Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nineteen patients with Paget's disease and four patients with hypercalcemia of malignancy underwent hypocalcemic therapy with etidronate disodium (etidronate) administered intravenously. The dosage for patients with Paget's disease was 4.3 mg/kg/day, infused on each of seven consecutive days. Nine of the 19 patients also received oral etidronate 5 mg/kg/day for three months after administration of intravenous therapy. Etidronate administered orally sustained the decreases in urinary hydroxyproline produced by the infusions, whereas levels returned to pretreatment values in most patients receiving only the intravenously administered drug. Serum alkaline phosphatase levels were not reduced in the 10 patients receiving only intravenously administered etidronate, but they declined by approximately 50 percent in the nine patients who received the additional orally administered etidronate. Transiliac-crest bone biopsy specimens obtained three months after intravenous therapy revealed a regular lamellar structure, compared with the characteristic woven pattern of pagetic bone. In all four patients with hypercalcemia of malignancy, normocalcemia was achieved by the 10th day of treatment using a dosage of 4.3 mg/kg/day. Oral etidronate therapy was beneficial in maintaining normocalcemia.
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PMID:Intravenous disodium etidronate therapy in Paget's disease of bone and hypercalcemia of malignancy. Effects on biochemical parameters and bone histomorphometry. 310 38

A radioimmunoassay for circulating levels of the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP) was developed and can be available as a kit on a commercial base. Using the kits, we evaluated basically and clinically the assay. The assayed values were reproducible and the assay can detect as low as 0.5 ng/ml of 1CTP. In healthy volunteers, circulating level was high under age 24 and over age 46. In patients with bone metastasis, serum levels elevated even in its early stage and correlated well with clinical status. In other bone diseases, such as primary hyperparathyroidism, hyperthyroidism, post-gastrectomy, hypercalcemia of malignancy and myeloma, serum levels elevated according to their clinical conditions. In patients with chronic renal failure, serum levels were high, suggesting decrease of renal clearance of 1CTP. The circulating 1CTP levels seemed to reflect well clinical bone destructive status. A high correlation between serum 1CTP level and urinary pyridinoline (r = 0.884) was shown, whereas essentially no correlation was observed between bone formation markers such as osteocalcin and alkaline phosphatase. Thus, the measurement of circulating 1CTP seems to be a simple and sensitive method to monitor bone destruction.
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PMID:[Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP)--some basic aspects of the RIA kit and clinical evaluation in various bone diseases]. 827 4

Parathyroid hormone-related peptide (PTHrP) induces pathological bone resorption in an endocrine manner, resulting in hypercalcemia of malignancy. However, the histopathological aspect of the action of PTHrP secreted by tumor cells on bone resorption has not well been documented. Therefore, we studied cell-cell interactions between bone cells, stromal cells, and PTHrP-secreting tumor cells (EC-GI-10) morphologically. Tumor cells injected subcutaneously into the parietal region formed a tumor mass, invading the bone marrow. The tumor mass was surrounded by a membrane structure consisting of stromal cells. These stromal cells were positive for alkaline phosphatase (ALPase). Tartrate-resistant acid phosphatase (TRAPase)-positive osteoclasts were localized close to the ALPase-positive cells, and numerous osteoclasts were observed on the neighboring bone surfaces. PTHrP, vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-9 were detected in the tumor cells. Using RT-PCR, expression of interleukin (IL)-1Alpha, IL-1Beta, and PTHrP, which are strong bone resorption factors, was detected in the tumor cells. Some ALPase-positive cells localizing on the neighboring bone surfaces and endothelial cells revealed PTH/PTHrP receptor immunoreactivity. Ultrastructurally, numerous blood vessels were observed between the tumor nests and the stromal cells. The nests were surrounded by a basement membrane, but it was discontinuous, therefore permitting direct contact between the tumor cells and the stromal cells. These results indicate that PTHrP secreted by tumor cells appears to stimulate osteoclast differentiation and bone resorption in a paracrine manner through PTH/PTHrP receptor-immunopositive cells. IL-1Alpha, IL-1Beta, VEGF, and MMP-9 may also be involved in facilitating osteoclast formation and the subsequent bone resorption.
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PMID:Ultrastructural and cytobiological studies on possible interactions between PTHrP-secreting tumor cells, stromal cells, and bone cells. 1458 91

Bisphosphonate therapy is a common and effective treatment for Paget's disease of bone, osteoporosis, hypercalcemia of malignancy and cancer metastatic to bone. Clinically significant hypocalcemia has not been reported in patients with Paget's disease of bone and normal parathyroid function treated with an aminobisphosphonate. We treated a 52-year-old woman with polyostotic Paget's disease of bone (serum alkaline phosphatase level-1971 IU/L [normal 31-110 IU/L]), who had not previously received bisphosphonates, with daily oral 30 mg risedronate, oral 1000 mg elemental calcium and oral 400 IU cholecalciferol. After 10 days of treatment, she developed severe hypocalcemia (5.4 mg/dL [normal 8.7-10.2 mg/dL]), requiring hospitalization and support with 5 days of intravenous calcium gluconate. On the day risedronate treatment began, her PTH was low normal at 14 pg/mL (normal 12-72 pg/mL), consistent with a relatively suppressed PTH axis due to high bone turnover. Her vitamin D level was within normal limits (serum 25(OH)D 19 ng/mL [normal 8-38 ng/mL]), although possibly not optimally repleted. We hypothesize that this case represents an example of hungry bone syndrome in a patient with extensive Paget's disease of bone who received risedronate, causing acute suppression of bone resorption while elevated bone formation rates continued. In the year following her recovery, the patient was successfully treated with slowly titrated anti-resorptive therapy (subcutaneous calcitonin followed by titrated doses of risedronate), and is now clinically well. Physicians should be aware of the potential for hypocalcemia when patients with polyostotic Paget's disease and markedly elevated indicators of bone remodeling are initiated on powerful anti-resorptive therapy.
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PMID:Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone. 1676 64