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 343 records · Page 19Linked to original sources

PubMed1989

Developmental disturbances of the rat molar induced by two diphosphonates.

Very few reports have been published about the effects of diphosphonates on the cells and tissues of developing teeth. The present study was designed to investigate possible morphological changes in ameloblasts and odontoblasts and relate these changes to defects in the enamel surface of erupted teeth. Young rats were injected subcutaneously with single or multiple doses of HEDP or Cl2MDP (10 mg P/kg b.w.). Light microscopic examination of developing maxillary first molars showed that single injections of HEDP or Cl2MDP induced subameloblastic cysts between the secretory ameloblasts and the developing enamel. The ameloblastic lining of the cysts contained numerous calcified deposits. A few days after injection, hypoplasias were seen in the enamel in areas previously occupied by cysts. In the erupted teeth, scanning electron microscopic examination revealed enamel hypoplasias which were mainly localized on the mesial sides of the cusps. In addition to the previously mentioned disturbances, multiple injections resulted in more extensive cysts, some of which contained non-mineralized enamel matrix. Inhibition of the mineralization of dentin and alveolar bone was also noticed.

Ameloblasts↗

PubMed1986

Treatment of malignancy-associated hypercalcemia with intravenous aminohydroxypropylidene diphosphonate.

Treatment of malignancy-associated hypercalcemia remains unsatisfactory. We have prospectively treated 26 consecutive hypercalcemic cancer patients with intravenous (IV) aminohydroxypropylidene diphosphonate (APD). The drug was administered daily as a 15-mg two-hour IV infusion until both serum and urinary calcium had been normalized for 48 hours. Twenty-four patients were fully evaluable (eight head and neck tumors, seven breast cancers, three epidermoid tumors of the lung, and six miscellaneous neoplasms). Whereas rehydration had only inconsistent effects, APD normalized serum calcium in all patients after a mean of three daily doses: serum calcium decreased from 13.3 +/- 0.4 mg/dL (mean +/- SEM) before APD to 8.0 +/- 0.1 mg/dL at the end of treatment. Ionized calcium declined in parallel to total calcium. APD was as effective in hypercalcemia due to bone metastases as in paraneoplastic hypercalcemia. The drug was tolerated without toxicity and had a prolonged effect: serum calcium remained normal during 3+ weeks (1 + to 8 +) in 17 patients who did not receive or did not respond to antitumoral treatment. APD normalized serum calcium by inhibiting bone resorption, as evidenced by the dramatic decrease in urinary excretion of calcium and hydroxyproline. Inhibition of bone resorption was probably also responsible for the decrease in serum phosphorus from 2.9 +/- 0.2 to 2.0 +/- 0.1 mg/dL. In summary, IV APD constitutes a major advance in the treatment of malignancy-associated hypercalcemia: it is very effective, well tolerated, and has a prolonged efficacy.

Adult↗

PubMed1981

Effect of growth hormone on metaphyseal uptake of 99mTc-methylene diphosphonate.

Eight children with short stature and GH deficiency were studied with 99mTc-methylene diphosphate before, during (occasionally), and after 4 months of GH therapy. Using digital images of the femoral shaft and distal metaphysis, the percent change in metaphysis-to-shaft, metaphysis-to-background (muscle), and metaphysis-to-injected dose ratios were calculated and compared to percent change in growth velocity over 4 months. The percent change in metaphysis-to-shaft and metaphysis-to-background ratios showed no significant correlation with percent change in growth velocity. The percent change in metaphysis-to-dose ratio demonstrated a significant correlation with change in growth velocity (r = 0.66; P less than 0.05). In addition, five of six patient studies before 4 months (after 1-68 days of GH therapy) demonstrated an increased metaphysis-to-dose ratio compared to baseline. In conclusion, GH therapy in GH-deficient children appears to increase the uptake of 9mmTc-methylene diphosphonate in the metaphysis, shaft, and muscle to a similar extent, and this increase appears to occur in most patients early after initiation of therapy.

Adolescent↗

PubMed1982

Secondary hyperparathyroidism associated with dichloromethane diphosphonate treatment of Paget's disease.

Six patients with extensive polyostotic Paget's disease were treated for 3 months with dichloromethane diphosphonate (CL2MDP; 1600 mg/day, orally). Serum alkaline phosphatase and urinary hydroxyproline excretion decreased 60-80% in each patient. Blood ionized calcium (ca++) and immunoreactive PTH (iPTH) were measured weekly during the first month of therapy and monthly thereafter. As an index of parathyroid function, PTH secretory reserve was assessed by EDTA infusions before treatment, at the end of treatment, and 3 months after Cl2 MDP therapy was stopped. Before therapy, iPTH and Ca++ were normal in all patients. During treatment, Ca++ decreased and iPTH increased in all patients; mean iPTH approximately doubled (95% confidence limits, 1.5- to 2.7-fold increase). At the end of 3 months of treatment, EDTA infusion raised iPTH in each patient to a level higher than that in the control infusion, indicating augmented PTH secretory reserve. Ca++, iPTH, and the iPTH response to EDTA-induced hypocalcemia returned toward baseline by 3 months after the end of CL2MDP treatment. The results indicate that secondary hyperparathyroidism developed as a result of Cl2MDP therapy. The cause of the parathyroid-gland adaptation is not known; the hyperparathyroidism is, however, at least partly reversible. Cl2MDP inhibits bone resorption while allowing bone mineralization to continue; this differential effect could lead to the hypocalcemia and parathyroid hyperfunction.

Aged↗

PubMed1977

A computer assisted comparison of 99Tcm-methylene-diphosphonate and 99Tcm-pyrophosphate bone imaging.

A total of 350 patient studies were carried out using clinical trials' batches of the Technetium (MDP) agent for bone scintigraphy (The Radiochemical Centre), and a commercially available Technetium pyrophosphate agent (CIS). The bone seeking properties of 99Tcm Sn-methylene-diphosphonate (MDP) and 99Tcm Sn-pyrophosphate (PYP) were evaluated by their comparative uptake in compact bone, cancellous bone and soft tissue using a region-of-interest technique. From these data uptake ratios were computed in order to correlate the values with (a) the amount of 99Tcm-MDP injected, (b) the time after injection and (c) the age of patients examined. All ratios derived with 99Tcm-MDP were superior to those using 99Tcm-PYP and were not dependent on the amount of 99Tcm-MDP injected. Uptake ratios determined for 99Tcm-MDP (1.5 h to 2.5 h after injection) were found to be higher than those for 99Tcm-PYP 2.5 to 3.5 h after injection. Soft tissue accumulation of 99Tcm-MDP, visible on scintiphotos, occurred only in 26% of cases but with 99Tcm-PYP, in 75% out of all cases studied. A decrease of cancellous bone/compact bone ratios with increasing age of the patients was found with both radiopharmaceuticals. This is most probably correlated with a diminished mass and/or surface of the cancellous bone in the elderly patient.

Adult↗

PubMed1980

Technetium 99m methylene diphosphonate scanning in Thompson hemiarthroplasties.

Fourteen patients who had had Thompson hemiarthroplasties at least ten months previously were scanned using 555 MBq (15mCi) 99Tcm methylene diphosphonate. No hips were infected, the control group of eight firmly fixed prostheses showed a weak diffuse uptake pattern whilst five of six patients with loose prostheses showed a characteristic focal distribution of increased uptake.

Aged↗

PubMed1981

Effects of acute administration of ethane hydroxydiphosphonate (EHDP) on skeletal scintigraphy with technetium-99m methylene diphosphonic acid (Tc-MDP) in the rat.

A study has been performed in the rat to assess the effect of EHDP on the distribution of 99Tcm-labelled MDP used for skeletal imaging. Profound alterations in bone, kidney and blood levels were observed. These observations cast doubt on the value of bone scans for monitoring the therapeutic effect of diphosphonates.

Animals↗

PubMed1979

Autoradiography of technetium-labelled diphosphonate in rat bone.

The passage of technetium-labelled methylene diphosphonate (99mTc-MDP) across rat bone was examined by autoradiography. The autoradiographs showed that shortly after an injection of the bone-seeking agent there was activity outside the bone, within the bone marrow and also adjacent to the highly vascular epiphysial plate; the distribution of the isotope in the incubated bone appeared to be non-uniform, a high concentration being seen adjacent to the epiphysial plate and also on the surfaces of the bone. The evidence suggested that a two-fold mechanism resulted in the uneven distribution of 99mTc-MDP. The first factor probably represented the regional distribution of blood flow with a transcapillary movement of the tracer from the capillary bed to the extravascular space; the subsequent incorporation of the tracer into bone appeared to depend on the nature of the bone matrix.

Animals↗

PubMed1979

Inhibition of diphosphonate-blocked bone mineralization. Evidence that calcitonin promotes mineralization.

There is much experimental evidence which indicates that calcitonin in hibits bone mineral resorption, but there are few data available in support of the proposal that calcitonin may also promote mineralization. Ethane-1-hydroxy-1,1-diphosphonate (EHDP) administered to immature rats inhibited mineralization as evidenced by widened tibial epiphyseal plates and decreased bone ash to dry weight ratios. Concurrent dosing with salmon calcitonin (SCT) prevented or reversed the EHDP-blocked mineralization in a dose dependent manner. Administration of SCT during the period after EHDP treatment significantly improved mineralization of tibial epiphyseal plates as shown by plate width narrowing and increased uptake of radioactive calcium. These results suggest that SCT increased mineralization in EHDP-treated rats, and provide supportive evidence for the proposal that calcitonin may also promote mineralization, in addition to its well known ability to inhibit bone mineral resorption.

Age Factors↗

PubMed1982

Abdominal masses in children: multiorgan imaging with 99mTc methylene diphosphonate.

Technetium-99m methylene diphosphonate (99mTc MDP) imaging was performed in 29 consecutive children with abdominal masses. Dynamic images of the inferior vena cava were obtained by injecting the radiotracer in the feet. Serial renal images were obtained for the next 30 min. Routine bone imaging was performed at about 3 hr. The radionuclide studies of the inferior vena cava accurately diagnosed total obstruction and displacement to the left but not partial obstruction and displacement to the right. The abnormalities on early renal imaging included displacement (14), distortion (seven), obstruction (eight), and nonvisualization (one). All patients with Wilms tumor (eight) had either nonvisualized or distorted renal parenchyma. Patients with neuroblastoma (17) and other tumors (four) had displacement and obstruction. Soft-tissue accumulation of 99mTc MDP was noted in two Wilms tumors and 12 neuroblastomas.

Abdominal Neoplasms↗

PubMed1984

Measurements of whole body retention of diphosphonate and other indices of bone metabolism in 125 normals: dependency on age, sex and glomerular filtration.

Measurements of 24-h whole body retention of 99m-Tc-MDP (WBR) has been performed in 125 normal volunteers, together with determinations of serum alkaline phosphatase, urinary hydroxyproline excretion and creatinine clearance. WBR decreased slightly from the 3rd to the 4th decade, after which it increased gradually in the older age-groups. Serum alkaline phosphatase followed an identical pattern, while the urinary hydroxyproline excretion demonstrated a marked but temporary rise in the post-menopausal age-groups. Finally, the creatinine clearance decreased gradually in the older age groups. Analysis of variance demonstrated that WBR varied independently with serum alkaline phosphatase and creatinine clearance, while no relationship between WBR and the hydroxyproline excretion was found. It seems likely that the increasing retention of diphosphonate in elderly persons reflects rising osteoblastic activity as well as decreasing glomerular filtration.

Adult↗

PubMed1977

Distribution of 99Tcm-labelled phosphorus compounds, 45Ca and 85Sr in diphosphonate-treated rats.

A similar distribution of 99Tcm, 45Ca and 85Sr was obtained when injected in rats as 99Tcm-labelled pyrophosphate or ethylene-1-hydroxy-1,1-diphosphonate (EHDP), 45Ca-chloride and 85Sr-choloride respectively. The highest concentrations occurred in bone and teeth. In EHDP-treated rats, isotopes were accumulated at sites of ectopic calcifications in the lung, kidney and stomach wall as well as in mineralized tissues. These results indicate that 99Tcm, when administered as 99Tcm-labelled EHDP accumulates predominatly in the inorganic rather than organic tissue components.

Animals↗

PubMed1979

Myositis ossificans progressiva. Clinical and metabolical observations in a case treated with a diphosphonate (EHDP) and surgical removal of ectopic bone.

A 20-year-old woman with a severely crippling myositis ossificans progressiva was treated with a diphosphonate (EHDP), 10-20 mg/kg/day. While being treated with this drug, surgical removal of ectopic bone was performed. Although ectopic calcification recurred postoperatively, considerable functional improvement was achieved. At the highest dosage of EHDP, hypercalcaemia gradually appeared, but was reversible upon cessation of drug treatment. It is probably related to a direct effect of EHDP on the bone.

Adult↗

PubMed1989

Hemodynamic effects of knee-joint tamponade. 99mTc-diphosphonate scintimetry in growing dogs.

We studied the influence of joint effusion on juxtaarticular vascularity and bone metabolism of the immature knee in puppies by dynamic and static 99mTc-diphosphonate scintimetry. Unilateral joint tamponade of 10 KPa (75 mmHg), introduced by intraarticular dextran-70 infusion, resulted in quantitatively similar scintimetric changes in an angiographic Phase I (0-20 sec), a blood pool Phase II (20-256 sec), and a bone-uptake Phase III (2 h). The uptake was reduced by 20 percent in the distal femoral epiphysis, by 15 percent in the distal femoral growth plate in Phases II-III, and by 8 percent in the proximal tibial growth plate in Phase III. The main part of scintimetric changes during joint tamponade could be ascribed to altered epiphyseal and metaphyseal intraosseous hemodynamics.

Animals↗

PubMed1976

[Study on tumor affinity of technetium-99m-labeled radiopharmaceuticals. (2) 99mTc-Sn-diphosphonate (99mTc-EHDP), 99mTc-Sn-dimercaptosuccinic acid (99mTc-DMSA), and 99mTc-Sn-diethyl stilbestrol diphosphate (99mTc-DSDP)].

The authors have examined the tumor affinity of various 99mTc-labelled radiopharmaceuticals to Ehrlich's tumor for the purpose of delineating positively human malignant neoplasm. This paper includes biologic distributions of 99mTc-Sn-diphosphonate (99mTc-EHDP), 99mTc-Sn-dimercaptosuccinic acid (99mTc-DMSA) and 99mTc-Sn-diethyl stilbestrol diphosphate (99mTc-DSDP, 99mTc-Honvan) as the second report on the tumor affinity to the Ehrlich-bearing mice. (a) Tumor concentration of 99mTc-EHDP was lowest and the positive delineation of implanted tumor with 99mTc-EHDP was poorest in sequential images, though the active accumulation to some soft tissue maglinant neoplasms, the breast cancer and the thyroid cancer, has been reported. (b) Tumor concentration and tumor to blood ratio of 99mTc-DMSA were not so high on the contrary of our expectation that 197Hg-DMSA may show the high tumor concentration and the high tumor to blood ratio like 197Hg chlormerodrin as same renal scanning radiopharmaceuticals. (c) Tumor concentration of 99mTc-DSDP was highest. Tumor to blood concentration ratio, however, was lower than that of the above mentioned radiopharmaceuticals but tumor to liver ratio and/or tumor to lung ratio was over 1.0 at the earlier time. Biologic distribution of 99mTc-DSDP was similar to that of 32P labeled DSDP and then it is presumed that 99mTc is labeled at phosphate ester of DSDP which is dephospholytated immediately by phospholylase in vivo following the intravenous injection. Therefore, it may be assumed that the accumulation mechanism of 99mTc-DSDP to Ehrlich's tumor is related to the phospholylase activity in neoplasms but is not known precisely.

Animals↗

PubMedDate not supplied

Technetium-99m methylene diphosphonate scintimammography for evaluation of palpable breast masses.

Technetium-99m-methylene diphosphonate (Tc-99m MDP) scintimammography (SMB) was used to investigate palpable breast masses during routine presurgical bone scintigraphy, for women at high risk for cancer and who were candidates for surgery or excisional biopsy. Upright anterior and prone lateral views of the breasts were acquired from 65 women with palpable breast masses, 5-10 min after intravenous injection of 740 MBq of Tc-99m MDP. Breast cancer was histologically diagnosed in 50 women (77%) and benign disease was found in 15 women (23%). Of these 50 breast cancer patients, 44 (88%) showed abnormal MDP uptake in breasts. Among the 15 cases of benign lesions, only 1 (7%) showed abnormal MDP uptake in the breasts. The diagnostic sensitivity, specificity, and accuracy were 88%, 93%, and 89%, respectively, for the differentiation of malignant and benign breast masses. Scintimammography with Tc-99m MDP is a useful and cost-effective tool for differentiating malignant breast masses from benign breast masses.

Adult↗

PubMed1981

Hypercalcemia of malignancy: treatment with intravenous dichloromethylene diphosphonate.

Twelve patients with hypercalcemia associated with various malignancies were treated with intravenous dichloromethylene diphosphonate (Cl2MDP), a potent inhibitor of osteoclastic bone resorption, in doses of 2.5 mg/kg of body weight initially and 5.0 mg/kg thereafter for up to 7 days. Mean serum calcium concentration fell from 13.8 +/- 0.6 mg/dL (SEM) before Cl2MDP to 9.8 +/- 0.7 mg/dL (SEM) (p less than 0.001) after 7 days. Urine calcium excretion fell from 775 +/- 95 mg/g creatinine (SEM) to 272 +/- 70 mg/g creatinine (SEM) (p less than 0.005), and urine hydroxyproline excretion fell from 144 +/- 28 mg/g creatinine (SEM) to 78 +/- 18 mg/g creatinine (SEM) (p less than 0.05) after treatment with Cl2MDP. The Cl2MDP was well tolerated, and adverse effects were limited to asymptomatic hypocalcemia in two patients. The ability of Cl2MDP to correct hypercalcemia and reduce urine calcium and hydroxyproline excretion in these patients is consistent with the hypothesis that increased bone resorption is primarily responsible for this complication of malignancy and suggests that Cl2MDP may be highly useful in managing this condition.

Adult↗

PubMed1981

Effects of dichloromethylene diphosphonate on serum and urinary calcium in primary hyperparathyroidism.

Dichloromethylene diphosphonate (Cl2MDP), an inhibitor of osteoclast function, was evaluated for its ability to lower the serum and urinary calcium in 14 patients with primary hyperparathyroidism. The study was double-blind, placebo-controlled, and cross-over in design. All patients received 12 weeks of Cl2MDP (1600 mg daily) and 12 weeks of placebo in a randomized sequence. The average serum calcium was lowered by Cl2MDP from 11.5 +/- 0.1 mg/dL to 10.8 +/- 0.2 mg/dL (p less than 0.001). In the 3-month follow-up after drug administration, the average serum calcium (11.0 +/- 0.2 mg/dL) remained significantly below pretreatment levels (p less than 0.01). The reduction in serum calcium was accompanied by a significant decline in the urinary hydroxyproline excretion from 37 +/- 3 to 28 +/- 2 mg/g creatinine (p less than 0.01) and by a 40% reduction in the average urinary calcium excretion from 185 +/- 29 to 113 +/- 23 mg/g creatinine (p less than 0.01). Administration of Cl2MDP was not associated with any significant changes in parathyroid hormone levels or in urinary cyclic adenosine monophosphate excretion. No side effects were observed. We conclude that Cl2MDP lowers the serum and urinary calcium in patients with primary hyperparathyroidism.

Adult↗