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  • Calcium
  • Osteoporosis
  • Springer  (281)
  • American Institute of Physics (AIP)
  • Institute of Electrical and Electronics Engineers (IEEE)
  • 2015-2019
  • 1990-1994  (176)
  • 1970-1974  (86)
  • 1965-1969  (19)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of comparative physiology 175 (1994), S. 415-423 
    ISSN: 1432-1351
    Keywords: Aplysia ; Calcium ; Circadian ; Light ; Serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The eye of the marine mollusk Aplysia californica contains an oscillator that drives a circadian rhythm of spontaneous compound action potentials in the optic nerve. Both light and serotonin are known to influence the phase of this ocular rhythm. The aim of the present study was to evaluate the role of extracellular calcium in both light and serotonin-mediated phase shifts. Low calcium treatments were found to cause phase shifts which resembled those produced by the transmitter serotonin. However, unlike serotonin, low calcium neither increased ocular cAMP levels nor could these phase shifts be prevented by increasing extracellular potassium concentration. Low calcium-induced phase shifts were prevented by the simultaneous application of the translational inhibitor anisomycin and low calcium treatment resulted in changes in [35S]methionine incorporation into several proteins as measured by a two-dimensional electrophoresis gel analysis. Finally, light treatments failed to produce phase shifts in the presence of low calcium or the calcium channel antagonist nickel chloride. These results are consistent with a model in which serotonin phase shifts the ocular pacemaker by decreasing a transmembrane calcium flux through membrane hyperpolarization while light-induced phase shifts are mediated by an increase in calcium flux.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 54 (1994), S. 44-49 
    ISSN: 1432-0827
    Keywords: Bone ; Stress ; Elasticity ; Mechanical properties ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Magnesium (Mg) participates in the normal formation and remodeling of bone. However, little is known about effects of Mg status on the biomechanical function of bone. We examined gross morphometry and composition as well as biomechanical properties of the femurs of male rats fed diets adequate or deficient in Mg. Comparison of deficient animals and controls yielded a number of differences (all significant at P〈0.05). Mg-depleted animals exhibited slow growth, inefficient food utilization, and greatly reduced concentrations of Mg in both serum and femur ash. Compared with controls, femurs from depleted animals were shorter, but wet weights, diameters, and midfemoral cross-sectional areas showed no differences. Bone length was reduced to a greater degree than could be accounted for by differences in body weights between the groups. Bones of Mg-deficient rats contained less dry matter and less ash (which contained more Ca/g) than those of controls, along with a higher percentage of moisture. Significantly reduced bone strength in depleted animals was evident from the lighter loads supported at the elastic limit (yield point) and at fracture and from decreased stresses accompanying those loads. Modulus of elasticity, however, was not affected by Mg depletion. Different yield and breaking loads were related to different body weights of groups, but stresses were reduced for deficient bones even after adjusting for body size. Our data establish abnormal biomechanical behavior of cortical bone in Mg-deficient animals and emphasize the importance of measuring such functional properties of bone in the assessment of responses to altered metabolic conditions under experimental conditions.
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  • 3
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    Electronic Resource
    Springer
    Calcified tissue international 54 (1994), S. 83-86 
    ISSN: 1432-0827
    Keywords: Ultrasound attenuation ; Bone ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Ultrasound transmission measurement through the os calcis is an emerging technique and a promising clinical tool for early assessment of osteoporosis. However, several previous studies showed that broadband ultrasonic attenuation (BUA) is sensitive to small variations in bone mass or structure. The os calcis is an inhomogeneous bone and therefore, the attenuation depends on the location in the os calcis. BUA distribution within the os calcis can be measured by rectilinear scanning over the entire bone. We used a mechanical scanning device with both unfocused and focused transducers. The spatial resolution of these was about 25 mm and 4 mm, respectively. There was good agreement (r=0.97) between the results with unfocused and focused transducers. In addition, imaging the variations of BUA is possible with the focused transducers, and high quality images are obtained. These images permit the selection of optimal regions of interest for ultrasound attenuation measurement.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 54 (1994), S. 365-369 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Incidence ; Femoral fractures ; Forearm fractures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract A population study was carried out over a period of 3 years (1987–1989) to determine the incidence of osteoporotic fractures. Fractures diagnosed in the two acute hospitals of the Maltese Islands were collected and classified according to the fracture site, age, sex, and patient's residence. Fractures in the Maltese Islands can only be diagnosed and adequately treated in these two general hospitals. A total of 8780 fractures were examined. Fracture of the neck of the femur was the most common fracture for which patients were admitted to the hospital. There were twice (1.96) as many females as males hospitalized for this fracture, giving an annual incidence of 262/100,000 females to 134/100,000 males over the age of 45. The fracture incidence was 2–3 times less than that found in North European countries, but was similar to the fracture rates obtained in Mediterranean studies. Fracture radius was the most frequent fracture treated on an outpatients basis. In over 45-year-olds, the female predominance persisted, giving a ratio of 3.65:1. This gave an annual incidence of 452/100,000 females to 150/100,000 males. Again, the fracture indicence obtained was significantly lower than that of Northern European countries. Other long bones showed a similar female to male (F:M) ratio in the cohort over 45 years of age. The bones showing this F:M ratio were the humerus (3.9:1), fibula (1.89:1), and tibia (1.6:1). Below 45 years of age males had more fractures than females for any bone studied. The epidimiological graphs obtained were similar to those of other studies suggesting that similar factors influence the development of osteoporosis. Further studies are required to analyze these factors in detail.
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  • 5
    Electronic Resource
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    Springer
    Calcified tissue international 54 (1994), S. 381-384 
    ISSN: 1432-0827
    Keywords: Pyridinoline ; Free pyridinoline ; Deoxypyridinoline ; Urinary excretion ; Pre- and postmenopausal ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The urinary excretion of pyridinolines either in the free form or linked to different peptide fragments of type I collagen are intensively studied as new biochemical markers of bone resorption. In the present study we compared the urinary excretion of free pyridinoline (F-Pyr) determined by enzyme-linked immunosorbent assay (ELISA) (Collagen CrosslinksTM Kit, Metra Biosystems) to pyridinoline (Pyr), and deoxypyridinoline (D-Pyr) determined by high performance liquid chromatography (HPLC) in early postmenopausal women treated with either hormone replacement therapy or placebo and in healthy age-matched premenopausal women. Other markers of bone metabolism were included for comparison. Compared with the premenopausal women, the postmenopausal women had significantly increased values of the biochemical parameters. F-Pyr, Pyr, D-Pyr, and T-Pyr (=Pyr+D-Pyr) decreased during hormone therapy. D-Pyr correlated with the rate of bone loss, whereas this was not the case for F-Pyr. The correlations between the markers yielded r values of 0.71 (F-Pyr vs Pyr), 0.67 (F-Pyr vs D-Pyr), and 0.71 (F-Pyr vs T-Pyr). In conclusion, the present study shows that the newly introduced ELISA for determination of the free pyridinolines is less sensitive than pyridinium crosslinks measured by high performance liquid chromatography (HPLC) in hydrolyzed urine for the changes in calcium metabolism that occur at menopause and during hormone replacement therapy. Whether this limitation will be balanced out by avoiding the inconvenience of the complicated, expensive, and timeconsuming HPLC procedure is still being debated.
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  • 6
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    Calcified tissue international 55 (1994), S. 82-86 
    ISSN: 1432-0827
    Keywords: Calcitonin ; Osteoporosis ; Bone mineral content
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract We examine the dose-related effect of intranasal salmon calcitonin (sCT) on the early postmenopausal bone loss and bone turnover; a 2-year, prospective, randomized, double-blind, placebo-controlled study was carried out with 134 healthy women who had passed a natural menopause within 6 months to 3 years. The women were allocated randomly to 2 years of treatment with either 100, 200, or 400 IU of sCT given intranasally or placebo. All groups received a calcium supplement of 500 mg. Twenty-one women left the study before its end and 91 complied with the study criteria throughout. Bone mineral content/density of the distal forearm and lumbar spine and biochemical parameters of bone turnover were measured. Although the measurements after 24 months revealed no significant difference between groups in bone mineral density of the lumbar spine, the average changes over time revealed prevention of bone loss in the groups treated with 200 and 400 IU of sCT (0.2 to-0.6%) and declines of 0.8-1.7% in the groups treated with 100 IU of sCT and placebo (P〈0.05−0.01; within-group testing). There was no dose-related response to sCT but there was a significant difference between the pooled groups treated with 200 plus 400 IU of sCT versus the 100 IU sCT and placebo-treated groups (P=0.030−0.005). The same difference between groups was seen for biochemical parameters of bone turnover (P=0.022−0.003). The biochemical parameters of bone turnover revealed decreases of 10–20% (P〈0.001; within group testing) in the groups treated with the two highest sCT doses. It was concluded that nasal sCT in doses of 200 and 400 IU has some effect in women soon after the menopause—preventing the bone loss in the spine throughout the first year of therapy and lowering the bone turnover. It may be used as an alternative to hormone replacement when estrogens are contraindicated. The present data indicate that discontinuous strategies should be preferred.
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  • 7
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    Springer
    Calcified tissue international 55 (1994), S. 128-133 
    ISSN: 1432-0827
    Keywords: Osteoblast ; Plasma membrane ; Calcium ; Ion channel ; Cell proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Patch clamp physiological techniques were used to characterize the voltage-activated calcium currents (VACC) expressed in the plasma membrane of osteoblastic cells as a function of time in culture and proliferative state of the cell. Osteoblast-enriched preparations were isolated by collagenase digestions of newborn rat calvaria and cultured under different conditions which affected cell proliferation (i.e., low serum in the media to arrest proliferation). VACC were isolated by replacing the intracellular potassium with cesium, and adding 1 μM tetrodotoxin to the bath. Under conditions that favored cell proliferation, low cell density, and media supplemented with 10% fetal calf serum (FCS), a transient calcium current was not expressed until day 3 in culture. There was a statistically significant relationship between the precentage of cells expressing this current and the time in culture. The magnitude of the current significantly increased as days in culture increased. Under the same conditions, the sustained VACC was detected after 7 or 8 days in culture. However, arresting cell proliferation after 2 days in culture by reducing the FCS concentration to 0.01% induced the expression of the sustained VACC the next day. The data suggest that the expression of VACC in the plasma membrane of rat calvarial osteoblasts depends on the time in culture and the state of proliferation of the cells. These results should prove to be valuable in studying the functional significance of VACC in osteoblastic cells and their regulation by various bone regulatory agents.
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  • 8
    ISSN: 1432-0827
    Keywords: Calcidiol ; Calcitriol ; Bone mineral density ; PTH ; Postmenopausal ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The relationship between vitamin D and bone density was studied in 150 selected, mature (45–74), postmenopausal women with a lumbar spine Z score below 0. Vitamin D status was evaluated using calcidiol serum levels. Serum calcitriol and parathyroid hormone (PTH) values were also evaluated in some subjects. Bone mass was evaluated by ascertaining bone density and Z and T scores in the lumbar spine and femur region. The reference group consisted of 25 premenopausal women. The postmenopausal group was divided into subgroups according to age, i.e., under or over 60 years old. Additionally, the whole group was also subdivided according to their lumbar spine Z scores into group I (Z〉-1), group II (Z〈-1; 〉-2), and group III (Z〈-2). Group III of postmenopausal women had higher PTH and lower calcitriol levels than premenopausal women. Calcidiol serum levels were lower in postmenopausal women groups II or III than in the group I and premenopausal women. Calcidiol serum levels and the bone mass values for the lumbar spine were correlated positively in all the postmenopausal women; in the women over 60 years of age, calcidiol levels also correlated with the bone mass values expressed as the bone density in three femur regions: femoral neck, trocanter, and Ward's triangle. In conclusion, mature postmenopausal woman showed high PTH levels and low calcidiol and calcitriol values. Calcidiol status is significantly related to bone mineral density in the lumbar spine and in women over 60 years, calcidiol levels also correlated with bone density in the femur regions.
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  • 9
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    Springer
    Calcified tissue international 55 (1994), S. 269-273 
    ISSN: 1432-0827
    Keywords: Islet amyloid polypeptide ; Amylin ; Calcium ; Urine ; Parathyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Islet amyloid polypeptide (IAPP) is a member of the calcitonin/CGRP family and has been isolated from the β-cell of pancreatic islets. Recent evidence suggests that this peptide may be involved in calcium metabolism in that its administration resulted in lowering of serum calcium levels. To determine the mechanism of IAPP-induced hypocalcemia, the peptide was infused at 50 pmol/min/kg for 90 minutes in conscious male mongrel dogs. Infusion of the peptide resulted in a modest decline in the total serum calcium concentration (10.4±0.2 to 9.4±0.2 mg/dl; P〈0.05) and a concomitant increase in urinary calcium excretion (3.6±0.6 to 6.9±2.0 mg/dl; P〈0.01). Based on an extracellular volume of 7 liter in a 28 kg dog, the total decrement in calcium due to IAPP was 41.3±2.4 mg, whereas the total increase in urinary calcium was 3.2±0.7 mg. There were no detectable changes in calcitonin. We conclude that IAPP lowers serum calcium and increases the renal excretion of calcium independently of calcitonin. However, the calciuria can only account for a small component of the hypocalcemic effect and therefore, an additional calcium lowering effect of IAPP exits.
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  • 10
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    Springer
    Calcified tissue international 55 (1994), S. 257-259 
    ISSN: 1432-0827
    Keywords: Mast cell ; Osteoporosis ; Mastocytosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract A new stain for mast cells (Mc) in bone was applied in 9 normal, 14 osteoporotic, and 1 case of systemic mastocytosis. Examination included the following calculations: Mc counts according to various area and perimetry referents including cortical (Ct) and cancellous (Cn) components; proportion of Mc types; and diameter and area of ovoid Mc. The following findings were noted: (1) in all groups, Mc counts were higher in the Ct compared with Cn bone, and Mc counts correlated with type but not size of Mc; (2) in osteoporotics compared with normals, Mc counts were higher in Cn but not Ct bone for both area and perimetry referents; (3) a lower proportion of ovoid Mc were seen in osteoporotics; (4) two cases of osteoporosis had similar Mc counts to a case of mastocytosis, but the latter had a higher proportion of spindle-and bizarre-shaped Mc and a higher proportion of Mc in contact with the bone surface. The Mc by virtue of an increase in number, closer contact with bone surface, and pattern of morphological types may have a role in osteoporosis in occasional instances.
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  • 11
    ISSN: 1432-0827
    Keywords: Interleukin-1 ; Interleukin-1 receptor antagonist ; Estrogen ; Osteoporosis ; Cytokine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The recent finding that treatment with the interleukin-1 (IL-1) inhibitor, interleukin-1 receptor antagonist (IL-1ra) decreases bone loss and bone resorption in ovariectomized rats, strongly suggested that IL-1 mediates, at least in part, the effects of estrogen deficiency on bone resorption. Although in vitro studies have shown that IL-1 activates mature osteoclasts and stimulates osteoclastogenesis, the two main mechanisms by which estrogen deficiency stimulates bone resorption, it is still unclear whether IL-1 mediates both effects of estrogen deficiency in vivo. To investigate this matter, we have examined the changes in bone mineral density (BMD) which occur in ovariectomized rats after completion of 1 month of estrogen or IL-1ra treatment begun at the time of ovariectomy. Ovariectomy caused a marked decreased in BMD which was blocked by 17β estradiol and decreased by IL-1ra. Cessation of estrogen therapy was followed by a rapid induction of bone loss, indicating that estrogen blocks the activation and utilization of mature osteoclasts without depleting the bone microenvironment of osteoclast precursors and mature, inactive osteoclasts. In contrast, ovariectomized rats treated with IL-1ra maintained a stable bone density for the first 4 weeks after completion of the treatment. In these rats, bone loss resumed not earlier than 6 weeks after discontinuation of the IL-1ra treatment. Estrogen deficiency was necessary to unveil the bone-sparing effect of IL-1ra because in a control experiment in which rats were treated with IL-1ra for the 4 weeks before ovariectomy, BMD began to decrease immediately after ovariectomy. Based on these results we propose the hypothesis that in conditions of estrogen deficiency, the main effect of IL-1ra is to block the proliferation and differentiation of osteoclast precursors, an event that results in the depletion of mature, rapidly responsive osteoclasts. We also suggest that estrogen may have important direct effects on the regulation of osteoclast activity.
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  • 12
    ISSN: 1432-0827
    Keywords: Pyridinolines ; Type I collagen carboxyterminal telopeptide ; Osteoporosis ; Calcium ; Calcitonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract As assessed by urine pyridinium cross-links, bone resorption increases at night. This has been ascribed to either the nocturnal rise of serum parathyroid hormone (PTH) or immobilization. ICTP is the carboxyterminal telopeptide region of type I collagen in bone, cross-linked via pyridinium cross-links and liberated during the degradation of type I collagen. To study whether the nocturnal rise in bone resorption is seen also in serum type I collagen carboxyterminal telopeptide (ICTP) and whether this rise is abolished by bedtime calcium or calcitonin, nine healthy postmenopausal women participated in three 24 hour sessions. At 2200 hours, either 1 g of oral calcium or 200 IU of intranasal calcitonin or no treatment (control session) were given. The participants were recumbent from 2200 hours to 0600 hours. Like urinary pyridinolines, serum ICTP showed a clearcut nocturnal rise during the control session, increasing from 3.7±0.3 μg/liter (mean±SE) at 2000 hours to 4.9±0.4 μg/liter at 0600 hours (P〈0.001). Administration of calcium did not affect either serum ICTP or urinary pyridinolines, although it decreased serum intact PTH by 18% (P〈0.001) as assessed by areas under curve (AUC) after 2200 hours. Serum ICTP and urinary pyridinolines remained unchanged also after administration of calcitonin which increased the AUC for serum intact PTH by 9% (P〈0.05). In conclusion, serum ICTP follows a circadian rhythm in healthy postmenopausal women. The nocturnal rise in markers of bone resorption is not due to PTH, and its dependency on the function of osteoclasts is open to question.
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  • 13
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Growth hormone ; Growth factors ; Proliferation ; Osteoblasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Decreased osteoblastic activity seems to play an important role in the pathogenesis of postmenopausal osteoporosis. The aim of the present study was to examine the direct effects of human growth hormone (GH) on proliferation and differentiation of osteoblastic cells obtained from patients with postmenopausal osteoporosis and age-matched normals and to compare the cellular responses induced by GH between the two groups. Osteoblast cultures (human marrow stromal osteoblast-like cells) were established from bone marrow aspirates obtained from 9 osteoporotic patients and 12 age-matched normals. Effects on cell proliferation and cell differentiation markers [alkaline phosphatase (AP)], procollagen type I propeptide (PICP), and osteocalcin] were assessed. GH stimulated 3H-thymidine incorporation into DNA in cell cultures of osteoporotic patients to a maximum of 158±14% of no-treatment controls (n=9, P〈0.001) and to 203±52% (n=9, P〈0.001) in normals. GH increased cell number as measured by methylene blue (MB) assay in cells of osteoporotic patients to 138±10% (P〈 0.05, n=7) and in normals to 138±12 (P〈0.05, n=7). GH alone reduced cellular AP production: 61±3.8% (P〈0.05, n=7) versus 65±16% (P〈0.05, n=7) and cellular PICP production: 79±6% (P〈0.05, n=7) versus 69±16% (n.s., n=7), in cell cultures of osteoporotics and normals, respectively. 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) (10-9 M) alone increased AP production in cell cultures of osteoporotics to 193±23% (P〈0.01, n=7) and to 266±51% (P〈0.05, n=7) in cell cultures of normals. 1,25(OH)2D3 had no effect on PICP production in either culture. Combining GH and 1,25(OH)2D3 reduced 1,25(OH)2D3-stimulated levels of AP and osteocalcin. No statistically significant differences were observed in cell proliferation or cell differentiation responses between cell cultures of osteoporotic patients and normals. Our results demonstrate that osteoblastic cells obtained from osteoporotic patients exhibit normal responsiveness to short-term stimulation with GH in vitro and do not support the hypothesis of the presence of major defects in osteoblastic responsiveness to stimuli in patients with osteoporosis.
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  • 14
    ISSN: 1432-0827
    Keywords: Corticosteroids ; Osteoporosis ; Parathyroid hormone ; Calcitonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The role of calcitonin and parathyroid hormone (PTH) in corticosteroid-induced osteoporosis is controversial. We therefore measured plasma calcitonin and PTH levels in 34 adults receiving chronic pharmacological corticosteroids for obstructive airways disease, and in controls matched for age, sex, menopause, and disease. In addition, the acute effect of a 7-day course of 15 mg prednisolone daily on fasting and calcium-stimulated calcitonin was studied in 10 normal male volunteers. There was no difference in calcitonin and PTH levels in the corticosteroid-treated patients when compared with controls. The corrected serum calcium was significantly higher in the steroid-treated patients (patients mean 2.40 (SEM 0.01) mmol/liter; controls mean 2.33 (SEM 0.01) mmol/liter; P〈0.001). The short course of corticosteroids in volunteers did not alter basal or stimulated calcitonin, PTH, or calcium levels. These results suggest that neither calcitonin deficiency nor PTH excess is a feature of corticosteroid-induced osteoporosis.
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  • 15
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    Calcified tissue international 54 (1994), S. 262-267 
    ISSN: 1432-0827
    Keywords: Biochemical markers ; Bone mineral density ; Life-style ; Menopause ; Osteoporosis ; Population study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Fifty-year-old women (n=519) attending a health examination were divided by their ovarian hormone status into four groups: premenopausal, perimenopausal, postmenopausal without ovarian hormone replacement therapy (HRT), and postmenopausal with HRT. Information on lifestyle factors was obtained with interviews and questionnaires. Bone mineral density at the calcaneus was assessed with single-photon absorptiometry, and several serum and urine markers of bone metabolism were measured. Postmenopausal women without HRT had significantly higher levels of fasting serum alkaline phosphatase, osteocalcin, total and ionized calcium, phosphate, and fasting urinary hydroxyproline than those in the three other study groups. No difference was found in bone mineral density between the premenopausal and postmenopausal groups. Postmenopausal women without HRT showed a marked correlation between serum osteocalcin and urine hydroxyproline. Both markers showed significant correlations with serum calcium, phosphate, and alkaline phosphatase. Multivariate analyses showed a statistically significant association of ovarian hormone status and body mass index with most measured markers of bone metabolism. The association between alcohol consumption and serum osteocalcin was highly significant. Cigarette smoking was associated with levels of serum alkaline phosphatase and total and ionized calcium. A weak association was found between coffee drinking and serum alkaline phosphatase.
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  • 16
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    Calcified tissue international 54 (1994), S. 421-425 
    ISSN: 1432-0827
    Keywords: Metabolism ; Secretion ; Balance ; Osteoporosis ; Magnesium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract This 30-day balance study with weanling rats was designed to determine the effects of plasma fluoride and dietary calcium concentration and their interaction on the absorption, balance, and tissue concentrations of fluoride. The three major groups differed according to the total exposure and plasma concentrations of fluoride. One group received fluoride only in the diet and the other two received additional fluoride by continuous infusion from miniosmotic pumps implanted S.C. Each group was divided into two subgroups with dietary calcium concentrations of 0.4% or 1.4%. Fluoride intake with the diet did not differ among the groups. Fecal fluoride excretion was directly related to plasma fluoride concentration. The absorption and balance of dietary fluoride were inversely related to plasma fluoride concentration. These effects were greatest in the groups fed the 1.4% calcium diet. The interactions of plasma fluoride and dietary calcium on these variables were highly significant (P〈0.0001). The balance of dietary fluoride was negative in the four groups that received additional fluoride by infusion. In the two groups that received fluoride only in the diet, the plasma and bone fluoride concentrations were 41% and 59% lower, respectively, in the 1.4% dietary calcium group. The findings indicate that net fluoride secretion into the GI tract can occur when plasma fluoride concentrations and calcium intake are elevated. They suggest that elevated plasma fluoride levels and calcium intake are factors that may diminish the effect of oral fluoride treatment in osteoporotic patients.
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  • 17
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Ultrasound ; Hip fractures ; Bone density ; DXA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract There is considerable interest in predicting risk of hip fracture in order to allow targeting of preventive care. This study aimed to determine which of two methods best discriminates a hip fracture population from controls. Fifty women with fractured neck of femur, and 50 control subjects were scanned using dual energy X-ray absorptiometry (DXA) of the spine and hip and broadband ultrasound attenuation (BUA) of the os calcis. Significant differences between the two populations could be found for both DXA and BUA, with BUA showing the largest percentage difference (27%). The mean z-scores showed that BUA had the lowest, with the exception of DXA trochanter. However, no significant difference between BUA and DXA trochanter Z-scores was found. A receiver operator characteristic (ROC) analysis showed that BUA has a superior sensitivity and specificity compared with DXA measurements, with DXA of the hip being better than the spine. This retrospective study shows that BUA is a better discriminator of hip fracture than DXA lumbar spine of DXA hip, which may have important implications for predicting those at risk of future hip fracture.
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  • 18
    ISSN: 1432-0827
    Keywords: Calcium ; Duration of cooking ; Soup
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Because low dietary calcium intake may accelerate bone loss, patients often are advised to increase their dietary intake of calcium. However, some patients may be unable to tolerate good calcium sources such as dairy products. We postulated that the calcium content of soups and stews could be increased by prolonged cooking with a beef bone. Three experiments were done to prove this theory: (1) a bone soup made with a beef bone and distilled water, cooked for 24 hours; (2) a bone-vegetable soup cooked the same way; and (3) a vegetable soup made the same way but without the bone. It was concluded that prolonged cooking of a bone in soup increases the calcium content of the soup when cooked at an acidic, but not at a neutral pH.
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  • 19
    ISSN: 1432-0827
    Keywords: Postmenopausal women ; Hypercalcemia ; Serum PTH ; Ionized calcium ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Estrogen influences the calcium-induced suppressibility of parathyroid hormone (PTH) in postmenopausal women. We tested the hypothesis that parathyroid gland function is also sensitive to the anabolic steroid, stanazolol. The calcium-induced suppressibility of PTH was investigated in 11 osteoporotic postmenopausal women on two occasions, before and after 1 month's oral treatment with stanazolol. Compliance to treatment was checked by the determination of serum luteinizing hormone (LH) and testosterone. Serum intact PTH and ionized calcium were estimated before and 5, 60, and 120 minutes after I.V. calcium load. Calcium-induced PTH suppression was of a similar magnitude before and after stanazolol, although calcium increments were identical. The results imply that stanazolol—at biologically effective doses—does not affect PTH responsiveness to hypercalcemia in postmenopausal women.
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  • 20
    ISSN: 1432-0827
    Keywords: IL-1α ; IL-1β ; IL-1 receptor antagonist ; Bone ; Calcium ; Parathyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Both interleukin-1α (IL-1α) and interleukin-1β (IL-1β) are powerful stimulators of bone resorption in vivo and in vitro. Interleukin-1 receptor antagonist (IL-1ra) binds to many interleukin-1 receptors. It does not activate the receptor and effectively blocks the action of IL-1α and IL-1β. In this study, human recombinant IL-1ra, at 100-fold excess, was found to block bone resorption in cultured mouse calvaria due to IL-1β but not IL-1α. These observations may be explained by differential affinities of receptors for IL-1α, IL-1β and rhIL-1ra on target bone cells.
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  • 21
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    Calcified tissue international 55 (1994), S. 33-37 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Rat ; Orchidectomy ; Exercise ; Strength
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The effect of exercise on castration-induced osteoporosis in 3-month-old male rats weighing 264±4 g at the beginning of the experiment was studied. A testosterone deficiency was induced by orchidectomy (ORC), and the exercise group ran 10 m/minute for 1 hour a day on a treadmill at 0% grade. There were seven groups of eight rats (n=56) randomized into a control group killed at time 0, and sham, ORC and ORC and exercise groups killed at 4 and 8 weeks. ORC reduced body weight gain (with analysis of variance (ANOVA) P〈0.001), and at 4 weeks the body weight was 343±14 g in ORC group and 301±4 g in the ORC and exercise group (P〈0.01). The increase in femoral length was slower in the ORC+exercise groups. The ash weight of the tibia did not decrease significantly after ORC or ORC+ exercise. ORC did not affect 45Ca incorporation, but exercise slightly increased it in the whole tibia 8 weeks after ORC (with ANOVA P=0.057). ORC had significantly lowered the trabecular bone volume in the secondary spongiosa of the distal femur at 4 and 8 weeks, and exercise did not prevent this. This is an opposite finding to our previous study with ovariectomized female rats [12]. ORC also significantly had reduced the osteoblast-lined trabecular bone surface and the number of osteoclasts by 8 weeks after the operation. Exercise increased the osteoblast-lined surface and the number of osteoclasts. The mechanical strength of the femoral neck also was reduced after ORC and this was not prevented by exercise either. In conclusion, ORC reduces bone growth and turnover which leads to osteopenia in growing rats. Moderate treadmill exercise does not reverse the ORC-induced loss of trabecular bone and the reduced mechanical strength of the femoral neck, although it has a positive effect on the osteoblast and osteoclast indices and on calcium incorporation into bone.
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  • 22
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    Calcified tissue international 55 (1994), S. 243-248 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Bone density ; Longitudinal studies ; Statistical models ; Decision models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract We calculated how long to wait before repeating bone mineral density (BMD) measurements to reassess fracture risk. Correlation results from serial measurements of 495 postmenopausal Japanese-American women were used to estimate 95% confidence intervals (CI) for future BMD. After 7 years of follow-up, BMD correlations with the initial measurement ranged between 0.81 and 0.94, depending on age group and measurement site. In this analysis, the period between measurements was defined as the time required for the lower 95% CI to fall below the BMD value corresponding to doubling of fracture risk. Progressive bone loss causes fracture risk to double after 10 years, on average. However, the 95% CIs indicate that a second BMD measurement will detect risk doubling after only 2 or 3 years for some women. For untreated, early postmenopausal women, the period between measurements was approximately 2–5 years for the radius and 4–6 years for the calcaneus, depending on the initial BMD level. The period was approximately 1 year longer for women age 60 and older. Treatments that halve the bone loss rate would increase the period by 1–3 years. In the absence of a second measurement of BMD, the CI will continue to expand with time, corresponding to a wider range in risk between individuals, and a greater proportion of women will be at increased fracture risk. Obtaining a second BMD measurement pinpoints the patient's status within the precision of the measurement. We conclude that repeated BMD measurements will provide a more accurate estimate of fracture risk than a single, baseline measurement.
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  • 23
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    Calcified tissue international 55 (1994), S. 324-329 
    ISSN: 1432-0827
    Keywords: Photodensitometry ; Radiogrammetry ; Metacarpal bone ; Bone mineral density ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The metacarpal bone mineral density (BMD) and metacarpal index (MCI) of the second metacarpal bone were measured by computed X-ray densitometry (CXD) (Teijin Ltd., Tokyo), which we have established with the development of microdensitometry of radiographs. In this study, we evaluated the basic attributes of this CXD method and determined the age-related changes in both metacarpal measurements in normal Japanese women. The precision in vivo was measured in eight subjects. The precision errors [coefficient of variation (CV)] were 0.2–1.2% CV for metacarpal BMD and 0.4–2.0% CV for MCI, respectively. We have obtained low precision error and more rapid analysis, within 3 minutes respectively, compared with the previous methods. Age-related changes in the metacarpal measurements were evaluated in 1438 normal women. Both measurements showed the most significant decrease in the sixth decade of life. The rate of decrease in the sixth decade was 1.6%/year for metacarpal BMD and 1.5%/year for MCI. On comparison between metacarpal BMD by CXD and spine BMD using dual energy X-ray absorptiometry (DXA) in 248 normal women with and without menstruation, the two measurements were found to be similarly decreased in the subjects within 5 years after menopause. There was also no significant difference in the Z-score between metacarpal BMD and spine BMD within 5 years after menopause. These results indicate that early postmenopausal bone loss occurs not only in the spine but also in the metacarpal bone. The metacarpal BMD for patients with osteoporosis was significantly lower than that for age-matched normal controls, although the Z-score for spine BMD (-1.46) was significantly better than that for metacarpal BMD (-0.82). In conclusion, because CXD has excellent low precision error and is widely available at relatively low cost, it appears potentially to be applicable to problems in the diagnosis and management of osteoporosis, when used in association with DXA.
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  • 24
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    Calcified tissue international 55 (1994), S. 376-380 
    ISSN: 1432-0827
    Keywords: Electromagnetic ; Bone ; Calcium ; Osteoblast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Low energy electromagnetic fields (EMF) exhibit a large number of biological effects. A major issue to be determined is “What is the lowest threshold of detection in which cells can respond to an EMF?” In these studies we demonstrate that a low-amplitude combined magnetic field (CMF) which induces a maximum potential gradient of 10-5 V/m is capable of increasing net calcium flux in human osteoblast-like cells. The increase in net calcium flux was frequency dependent, with a peak in the 15.3–16.3 Hz range with an apparent bandwidth of approximately 1 Hz. A model that characterizes the thermal noise limit indicates that nonspherical cell shape, resonant type dynamics, and signal averaging may all play a role in the transduction of lowamplitude EMF effects in biological systems.
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  • 25
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Bone remodeling ; Physical activity ; Aging ; Calcium
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    Notes: Abstract To determine whether growth hormone administration would potentiate bone response to the stimulation of exercise, 80 female rats aged 14 months were divided into control (CON), ovine growth hormone administration (0.5 mg/kg daily) (GH), treadmill exercise (17 m/minute, 60 minutes daily) (EX), and GH+EX groups for 9 and 16 weeks. Static and dynamic histomorphometry were measured on the tibial shaft and (L-5) vertebral cortical bone. The periosteal and endocortical bone formation rate of the tibial shaft were higher in both EX and GH+EX than in the CON group in the 9-week study. There is a synergistic interaction between the two interventions in both cortical surfaces. After 16 weeks of study, the cortical bone area and periosteal bone formation rate were higher only in the EX than in the CON group. In the L-5 vertebra, the labeled surface on the periosteum was higher in the EX and the bone formation rate on the endocortical surface was higher in the GH than in the CON group. However, there was a negative interaction when the two interventions were combined. We conclude that a low-dose of growth hormone administration could initially potentiate long bone response to exercise. However, from the present study, long-term treatment with low-dose growth hormone administration does not enhance the increase in bone mass from exercise.
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  • 26
    ISSN: 1432-0827
    Keywords: Diabetes mellitus ; Osteocalcin ; Osteoblast number ; Osteoporosis
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    Notes: Abstract The accumulated data indicate that bone mineral density (BMD) is decreased in humans with insulin-dependent diabetes mellitus. The purpose of this study was to prospectively determine sequential lumbar and femoral BMD utilizing dual energy X-ray absorptiometry in rats that spontaneously become diabetic to determine if weight and blood glucose control would prevent the diabetes-related bone mass changes. BMD of the lumbar spine and femur was measured prior to the onset of diabetes and at 3-week intervals after the diagnosis of diabetes for 12 weeks in 14 diabetes-prone BB/Wor rats (DP) and eight diabetes-resistant BB/Wor control rats (DR). At 12 weeks, the lumbar (0.238±0.013 vs 0.262±0.007 g/cm2, P〈0.001) and femoral (0.313±0.013 vs 0.343±0.013 g/cm2, P〈0.001) BMD were significantly lower in the DP rats despite significantly greater body weights (387±26 vs 329±46 g, P〈0.001) and plasma glucose levels of only 178 mg/dl. There was no difference in plasma values of calcium, phosphorus, osteocalcin, or tartrate-resistant acid phosphatase between groups or differences in osteoblast numbers in histologic sections. There was a significant (P〈0.001) decrease in plasma creatinine in the diabetic animals. The results indicate that in this animal model of type I diabetes, spine and femoral BMD do not increase comparable to control despite weight and blood glucose control. This would suggest that the diabetic condition itself affects bone mass in the absence of weight loss and poor blood glucose control.
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  • 27
    ISSN: 1432-0827
    Keywords: Calcium ; Lactate ; Acidosis ; Treadmill ; Bone
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    Topics: Biology , Medicine , Physics
    Notes: Abstract The purpose of this study was to examine the influence of exercise on the serum concentrations of intact parathyroid hormone (PTH). Serum PTH and plasma lactate were measured in 15 well-trained men, 9 long-distance runners and 6 fire-fighters, during two running exercises. Test one consisted of 40-minute treadmill running with a stepwise increased load and test two consisted of 50-minute treadmill running with a constant velocity. When the load was step-wise increased, the PTH concentrations increased moderately at the slower running paces but reached a final value that was about 50% higher than the starting value. This rise occurred despite a concomitant increase of total serum calcium from 2.38±0.06 to 2.49±0.05 mmol/liter (P〈0.01). During the constant running exercise, the long-distance runners, but not the fire-fighters, displayed a significant increase in PTH concentrations although the rise in total serum calcium was similar in both groups. There was a weak correlation between the changes in PTH and lactate in both exercises. The findings demonstrate that both high and low intensity exercise enhance release of PTH in long-distance runners through a mechanism that does not involve serum calcium. This relationship might be of importance for bone mass in men performing long-distance training.
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  • 28
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    Calcified tissue international 54 (1994), S. 268-273 
    ISSN: 1432-0827
    Keywords: Aging ; Aorta ; Calcium ; Elastin ; Arteriosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The rate of calcification within the human thoracic aorta from completion of body growth to advanced old age was examined. Fifty-eight aortae, obtained at necropsy, were dissected into four layers: the complete intima and the separated media, which was subdivided into three tissue samples of equal thickness, defined as the media-inner,-middle, and-outer layers. The sampling sites selected for analysis were from regions of the aortic surface that were free of atherosclerotic plaques. The calcium content within each tissue layer of the aorta was determined. Arterial wall thickness and the cholesterol content of the four layers were also measured. Intimal calcification increased progressively during aging: from 1.6 μg Ca/mg tissue at 20 years of age to 5.2 μg Ca/mg tissue by 90 years of age. When intima calcium concentration was expressed by tissue volume (w/v), no significant change during aging was found. Medical calcification, as w/v and by w/w, increased throughout aging. Calcium accumulation was most marked in the middle, elastin-rich layer of the media, increasing from 1.4 μg Ca/mg tissue at 20 years of age to 49.50 μg Ca/mg tissue by 90 years of age. Calcium levels also increased in the other media layers, but at a slower rate then that found within the middle media.
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  • 29
    ISSN: 1432-0827
    Keywords: Osteoporosis ; 1α-Hydroxyvitamin D3 ; Bone mineral density ; Fracture rate
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    Topics: Biology , Medicine , Physics
    Notes: Abstract The effects of 1α-hydroxyvitamin D3 [1α(OH)D3] on bone mineral density, fracture incidence, and bone metabolism were evaluated by a double-blind, placebo-controlled study. Eighty postmenopausal osteoporotic Japanese women (71.9±7.3 years, mean±SD) were randomly assigned to 1 μg of 1α(OH)D3 daily or inactive placebo for 1 year. All patients were given supplemental calcium (300 mg of elemental calcium daily). Lumbar (L2–L4) bone mineral density (BMD) determined by dual energy X-ray absorptiometry increased 0.65% with 1α(OH)D3 treatment and decreased 1.14% with placebo (P=0.037). BMD in both the femoral neck and Ward's triangle did not yield any significant differences between the two groups, whereas trochanter BMD in the 1α(OH)D3-treated group increased 4.20% and decreased 2.37% with placebo (P=0.055). X-ray analysis demonstrated that new vertebral fractures occurred in two patients with 1α(OH)D3 and in seven patients with placebo. The vertebral fracture rate in the treated group was significantly less (75/1000 patient years) than in the control group (277/1000 patient years; P=0.029). Hypercalcemia (12.1 mg/100 ml) occurred in one patient receiving 1α(OH)D3; however, the serum calcium level in this patient promptly decreased to the reference range after cessation of the treatment. There were no significant changes in serum creatinine level in either group. A significant increase in urinary excretion of calcium was found but there was no significant change in urinary excretion of hydroxyproline in the treated group. The serum level of bone-derived alkaline phosphatase activity significantly decreased by−26±26 (mU/ml) after the treatment (P=0.003). These results indicate that 1α(OH)D3 treatment is effective for maintaining trabecular bone mass and prevents further vertebral fractures without any serious adverse effects in postmenopausal osteoporosis.
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  • 30
    ISSN: 1432-0827
    Keywords: Bone ; Diphosphonate ; Osteoporosis
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    Notes: Abstract During intermittent cyclical etidronate treatment, a lower extremity pain syndrome associated with stress fractures was observed in three osteoporotic patients. This report describes the development of stress fractures during initial cycles of treatment, with recurrence of symptoms in two patients when etidronate therapy was resumed. Further studies are needed to confirm whether stress fractures are associated with cyclic etidronate treatment and if so, the incidence and pathophysiology need to be determined.
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  • 31
    ISSN: 1432-0827
    Keywords: Calcitonin ; Follow-up ; Osteoporosis ; Biochemical markers
    Source: Springer Online Journal Archives 1860-2000
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    Notes: Abstract We reviewed data on 42 postmenopausal women with established osteoporosis (forearm fracture or a low bone mass0 who had been randomly treated for 1 year with either rectal salmon calcitonin (sCT), 100 IU daily (n=25) or nasal sCT, 200 IU daily (n=17) applying an estimation algorithm for bone loss rates. Both groups received a daily calcium supplement of 500 mg. A group of 18 age-matched women who received no treatment served as controls. The bone mineral content of the distal forearm (BMCarm) was measured every 3 months by single photon absorptiometry. The individual rates of change during the 1-year period were calculated by linear regression analysis (αBMCarm). Bone loss rates were estimated initially and after 1 year of therapy by measurements of serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxyproline and calcium (both corrected for creatinine excretion) according to the estimation algorithm. Both administration forms revealed significant control group-corrected decreases in serum and urine markers of bone turnover of 15–40% (P〈0.05–0.01) and positive outcomes of 2% in αBMCarm (P〈0.01). The estimated effect on bone mass was expressed as the difference between the bone loss estimated after 1 year and initially (ΔESTBIO). A significant correlation was seen between αBMCarm and ΔESTBIO (r=0.5, P〈0.0001). We conclude that the effect of sCT on bone can be followed up by biochemical markers for bone turnover, i.e., by an annual blood and fasting urine sample, applying an estimation algorithm for the rate of bone loss.
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  • 32
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Bone mineral density ; Risk factors ; Population-based study
    Source: Springer Online Journal Archives 1860-2000
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    Notes: Abstract Population-based epidemiological studies on osteoporosis are few. Our study evaluated the effects of menopause and certain putative behavioral risk factors on bone mineral density (BMD). Spinal and femoral neck BMD were measured with dual X-ray absorptiometry (DXA) from 1600 perimenopausal women aged 48–59 years (mean 53.2 years) with no diseases or medications known to affect bone metabolism. These women were a selected sample of the Kuopio Osteoporosis Risk Factor and Prevention Study population (n=14,220). There was a wide variation of BMD among perimenopausal women. Menopause had a major effect on BMD. Postmenopausal women had significantly lower BMD in both spine (-6.2%) and femoral neck (-3.9%) as compared with premenopausal women. Multiple regression analysis showed that weight, menopausal status, age, and grip strength were significant independent predictors of both spinal and femoral BMD. Additionally, physical activity was found to be a significant predictor of femoral BMD, and alcohol consumption was a significant predictor of spinal BMD. However, current anthropometric and lifestyle factors explained only 18.7–25.4% of the variability of BMD. Therefore, the estimation of the risk factor status at menopause is not an adequate substitute for bone densitometry. However, our results may in part help clinicians to identify the risk groups at which to direct bone density measurements.
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  • 33
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    Calcified tissue international 55 (1994), S. 46-52 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Ultrasound ; Bone densitometry ; Bone structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract We investigated whether quantitative ultrasound (QUS) parameters are associated with bone structure. In an in vitro study on 20 cubes of trabecular bone, we measured broadband ultrasound attenuation (BUA) and two newly defined parameters—ultrasound velocity through bone (UVB) and ultrasound attenuation in bone (UAB). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) and bone structure was assessed by microcomputed tomography (μCT) with approximately 80 μm spatial resolution. We found all three QUS parameters to be significantly associated with bone structure independently of BMD. UVB was largely influenced by trabecular separation, UAB by connectivity, and BUA by a combination of both. For a one standard deviation (SD) increase in UVB, a decrease in trabecular separation of 1.2 SD was required compared with a 1.4 SD increase in BMD for the same effect. A 1.0 SD increase in UAB required a reduction in connectivity of 1.4 SD. Multivariate models of QUS versus BMD combined with bone structure parameters showed squared correlation coefficients of r2=0.70–0.85 for UVB, r2=0.27–0.56 for UAB, and r2=0.30–0.68 for BUA compared with r2=0.18–0.58 for UVB, r2〈0.26 for UAB and r2〈0.13 for BUA for models including BMD alone. QUS thus reflects bone structure, and a combined analysis of QUS and BMD will allow for a more comprehensive assessment of skeletal status than either method alone.
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  • 34
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    Calcified tissue international 55 (1994), S. 87-89 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Hip fracture ; Aging ; Cohorts ; Epidemiologic bias
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Osteoporosis, although a disorder of antiquity, has become more prevalent in developed countries and is a major risk factor for skeletal fracture. Accordingly, the increasing incidence of hip fracture among the elderly within developed nations has been attributed to an increased prevalence of osteoporosis. An increasingly sedentary lifestyle has been suggested as a significant contributing factor for the increased prevalence of osteoporosis. However, differential survival, reflecting changing competing mortality risks, will alter the gene pool of a surviving population cohort. Thus, the gene pool (and hence, disease susceptibilities) of 70-year-old individuals in 1990, for example, should not implicitly be assumed to be the same as 70-year-old individuals in 1950. Consequently, differences in the prevalence of osteoporosis or incidence of hip fracture between current and past elderly cohorts do not necessarily imply differences in environmental risk factors such as levels of physical activity. Instead, variation in competing mortality risks over time may produce differential survival with selection bias and “naturally” lead to increases in the incidence and prevalence of some aging-related disorders such as osteoporosis.
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  • 35
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Exercise ; Ovariectomy ; Bone strength ; DXA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The effect of treadmill running on the development of osteopenia was investigated in adult ovariectomized (OVX) rats compared with sedentary OVX and sedentary sham-operated rats. The rats were 3 months old with a mean weight of 214 g. OVX rats were fed a low calcium diet (0.01%), and the sham rats received the normal diet (1.1% calcium). The training consisted of treadmill running at a speed of 27 m/minute for 1 hour 5 out of 7 days during a period of 81/2 weeks. The weight gain was higher in the sedentary OVX (108 g) than in the training OVX (62 g) and sham-operated rats (61 g) (P〈0.001). Comparing the two OVX groups, training had no significant effects on the development of femoral osteopenia as assessed by mechanical testing of the femoral shaft and neck, and by bone mass measurements by dual energy X-ray absorptiometry (DXA) or by ashing. Comparing all three groups bone mineral content (BMC) and bone mineral density (BMD) were reduced by more than 40% in both the OVX groups compared with the sham-operated rats (P〈0.001). Ash weight and calcium content were reduced by approximately 40% in both OVX groups. Femoral volume and length were 10% higher in the sedentary OVX animals compared with the trained (P〈0.05), indicating that the training had had a negative effect on the growth changes induced by ovariectomy. The fracture strength of the femoral shaft was reduced by 26% and 22% in the trained and sedentary OVX rats, respectively compared with the sham-operated group (P〈0.001). The fracture strength of the femoral neck was reduced by 18% and 15% but due to one very weak neck in the sham group, this difference was not significant. The accuracy of BMC measured by DXA was high when compared with calcium content (r=0.98, P〈0.001) and ash weight (r=0.96, P〈0.001). DXA underestimated the BMC of the femur by 27% as compared with ash weight. BMC was also highly correlated to fracture strength of the shaft (r=0.85, P〈0.001), but not to fracture strength of the neck. This study shows that high intensity training had no positive effect on the development of osteopenia in rats, and we have also validated and found DXA to be a precise and useful tool for experimental studies on osteoporosis in the rat.
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  • 36
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    Planta 193 (1994), S. 67-73 
    ISSN: 1432-2048
    Keywords: Arabidopsis (root hairs) ; Calcium ; Electrical coupling of cells (pH, voltage) ; Inositol trisphosphate ; Plasmodesma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Voltage clamp was used to measure the voltage dependence of cell-to-cell coupling via plasmodesmata between higher-plant cells (root hairs of Arabidopsis thaliana (L.) Heynh.). In addition, ionophoresis was used to introduce a variety of ions [Ca2+, inositol-trisphosphate, Li+, K+, Mg2+, ethylene glycol-bis(β-aminoethyl ether)-N,N,N′, N′-tetraacetic acid (EGTA), 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), H+, and OH−] to examine whether they regulate cell-to-cell coupling. Electrical coupling showed high variability in this single cell type at the same developmental stage; the coupling ratio ranged from near 0% to about 90% with a mean value of 32%. It was voltage independent for intracellular voltage gradients (transplasmodesmatal) of -163 to 212 mV. While Ca2+ closes the plasmodesmatal connections (at concentrations higher than those causing cessation of cytoplasmic streaming), inositol-trisphosphate and lithium are without effect. Apparently, inositol-trisphosphate may not cause increased cytosolic Ca2+ in root hairs. Alkalinization by OH ionophoresis caused a modest decline in cell-to-cell coupling, as did acidification by H+ ionophoresis (to an extent causing the cell to become flacid). Increases in cytosolic K+, Mg2+, and the calcium chelator BAPTA by ionophoresis had no effect on cell-to-cell coupling. The regulation (and lack thereof) reported here for plant plasmodesmata is quite similar to that of gap junctions.
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  • 37
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    Archives of microbiology 161 (1994), S. 352-358 
    ISSN: 1432-072X
    Keywords: Calcium ; binding protein ; Calmodulin ; Nostoc sp. PCC 6720
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A 21-kDa novel polypeptide which possesses characteristics normally considered to be diagnostic of the calmodulin present in eukaryotic cells was isolated from the cyanobacterium Nostoc sp. PCC 6720. The major technique employed in the isolation of the polypeptide was ion-exchange chromatography on a Mono Q column. The 21-kDa polypeptide was shown: to activate pea NAD kinase in vitro, in a Ca2+ requiring reaction; to react with polyclonal antibodies raised against spinach calmodulin, but not with those raised against bovine brain calmodulin; and to exhibit a Ca2+ dependent shift in migration during SDS-PAGE.
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  • 38
    ISSN: 1432-2048
    Keywords: Calcium ; Gossypium (root, solutes) ; Root ; Salinity ; Stress ; Solute ; Deposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Cotton (Gossypium hirsutum L. cv. Acala SJ-2) seedlings were grown in modified Hoagland nutrient solution with or without 150 mM NaCl and supplemental 10 mM CaCl2. The spatial distribution of bulk-tissue osmotic potential (ΨS) and total osmotica, K, Na and Ca contents were determined in the growth zone of the primary root. This information was combined with the growth-velocity data from an earlier study (Zhong and Läuchli 1993) to estimate net deposition rates of osmoticum, water, K, Na and Ca by using the continuity equation. The ΨS was essentially uniform along the growth region for all treatments and considerably lowered by 150 mM NaCl in the medium. Total osmotica deposition was well synchronized with growth and deposition rates were enhanced by 150 mM NaCl. Osmoregulation in the treatments with 150 mM NaCl was indicated by an apparent solute accumulation which appeared to be due to the enhancement of osmoticum deposition rates. The presence of 150 mM NaCl greatly reduced the deposition rates of K and Ca throughout the growth zone; 10 mM Ca mitigated this effect only on K deposition in the apical 2.5-mm region. The deposition rate of Na was increased greatly by 150 mM NaCl; the increase was reduced by 10 mM Ca. At 150 mM NaCl, selectivity of K versus Na of the root was enhanced greatly in the apical 2mm region by the presence of 10 mM Ca; this mitigating effect by Ca declined rapidly with distance from the root tip. We conclude that one possible mechanism by which supplemental Ca alleviates the inhibitory effects of NaCl on cotton root growth is by maintaining plasma-membrane selectivity of K over Na.
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  • 39
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    The journal of membrane biology 141 (1994), S. 83-90 
    ISSN: 1432-1424
    Keywords: Phospholipid bilayers ; Triton X-100 ; Ion channels ; Calcium ; Zinc ; Protons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Addition of Triton X-100 to planar bilayers composed of dioleoyl phosphatidyl choline, diphytanoyl phosphatidyl choline or mono-oleoyl glycerol induces single channel-like events when electrical conductivity across the bilayer is measured. Addition of divalent cations or protons causes channels to disappear; single channel conductance of remaining channels is not significantly altered; addition of EDTA or alkali (respectively) reverses the effect. It is concluded that sensitivity to divalent cations and protons need not be dependent on specific channel proteins or pore-forming toxins, but may be a feature of any aqueous pore across a lipid milieu.
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  • 40
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    The journal of membrane biology 141 (1994), S. 59-68 
    ISSN: 1432-1424
    Keywords: Chloride conductance ; cAMP ; Calcium ; Ion Channel ; Cardiac Myocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Cl− conductance in cultured embryonic chick cardiac myocytes was characterized using whole-cell patch clamp techniques. Following elimination of cation currents in Na+and K+-free internal and external solutions, the basal whole-cell current was predominantly a Cl− current. Cl−-sensitive current (I Cl) was defined as the difference between the whole-cell currents recorded in normal and low [Cl−] o when measured in the same cell. The whole-cell current in the absence or presence of 10 μm cAMP was time independent, displayed outward rectification with the pipette [Cl−] 〈 40 mm, and was not saturated with a physiological Cl− gradient. The Cl− current was also activated by 1 μm forskolin and inhibited by 0.3 mm anthracene-9-carboxylic acid (9-AC). Forskolin was less effective than cAMP (internal dialysis) in activating the Cl− current. The cAMP- or forskolin-activated and basal Cl− current were reasonably fit by the Goldman-Hodgkin-Katz equation. The calculated P Cl in the presence of cAMP was increased by fiveto sixfold over the basal level. In the presence of 5 mm EGTA to decrease free [Ca2+] i , the whole-cell current could not be stimulated by cAMP, forskolin or IBMX (0.1 mm). These data suggest that cultured chick cardiac myocytes have a low basal Cl− conductance, which, as in some mammalian cardiac ventricular myocytes, can be activated by cAMP. However, this study shows that the activation process requires physiological free [Ca2+] i . This study was supported by grants from the National Institutes of Health (HL-17670, HL-27105 and HL-07107) for M.L. and by Institutional funds of the University of Arkansas for Medical Sciences for S.L.
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  • 41
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    The journal of membrane biology 141 (1994), S. 139-148 
    ISSN: 1432-1424
    Keywords: Calcium ; Cholesterol ; Liposomes ; Membrane fusion ; Phosphatidic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Degranulation involves the regulated fusion of granule membrane with plasma membrane. To study the role of lipid composition in degranulation, large unilamellar vesicles (LUVs) of increasing complexity in lipid compositions were constructed and tested for Ca2+-mediated lipid and contents mixing. Lipid-mixing rates of LUVs composed of phosphatidylethanolamine (PE) and phosphatidylserine (PS) were strongly decreased by the addition of either phosphatidylcholine (PC) or sphingomyelin (SM), while phosphatidylinositol (PI) had little effect. “Complex” LUVs of PC∶PE∶SM∶PI∶PS (24∶27∶20∶16∶13, designed to emulate neutrophil plasma membranes) also showed very low rates of both lipid mixing and contents mixing. The addition of cholesterol significantly lowered the Ca2+ threshold for contents mixing and increased the maximum rates of both lipid and contents mixing in a dose-dependent manner. Membrane remodeling, which occurs in neutrophil plasma membranes upon stimulation, was simulated by incorporating low levels of phosphatidic acid (PA) or a diacylglycerol (DAG) into complex LUVs containing 50% cholesterol. The addition of PA both lowered the Ca2+ threshold and increased the rate of contents mixing in a dose-dependent manner, while the DAG had no significant effect. The interaction of dissimilar LUVs was also examined. Contents-mixing rates of LUVs of two different cholesterol contents were intermediate between the rates observed for the LUVs of identical composition. Thus, cholesterol needed to be present in only one fusing partner to enhance fusion. However, for PA to stimulate fusion, it had to be present in both sets of LUVs. These results suggest that the rate of degranulation may be increased by a rise in the cholesterol level of either the inner face of the plasma membrane or the outer face of the granule membrane. Further, the production of PA can promote fusion, and hence degranulation, whereas the subsequent conversion of PA to DAG may reverse this promotional effect.
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  • 42
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    The journal of membrane biology 142 (1994), S. 229-240 
    ISSN: 1432-1424
    Keywords: Calcium ; Exocytosis ; Membrane fusion ; Paramecium tetraurelia ; Veratridine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Paramecium tetraurelia wild-type (7S) cells respond to 2.5 mm veratridine by immediate trichocyst exocytosis, provided [Ca2+] o (extracellular Ca2+ concentration) is between about 10−4 to 10−3 m as in the culture medium. Exocytosis was analyzed by light scattering, light and electron microscopy following quenched-flow/ freeze-fracture analysis. Defined time-dependent stages occurred, i.e., from focal (10 nm) membrane fusion to resealing, all within 1 sec. Veratridine triggers exocytosis also with deciliated 7S cells and with pawn mutants (without functional ciliary Ca channels). Both chelation of Ca2+ o or increasing [Ca2+] o to 10−2 m inhibit exocytotic membrane fusion. Veratridine does not release Ca2+ from isolated storage compartments and it is inefficient when microinjected. Substitution of Na+ o for N-methylglucamine does not inhibit the trigger effect of veratridine which also cannot be mimicked by aconitine or batrachotoxin. We conclude that, in Paramecium cells, veratridine activates Ca channels (sensitive to high [Ca2+] o ) in the somatic, i.e., nonciliary cell membrane and that a Ca2+ influx triggers exocytotic membrane fusion. The type of Ca channels involved remains to be established.
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  • 43
    ISSN: 1615-6102
    Keywords: Calcium ; Cationic gold ; Cell wall ; Fruit ; Pectin ; Ripening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The ripening and softening of fleshy fruits involves biochemical changes in the cell wall. These changes reduce cell wall strength and lead to cell separation and the formation of intercellular spaces. Calcium, a constituent of the cell wall, plays an important role in interacting with pectic acid polymers to form cross-bridges that influence cell wall strength. In the present study, cationic colloidal gold was used for light and electron microscopic examinations to determine whether the frequency and distribution of anionic binding sites in the walls of parenchyma cells in the apple were influenced by calcium, which was pressure infiltrated into mature fruits. Controls were designed to determine the specificity of this method for in muro labelling of the anionic sites on the pectin polymers. The results indicate that two areas of the cell wall were transformed by the calcium treatment: the primary cell walls on either side of the middle lamella and the middle lamella intersects that delineate the intercellular spaces. The data suggest that calcium ions reduce fruit softening by strengthening the cell walls, thereby preventing cell separation that results in formation of intercellular spaces.
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  • 44
    ISSN: 1615-6102
    Keywords: Algae ; Calcium ; Coccolithophorids ; Golgi ; Mineralization ; Polyanions ; Polysaccharides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Immunolocalization of two highly acidic polysaccharides (PS-1 and PS-2) in a calcifying algaPleurochrysis carterae is described throughout the mineralization process, from before crystal nucleation through the cessation of crystal growth. This unicellular coccolithophorid alga is a useful model for mineralization because it produces calcified scales known as coccoliths in homogeneous cell culture. PS-1 and PS-2 were localized in the crystal coats of mature coccoliths and in electron dense Golgi particles. The polyanions are synthesized in medial Golgi cisternae and co-aggregate with calcium ions into discrete 25 nm particles. Particle-laden vesicles bud from cisternal margins and fuse with a coccolith-forming saccule containing an organic oval-shaped scale which forms the base of the future coccolith. The particles are localized on the base before the onset of mineral deposition and are present in the coccolith saccule throughout the period of crystal (CaCO3) nucleation and growth. During the final phase of coccolith formation, the particles disappear, and the mature crystals acquire an amorphous coat containing PS-1 and PS-2 polysaccharides which remain with the mineral phase after the coccoliths are extruded from the cell. Postulated mechanisms of polyanion-mediated mineralization are reviewed and their relevance to the calcification of coccoliths is addressed.
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  • 45
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    Pharmacy world & science 16 (1994), S. 34-35 
    ISSN: 1573-739X
    Keywords: Calcium ; Chronotropic response ; Inotropic response ; Ischemia ; Receptors, adrenergic ; Receptors, muscarinic ; Signal transduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 46
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    Plant foods for human nutrition 45 (1994), S. 35-46 
    ISSN: 1573-9104
    Keywords: Carotene ; Chloroplasts ; Leaf protein ; Alum ; Calcium ; Citrate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Loss of β carotene from moist leaf protein stored with a preservative, is closely simulated by the destruction of β carotene by acetone extracted chloroplasts (stroma) suspended in acetone containing 30% water. During this exposure, stroma lose destructive ability, but it is restored by mercaptoacetate and other reducing agents. Stroma can therefore be used repeatedly. This catalytic process is activated by removing intrinsic inhibitors, predominantly calcium, by extraction at pHs less than 4, or by alum. The objective is to find inhibitors which would be acceptable in a food. That restricts choice. Citrate, tartarate and phosphate are among the more attractive possibilities.
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  • 47
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    Annals of biomedical engineering 22 (1994), S. 532-539 
    ISSN: 1573-9686
    Keywords: Osteoporosis ; Trabecular structure ; Bone metabolism ; Femoral neck fracture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Progression of osteoporosis is caused by a decline in bone formation activity relative to the resorption activity. In this paper, the authors carried out a theoretical analysis of the progression of osteoporosis to estimate the osteoporotic change in the upper end of the femur. According to this analysis, the progression rate of osteoporosis in cancellous bone depends on the product of remodeling activity,R act, and the trabecular structure parameter,K tr. To confirm that the theoretical results were reasonably comparable to actual osteoporotic change, these two factors were measured in rabbits. From the results, it was concluded that the highest progression rate was shown in bar/barlike trabecular structure (type 3); the next highest rate, was shown in plate/bar-like structure (type 2); and the plate/plate-like structure (type 1) was the most insensible. Furthermore, the bone volume fractions of cancellous bone were measured at the upper end of human femurs with and without osteoporosis. Then the measured value was compared with the theoretical value for each type of trabecular structure. Results showed that the decrease in bone volume fraction predicted by Eq. 7 was well in accord with the actual decrease.
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  • 48
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    World journal of microbiology and biotechnology 10 (1994), S. 303-307 
    ISSN: 1573-0972
    Keywords: Calcium ; cyanobacterium ; herbicide ; nitrogenase ; insecticide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Methylparathion and Benthiocarb inhibition of N2 fixation in the cyanobacterium Nostoc muscorum was reversed by Ca2+ at 1 mm but not at 0.1 mm. The concentration of intracellular Ca2+ was relatively high in the presence of these pesticides when 1 mm Ca2+ was also present, indicating that intracellular Ca2+ may participate in protecting nitrogenase activity against Methylparathion and Benthiocarb.
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  • 49
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Vertebral fracture ; Bone histomorphometry ; 85Sr
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The histologic heterogeneity of osteoporosis relative to normal controls has attracted great interest. There has been controversy as to whether patients with high turnover osteoporosis may convert to a normal or low turnover form, and vice versa. We have studied 44 patients over 12 years by dynamic histomorphometry and85Sr kinetics + calcium balance performed within 60 days in 20 patients (Group 1) and 75–808 days apart in the remainder (Group 2). In the first group, the histologic tissue level bone formation rate (BFR/BV or BFR/BS) was predictive of the85Sr measurements of bone formation (r=0.66P〈0.01). There was no statistically significant correlation in Group 2 and the regression coefficients were significantly different (P=0.01). Periodic regression was used to determine if seasonal changes were responsible for this loss of correlation; none was found that was of statistical significance. No systematic changes with time in bone formation were found in Group 2 during the period of observation; nor were consistent secular changes detected when the data for both groups were examined according to procedure data. In conclusion, bone formation may change with time in postmenopausal osteoporosis. Evidence that these changes are systematic was not found and this has implications for the design of treatment studies.
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  • 50
    ISSN: 1432-0827
    Keywords: Osteoblastic cell lines ; Human osteosarcoma cell ; Aromatase ; Adrenal androgen ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Aromatase activity was studied in cultured human osteosarcoma cell (HOS). HOS was incubated from 12 to 72 hours with 10-10 M-10-5 M dexamethasone. Aromatase activity was determined by measuring [3H]H2O released upon the conversion of [1β-3H]androstenedione to estrone. HOS showed aromatase activity, and apparent km for [1β-3H]androstenedione was 4.46±0.98 nm (mean±SD). The aromatase activity was significantly increased by 10-9 M-10-5 M dexamethasone in a dose-dependent manner. Dexamethasone increased Vmax of aromatase activity but did not change its km value. These results suggest that osteoblastic cells have aromatase activity which is regulated by glucocorticoid, and directly convert androgen to estrogen in itself.
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  • 51
    ISSN: 1432-0827
    Keywords: Hip fracture ; Falls ; Osteoporosis ; Biomechanics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Hip fractures among the elderly are a significant and rapidly growing public health problem. The prevailing view is that most hip fractures are the consequence of age-related bone loss or osteoporosis. However, because over 90% of hip fractures are the result of falls, we have undertaken a falls surveillance study to determine if factors related to the mechanics of falling are associated with increased risk of hip fracture. Case subjects with hip fracture and control subjects without hip fracture were sampled from falls recorded at the Hebrew Rehabilitation Center for Aged, a chronic care facility. Fall information was obtained by interview of the subject and witnesses if the fall was witnessed. Data were analyzed by multiple logistic regression. Increased risk of hip fracture from a fall was associated with impacting on the hip or side of the leg and potential energy associated with the fall. Quetelet, or body mass index, was inversely related to fracture risk. The adjusted odds ratio of hip fracture for a fall involving impact on the hip region was 21.7 (95% confidence interval, 8.2–58). The potential energy associated with these falls was an order of magnitude greater than the average energy required to fracture elderly, cadaveric, proximal femurs in earlier in vitro experiments. We conclude, therefore, that a fall from standing height should no longer be considered minimal trauma but rather trauma of sufficient magnitude to pose a high risk of hip fracture if impact occurs on the hip and if energy-absorbing processes are inadequate. These new findings suggest that fall mechanics play an important role in the etiology of hip fracture among the elderly.
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  • 52
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    Calcified tissue international 52 (1993), S. 263-268 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Bone density ; Postmenopausal ; Vertebral collapse ; Bisphosphonate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Bone mineral density (BMD) at the lumbar spine, femoral neck, trochanteric region, and Ward's triangle was measured using dual-energy X-ray absorptiometry (DXA) in 118 women with osteoporotic vertebral collapse (average age 65 years), divided into four groups according to numbers and SD of vertebral deformation below norms: group 1:-3SD deformations only; group 2: one-4SD deformation; group 3: two-four-4SD deformations; and group 4: 5 or more-4SD deformations. There were no significant differences between the groups. Results were compared with those from 80 premenopausal (average age 32 years, range 20–40 years) and 109 postmenopausal normal women (average age 64, range 60–70 years). Mean BMD in osteoporotic group 1 was lower than premenopausal normal women by 32% at the lumbar spine, 31% femoral neck, 30% trochanteric region, and 44% at Ward's triangle, and postmenopausal controls by 17% lumbar spine, 16% femoral neck, 17% trochanter, and 14% Ward's triangle. There was a clear trend to reduction in mean BMD between osteoporotic groups 1 and 4 at all four measured sites with significant differences at the spine of 0.102 g/cm2 (P〈0.01) and Ward's triangle 0.059 g/cm2 (P〈0.01). When compared with premenopausal controls, there was a reduction in mean BMD between osteoporotic groups 1 and 4 of 10% at the lumbar spine, 7% femoral neck, 8% trochanteric region, and 13% Ward's triangle. Receiver operating characteristic analysis showed no significant differences in diagnostic sensitivities among the four measured sites for vertebral fractures. We conclude from this crosssectional data that the majority of bone loss in spinal osteoporosis occurs before the onset of fractures.
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  • 53
    ISSN: 1432-0827
    Keywords: Interleukin 1 ; Calcium ; Inflammation ; Granuloma ; Potassium permanganate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Interleukin-1 (IL-1) is a monokine that exerts multiple biological activity, including immunity and inflammation. Moreover, IL-1 is involved in Ca2+ release causing hypercalcemia and bone resorption. Recently, a 22 kDa natural inhibitor to IL-1 called interleukin-1 receptor antagonist (IL-1ra) has been described in human fluids, which specifically binds IL-1α or IL-1β receptors. In this study, we found that experimental granuloma induced by subcutaneous injections (0.2 ml) of potassium permanganate (KMnO4) 1:40 saturated crystal solution, after 7 days was strongly inhibited in size, weight and calcium content (measured as dry ash weight by incineration of granuloma tissue) compared with untreated controls, in mice treated intraperitoneally with IL-1ra (20 μg/bolus) given twice; the first at the same time of the induction of the granuloma and the second 24 hours later. In addition, leukotriene B4 and prostaglandin E2 were also inhibited in fresh granuloma of mice treated with IL-1ra. Taken together, these findings conclude for the first time, that the accumulation of calcium in chronic inflammatory states is strongly inhibited by IL-1ra, which decreases tissue calcergy and can potentially be useful for the treatment of calcium-related inflammatory diseases and malignancy-associated hypercalcemia.
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  • 54
    ISSN: 1432-0827
    Keywords: Growth hormone ; Osteoblast ; Growth factors ; Osteoporosis ; Bone cell cultures ; Bone formation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary In this study we investigated the direct, shortterm effects of human growth hormone (hGH) on the biology of normal adult human osteoblast-like (hOB) cells cultured from trabecular bone explants. In Subconfluent cultures, hGH stimulated hOB proliferation in a dose-dependent fashion (P〈0.001, n=15) with half-maximal effects at a concentration of 10 ng/ml. These mitogenic effects were detectable within 24 hours as shown by bromodeoxyuridine labeling. In confluent cultures containing mainly quiescent cells, hGH increased levels of alkaline phosphatase (P〈0.05, n=10) and to a lesser degree levels of procollagen type I carboxyterminal propeptide (PICP) (P=0.07, n=9). Effects on osteocalcin (bone GLa protein, BGP) levels were highly variable among different cell strains and only 7 of 10 cell strains showed a stimulatory response (P=0.16). We also studied the effects of hGH on osteoblastic production of insulin-like growth factor I (IGF-I) and IGF-II as well as the production of GH-dependent, insulin-like growth factor binding protein 3 (IGFBP-3). Under basal conditions, human osteoblasts produced IGF-II and IGFBP-3 in the conditioned medium. When stimulated with hGH, minor insignificant increase in both IGF-II and IGFBP-3 (125% and 126% of control, respectively) were detectable. No IGF-I was detectable in the conditioned medium under basal conditions or after stimulation with hGH. In conclusion, the results obtained in this study suggest that GH exerts direct anabolic effects on human osteoblasts.
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  • 55
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Exercise ; Ovariectomy ; Bone strength
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The effects of non-endurance exercise on bone properties were evaluated in 9-month-old sham-operated (SH) and ovariectomized (OVX) rats. The studies were started 3 months postsurgery, after bone mass was decreased in OVX rats. The sham and OVX rats were either kept sedentary (SED) or were trained to run with one of two protocols: 12 m/minute, 50 minutes/day, 4 days/week (low intensity, frequent, EX-1); or 21 m/minute, 40 minutes/day, 1 day/week (moderate intensity, infrequent, EX-2). A group of seven rats evaluated at the beginning of the study served as baseline control. The bone mineral was assessed by the ash weight of the left femur, tibia, and 4th lumbar vertebra. Biomechanical (strength, deformation, stress, strain, and stiffness) and morphometric (length, cortical and medullary area, moment of inertia) properties were evaluated for the right femur. There was a significantly lower bone mineral and mechanical properties in OVX-SED (n=7) than in SH-SED (n=10) rats. The OVX-EX-1 (n=6) rats had higher ash content of femur and tibia than OVX-SED rats, but the change was significant only for tibia. The EX-2 had no effect on the ash content, but femur stress was higher in OVX-EX-2 (n=8) than in OVX-SED rats. The femur yield force and deformation were improved in OVX rats with both exercise protocols, whereas the vertebra ash weight, femur strain, modulus of elasticity, length, cortical area, and moment of inertia were not changed. Non-endurance exercise did not affect bone properties in either SH-EX-1 (n=7) or SH-EX-2 (n=8) groups. We conclude that non-endurance exercise has beneficial effects on established osteopenia in ovariectomized rats.
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  • 56
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    Calcified tissue international 52 (1993), S. 244-247 
    ISSN: 1432-0827
    Keywords: Bone density ; Material damping ; Aging ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The aim of this work was a preliminary assessment of the feasibility of using in vivo measurements of mechanical properties of bones to detect mineral loss and further to relate them to the tendency of the bone to fracture in the case of loss of minerals, such as in osteoporosis. Previous studies of bone strength in vitro have demonstrated that the decrease in bone strength in both the spine and the femur has strong correlation with the mineral content (BMC) measured with bone densitometry. It was demonstrated that loss of mineral in the bone is accompanied by substantial change of the main mechanical properties, decrease of the Young's modulus, and increase of the damping factor. The change in those properties is one order of magnitude greater than the change in bone density. Moreover, increase of bone density, by was of training, resulted in decrease of the damping factor that also was substantially greater than the change in density. The tests showed clearly that the change in mechanical properties was much greater than the change in bone mass density. This offers an attractive new alternative to the detection of bone mass loss as it appears that the change of the bone mass is well correlated to the change in these mechanical properties. In particular, the change in the damping factor of the material was found to be much more substantial than the bone density change. Therefore, the damping mechanism offers the vehicle for a direct assessment of the bone tendency to fracture due to the loss of mass, as tendency to fracture and mass loss are known to be related. Increasing bone density due to training showed similar results. The decrease in damping, though still much greater than the increase in density, is not as much different as in the case of loss of mass because there is a point when density increases to the extent that the bone becomes compact (no voids) and its damping would not drop further with increasing mass. This method, as compared with the bone density measurement methods, appears to have some definite advantages for monitoring the mineral loss in bones.
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  • 57
    ISSN: 1432-0827
    Keywords: Colles' fracture ; Hip fracture ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Objective: To determine the long-term risk of hip fracture following fracture of the distal forearm. Design: Registry-based cohort study comparing patients with a fracture of the distal forearm with a population-based cohort. Fracture cohort: All women and men above 40 years of age with a radiologically verified fracture of the distal forearm during a 5-year period. 1968–1972, in all 1,126 women and 212 men. Control cohort: An equal number of population-based, age-and sex-matched control persons selected from a population register. Measurements: All cohort members were followed up individually through record linkage until the first hip fracture, emigration, death, or the end of 1991. The cohort members contributed a total of 40,832 person-years of observation, and altogether 365 cases of hip fractures were observed. Results: Both women and men with a fracture of the distal forearm ran an increased risk of sustaining a subsequent hip fracture. The overall relative hazard for the women was 1.54 and for men 2.27. The increased risk in the women was independent of age at inclusion, but that in the men was more pronounced in the younger age groups. Conclusions: Patients with a fracture of the distal forearm run an increased risk of sustaining a subsequent hip fracture. They therefore appear to constitute a group in which appropriate prophylactic measures against osteoporosis and fractures should be considered.
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  • 58
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    Calcified tissue international 52 (1993), S. 331-333 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Nutrition ; Biochemical markers ; Crush fracture syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Thirty-six women with vertebral osteoporosis showed significantly decreased levels of biochemical markers of nutrition, transferrin (P〈0.001), prealbumin (P〈0.001), retinol binding-protein (P〈0.001), and fibronectin (P〈0.001), compared with 40 healthy women of similar age. Multiple regression analysis showed a significant (R2=0.509; P=0.0068) correlation between bone mineral content and biochemical markers of nutrition in the osteoporotic patients but not in the control group. These data suggest that postmenopausal osteoporosis may be associated with a nutritional deficiency.
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  • 59
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Menopause ; Estrogen ; Pyridinoline ; Bone resorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Objective: To evaluate and compare the effects or oral and transdermal estrogen replacement therapy on biochemical markers of bone resorption in early postmenopausal women Design: Controlled, randomized group comparison. Setting: Outpatient clinic for menopausal women and research into osteoporosis. Subjects: Sixty healthy women menopausal for less than 5 years and who had never received any medications interfering with bone metabolism. Interventions: The 60 women were randomly allocated to 3 months therapy with either oral conjugated estrogens (0.625 mg/day) (n = 28) or transdermal estradiol (50 jig/day) (n = 32) in cyclical combination with medroxyprogesterone acetate (5 mg/day). Main outcome measures: Traditional (urinary calcium/creatinine and hydroxyproline/creatinine) and the new specific (urinary pyridinoline/creatinine and deoxypyridinoline/creatinine) markers of bone resorption were determined before and after 3 months of treatment. Results: In both groups, circulating levels of estrone and estradiol were significantly (P 〈 0.001) increased during treatment. In women treated with oral conjugated equine estrogens, urinary calcium/creatinine and hydroxyproline/creatinine ratios were significantly (P 〈 0.05) reduced. Pyridinoline/creatinine ratio fell from 69.1 (4) [mean (SEM)] to 50 (4) μmol/μmol (P 〈 0.01) and deoxypyridinoline/creatinine ratio fell from 10.8 (1) [mean (SEM)] to 8.3 (0.8) μmol/μmol (P 〈 0.01). In the group treated with transdermal estradiol, urinary hydroxyproline/creatinine ratio was significantly (P 〈 0.05) reduced. Pyridinoline/creatinine ratio fell from 66.3 (4) [mean (SEM)] to 46.2 (3) μmol/μmol (P 〈 0.01) and deoxypyridinoline/creatinine ratio fell from 11.5 (1.5) [mean (SEM)] to 7.7 (0.6) μmol/μmol (P 〈 0.01). There were no differences between the evolution of the biochemical variables in the two groups. Conclusion: These results suggest that oral conjugated equine estrogens and transdermal estradiol, in the given doses, are equally effective in reducing postmenopausal bone resorption.
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  • 60
    ISSN: 1432-0827
    Keywords: Osteocalcin ; Prednisolone ; Deflazacort ; Osteoporosis ; Plasma glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Glucocorticoids adversely affect bone and mineral metabolism through a number of mechanisms, including inhibition of bone formation. Deflazacort is a glucocorticoid which has been reported to be relatively “bone-sparing.” We compared the effects in oophorectomized sheep of deflazacort and prednisolone on the metabolism of osteocalcin (OC), a marker of osteoblast function. An [125I]OC infusion method was used to measure the OC plasma clearance rate (PCR) and OC plasma production rate (PPR). Six-day intravenous infusion of deflazacort and prednisolone (in the dose range 0.007–1.00 mg/hour) induced dose-dependent decreases in OC PPR which were of a similar pattern but significantly different magnitude (P 〈 0.02); deflazacort demonstrated a potency about 150% that of prednisolone. Both steroids decreased plasma OC levels on a dose-related basis but at the lower doses 0.05 mg/hour (P 〈 0.05) and 0.013 mg/hour (P 〈 0.0005), deflazacort caused greater decrements. OC PCR was significantly increased only by higher doses of deflazacort (1.00 mg/hour, 0.25 mg/hour;P 〈 0.05). Deflazacort and prednisolone increased both postabsorptive plasma glucose and plasma calcium levels, but there were no significant differences between their effects. We conclude that plasma OC levels and OC PPR in sheep were more sensitive to the effects of deflazacort than to prednisolone. At high doses, the depressive effect of deflazacort on plasma OC levels may have been due in part to an increased OC PCR which was not evident with prednisolone treatment. However, the agents appeared to have a similar dose-dependent hyperglycemic effect, and both caused a small dose-dependent increase in plasma calcium. These findings indicate that prednisolone had similarly potent effects on both bone and glucose metabolism while deflazacort exhibited differential potency on the two systems. The greater potency of deflazacort on bone in sheep may be due to species differences in steroid metabolism or steroid-receptor interaction.
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  • 61
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    Calcified tissue international 53 (1993), S. S68 
    ISSN: 1432-0827
    Keywords: Bone strain ; Fatigue failure ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Functionalin vivo strain data are examined in relation to bone material properties in an attempt to evaluate the relative importance of osteoporotic bone loss versus fatigue damage accumulation as factors underlying clinical bone fragility. Specifically, does the skeleton have a sufficiently large safety factor (ratio of bone failure strain to maximum functional strain) to require that fatigue damage accumulation is the main factor contributing to increased risk of fracture in the elderly? Existing methods limitin vivo strain measurements to the surfaces of cortical bone. Peak principal compressive strains measured at cortical sites during strenuous activity in various mammalian and avian species range from −1700 to −5200 με, averaging - 2500 με (−0.0025 strain). Much of this threefold variation reflects differences in the intensity of physical activity, as well as differences among species and bones that have been studied. Peak strains can also vary as much as tenfold at different cortical sites within the same bone. No data exist for cortical bone strain during strenuous activity in humans, but it is likely that human bones experience a similar range of peak strain levels. Compact bone fails in longitudinal compression at strains as high as −14,000 to −21,000 με, but begins to yield at strains between −6000 and −8000 με. Given that yielding involves rapid accumulation of microdamage within the bone, it seems prudent to base skeletal safety factors on the yield strain, rather than the ultimate failure strain of bone tissue. Safety factors to yield failure therefore range from 1.4 to 4.1. This safety factor range is likely diminished further by age-related increases in mineralization and secondary remodeling that reduce the strength and energy-absorbing capacity of bone. Although no one safety factor applies to all skeletal sites within an individual, it seems clear that osteoporotic bone loss of 40 to 50% of normal constitutes a causative factor of clinical bone fragility, particularly if bone loss is high at sites of high functional strain. Theoretical consideration of the statistical distribution of bone strength in relation to functional loading events within a population over a lifetime of use further supports this interpretation, by indicating an increased probability of fracture with increasing age. Fatigue damage accumulation will serve to exacerbate these trends. Bone loss and fatigue damage accumulation therefore, should be viewed as mutually reinforcing agents of bone fragility. Improved correlation of peak functional strain patterns with localized bone loss and bone turnover dynamics at sites of high fracture risk, together with assessment of microdamage, is needed to resolve the relative contribution of these factors to osteoporotic bone fragility.
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  • 62
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    Calcified tissue international 53 (1993), S. S143 
    ISSN: 1432-0827
    Keywords: icrocallus ; Cancellous bone ; Osteoporosis ; Osteoarthrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Healing trabecular microfractures are a common feature in cancellous bone. These lesions, when observed in macerated cancellous bone slices, measure about 500 μm in diameter and surround fractures in trabeculae with microcallus. Whether microcallus is a structure acting primarily as a transient brace, preventing relative movement of the fragmented segments and enabling the trabecula to heal, or whether it is a permanent buttress reducing the stress on the fractured strut, preventing the healing process, is not known. Microfractures are the result of normal physical activity. Hence, the widespread occurrence of trabecular microfracture in cancellous bone implies that a reasonable rate of microfracture is physiologically tolerable. There are three putative effects for trabecular microfracture. One is that, in response to impulse loading, cancellous subchondral bone increases its rigidity due to osteosclerosis resulting from bone formed around microfractures. Another hypothesis is that, if sufficient trabecular microfractures occur, they will compromise the trabecular structure of the vertebra and the proximal femur leading to osteoporotic fracture. By inducing remodeling changes, microfractures have an effect on the maintenance of joint structure. There are two histological patterns for microfractures: an early stage, when actively forming woven bone is bridging the fracture; and a more common late stage, when woven bone is inactive. Femoral studies fail to demonstrate that an increasing number of healed or healing microfractures in osteoarthrosis causes the increase of bone in the head of femur. Only one study has reported a significant increase in the number of trabecular microfractures in osteoarthrotic femoral heads compared with normal controls. This significant increase was in patients taking antiinflammatory drugs. In osteoporotic fracture, sufficient trabecular microfracture may lead to femoral fracture. The bone loss in the vertebral bodies is by a loss of horizontal trabeculae. This loss reduces the resistance of vertical elements to deformation under load and creates the conditions for trabecular fracture. Coincident with this observation, microfracture is most prevalent on the vertical structure. The increase of microfractures with increasing age has three possible explanations: (l) the incidence of microfracture increases as trabeculae become thinner; (2) the incidence of microfracture is constant but the rate of healing decreases; or (3) these two factors combine to increase the number of microfractures. The occurrence of trabecular microfracture has been shown to correlate with factors such as physical activity, age, bone viability and remodeling potential, cancellous bone volume, bone mineral content, bone fatigue properties, and the direction of cancellous bone loading. As trabecular microfracture is not an event that initiates a pathological process, a number of important questions need to be addressed. Whatever the answers to these questions, trabecular microfracture is intimately linked to the nature of cancellous bone structure, and the conditions under which microfracture will compromise this structure are fundamental to the question of bone quality.
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  • 63
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    Calcified tissue international 53 (1993), S. 149-152 
    ISSN: 1432-0827
    Keywords: Ultrasound ; Bone mineral density ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary A new ultrasound bone densitometer has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and a proprietary factor derived from SOS and BUA, termed “stiffness.” Short-term precision of ultrasound measurements was 1.4% for BUA, 0.2% for SOS, and 1.5% for stiffness in healthy women, and 1.1% for BUA, 0.1% for SOS, and 1.5% for stiffness in osteopenic women. One hundred seven women underwent measurements by ultrasound, together with dual energy X-ray absorptiometry (DXA) bone mineral density (BMD) measurements of the lumbar spine and proximal femur. Correlations between SOS, BUA, and stiffness measurements and DXA BMD measurements were all highly significant (P 〈 0.001) with r values varying from 0.54 to 0.67. BUA, SOS, and stiffness measurements were all significantly different between normal and osteopenic women even after adjusting for age, height, and weight (P 〈 0.05,P 〈 0.001, andP 〈 0.01, respectively). These results demonstrate that this ultrasound system measures ultrasonic properties of the os calcis with good precision, the measurements correlate moderately well with DXA BMD measurements and they can differentiate between normals and those with osteopenia.
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  • 64
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    Calcified tissue international 53 (1993), S. S151 
    ISSN: 1432-0827
    Keywords: Ultrasound ; Bone fragility ; Osteoporosis ; Fracture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Progress in clinical characterization of bone relies on developing a means to clinically assessall of the important determinants of bone quality, specifically, the intrinsic material properties of a bone (stiffness and brittleness) versus the macroscopic structural properties [apparent mass density (g/cc), structural shape and distribution of cortical mass, trabecular architecture, extent of unrepaired microdamage, and defects associated with the accelerated remodeling in early menopause]. Ultrasound devices currently measure parameters related to either of only two basic properties: bone ultrasound attenuation (BUA) or the apparent velocity of wave propagation (AVU). Theory and repeated corroboration in the laboratory have shown that the velocity of sound in solids such as bone has a quantitative relationship to the elastic modulus (or stiffness) and mass density. Although no comparable physical model exists for BUA, growingin vitro andin vivo empirical evidence shows a relationship to stiffness and mass density as well. Therefore, the question of ultrasound's ability to provide additional, clinically useful information about bone quality reduces to this:Does bone quality depend significantly on bone stiffness and does stiffness depend on factors other than bone mass alone? Clinical study results provide mounting evidence of ultrasound's abilities. (1) Numerous studies compare either velocity or BUA with BMC or BMD. The correlation coefficients vary widely between studies, even when repeated by the same investigators and laboratories. Two studies demonstrated this by comparing groups of subjects who are indistinguishable by BMD at the lumbar spine, but whose mean AVU readings are significantly different. (2) Multiple studies of AVU and BUA by different investigators have shown the ability of ultrasound to distinguish, as effectively as BMC or BMD, women with osteoporotic vertebral crush deformities from normal women. Prospective studies have shown that AVU and BUA each indicated risk of future osteoporotic fractures. In a population-based, randomized, cross-sectional study of men and women, AVU discriminated between groups of subjects who had suffered low trauma fractures versus those free of fracture. Such repeated clinical evidence of the ability of BUA and AVU to detect bone fragility provides mounting evidence that ultrasound measures a clinically relevant property of bone quality in addition to and distinct from bone mass.
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  • 65
    ISSN: 1432-0827
    Keywords: Male ; Osteoporosis ; Free testosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary It is unclear what proportion of the variance in bone density in elderly males is accounted for by testosterone status. We studied 112 ambulatory, elderly volunteers (mean age 71.7 years) and determined free testosterone (FT), as well as bone density measurements by photon absorptiometry at multiple sites. Our studies of 35 of these subjects 4 years later includedmorning FT and dual energy X-ray absorptiometry. There were no significant correlations between FT and bone density at multiple scanning sites with the effects of age partialed out. We suspect that our inability to detect a significant effect of FT on bone density was related to the relative strength of other determinants of bone density, as well as to the fact that FT values are far more dynamic than bone density.
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  • 66
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    Calcified tissue international 52 (1993), S. 99-102 
    ISSN: 1432-0827
    Keywords: Bone density ; Osteoporosis ; Normal population
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Bone density of the spine and femoral neck and broadband ultrasound attenuation of the calcaneus were measured in 111 normal Spanish women between the ages of 30 and 70 years. The cross-sectional study showed that spine and hip density decreased by 36 and 29%, respectively, and the ultrasound attenuation value decreased by 32% between 30 and 70 years of age. The rate of bone loss at the three sites was significant in women over age 50 and in postmenopausal women. These normative data will be helpful in assessing bone mass in Spanish women suspected of having osteoporosis.
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  • 67
    ISSN: 1432-0827
    Keywords: SHR-WKY rats ; Calcium ; Calcitriol ; Intestine ; Calbindin ; Alkaline phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary the response pattern of plasma calcitriol level and related intestinal adaptation to short-term moderate calcium (Ca) restriction was examined in adolescent male, spontaneously hypertensive rats (SHR) and normotensive WKY control rats. Twelve-week-old SHR and WKY fed a low (0.1%) Ca diet for 3, 6, or 12 days were compared with rats of either strain fed a normal (1.0%) Ca diet. Plasma calcitriol response was measured and duodenal adaptation to Ca restriction was investigated by evaluating active Ca transport, calbindin-D9K (CaBP9K) protein, CaBP9k mRNA, and alkaline phosphatase activity (ALP). Under the normal Ca diet, no significant difference between strains was observed for all five parameters. In response to the low Ca diet, the SHR and WKY showed a similar increase (nearly 50%) in plasma calcitrol, starting at day 3 of this diet. However, only the WKY displayed the expected duodenal adaptation: active Ca transport increased at day 6 and CaBP9K as well as ALP increased at day 3 of the low Ca diet. The stimulation of the latter three parameters was maintained until day 12 of Ca restriction. Moreover, CaBP9K mRNA was increased in WKY after 3 days of Ca restriction. In contrast, the SHR had either no or only a minor increase of duodenal parameters in response to Ca restriction. Finally, a significant and positive correlation between Ca transport and plasma calcitriol and between Ca transport and CaBP9K was found in WKY but not in SHR. In conclusion, this study showed that the adolescent SHR was able to increase calcitriol production but unlike the WKY, it failed to fully adapt at the intestinal target level during a 12-day low Ca diet. Thus, our results provide further evidence for an impairment of the vitamin D endocrine system in adolescent SHR as demonstrated by an abnormal intestinal responsiveness to circulating calcitriol during moderate, short-term Ca restriction.
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  • 68
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    Calcified tissue international 52 (1993), S. 344-347 
    ISSN: 1432-0827
    Keywords: Bone mineral measurement ; Osteoporosis ; Menopause
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The aim of our study was to compare the results provided by the measurement of vertebral and femoral bone mineral density (BMD) for assessing the individual risk of osteoporosis as defined by either low BMD and/or rapid bone loss. Vertebral and femoral BMD were measured twice at a mean interval of 21 months in 85 normal, early post-menopausal women who had passed a natural menopause 6 months to 3 years previously. According to the measurement site, 36% (spine), 29% (femoral neck), 35% (Ward's triangle), and 25% (trochanter) fall in the “at risk” category, defined by a BMD value of 1 SD or more below the normal values for premenopausal women. Based on vertebral BMD, 39–48% of the women at risk had a normal femoral BMD. On the other hand, 24–37% of the women classified at risk based on femoral BMD maintained a low risk at the vertebral level. The annual rate of bone loss was significantly greater for the Ward's triangle (-2.7±3.8%) and femoral neck (-2.1±2.5%) than for the spine (-1.5±2.1%) and trochanter (-1.5±3.4%). There was a significant relationship between the rate of loss measured at the spine and femoral levels (r=0.34–0.58). Among the 21 women with a rapid vertebral bone loss, 48–67% had a low bone loss at the femoral level and vice versa. The ratio between mean rate of loss and the precision of the measurement sites was greater for the spine (1.6) compared with the femur (1.1–0.71). Our results indicate that vertebral and femoral BMD measurements produce discordant results in assessing the individual risk for osteoporosis.
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  • 69
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    Calcified tissue international 53 (1993), S. 26-28 
    ISSN: 1432-0827
    Keywords: Calcitonin ; Calcitriol ; Calcium ; Densitometry ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Twenty-two middle-aged women with severe osteoporosis were treated for 2 years with either 0.5 mg of synthetic human calcitonin subcutaneously three times per week combined with 0.5 μg of calcitriol and 0.5 g of calcium per day orally or calcium only. The treatment with calcitonin plus calcitriol (12 patients) resulted in a significantly increased calcium absorption rate. The mean values for serum phosphate did not change during the treatment period and the mean values did not differ between the treatment groups, but the serum calcium and urinary Ca/Cr ratio increased somewhat in the group given the combined treatment. There was no evidence that the combined treatment improved the bone density in this study. It is possible that calcitriol, instead of increasing the effect of calcitonin by suppression of the parathyroid, might have counteracted its effect by increasing the bone resorption.
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    Calcified tissue international 53 (1993), S. S14 
    ISSN: 1432-0827
    Keywords: Stereology ; Morphology ; Osteoporosis ; Vertebral body
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Osteoporotic compression fractures of the spine differ from most other age-related fractures in that they usually are associated with minimal trauma and with loads no greater than those encountered during normal activities of daily living. With aging and osteoporosis, there is progressive resorption of bone, resulting in reductions in bone density, thinning of trabeculae, and loss of trabecular contiguity. These changes in trabecular bone structure are associated with losses in bone strength which are disproportionate to the reductions in bone mass alone. To explain this disproportionate loss of bone strength, the prevailing opinion is that density reductions in the vertebral centrum are accompanied by a reduction in the number of trabeculae, by preferential resorption of horizontal trabeculae, and by hypertrophy of the remaining vertical trabeculae. To evaluate this view of vertebral morphology, we performed three-dimensional stereological analysis of trabecular bone extracted from midsagittal sections of first lumbar vertebral bodies from 12 donors spanning an age of 27–81 years. We found that both the number (R2 = 0.63,P 〈 0.01) and thickness (R2 = 0.91,P 〈 0.01) of trabeculae decreased linearly with density (as expressed by bone volume fraction) whereas the spacing between the trabeculae (R2 = 0.61,P 〈 0.01) increased reciprocally. There were more vertical trabeculae with transverse trabeculae at all densities, and the number of vertical trabeculae changed with density at twice the rate of the number of transverse trabeculae (P 〈 0.001). These data do not support the prevailing view that there is preferential resorption of horizontal trabeculae or hypertrophy of the remaining vertical trabeculae. Bone density was also a strong (R2 = 0.90,P 〈 0.01) power law function of the ratio of trabecular thickness to mean intertrabecular spacing. From buckling theory, the critical buckling load of a trabecula is related to this ratio of trabecular thickness to effective length. The changes in trabecular morphology observed with decreasing bone density thus pose a “triple threat” to the strength and stability of vertebral trabecular bone, as not only are there fewer trabeculae, but the remaining trabeculae are both thinner and longer.
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  • 71
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Glucocorticoids ; Rheumatoid arthritis ; Quantitative computed tomography ; Single photon absorptiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The susceptibility to glucocorticoid-induced bone loss may vary in different parts of the skeleton. We studied 62 patients with rheumatoid arthritis, 26 of whom were on low-dose glucocorticoid treatment. Bone mineral content (BMC) in the forearm was measured by single photon absorptiometry at a cortical, diaphyseal, and at a mixed cortical and trabecular, metaphyseal site. Lumbar BMC was measured by dual energy computed tomography in a trabecular and a cortical region of interest. The presence of vertebral deformities was evaluated on lateral spine radiographs. After correction for possibly confounding variables, prednisone therapy significantly influenced BMC at both the trabecular (-22.0%, 95% confidence interval-36.0% to-8.1%) and cortical (-24.8%, 95% confidence interval-39.3% to-10.3%) lumbar site. A significant effect was also seen at the metaphyseal (-15.7%, 95% confidence interval-27.1% to-4.2%), but not the diaphyseal (-3.9%, 95% confidence interval-14.1% to 6.4%) site in the forearm. Correlations between peripheral and vertebral BMC were moderate at best. The diaphyseal to metaphyseal BMC ratio did not identify patients with vertebral osteoporosis. It is concluded that the anterior cortical rim of the vertebral body is more susceptible to the effects of glucocorticoids than the cortical bone in the forearm, and that measurements of trabecular and anterior cortical vertebral BMC are essential in the management of patients with possible glucocorticoid-associated osteoporosis.
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  • 72
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Biomechanics ; Bisphosphonates ; Bone resorption ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Alendronate (4-amino-1-bydroxybutylidene bisphosphonate) is a novel amino bisphosphonate that is being developed for the treatment of osteolytic bone disorders such as osteoporosis. As part of a 2-year carcinogenicity study, we investigated the morphologic and biomechanical effects of long-term alendronate (ALN) therapy, given throughout skeletal growth, maturation, and aging, on rat vertebrae and femora. Three treatment groups, receiving either deionized water, low- (1.00 mg/kg), or high-dose (3.75 mg/kg) ALN, were given daily oral treatment for 105 weeks. Results from mechanical tests indicate that ALN therapy (in males) increased the vertebral ultimate compressive load by 96% in the high- and 51% in the low-dose groups when compared with controls. ALN similarly increased the male ultimate femoral bending load by 59% in the high- and 31% in the low-dose groups. Vertebrae and femora from female rats treated with both high- and low-dose ALN also failed at significantly higher loads than controls, but no differences were seen between low- and high-dose groups. Morphologic analysis of both male and female vertebrae revealed a dose-dependent increase in area fraction of bone. Rats receiving high-dose ALN had a greater area fraction of bone than those receiving low doses. Both groups were greater than controls. Thus, the administration of ALN resulted in increased femoral cortical bending load when compared with control animals, as well as increased vertebral ultimate compressive load commensurate with a dose-related preservation of vertebral bone. We therefore conclude that long-term ALN treatment preserves the structural and morphologic properties of both cortical and trabecular bone in rats and, with further study, may provide a valuable alternative to current therapy for the treatment of osteoporosis.
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    Calcified tissue international 53 (1993), S. S7 
    ISSN: 1432-0827
    Keywords: Bone density ; Fractures ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary New technology for noninvasive measurement of bone mass has enabled many studies of bone mass and its relationship to fracture, which challenge the view that bone mass is the only relevant factor in the etiology of fractures. Several studies have reported ROC curves that generally show values of about 80%. No convincing evidence suggests that one technique is superior to another. The reported relative risks or odds ratios for a fracture usually range between 1.2 and 2.5 per SD. There is no doubt that the risk of a fracture increases as the bone density decreases. However, even with a low bone mass, the risk ofnot fracturing a bone over the next year is over 90%. Most of the data suggest that patients with severe vertebral fractures have lower bone mass than those with mild fractures, but some women with similarly low bone mass have mild or no fractures. The weight of the evidence suggests that age has an effect on fracture incidence which is independent of bone mass. Trauma is such a major factor that it is surprising to find almost no studies that have controlled for it. The relationship between bone mass and bone failure is strong, but other factors must also be contributing to the bone failure which, like heart failure or renal failure, is a complex, multifactorial disease.
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  • 74
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    Calcified tissue international 52 (1993), S. 90-93 
    ISSN: 1432-0827
    Keywords: Metabolic bone disease ; Tumors ; Paget's disease ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Forty-three patients were treated for a total duration of 301 patient-years with calcitonin (CT) (range 3–16 years, median duration 6 years 6 months). Eighty-four percent of patients were suffering from complications associated with Paget's disease and the remainder from osteoporosis. In the majority of patients, CT was administered by the subcutaneous route and one patient was psychologically dependent on calcitonin injections. There were no long-term side effects associated with CT therapy. In a separate group of 105 patients consisting of 83 patients on human CT and 22 patients on salmon CT, injections showed short-term side effects in 77% and 64% of these patients, respectively (NS). Side effects associated with nasally administered salmon CT in 25 patients were mild and of low incidence (32%). Long-term administration of calcitonin in humans is safe and devoid of any serious or long-term side effects.
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    Calcified tissue international 52 (1993), S. 130-138 
    ISSN: 1432-0827
    Keywords: Fluoride ; Bone ; Osteoporosis ; Bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary A mathematical model was developed that prediets fluoride accumulation and clearance from the skeleton based upon fluoride bioavailability, bone remodeling rate, and the fluoride binding characteristics of bone. It was assumed that fluoride binds to bone in a nonlinear fashion such that a smaller percentage of fluoride is bound to bone if fluoride intake is increased to high levels. Bone resorption rate was assumed to be proportional to the solubility of hydroxyfluorapatite which is inversely related to bone fluoride content. The predictions made by the model compared favorably with experimental results from fluoride uptake and clearance studies. Parametric studies done using the model showed the following: (1) fluoride can be cleared from the skeleton by bone remodeling, but fluoride clearance takes over four times longer than does fluoride uptake; and (2) fluoride uptake by the skeleton was positively associated with bone remodeling rate. However, the concentration of fluoride in newly formed bone does not decrease with reduced remodeling rates and surpasses 10,000 ppm for intakes of fluoride greater than 9 mg/day. For osteoporosis, daily dose and duration of fluoride treatment should be selected to avoid reaching a toxic cumulative bone fluoride content.
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  • 76
    ISSN: 1432-0827
    Keywords: Vitamin D ; Calcitriol ; Osteoporosis ; Femoral Fracture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary In a previous study we were able to show that in women over the age of 45 the level of 1,25-dihydroxyvitamin D (1,25(OH)2D) in bone, but not in serum, is significantly reduced when compared with younger women. In the present study we measured the concentration of 1,25(OH)2D in sera and bones of 19 female patients with subcapital fractures of the femur, mean age 78±2 years. We were able to show that serum levels of 1,25(OH)2D were within the normal range, while bone levels were markedly reduced compared to levels in femoral bone obtained from young female cadavers or to the previously reported levels in non-osteoporotic elderly women. Thus, reduced levels of 1,25(OH)2D in bones of elderly women may lead, together with other factors, to subcapital fractures.
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  • 77
    ISSN: 1432-0827
    Keywords: Exercise ; Parathyroid hormone ; Vitamin D ; Calcitonin ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Nine male marathon runners were investigated during habitual training (week 0), after 3 weeks of training break (week 3), and after 2 weeks (week 5) and 4 weeks (week 7) of retraining. Maximal oxygen uptake, body fat (BF), and plasma levels of 25(OH)D3, 1,25(OH)2D3, parathyroid hormone (PTH), calcitonin (CT), albumin, and albumincorrected calcium were determined throughout weeks 0–7. The maximal oxygen uptake decreased after training break and increased during retraining (P=0.002). BF did not change significantly. Plasma 1,25(OH)2D3 was elevated after training break and decreased after 2 and 4 weeks of retraining [week 0: 44.0±3.7 (SEM) pg×1-1; week 3: 52.4±6.0 pg×1-1; week 5: 42.0±2.8 pg×1-1; week 7: 36.9±2.3 pg×1-1; P=0.03]. Plasma 25(OH)D3 did not change significantly. Plasma PTH increased throughout the training break and retraining (week 0: 1.36±0.25 pmol×1-1; week 3: 2.02±0.43 pmol×1-1; week 5: 2.23±0.60 pmol×1-1; week 7: 2.63±0.34 pmol×1-1; P=0.03). Albumincorrected calcium values were transiently decreased during retraining (week 3: 2.77±0.08 mM; week 5: 2.47±0.05 mM; week 7: 2.66±0.07 mM; P=0.01). Plasma CT did not change during training break, but was transiently decreased during retraining (week 0: 9.97±0.39 pmol×1-1; week 3: 9.91±0.37 pmol×1-1; week 5: 8.19±0.50 pmol×1-1; week 7: 9.02±0.45 pmol×1-1; P=0.01). Plasma CT was correlated to albumin (r=0.46, P=0.005), albumin-corrected calcium (r=0.34, P=0.04), and maximal oxygen uptake (r=0.45, P=0.006). Plasma 1,25(OH)2D3 was correlated to 25(OH)D3 (r=0.04, P=0.02), and BF (r=0.50, P=0.002). The described endurance training induced significant changes of plasma 1,25(OH)2D3 and PTH despite only transient changes of albumin-corrected calcium and CT.
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  • 78
    ISSN: 1432-0827
    Keywords: Early postmenopause ; Vertebral bone mass ; Combined regimen ; Calcitonin ; Estrogen ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The study was carried out to determine the effect of a combination regimen of a small dose of calcitonin added to conjugated estrogens with medroxyprogesterone acetate on vertebral bone mass in early postmenopausal women. Comparisons were made with groups of women on calcitonin alone, on conjugated estrogens with medroxyprogesterone acetate alone, or on no treatment. The study was carried out over a 2-year period. The results of the study suggest that the combined regimen of calcitonin and estrogens increased vertebral bone mass in early postmenopausal women to a greater extent than calcitonin alone or estrogen alone. Increases in vertebral bone mass of 11.2% after 1 year and 9.2% after 2 years were demonstrated using the combined regimen. Both estrogens alone and calcitonin alone were, however, very effective in preventing rapid bone loss in the postmenopausal women studied.
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  • 79
    ISSN: 1432-0827
    Keywords: Clodronate ; Liposomes ; Macrophages ; Calcium ; Iron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Clodronate (dichloromethylene bisphosphonate) inhibits the activity of osteoclasts, thereby preventing bone resorption in disorders characterized by excessive bone loss. Intravenously injected clodronate encapsulated in liposomes is also known to inactivate phagocytic cells in spleen and liverin vivo. The macrophage suppressive effect of clodronate is of interest in autoimmune diseases, like rheumatoid arthritis, in which phagocytic cells are involved in inflammatory processes, but knowledge of the interaction of clodronate with phagocytic cells is scarce. We have studied the uptake of clodronate, both free and encapsulated in negatively charged liposomes, by the macrophage-like cell line RAW 264 and by other types of cell lines. The uptake was assessed by a growth inhibition assay. The liposome-encapsulated lodronate was 50 and 350 times more potent than free drug for RAW 264 and CVI-P, respectively. Cell lines with a lower endocytotic capacity were insensitive to liposome-mediated delivery of the drug. The action of free clodronate seemed to be extracellular in all cell lines studied. Calcium and/or iron have been suggested to be involved in the intracellular uptake and action of clodronate in phagocytic cells. We found that the uptake of free clodronate by RAW 264 cells was indeed mediated by calcium and iron, while the uptake of liposomal drugs was only slightly affected by calcium. The increased intracellular calcium concentration in macrophages did not significantly affect the growth-inhibitory properties of clodronate, whereas iron loading of the cells partially restored the cell growth. The data do not support the role of calcium chelation as a mechanism of action of clodronate, but suggest that intracellular iron is, at least partially involved.
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  • 80
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    Calcified tissue international 53 (1993), S. 187-192 
    ISSN: 1432-0827
    Keywords: Fluoride ; Osteosarcoma cells ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Previousin vitro studies have shown that the effect of fluoride to increase avian osteoblast-like cell proliferation was dependent on the phosphate concentration.In vitro studies have further revealed that fluoride could also have direct effects on osteoblast-like cells to increase phosphate uptake and transiently increase cytosolic calcium. The current studies were intended to determine whether fluoride could increase net45Ca uptake by human osteosarcoma (SaOS-2) cells and, if so, whether those effects would also be phosphate dependent. The results of these studies indicate that fluoride increased net45Ca uptake by SaOS-2 cells, with biphasic dose and time dependencies. After 30 minutes of exposure, net45Ca uptake was increased to a greater extent by 50 μM fluoride (217 ± 16% of control,P 〈 0.001) than by 200 μM fluoride; and the stimulatory effect of 100 μM fluoride on net45Ca uptake was greater after 20 minutes (187 ±22% of control,P 〈 0.001) than after 60 minutes (122 ± 7% of control,P 〈 0.05). These effects of fluoride to increase net45Ca uptake were dependent on the phosphate concentration in the medium. Fluoride had no effect on net45Ca uptake in medium containing 0.4 mM phosphate, but increased net45Ca uptake in medium containing 1.2 or 2.0 mM phosphate (P 〈 0.005). As the phosphate concentration was increased, the biphasic fluoride dose-response curve was shifted to a lower range of fluoride concentrations. These effects of fluoride were not unique to SaOS-2 cells with very high steady-state levels of skeletal alkaline phosphatase; similar effects were seen in a subpopulation of SaOS-2 cells with much lower alkaline phosphatase levels. Further studies indicated that the effects of fluoride to increase SaOS-2 cell proliferation and skeletal alkaline phosphatase activity showed a similar pattern of phosphate dependency. As the fluoride-dependent increases in3[H]-thymidine incorporation and net45Ca uptake were blocked by verapamil, these data are consistent with the general hypothesis that the osteogenic effects of fluoride are associated with acute effects to increase net Ca uptake.
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  • 81
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    Calcified tissue international 53 (1993), S. 225-228 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Hormone replacement therapy ; Menopause ; Bone density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The purpose of this study was to determine whether bone mineral density (BMD) measurements at the lumbar spine and femoral neck provided comparable information to women planning to use that knowledge to help them make a decision about hormone replacement therapy. Eighty-eight healthy Caucasian women, aged 44–59 and within 0 to 5 years of menopause, participated in the study. BMD measurements were performed at the lumbar spine (L1-L4) and the femoral neck by dual energy X-ray absorptiometry (DXA). Criteria suggested by the National Osteoporosis Foundation were used to categorize women as “at risk” for osteoporosis, bone density more than one standard deviation (SD) below the young adult mean, or as “low risk”, bone density at or above this level. The re that 46 women would be classified into the low risk category on the basis of spinal BMD alone. However, 28 of these 46 women would fall into the at risk category when the femoral neck BMD was measured. Sixty-one percent of women informed they were at low risk on the basis of spinal BMD would be considered at risk based on femoral neck BMD. When femoral neck BMD was used as the primary risk indicator, 14% of the women classified as low risk would be at risk if spinal BMD were added. These results suggest that both lumbar spine and proximal femur measurements should be made when women are using bone density measurements as an aid in deciding whether or not to use hormone therapy in their postmenopausal years.
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  • 82
    ISSN: 1432-0827
    Keywords: Bone mass ; Bone density ; Osteoporosis ; Muscle training ; Exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary On the premise that bone response to exercise is locally controlled [1], we conducted a randomized trial to evaluate the effects of a 1-year training of psoas muscles (treatment group: TG) versus a 1-year training of deltoid muscles (control group: CG) on the lumbar trabecular bone mineral density (TBMD). TBMD was measured with computed tomography scan. Seventy-eight subjects were included and 67 completed the study. Intention to treat analysis revealed no significant change in TBMD from 0 to 12 months. Data analysis in the 67 remaining women, including both assiduous and nonassiduous subjects, revealed greater bone loss in CG than in TG although the difference was not significant. Similar analysis in a subgroup of subjects who performed the exercises assiduously (TG: n = 23, CG: n = 26) showed that the mean bone loss of all four vertebrae from 0 to 12 months was significantly greater in the CG (−8.87 ± 12.75 mg/cm3, mean ± SD) than in the TG (0.14 ± 11.21 mg/cm3, mean ± SD,P = 0.01). These results suggest that continuous 1-year psoas training can prevent lumbar bone loss in postmenopausal women and support the hypothesis of local action of physical activity.
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  • 83
    ISSN: 1432-0827
    Keywords: Cancellous bone ; Bone strength ; Osteoporosis ; Trabecular bone quality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary This paper discusses two novel applications of nuclear magnetic resonance (NMR) as an investigational tool for the assessment of cancellous bone microarchitecture. It further outlines extensions of the method forin vivo clinical evaluation of bone strength in patients with skeletal disorders such as osteoporosis. The first method relies on the hypothesis that the presence of two phases of different magnetic permeability, i.e., bone and bone marrow, causes a spatial nonuniformity of the magnetic field across the measurement volume. The resulting spread in resonance frequency shortens the decay time constant (T2*) of the time domain proton signal in bone marrow or its substitute (water). Increased trabecular spacing, such as it occurs in osteoporosis, reduces the spatial field inhomogeneity and thus prolongs T2*, which has been shown bothin vitro andin vivo. Subjects with osteoporosis, characterized by either low bone mineral density and/or spine compression fractures, have T2* values that are significantly prolonged. The second method focuses on a direct measurement of micromorphometric parameters of cancellous bone, using the principles of proton NMR microscopy in conjunction with computer processing of the resulting digital images. Image contrast between the trabeculae and the intertrabecular space is based on the marrow protons providing a signal, as opposed to bone, which appears with background intensity. Once tissues have been classified (into bone and marrow), for example, by means of a histogram-based segmentation algorithm, bone area fraction, mean trabecular plate density (MTPD), and mean trabecular plate thickness (MTPT) can be computed without the need for further operator intervention. The most critical parameter for successful implementation is image slice thickness which determines the extent of partial volume blurring. At 400 MHz spectrometer frequency (9.4 T field strength), images of appropriate resolution can be obtained from a 1 cm3 specimen of vertebral cancellous bone in 1 hour or less. It is shown that for relatively isotropic cancellous bone such as the one found in the vertebrae, a slice thickness on the order of 200 μm is adequate, with an inplane resolution on the order of 50 × 50 μm2 As an illustration of the technique, the relationship among the different stereologic parameters in cadaver specimens of human lumbar vertebrae is reported, showing a strong association between the area fraction and both MTPD and MTPT. The chief benefit of the new technique is its nondestructive nature and its ability to provide histomorphometric images from multiple physical locations and in multiple planes, which is desirable because of the large spatial variations in the morphologic parameters within the bone. Finally, the technique is demonstrated to be potentially also noninvasive, as illustrated with images from the human finger, acquired on a modified 1.5 Tesla clinical magnetic resonance imaging system at a pixel size of 95 × 95 μm2
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  • 84
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    Calcified tissue international 53 (1993), S. S23 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Epidemiology ; Hip fracture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Fragility fractures, particularly those of the hip, vertebrae, and distal forearm, constitute a major public health problem. The two ultimate determinants of fracture are bone strength and propensity to trauma. Bone strength depends not only upon bone mass but also upon a variety of qualitative aspects of bone structure. These include its architecture, the amount of fatigue damage it has sustained, and changes in its bulk material properties, indices that are collectively subsumed into the term “bone quality” Fragility fractures show differences in their patterns of incidence by age, sex, ethnic group, geographic area, and season. Many of these differences are currently unexplained, and disorders of bone quality might contribute to them. There are two fracture sites at which evidence implicates bone quality more directly—the spine and proximal femur. Many vertebral compression fractures follow minimal trauma, and controlled studies suggest that vertebral microarchitecture contributes to fracture risk independently of vertebral bone mass. At the hip, observational studies have pointed to a role for disordered trabecular architecture, accumulation of microfractures (fatigue damage), and the accumulation of osteoid. The extent to which these phenomena act independently of bone mass, however, remains uncertain.
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  • 85
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    Calcified tissue international 53 (1993), S. S157 
    ISSN: 1432-0827
    Keywords: Ultrasound ; Biomechanical competence ; Bone strength ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Ultrasound has been investigated as a tool for characterizing the biomechanical competence of bone. The rationale for using ultrasound rests on two points. First, its interaction with tissues can be used to measure their density, velocity, and structure, and thus to characterize the elasticity and to infer the strength of bone. Second, ultrasound may be used to characterize tissue properties over a wide range of spatial dimensions and organizational levels, ranging from its constituents (e.g., trabeculae for cancellous bone) to the entire organ. Different ultrasound techniques can be used to investigate diverse bone properties, but two techniques have emerged as having the potential for providing useful information on problems of current biomedical interest. These measure two parameters, density and velocity, which correlate with the elastic and ultimate properties of bone. In particular, the elasticity E is formally related to the product of density and velocity squared, E = ϱv2. Moreover, it has been shown by mechanical testing that there is a single linear correlation between elasticity and strength at all orientations, both in cortical and in cancellous bone, materials with a strong intrinsic anisotropy. At the tissue level, it may therefore be expected that the ultrasound parameters will prove to be useful predictors of bone strength and of its dependence on orientation.In vitro ultrasound studies have shown that these properties can be measured specifically and quantitatively, and that they vary under different physiological conditions.
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  • 86
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    Calcified tissue international 53 (1993), S. S75 
    ISSN: 1432-0827
    Keywords: Microdamage ; Remodeling ; Fatigue ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary This paper reviews the direct and indirect evidence for and against the idea that bone remodeling repairs fatigue damage. It defines experiments that should be performed to determine whether the accumulation and repair of fatigue damage is relevant to the pathogenesis of osteoporotic fracture. The experimental evidence favors the hypothesis that microdamage evokes local remodeling. The data suggest that the balance between the microdamage burden and bone repair is nearly constant. The indirect evidence comes from clinical observations that show positive relationships between depressed bone formation rate or prolonged remodeling period with bone fracture. More compelling indirect evidence comes from studies in which bone remodeling was pharmaceutically depressed, and fracture incidence rose in direct proportion. Data on microdamage accumulation were not collected in these studies. Conversely, some experimental evidence disputes a direct relationship between fatigue microdamage and repair. In these studies, increased amounts of bone microdamage in hyperadrenocortical dogs, and in irradiated dogs, could not be demonstrated even though bone fragility increased without associated osteopenia. Finally, the indirect evidence that argues that microdamage does not initiate repair is based on inference and does not provide an adequate test of the hypothesis. In balance, the current body of evidence favors the contention that bone remodeling repairs fatigue damage and thereby prevents fracture. Future studies should verify that microdamage accumulates when bone fracture occurs in conjunction with depressed remodeling activation frequency.
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  • 87
    ISSN: 1432-2048
    Keywords: Acid-growth ; Auxin ; Avena ; Calcium ; Fusicoccin ; Ion exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Elongation growth of plant cells occurs by stretching of cell walls under turgor pressure when intermolecular bonds in the walls are temporarily loosened. The acid-growth theory predicts that wall loosening is the result of wall acidification because treatments (including IAA and fusicoccin) that cause lowered wall pH cause elongation. However, conclusive evidence that IAA primarily reduces wall pH has been lacking. Calcium has been reported to stiffen the cell walls. We have used a microelectrode ion-flux measuring technique to observe directly, and non-invasively, the net fluxes of protons and calcium from split coleoptiles of oats (Avena sativa L.) in unbuffered solution. Normal net fluxes are 10 nmol · m−2 · s−1 proton efflux and zero calcium flux. The toxin fusicoccin (1 μM) causes immediate efflux from tissue not only of protons, but also of calcium, about 110 nmol · m−2 · s−1 in each case. The data fit the “weak acid Donnan Manning” model for ion exchange in the cell wall. Thus we associate the known “acid-growth” effect of fusicoccin with the displacement of calcium from the wall by exchange for protons extruded from the cytoplasm. Application of 10 μM IAA causes proton efflux to increase transiently by about 15 nmol · m−2 · s−1 with a lag of about 10 min. The calcium influx decreases immediately to an efflux of about 20 nmol · m−2 · s−1. It appears that auxin too causes an “acid-growth” effect, with extruded protons exchanging for calcium in the cell walls.
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  • 88
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    Biology and fertility of soils 15 (1993), S. 153-159 
    ISSN: 1432-0789
    Keywords: Calcium ; Maize ; Nitrogen ; Brazilian Amazon ; Cation leaching ; Canavalia ensiformes ; Mucuna aterrima
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary This work investigated the effectsof amendments of fertilizer N and lime on subsoil acidity and maize rooting depth in an acid soil of the central Amazon basin. A split-plot designed field experiment was conducted on a clayey Oxisol (Typic Acrudox) during a 16-month period. Main plots received 0 or 4 Mt ha-1 of lime. Subplots were four crop sequences: (1) Maize-green manure (Canavalia ensiformes); (2) maize-green manure (Mucuna aterrima); (3) maize-bare fallow, with the maize receiving 300 kg ha-1 of urea-N; and (4) bare fallow, with an application of 300 kg ha-1 of urea-N at the same time as sequence 3. Plots were periodically sampled to 1.2 m. The experimental site received 4265 mm of precipitation during 16 months; approximately 60%–90% of this rain percolated through the profile. Substantial amounts of Ca were leached from the 0–30 cm horizon during the experimental period, but only limited amounts accumulated in the subsoil. Base saturation below 45 cm was less than 50% at the end of the experiment regardless of lime treatment. Roots of maize were concentrated in the 0–30 cm layers in limed plots and the 0–20 cm layers in unlimed plots. In all treatments less than 5% of the roots was found below 50 cm. An acidity balance indicated that considerable acidity was leached below the plow layer and out of the profile.
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  • 89
    ISSN: 1432-072X
    Keywords: Calcium ; Nitrogen fixation ; Nodulation ; Periplasmic proteins ; Rhizobium fredii
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Calcium is essential for the growth of rhizobia and the formation of nitrogen-fixing root-nodules on legumes, but its precise role in these processes remains unknown. We have found that Rhizobium fredii USDA208 accumulates a major 38 kDa protein when grown in media supplemented with 0.3–2 μmM CaCl2. We have purified this protein and raised polyclonal antibodies against it. The protein initially is synthesized as a 40 kDa precursor which subsequently undergoes calcium-dependent processing to give rise to the mature polypeptide. Subcellular and immunocytochemical localization studies indicate that the 38 kDa protein accumulates preferentially in the periplasmic space. Its N-terminal sequence, AETIKIGVAGPMTG, shows significant homology to the N-termini of amino acid binding proteins from the periplasm, including leucine-, isoleucine-, and valine-specific binding proteins of Pseudomonas aeruginosa and Escherichia coli and a leucine-specific binding protein of E. coli. The R. fredii protein does not, however, bind [3H]-leucine. The 38 kDa protein is encoded by the bacterial chromosome. It is absent in several rhizobia other than R. fredii, but antigenically related polypeptides are present in Escherichia coli and Erwinia carotovora subsp. carotovora.
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  • 90
    ISSN: 1432-072X
    Keywords: Methanospirillum ; Morphology ; Flagella ; Archaea ; Growth conditions ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Methanospirillum hungatei strains GP1 and JF1 when cultivated at 37°C in JMA medium grew as motile single cells or short chains of cells (typically 10–30 μm long). When M. hungatei was grown in low Ca2+ concentrations or with the divalent cation chelator EDTA, the organism grew as long non-flagellated filaments (up to 900 μm long). The two strains had different thresholds of calcium concentrations for long filament formation (〈0.25 mM for GP1 and 〈0.15 mM for JF1) as well as different minimal Ca2+ requirements for growth. Both strains produced long, almost straight, filaments at Ca2+ concentrations near the minimum required for growth. At suboptimal growth temperatures the organisms still grew as short filaments but no longer possessed flagella. Western blot analysis indicated that flagellin monomer was present in cultures of long non-flagellated filaments and short non-flagellated cultures grown at suboptimal temperatures. The amount of flagellin present appeared to be equal in both non-flagellated and flagellated cultures. When cells were grown as long non-flagellated filaments and switched to growth conditions inducing short, flagellated forms, flagella were first observed at 2.5 h after this switch.
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  • 91
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    Planta 189 (1993), S. 491-498 
    ISSN: 1432-2048
    Keywords: Blue light ; Calcium ; Calcium ionophore ; Chloroplast movement ; Lemna
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The presence of calcium is essential for chloroplast movement induced by blue light in Lemna trisulca L. The regulatory role of calcium was confirmed by the inhibition of chloroplast movement by cytochalasin B and trifluoperazine. The calcium concentration in tissues was modified by ethylene glycol-bis(2-aminoethylether)-N,N,N′, N′-tetraacetic acid (EGTA), the calcium ionophore A23187 and La3+. Only a long period of incubation (12h) in EGTA or La3+ caused distrubances in chloroplast movement. This indicates that calcium influx is not essential for chloroplast movement. Those conditions that dramatically changed the internal calcium concentration, either applications of calcium ionophore A23187 and EGTA, or ionophore and La3+, markedly decreased the amplitude of response to blue-light pulses. This demonstrates that disturbances of chloroplast movement are observable only when internal stores of calcium are affected by Ca2+-antagonists. We suggest that the calcium involved in blue-light-induced chloroplast movement is derived from intracellular stores. The addition of Mg2+ to EGTA buffer counteracted its effect, indicating that Mg2+, as well as Ca2+, might possibly be involved in chloroplast movement.
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  • 92
    ISSN: 1432-2048
    Keywords: Auxin ; Calcium ; Cucurbita ; 31P nuclear magnetic resonance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Calcium deficiency in zucchini (Cucurbita pepo L.) is associated with reduced growth and a reduced ability to transport auxin (Allan and Rubery, 1991, Planta 183, 604–612). An investigation of the effects of calcium-deficiency on zucchini hypocotyl cells was made using weak-acid uptake and 31P-nuclear-magneticresonance (31P-NMR) spectroscopy in vivo and in tissue extracts. Calcium-deficient tissue had the same cytoplasmic and vacuolar pHs as normal tissue when extracellular pH was near neutral. At acidic external pH the vacuolar pH was lower in deficient tissue. Adenine nucleotides were present predominantly as ATP in both control and calcium-deficient tissues. Addition of calcium to calcium-deficient tissue, under conditions which cause recovery of auxin transport induced no changes in the 31P-NMR spectra of deficient tissue. The content of mobile, phosphorylated metabolites was reduced in calcium-deficient tissue in comparison to control tissue. However, a substantial increase in the content of phosphorylcholine occurs in calcium-deficient tissues compared with controls; this may reflect changes in lipid turnover in calcium-stressed cells.
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  • 93
    ISSN: 1432-1424
    Keywords: Maxi K+ channel ; Calcium ; pH ; Charybdotoxin ; Rabbit distal colon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract To determine if their properties are consistent with a role in regulation of transepithelial transport, Ca2+-activated K+ channels from the basolateral plasma membrane of the surface cells in the distal colon have been characterized by single channel analysis after fusion of vesicles with planar lipid bilayers. A Ca2+-activated K+ channel with a single channel conductance of 275 pS was predominant. The sensitivity to Ca2+ was strongly dependent on the membrane potential and on the pH. At a neutral pH, the K 0.5 for Ca2+ was raised from 20nm at a potential of 0 mV to 300nm at −40 mV. A decrease in pH at the cytoplasmic face of the K+ channel reduced the Ca2+ sensitivity dramatically. A loss of the high sensitivity to Ca2+ was also observed after incubation with MgCl2, possibly a result of dephosphorylation of the channels by endogenous phosphatases. Modification of the channel protein may thus explain the variation in Ca2+ sensitivity between studies on K+ channels from the same tissue. High affinity inhibition (K 0.5=10nm) by charybdotoxin of the Ca2+-activated K+ channel from the extracellular face could be lifted by an outward flux of K+ through the channel. However, at the ion gradients and potentials found in the intact epithelium, charybdotoxin should be a useful tool for examination of the role of maxi K+ channels. The high sensitivity for Ca2+ and the properties of the activator site are in agreement with an important regulatory role for the high conductance K+ channel in the epithelial cells.
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  • 94
    ISSN: 1432-1424
    Keywords: Endocytosis ; Exocytosis ; Calcium ; Adrenal medulla
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The intracellular requirements for membrane recapture in permeabilized chromaffin cells were compared to the requirements for exocytosis from the same cells. In permeabilized bovine chromaffin cells, calcium-driven exocytosis also triggers, with a short delay, uptake of extracellular horseradish peroxidase (HRP). This internalized HRP remains compartmentalized within the cell and migrates to a low density band on a Percoll gradient which is distinct from the heavier chromaffin granules. The amount of horseradish peroxidase internalized is similar in intact and leaky cells and is approximately equivalent to the volumes secreted. Endocytosis in both preparations is blocked by botulinum toxin, operates in a collapsed membrane potential, and is inhibited by low temperature. In permeabilized cells, exocytosis and coupled endocytosis are activated by the same concentrations of Ca2+ and MgATP. Although secretion requires Ca2+ and MgATP, once exocytosis has occurred the subsequent endocytosis can proceed in the virtual absence of Ca2+ or MgATP, and is largely unaffected by a variety of nucleotide triphosphates (including nonhydrolyzable analogues), and cyclic nucleotides. These data suggest that endocytosis can proceed, once exocytosis has been triggered, under conditions that are quite different from those necessary to support exocytosis, and that the specific requirements for Ca2+ and MgATP in secretion are for the exocytotic limb of the secretory cycle rather than for the associated endocytotic pathway.
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  • 95
    ISSN: 1432-1424
    Keywords: Amphibian skin ; Amphibian urinary bladder ; Tight junction ; Paracellular path ; Calcium ; Barium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Selective deposition of BaSO4 in the tight junctions (TJs) of frog skins led to profound and reversible functional alterations of these structures, as revealed by changes of tissue conductance (G), clamping current (I), and fluxes of extracellular markers (sulfate (JSO 4) and sucrose (JSUC)). Experiments were performed with nominally Ca2+ -free simple salt solutions on the apical side (usually KCl) and Na2SO4-Ringer on the inner side of skins. The deposition of BaSO4 in the TJs was obtained by diffusion and/or migration through the paracellular path of Ba2+ from the apical solution and SO 4 2− from the inner solution. A brief presence (2 to 6 min) of apical Ba2+ (Ba2+ pulse) is followed (i.e., when Ba2+ is removed from the apical fluid) by a large increase of G, I, JSO 4 and JSUC, above pre-Ba2+ levels. These attain a steady state within 15 to 30 min (overshoot phase), characterizing a conspicuous increase of the paracellular permeability. During the overshoot phase, a second Ba2+ pulse blocks the paracellular route while apical Ba2+ is present, leading to a new and larger overshoot when the Ba2+ pulse is terminated. Addition of apical Ca2+ triggers the resealing of the TJs, resulting in a full recovery of G, I, JSO 4 and JSUC. This Ca2+ -induced recovery persists when apical Ca2+ is removed. The presence of a normal Ca2+ concentration in the inner bathing Ringer does not induce the recovery process. Tissues remain viable after being submitted to the Ba2+ treatment and the subsequent overshoot. Experiments performed in the urinary bladder of Rana catesbeiana and skins and urinary bladders of Bufo marinus indicate that Ba2+ effect can also be elicited in these tissues. The above results seem to report general properties of the TJs. Incidentally, they warn about the use of Ba2+ as an ion channel blocker in epithelial membranes in association with SO 4 2− -containing solutions on the contralateral side.
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  • 96
    ISSN: 1615-6102
    Keywords: Action potential ; Calcium ; Cytoplasmic streaming ; Nitella
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Taking advantage of prolonged action potential under low temperature, we studied temporal relationship among the action potential, increase of cytoplasmic Ca2+ concentration and cessation of cytoplasmic streaming inNitella. The Ca2+ concentration began to increase at a very early stage of the action potential and the cessation of streaming followed that increase.
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  • 97
    ISSN: 1615-6102
    Keywords: Mechanical stimulation ; Bryonia dioica ; Calcium ; Fluorescent probes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The distribution of membrane-bound calium, activated calmodulin, and callose synthesis was visualized inBryonia dioica internodes before and after mechanical stimulus, using fluorescent probes, respectively, chlorotetracycline, fluphenazine, and aniline blue. Bright chlorotetracycline fluorescence remains localized in the plasma membrane of control cells, 30 s after stimulation calcium left the plasmalemma. A delocalization of activated calmodulin was observed after wounding and deposition of callose, which could not be detected before, appeared in the same times in most cells. The callose formation and the decrease in membrane-associated calcium suggest a rapid influx of calcium in the cytosol and an intervention of this ion in the cascade of the early events underlyingBryonia dioica thigmomorphogenesis.
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  • 98
    ISSN: 1615-6102
    Keywords: Calcium ; Cyclopiazonic acid ; Endoplasmic reticulum ; Golgi apparatus ; Membrane traffic ; Secretory cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary An electron microscopic study of cress (Lepidium sativum L.) roots treated with cyclopiazonic acid (CPA), an inhibitor of the Ca2+-ATPase in the endoplasmic reticulum (ER) has been carried out. Drastic changes in the endomembrane system of the secretory root cap cells were observed. After treatment with CPA dense spherical or elliptoidal aggregates of ER (diameter 2–4 μm) were formed in addition to the randomly distributed ER cisternae characteristic for control cells. The formation of ER aggregates indicates that in spite of an inhibition of the Ca2+ -ATPase in the ER by CPA, membrane synthesis in the ER continued. The ER aggregates are interpreted as a reservoir of ER membrane material newly synthesized during the 2 h CPA-treatment. Hypertrophied Golgi cisternae and secretory vesicles, which are characteristic for secretory cells under control conditions, were completely absent. Additionally the shape of the Golgi stacks was flat and the diameter of the cisternae was shortened by about one third. These phenomena are indicative of an inactive state of the Golgi apparatus. The cellular organization of both other cell types of the root cap, meristematic cells and statocytes, was not visibly affected by CPA, both having a relatively low secretory activity. The formation of ER aggregates as well as the reduction of Golgi compartments are indications for the existence of a unidirectional transport of membrane material from the ER to the Golgi. It is suggested that the membrane traffic from the ER to the Golgi apparatus is regulated by the cytosolic and/or luminal calcium concentration in secretory cells of the root cap.
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  • 99
    Electronic Resource
    Electronic Resource
    Springer
    Protoplasma 176 (1993), S. 174-177 
    ISSN: 1615-6102
    Keywords: Cytoplasmic streaming ; Nitellopsis ; Characeae ; Low temperature ; Actin ; Myosin ; Calcium ; pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The temperature dependence of cytoplasmic streaming in intact and tonoplast-free cells ofNitellopsis obtusa was studied using a cryomicroscope. The streaming velocity decreases linearly with decrease in the temperature in well-buffered tonoplast-free cells but non-linearly in some intact cells. These results suggest that low temperature causes a disturbance in the homeostasis of calcium and protons, which inhibit cytoplasmic streaming in intact cells.
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    International journal of anthropology 8 (1993), S. 205-212 
    ISSN: 1824-3096
    Keywords: Osteoporosis ; Menopause ; Risk factors ; Bone densimetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Osteoporosis represents an important sociomedical problem as causes a high morbidity, mortality and medical costs. Postmenopausal and ovariectomized women present, in a few years, the first outbreak of osteoporosis. The incidence of this illness, is much more common in menopausal women than in men of similar age. The objective of the present study is to find the morphophisiological and environmental characteristics as well as the risk factors in 200 women patients (aged 46–60 years), who were selected from the Menopause Department of the Jimenez Diaz Foundation in Madrid. About the 60% of women were found to be osteoporotics. Besides osteoporosis, the reproductive period, social habits, morphophysiological patterns and bone disease have been studied.
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