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Query: UMLS:C0005940 (bone disease)
7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of hypercalcemia of malignancy is troublesome. Personal experience with breast cancer associated hypercalcemia is presented. Eight patients were hydrated with intravenous administration of saline solution containing high doses of salmon calcitonin and subsequently six were treated with antiblastic polychemotherapy. Calcium level fell to normal in all patients. Hypercalcemia, with or without evidence of metastatic bone disease, may be caused by the production of humoral substance by tumoral tissue. In our experience the first therapeutic stage is the infusion of saline solution containing high doses of calcitonin, while the elective treatment is antiblastic polychemotherapy which, acting on tumour growth, may inhibit the release of humoral mediators of hypercalcemia causing a slower but stable reduction in serum calcium level.
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PMID:[Update on paraneoplastic hypercalcemia. Our experience in the treatment of hypercalcemic states of patients with advanced breast carcinoma]. 340 54

Studies of osteoclasts and their precursors in normal and pathological states have been severely hampered by the lack of an in vitro system for forming osteoclasts. We developed a human marrow culture system in which multinucleated cells with several characteristics of osteoclasts form. Multinucleated cells began to form during the first week of culture, with maximum numbers formed after 3 weeks. PTH (25-50 ng/ml) and 1,25-dihydroxyvitamin D3 (10(-10)-10(-8) M) increased formation of these cells, and these effects were inhibited by calcitonin. These multinucleated cells contained nonspecific esterase and tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts, and had several ultrastructural features of osteoclasts. We used this marrow cell culture technique to study a patient with hyperparathyroidism and markedly increased osteoclasts on bone marrow biopsy. The marrow from this patient formed increased numbers of multinucleated cells in vitro. After parathyroidectomy both multinucleated cell formation in vitro and osteoclast numbers on bone biopsy decreased significantly. This long term marrow culture system represents the first demonstration of human osteoclast-like cell formation in vitro. This system should permit studies to evaluate factors controlling formation of cells with certain osteoclast characteristics in vitro and their precursors as well as to evaluate abnormalities in osteoclast formation in patients with metabolic bone disease.
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PMID:Formation of multinucleated cells that respond to osteotropic hormones in long term human bone marrow cultures. 356 33

Osteoporosis is a serious metabolic bone disorder that results in fractures of the wrist, hip and vertebrae. These fractures frequently occur with little or no trauma. Osteoporosis is seen more frequently in women than men. While the pathogenesis of osteoporosis is incompletely understood at this time, certain risk factors are emerging as important. Among the more important of these are family history, low calcium intake, early menopause and sedentary lifestyle. Other suggested risk factors include high intakes of protein, alcohol and caffeine; low body weight; exercise-induced amenorrhea; and cigarette smoking. No single therapy or combination of therapies for osteoporosis has proven to be uniformly successful. Indeed, once fractures occur, full restoration of the skeleton may not be possible. Currently, calcium, exercise and estrogen form the treatment for osteoporosis. When these conservative measures are ineffective or inadequate, treatment with fluoride, calcitonin, vitamin D or anabolic steroids may be attempted. Research to clearly identify and quantify risk factors and find an effective treatment for osteoporosis continues.
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PMID:Osteoporosis: significance, risk factors and treatment. 376 61

The paper challenges the widely held notion that calcitonin antagonizes effects of the parathyroid hormone (PTH) on bone and inhibits the development of hyperparathyroid bone disease in uremic patients. This was done by studying 16 patients on chronic maintenance dialysis with various levels of PTH and endogenous calcitonin. In addition, 2 patients with normal kidney function and high calcitonin levels due to medullary carcinoma of the thyroid were evaluated, one of them with an excessive, the other with a low-normal PTH level. Undecalcified bone histology was done in all patients and quantitative static and dynamic parameters of bone structure, bone formation, mineralization and resorption were correlated with serum calcitonin and PTH levels using Dunn's multiple comparison procedure. Covariables such as bone aluminum accumulation, immobilization or other diseases were taken into consideration or avoided. In contrast to the literature, no correlations were found between calcitonin and PTH or between calcitonin and bone histology, whereas PTH correlated with parameters of bone resorption and formation. One uremic patient with no circulating calcitonin and high PTH did not show excessive signs of PTH activity on bone. In addition, bone histology in the nonuremic patient with high PTH and high calcitonin did reveal signs of a PTH overactivity on bone which were not seen in the other nonuremic patient with high calcitonin only. These findings indicate that endogenous calcitonin is not protective against hyperparathyroid bone disease.
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PMID:Endogenous calcitonin does not protect against hyperparathyroid bone disease in renal failure. 396 14

Paget's bone disease is rare in young adults. Severe osteolytic Paget's bone disease in a 28-year-old man was found to respond, clinically, biochemically, and radiographically, within one month to daily subcutaneous injections of 0.5 mg of synthetic human calcitonin. After two years of therapy, he remains asymptomatic and has no biochemical evidence of Paget's bone disease while receiving injections three times a week. Despite aggressive disease, young patients may rapidly demonstrate the same beneficial response to synthetic human calcitonin therapy as has been observed in middle-aged or elderly patients with Paget's bone disease.
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PMID:Osteolytic Paget's bone disease in a young man. Rapid healing with human calcitonin therapy. 397 56

Free hydroxyproline was measured in plasma of 67 normal subjects and in 70 patients with bone disease including primary hyperparathyroidism (n = 19), osteoporosis (n = 18), Paget's disease (n = 14), cancer involving bone (n = 8), chronic renal failure (n = 6), and osteomalacia (n = 6), and osteomalacia (n = 5). A good correlation was found between plasma and urinary values of the amino acid in normal subjects (r = 0.66; p less than 0.001). In patients with skeletal disorders a highly significant direct correlation was observed between free plasma hydroxyproline on the one hand and urinary hydroxyproline (r = 0.92; p less than 0.001) and serum alkaline phosphatase activity (r = 0.86; p less than 0.001) on the other, even though there were a few examples of dissociations among these parameters. Free plasma hydroxyproline decreased in the patients with Paget's disease following chronic administration of salmon calcitonin. Following successful parathyroidectomy, free plasma levels of hydroxyproline decreased in all the cases studied. Measurement of free plasma hydroxyproline thus appears to provide a specific index of bone metabolism that may be usefully employed as an alternative to the assay of other markers of bone turnover.
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PMID:Clinical significance of free plasma hydroxyproline measurement in metabolic bone disease. 406 20

Fifty-four patients with Paget's bone disease have been treated with the bisphosphonate APD. Twenty-six patients had not previously received treatment for Paget's disease; and 28 had been treated before with EHDP alone or in combination with calcitonin. APD was given orally in a mean dose of 500 mg daily (congruent to 6.8 mg/kg of body weight) for 4 to 12 months. Bone pain diminished or disappeared in 34 of 39 patients with symptoms. A very significant diminution of the biochemical indices of bone turnover was observed in all patients, but the responses were faster in patients who had not previously received treatment for Paget's disease. After 4 months of treatment the serum levels of alkaline phosphatase of previously untreated patients diminished from 58.8 +/- 8.0 to 20.0 +/- 3.9 KA units (P less than 0.001) and urinary excretion of hydroxyproline diminished from 108.6 +/- 16.9 to 42.4 +/- 8.3 mg/24 h (P less than 0.001). In 23 of 26 previously untreated patients the biochemical indices decreased to the normal range (complete response). A reduction of 50% or more without reaching the normal range was observed in the other 3 patients (partial response). Actuarial analysis of the duration of the effect 12 months after stopping APD disclosed that 63% of patients who had achieved a complete response but only 23% of those with a partial response were in biochemical remission. A second course of APD was administered to 11 patients. The results were as effective during the second as the first course in 9 patients, whereas 2 patients had no response to retreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy of the bisphosphonate APD in the control of Paget's bone disease. 409 79

15 patients with Paget's bone disease were treated with varying schedules of porcine (3.8-157.5 MRCU/kg per wk) and/or salmon (1.5-210 MRCU/kg per wk) calcitonins over periods ranging from 4 to 24 months. All of the subjects experienced a striking decrease in serum alkaline phosphatase during the first 4 months of treatment. In six patients, however, resistance to these peptides was suggested by a subsequent elevation of alkaline phosphatase activity in spite of continued and augmented hormone administration. These rebounds in alkaline phosphatase levels correlated with the appearance of calcitonin-binding substances and neutralizing material in serum. Incubations of calcitonins-(125)I and sera from these six subjects resulted in the association of radioactivity with material whose behavior on chromatoelectrophoresis (6/6), sucrose density ultracentrifugation and immunoelectrophoresis (one subject) was identical with that of 7S immunoglobulin. Specific, reversible in vitro binding of salmon calcitonins-(125)I was observed in sera obtained from these patients 5 to 12 months after initiation of salmon calcitonin therapy. All six of these subjects' sera acquired the capacity to neutralize salmon calcitonin's hypocalcemic effect in rat bioassay. Neutralization titers correlated with maximal binding capacities, which ranged from 0.042 to 6.6 mg/liter of serum. Competitive displacement of calcitonins-(125)I from the sera of one patient treated with both porcine and salmon calcitonin indicated separate populations of antibodies to these hormones. In spite of return of disease activity comparable to baseline levels, 3/5 resistant subjects treated with salmon calcitonin failed to develop hypocalcemia after injection of 300-1000 MRCU of salmon calcitonin, but two of these patients developed hypocalcemia in response to the porcine hormone. The disappearance of total radioactivity from the circulation after intravenous administration of salmon calcitonin-(125)I was retarded and the amount of serum radioactivity precipitable in 50% (NH(4))(2)SO(4) greater in 3/3 resistant patients compared to control subjects. These observations on the incidence of significant titers of neutralizing antibodies to salmon (40%) and porcine (66%) calcitonins during their chronic (> 4 months) administration to man clearly indicate that an appraisal of this possibility be included in studies involving protracted use of these hormones.
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PMID:Calcitonin resistance: clinical and immunologic studies in subjects with Paget's disease of bone treated with porcine and salmon calcitonins. 467 98

A second potent plasma calcium-lowering peptide, katacalcin (PDN-21), flanks calcitonin within the human calcitonin precursor. Plasma katacalcin was present in 57 healthy volunteers. Concentrations were higher in males than in females and approximately equimolar with calcitonin. Plasma katacalcin doubled within 5 min of calcium infusion. Plasma katacalcin was markedly raised in 20 patients with medullary carcinoma of the thyroid. Measurement of plasma katacalcin concentrations may prove useful in the diagnosis and follow-up of this condition. Katacalcin, like calcitonin, may be involved in both plasma calcium regulation and skeletal maintenance and thus may prove useful in the treatment of bone disease.
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PMID:Katacalcin: a new plasma calcium-lowering hormone. 613 80

Patients with Paget's disease of bone were found to have elevated serum levels of type I procollagen carboxyterminal peptide (pColl-I-C) which correlated with other measurements of disease activity. The elevated levels of pColl-I-C decreased within hours after the injection of salmon calcitonin and within weeks after oral dichloromethylene diphosphonate treatment. The decrease in serum pColl-I-C after a single injection of salmon calcitonin was associated with a decrease in urinary hydroxyproline excretion, both of which rose toward pretreatment values within 7 h. The pColl-I-C levels remained normal for months after dichloromethylene diphosphonate therapy was discontinued. Using a RIA for the type III procollagen amino-terminal peptide (pColl-III-N), it was found that serum levels were also elevated in patients with Paget's disease. The levels of pColl-III-N also decreased after the injection of salmon calcitonin, but not to the same extent as those of pColl-I-C. After chronic therapy with dichloromethylene diphosphonate, serum levels of pColl-III-N decreased, but not into the normal range. We postulate that whereas pColl-I-C is derived from synthesis of mineralized bone collagen, pColl-III-N is derived from the loose fibrous stroma replacing marrow in areas closely associated with active Pagetic bone disease.
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PMID:Serum levels of type I and III procollagen fragments in Paget's disease of bone. 622 28


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