Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapid detection of the exact changes in bone remodelling is exceptionally important. In this paper, the latest bone remodelling biochemical markers are reviewed. Some of them have already been used for a long time, and their utility has been widely demonstrated. The newest ones, in experimental stage, can be used as a complement to the others. The bone remodelling markers reviewed are: 1) Alkaline phosphatase; 2) osteocalcin; 3) Other noncollagen of bone matrix such as osteonectin, GLA-protein of the matrix, osteopontine and alpha 2-HS-glycoprotein; 4) Procollagenous and other collagenous peptides of the matrix (C terminal of type-I procollagen and urinary elimination of nondialysis hydroxyproline. Amongst the bone resorption markers studied are: 1) Calcium/creatinine urinary quotient; 2) Tartrate resistant acid phosphatase; 3) Urinary hydroxyproline; 4) Other substances derived from collagen disruption such as hydroxilysin glycoside, piridinolinic intermolecular bridges and the enzymatic activity of proline iminopeptidase. We endeavoured to collect all the most important references on the matter, especially those relating to Paget's disease of the bone, primary hyperparathyroidism, tumoral hypercalcemia and postmenopausal osteoporosis.
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PMID:[The usefulness of biochemical markers of bone remodelling in the diagnosis and follow-up of Paget's disease of bone, primary hyperparathyroidism, tumoral hypercalcemia and postmenopausal osteoporosis. I. The markers of bone formation]. 210 91

Rapid detection of the exact changes in bone remodelling is exceptionally important. In this paper, the latest bone remodelling biochemical markers are reviewed. Some of them have already been used for a long time, and their utility has been widely demonstrated. The newest ones, in experimental stage, can be used as a complement to the others. The bone remodelling markers reviewed are: 1) Alkaline phosphatase; 2) osteocalcin; 3) other noncollagen of bone matrix such as osteonectin, GLA-protein of the matrix, osteopontine and alpha 2-HS-glycoprotein; 4) Procollagenous and other collagenous peptides of the matrix (C terminal of type I procollagen and urinary elimination of non-dialysis hydroxyproline. Amongst the bone resorption markers studied are: 1) Calcium/creatinine urinary quotient; 2) Tartrate resistant acid phosphatase; 3) Urinary hydroxyproline; 4) Other substance derived from collagen disruption such as hydroxylysine glycoside, piridinolinic intermolecular bridges and the enzymatic activity of proline iminopeptidase. We endeavored to collect all the most important references on the matter, especially those relating to Paget's disease of the bone, primary hyperparathyroidism, tumoral hypercalcemia and postmenopausal osteoporosis.
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PMID:[Usefulness of bone remodelling biochemical markers in the diagnosis and follow-up of Paget's bone disease, primary hyperparathyroidism, tumor hypercalcemia, and postmenopausal osteoporosis. II. Bone resorption markers]. 210 1

Treatment with 1,25-(OH)2D3 (calcitriol) was compared with placebo in a double-blind, randomized, parallel clinical trial of 24 months' duration. Subjects were white women with postmenopausal osteoporosis. The study was completed by 15 patients who received placebo and 12 patients who received calcitriol. Positive slopes were observed in the active treatment group for total body calcium, bone mineral content of the radius, bone mineral density of the lumbar spine, and radiographic absorptiometry of the middle phalanges. In contrast, negative slopes were observed for the bone mineral measurements in the placebo group. Measurement of urinary hydroxyproline and of serum alkaline phosphatase and osteocalcin suggested that the mechanism of action of 1,25-(OH)2D3 involved reduction of bone resorption. Hypercalciuria occurred regularly and preceded hypercalcemia by about 2 weeks. A decline in creatinine clearance was observed in two patients, one of whom had nephrolithiasis on sonography. Calcitriol is effective in preventing bone loss, but must be used with caution.
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PMID:Role of calcitriol in the treatment of postmenopausal osteoporosis. 218 76

We have previously shown that cyclosporin A (CsA) produces high bone remodeling with resorption exceeding formation and loss of bone volume in the rat. This may have important clinical implications where CsA is widely used in organ transplantation. 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is a bone mineralizing hormone which also has immune modifying properties. Consequently, we studied the effect of combined CsA and 1,25(OH)2D3 administration over 28 days in four groups of rats. Group A received vehicle (n = 10), group B CsA (15 mg/kg) (n = 10) alone, group C 1,25(OH)2D3 plus CsA (n = 15), and group D 1,25(OH)2D3 alone (20 ng/100 g) (n = 15). Rats were bled periodically at day 0, 7, 14, and 28 and Ca, parathyroid hormone (PTH), 1,25(OH)2D, osteocalcin (bone Gla-protein, BGP), BUN, and creatinine were measured. Rats were sacrificed on day 28 and bones were examined histomorphometrically. Compared to controls, CsA resulted in significant elevation of BGP and a transient increase in 1,25(OH)2D with excess bone remodeling and loss of bone volume. 1,25(OH)2D3 administration produced hypercalcemia, a significant rise in BGP, with suppression of PTH and increased osteoid volume. Combined therapy prevented the loss of bone volume probably due to increased osteoid tissue and enhanced osteoblast activity. Renal dysfunction, a side-affect of CsA, was not a factor. In conclusion, 1,25(OH)2D3 combined with CsA restores bone volume which is accompanied by increases in serum calcium and BGP.
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PMID:1,25 Dihydroxyvitamin D3 modifies cyclosporine-induced bone loss. 222 90

The signification of serum bone Gla protein (serum BGP, osteocalcin) has been investigated in multiple myeloma. As a first step, quantitative iliac crest bone biopsies were performed in 19 patients; the serum BGP levels strongly correlated with histologic parameters of bone formation (r = 0.72-0.84, P less than 0.001) but not with those of bone resorption (r = 0.10). These results confirm that serum BGP is a marker of bone formation in multiple myeloma, as previously described in many other bone disorders. As a second step, serum BGP was measured in 117 patients with multiple myeloma as a systemic indicator of the degree of bone formation. Twenty-one percent of the patients had abnormal serum BGP levels (25 cases). The 14 patients with increased values (mean, 13.2 +/- 2.7 ng/ml) and thus increased bone formation belonged to a subgroup characterized by a lower osteolytic potential and a more indolent disease. On the other hand, the 11 patients with decreased values (mean, 1 +/- 0.3 ng/ml) and thus reduced bone formation had an advanced disease, extensive lytic bone lesions, a hypercalcemia frequently and a poor survival (mean, 4 months; range, 1-12). The biochemical investigations of the whole patient population, including serial studies in individual patients, have shown a large scatter of serum BGP levels, suggesting major differences in the bone formation rates. However, an overall inverse correlation was found between serum BGP and osteolytic potential. These results have confirmed the important role of the inhibition of bone formation in the occurrence of bone lesions in multiple myeloma and the interest of serum BGP to select a myeloma patient subgroup with low osteolytic potential and characterized by abnormally increased levels of this marker.
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PMID:Abnormal serum bone Gla protein levels in multiple myeloma. Crucial role of bone formation and prognostic implications. 235 3

We evaluated the serum osteocalcin and alkaline phosphatase levels and the urinary hydroxyproline excretion in patients with blastic, lithic or mixed metastases, humoral malignant hypercalcemia (HMH) and myeloma. In patients with metastasis of any type osteocalcin did not reach a significant increase although in blastic metastases an increase approaching signification was observed. However, the sensitivities of alkaline phosphatase or hydroxyproline were much higher. In HMH hydroxyproline increased to levels similar to those found in primary hyperparathyroidism. By contrast, although osteocalcin had a significant increase, its values were much lower than in parathyroid disease. The changes in alkaline phosphatase were nonevaluable. In myeloma none of the three markers changed. The major conclusion of the present study is that osteocalcin has little practical usefulness for the investigation of neoplastic patients.
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PMID:[Bone turnover markers in tumor pathology with bone involvement]. 235 62

Male Copenhagen rats were inoculated with monodispersed R3327-MatLyLu prostate tumor cells via the tail vein under concomitant temporal occlusion of the inferior vena cava to develop an animal model for skeletal metastasis of prostate cancer. This procedure reproducibly resulted in metastatic tumor growth in the lumbar region of the vertebral column. Microscopically, tumor growth became visible in the fifth and sixth lumbar vertebrae within 4 days after inoculation. Clinical signs of nerve function disablement (hind leg paresis and paralysis) followed within 14 days of such a procedure. Cell culture technique confirmed the presence of a viable, proliferating tumor cell population within the spinal canal of the fifth and sixth lumbar vertebrae. Histologically, a clear response of osteoclastic and concomitant osteoblastic activities was observed in the lumbar spinal column. In the serum, a transient phase of hypercalcemia could be demonstrated. The development of skeletal metastases in these animals was not reflected by significant alteration in serum levels of acid phosphatase, prostatic-specific antigen, or osteocalcin. These observations support the concept of the vertebral venous plexus being involved in the dissemination of prostate tumor cells. The surgical procedures described permit experimental investigations of bone metastasis of prostatic cancer.
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PMID:Prostatic tumor (R3327) skeletal metastasis. 237 Nov 74

MC-903 is a novel vitamin D analogue which has been shown to promote epidermal cell differentiation but is 100 times less active than 1,25 dihydroxyvitamin D3 (1,25(OH)2D) in causing hypercalcemia. In order to determine the activity of this compound on bone cells, we have compared the effects of MC-903 and 1,25 dihydroxyvitamin D3 (1,25(OH)2D) on parameters of cell proliferation and differentiation in cultured normal human osteoblastic cells derived by migration from trabecular bone fragments. Dose response curves showed that MC-903 was 10 to 100 times less effective than 1,25(OH)2D in stimulating the synthesis of the osteoblast specific protein osteocalcin by human bone cells depending on the basal osteocalcin production. In cells showing high basal osteocalcin synthesis, 1,25(OH)2D (10(-8) M) was 2- to 3-fold more potent than MC-903 (10(-8) M) in inducing osteocalcin from 48 to 96 h of treatment. The greater activity of 1,25(OH)2D over MC-903 was observed in human bone cell cultures with elevated basal osteocalcin levels, indicating that the response to 1,25(OH)2D but not to MC-903 was amplified in cells with the higher osteoblastic characteristics. The effects of MC-903 and 1,25(OH)2D on alkaline phosphatase activity were not markedly different. Transforming Growth Factor-beta (TGF beta) (0.5 ng/mL, 48 h) was found to completely suppress the osteocalcin synthesis induced by 1,25(OH)2D (10(-8) and 10(-9) M), whereas the MC-903-induced osteocalcin synthesis was not affected, suggesting a negative interaction between TGF beta and 1,25(OH)2D but not MC-903 on osteocalcin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of a novel vitamin D analogue MC-903 and 1,25-dihydroxyvitamin D3 on alkaline phosphatase activity, osteocalcin and DNA synthesis by human osteoblastic cells in culture. 239 Mar 75

Bone metastasis is one of the characteristic behavior of recurrent breast cancer. Usually, X-ray detect and/or bone scintigraphy are used to evaluate bone metastasis. However, false positive cases are occasionally encountered in these modalities. This is a report of the results from the measurement of serum osteocalcin (OC) in breast cancer with bone metastasis. OC is one of the protein dependent on Vitamin K. The results were as follows: 1) Serum levels of OC in 56 patients with primary breast cancer were measured. The mean level of serum OC was significantly higher than that in patients with benign breast disease. But the comparisons in each stage were not statistically significant. 2) The mean serum OC level in patients of primary breast cancer with bone metastasis was higher than that in breast cancer without bone metastasis (p less than 0.05). This was remarkable in the patients of recurrent breast cancer (p less than 0.01). 3) Serum OC levels in bone metastasis patients were increased in group with normocalcemia, while it was normal or decreased in that with hypercalcemia. There was no significant correlation between either serum OC and ALP values, or between serum OC and serum Ca values. The slight positive and reverse correlation were observed between OC and ALP, OC and sCa, respectively. 4) In many cases with bone metastasis, serum OC levels were elevated before bone lesions were detected by bone scintigraphy. 5) In advanced stage of the patients with bone metastasis and hypercalcemia, serum OC level decreased. The increased level of serum OC was maintained when high dose of calcitonin was administered.
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PMID:[Clinical evaluation of serum osteocalcin in patients with bone metastasis of breast cancer]. 261 77

Carbetimer is a new antineoplastic agent whose limiting toxicity consists of dose- and treatment duration-dependent hypercalcemia. We examined the short-term effects of Carbetimer on calcium metabolism on days, 1, 3 and 5 during 11 5-day courses (6.5-8.2 g/m2/day given over daily 2-h infusions, q 3-4 weeks). Blood parameters were measured before and after Carbetimer, whereas urinary parameters were studied in three consecutive 2-h collections before, during and after Carbetimer infusions. Carbetimer effects were similar regardless of the infusion day. We found a consistent decrease of plasma ionized Ca (Ca2+) levels from 4.56 +/- 0.05 mg/dl before infusion to 4.28 +/- 0.06 mg/dl after infusion (P less than 0.001) whereas total serum Ca (corrected for protein levels) did not change. The fall of Ca2+ stimulated parathyroid function, as suggested by the increased plasma PTH levels, the decreased serum phosphorus and TmP/GFR index, or the increased urinary phosphate and cyclic AMP excretion. Carbetimer infusions also induced a marked increase in urinary Ca excretion (expressed as mg Ca/mg creatinine) from 0.093 +/- 0.011 before to 0.359 +/- 0.042 during and 0.177 +/- 0.031 after infusion (P less than 0.011). These changes were best explained by Carbetimer-induced Ca chelation that we confirmed in vitro by incubating Carbetimer at various concentrations in whole blood for 2 h at 37 degrees C, e.g. 2 mg of Carbetimer/ml lowered Ca2+ from 4.82 to 3.20 mg/dl without changing total Ca levels. On the other hand, a direct effect of Carbetimer on bone cannot be excluded since we observed an increase of serum osteocalcin levels from 2.0 +/- 0.3 to 2.5 +/- 0.4 ng/ml after infusion (P less than 0.001). In summary, the short-term effects of Carbetimer on calcium metabolism markedly differ from the long-term effects. They mainly consist of a dose-related calcium chelation leading to a decrease in Ca2+ levels, an increase in urinary Ca excretion and a stimulation of parathyroid function.
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PMID:Short-term effects of Carbetimer on calcium and bone metabolism in man. 263 64


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