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)

A case of idiopathic myelofibrosis (IMF) presenting with hypercalcemia and hypercalcitriolemia is reported. It is proposed that ectopic production of the active vitamin D metabolite related to ongoing clonal expansion in the bone marrow accounts for the hypercalcemic state. Consistently low levels of circulating type I procollagen propeptide (PICP) and lack of progression of the bone marrow fibrosis during almost 6 months of follow-up point to an in vivo inhibition of type I collagen synthesis by 1,25-dihydroxyvitamin D3.
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PMID:Hypercalcemia in idiopathic myelofibrosis: modulation of calcium and collagen homeostasis by 1,25-dihydroxyvitamin D3. 154 20

Clodronate, one of the most investigated bisphosphonates, has been clinically utilised for over 10 years in malignancy. It is the most used, most effective and safest drug in the treatment of hypercalcaemia. It inhibits lytic bone destruction, prevents bone fractures and relieves bone pain. Supportive clodronate therapy may even reduce hypercalcaemia mortality and the morbidity caused by osteolysis. These results have stimulated studies on the patients' quality of life. New methods for the measurement of bone resorption, such as the degradation product of type I collagen (ICTP), may improve the possibility of monitoring the effect of clodronate. Comparative studies with different bisphosphonates in hypercalcaemia and long-term controlled trials using bisphosphonates as supportive therapy in osteolysis due to malignancy are reviewed.
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PMID:Clodronate and other bisphosphonates as supportive therapy in osteolysis due to malignancy. 754 30

The effects of chronic GH and insulin-like growth factor-I (IGF-I) excess on bone metabolism were examined by measuring serum markers of bone formation and urine markers of bone resorption as well as vertebral bone densities in patients with active acromegaly. Fasting serum GH levels were elevated in all 27 patients (31 +/- 11 micrograms/L). Serum calcium levels were within the normal range, except in 3 of 27 (10%) patients with mild hypercalcemia. Urinary calcium excretion, however, was increased in 6 (22%) patients despite mainly normal serum PTH and 1,25-dihydroxyvitamin D levels, suggesting a direct renal GH and/or IGF-I-mediated calciuric effect. Urinary hydroxyproline/creatinine excretion was increased in all except 1 patient and correlated with plasma IGF-I levels (r = 0.49; P < 0.02; n = 22). A more specific indicator of bone collagen turnover, urinary type I collagen cross-linked N-telopeptide, was elevated in all except 1 patient and correlated with serum GH (r = 0.47; P < 0.02), IGF-I (r = 0.60; P < 0.005), and urinary hydroxyproline/creatinine excretion (r = 0.62; P < 0.001). Serum bone Gla protein (osteocalcin), a specific marker of osteoblastic activity, was also increased in 50% of the patients and correlated with urinary N-telopeptide (r = 0.47; P < 0.02), but not with serum GH or IGF-I concentrations. Trabecular bone density, as determined by quantitative computerized tomography of the lumbar spine, was increased in only 1 patient; 13 others had subnormal bone density. The results suggest that in long-standing acromegaly, osteoblastic and osteoclastic activities are increased. Vertebral trabecular bone mass is usually reduced. Urinary collagen cross-links may serve as a more specific marker of bone resorption in acromegaly.
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PMID:Biochemical assessment of bone formation and resorption in acromegaly. 850 Nov 50

In our previous double-blind trial, we reported that clodronate reduced the incidence of bone lesions, fractures, pain and hypercalcaemia in multiple myeloma. Recently, it has been assumed that the antiresorptive effect of bisphosphonates on the osteoclasts is mediated through the osteoblasts. We therefore determined, in 244 patients of the same trial, serum assays of aminoterminal propeptide of type I procollagen (PINP) and type I collagen degradation product (ICTP). PINP is an early synthesis product of proliferating osteoblasts, in comparison to the alkaline phosphatase (AP) which is secreted by differentiated osteoblasts during the maturation phase of collagen. ICTP circulates in serum when old bone is resorbed. Our results indicate that after 25 months, the PINP levels decreased in the clodronate group (from 68.9 +/- 4.4 micrograms/l to 37.2 +/- 3.5 micrograms/l; P < 0.001) but not in the control group (from 61.5 +/- 3.2 micrograms/l to 69.3 +/- 7.5 micrograms/l; P < NS). The fall in the ICTP levels was markedly steeper in the patients receiving clodronate (from 8.38 +/- 0.80 micrograms/l to 4.58 +/- 0.32 micrograms/l; P < 0.01) than placebo (from 7.84 +/- 0.53 micrograms/l to 6.45 +/- 0.95 micrograms/l; P = NS). A significant difference between the study groups was seen at 4 months in the PINP, at 7 months in the ICTP and at 13 months in the AP levels, suggesting that clodronate affected through the proliferating osteoblasts, the osteoclasts, and through the osteoclasts, the differentiated osteoblasts. High baseline ICTP, PINP and AP levels indicated a poor prognosis. The decrease of the markers by clodronate was more marked in survivors than in non-survivors.
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PMID:Monitoring the action of clodronate with type I collagen metabolites in multiple myeloma. 875 48

The purpose of the present study was to evaluate the serum levels of two new markers, and to compare their clinical usefulness with two conventional markers. Healthy women and patients with aberrant bone metabolism were evaluated for serum or urine levels of different bone markers. We measured serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (S-ICTP) and carboxy-terminal propeptide of type I procollagen (S-PICP) as markers of bone resorption and formation, respectively. These levels were compared to the concentrations of serum bone gamma-carboxyglutamic acid protein (S-BGP) and total urinary pyridinium cross-links (U-PYD). The control group included 222 premenopausal and postmenopausal women, and the disease groups consisted of 61 individuals with malignancy-associated hypercalcemia, Graves' thyrotoxicosis or primary hyperparathyroidism. Both S-PICP and S-BGP reflected higher bone turnover in postmenopausal than premenopausal women. All patient groups had significantly higher S-ICTP and U-PYD than the controls. Increased S-PICP was seen in malignancy-associated hypercalcemia and Graves' thyrotoxicosis, but not in primary hyperparathyroidism, while higher S-BGP was seen in Graves' thyrotoxicosis and primary hyperparathyroidism, but not in malignancy-associated hypercalcemia. Discrepancy between S-PICP and S-BGP in malignancy-associated hypercalcemia and primary hyperparathyroidism was noted. S-ICTP and U-PYD had higher sensitivity and specificity in discriminating patients from controls. We conclude that S-ICTP is superior to U-PYD as an index of bone resorption in aberrant bone metabolism. S-PICP may also be a useful bone turnover marker but discrepancies between it and S-BGP in malignancy-associated hypercalcemia and primary hyperparathyroidism need further investigation.
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PMID:Type I collagen and procollagen fragments in patients with metabolic bone diseases. 884 Jul 53

Significant bone mass reduction occurs in stroke patients on the hemiplegic side compared with the intact side, correlating with the degree of paralysis and vitamin D deficiency. To evaluate the influence of long-standing immobilization on this osteopenia, we measured various serum markers of bone metabolism in 93 hemiplegic elderly patients with a long-standing stroke and in 37 controls. The bone mineral density (BMD) of the second metacarpal was determined bilaterally. The scoring of the stroke patients activity was based on the Barthel Index (BI). The serum ionized calcium was higher in the patients than in the controls, correlating negatively with the BI in the patients. The concentrations of parathyroid hormone (PTH), pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen and bone Gla protein were normal or low. The serum 25-hydroxyvitamin D level was low in the patients, correlating positively with the BMD on both sides. The serum 1,25-dihydroxyvitamin D (1,25-[OH]2D) level was markedly reduced in the patients. Hemiplegia from a stroke can result in immobilization hypercalcemia which inhibits PTH secretion and 1,25-[OH]2D production. Bone remodelling may have almost reached an equilibrium, resulting in a steady rate of bone loss. This and the hypovitaminosis D appear to be the dominant causes of immobilization-induced osteopenia in elderly, long-standing hemiplegic stroke patients.
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PMID:Influence of immobilization on bone mass and bone metabolism in hemiplegic elderly patients with a long-standing stroke. 1022 20

We measured the levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) and carboxyterminal parothyroid hormone-related protein (C-PTHrP) in serum of patients with hematological malignancies. ICTP and C-PTHrP levels in serum of multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) and adult T-cell leukemia (ATL) patients with bone lesions and hypercalcemia were significantly higher than those of patients without bone lesions and hypercalcemia. ICTP and C-PTHrP levels in ATL were significantly higher than in MM and NHL. There was a correlation between ICTP and C-PTHrP in serum of ATL patients, but no correlation in MM and NHL. Serum ICTP levels tended to correlate with serum beta 2-microglobulin and survival in patients with MM. Therefore, ICTP and C-PTHrP levels in serum may be useful in the diagnosis of bone lesions and hypercalcemia in hematological malignancies. In particular, ICTP may be a useful bone resorption marker in MM.
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PMID:[Serum levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) and carboxyterminal parathyroid hormone-related protein (C-PTHrP) in hematological malignancies with bone lesions and hypercalcemia]. 959 94

Significant reduction in bone mineral density (BMD) occurs in stroke patients on the hemiplegic and contralateral sides, correlating with the degree of paralysis and vitamin D and K deficiency due to malnutrition, and increasing the risk of hip fracture. We evaluated the efficacy of vitamin K2 (menatetrenone: menaquinone-4; MK-4) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients. In a random and prospective study, of 108 hemiplegic patients following stroke, 54 received 45 mg menatetrenone daily (MK-4 group, n = 54) for 12 months, and the remaining 54 (untreatment group) did not. Nine patients excluded from the study. The BMD in the second metacarpals and serum indices of bone metabolism were determined. BMD on the hemiplegic side increased by 4.3% in the MK-4 group and decreased by 4.7% in the untreated group (p < 0.0001), while BMD on the intact side decreased by 0.9% in the MK-4 group and by 2.7% in the untreated group (p < 0.0001). At baseline, patients of both groups showed vitamin D and K1 deficiencies, high serum levels of ionized calcium, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), and low levels of parathyroid hormones (PTH) and bone Gla proteins (BGP), indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D) and compensatory PTH secretion. Both vitamins K1 and K2 increased by 97.6% and 666.9%, respectively, in the MK-4 group. Correspondingly, a significant increase in BGP and decreases in both ICTP and calcium were observed in the MK-4 group, in association with a simultaneous increase in both PTH and 1, 25-[OH]2D. One patient in the untreated group suffered from a hip fracture, compared with none in the MK-4 group. The treatment with MK-4 can increase the BMD of disused and vitamin D- and K-deficient hemiplegic bone by increasing the vitamin K concentration, and it also can decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1, 25-[OH]2D concentration.
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PMID:Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients. 973 52

A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side, correlating with the degree of paralysis and vitamin D deficiency due to malnutrition, sunlight deprivation, and immobilization-induced hypercalcemia, and increases the risk of hip fracture. We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [1alpha(OH)D3; vitamin D3] administration on bone mineral density preservation as compared with untreated controls. In a randomized and prospective study of 103 patients with hemiplegia after stroke (the mean duration of illness was 4.8 yr), 68 (34 patients in each group) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo, whereas the remaining 35 patients received no drug. Bone mineral density on the hemiplegic side decreased by 1.4% in the ipriflavone group, 3.8% in the vitamin D3 group, and 5.4% in the control group (P < .0001, ipriflavone v vitamin D3 and control). At baseline, all three groups of patients showed a 25-hydroxyvitamin D insufficiency, increased serum ionized calcium, and low levels of 1, 25-dihydroxyvitamin D, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1, 25-dihydroxyvitamin D. After treatment, the serum 1, 25-dihydroxyvitamin D level increased by 139.9% in the ipriflavone group and by 26.9% in the vitamin D3 group. Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group, whereas no changes occurred in the other two groups. One patient in the untreated group suffered a hip fracture, compared with none in the ipriflavone and vitamin D3 groups. These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1, 25-dihydroxyvitamin D concentration.
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PMID:Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D. 2935 Nov 3

Advanced tumor osteopathy is characterized by abnormal bone turnover. Using a rat model of parathyroid hormone-related peptide (PTHrP)-mediated tumor osteolysis, the aim of the present study was to define the sequential changes in, and the association between, biochemical and histomorphometric indices of bone metabolism during the early stages of developing tumor osteopathy. Eight-month-old Wistar rats (n = 48) were subcutaneously inoculated with either 2 x 10(6) cells of the Walker carcinosarcoma 256, or saline on day 0, and treated with either saline or the bisphosphonate ibandronate until killing on day 8. Serum calcium (sCa), alkaline phosphatase (sTAP), and osteocalcin (sOC) and urinary calcium (uCa), deoxypyridinoline (uDPD), and pyridinoline (uPYD) were measured daily. In a second semilongitudinal experiment (n = 70), the number of osteoclasts and osteoblasts (N.Oc, N.Ob), trabecular bone volume (BV/TV), and osteoid volume (O.Ar) were assessed by histomorphometry. In untreated tumor-bearing animals, osteoclast numbers increased by 74% on day 3 (5.4 +/- 2.4 vs. 3.1 +/- 1.5/mm(2), p < 0.05), and trabecular bone volume fell by 24% on day 4 (12.5 +/- 2.0 vs. 15.8 +/- 1.2%, p < 0.05). Both time course and magnitude of these changes were closely reflected by an increase in uDPD (0.46 +/- 0.14 vs. 0. 31 +/- 0.15 nmol/12 h, p < 0.05) and uPYD on day 4 (1.44 +/- 0.25 vs. 1.03 +/- 0.3 nmol/12 h, p < 0.05), sCa (3.8 +/- 0.52 vs. 3.0 +/- 0. 13 mmol/L, p < 0.01), and uCa (0.13 +/- 0.08 vs. 0.03 +/- 0.01 mmol/12 h, p < 0.001) on day 6, and sTAP (254 +/- 127 vs. 120 +/- 40 U/L, p < 0.001) on day 7 (mean +/- SD), whereas sOC remained unchanged until day 8. When combining the results of the two experiments, a high correlation was found between the number of osteoclasts and the urinary excretion of PYD (r = 0.91) and DPD (r = 0.89). Treatment with ibandronate delayed hypercalcemia, abolished hypercalciuria, and accelerated bone resorption. We conclude that osteoclast activation is an early event in PTHrP-mediated osteolysis, which is closely reflected by the renal excretion of pyridinium cross-links of type I collagen. Therefore, specific biochemical markers of collagen breakdown may be useful as early indicators of developing tumor osteopathy.
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PMID:Association between histomorphometry and biochemical markers of bone turnover in a longitudinal rat model of parathyroid hormone-related peptide (PTHrP)-mediated tumor osteolysis. 1077 87


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