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)

Prevention of postmenopausal osteoporosis is an alternative to the currently problematic goal of reversing the trabecular plate thinning and perforation that constitute the major pathologic defects in patients with established osteoporosis. 1,25(OH)2D3 (calcitriol) has been suggested as a drug that may decrease bone resorption sufficiently to preserve trabecular structure in perimenopausal women. In the present study, we compared the effects of calcitriol and an investigational analog, 1,25,26-(OH)3delta22-D3 (Ro-23-8525), to those of an inert vehicle in maintaining the bone mass of oophorectomized adult beagles. In these studies, we used dual-energy radiography to serially quantitate the bone density of control and treated animals. Treatment for 1 year with either agent resulted in no evidence of hypercalcemia or decreased renal function. Moreover, calcitriol and Ro-23-8525 effectively abolished the loss of bone mass observed in untreated oophorectomized controls. Indeed, treated animals displayed variations in bone density similar to that observed in sham-operated untreated animals. These data suggest that calcitriol and Ro-23-8525 may be potentially effective agents for prophylaxis of postmenopausal osteoporosis.
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PMID:Role of calcitriol in prevention of osteoporosis: Part I. 232 66

The growth and differentiation of epidermal cells in vitro show a marked dependence on the calcium concentration of the medium. In this study the effect of experimentally produced hyper- and hypocalcaemia on the rat epidermis in vivo has been investigated. Hypercalcaemia, induced by injections of calcium chloride, produced a decrease in epidermal labelling index and some epidermal thinning. On the other hand hypocalcaemia, induced by calcitonin, failed to lead to changes in these measurements. The diurnal variation in epidermal labelling index and serum calcium levels was also measured. Whilst the labelling index decreased considerably over the period 09.00 hours to 18.00 hours, no significant changes were observed in serum calcium. These results suggest that while, under certain circumstances in vivo, the epidermal cell shows the same sensitivity to calcium as it does in vitro, calcium is not a major regulator of epidermopoiesis.
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PMID:The effect of serum calcium levels on the rate of epidermal renewal in the rat. 654 May 96

The left thoracic limb was immobilized in a plaster cast in 6 grade weanling ponies for 6 weeks. Two ponies were injected intramuscularly each day with 2.4 micrograms of 25-hydroxycholecalciferol [25(OH)D3] per kg bodyweight, two with 1.2 micrograms and two received no injections. Immobilization of 25(OH)D3 treatment had no significant effect on mineral metabolism. Immobilization resulted in significantly decreased weight and specific gravity of metacarpus III (MCIII). Histologic examination and triple fluorochrome incorporation showed that the osteopenia was caused by atrophy of osteoblasts with failure of bone apposition. Immobilization caused retardation or cessation of proliferation of cartilage in the epiphyseal plate with thinning or premature closure. Treatment with 25(OH)D3 further reduced apposition and enhanced significantly the osteopenia as shown by quantitative morphometry of microradiographs of the MCIII metaphyses. There was parathyroid gland atrophy and fibrosis in proportion to the level of 25(OH)D3 treatment, which, in absence of hypercalcemia in all ponies, was interpreted to be a direct result of vitamin D treatment. It was concluded that immobilization osteopenia under the present design and duration is caused by failure of bone apposition and that treatment with 25(OH)D3 at dose levels applied is contraindicated.
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PMID:Mineral metabolism and immobilization osteopenia in ponies treated with 25-hydroxycholecalciferol. 714 Mar 1

We recently reported that mice treated with 1,25-dihydroxyvitamin D3 ( 1,25-(OH)2D3) or 19-nor-1,25-(OH)2D2 experienced a severe loss of their thymocytes and decreased proliferation in response to concanavalin A mitogen. The present study investigated the effect of short-term treatment with 1,25-(OH)2D3 on the thymic architecture and thymocyte subsets. Daily treatment with 1,25-dihydroxyvitamin D3 at 20 ng per mouse for 4 days induced significant involution of thymic tissue. The atrophy was predominantly observed in the cortical component. Flow cytometric analysis of thymocyte subsets showed that the CD4 + CD8 + population was the primary target. Since the treated mice experienced profound hypercalcemia, we studied the effect of 1,25-(OH)2D3 on animals fed a vitamin D-deficient, low calcium diet or the same diet containing vitamin D for 25 days prior to treatment. The low calcium fed mice showed severe hypocalcemia and slight thinning of thymic cortex. Treatment with 1,25-(OH)2D3 moderately improved the hypocalcemia but had no further effect on the thymus of these animals. On the other hand, hypercalcemia and thymic atrophy were found in the animals fed the diet containing vitamin D. Overall, the atrophy effect on the thymus caused by 1,25-(OH)2D3 treatment was prevented by eliminating the hypercalcemia observed in + D + Ca treated animals. Thus, thymic atrophy probably resulted from hypercalcemia and not from 1,25-(OH)2D3 itself.
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PMID:Effect of 1,25-dihydroxyvitamin D3 on mouse thymus: role of extracellular calcium. 860 Sep 85

Expansile skeletal hyperphosphatasia (ESH) is a singular disorder characterized in the year 2000 in a mother and daughter with early-onset deafness, premature loss of teeth, progressive hyperostotic widening of long bones causing painful phalanges in the hands, accelerated bone remodeling, and episodic hypercalcemia likely inherited as a highly penetrant, autosomal dominant trait. Absence of large osteolytic lesions with cortical thinning in major long bones, together with bouts of hypercalcemia, indicated that ESH is not a variant of familial expansile osteolysis (FEO). Here, we investigated the molecular basis of ESH after three families with FEO were reported to have an identical 18-base pair tandem duplication (84dup18) in the signal peptide sequence of the TNFRSF11A gene that encodes receptor activator of nuclear factor-kappaB (RANK). We find that ESH is caused by a remarkably similar 15-base pair tandem duplication (84dup15) in TNFRSF11A. Hence, ESH and FEO are allelic diseases and ESH, like FEO, probably reflects increased activity in the skeleton of the RANK target, nuclear factor-kappaB (NF-kappaB).
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PMID:Expansile skeletal hyperphosphatasia is caused by a 15-base pair tandem duplication in TNFRSF11A encoding RANK and is allelic to familial expansile osteolysis. 1177 66

Over the past 10 years, therapeutic optimism in osteoporosis has been fueled by the development of agents that inhibit the resorption of bone. An increase in bone density with the bisphosphonates alendronate and risedronate, for example, is associated with significant reductions in vertebral and hip fracture incidence. Although bone is clearly stronger when these agents are used, there is no conclusive evidence that they improve the microarchitectural defects that characterize the disorder. It has been known for years that parathyroid hormone (PTH) can be an anabolic agent in animals. Recently, it has been confirmed that low-dose, intermittent administration of PTH is associated with selective anabolic effects in human subjects, whereas higher doses administered continuously are associated with catabolic effects. This observation has led to an experimental design in which PTH is administered to human subjects once daily in doses that do not regularly lead to adverse events, such as hypercalcemia. Two-year studies using PTH alone have been directed at postmenopausal osteoporosis (PMO) in women and at men with idiopathic osteoporosis. In both women and men, PTH leads to marked increases in bone density at the lumbar spine and also, significantly, in the hip. In PMO, PTH is associated with significant reductions in vertebral and nonvertebral fractures. When PTH is used in combination with an anti-resorptive agent, like estrogen, the markedly positive effects on bone mass are also seen in PMO and in those with glucocorticoid-induced osteoporosis. After PTH is withdrawn, but estrogen therapy is continued, the gains in bone mass are maintained. It is not known whether gains in bone mass are maintained if PTH is withdrawn without continuing therapy with an anti-resorptive agent; however, preliminary data suggest that the gains in bone mass begin to be lost. Bone biopsy samples in PMO and in men with idiopathic osteoporosis, before and after therapy with PTH, when subjected to histomorphometric analysis show marked increases in cortical thickness and improvements in indices of trabecular connectivity, thus allaying concerns that PTH may cause cortical thinning. It would appear that the increase in cortical wall thickness is due, in part, to stimulation by PTH of periosteal apposition at a rate greater than its effect to cause endocortical resorption. In all studies reported to date, PTH appears to be well tolerated. The era of anabolic therapy for osteoporosis is at hand, with PTH being the first to be tested with sufficient rigor to demonstrate its efficacy.
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PMID:The potential of parathyroid hormone as a therapy for osteoporosis. 1208 Dec 55

Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). The present study elucidates the histopathological characters of incisor lesions in the HHM rat model. Nude rats were implanted with PTHrP-expressing tumor (LC-6) cells, maintained for 12 weeks, after which the mandibular incisors were collected. Incisor fractures were observed grossly. Microscopically, hypercalcified dentin, dentin niche with osteodentin, and thinning of dentin were observed. Hypercalcified dentin was observed as a basophilic line of calcified dentin without associated odontoblastic changes, whereas dentin niche and thinning of dentin occurred with osteodentin and loss of cell height, respectively. In contrast with hypercalcified dentin, which was distributed throughout the dentin, dentin niche and thinning of dentin were localized to the labial area of the apical and middle region, and to the labial and lingual areas of the middle and incisal region, respectively. These results suggest that hypercalcemia affected the entire calcification process resulting in hypercalcified dentin, and that high PTHrP concentrations affected selective populations of odontoblasts resulting in formation of dentin niche and thinning of dentin. The localization of dentin niche and thinning of dentin also suggest that PTHrP may also be involved odontoblastic development in the rat.
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PMID:Histopathological study on the PTHrP-induced incisor lesions in rats. 1469 15