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)

Serum bone gamma-carboxyglutamic acid-containing (Gla) protein (sBGP), a sensitive and specific marker of bone turnover, was measured in 25 patients with primary hyperparathyroidism and in 24 patients with bone metastases with or without hypercalcemia. Despite similar levels of hypercalcemia, sBGP was increased in primary hyperparathyroidism (14.2 +/- 9.6 ng/ml, P less than 0.001), was decreased in malignant hypercalcemia (3.1 +/- 2.8 ng/ml, P less than 0.001), and was normal in patients with bone metastases without hypercalcemia (6.6 +/- 2.7 ng/ml). In primary hyperparathyroidism, sBGP was correlated with serum immuno-reactive parathyroid hormone (r = 0.90), calcium (r = 0.73), and with the adenoma weight (r = 0.79). After parathyroidectomy, sBGP slowly returned to normal values within 2-6 mo, suggesting that sBGP reflects increased bone turnover rather than a direct effect of parathyroid hormone on BGP synthesis at the cell level. An iliac crest biopsy was performed in 11 patients with primary hyperparathyroidism and in 9 cancer patients in a noninvaded area. sBGP was significantly correlated with all parameters reflecting bone formation but not with bone resorption. Patients with bone metastases were analyzed according to the presence or the absence of hypercalcemia. In contrast to normocalcemic patients who had normal sBGP, hypercalcemic patients had decreased sBGP (P less than 0.001) and a lower bone formation at the cellular level (P less than 0.05). Thus, biochemical and histological data suggest that an unknown humoral factor might be responsible for this uncoupling between increased resorption and decreased formation. This uncoupling, rather than local release of calcium by the metastatic process, might be responsible for hypercalcemia in patients with bone metastases.
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PMID:Serum bone gamma carboxyglutamic acid-containing protein in primary hyperparathyroidism and in malignant hypercalcemia. Comparison with bone histomorphometry. 348 13

The relation between circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) levels and intestinal calcium absorption--as determined by an oral calcium load test--was studied in 16 patients with hypercalcaemia of malignancy (HM) and 16 with hypercalcaemic primary parathyroidism (HPT). In the HPT group serum calcium rose significantly after the oral calcium load and the increment correlated significantly with 1,25(OH)2D levels. While 1,25(OH)2D levels were raised to within the hyperparathyroid range in a number of HM patients, there was no correlation between change in serum calcium and 1,25(OH)2D level in the HM group and serum calcium did not rise significantly after the oral calcium load. HM patients with detectable or raised 1,25(OH)2D levels typically had few, or no, bone metastases in association with squamous lung cancers. A high proportion of these patients exhibited other aspects of hyperparathyroid-like activity such as increased renal tubular calcium reabsorption, depressed renal tubular phosphate reabsorption and elevated urinary cyclic AMP excretion. Conversely, HM patients with undetectable 1,25(OH)2D levels typically had extensive metastatic bone disease in association with breast carcinoma and were less likely to exhibit other hyperparathyroid-like features. It is postulated that in the former, the 'inappropriately' detectable or raised 1,25(OH)2D levels may have been due to enhanced renal 1 alpha-hydroxylase activity stimulated by the parathyroid hormone (PTH)-like effect of a non-PTH ectopic humoral mediator. In the latter the suppressed 1,25(OH)2D levels would be the predicted result of a non-humorally mediated hypercalcaemia. It is currently unclear why intestinal calcium absorption was depressed in all HM patients when 1,25(OH)2D levels were normal or raised in some cases. It is possible, however, that in HM there is 'end organ' resistance to the effects of 1,25(OH)2D due to a generalized malabsorptive process.
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PMID:Comparison of intestinal calcium absorption and circulating 1,25-dihydroxyvitamin D levels in malignancy-associated hypercalcaemia and primary hyperparathyroidism. 365 75

Serum parathyroid hormone (PTH) levels have been measured in 8 patients with hypercalcaemia associated with urological malignancy: 3 renal cell carcinomas, 2 adenocarcinomas of prostate, 2 transitional cell carcinomas of bladder and one transitional cell carcinoma of kidney. Five (63%) of these 8 patients had bone metastases. PTH was detectable in the serum of all 8 hypercalcaemic patients, but in only 2 cases was the PTH level above the normal range, and in one of these a coincidental parathyroid adenoma was found to be responsible for the hypercalcaemia. It appears that these tumours can produce a hormone-like substance with biological effects similar to PTH.
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PMID:Serum parathyroid hormone levels in the hypercalcaemia of urological malignant disease. 372 31

Hypercalcemia associated with malignancy was diagnosed in a 2-year-old Thoroughbred filly admitted because of weight loss and reduced exercise tolerance of approximately 2 months' duration. Laboratory findings included hypercalcemia, hypophosphatemia, anemia, marked neutrophilia with lymphopenia and eosinopenia, and normal immunoreactive parathyroid hormone concentration. At necropsy, a 53.6-kg tumor was located in the cranioventral aspect of the abdominal cavity. Gross renal lesions were not noticed. Bone tissue appeared to be normal on gross and histologic examinations. The parathyroid glands were not grossly identified at necropsy. A specific test does not exist for detection of hypercalcemia associated with malignancy. The diagnosis of hypercalcemia associated with malignancy was made on the basis of clinical history, physical examination, radiographic interpretation, laboratory findings, histologic examination, and ruling out other causes of hypercalcemia. Hypercalcemia, increased renal phosphate excretion in the presence of hypophosphatemia, absence of bone metastases, and identifying an abdominal mesenchymal tumor that may have originated from the left ovary satisfied the basic criteria for hypercalcemia associated with malignancy from a solid tumor.
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PMID:Hypercalcemia associated with malignancy in a horse. 373 8

Bone metastases are a major source of morbidity in patients with cancer. Previously, we found that gallium nitrate was a highly effective treatment for cancer-related hypercalcemia. Laboratory studies have shown that this drug inhibits bone resorption in vitro and that short-term treatment in vivo increases the calcium content of bone. We evaluated the clinical effects of gallium nitrate on biochemical parameters of increased bone turnover in 22 patients with bone metastases. Treatment with gallium nitrate for five to seven days caused a median reduction in 24-hour urinary calcium excretion of 66% relative to baseline measurements (P less than .01). Hydroxyproline (OHP) excretion was also significantly reduced (P less than .01). The greatest reduction in hydroxyprolinuria occurred in patients with high baseline excretion. Ionized serum calcium and serum phosphorous declined significantly after treatment (P less than .01 for each). Serum immunoreactive parathyroid hormone (PTH) increased significantly (P less than .01), as did serum levels of 1,25 (OH)2-vitamin D3 (P less than .05). Urinary phosphorous excretion and serum levels of 25-OH-vitamin D3 were not significantly changed. No major toxic reactions occurred as a result of this treatment. These results indicate that gallium nitrate significantly reduces biochemical parameters associated with accelerated bone turnover and that this agent may be useful for preventing pathologic conditions associated with bone metastases.
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PMID:Gallium nitrate inhibits accelerated bone turnover in patients with bone metastases. 380 70

The biochemical parameters of calcium metabolism were measured in patients suffering from bone metastases of prostatic origin. In 14 patients with sclerotic bone lesions, serum calcium and serum phosphorus were significantly lower than in controls. Serum alkaline phosphatase levels, which reflect osteoclastic bone formation, and urinary hydroxyproline, which reflects osteoclastic bone resorption, were both increased. 25-Hydroxyvitamin D (25-OHD) levels were appropriate for the age of the patients but serum immunoreactive parathyroid hormone (iPTH) and 1,25-Dihydroxyvitamin D (1,25-(OH)2D) levels were significantly increased. In contrast, no significant changes wee noted in 3 patients with pure osteolytic lesions. We conclude that the patients with sclerotic bone metastases have a high bone formation which frequently induces a secondary hyperparathyroidism and increased 1,25-(OH) 2D levels. A calcium and/or vitamin D supplement could therefore be advantageous in patients having symptomatic hypocalcemia or osteomalacia.
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PMID:Parathyroid function and vitamin D status in patients with bone metastases of prostatic origin. 383 94

Histologic sections of squamous cell carcinomas of four hypercalcemic patients were investigated for the presence of parathyroid hormone (PTH)-like substance. None of the patients had clinical or radiographic evidence of bone metastases. The Sternberger-peroxidase-antiperoxidase-immunoperoxidase technique utilizing monospecific antibody to whole (1 to 84) bovine PTH demonstrated immunoreactive material in all cases. Electron microscopy of the four tumors revealed dense-core secretory granules resembling those seen in parathyroid chief-cell adenomas. The patients did not have elevated serologic levels of PTH or evidence of bone metastases; however, in two cases, osteoclastic bone resorption was seen in bone marrow biopsy specimens. All patients became normocalcemic after definitive tumor resection. The hypercalcemia associated with some nonmetastatic squamous cell carcinomas is associated with the production of PTH-like substance.
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PMID:Localization of parathyroid hormone-like substance in squamous cell carcinomas. An immunoperoxidase study with ultrastructural correlation. 389 84

Immunoreactive parathyroid hormone (PTH) in nonparathyroid malignant tumors associated with hypercalcemia and hypophosphatemia in the absence of demonstrable bone metastases was determined by radioimmunoassay and immunofluorescent techniques. Six of seven tumors contained material with immunological cross-reactivity to bovine PTH by radioimmunoassay and immunofluorescence. The intensity of the immunofluorescent stain varied considerably in the different tumors. From 15 to 90% of neoplastic cells were stained specifically with fluorescein-labeled anti-PTH. In contrast, normal parathyroid glands and parathyroid adenomas showed uniform distribution of immunofluorescence in all parenchymal cells. In one malignant tumor, PTH was localized also by immunoautoradiography. In every case PTH was detected only in the cytoplasm of parenchymal cells. One patient lacked detectable PTH in his tumor, yet showed regression of the hypercalcemia to normal values after removal of large masses of neoplastic tissue and recurrence of hypercalcemia when new growth occurred.Dilutional radioimmunoassay curves of nonparathyroid malignant tumors were in most cases different from those obtained with extracts of normal parathyroid glands and parathyroid adenomas. Although both nonparathyroid neoplasmas and parathyroid extracts demonstrated immunoheterogeneity by gel filtration, greater heterogeneity was found in nonparathyroid malignant tumors. In those tumors in which immunological cross-reactivity to PTH was detected, the capability of secreting PTH may be restricted to derepressed cell clones amidst other neoplastic cells, whereas the greater heterogeneity of ectopic PTH may reflect hormone cleavage by proteolytic enzymes in the tumor that is less specific than the Pro-PTH cleaving enzyme in the parathyroids.
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PMID:Immunochemical localization of parathyroid hormone in cancer tissue from patients with ectopic hyperparathyroidism. 436 10

Dichloromethylene diphosphonate (Cl2MDP), an inhibitor of osteoclast-mediated bone resorption, lowers serum calcium in hypercalcemia associated with malignancies and with primary hyperparathyroidism. We have evaluated the effectiveness of Cl2MDP in three patients who had multiple osteolytic bone metastases due to breast cancer and coincident primary hyperparathyroidism and who refused neck exploration. Cl2MDP was added to the tamoxifen treatment and was given orally at a dose of 1600 mg/day for 12 months. All patients had a reduction in serum calcium level which was accompanied by a decline in the fasting urinary calcium and hydroxyproline excretion. Administration of Cl2MDP was not associated with any changes in parathyroid hormone levels. New bone metastases were observed neither during the treatment nor in the follow-up period. No side effects were observed.
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PMID:Long-term effects of dichloromethylene diphosphonate in patients with osteolytic bone metastases and coincident primary hyperparathyroidism. 623 89

Postmortem bone and parathyroid gland histology in nine hypercalcemic cancer patients without bone metastases was compared to bone and parathyroid histology in ten normocalcemia patients. Parameters of parathyroid function, including serum immunoreactive parathyroid hormone, acid base status, serum phosphate, and nephrogenous cyclic AMP were measured in the hypercalcemic group and compared to normals and to patients with primary hyperparathyroidism. Bone histology in all nine hypercalcemic cancer patients showed increased osteoclastic bone resorption and increased fibrous connective tissue in the bone marrow. Parathyroid glands were of normal size in all nine patients but contained little or no fat, one criterion of parathyroid hyperplasia. In the normocalcemic cancer patients only 2/10 had minimally increased bone resorption while 7/10 had decreased or absent stromal fat in the parathyroid glands. Despite the hyperplastic appearance of the parathyroid glands, serum biochemical parameters in the hypercalcemic cancer patients indicate a state of suppressed parathyroid function suggesting that the osteoclastic bone resorption is related to a humoral substance elaborated by the tumors which is distinct from parathyroid hormone.
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PMID:Abnormal bone and parathyroid histology in carcinoma patients with pseudohyperparathyroidism. 627 64


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