Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three patients with Paget's disease of bone were treated by disodium etidronate (EHDP) without interruption during periods of 18 to 30 months. In one case the daily dose was also unduly high (approximately equal to 18 mg/kg/day). A moderate to conspicuous diminution of the renal function was observed in all cases. The three patients developed skeletal pain in a gradual but progressively severe pattern. Seven nontraumatic fractures in nonpagetic bones were encountered. EHDP produces blockage of bone mineralization and excessive suppression of bone remodeling, therefore increasing the risks of fracture. EHDP affects not only pagetic bones but normal skeleton. A baseline evaluation of the renal function might help to identify those patients with greater risk to develop skeletal side effects during EHDP treatment.
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PMID:Spontaneous fractures of uninvolved bones in patients with Paget's disease during unduly prolonged treatment with disodium etidronate (EHDP). 308 70

Heterotopic bone formation after total hip arthroplasty is a common occurrence in patients with osteoarthritis, and severe amounts of ectopic bone may limit motion or cause pain. Diphosphonates have been suggested as a method of preventing ectopic bone formation, but no long-term clinical evaluation of their effectiveness has been published. Because patients with osteoarthritis appeared to respond well to diphosphonate therapy in an earlier study, we thought that they would be an appropriate group of patients to study. We evaluated the results of 177 patients with 200 total hip arthroplasties performed for primary osteoarthritis. Considerable postoperative heterotopic bone formation (classes III and IV according to the classification system of Brooker and associates) was found in 36 hips (18%). The incidence of heterotopic bone formation was found to be as high as in the patients who had received either a placebo or no drug therapy. The postoperative range of motion of the hips, as well as ratings for pain, walking, and function, did not differ significantly between the treated and untreated groups. Diphosphonates (EHDP) have been demonstrated to inhibit the growth of hydroxyapatite crystals in vitro by chemisorption onto the crystal surface and thus have been thought to have the potential of preventing pathological calcification in vivo. However, diphosphonates have no inhibitory effect on the formation of osteoid matrix, and the delay in mineralization of matrix is reversed when therapy is discontinued. Although this delay in mineralization was known at the onset of these clinical trials, we hoped that the ultimate amount of heterotopic bone would be less in the treated patients and that the range of motion would be improved as a result of delaying the process of mineralization. Unfortunately, the final range of motion in the diphosphonate-treated patients did not differ significantly from that in the untreated group, and the final amount of heterotopic ossification was not reduced. Therefore diphosphonate therapy must be considered ineffective.
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PMID:Prevention of heterotopic bone formation: clinical experience with diphosphonates. 310 7

The effects of therapy on the osteolytic bone lesions of Paget's disease have been assessed from serial bone radiographs. Changes in the rate of progression of lytic "wedge" lesions were measured and alterations in the texture of lytic "blade" lesions were graded on an empirical scale. Useful matching was possible using standard radiographs, although special care was needed to avoid artefacts from suboptimal positioning, magnification and variation in exposure. Serial radiographs were obtained of 57 lytic blade lesions in 54 patients receiving treatment with the bisphosphonate 1-hydroxyethylidene-1, 1-bisphosphonate (EHDP) and of 20 lesions in 20 patients treated with oral or intravenous 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (APD). Treatment with EHDP was associated with a significant deterioration in bone texture in 50% of lytic blade lesions, and with healing in only 20%. Deterioration was accompanied by an increase in local bone pain in 17% of these patients. In contrast, significant healing was observed in 17 of 20 lytic lesions (eight wedge, nine blade) within 6 months of beginning a course of intravenous or oral APD. In four of eight patients the progression of a lytic tibial wedge was arrested and in the remaining four the direction of wedge movement was reversed. In two patients the wedge had almost completely "filled in", making measurement difficult. Bone healing was usually accompanied by pain relief, reduction in skin temperature and rapid suppression of the urine hydroxyproline (uHP) into the normal range. However, in four patients who received intravenous APD, repair of lytic bone lesions was observed despite persisting elevation of uHP. These improvements with APD were sustained at 12 months, although in one patient whose biochemical indices were restored to normal the resorption front showed further progression, despite initial temporary reversal. The trends apparent in these short-term studies were also seen in four patients in whom wedge velocities were measured over periods of 6-10 years. These results confirm that after treatment of Paget's disease, bone healing or deterioration can be accurately assessed from serial standard radiographs. Reproducible matching is best achieved by ensuring that all radiographs are taken by the same radiographer. Minor alterations in radiological bone texture provide an important index of drug effect which is not always apparent from measurement of biochemical and other indices.
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PMID:Radiological assessment of Paget's disease of bone after treatment with the bisphosphonates EHDP and APD. 311 59

13 patients with polyosseous Paget's disease were treated for a mean period of 7 months with disodium etidronate (EHDP, ethylidene-1-hydroxy-1,1-diphosphonate); the average daily dosage was 5 mg/kg body weight. Subjectively, all patients reported a considerable improvement, in particular with regard to pain. Objectively, a significant decrease in plasma alkaline phosphatase activity and in urinary hydroxyproline excretion was observed. Bone scintigraphy showed a decreased activity of bone lesions after therapy, but no clear-cut regression was found radiologically. No serious side-effects were observed during treatment with EHDP and oral administration of the drug proved to be advantageous.
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PMID:[EHDP (ethylidene-1-hydroxy-1,1-diphosphonate) in the treatment of polyosseous Paget disease]. 392 24

This report presents clinical pictures of 11 patients with Paget's disease of bone treated at our clinic since 1977 and discusses the disease progress in seven patients who were given Elcatonin and EHDP and followed-up for a mean period of four years and eight months. All the patients responded to the drugs and the main clinical effect was disappearance of pain. They did not develop side effects which were especially a problem. Although both of the drugs exerted excellent effect on Paget's disease of bone, they have both strong and weak points with respect to administration route and side effects. These drugs should be selected with combined therapy, clinical effectiveness, side effects and other factors taken into account. Bone scintigram, serum alkaline phosphatase and urinary hydroxyproline were employed as therapeutic effect of these drugs. However, their handiness and reliability were unsatisfactory. More convenient parameters reflecting the disease activity more accurately are needed.
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PMID:[Treatment of Paget's disease of bone]. 393 94

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

Paget's disease of bone seems to be a slow virus infection of a single or several areas of the skeleton. Pagetic lesions are rather common among elderly people, but the disease does not manifest itself very often. Compared to the incidence of Paget's disease in England it seems to be rarer in this country. The pelvis is most frequently involved, followed by bones of the leg, skull, lumbar spine. The patients suffer from pain and deformities, arthroses of the adhering ankles, increased temperature of the area, nerve irritation and nerve damage due to increased bone growth (e.g. hearing loss due to Paget's disease of the skull). The development of sarcoma is rare and is only seen in severe cases. Diagnosis is made by X-ray, confirmed by bone biopsy, if necessary. Asymptomatic lesions are detected by bone scintigraphy. The activity of the disease is expressed by increased alkaline serum phosphatase and urinary hydroxyproline excretion. For treatment calcitonins and diphosphonates (especially EHDP, Diphos) are used. Both inhibit the overactive osteoclasts, and the increased bone turnover is normalized. The patients feel considerable relief; the elevated biochemical parameters fall to about 50% of initial values after calcitonin or EHDP monotherapy. In severe cases the combination of both substances may be profitable. The cytostatic drug mithramycin which can also be effective is only needed in exceptional cases.
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PMID:[Paget disease of the skeleton. Internal medicine aspects]. 623 41

Localised foot pain occurred in four patients with Paget's disease of bone or myositis ossificans who were treated with disodium etidronate (EHDP) in a dose of 10 to 20 mg/kg body weight/day for four to six months. There was localised tenderness and sometimes slight swelling at the painful areas. Bone x-rays were normal, but bone scans showed increased uptake of the isotope at these areas. The pain persisted for several weeks, causing considerable difficulty in walking. The symptoms were most likely due to diphosphonate-induced stress fractures. These cases emphasise the importance of administering EHDP in low dosage for short periods only.
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PMID:Diphosphonates and painful feet. 641 74

We determined that the concentration of radioactivity in a lesion of Paget disease correlates with the grade of radiological deformation and the frequency of pain; the total skeletal uptake correlates with the severity of the biochemical abnormalities. We suggest that the major determinant of uptake in untreated lesions is abnormal metabolic activity, and in lesions in remission it is structural deformation of mineralized tissue. It is likely that the metabolic activity, and possibly also the rate of progression of the individual lesions, will differ in the individual patient, and that metabolic activity determines the amount of deformation and the chance of pain. Lesions not visible on the radiograph usually show only low uptake of Tc-99m-Sn-EHDP; the majority of these lesions are asymptomatic and reflect low activity of the disease. Radiological differentiation between sclerotic and osteolytic lesions does not reflect differences in either scintigraphic uptake, metabolic activity, or pain.
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PMID:Untreated Paget disease of bone studied by scintigraphy. 649 76

Fifty-one patients with Paget's disease were treated during 6 months with ethane-01 hydroxy-1, 1 diphosphonate (EHDP, etidronate) in doses of 5 mg/kg/day. The drug was most effective in relieving pain, at the same time diminishing the uptake of pagetic lesions on quantitative bone scans and lowering by almost 70% the abnormally high serum alkaline phosphatase levels and 24-hour hydroxyproline urinary levels. Histologically, the resorption surfaces and the number of osteoclasts per mm2 of bone tissue were significantly reduced. On follow-up, the improvement persisted for at least one year after treatment was discontinued. EHDP was well tolerated clinically and biologically, and on histological sections no accumulation of osteoid tissue due to impaired mineralization was seen. EHDP at the 5 mg/kg/day dose appears to be effective in the treatment of Paget's disease.
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PMID:[Treatment of Paget's disease of bone with ethane-1 hydroxy-1, 1 diphosphonate at low dosage (author's transl)]. 677 52


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