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PubMed1984

[Dichloromethylene diphosphonate in the treatment of lytic bone metastases].

Dichloromethylene diphosphonate (Clodronate) has powerful activity against osteoclasts. We studied its effects on calcium balance in patients with malignant osteolytic lesions. Ten normocalcemic patients with advanced metastatic bone disease or myeloma were evaluated in a baseline 20-day calcium balance and kinetic study. They were then randomized to a clodronate or placebo regimen, treated intravenously for two weeks and orally for a month, and finally re-evaluated in another 20-day balance and kinetic study, conducted while they were still receiving treatment. The results show that both calcium balance and calcium absorption increased from base line in the clodronate group and that these changes were significantly different from those in the placebo group. There was a marginal decrease in bone resorption in the clodronate group and no change in bone accretion. Our results suggest that clodronate may be a useful adjuvant in managing metastatic bone disease.

Adult↗
PubMed1984

[Treatment of hypercalcemia in osteolytic metastases with oral amino-hydroxypropylidene-diphosphonate].

Twelve patients with malignant hypercalcemia were treated with amino-hydroxypropylidene-diphosphonate (APD), a potent inhibitor of osteoclast-mediated bone resorption. The mean serum calcium levels fell from 3,48 +/- 0,27 mmol/l before treatment to 2,66 +/- 0,31 after 10 days of oral APD (10 to 15 mg/kg/d) as the sole agent (p less than 0,001). The molar calcium/creatine ratio in the 24-h urine was significantly reduced from 2,11 +/- 0,73 to 0,70 +/- 0,52 after ten days of treatment (p less than 0,001). Serum phosphorus and urine hydroxyproline did not change significantly. Tolerance was good except for two patients with hiatal hernia who developed oesophagitis. Ours results confirm that oral APD is an effective and simple treatment of malignant hypercalcemia.

Administration, Oral↗
PubMed1984

Long-term effects of dichloromethylene diphosphonate in patients with osteolytic bone metastases and coincident primary hyperparathyroidism.

Dichloromethylene diphosphonate (Cl2MDP), an inhibitor of osteoclast-mediated bone resorption, lowers serum calcium in hypercalcemia associated with malignancies and with primary hyperparathyroidism. We have evaluated the effectiveness of Cl2MDP in three patients who had multiple osteolytic bone metastases due to breast cancer and coincident primary hyperparathyroidism and who refused neck exploration. Cl2MDP was added to the tamoxifen treatment and was given orally at a dose of 1600 mg/day for 12 months. All patients had a reduction in serum calcium level which was accompanied by a decline in the fasting urinary calcium and hydroxyproline excretion. Administration of Cl2MDP was not associated with any changes in parathyroid hormone levels. New bone metastases were observed neither during the treatment nor in the follow-up period. No side effects were observed.

Aged↗
PubMed1980

Comparison of Tc-99m pyrosphosphate and Tc-99m hydroxymethylene diphosphonate in acute myocardial infarction: concise communication.

A clinical comparison between a new bone seeking radiopharmaceutical, Tc-99m hydroxymethylene diphosphonate (TcHMDP) and the standard agent, Tc-99m pyrophosphate (TcPPi), was performed in 18 patients with acute myocardial infarction. Each patient was imaged initially with either TcHMDP or TcPPi, and imaged 24 hr later with the other tracer. All 18 patients had images positive for acute myocardial infarction with TcPPi, whereas 16 of 18 patients (89%) had positive studies with TcHMDP. The TcPPi images were graded significantly superior to those obtained with TcHMDP in 61% of the patients, and they were equal in 33%. In only one patient (6%) was TcHMDP better. The results indicate that compared with TcHMDP, TcPPi not only has a superior sensitivity for acute myocardial infarction but also has a significantly increased intensity of uptake in positive areas. TcPPi remains the agent of choice for myocardial infarct imaging.

Acute Disease↗
PubMed1982

Comparative evaluation of 99mTc-pertechnetate, 99mTc-diphosphonate, 99mTc-Solcocitran, 99mTc-iron-ascorbic acid and 67Ga-citrate as brain scanning agents.

The uptake of 99mTc-pertechnetate (TcO4), 99mTc-iron-ascorbic acid (Feasc), 99mTc-Solcocitran (Solcocitran), 99mTc-diphosphonate (HEDP) and 67Ga-citrate (Ga) in various brain lesions was compared. Influence of time from injection was also studied on the first three compounds. A rank correlation method was used to compare the scans which were judged visually by three independent observers. There was good agreement between the observers, as measured by Kendall's tau, but the concordance between rankings within the same type of lesion, as measured by Kendall's W, was rather poor. There was no significant difference in the uptake of TcO4, Feasc and Solcocitran. Ga showed generally poor uptake and its uptake in tumours and infarcts did not differ significantly. However, when HEDP and TcO4 were compared in two groups (I: Infarcts, haemorrhages and bone invading meningiomas, and II: Tumours not invaded into bone) a highly significant difference was obtained with much higher uptake of HEDP in Group I.

Adult↗
PubMed1981

Effect of dichloromethane diphosphonate on cortisol-induced bone loss in young adult rabbits.

Cortisol, 2.5 mg/kg, dichloromethane diphosphonate (Cl2MDP), 0.1, 1.0 and 4.0 mg/kg, and combinations of the two were administered daily for 42 days to young adult rabbits (3.9 kg) to determine if Cl2MDP could inhibit development of cortisol-induced osteopenia. A beginning and a terminal control group were included in the experiment. In the terminal controls compared with the beginning controls, the proximal tibia lost cortical and trabecular bone, the distal femur gained cortical bone and the lumbar vertebral body lost trabecular bone. The administration of Cl2MDP alone inhibited bone resorption at those sites where bone loss was occurring. Two cortical bone sites showed gains in bone. The 1.0 mg/kg dose was most effective. In rabbits administered cortisol, bone formation was inhibited; the number of osteoclasts was markedly increased, cortical bone was lost in all the bones examined, and there was no marked effect on trabecular bone. Cl2MDP administered with cortisol partially inhibited cortisol-induced bone loss. The concomitant administration of Cl2MDP did not alter the number of osteoclasts and osteoblasts. The 1.0 mg/kg dose was most effective. The results of this study clearly demonstrated the need to evaluate several bones and different sites within individual bones if erroneous conclusions are to be avoided when studying agents that affect bone metabolism.

Aging↗
PubMed1981

Inhibition by two diphosphonates of bone lysis in tumor-conditioned media.

In order to test the effect of diphosphonates in inhibiting bone lysis induced by human tumors, neonatal mouse calvaria are cultured in sterile conditions in different media. Osteolysis is estimated by the amount of 45Ca released from bone to medium, the mice being given injections of 45Ca on their day of birth. An increased bone lysis is observed when calvaria are incubated in the same medium conditioned from cultured tumor fragments. This effect is significantly decreased when the mice have been treated with either ethanehydroxydiphosphonate or dichloromethylenediphosphonate. These experiments represent a first step in estimating the potential effects of different drugs on malignant osteolysis.

Animals↗
PubMed1981

Pulmonary uptake of Tc-99m-Labeled methylene diphosphonate in a patient with a parathyroid adenoma.

Intense diffuse uptake of Tc-99m-labeled methylene diphosphonate was seen in both lungs of a patient submitted to surgery for a primary parathyroid adenoma. Five scans performed over the 3 yr following the operation showed persistence of lung uptake despite restoration of normal blood calcium concentration. Mild chronic renal failure caused by the hypercalcemia also persisted postoperatively. The present case confirms that pulmonary uptake of bone tracer can occur asymptomatically when both hypercalcemia and renal failure are present. Lung uptake of a bone tracer probably reflects tissue deposition of hydroxyapatite rather than of amorphous structures. Correction of the hypercalcemia failed to resolve the abnormal scan pictures.

Adenoma↗
PubMed1981

Detection of lung metastases from osteosarcoma by scintigraphy using 99mTc-methylene diphosphonate.

The results of 99mTc-methylene diphosphonate 99mTc-MDP scintigraphy in 37 osteosarcoma patients were evaluated. In 11 of 12 patients with pulmonary metastases these were demonstrated by the scintigram. In 2 of these 11 patients the lung metastases could be shown earlier by scintigraphy than by X-ray tomography. Uptake of 99mTc-MDP appeared to be correlated with the formation of osteoid by the tumor. 99mTc-MDP scintigraphy demonstrated metastases not only in the lungs and the skeleton, but also in the lymph nodes and soft tissues. 99mTc-MDP whole-body scintigraphy should be used routinely for the early detection of osteosarcoma metastases.

Adolescent↗
PubMed1984

Tc-99m diphosphonate and sulfur colloid uptake by the spleen in sickle disease: interrelationship and clinical correlates: concise communication.

To determine the clinical significance of splenic uptake in bone scintigraphy and functional asplenia on the radionuclide liver-spleen image, bone and spleen scintigrams of 38 patients with sickle cell disease were reviewed. Eighteen underwent bone and liver-spleen studies, 15 had only bone images, and five had only liver-spleen studies. Sixteen of 33 who had bone scintigraphy showed splenic uptake, but the frequency of homozygous sickle cell (SS) disease was not greater than heterozygous sickle cell disease (S-hetero) in this group. SS patients with splenic uptake of Tc-99m diphosphonate had significantly fewer painful crises of the abdomen and extremities, and fewer inpatient and outpatient hospital visits than SS patients whose bone imaging did not visualize the spleen. Functional asplenia on liver-spleen images (16 cases) was seen only in SS disease. One SS patient, age 8, still had a spleen capable of phagocytizing colloid.

Adolescent↗
PubMed1982

Age-related alterations in skeletal metabolism--24-hr whole-body retention of diphosphonate in 250 normal subjects: concise communication.

Twenty-four-hour measurements of whole-body retention (WBR) of Tc-99m diphosphonate (a sensitive measure of skeletal metabolism) have been obtained in 250 healthy volunteer subjects. WBR values were found to fall from the age of 20 yr until 35 yr and then in men to rise linearly thereafter. Women showed a similar pattern initially but there was a marked rise in WBR corresponding to the menopausal years. Our results lend support to the belief that skeletal metabolism increases with age. It is suggested that some imbalance must always exist between resorption and formation in bone, with net loss of bone mineral, and increasing levels of skeletal metabolism will exaggerate this imbalance and accelerate the rate of bone loss.

Adult↗
PubMed1978

[Protective effect of several diphosphonic compounds against damage to lymphocytes by antilymphocyte serum].

Rabbit antilymphocytic serum and complement were taken in quantities provoking the death of 50 per cent of human lymphocytes secreted in the phycol-verographin density gradient. Compounds (dinatrium salt of oxyethylendiphosphonate acid, alkylated oxyethylendiphosphonate acid, aminoethyloxyethylendiphosphonate acid, aminobenzyldiphosphonate, and aminoisopropyldiphosphonate acids) of 10 mM diphosphonic composition solutions in quantities of from 0.001 ml to 0.2 ml were added to experimental samples of 0.2 ml lymphocytes suspension containing 2.4 X 10(4)--6.0 X 10(4) cells. A decrease in the dead cell count in staining with a 0.1 per cent trypan blue solution was observed. Dinatrium salt of oxyethylendiphosphonate acid and alkylated oxyethylendiphosphonate acid proved to be most effective: it showed protective properties already in a dose of 0.01 ml. All the tested components had a pronounced protective action in a dose of 0.1 ml.

Antilymphocyte Serum↗
PubMed1982

[Histomorphometric study of nonpagetic bone in Paget patients. Results before and after diphosphonates].

An histomorphometric study with double tetracycline labelling was carried out on iliac biopsies taken from patients suffering from Paget's bone disease; 64 of the cases revealed non-pagetic bone in radiology, and 72 revealed a pagetic incidence. The purpose was to better compare non-pagetic bone with pagetic bone. 5 biopsies performed in a radiologically non-pagetic area were shown to be histologically pagetic. An histomorphometric profile of non-pagetic bone in a patient suffering from Paget's disease was established: increase in the reabsorption surfaces, of the periosteocytic uneven surfaces, of the volume and of the osteoid surfaces in the women; decrease in the osteoid thickness indicator and in the speed of normal calcification. These signs of hyperremodelling were, for the authors, connected with a hyperparathyroid condition which was secondary to calcium needs in the pagetic areas. The effects of diphosphonates on non-pagetic bone in the patients suffering from Paget's disease are clarified. This therapy has a beneficial action on the bone volume of non-pagetic bone, when the initial bony trabecular column is small.

Bone and Bones↗
PubMedDate not supplied

Whole body retention of diphosphonate in rheumatoid arthritis.

The skeletal metabolism of patients with rheumatoid arthritis (RA) osteoarthritis (OA) and ankylosing spondylitis (AS) has been assessed by 24-h whole body retention of 99mTc diphosphonate (WBR). Values for RA and AS patients were significantly elevated but those of OA patients were not when compared to age and sex matched controls (27.0 +/- 8.6 vs 20.5 +/- 1.8%; 24.8 +/- 5.4 vs 19.4 +/- 1.5% greater than and 21.4 +/- 4.1 vs 21.2 +/- 1.4%, respectively). The WBR of patients taking steroids was greatly elevated and RA inpatients had higher values than outpatients, but the increased WBR could not be correlated with disease activity. The increased WBR in RA may represent an indirect effect possibly related to immobility.

Aged↗
PubMed1981

[Duodenal absorption of calcium in rats treated with 25 OHD3, diphosphonates and synthetic anabolics].

In this study the authors developed new technics of study of duodenal absorption of calcium in rats: atomic absorption spectrophotometry, and dialysis to equilibrium. We considered that the main factors necessary for evaluation of duodenal absorption of calcium are the serum calcium, the calcium and alkaline phosphatase present in the duodenal cells and the calcium-binding proteins. The authors demonstrate that these factors are highest in rats treated with 25 OHD3 and norandrostenolone decanoate, than in control rats. In rats treated with diphosphonate, on the contrary, they obtained a reduction in the values of calcium and alkaline phosphatase contained in the duodenal cells.

Anabolic Agents↗
PubMed1981

Disappearance of soft tissue 99mTc diphosphonate activity following radiation therapy.

The appearance of soft tissue concentrations of technitium labeled phosphate compounds has been observed in a variety of pathological conditions. The mechanism and pathophysiology of this phenomenon remain unclear.Seven new patients diagnosed with lung cancer received (99m)Tc diphosphonate bone scans during the period of January 1975 to November 1975. Three of the seven subjects showed a significant accumulation of isotope in the region of the chest infiltrate at the time of diagnosis. Upon repeat technitium bone scans six months post radiation, two patients showed a sharp reduction in the soft tissue activity previously observed.The material is presented and a possible explanation of this phenomenon is offered.

Adenosine Triphosphate↗