Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151825 (bone pain)
 3,118 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After describing the problems involved in the therapy of psoriatic osteoarthropathy, we discuss the specific accumulation of EHDP at the site of the disease. Because of its pharmacological properties, EHDP may have a regulatory effect on the pathological changes in psoriatic osteoarthropathy. In an open experiment using 20 patients with psoriatic osteoarthropathy, we evaluated the influence of EHDP on the extent and seriousness of bone and joint disease. We carefully studied the case history, laboratory tests, and rheumatological status; in some cases, bone scintigrams were also carried out. The patients received an oral dosage of about 20 mg/kg body weight the first 2 months and about 5 mg/kg from month 3-6. Two-thirds of the patients (n = 12) indicated a decrease in joint and bone pain, and there was also detectable improvement in the bone scintigrams. Only one patient noticed a side effect from the therapy. He complained of severe itching.
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PMID:[Therapy of psoriatic osteoarthropathy with EHDP]. 392 20

Fifty-four patients with Paget's bone disease have been treated with the bisphosphonate APD. Twenty-six patients had not previously received treatment for Paget's disease; and 28 had been treated before with EHDP alone or in combination with calcitonin. APD was given orally in a mean dose of 500 mg daily (congruent to 6.8 mg/kg of body weight) for 4 to 12 months. Bone pain diminished or disappeared in 34 of 39 patients with symptoms. A very significant diminution of the biochemical indices of bone turnover was observed in all patients, but the responses were faster in patients who had not previously received treatment for Paget's disease. After 4 months of treatment the serum levels of alkaline phosphatase of previously untreated patients diminished from 58.8 +/- 8.0 to 20.0 +/- 3.9 KA units (P less than 0.001) and urinary excretion of hydroxyproline diminished from 108.6 +/- 16.9 to 42.4 +/- 8.3 mg/24 h (P less than 0.001). In 23 of 26 previously untreated patients the biochemical indices decreased to the normal range (complete response). A reduction of 50% or more without reaching the normal range was observed in the other 3 patients (partial response). Actuarial analysis of the duration of the effect 12 months after stopping APD disclosed that 63% of patients who had achieved a complete response but only 23% of those with a partial response were in biochemical remission. A second course of APD was administered to 11 patients. The results were as effective during the second as the first course in 9 patients, whereas 2 patients had no response to retreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy of the bisphosphonate APD in the control of Paget's bone disease. 409 79

The presentation of Paget's disease varies from a painful or deforming skeletal affliction to an asymptomatic disorder diagnosed on routine biochemical or radiological assessment. When involvement of the peripheral skeleton by Paget's disease is extensive, the clinical diagnosis is usually clear. Affected bones are thickened and deformed and the overlying skin is warm. Bone pain is sometimes severe and malignant change rarely occurs. The new bone formed is structurally abnormal and is consequently liable to deformity and fractures. Serum alkaline phosphatase concentrations and urinary hydroxyproline excretion are raised. Characteristic X-ray changes are seen. Paget's disease should be treated when it causes skeletal pain and tenderness, or when there are neurological symptoms, fractures, marked deformities, or other complications. New therapeutic agents offer both symptomatic relief and some control of the basic disease process. Simple analgesics should be tried before proceeding to the anti-osteoclastic agents, calcitonin, diphosphonates and mithramycin. All are effective in relieving bone pain and improving biochemical indices. The major advantage of the diphosphonates lies in their oral usage and thus, the number of patients who nowadays require calcitonin is small. The majority of patients should be commenced on a course of diphosphonate therapy (EHDP in most instances), but if clinical response is unsatisfactory calcitonin should be tried. Mithramycin should be reserved for special indications e.g. an elderly patient with severe disabling pain.
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PMID:Therapeutic progress--review VII. The medical treatment of Paget's disease. 622 Oct 33

Rhenium-186 hydroxyethylidene diphosphonate (186Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using 186Re-HEDP. Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the 186Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq 186Re-HEDP showed grade 3 toxicity (thrombocytes 25-50 x 10(9)/l), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% +/- 10% IU/l; range: 11%-44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of 186Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of 186Re-HEDP has been initiated.
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PMID:Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer. 753 Jan 99

The bisphosphonates are analogs of naturally occurring pyrophosphate. They appear to block bone resorption much more than mineralization. A series of compounds has been investigated. These have antiresorptive potencies ranging from 1 to 10,000. So far, structure-function relationships have eluded definition. These drugs increase the bone density in women with postmenopausal osteoporosis by about 5%-10% over 1 year. The bone density then appears to plateau, but most studies are of short duration. Improved bone density does not necessarily result in stronger bone, but no studies have had adequate power to assess fracture incidence. Bone formation rates decrease as measured histomorphometrically. This occurs while the bone density is improving, which implies an inhibition of bone resorption that is probably due to direct toxicity to the osteoclasts. Etidronate blocks mineralization as well as resorption and can cause osteomalacia, which is not seen with low-dose cyclical etidronate or with the second-generation compounds. The long-term effects of interfering with the remodeling cycle are still not known. Subtle side effects may be those on the bone itself. These might go undetected, since bone pain or fractures usually are attributable to the underlying disease.
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PMID:Clinical effects of bisphosphonates in involutional osteoporosis. 812 31

Bone pain is a common symptom in disseminated malignancy and may be difficult to manage effectively. Radiation is of proven benefit for pain palliation and there is growing interest in the therapeutic potential of bone-seeking radiopharmaceuticals. Clinical data relating to the use of phosphorus-32, strontium-89, samarium-153 EDTMP, rhenium-186 HEDP and tin-117m DTPA are reviewed in the context of the pathophysiology of metastatic bone pain. Possible mechanisms of action of palliative radiotherapy and, in particular, the theoretical role of early response genes are discussed. The application of Monte Carlo simulation to targeted radiotherapy for bone metastases may provide the basis for a clearer understanding of the microdosimetry and radiobiology of bone pain palliation and for reliable prediction of clinical response and toxicity.
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PMID:Cancer therapy using bone-seeking isotopes. 891 78

Recent advances in radionuclide therapy offer a new approach for the management of metastatic bone pain. This paper reports the results of dosage escalation studies with 186Re-HEDP as a bone-seeking radiopharmaceutical in patients with bone metastases originating from breast or prostate cancer with regard to toxicity, pharmacokinetics and bone marrow dosimetry and the palliating effect on bone pain. Thrombocytopenia proved to be the dose limiting factor and 186Re-HEDP showed a considerable efficacy in end-stage patients with metastatic bone pain.
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PMID:Treatment of metastatic bone pain using the bone seeking radiopharmaceutical Re-186-HEDP. 917 33

A postal survey was conducted in the UK in 1996 to determine the facilities available and the level of activity at centres where radionuclide therapy was practised in 1995. A response rate of 79% indicated that 102 centres were providing radionuclide therapy, with 339 clinicians holding ARSAC certificates, 57% of whom were clinical oncologists. There were 84 beds available for therapy and the total number of patients treated was 11,435. Patient numbers treated by disease or procedure were: haematological, 569 (5%); benign thyroid disease, 9059 (79.2%); malignant thyroid disease, 911 (8%); bone pain palliation, 425 (3.5%); radiosynovectomy, 321 (2.8%); neuroendocrine tumour therapy, 76 (0.7%); and intra-cavitary, 56 (0.5%). The total amounts of activity of individual radiopharmaceuticals administered in GBq were: 131I, 16,695; 90Y-colloid, 88; 32P, 94.6; 131I-MIBG, 646; 89Sr, 57.6; and 186Rh-HEDP, 16. Average waiting times varied from 1 to 5 weeks, with a range of 0 to 52 weeks for some therapies. Most centres had the services of a physicist available. Compared with teaching hospitals, the 61 district hospitals had fewer allocated beds, but treated almost half of all patients. The numbers of therapies undertaken were increasing at many centres and this has implications for long-term planning.
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PMID:Radionuclide therapy in the United Kingdom in 1995. 1045 75

Rhenium-188 hydroxyethylidene diphosphonate (Re-188 HEDP) is a new radiopharmaceutical for treatment of metastatic bone pain. Re-188 is a generator-produced radionuclide emitting high energy beta and gamma rays and having a relative short physical half-life makes it of especially interesting for therapeutic purpose. Seven patients (pts) with multiple painful bone metastases were treated with Re-188 HEDP. Five pts with prostate cancer and 2 pts with breast cancer received a fixed activity of 3000 MBq of Re-188 HEDP intravenously in two steps. Complete blood counts were determined, blood chemistry examinations and urine-analysis were performed before and 1, 2, 3, 4, 6, 8, 12 weeks following the treatment. A visual analogue score, a verbal rating scale, the Spitzer index and the Karnofsky score were used to assess pain and performance status. Three hours after Re-188 HEDP administration at 1 m from the anterior mid-trunk of the pts gamma and at the patient body surface beta-radiation dose measurements were made, together with urine radioactivity measurements. Three pts become pain-free, 2 pts exhibited partial pain improvement and 1 patient gave no response to the Re-188 HEDP therapy. In 1 patient due to central nervous system metastasis the modification of the pain intensity could not be evaluated. Three pts displayed a flare reaction within 1 week after the treatment. Transient decreases in platelet and white blood cell counts were observed. There were no significant changes in the liver and renal functions. Radiation dose rate values of 6.3 +/- 1.0 microSv/h for gamma, and of 183 +/- 40 s-1 for beta-radiation were found. 25-32% of the administered dose was eliminated via the urinary tract in the first three hours. The preliminary data suggests that Re-188 HEDP is an effective radiopharmaceutical in treatment for metastatic bone pain. An administered activity of 3000 MBq can bring about a pain reduction without causing any clinically significant bone marrow toxicity.
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PMID:[Clinical experience with rhenium-188 HEDP therapy for metastatic bone pain]. 1084 24

In connection with our work on the development of 186Re-tetra-phosphonates with optimum properties for use in bone pain palliation, a novel cyclic tetraphosphonate derivative, has been synthesized, complexed with 186Re and evaluated with promising results. The ligand, which consists of a cyclic array of tetra-aminomethylphosphonate groups, was synthesized using orthophosphorus acid, 1,4,8,11-tetraazacyclotetradecane and formaldehyde. The labeling conditions with 186Re have been standardized under varying reaction conditions to give maximum yield. In a reaction volume of 1 mL, maximum complexation yield of 98% was observed at pH 2 using 0.1 mg Re (37-370 MBq) for a ligand concentration at 9 x 10(-2) M/L, under heating at 100 degrees C for 30 min with 2 mg of stannous chloride. The complex was found to be stable for 6 days with RC purity remaining approximately 97%. The complex was characterized by paper chromatography in saline and acetone, wherein the R(f) exhibited were 0.9 and 0, respectively. Biodistribution studies of the complex were performed in male Wistar rats. Activity in femur which was observed to be 1.8%/g (equivalent to about 23% of the injected activity in skeleton) at 3 h post injection remained almost constant up to 48 h. Minimum activity was observed in blood and other soft tissues. The complex showed major renal clearance. Scintigraphic images in rabbits after injecting 70-100 MBq of 186Re-CTMP and using a dual head gamma camera were observed to be superior to 186Re-HEDP, prepared by a procedure standardized by us. Insignificant activity was observed in other vital organs. The results suggest the suitability of the complex for further evaluation in higher animals for bone pain palliation.
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PMID:186Re-1,4,8,11-tetraaza cyclotetradecyl-1,4,8,11-tetramethylene phosphonic acid: a novel agent for possible use in metastatic bone-pain palliation. 1151 53


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