SEARCH · Search PubMed
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.
Radionuclide imaging in a patient who had acute renal failure with severe loin pain and patchy renal vasoconstriction is described. The patient was studied 3h after the intravenous bolus injection of 25 mCi99mTc-methylene diphosphonate (99mTc-MDP). An intense patchy renal concentration of 99mTc-MDP was observed.
Patients on long-term haemodialysis suffer from dialysis arthropathy due to the deposition of dialysis amyloid. We investigated the use of 99Tc-labelled methylene diphosphonate bone scans in 17 patients as a possible in vivo diagnostic technique. In most clinically affected joints, with the exception of shoulders and hands, there was increased radioisotope uptake consistent with uptake by periarticular bone. In addition, we describe intense soft-tissue uptake around some clinically affected large joints. In contrast, control groups of patients on haemodialysis without arthropathy and patients without renal failure did not have increased uptake. A semi-quantitative scale of uptake was devised, and the following correlations were significant: pain perception and isotope uptake score in the ankles and feet, and the number of radiological lesions and isotope uptake scores in the wrists and knees. The following sites where the radioisotope might bind in the affected joints are proposed: amyloid deposits, areas of soft-tissue calcification, or areas of increased bone turnover. It is concluded that whereas the scanning technique cannot make a definite diagnosis of amyloid and, therefore, cannot be expected to supersede histological diagnosis, it is a useful adjuvant investigation, of particular importance in those patients unable or unwilling to undergo biopsy.
Thirty-eight normocalcemic patients with bone metastases from breast carcinoma were randomized to receive dichloromethylene diphosphonate (CL2MDP) in addition to their specific antitumor treatment (chemotherapy and/or hormone therapy), at a dose of 300 mg/day/i.v. or placebo for the first 7 dys. The CL2MDP treatment then continued at a dose of 100 mg day/i.m. for 3 weeks and finally at 100 mg i.m. on alternate days for at least another 2 months. In both groups of patients there was a reduction in the intensity of pain (Scott-Huskisson analog), but there was a more frequent reduction in the daily consumption of analgesics in patients treated with CL2MDP (p = 0.02). Unlike the controls, the patients who received CL2MDP presented a significant reduction in urinary calcium (p = 0.003) and in hydroxyproline (p = 0.05) on the 7th day. As regards the clinical evolution, negative events such as the appearance of hypercalcemia, pathological fractures, new bone lesions or a substantial increase in the preexisting ones, were observed in 9 of the 12 evaluable patients treated with placebo and in 3 out of 9 treated with CL2MDP. Thickening of the preexisting osteolytic lesions was reported in 2 patients treated with CL2MDP. Tolerance was excellent: only a few patients complained of pain at the intramuscular drug injection site.
In a prospective, controlled, and randomized clinical trial, we examined the effects of treatment with vitamin D (1,000 IU/d), calcium (1 g/d), and ethane-1-hydroxy-1,1-diphosphonate (EHDP; 7.5 mg/kg body weight) on vertebral bone mass in fourteen asthmatics undergoing long-term treatment with systemically applied corticosteroids. The extent of steroid-induced bone loss was judged by vertebral bone density of the lumbar spine measured by dual-photon absorptiometry as well as by vertebral crush fracture incidence examined by conventional X-ray. Results of the measurements before treatment and after six mo were compared with those of an untreated control group of nineteen asthmatics. Bone density increased during the observation period by 5% in the treated group, compared with a decrease of 4.3% in the untreated control group (p < 0.01). Moreover, in the treated group no radiologically visible new fractures occurred; in the control group new fractures were observed in four patients. There were no serious side effects of the applied drugs during the 6-mo period. Therefore, the combination of EHDP, calcium, and vitamin D appears to be a useful regimen for the management of steroid-induced bone loss in adult asthmatics.
21 paraplegic patients with recent traumatic spinal cord injury were orally administered 400 (n = 7) or 1,600 (n = 7) mg/d of disodium dichloromethylene diphosphonate (Cl2MDP) and compared with a placebo group (n = 7) to test the preventive effects of the drug on acute bone loss and osteoclastic resorption. Cl2MDP therapy was initiated at a mean of 17.6 d after the onset of paraplegia. The study lasted at least 6 mo, consisting of a 3.5-mo treatment period, and a variable follow-up period. The effects of Cl2MDP were assessed by blood and urine biochemistry, bone histomorphometry on transilial samples, photon absorptiometry of the tibia and fibula, and radiomorphometry of the femur. The elevation in serum and urinary calcium and in urine hydroxyproline observed in the placebo group did not appear under treatment. With both doses of Cl2MDP there was no further decrease in the bone mineral content. In the treated groups, a smaller percentage increase in osteoclastic population was also noted when compared with the placebo group, but this difference was not significant. There was no mineralization defect induced by Cl2MDP, as shown by tetracycline double labeling. It thus appears that at doses ranging between 400 and 1,600 mg, given as early as possible, Cl2MDP can prevent or reduce the development of the acute bone loss of paraplegic patients, without adverse side effects, though it does not prevent the development of heterotopic ossification.
A chelator, dichloromethane diphosphonate (Cl2MDP), used to treat for malignancy-induced hypercalcemia, has nephrotoxic potential. An acute animal model developed to examine the mechanism was used to further characterize the renal effects. NAG enzymuria appears to be an early premonitor of injury. Ultrastructurally, an increase in size and number of protein-containing phagolysosomal reabsorption droplets in proximal convoluted tubules associated with proteinuria precedes advent of tubular cell necrosis indicating these organelles to be a potential target site for Cl2MDP in the kidney. In vitro studies using rabbit cortical tubules and rat brush border membrane vesicle preparations suggest that the renal toxicity is not due to perturbation of phosphate transport or oxidative metabolism. An operational hypothesis emerges indicating that Cl2MDP may be protein bound affecting carrier protein charge facilitating glomerular leakage with tubular accumulation via protein transport. Cl2MDP may induce critical cation perturbation at the subcellular level as the mechanism of cell death.
Bone scintigraphy of the facial skeleton with 99Tcm-diphosphonate using gamma-camera was performed in 10 cases without, and in 4 cases with pathologic processes. A. p. and lateral projections were used and a converging collimator. The normal distribution of the isotope in the bones of the face seemed to be uniform with minor variations. Increased uptake varying in intensity was evident in the region of the lesion.
The effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDPTM) on bone mineral metabolism was tested in 4 healthy young men during 20 weeks of continuous bed rest. Two subjects received an oral dose of 5 mg/kg/day and the other 2 20 mg/kg/day. The low dose had two minor effects: the increase in bone accretion rate which usually occurs during bed rest was prevented, and there was an accentuation of the bed rest induced increase in hydroxyproline excretion. Skeletal mineral loss, assessed by calcium balance measurements and gamma ray absorptiometry of the calcaneus, occurred at the rate previously noted in untreated control subjects. Two types of drug effect were apparent at the higher dosage: one was immediate and sustained--a rise in serum phosphorus concentration and a fall in serum alkaline phosphatase activity. The other was delayed and progressive--a decline in urinary hydroxyproline excretion and in the rates of bone accretion and resorption. Skeletal mineral loss may have been affected; the usual negative mineral balance developed during the first half of the study, then disappeared during the last few weeks. However, gamma ray absorptiometry revealed no attenuation of the calcaneal mineral losses.
The use of disodium ethane-1 hydroxy-1, 1-diphosphonate (EHDP) therapy for Paget's disease of bone was examined in 75 affected patients. Forty-eight patients received randomly assigned oral doses of either 0, 2.5, 5, 10, or 20 mg/kg/day in a controlled, double-blind protocol, and the remainder received either 10 or 20 mg/kg/day in a non-random protocol. The clinical status of the patients and appropriate laboratory tests were evaluated before treatment and at frequent intervals during a six-month period of initial therapy. There were no significant changes in either urinary hydroxyproline or serum alkaline phosphatase in those patients receiving placebos, while both these parameters decreased significantly at all dose levels of EHDP, with the greatest decline noted in the highest dose group. However, statistical analysis of the data related to changes in symptoms in the double-blind study revealed that patients receiving the higher dose of EHDP (10 or 20 mg/kg/day) had less favorable outcomes than those receiving the lower doses (2.5 or 5 mg/kg/day). The high does group had a relatively lower rate of symptom improvement and a relatively greater rate of deterioration than did the low dose group. Twenty-one of forty-nine patients followed for at least 18 months have shown a sustained suppression of their serum alkaline phosphatase and urinary hydroxyproline values for 12 months following cessation of EHDP, while therapy has been reinstituted for the other 28 patients because of increases in these measurements, with or without accompanying symptomatic deterioration. Eight patients sustained fractures through Pagetic bone during the period of study and all of these were treated with higher doses of EHDP. On the basis of the biochemical and clinical data in this study it appears that initial therapy of Paget's disease of bone with 5 mg EHDP/kg/day maximizes benefits while minimizing possible adverse effects.
In rats with ischemic myopathy induced by aortic ligation and 5-hydroxytryptamine, there was good correlation of the skeletal muscle concentration of 99mTc-diphosphonate with the increase of plasma creatine phosphokinase and the decrease in muscle potassium. This radionuclide tracer method can be used to quantitate acute injury in individual muscles and provides a basis for clinical nuclear imaging in patients with a variety of disorders involving muscle fiber damage.
Local infection following total hip joint replacement is often difficult to diagnose. Bone scanning with 99Tcm-diphosphonate has been used in an attempt to detect such infection by assessing uptake of 99Tcm in the hip. Posterior view dot scans of patients with total hip joint replacements were analysed quantitatively to determine the ratios of dots in regions around the acetabular, trochanteric and femoral parts of the prosthesis compared with normal bone. The scans were also assessed visually. Patients with definite evidence of infection showed higher uptake than control patients. The clearest distinction in uptake between the two groups was in the femoral shaft region. The data from these two groups of patients were used to propose diagnostic criteria for detecting abnormalities on scans. These criteria were applied to scans of a third test group of patients who had painful hips, but no definite evidence of infection. The numerical method of analysis is less subjective and may therefore be preferable as a means of providing evidence for or against a diagnosis of infection in patients with painful hip replacements.
Technetium-99m hydroxymethylene diphosphonate scans were performed on 29 consecutive patients with acute ankle ligament injuries. Scanning reliably differentiated a severe from a minor injury. Severe injuries gave a diffuse uptake on the scan and the minor injuries a more localized increase in uptake.
Liposome-entrapped dichloromethylene diphosphonate (Cl2MDP) was injected locally into the thymus of adult rats. This treatment, which has been found to deplete resident macrophages in other organs, also reduced the number of thymic macrophages. The depletion was evident in the cortex and the corticomedullary zone at 5, 13 and 23 days after Cl2MDP treatment, while the decrease in medullary macrophages only became significant 13 and 23 days after injection. However, the maximal reduction of macrophages was evident 13 days after this treatment. Thirty-five days after Cl2MDP treatment, macrophages repopulated the thymus. Our results suggest that the cortical and cortico-medullary macrophages have a high phagocytic activity consistent with their predominant role as scavengers of the large numbers of thymocytes that die under physiological conditions. It is concluded that liposome-mediated depletion of thymic macrophages can serve as an experimental model to study the roles of these cells.
The results of combined scintigraphy in which indium-111-labeled leukocytes and technetium-99m methylene diphosphonate were used were compared with the results of cultures of open bone at 102 sites of delayed union or non-union, to determine the effectiveness of this combination as a preoperative indicator of osteomyelitis. There were twenty-five true-positive, fifty-nine true-negative, eleven false-positive, four false-negative, and three indeterminate interpretations, yielding, for the diagnosis of osteomyelitis, a sensitivity of 86 per cent, a specificity of 84 per cent, an accuracy of 82 per cent, a positive predictive value of 69 per cent, and a negative predictive value of 94 per cent. There were few false-negative scans; false-positive results were most likely at a metaphyseal site adjacent to a joint in which there was post-traumatic arthropathy, at the site of a failed arthrodesis, and at the site of an unstable delayed union or non-union.
We describe herein a case of parathyroid carcinoma accompanied with metastatic calcification identified by technetium-99m methylene diphosphonate (Tc-99m MDP) scintigraphy in the lungs, kidneys and stomach. Parathyroid carcinoma remains a rare disorder despite the increased prevalence of primary hyperparathyroidism. Metastatic calcification is noted infrequently even in primary hyperparathyroidism and it may cause respiratory failure. Tc-99m MDP scintigraphy three months after surgery showed a complete disappearance of Tc-99m uptake in the stomach and an obvious reduction in the kidneys but no significant change in the lungs, indicating metastatic calcification can be reversibly reabsorbed. This case indicates that the adequate excision of parathyroid carcinoma as well as the early detection of metastatic calcification by Tc-99m MDP are obligatory.
A technetium 99m diphosphonate scan is a sensitive detector of bony metastases of breast, prostate, and lung cancer. For these particular neoplasms, a negative bone scan in an asymptomatic patient is adequate evidence for absence of bony metastases and a correlative roentgenographic examination may not be necessary. Positive studies demonstrating multiple characteristic discrete areas of increased activity should be considered strong evidence for metastases. Single equivocal lesions require roentgenographic and occasionally biopsy correlation. If roentgenography fails to reveal the source of increased uptake, (e.g., degenerative disease) the scan lesion should remain suspicious for metastases.
Marked uptake of 99mTc-diphosphonate was noted in an extraadrenal neuroblastoma. Calcification was not demonstrable on radiographic or light microscopic examination, nor was crystalline material identified on electron microscopic examination; capillaries in the lesion appeared to be intact. Similar uptake of phosphate radiopharmaceuticals by a variety of lesions has been reported, and possible mechanisms for this phenomenon are discussed.
99mTc-methylene diphosphonate (99mTc-MDP) bone scans in 80 patients, 30-80 years old (average, 62 years old) with uterine cancer who received high doses of radiation (10-60 Gy; average, 46 Gy) were reviewed retrospectively to evaluate the frequency of pelvic insufficiency fractures caused by radiotherapy and to study the appearance of the fractures on bone scans. Bone scans in 29 of 80 patients showed abnormalities in the pelvis: insufficiency fractures were identified in 27 patients (34%) and osseous metastases were found in two patients (3%). The fractures and metastases were diagnosed by CT and were confirmed by observing the patients' clinical courses. Fractures were identified in 27 (39%) of 69 postmenopausal women and in none of 11 premenopausal patients (p greater than .05). Fractures were found in 21 (84%) of 25 patients who had pelvic pain and in six (11%) of 55 patients who were asymptomatic (p greater than .001). Scintigrams in patients with fractures showed more than one fracture in most patients (85%), and fractures were often symmetric (67%). Scintigrams in two patients with osseous metastases showed increased activity in an iliac wing that was outside the radiation field. Our results suggest that a marked increase in insufficiency fractures occurs after radiation therapy, especially in postmenopausal patients. A symmetric area of increased uptake of radionuclide is a characteristic scintigraphic appearance of an insufficiency fracture.