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  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 18 (1967), S. 299-312 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 66 (2000), S. 370-374 
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. For steroid hormone function to occur, nuclear receptors interact with a series of coactivators including steroid receptor coactivator-1 (SRC-1). The SRC-1 binds the vitamin D receptor (VDR) in the presence of ligand in an activation function 2 (AF-2)-dependent manner. In order to understand the role of this interaction in 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-mediated gene expression, the level of SRC-1 expression was altered in MG-63 cells. Previous studies had demonstrated that MG-63 cells express the VDR and that 1,25(OH)2D3 regulates expression of alkaline phosphatase (ALP). Analysis of MG-63 cells demonstrated that SRC-1 is expressed. A full-length cDNA coding for SRC-1 was inserted in antisense orientation into an expression vector (anti-SRC-1). The MG-63 cells were transfected with anti-SRC-1 or mock vector and stable transformants were selected. Western blot analysis showed a 95% reduction in SRC-1 protein as compared with mock cells. We determined the effect of normal and reduced SRC-1 expression in MG-63 cells on 1,25(OH)2D3-mediated stimulation of ALP. Whereas 10−8 M 1,25(OH)2D3 produced a 3.6-fold stimulation in ALP in mock cells expressing normal levels of SRC-1, it did not alter ALP in cells expressing reduced levels of SRC-1. Thus, SRC-1 is required for 1,25(OH)2D3-mediated gene expression of ALP by human MG-63 cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Leukemia inhibitory factor (LIF) is a single-chain polypeptide that previously was shown in mice to produce hypercalcemia and influence skeletal growth and turnover. We performed dose-response studies to determine if LIF alters the serum calcium or histomorphometry of the tibia in growing male rats. Forty animals were divided into five groups of eight animals each. Recombinant human LIF, 0.01, 0.1, 1, or 10 μg/100 g body wt, or vehicle was administered daily S.C. for 3 weeks. Compared with controls it was found that LIF increased mean serum calcium at the two highest doses (11.4 ± 0.1 versus 10.8 ± 0.1 mg/dl, P= 0.0005 by one-way analysis of variance (ANOVA) but did not alter static or dynamic measurements of histomorphometry or length of the tibia. We conclude that in growing rats, high systemic concentrations of LIF result in hypercalcemia with no changes in bone turnover.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0827
    Keywords: Blacks and whites ; Bone mineral density ; Dual energy X-ray absorptiometry ; Femoral neck ; Lumbar spine ; Men ; Midradius
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The incidence of osteoporosis and fractures of the hip and spine is lower in black than in white subjects. To determine whether bone mass is increased in black men and to assess the influence of body weight and age, bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual-photon absorptiometry in 59 normal white men and 40 black men between the ages of 20 and 50 years. Body weight and age were not different from each other in the two groups. BMD of the midradius was measured by single-photon absorptiometry. Multivariate regression was used for independent analysis of each group and for analysis of the two groups together. After adjusting for body weight, age was inversely related to BMD of the femoral neck in both blacks and whites and of the trochanter in blacks. When body weight was analyzed independently of age, it was a positive predictor for BMD of the midradius of black men and of the femoral neck in white men. Despite the racial differences in age and weight on BMD, there were no significant interactions between race and age or race and weight when the data from black and white men were combined. Race had a highly significant effect on BMD of the lumbar spine, trochanter, and femoral neck midradius, and BMD was higher in blacks than in whites at these sites. There were significant declines in BMD with age at the midradius and femoral neck and significant increases in BMD with body weight at the trochanter and femoral neck. Thus, bone mass is higher in black than in white men and the difference in bone mass may contribute to the lower incidence of osteoporosis and fractures in blacks.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0827
    Keywords: Key words: Growth hormone — 1,25(OH)2D — Calcium — Phosphorus — PTH — IGF-I — IGFBP3 — TRP — TMP/GFR.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. To assess the effects of growth hormone (GH) on serum 1,25-dihydroxyvitamin D [1,25(OH)2D], we performed the following prospective crossover study in six healthy, young, adult, white men. During each of two admissions for 2½ days to a general clinical research center, subjects were placed on a daily dietary calcium intake of 400 mg. Serum calcium, phosphorus, 1,25(OH)2D, immunoreactive intact parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP3), tubular reabsorption of phosphate (TRP), and maximum tubular reabsorption of phosphate (TMP/GFR) were measured. Recombinant human GH (rhGH, Humatrope) (25 μg/kg/day subcutaneously for 1 week) was administered prior to and during one of the admissions. Results are expressed as mean ± SEM. Whereas serum 1,25(OH)2D (58.9 ± 7.7 versus 51.6 ± 7.4 pg/ml, P 〈 0.01), serum phosphorus (4.5 ± 0.1 versus 3.7 ± 0.1 mg/dl, P 〈 0.01), TRP (92.0 ± 0.5 versus 87.8 ± 0.7 mg/dl, P 〈 0.005), TMP/GFR (4.6 ± 0.1 versus 3.5 ± 0.2, P 〈 0.005), and urinary calcium (602 ± 49 versus 346 ± 25 mg/day, P 〈 0.001) increased significantly, serum PTH decreased significantly (19.9 ± 1.9 versus 26.8 ± 4.0 pg/ml, P 〈 0.05) and serum calcium did not change when subjects received rhGH. These findings indicate that in humans, GH affects serum 1,25(OH)2D independently of circulating PTH and that this effect is mediated by IGF-I. We propose, therefore, that one potential mechanism by which GH stimulates increases in bone mass is via modest increases in serum 1,25(OH)2D.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 56 (1995), S. 311-315 
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Prednisone inhibits bone formation and causes bone loss. To investigate possible mechanisms and sites, the effects of sham operation, ovariectomy, and prednisone were determined on bone and mineral metabolism in 7-week-old growing female rats. Forty animals were divided into groups of 10 each. Sham operation and ovariectomy were performed. One week later, pellets containing 5 mg prednisone or drug free were implanted S.C. at the back of the neck. Four weeks later, animals were sacrificed and tibiae were removed for histomorphometric analysis of the middiaphysis and proximal metaphysis. In both sham-operated and ovariectomized rats, prednisone (1) reduced weight gain (P〈0.02) and did not alter uterine weight; (2) lowered serum magnesium (Mg) (P〈0.001) and did not change serum calcium (Ca), phosphate (P), 25-hydroxyvitamin D (25OHD), or 1,25-dihydroxyvitamin D [1,25(OH)2D]; (3) produced striking increases in calcified cartilage, reduced cross-sectional area (P〈0.05) and cortical area (P〈0.01) and did not change medullary area of the tibial diaphysis; (4) lowered periosteal and endocortical bone formation and apposition rates; and (5) increased mean cancellous bone area (P〈0.05) and cancellous bone perimeter (P〈0.01) of the tibial metaphysis. In both control and prednisone-treated rats, ovariectomy (1) reduced uterine weight (P〈0.001); (2) did not change serum Ca, P, Mg, 25OHD, or 1,25(OH)2D; (3) did not change mean cross-sectional, medullary, or cortical areas; (4) increased periosteal bone formation and apposition rates (P〈0.01) and did not alter endosteal bone formation and apposition rates, and (5) decreased cancellous bone area (P〈0.01) and cancellous bone perimeter (P〈0.01). Thus, in short-term studies, prednisone increased calcified cartilage and inhibited the formation of cortical bone at periosteal and endosteal surfaces and reduced cortical bone of the tibia in both sham-operated and ovariectomized, rapidly growing animals.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1433-2965
    Keywords: Key words:Bone turnover markers – Clinical management – Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of bone mineral density (BMD). This review evaluates the use of commercially available bone turnover markers as aids in diagnosis and monitoring response to treatment in patients with osteoporosis. High within-person variability complicates but does not preclude their use. Elevated bone resorption markers appear to be associated with increased fracture risk in elderly women, but there is less evidence of a relationship between bone formation markers and fracture risk. The critical question of predicting fracture efficacy with treatment has not been answered. Changes in bone markers as currently determined do not predict BMD response to either bisphosphonates or hormone replacement therapy. Single measurements of markers do not predict BMD cross-sectionally (except possibly in the very elderly), or change in BMD in individual patients, either treated or untreated. On the other hand, research applications of bone turnover markers are of value in investigating the pathogenesis and treatment of bone diseases. Markers have potential in the clinical management of osteoporosis, but their use in this regard is not established. Additional studies with fracture endpoints and information on negative and positive predictive value are needed to evaluate fully the utility of bone turnover markers in individual patients.
    Type of Medium: Electronic Resource
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