Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone scans with 99mtechnetium diphosphonate were performed on 2 patients with gynecomastia induced by diethylstilbestrol therapy for adenocarcinoma of the prostate. Neither patient had evidence of bone metastases but both scans revealed increased isotope concentration over the anterior rib cage at the lateral margin of the chest wall, corresponding in location to the hypertrophic breasts. This observation may be related to similar radionuclide uptake in normal and abnormal female breasts. One should not mistake the finding of gynecomastia for metastases of the ribs.
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PMID:Gynecomastia demonstrated on the bone scan. 87 1

Pamidronate [aminohydroxypropylidene diphosphonate disodium (APD), disodium pamidronate] is an orally and intravenously active amino-substituted bisphosphonate which produces potent and specific inhibition of bone resorption at doses devoid of any significant detrimental effect on bone growth and mineralisation. Clinical trials indicate that pamidronate is effective in a variety of conditions characterised by pathologically enhanced bone turnover, including Paget's disease, hypercalcaemia of malignancy, osteolytic bone metastasis, steroid-induced osteoporosis and idiopathic osteoporosis. Pamidronate is highly effective in restoring normocalcaemia in patients with hypercalcaemia of malignancy associated with bone metastases but, in common with other bisphosphonates, is marginally less effective against humoral hypercalcaemia of malignancy. Comparative studies in this area have suggested that, at therapeutic doses, pamidronate has a more pronounced calcium-lowering action than etidronate (etidronic acid) and clodronate (clodronic acid) and provides a longer period of normocalcaemic remission. In Paget's disease arrest and, in some patients, reversal of the progression of osteolytic lesions by pamidronate is associated with a sustained reduction in bone pain, improved mobility and a possible reduced risk of bone fracture. In patients with osteolytic bone metastasis pamidronate reduces skeletal morbidity and slows the progression of metastatic bone destruction. Long term use of low-dose pamidronate in conjunction with conventional antiosteoporotic therapy may halt bone loss in steroid-induced and idiopathic osteoporosis. Pamidronate appears to represent a valuable addition to the drugs currently available for the treatment of symptomatic Paget's disease and cancer-associated hypercalcaemia, and shows promise in the treatment of osteolytic bone metastasis and osteoporosis.
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PMID:Pamidronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. 170 54

Pamidronate has been demonstrated to be an effective agent in the treatment of cancer-associated hypercalcaemia. The dose regime, however, remains controversial. In this study 16 patients with cancer-associated hypercalcaemia were given 30 mg pamidronate by intravenous infusion and 16 were given 90 mg also by infusion. Groups were well-matched in terms of tumour types, bone metastases, pre-treatment serum calcium and creatinine, fasting urinary calcium/creatinine ratio, nephrogenous cAMP and the renal tubular threshold for phosphate reabsorption (TmPO4). The calcium lowering effect was similar in both treatment groups with nadir at day 6 of mean (+/- SEM) 2.48 mmol/l (+/- 0.06) in the 30 mg group and at day 9 in the 90 mg group of 2.51 mmol/l (+/- 0.03) (P less than 0.01). 10 patients in the 30 mg group and 8 in the 90 mg group were normocalcaemic at this point. Similarly when those patients with more severe hypercalcaemia (greater than 3.30 mmol/l, n = 7 in each group) were analysed separately, no significant difference was evident between the two groups. Urinary calcium/creatinine ratios fell to a nadir at day 6 in both groups of 0.33 (+/- 0.05) (30 mg group) and 0.37 (+/- 0.10) (90 mg group) (P less than 0.01). Follow-up results after the initial 9 days showed the mean time to relapse to be 38 days (range 18-90) in the 30 mg group and 34 days (11-105) in the 90 mg group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison of low versus high dose pamidronate in cancer-associated hypercalcaemia. 177 37

The pathophysiological mechanisms of hypercalcaemia were assessed in 50 rehydrated patients with cancer-associated hypercalcaemia. Surprisingly, renal tubular calcium reabsorption appeared to increase progressively as serum calcium rose, suggesting that the nomogram used for the calculation may have been inaccurate, in absolute terms, probably due to its failure to take account of the levels of urinary sodium excretion. There were significant differences in the mechanisms of hypercalcaemia in different patient subgroups, however, independent of differences in urinary sodium excretion. In those with few or no bone metastases, increased renal tubular calcium reabsorption was the principal cause of hypercalcaemia, often in association with increased bone resorption. These abnormalities were thought to reflect the renal and skeletal actions of a tumour-associated humoral mediator. The main cause of hypercalcaemia in those with extensive metastatic bone disease was increased bone resorption, with contributions from impairment of glomerular filtration rate and, to a minor extent, increased renal tubular calcium reabsorption. These abnormalities were thought to reflect a mainly local-osteolytic mechanism of hypercalcaemia with secondary impairment of GFR. Of all the biochemical variables assessed pre-treatment, the renal tubular component of hypercalcaemia correlated most strongly with post-treatment serum calcium values (r = 0.61, P less than 0.001). Because of their generally lower levels of renal tubular calcium reabsorption, patients with extensive skeletal metastases also had significantly lower post treatment calcium values than patients with few or no metastases (P less than 0.05). These data indicate that the pathophysiological mechanisms of hypercalcaemia are a major determinant of the calcium lowering response after antihypercalcaemic treatment. This should be taken into account during comparative studies of antihypercalcaemic therapy in patients with malignancy.
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PMID:Malignancy-associated hypercalcaemia: relationship between mechanisms of hypercalcaemia and response to antihypercalcaemic therapy. 297 9

Fifty-five patients with bone lesions underwent 201Tl-chloride (201TlCl) scintigraphy to evaluate its findings and usefulness for the diagnosis of bone metastases. 201TlCl scintigraphy was performed 15 minutes (early scan) and 2 hours (delayed scan) after intravenous administration of 5.55 MBq/kg of 201Tl-chloride. To evaluate the degree of tracer retention at the lesions, we calculated retention index after setting regions of interest in each lesions demonstrated tracer uptake in both early and delayed scans. Among 118 lesions of pathologically and/or clinically confirmed bone metastases, 201TlCl planar images disclosed 90 (76.3%) and 88% (74.6%) lesions on early and delayed scans, respectively. SPECT images were preferable for the evaluation of the lesions in the spine, the thoracic cage and pelvis. Correlation of tumor size with findings on 201TlCl images demonstrated 90.5% sensitivity for the metastases more than 7 cm3. No correlational difference was seen in the sensitivity depending on primary cancers. The overall retention index of bone metastases was -21.4 +/- 47.1. Bone metastases of pulmonary adenocarcinomas and small cell carcinomas demonstrated higher retention index than those of pulmonary squamous cell carcinomas and breast cancers. On 201TlCl images, no abnormal tracer uptakes were seen in benign lesions detected by 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) images except 5 lesions. The retention index of these benign lesions demonstrated abnormal uptakes on 201TlCl images was -48.3 +/- 15.0, which found no significant difference between that of metastases. In cases of vertebral compression fractures, abnormal tracer uptakes were demonstrated in 9 of the 12 pathologic fractures against 2 of the 10 benign ones. Those 2 benign fractures proved to be vertebral tuberculosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical usefulness of 201Tl-chloride scintigraphy for the diagnosis of bone metastases]. 789 73

Normal skeletal integrity is maintained by physiological bone turnover through a coupled process of bone resorption, mediated by osteoclasts, followed by new bone formation, mediated by osteoblasts. Major features of the pathogenesis of cancer-associated skeletal destruction are enhanced osteoclast-mediated bone resorption and disruption of normal bone formation. In this article, the literature on the pathogenesis and clinical manifestations of metastatic bone disease is discussed. Animal and clinical trials investigating novel bone targeted agents, emphasizing the bisphosphonates, are critically assessed. The most frequent clinical manifestations of bone metastases are pain, fracture, immobility, spinal cord compression, and hypercalcemia. New treatments under study for patients with bone metastases include agents specifically targeted to the skeleton such as bone-seeking radioisotopes and bisphosphonates. Studies in animal models of metastatic bone disease show that these bisphosphonates are able to inhibit tumor-induced osteolysis and are potentially useful in this condition. Bisphosphonates have been investigated in several clinical trials of patients with skeletal metastases from breast cancer, prostate cancer, and multiple myeloma. Overall, the studies investigating bone targeted radioisotopes or bisphosphonates for the treatment of morbidity due to skeletal metastases have been inconclusive. An improved understanding of the pathogenesis of metastatic bone disease and preclinical studies with bisphosphonates suggest that these agents may have a role in the treatment of this disorder. Additional trials of new generation bisphosphonates, employing a rigorously controlled, randomized study design with adequate numbers of subjects, are needed to demonstrate the safety and efficacy of this class of agents in this setting.
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PMID:New bisphosphonates in the treatment of bone metastases. 824 77

Hypercalcaemia is the most common metabolic complication of malignant disease. It is an important cause of morbidity in cancer patients and is potentially amendable to treatment. Bone metastases are rarely the cause of hypercalcaemia in malignancy, the elevation in calcium concentrations usually resulting from the effects of humoral mediators released by the tumour. Many factors isolated from tumours have the potential to cause hypercalcaemia, but the most important is parathyroid hormone related protein (PTHrP), a peptide which mimics the effect of PTH. Treatment of cancer associated hypercalcaemia is based on an initial phase of volume repletion with isotonic saline, followed by drug treatment to inhibit bone resorption. Bisphosphonates are the most widely used agents in the treatment of such bone resorption, are very effective and have minimal toxicity. Gallium nitrate is also effective but less widely used. The combination of bisphosphonates and calcitonin has been found to be particularly useful in patients with severe hypercalcaemia, since this gives a more rapid reduction in serum calcium values than can be achieved with bisphosphonate alone. In the longer term, effective control of hypercalcaemia depends on treating the primary tumour. In the majority of cases this is not possible, however, because of the state of disease progression or the nature of the tumour. Anti-hypercalcaemic therapy is an important palliative measure in cancer patients who have symptoms of hypercalcaemia. Treatment does little to alter the long term prognosis but often results in an improvement in symptoms such that the majority may be made well enough to be discharged from hospital care.
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PMID:Pathogenesis and management of cancer associated hypercalcaemia. 856 93

This study was designed to evaluate new bone resorption and tumour markers as possible alternatives to serial plain radiographs for the assessment of response to treatment. Thirty-seven patients with newly diagnosed bone metastases from breast cancer, randomized to receive oral pamidronate or placebo tablets in addition to anticancer treatment within the context of a multicentre EORTC trial, who were both assessable for radiographic response in bone and had serum and urine samples collected for more than 1 month were studied. The markers of bone metabolism measured included urinary calcium (uCa), hydroxyproline (hyp), the N-telopeptide cross-links of type I collagen (NTx) and total alkaline phosphatase. The tumour markers measured were CA15-3 and cancer-associated serum antigen (CASA). Before treatment, levels of Ntx, uCa and Hyp were elevated in 41%, 24% and 28% respectively, and CA15-3 and CASA increased in 69% and 50%. For assessment of response and identification of progression, Ntx was the most useful bone marker. All markers behaved similarly in no change (NC) and partial response (PR) patients. There was a significant difference (P < or = 0.05) in Ntx levels (compared to baseline) at 1 and 4 months and in CA15-3/CASA at 4 months between patients with PR or NC and those with progressive disease (PD), and at 4 months between those with time to progression (TP) > 7 and those with TP < or = 7 months. The diagnostic efficiency (DE) for prediction of PD following a > 50% increase in Ntx or CA15-3 was 78% and 62% respectively. An algorithm to predict response to therapy has been developed for future prospective evaluation.
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PMID:Assessment of bone response to systemic therapy in an EORTC trial: preliminary experience with the use of collagen cross-link excretion. European Organization for Research and Treatment of Cancer. 1039

Alendronate, a bisphosphonate compound, lowers serum calcium in patients with cancer-associated hypercalcemia through its inhibitory effect on bone resorption and as a result symptoms associated with hypercalcemia improve. This study was carried out to investigate the effects of alendronate in patients with hypercalcemia due to bone metastasis of hepatocellular carcinoma (HCC). Two patients were evaluated. Their corrected serum calcium and alpha-fetoprotein (AFP) levels and their computed tomography (CT), bone scintigraphy and magnetic resonance imaging (MRI) findings were evaluated before and during alendronate treatment. After treatment, not only the corrected serum calcium levels but also AFP levels and bone pain decreased; in addition, the regression of the metastatic focus was noted in the MRI analysis. These tumor inhibitory effects of alendronate have not been reported in HCC before; and alendronate might serve to prevent bone metastases in patients with HCC. In conclusion, two patients who developed hypercalcemia associated with bone metastasis after surgery for HCC were treated with alendronate and they experienced alleviation of the pain due to bone metastasis, improvement of their quality of life and a marked decrease in AFP levels with tumor regression.
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PMID:Effects of alendronate on bone metastases and hypercalcemia after surgery for hepatocellular carcinoma. 1109 40

This manuscript reviews the theories behind the propensity of prostate cancer to cause bone metastases and skeletal implications of the prostate cancer biology and treatment modalities. The escape of tumor cells from the primary tumor in the prostate to secondary tumor sites in the axial skeleton probably occurs before the primary tumor is detected. Several theories offer explanations for the observed proclivity of prostate tumors to selectively colonize the axial skeleton. The interaction between the tumor cells and cells that populate bone marrow, in particular osteoblasts and osteoclasts, is important for creating a 'fertile' environment where tumor cells can establish and grow. Prostate cancer cells are capable of producing growth factors that can affect both osteoblasts, resulting in osteoblastic bone formation, and osteoclasts, resulting in excessive bone resorption. In addition to the capability to progress from testosterone-dependent to testosterone-independent phenotype, the hallmark of metastatic prostate cancer is osteosclerosis similar to one induced experimentally in nude rats using CWR22 human prostate cancer cell line. Metastatic bone disease caused by excessive bone formation and bone resorption is the major cause of morbidity in patients with prostate cancer. The most common symptoms include pain, pathological fractures, spinal cord compression, cranial nerve palsies, bone marrow suppression and hypercalcemia. The introduction of prostate-specific antigen in clinical practice created a shift to where more prostate cancer patients with early disease receive androgen ablation treatment, which in return causes more bone loss and cancer-associated osteoporosis. Introduction of third generation bisphosphonates to treat skeletal consequences of malignancy further stressed the important interaction between the bone marrow stroma and cancer cells. Nevertheless, animal models and human prostate tumor cell lines that mimic all aspects of skeletal conditions in prostate cancer patients including osteoblastic bone response are needed to develop and screen for novel therapeutic and diagnostic modalities.
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PMID:Skeletal implications of prostate cancer. 1575 51


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