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)

In an initial safety study, phosphorus-32 (as diphosphonate) was administered intravenously to five patients with painful bone metastases from prostatic carcinoma; two patients received 9 mCi and three were given 3 mCi. Hematological, biochemical, ECG, x-ray, bone-scan data, and clinical observation, were followed for 2 mo. At both dose levels, bone-marrow depression was noted. One of the patients, who received 9 mCi, had only a slight dip in the levels of circulating white blood cells and platelets. The other 9-mCi patient was the only one with discrete metastases by bone scan; he had bone-marrow depression, from which he recovered, and was the only one of the five who had relief of bone pain.
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PMID:[32P] diphosphonate dose determination in patients with bone metastases from prostatic carcinoma. 41 89

We evaluated the incidence of hypo- versus hypercalcemia and hypo- versus hyperphosphatemia in a survey of 158 patients with malignancy; 55/158 had bone metastases. When serum calcium levels were corrected for albuminemia, the incidence of hypo- and hypercalcemia was respectively 10.8% and 10.1%. Hypophosphatemia was found in 29.7% patients, hyperphosphatemia in 2.5%. The incidence was slightly different in presence of bone metastases. Hypocalcemia and hypophosphatemia prevailed in osteoblastic metastases and hypercalcemia in osteolytic metastases. The incidence of hypocalcemia and hypophosphatemia in malignancy was therefore surprisingly high, even apart from the presence of bone metastases. Both hypo- and hypercalcemia were associated with elevated serum alkaline phosphatase levels. Moreover, a calcium-phosphorus product reduction was observed in osteoblastic metastases, suggesting a condition of secondary hyperparathyroidism.
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PMID:A hospital survey of hypocalcemia and hypophosphatemia in malignancy. 174 50

Secondary hyperparathyroidism can develop as a result of bone metastases from prostatic cancer, but this has not been studied from the multiple aspects of biochemistry, hormonal status and histomorphometry. In 20 patients with stage-D prostatic cancer, a transiliac bone biopsy was performed for histomorphometric study. In all of them, molecular parathormone (PTH-M) and osteocalcin were determined by radioimmunoassay together with other parameters considered to be biological markers of bone remodelling. Of these 20 patients, only 2 (10%) had elevated PTH-M (240 +/- 20.6 pmol/l), differing significantly from the other 18 (58.6 +/- 11.7 pmol/l) and from controls (60.4 +/- 7.2 pmol/l). In the high PTH-M patients, corrected calcium was low (7.8 +/- 0.4 mg/dl) as compared to normal PTH-M patients (9.2 +/- 0.5 mg/dl, p less than 0.001), and this was also the case for serum phosphorus (2.2 +/- 0.6 vs. 3.2 +/- 0.3 and 3.4 +/- 0.4 mg/dl, respectively p less than 0.001). Alkaline phosphatase was raised in the patient groups as compared to controls (p less than 0.001) and was higher in the high PTH-M group (362 +/- 58 vs. 224 +/- 62 U/l, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperparathyroidism in metastases of prostatic carcinoma: a biochemical, hormonal and histomorphometric study. 231 37

The kinetics, dosimetry, and response of iodine-131 alpha-amino-(4-hydroxybenzylidene)-diphosphonate ([131I]BDP3) treatment were investigated with patients who had pain symptoms from bone metastases of various primary carcinoma. The blood clearance of [131I]BDP3 was rapid. More than 90% disappeared from the blood pool at 2 hr after injection. The excretion of the activity occurred solely through the kidneys and mean total-body retention at 48 hr was 48.6%. The urinary activity showed a metabolite which must be formed by an in vivo cleavage reaction of a phosphorus-carbon bond. The uptake of in vivo cleaved [131I]iodide in the unblocked thyroid was approximately 0.5%. The effective half-life of [131I]BDP3 in metastatic bone (median 182 hr; range 177-205 hr) proved to be longer than in unaffected areas (145 hr; 140-165 hr). Palliative therapies were performed with 18 patients. They received doses ranging between 6 and 48 mCi [131I]BDP3. The response was 44% complete pain relief, 6% substantial pain relief, 22% minimal improvement, and 28% no change. The duration of response ranged between 1 and 8 wk.
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PMID:Iodine-131-labeled diphosphonates for palliative treatment of bone metastases: II. Preliminary clinical results with iodine-131 BDP3. 242 28

Radiation is an effective modality for palliation of osseous metastases. In patients with a limited number of lesions, local external beam irradiation is the most expedient method of delivering radiation therapy. Complete or partial relief of pain will occur in 80-90% of patients. When metastases are widespread or when new sites continue to appear, localized external irradiation becomes logistically difficult. In such cases, hemibody irradiation has been effective with an overall response rate of 85%. However, nausea, vomiting, diarrhea, and bone marrow and pulmonary toxicity may complicate therapy. In these cases, an effective alternative is systemic phosphorus-32 (32P) or strontium-89 (89Sr). Relief of pain in the range of 60-90% has been reported. Toxicity of 32P is largely that of bone marrow suppression, while 89Sr appears to be relatively marrow-sparing. In this review, we consider systemic 32P or 89Sr as viable options to external beam or hemibody irradiation in the presence of numerous bone metastases.
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PMID:The palliation of osseous metastasis with 32P or 89Sr compared with external beam and hemibody irradiation: a historical perspective. 247 19

A serially transplantable tumor line, designated CAC-8, has been developed in nude mice from a spontaneously occurring adenocarcinoma of the anal sac from a hypercalcemic dog. Nude mice with transplanted CAC-8 developed hypercalcemia (mean 16.3 +/- 0.6 mg/dl) and moderate hypophosphatemia without bone metastasis. Urinary excretion of calcium and hydroxyproline were increased 6- and 2.3-fold, respectively. Urinary excretion of cAMP was moderately increased but phosphorus excretion was not significantly altered. Serum 1,25-dihydroxycholecalciferol was increased significantly in tumor-bearing nude mice in proportion to the magnitude of tumor-induced hypercalcemia. Histomorphometric evaluation of lumbar vertebrae from nude mice with CAC-8 revealed decreased total and cortical bone volume, a 3.3-fold increase in bone resorption rate and a 2.5-fold increase in bone formation rate at the tissue level. The transplanted CAC-8 has maintained the histologic pattern of the original carcinoma up to the present sixth passage. Ultrastructural evaluation of transplanted tumor cells revealed 150-250-nm secretory-like granules. The granules did not stain by using an ultrastructural cytochemical (uranaffin) stain specific for neuroendocrine secretory granules. Ultrastructurally, the parathyroid glands of nude mice with CAC-8 appeared inactive with large intracytoplasmic whorl of agranular membranes. These data suggest the transplanted carcinoma secreted a humoral factor which resulted in hypercalcemia. The tumor line (CAC-8) propagated in nude mice represents an animal model of humoral hypercalcemia of malignancy that shares many features with the syndrome described in human patients. Unique features of this transplanted carcinoma associated with hypercalcemia include increased serum dihydroxycholecalciferol, increased rate of bone formation as well as bone resorption, an absence of bone metastases, and evidence of parathyroid gland suppression.
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PMID:Humoral hypercalcemia of malignancy in nude mouse model of a canine adenocarcinoma derived from apocrine glands of the anal sac. Biochemical, histomorphometric, and ultrastructural studies. 301 99

Treatment of malignancy-associated hypercalcemia remains unsatisfactory. We have prospectively treated 26 consecutive hypercalcemic cancer patients with intravenous (IV) aminohydroxypropylidene diphosphonate (APD). The drug was administered daily as a 15-mg two-hour IV infusion until both serum and urinary calcium had been normalized for 48 hours. Twenty-four patients were fully evaluable (eight head and neck tumors, seven breast cancers, three epidermoid tumors of the lung, and six miscellaneous neoplasms). Whereas rehydration had only inconsistent effects, APD normalized serum calcium in all patients after a mean of three daily doses: serum calcium decreased from 13.3 +/- 0.4 mg/dL (mean +/- SEM) before APD to 8.0 +/- 0.1 mg/dL at the end of treatment. Ionized calcium declined in parallel to total calcium. APD was as effective in hypercalcemia due to bone metastases as in paraneoplastic hypercalcemia. The drug was tolerated without toxicity and had a prolonged effect: serum calcium remained normal during 3+ weeks (1 + to 8 +) in 17 patients who did not receive or did not respond to antitumoral treatment. APD normalized serum calcium by inhibiting bone resorption, as evidenced by the dramatic decrease in urinary excretion of calcium and hydroxyproline. Inhibition of bone resorption was probably also responsible for the decrease in serum phosphorus from 2.9 +/- 0.2 to 2.0 +/- 0.1 mg/dL. In summary, IV APD constitutes a major advance in the treatment of malignancy-associated hypercalcemia: it is very effective, well tolerated, and has a prolonged efficacy.
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PMID:Treatment of malignancy-associated hypercalcemia with intravenous aminohydroxypropylidene diphosphonate. 301 5

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

Gallium nitrate was recently found to be effective treatment for resistant cancer-related hypercalcemia. In vitro and in vivo experiments have suggested that the drug directly inhibits calcium resorption from bone; however, the overall effects of gallium nitrate on calcium balance were unknown. We have completed metabolic balance studies in four patients who received this drug by prolonged infusion. All patients were in positive calcium balance while receiving the drug. Each patient also showed a substantial decrease in urinary calcium excretion. Serum phosphorus decreased in all four patients. There was no change in phosphorus, sodium, chloride, or magnesium balance or in creatinine clearance. We conclude that prolonged infusions of gallium nitrate reduce urinary calcium excretion and that the hypocalcemic effect of this drug is primarily due to inhibition of calcium resorption from bone. Thus, the drug may prove useful in reducing accelerated bone resorption in patients with bone metastases or chronic cancer-related hypercalcemia.
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PMID:Metabolic effects of gallium nitrate administered by prolonged infusion. 401 69

Cl2MDP, a potent inhibitor of osteoclast-mediated bone resorption, was tested in 8 patients with malignant hypercalcaemia. In a 2 months' double-blind, cross-over study the patients received Cl2MDP (3200 mg/day) during 4 weeks and a placebo during 4 weeks in a randomized sequence. The serum Ca level fell from a mean pre-trial value of 12.2 +/- 1.7 mg/dl to 10.3 +/- 1.4 mg/dl after 4 weeks of Cl2MDP (p = 0.01). Reduction was rapid, with a mean serum Ca value of 10.5 +/- 1.4 mg/dl as early as the 3rd day. At the end of the Cl2MDP treatment, 6 out of the 8 patients had normal serum Ca levels. Following active treatment, the serum Ca level significantly increased in 2 patients and remained low in one patient under placebo. Treatment with Cl2MDP resulted in a decrease in calciuria from 397 +/- 193 mg/g creatinine/24 hours to 241 +/- 211 mg/g creatinine/24 hours (p = 0.05), but there was no decrease in hydroxyproline. Serum phosphorus and PTH levels remained normal. It is concluded that Cl2MDP is an effective and convenient oral treatment of hypercalcaemia due to bone metastases.
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PMID:[Dichloromethylene diphosphonate (Cl2MDP) treatment of hypercalcaemia produced from bone metastases (author's transl)]. 621 Aug 78


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