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  • 1
    ISSN: 1433-2965
    Keywords: Calcium ; Cardiac transplantation ; Fluoride ; Glucocorticoid-induced osteoporosis ; Parathyroid hormone ; Vitamin D
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Of 203 patients who underwent cardiac transplantation and were given long-term treatment with cyclosporine and 0.3 mg/kg per day prednisone, 123 were studied prospectively for at least 6 months and 46 for up to 2 years to evaluate the effects on lumbar bone mineral density (BMD) and calcium metabolism of a combined therapy with calcium, calcidiol and disodium monofluorophosphate (MFP). The population was arbitrarily assigned to one of two groups. Group I consisted of patients who had a lumbar spine BMDZ score above −1.5 SD as compared with an age-and sex-matched population and no vertebral fractures. They received daily 1 g elemental calcium and 25 µg (1000 IU) calcidiol. Group II consisted of patients who received daily the same doses of calcium and calcidiol combined with 200 mg MFP, and was divided into two subgroups: (a) osteopenic subjects who had a lumbar spine BMD Z score below −1.5 SD without vertebral fractures and (b) osteoporotic subjects with vertebral fractures. If serum creatinine was higher than 140 µmol/l the daily dose of MFP was tapered to 100 mg. Fifty-four and 27 patients from group I and 38 and 19 patients from group II were followed respectively for 12 and 24 months. In both groups serum parathyroid hormone levels were significantly reduced from the twelfth month in parallel with a significant increase in serum 25-OHD levels. No decline in lumbar BMD occurred in non-osteopenic and non-osteoporotic patients (group I) who received the calcium and calcidiol supplement. In group II, where MFP was added, a significant and linear increase in lumbar BMD was observed. The average increase reached 12.5% after 12 months and 29.5% after 24 months (p〈0.0001). The magnitude of the response was similar to the response previously reported in patients suffering from vertebral fractures due to postmenopausal osteoporosis and treated with the same daily dose of MFP. Because osteoporosis and fractures are not rare in patients after cardiac transplantation, these pilot results may be useful for further prevention and treatment trials of bone loss in this condition.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1433-2965
    Keywords: Bone ; Histomorphometry ; Osteoporosis ; Osteoblasts ; Osteocalcin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To assess the bone turnover abnormalities which characterize postmenopausal osteoporosis with vertebral fractures (PMOp), a transiliac bone biopsy was performed after double labeling of the mineralizing front with tetracycline in 50 untreated PMOp patients who were compared with 13 healthy age-matched volunteer females. The analysis of bone remodeling and structure parameters demonstrated that PMOp is a disease affecting both the cancellous and the endocortical envelopes and characterized by increased resorption and by a marked decrease in the osteoblastic apposition rate due to a reduced duration of bone formation. This induces a decrease in the width of both individual osteons and trabeculae. In PMOp, the wide spectrum of bone turnover as compared with the controls, associated with the typical bimodal distribution of cancellous osteoid perimeter, allowed us to identify two subsets, one with normal turnover (NT) and one with high turnover (HT) representing 30% of the cases. When compared to NT, HT was characterized by increased osteoclast number, lower bone volume, thinner osteons, increased formation at the tissue-level and markedly decreased duration of formation. In HT the marked decrease in the duration of activity of osteoblasts and the markedly increased number of osteoclasts induced a greater decrease in bone volume, despite the increase of bone formation at the tissue level. These subsets could not be distinguished by any clinical or biochemical parameter except for serum bone gla protein (osteocalcin) which was significantly higher (as a group) in HT than in NT. The underlying cause for these two subsets is unknown. We conclude that PMOp affects the cancellous and the endocortical bone. Bone loss results from a wide spectrum of bone turnover abnormalities, with two distinct subsets, one with normal turnover and one with high turnover.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-2965
    Keywords: Bone formation ; Ewes ; Glucocorticoids ; Histomorphometry ; Osteocalcin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanisms underlying glucocorticoid-induced osteoporosis in humans are a defect in bone formation associated with increased bone resorption. The latter may be due to elevated parathyroid hormone (PTH) levels induced by the impairment of intestinal calcium absorption caused by corticosteroids. In this study we analysed the effects of corticosteroids in old ewes, a potential model for the study of human bone turnover. Two groups of seven 9-year-old female sheep were selected. The first group was injected intramuscularly with a daily dose of 30 mg methylprednisone (MP) during the first 2 months and 15 mg during the last month. After 2 and 3 months of treatment, blood samples were taken. At the end of the experiment the animals were slaughtered and the iliac crest kept for bone histomorphometry. Serum osteocalcin (sOC) rapidly and markedly decreased in the MP-treated group compared with controls (−77%;p〈0.01). In contrast, at the end of the experiment serum calcium and PTH levels were similar in both groups. Histomorphometric analysis showed a significant reduction in the wall width of trabecular packets. Dynamic parameters reflecting bone formation at the tissue and cell levels were significantly lower in the MP-treated group than in controls, with a highly significant decrease in the mineralization rate (MAR: −63%,p〈0.05) and double-labeled perimeter (dLPm/B.Pm: −92%p〈0.05). The bone formation rate (BFR/B.Pm) also decreased by 84% and the adjusted apposition rate (Aj.AR) by 80%. The increase in the total formation period was mainly due to an increase in the inactive period. Significant correlations were found between sOC and MAR, dLPm/B.Pm and BFR/B.Pm (withr′ respectively 0.67, 0.76 and 0.51). In conclusion, the effects of corticosteroid on ewe bone remodeling are essentially characterized by a major bone formation defect without evidence of secondary hyperparathyroidism, although this cannot be totally excluded by our results. Ewes treated with glucocorticoids could represent a good model for evaluating the effects of drugs candidates for all bone conditions characterized by reduced bone formation resulting from osteoblastic depression.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0878
    Keywords: Calcitonin ; Parathyroid hormone ; Estradiol ; Estradiol receptors ; Osteoblasts ; Immunocytochemistry ; Cryo-ultramicrotomy ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immunoreactivities to endogenous calcitonin, endogenous parathyroid hormone, endogenous estradiol and estradiol receptors were studied in osteoblasts from the calvaria of neonatal mice by immunocytochemistry with the use of ultrathin sections obtained by cryo-ultramicrotomy. Tissues were fixed in glutaraldehyde, postfixed in osmium tetroxide and frozen in liquid nitrogen. Estradiol and estradiol receptors could not be detected in osteoblasts, whereas calcitonin- and parathyroid hormone-like immunoreactivities were observed in this cell type. Calcitonin and parathyroid hormone had similar subcellular localizations: immunoreactivities were observed at the plasma-membrane level, in the cytoplasmic matrix, and in the nucleus. These results provide immunocytological evidence for: 1) the internalization of calcitonin and parathyroid hormone in osteoblasts; 2) a direct participation of calcitonin and parathyroid hormone in the regulation of osteoblasts; 3) the absence of estradiol receptors and estradiol in osteoblasts.
    Type of Medium: Electronic Resource
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