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PubMed2003

[Patient compliance with drug therapy in temporal arteritis].

OBJECTIVE: To evaluate patient compliance with drug therapy in temporal arteritis and to determine the characteristics of compliant or non-compliant patients. METHODS: Inpatients and outpatients from an Internal Medicine Unit were interviewed. Compliance with drug dosage and administration time was assessed with a questionnaire for the following drugs: glucocorticoids, calcium, vitamin D, diphosphonates (prevention of glucocorticoid-induced osteoporosis). RESULTS: Forty-nine patients were interviewed (61% female, mean age = 73.7 years). Glucocorticoids were prescribed to 96% of the patients, calcium and vitamin D to 86% and diphosphonates to 49%. Compliance with drug therapy was 87%, 60%, 68% and 51%, respectively, for all treatments. It was independent from the disease duration. Male were more compliant than female (P = 0.012). CONCLUSION: Half of the patients with temporal arteritis are non-compliant with drug therapy. The questionnaire is simple. It can be used in everyday clinical practice to study and improve patient compliance.

Aged↗
PubMed1991

[Severe hypercalcemia after rhabdomyolysis and acute renal failure].

Two cases of rhabdomyolysis with renal failure followed by hypercalcaemia are reported. Both had major hyperphosphataemia and hypocalcaemia, requiring haemodialysis. Hypercalcaemia developed during the diuretic phase, when renal function was still abnormal, and before phosphate blood levels had returned to normal. Soft tissue calcifications occurred in one of the patients. The pathogenesis and treatment of this condition are discussed. Increased levels of serum calcitriol may play an important role in the genesis of hypercalcaemia, which may last for several months. Giving calcium salts and or vitamin D to these patients during the hypocalcaemic phase is dangerous, and should be avoided. The usual treatment for hypercalcaemia my remain ineffective. Mithramycin can lower the serum calcium concentration but the new diphosphonates (sodium etidronate) are very effective in the treatment of this hypercalcaemia. However, in serious or urgent cases, hypocalcaemic haemodialysis may be required, with the simultaneous administration of calcitonin and diphosphonates.

Acute Kidney Injury↗
PubMed1988

Paget's disease of bone.

Paget's disease is a common disorder of bone of presumed viral aetiology which, in a minority of patients, may cause severe symptoms. Both calcitonin and the diphosphonates have specific anti-pagetic effects. Newer diphosphonates, unlike etidronate, do not impair mineralization, and when they become available these will be the drugs of choice. Until that time, both calcitonin and etidronate continue to have a useful place in the management of this disorder.

Calcitonin↗
PubMedDate not supplied

Development of a conjugate of (99m)Tc-EC with aminomethylenediphosphonate in the search for a bone tracer with fast clearance from soft tissue.

For the currently used (99m)Tc-labeled diphosphonates such as (99m)Tc-MDP and (99m)Tc-HDP, the required interval of 2.5 to 3 h between injection and the scintigraphic bone imaging is an inconvenience. The present study was set up in an attempt to develop a technetium-99m-labeled diphosphonate with efficient bone uptake and more rapid clearance from blood and soft tissue by renal extraction and excretion so that it would be possible to start imaging as early as 1 h after injection. A conjugate of the new renal tracer agent (99m)Tc-ethylene dicysteine ((99m)Tc-L,L-EC), covalently bound via one of its carboxylates with aminomethylenediphosphonic acid (AMDP), was synthesized in seven steps. EC-AMDP could be labeled easily and efficiently with (99m)Tc at pH > or = 12 and room temperature. Analysis using ion pair reversed phase high performance liquid chromatography showed the formation of a mixture of two main compounds with reproducible relative ratios, which were stable as a function of time. In a baboon, the scintigraphic images obtained with the new agent showed good quality bone scans, with clear visualization of the skeleton and low soft tissue activity at respectively 1 and 2 h after injection.

Animals↗
PubMed1978

Stimulation of precipitation of calcium phosphate by matrix vesicles.

The ability of matrix vesicles isolated from the epiphysial growth plate of 6-week-old chicks to facilitate the precipitation of calcium phosphate was studied in vitro. The vesicles lowered the minimum concentration product [ca2+]X[p1] needed to induce crystal formation, thereby showing the vesicles are nucleators of crystallization. After freezing and thawing the vesicles at pH6.0, part but not all of this ability to nucleate disappeared. Freezing and thawing markedly decreased the Ca and Pi content of the vesicles, suggesting that part of the nucleating activity may have been due to mineral already present. After removal of the mineral the residual nucleating activity could be destroyed by extracting the vesicles with lipid solvents or by treatment with enzymes such as phosphoilipase C, neuraminidase or proteinase. Matrix vesicles obtained from chicks treated with 1-hydroxyethane-1, 1-diphosphonate, a compound that inhibits calcification in vivo, showed impaired nucleating activity, both before and after treatment at pH6.0. The vesicle preparation bound some diphosphonate in vitro, probably to the mineral present in the preparation, since no binding could be detected in vesicles preincubated at pH6.0. No difference was found in the nucleating activity of vesicles isolated from rachitic chicks which had or had not received cholacalciferol 48 h before death. These results suggest that matrix vesicles possess intrinsic nucleating activity that may be important in biological calcification.

Alkaline Phosphatase↗
PubMed1978

Doughnut phenomenon in bone scintigraphy.

A doughnut phenomenon was observed in bone scintigraphy in three cases of metastatic thyroid carcinoma to the skull. Additional dynamic and static studies were performed to evaluate the relative roles of vascularity, vessel permeability and new bone formation in producing this phenomenon. This was accomplished through the use of 99mTc-diphosphonate, 99mTc-labeled red blood cells and 99mTc-pertechnetate. The important factor was found to be a new bone formation. Late uptake of diphosphonate was shown only in the periphery of the lesion, where formation of new bone takes place. This occurred even in the presence of increased vascularity and vessel permeability in the lesion as a whole.

Adenocarcinoma↗
PubMed1982

A clinical comparison of MDP and DMAD.

Tc-99m labeled dimethyl-amino-diphosphonate (DMAD) was compared with methylene diphosphonate (MDP) in five healthy volunteers and 28 patients with a variety of bony afflictions. Although the normal bone uptake of DMAD is less than MDP, the lesion-to-normal bone ratio is significantly higher with DMAD. All 71 lesions detected with MDP were also seen with DMAD. However, 10 lesions were disclosed with DMAD that were not seen with MDP. These lesions tended to have low grade concentrations of the radiopharmaceutical and were detected with DMAD by virtue of the lower normal bone uptake rather than higher lesion uptake.

Adult↗
PubMedDate not supplied

Experimental drug-induced changes in renal function and biodistribution of 99mTc-MDP.

Increased renal uptake of 99mTc methylene diphosphonate (MDP) was observed irregularly in rats after methotrexate, vincristine or gentamicin, administered separately. Cisplatin regularly induced a dose-related increased MDP uptake which correlated with the degree of tubular damage histologically. The augmented MDP renal uptake was not consistently accompanied by a decreased clearance of simultaneously injected I-131 Hippuran, particularly at lower drug dose levels. This observation agreed with previous evidence that the mechanisms of tubular transport of diphosphonates and organic acids like Hippuran are different. At higher dose levels, the augmented MDP uptake was accompanied by increased renal calcium, hypophosphatemia, elevated serum urea nitrogen and creatinine, and only occasional, mild hypercalcemia. The magnitude of the increased renal uptake of MDP observed could not be explained by alterations in iron metabolism or by dehydration. Drug-induced renal retention of MDP by a factor of 2 or more above normal appears to be a useful indicator of tubular damage when other parameters of renal function are sometimes normal.

Animals↗
PubMed2004

Bone lesion detection with carrier-added 99mTc-EDTMP in comparison with 99mTc-DPD.

An increased uptake of bone-seeking radiopharmaceuticals into malignant bone lesions could further improve the diagnostic accuracy of routine bone scanning. The tracers used in clinical routine for bone scanning are methylene-diphosphonate (MDP), dicarboxypropane-diphosphonate (DPD) and ethylenediaminetetramethylene-phosphonate (EDTMP). MDP and DPD are usually labelled with 99mTc for diagnostic use, whereas EDTMP is labelled with 153Sm for therapeutic purposes. This study aimed to compare, for the first time, bone scanning with an improved preparation of 99mTc-EDTMP (by the addition of rhenium) (carrier-added) with 99mTc-DPD. Twenty malignant bone lesions were investigated in 10 patients. The ratios of bone lesion to soft tissue (BL/ST) and of bone lesion to normal bone (BL/NB) were compared 3 h after the injection of either compound. Quantitative analysis demonstrated a significant (P<0.05) difference in BL/ST ratio in favour of 99mTc-DPD. The BL/NB ratio was not significantly different. Visual image analysis resulted in a clinically comparable interpretation of imaging studies with the use of 99mTc-DPD and carrier-added 99mTc-EDTMP. These preliminary data support the concept of carrier addition to increase bone uptake by the modification of the complex structure of 99mTc-EDTMP. However, any advantage over conventional 99mTc-based tracers for bone scintigraphy in clinical use needs to be demonstrated in controlled trials.

Aged↗
PubMed1995

Amino acid phosphatase activity of alkaline phosphatase. A possible role of protein phosphatase.

Alkaline phosphatase (ALP) hydrolyzed phosvitin and amino acid phosphates demonstrating nonisotropy at different pH. Orthovanadate, a protein phosphatase inhibitor, more specifically inhibited the serine and tyrosine phosphatase activities of ALP than that of threonine phosphatase at concentrations > 0.1 mM or 0.01 mM, respectively. Calyculin A and okadaic acid at increased concentrations increased ALP amino acid phosphatase activity. Bisphosphonates, such as disodium-1-hydroxy-1-aminopropylidine-1,1-diphosphonate (APD) and ethane-1-hydroxy-1,1-diphosphonate (HEBP), at increased concentrations, inhibited ALP amino acid phosphatase activity. These results suggest that ALP may function as a protein phosphatase. In terms of protein kinase inhibitors, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide, N-(6-aminoheyxl)-5-chloro-1-naphthalenesulfomide hydrochloride and 4',5,7-trihydroxyisoflavone had little effect on ALP amino acid phosphatase activity. Staurosporine slightly enhanced ALP serine and threonine phosphatase activities at a concentration of 0.1 mM. These results suggest that protein phosphatase activity does not depend on the protein kinase activity of ALP, since duality between the former and the latter is not supported. ALP may function less as a protein kinase than as a protein phosphatase. The coupling mechanism of phosphate dynamics may be regulated indirectly.

Alkaline Phosphatase↗
PubMed1989

Anticalcification treatments of bioprosthetic heart valves: in vivo studies in sheep.

Studies performed by other investigators have shown that a number of preimplantation processes inhibit the calcification of pieces of porcine aortic valves and of bovine parietal pericardium subcutaneously implanted in rats. To evaluate biological reactivity with these biomaterials functioning in an intracardiac position, mitral and tricuspid valve replacements were performed in young sheep to assess the effects of the following preimplantation processes: (1) surfactants, including sodium dodecyl sulfate, polysorbate-80, Triton X-100 and N-lauryl sarcosine; (2) covalently bound aminohydroxypropane diphosphonic acid; (3) toluidine blue; and (4) incorporation of polyacrylamide into valvular tissues. Quantitative calcium analyses showed that only the surfactants substantially reduced calcification, and only in porcine aortic valvular bioprostheses. However, morphological studies showed that some of these agents also induced alterations that decreased the durability of the valves. Toluidine blue decreased calcification to a degree that was statistically significant, but not biologically important. Polyacrylamide incorporation and diphosphonate binding increased calcification. Thus, data regarding anticalcification treatments obtained from subcutaneous implantation studies in small animal models should be cautiously interpreted and validated by studies with intracardiac valvular implantation in large animals.

Acrylic Resins↗
PubMed1984

Frozen shoulder: an arthrographic and radionuclear scan assessment.

The diagnostic criteria and nomenclature used to describe the painful stiff shoulder remain confused. Arthrographic features of capsulitis have come to be accepted as characteristic of the frozen shoulder. Increased technetium uptake has also been noted. Both features have been considered to have possible prognostic and therapeutic importance. During a therapeutic study of strictly defined clinical frozen shoulder 35 of 38 patients showed increased technetium diphosphonate uptake in the affected shoulder in comparison with the opposite side. Of 36 patients who had arthrography 15 showed evidence of capsulitis, 11 rupture of the rotator cuff, and five no abnormality. Five tests failed owing to technical difficulty. There was no association between the technetium uptake and the arthrographic features, and neither was useful in predicting the rate or extent of recovery. Frozen shoulder of traumatic onset behaved no differently from that which arose spontaneously. We do not therefore consider that arthrography or technetium diphosphonate scanning performed at presentation contributes to the assessment of the painful stiff shoulder.

Adult↗
PubMedDate not supplied

99Tcm-MDP and 99Tcm-DPD in pathologic bone lesions. A visual and quantitative comparison.

The efficiency of 99Tcm-methylene diphosphonate (MDP) and 99Tcm-dicarboxypropane diphosphonate (DPD) to detect pathologically increased bone uptake was evaluated both by computed quantitative intra-individual and visual inter-individual comparison. Twelve patients with altogether 44 metastases in ribs and lumbar vertebrae were evaluated quantitatively. The lesion to normal bone ratio (mean +/- SD) was, with MDP, 2.9 +/- 1.6 and with DPD 2.4 +/- 1.2 (p less than 0.001), and the normal bone to soft tissue ratios with MDP 8.5 +/- 5.0 and with DPD 9.4 +/- 6.1 (NS). Visual analysis of 162 patients with 334 focal lesions showed no significant difference between two MDP preparations and one DPD preparation. Visual and quantitative comparison in the three most common malignancies studied (breast, prostatic, and lung carcinoma) gave the same result. Because the lesion to normal bone ratios were high with both agents, and there was no significant difference on visual analysis, both radiopharmaceuticals are considered to be relevant bone seeking agents and the difference between MDP and DPD is only academic and not of practical value.

Adult↗
PubMed1985

Paget's disease of bone. An update on management.

The essential requirement for effective treatment of Paget's disease of bone is that the characteristic abnormality of bone remodelling is predictably corrected without the occurrence of significant side effects. Although the ideal agent is not currently available, appropriate use of the calcitonins or diphosphonates goes a long way to achieving this goal. Calcitonin (50 to 100 MRC units subcutaneously daily or 3 times weekly) will generally reduce bone turnover by approximately 50% within 6 months. However, very active disease will not be controlled and bone turnover will generally increase once treatment is withdrawn. Calcitonin is without significant side effects, although some patients will develop antibody-mediated resistance to the exogenous calcitonin species. An advantage of calcitonin is that there is radiographic evidence of a return to normal bone remodeling during treatment. Although a number of diphosphonates (now more correctly termed bisphosphonates) are available for experimental use, only the first generation compound, disodium etidronate (EHDP) is commercially available. It too will reduce bone turnover by about 50% within 6 months when given in a dose of 5 mg/kg daily. Unlike calcitonin, it results in a more sustained control of bone turnover while having the additional advantage that it can be given by mouth. Although larger doses are more effective in controlling very active disease, there is a real risk of causing defective bone mineralisation which may result in the development of atraumatic long bone fractures or diffuse bone pains. Combinations of calcitonin and disodium etidronate in conventional dosage seem to result in an additive suppressant effect on bone turnover and may be indicated for more active disease. Advances in treatment are progressing rapidly and it seems likely that in the next few years the introduction of new agents for the control of Paget's disease will more nearly approach the ideal goal of treatment.

Bone and Bones↗
PubMed1988

Lymphoma of the skeleton: scintigraphic evaluation.

We retrospectively reviewed the 99mTc-diphosphonate scans of 980 patients with Hodgkin or non-Hodgkin lymphoma to define the typical appearance and distribution of skeletal lesions. The results were compared with the presence of skeletal symptoms and the findings on 67Ga-citrate scintigraphy, when available. Forty (4%) of the 980 patients had 77 scintigrams showing osseous involvement; there was an average of 3.5 lesions per study. Compared with patients with non-Hodgkin lymphoma, patients with Hodgkin disease had significantly fewer axial lesions (44% vs 82%, p less than .000001, two-tailed test) and more frequent involvement of the extremities. Subtle lesions were common. Of the lesions detected by scintigraphy, significantly more were detected by 99mTc-diphosphonate imaging (95%) than were detected by 67Ga-citrate (44%) (p less than .00001, two-tailed test), and most of these were far less apparent on the 67Ga-citrate study. Skeletal pain was an insensitive but specific indicator of skeletal disease. These results show that skeletal scintigraphy in patients with lymphoma typically reveals multiple subtle and asymptomatic lesions with frequent extremity involvement. Diffusely increased calvarial activity is commonly seen and often persists in proved remission. Increased juxtaarticular activity is specific for malignant skeletal involvement.

Adolescent↗
PubMed1986

99mTc-DPD uptake in juvenile arthritis. Scintimetry and autoradiography of the knee in dogs.

Unilateral arthritis of the knee was induced in mongrel puppies by intraarticular injections of 1% Carragheenan. Bone metabolism was studied by a scintimetric technique on static 99mTc-diphosphonate bone scans every 2nd week during the induction of arthritis for 3 months and monthly in a postarthritic phase of another 3 months. Changes in uptake of radionuclide were present after 2 weeks. The induction phase was characterized by a decreased uptake in the calcification layer of the juxta-articular growth plates and a moderately increased epiphyseal uptake. The postarthritic phase was characterized by normalization of growth plate uptake and a marked increase in epiphyseal uptake. Using contact autoradiography, the epiphyseal uptake was seen mainly in a narrow subchondral and subsynovial bone layer, around bone cysts and osteophytes, whereas central epiphyseal bone was osteopenic with decreased uptake of tracer. The study suggests that the early scintigraphic appearance of juvenile non-suppurative arthritis may be an overall decrease in uptake of 99mTc-diphosphonate due to a depression of growth plate metabolism.

Animals↗
PubMed2000

Radiosynovectomy in pigmented villonodular synovitis.

BACKGROUND: Pigmented villonodular synovitis (PVS) is a very rare disorder characterized by a slowly progressive benign proliferation of synovial tissue. As yet, the mainstay of its treatment has been surgical or athroscopic synovectomy. However, the relapse rates reported are relatively high, ranging between 8% and 46%. The aim of this study was to evaluate the efficacy of a combined treatment with radiosynovectomy (RS) and surgical synovectomy. METHOD: We studied the effect of thirteen radiosynovectomies performed in eleven pigmented villonodular synovitis patients with Y-90 citrate or Re-186 sulfide. All patients had undergone intraarticular radiation therapy within 6 months after surgical synovectomy. Eight patients suffered from pigmented villonodular synovitis in the knee, the remaining three from pigmented villonodular synovitis in the hip. Two of eleven patients had to be treated twice, due to a relapse of symptoms occurring four months after the first treatment. Therapy responses were evaluated one year after the initial radiosynovectomy. Clinical response was assessed on three-point rating scales evaluating the degree of hydrops, rubor, and motility as well as the degree of pain, these four parameters were then averaged to an overall clinical score (CS). We also quantified the relative uptake of Tc-99m-diphosphonate in the joint involved on the blood pool (BUR) and delayed images (DUR). RESULTS: Clinical score decreased from 5.45 +/- 1.04 to 1.18 +/- 1.16 at one year after treatment (p < 0.005), and the blood pool from 0.51 +/- 0.36 to 0.08 +/- 0.44 (p < 0.005). Delayed images were not significantly changed: 0.66 +/- 0.71 versus 0.66 +/- 0.73 (p = 0.3). CONCLUSION: A combination of surgical synovectomy with radiosynovectomy is highly efficacious in treating clinical symptoms of pigmented villonodular synovitis. It also improves bone scintigraphic signs of inflammation, but has no influence on late diphosphonate uptake.

Adult↗