to fracture.

Adult↗
PubMed2000

Evaluation of toxicity and efficacy of 186Re-hydroxyethylidene diphosphonate in patients with painful bone metastases of prostate or breast cancer.

UNLABELLED: Twenty-eight patients (12 men with prostate cancer, 16 women with breast cancer) were included in a phase II trial to evaluate the efficacy of 186Re-hydroxyethylidene diphosphonate (HEDP) on pain from bone metastasis and the toxicity of this agent. METHODS: After intravenous administration of 1295 MBq 186Re-HEDP, the efficacy was evaluated by means of a daily log. RESULTS: We observed an objective response in 67% of prostate cancer patients and in 36% of breast cancer patients. The mean duration of response was 45 d for prostate cancer patients and 24 d for breast cancer patients. No major adverse effects were observed. Marrow toxicity did not exceed grade 2 for white blood cells and grade 3 for platelets using National Cancer Institute criteria. CONCLUSION: 186Re-HEDP provides safe symptomatic relief of pain in prostate cancer patients. The benefit of this treatment is less clear in breast cancer patients. Further studies should be conducted to evaluate treatment by 186Re-HEDP at an earlier stage of the disease.

Adenocarcinoma↗
PubMed1975

Technetium-99m-diphosphonate accumulation in amyloid.

A well-documented case of multiple myeloma complicated by histologically demonstrable amyloidosis is presented. Technetium-99m-diphosphonate in the areas of amyloid deposition about the shoulders and hips is shown. This adds another dimension to the extraosseous sites without demonstrable calcification where accumulation of bone-seeking radiopharmaceutical can be observed. In patients where symmetrical uptake of such agents is noted in the periarticular soft tissue, particularly of the hips and shoulders, amyloidosis must become a diagnostic consideration. This is particularly true in patients presenting with undiagnosed arthralgia.

Amyloidosis↗
PubMedDate not supplied

Complexometric determination of diphosphonic acid derivatives. Part II.

The purpose of the study is to develop complexometric method determination of diphosphonic acid derivatives in pharmaceutical preparations used in the treatment of osteoporosis, vis., disodium etidronate, disodium tiludronate, disodium pamidronate and sodium alendronate. The visual end-point titration method involving either as complexing reagent Th(DCTA) or Th(EDTA) in the presence of xylenol orange or methyl thymol blue, uses the ability of these compounds to form complexes.

Indicators and Reagents↗
PubMed2001

Idiopathic hepatic uptake of (99m)Tc methylene diphosphonate: a case report.

OBJECTIVE: Two sequential (99m)Tc methylene diphosphonate (MDP) scans were performed on a 42-y-old woman with insulin-dependent diabetes mellitus, chronic right pyelonephritis and anemia. The initial scan showed reduced skeletal uptake with intense and diffuse hepatic uptake. Because these findings were similar to those seen when excessive hydrolyzed-reduced (99m)Tc colloids are present in the radiopharmaceutical, the scan was repeated after an adequate time delay. Increased skeletal uptake was evident in the second scan, but the hepatic uptake persisted. Although there are numerous causes of soft tissue activity on (99m)Tc MDP bone scans, the responsible pathologic entity is not always clear. This study reviews several possible reasons for such uptake, although the exact mechanism in this case remains conjectural.

Adult↗
PubMed2001

Alendronate does not interfere with 99mTc-methylene diphosphonate bone scanning.

UNLABELLED: Several studies have found that administration of etidronate results in competitive interference with 99mTc-labeled bone scanning reagents. In contrast, in other studies this problem was not encountered with other bisphosphonates. METHODS: We prospectively studied 9 patients with hormone-refractory prostate cancer. 99mTc-methylene diphosphonate (MDP) bone scanning was performed before they received alendronate, and scanning was repeated a mean of 16.6 d afterward, when the patients had been receiving 40 mg alendronate daily for a mean of 6 d. In addition, 7 patients who underwent delayed scanning when they had been receiving alendronate for a mean of 111 d were also restudied. Quantitative whole-body bone scanning was performed, and radioactivity deposited in the bone metastasis was determined using region-of-interest analysis. RESULTS: A <6% increase in whole-body retention of 99mTc-MDP was seen on the initial postalendronate scan compared with the baseline scan. No significant differences in activity were seen in the bone lesion evaluated on the baseline and initial postalendronate studies. The delayed postalendronate scan generally showed similar or higher tracer accumulation compared with the baseline scan. CONCLUSION: Alendronate did not competitively inhibit uptake of 99mTc-MDP in the skeleton or tumor metastasis. Use of alendronate before bone scanning is unlikely to result in decreased detection of lesions or falsely decreased 99mTc-MDP activity at metastatic bone tumor sites.

Aged↗
PubMed1975

[Technetium polyphosphate and technetium diphosphonate. A comparative study].

99mTc-labelled phosphates are the bone seeking agents of choice. The comparison of 99mTc-polyphosphate (Poly-P) and 99mTc-ethane-1-hydroxy-1,1-diphosphonate (EHDP) shows a better in vitro stability of the latter during the first two hours after preparation. The blood clearance of EHDP is superior to Poly-P resulting in reduced background activity at scanning time. Renal excretion over a 4-hour period of urine sampling showed no significant differences between both substances. Blood activity is independent of diuresis.

Adult↗
PubMed2002

Quantitative studies of bone in postmenopausal women using (18)F-fluoride and (99m)Tc-methylene diphosphonate.

UNLABELLED: Quantitative radionuclide studies of bone using the short-lived tracers (18)F-fluoride and (99m)Tc-methylene diphosphonate (MDP) are an alternative method to biochemical markers of bone turnover for investigating the dynamic state of the skeleton. In this study we evaluated their use to quantify bone turnover in women receiving antiresorptive therapy compared with that of untreated control subjects. METHODS: The patients were 69 healthy postmenopausal women. Twenty-six women were receiving hormone replacement therapy (HRT) and 43 were untreated age-matched control subjects. After bolus injection of (18)F-fluoride (1 MBq), (99m)Tc-MDP (1 MBq), (51)Cr-ethylenediaminetetraacetic acid (3 MBq), and (125)I-labeled human serum albumin (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h. The clearance to bone mineral K(bone) was first evaluated using the area under the plasma concentration curve (AUC) on the assumption that the rate constant k(4) for the outflow of tracer from bone was negligibly small. AUC values of K(bone) were then compared with those found using a compartmental model method that allowed k(4) to be fitted as a free parameter. RESULTS: Using the AUC method the mean plus minus SD for K(bone) for the 2 tracers were: (18)F-fluoride, 61.8 plus minus 12.0 mL center dot min(-1) (HRT group) versus 67.2 plus minus 12.6 mL center dot min(-1) (control group) (P = 0.045); and (99m)Tc-MDP, 40.3 plus minus 8.2 mL center dot min(-1) (HRT group) versus 44.2 plus minus 7.6 mL center dot min(-1) (control group) (P = 0.024). Values for the 2 tracers in individual patients were moderately well correlated (r = 0.76; P < 0.001). Using the compartmental model method, k(4) for (18)F-fluoride was shown to lie in the range 0--0.0025 min(-1) with a best-fit value of 0.0018 min(-1). Values of K(bone) determined using k(4) = 0.0018 min(-1) were highly correlated with the AUC values (r = 0.989; SEE = 2.05 mL center dot min(-1)) with numeric values that were larger by a factor of 1.53. Analysis of the (99m)Tc-MDP data was more difficult because of uncertainties in protein binding in the extracellular fluid compartment space. The best fit for k(4) was in the range 0.0010--0.0014 min(-1) with values of K(bone) similar to those found using the AUC method. CONCLUSION: Values of K(bone) determined using the AUC method were able to differentiate between HRT-treated women and postmenopausal women who were not treated and were highly correlated with those determined using a compartmental model method with nonzero values of k(4).

Aged↗
PubMed2002

Diagnostic value of 99mTc-methylene diphosphonate and 99mTc-pentavalent DMSA compared with 99mTc-sestamibi for palpable breast lesions.

UNLABELLED: Different radiopharmaceuticals have been used to detect breast cancer. Among them, sestamibi has been extensively studied and has come to have a well-recognized role in the evaluation of palpable breast lesions. The goal of this study was to compare the diagnostic value of 99mTc-labeled compounds, such as methylene diphosphonate (MDP) and pentavalent dimercaptosuccinic acid (DMSA-V), with sestamibi for palpable breast lesions, in the scope of a multicenter trial sponsored by the International Atomic Energy Agency. METHODS: Patients from 7 countries were included: 47 women (mean age, 54 +/- 13 y) examined with MDP and sestamibi and 111 women (mean age, 55 +/- 12 y) examined with DMSA-V and sestamibi. Cancer was diagnosed in 41 of 49 lesions from the MDP group and in 78 of 113 lesions from the DMSA-V group. Axillary lymph node involvement was observed in 18 of 30 patients from the first group and in 27 of 53 patients from the second group. Prone scintimammography was performed using a dose of 740 MBq of each tracer, and diagnostic values were calculated from a masked interpretation of scans. RESULTS: In the first group, the sensitivity for sestamibi and MDP studies was 82.9% and 65.9%, respectively, with a specificity of 87.5% and 50%, respectively. In the second group, the sensitivity for sestamibi and DMSA-V studies was 87.2% and 65.4%, respectively, with a specificity of 77.1% and 74.3%, respectively. Regarding axillary involvement, the sensitivity was 33.3% for sestamibi in both groups, whereas the values for MDP and DMSA-V were 16.7% and 7.4%, respectively. In contrast, the specificity for sestamibi was 83.3% and 92.3% for the first and second groups, respectively, and the specificity for MDP and DMSA-V was 91.7% and 100%, respectively. CONCLUSION: Sestamibi is the most adequate alternative among the mentioned 99mTc-labeled radiopharmaceuticals for the evaluation of palpable breast lesions.

Axilla↗
PubMed2002

Prognostic significance of (18)F-FDG and (99m)Tc-methylene diphosphonate uptake in primary osteosarcoma.

UNLABELLED: The purpose of this retrospective analysis was to evaluate the prognostic significance of both initial glucose metabolism as measured by (18)F-FDG PET and osteoblastic activity as measured by (99m)Tc-methylene diphosphonate (MDP) bone scintigraphy in osteosarcoma. METHODS: In 29 patients (18 male, 11 female; age range, 5-41 y) with primary osteosarcoma, (18)F-FDG uptake and (99m)Tc-MDP uptake were measured semiquantitatively (average and maximum tumor-to-nontumor ratios [T/NT(av) and T/NT(max), respectively]) using PET and bone scintigraphy at the time of diagnosis. After chemotherapy, the patients underwent surgery for their primary tumor, and the response was determined histologically. Cumulative overall survival and event-free survival were determined by clinical and imaging follow-up of 7-72 mo (median, 28 mo). RESULTS: Clinical and imaging follow-up revealed that the disease relapsed or failed to achieve complete remission in 9 patients and that 6 patients died of the disease. Both overall and event-free survival were significantly better in patients with a low (18)F-FDG T/NT(max) (less than the median) than in patients with a high (18)F-FDG T/NT(max) (at least the median). The negative relationship of (18)F-FDG T/NT(av), (99m)Tc-MDP T/NT(max), and (99m)Tc-MDP T/NT(av) with overall and event-free survival did not reach a level of significance. (18)F-FDG uptake values correlated moderately and positively with (99m)Tc-MDP uptake values, but a level of significance was reached only between (18)F-FDG T/NT(max) and (99m)Tc-MDP T/NT(av). CONCLUSION: The initial glucose metabolism of primary osteosarcoma as measured by (18)F-FDG PET using T/NT(max) provides prognostic information. High (18)F-FDG uptake correlates with poor outcome. Thus, (18)F-FDG uptake may be complementary to other well-known factors in judging the prognosis in osteosarcoma.

Adolescent↗