Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteocalcin, also called bone gla-protein, is a bone matrix protein synthetized specifically by osteoblasts. It circulates in blood where it can be assayed by the radioimmune method. We measured osteocalcin serum levels in 169 adult controls and 161 patients with different disseminated or localized bone diseases. The normal concentration of 6.2 +/- 0.2 ng/ml increases significantly with age. Serum osteocalcin levels are considerably increased in renal osteodystrophy (114 +/- 23 ng/ml) and to a lesser degree in primary hyperparathyroidism (15.9 +/- 2.8 ng/ml) and Paget's disease (11.4 +/- 0.9 ng/ml), all diseases characterized by increased bone turnover. High levels are also encountered in osteomalacia (9.7 +/- 0.9 ng/ml). Conversely, serum osteocalcin levels are significantly decreased in patients under long-term corticosteroid therapy (4.3 +/- 0.5 ng/ml); they remain normal in patients with bone myeloma and bone metastases under treatment. Finally, osteocalcin is normal in patients with osteoporosis, but its level reflects that of bone turnover as evaluated by iliac bone biopsy. The circulating osteocalcin therefore is the first specific and sensitive marker for bone turnover. Serum osteocalcin measurements make it possible to evaluate the osteoblastic bone formation without biopsy and should provide information on the effectiveness of drugs acting on the bone-forming process.
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PMID:[Osteocalcin (or bone gla-protein), a new biological marker for studying bone pathology]. 293 33

Increased bone resorption (BR) and increased renal tubular reabsorption of calcium (TRCa) may both be involved in the pathogenesis of hypercalcemia of malignancy (HM). We have evaluated the relative importance of these two mechanisms in 33 patients with HM after extracellular volume expansion and after single infusion of clodronate (C12MDP: 500 mg iv over 8 h). The fasting urine Ca/creatinine ratio was taken as an index of BR (BRI). An index of TRCa was calculated (TRCaI) from a nomogram based on the relationship between urine Ca excretion per unit of glomerular filtration rate and plasma Ca (PCa). Mean (+/- SEM) PCa fell from 3.29 +/- 0.07 to 2.69 +/- 0.05 mmol/l three days after C12MDP (n = 33, p less than 0.001), a response similar to that obtained with repeated daily iv injections of 500 to 1000 mg C12MDP. The pathogenesis of hypercalcemia varied according to the type of neoplasm. BRI was the highest in multiple myeloma and breast tumors. TRCaI was markedly increased in squamous-cells lung, bladder, kidney and liver carcinomas, reaching levels observed in primary hyperparathyroidism. TRCaI was normal in most cases of multiple myeloma. Breast tumors appeared to be heterogeneous with respect to TRCaI. The fall in PCa in response to a single infusion of C12MDP was usually most marked in cancer patients with elevated BRI and normal TRCaI. It was very modest in patients with high TRCaI and slightly elevated BRI. In conclusion, this study confirms that stimulation of bone resorption is not the only mechanism of the maintenance of hypercalcemia of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate. 297 82

Osteopenia in the elderly is responsible for 1.3 million fractures per year in the United States. The acute care costs associated with this disorder are between $6 and $10 billion dollars annually. Although much has been learned over the last few years of the factors that predispose patients to osteoporosis and how these factors may be avoided, the precise pathophysiologic mechanisms for bone loss remain obscure. Significant technological advances have been made in the 1980s in the development of noninvasive methods for measuring bone mineral density that give indirect assessments of bone mass. However, these methods are very controversial, are not suitable for mass screening for detecting subjects potentially at risk, and have a limited place in routine clinical care. Osteoporosis is characterized by thinning and fragmentation of trabecular bone, which is probably irreversible when it is far advanced. The most reasonable therapeutic approach may be prevention, which can be achieved in many patients by estrogen therapy in the perimenopausal years and insuring an adequate dietary calcium intake, particularly in adolescents and in the elderly. Physical activity throughout life is also likely to be important in maintaining adequate bone mass. It is important to differentiate osteoporosis from other causes of osteopenia, for example, osteomalacia, primary hyperparathyroidism, and malignant diseases such as myeloma, since these bone diseases have a different natural history, pathophysiology, and treatment.
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PMID:Osteopenia. 331 29

Results are presented of measurements of skeletal blood flow made in 80 patients with painful benign or malignant diseases of the skeleton, excluding patients with Paget's disease. In crush fracture osteoporosis, total bone blood flow was slightly lower than normal although skeletal perfusion was normal. High values of bone blood flow were seen in 14/20 patients with osteomalacia and 3/12 patients with primary hyperparathyroidism. Very high values, comparable to those seen in the most severely affected patients with Paget's disease, were seen in polyostotic fibrous dysplasia, 2 out of 4 cases of Engelmann's disease and 1 out of 3 cases of renal osteodystrophy. Results were less elevated in myositis ossificans, secondary skeletal involvement with breast and prostatic carcinomata, myelomatosis and sympathetic osteodystrophy.
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PMID:Skeletal blood flow in metabolic disorders of the skeleton. 342 88

Serum concentrations of immunoreactive parathyroid hormone (iPTH) measured with a mid-region specific radioimmunoassay and total calcium were correlated in 300 healthy subjects and 158 patients with surgically verified primary hyperparathyroidism (HPT). All the healthy individuals could be separated from the patients by a monoexponential declining curve in which iPTH at concentrations of 0.60 micrograms/l and 0.33 micrograms/l corresponded to calcium concentrations of 2.20 mmol/l and 2.60 mmol/l, respectively. In 22 patients more than one sample was analysed and serum iPTH and calcium were inversely correlated. In contrast, three patients with parathyroid carcinoma showed no reciprocal fluctuations between serum iPTH and calcium. Of 75 patients with hypercalcaemia due to malignant diseases (metastatic mammary carcinoma, bronchial carcinoma, renal carcinoma, myelomatosis), 62 had a normal iPTH/calcium relationship. Two patients with myelomatosis had a temporary elevation of serum iPTH and calcium due to renal impairment. One patient with bronchial carcinoma probably had ectopic production of iPTH. The remaining 10 patients (six mammary carcinomas and four bronchial carcinomas) were found in the pathological iPTH/calcium range. In conclusion, we have demonstrated that an inverse relationship exists between serum iPTH and calcium in patients with non-malignant, primary HPT. Evaluation of iPTH and calcium in the same serum sample gave a correct diagnosis in more than 90% of patients with primary HPT.
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PMID:Improved diagnosis of primary hyperparathyroidism by defining the inverse relationship between serum immunoreactive parathyroid hormone and calcium. 374 90

Osteocalcin is synthesized by osteoblasts and its concentration in serum is increased when bone metabolism is raised. Radioimmunoassay of serum from 88 healthy adults gave a mean osteocalcin value for the whole group of 4.11 +/- 1.43 ng/ml. The level rose with age. In seven patients with primary hyperparathyroidism the mean value was markedly raised to 19.37 +/- 9.2 ng/ml, in 23 with metastasizing carcinoma of the breast it was elevated to 6.57 +/- 2.98 ng/ml. Serial measurements in 14 female patients over seven months revealed different changes in osteocalcin and alkaline phosphatase in some of them. In patients with breast cancer and soft-tissue metastases or without metastases both osteocalcin and alkaline phosphatase levels were normal. Three of 17 patients with multiple myeloma had increased osteocalcin levels. These results indicate that it is clinically helpful to know osteocalcin levels in primary hyperparathyroidism. Determination of osteocalcin concentration, in addition to that of alkaline phosphatase, can be of value in the postmastectomy management of patients with breast cancer, especially in the early recognition of bone metastases. The diagnostic value of osteocalcin levels in multiple myeloma remains undecided.
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PMID:[Osteocalcin, a marker in diseases with elevated bone metabolism]. 387 69

After confirming hypercalcemia by 3 successive measurements of the total plasma calcium corrected for a plasma protein concentration of 72 g/l, which excludes spurious hypercalcemia due to dehydration, the physician orientates the aetiological diagnosis bearing in mind that primary hyperparathyroidism PHPT is the cause of 85 p. 100 of all asymptomatic forms of hypercalcaemia whilst overt or occult malignancy is the main cause (60 p. 100) of symptomatic forms of hypercalcaemia with PHPT responsible for 20 p. 100 of cases. Other causes, including drug toxicity with Vit D, calcium, Vit A, lithium, thiazide and aluminium hydroxide, sarcoidosis, hyperthyroidism, Addison's disease, pheochromocytoma and familial endocrine disorders are much rarer. Nevertheless, these rarer causes must be excluded on the clinical history and examination followed by radiological (chest X ray, plain abdomen X ray, bone X rays) and simple biological tests. The latter and/or scans tests should also help in a rapid diagnosis of metastatic carcinoma and multiple myeloma, so that the major diagnostic problem is to distinguish primary HPT from occult malignancy. This problem is greatly facilitated by reliable assays of C terminal or medium PTH rather than renal CAMP which is increased in 80 p. 100 of occult malignancies. When PTH assays is unavailable or unreliable Dent's hydrocortisone suppression test may be useful as a fall in'serum calcium is associated with occult malignancy in 70 p. 100 of cases and non-suppression is associated with PHPT in 91 p. 100 of cases. Discriminant analysis of the usual biochemical parameters may be helpful in this differential diagnosis and is accurate in about 90 p. 100 of cases. However, the association of PHPT and malignancy is also possible and not fortuitous.
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PMID:[Stages of the etiological diagnosis of hypercalcemia]. 389 Jun 61

Dichloromethylene diphosphonate (Cl2MDP) a potent inhibitor of osteoclast-mediated bone resorption, lowers serum calcium in hypercalcemia associated wit malignancies and with primary hyperparathyroidism, and reduces excess calcium mobilization from bone in multiple myeloma and in Paget's disease. We have evaluated the effectiveness of intravenously administered Cl2MDP in five patients with parathyroid carcinoma, a disorder characterized by severe hypercalcemia, very high parathyroid hormone (PTH) levels, and marked osteoclast-mediated bone resorption. All patients had biopsy-proved metastatic parathyroid carcinoma and hypercalcemia which persisted after multiple surgical procedures and other attempts at management. During a three-day observation period, each patients continued to demonstrate stable or progressive hypercalcemia despite infusion with saline solution and furosemide. Cl2MDP was administered over 2 hours at 2.5 mg/kg on day 1 and 5 mg/kg on days 2 through 7. Response was noted in all five patients; there was a gradual decline in the average serum calcium from 16.0 +/- 1.1 mg/dl (SEM) to 11.1 +/- 0.9 mg/dl by the eighth day (p less than 0.01). There were concomitant reductions in urinary calcium excretion, from 798 +/- 153 mg/g creatinine to 350 +/- 96 mg/g creatinine (p less than 0.05) and in the urinary hydroxyproline excretion, from 155 +/- 38 mg/g creatinine to 94 +/- 29 mg/g creatinine (p less than 0.02). Serum PTH levels remained markedly elevated (460 +/- 141 micrograms eq/ml to 493 +/- 169 micrograms eq/ml). In three patients, all indices returned to pretreatment levels by 10 days after the last infusion. In two of these patients there was a response to retreatment with Cl2MDP with a fall in calcium from 16.9 +/- 0.5 mg/dl to 12.4 +/- 1.5 mg/dl. There was no response in one patient. No adverse reactions to Cl2MDP were observed. The decrease in serum calcium and concomitant declines in urinary calcium and hydroxyproline suggest that Cl2MDP can effectively inhibit the excessive bone resorption associated with parathyroid carcinoma.
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PMID:Therapy of hypercalcemia due to parathyroid carcinoma with intravenous dichloromethylene diphosphonate. 621 78

A patient with multiple myeloma and hypercalcemia responded to cytotoxic chemotherapy. However, hypercalcemia persisted. Because of the absence of lytic bone lesions, the presence of a low serum phosphate level, and a family history of possible primary hyperparathyroidism, the patient was evaluated for this disorder. Serum parathyroid hormone and urinary cyclic adenosine monophosphate levels were elevated. Exploration of the neck disclosed two enlarged parathyroid glands (1,850 mg and 210 mg), which were excised. After surgery, the patient's serum calcium levels remained normal for one year. Progressive myeloma bone disease developed that eventually resulted in recurrent hypercalcemia and death. Autopsy revealed only evidence of myeloma.
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PMID:Coexistent multiple myeloma and primary hyperparathyroidism. 627 81

Hypercalcemia secondary to malignancies can be divided into two groups according to their calcium elevating mechanism: solid tumors with bony metastases, most frequently originating from the breast or the bronchi, and solid tumors without bony metastases, associated with secretion by the tumor of a substance which increases the calcium level. This substance resembles parathormone in pseudo-hyperparathyroidism, prostaglandins, or other substances not yet identified. The most common tumors involved are bronchial or renal cancers. Diagnostic problems vary depending on whether the cancer has been identified or not, and if bony metastases have or have not been discovered. Primary hyperparathyroidism must also be considered since it is frequently associated with cancer. Hypercalcemia from blood dyscrasias (myeloma and lymphoma) originates from the same mechanisms. It may or may not be associated with bony lesions. The hypercalcemia could be due to a "parathormone like" substance, to prostaglandins, to a substance that stimulates osteoclasts (OAF), or to calcitriol (1,25-dihydroxycholecalciferol). The treatment of hypercalcemia due to malignancies is primarily through the use of antiosteoclastic agents: calcitonin, mithramycin, and more recently diphosphonates. Corticosteroids and the prostaglandin inhibitors can have an additional calcium lowering effect.
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PMID:[Hypercalcemia of cancer and myeloma]. 639 3


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