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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 35 (1983), S. 410-417 
    ISSN: 1432-0827
    Keywords: Bone remodeling ; Histomorphometry ; Corticosteroid therapy ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary We have compared the mean wall thickness (MWT) and active formation periods (sigmaf(A)) of trabecular bone packets in iliac crest biopsies from 20 patients (7 male, 13 female) with corticosteroid-induced osteoporosis (CS-OP) and 20 age- and sex-matched controls. The trabecular bone volume (TBV) of the CS-OP patients (9.6%±2.2% [SD]) was significantly reduced compared to controls (19.3%±5.1%). The MWT of CS-OP patients (32.7±4.3 µm) was also significantly lower than the control value (48.0±6.2 µm). There was a positive correlation between MWT and TBV in both groups. The mineralization rate (M) of the CS-OP patients (0.54±0.25 µm/day) was within the normal range, and since there was no increase in osteoid seam thickness, so therefore was the osteoblastic appositional rate (OAR). The active formation period of trabecular bone packets (sigmaf(A)=MWT/M) was significantly lower in the CS-OP patients (55.9 ± 14.4 days) than in the control group (68.1 ± 9.4 days). MWT and sigmaf(A) both decreased with age in the control group, whereas in the CS-OP group they were independent of age. We conclude that corticosteroid therapy results in a reduction of the MWT of trabecular bone packets and, consequently, of TBV. In these patients, where the OAR was normal, the reduction in MWT was apparently caused by a shortening of the lifespan of the active osteoblastic population at the basic multicellular unit (BMU) level.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 33 (1981), S. 199-204 
    ISSN: 1432-0827
    Keywords: Bone remodeling ; Histomorphometry ; Trabecular bone ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The mean wall thickness (MWT) and duration of formation periods (sigmaf) of trabecular bone packets have been measured in iliac crest biopsies following double tetracycline labeling from 9 women having primary osteoporosis, with vertebral crush fractures and reduced trabecular bone volume (TBV), and 9 age- and sex-matched controls. The MWT of the osteoporotic biopsies was significantly less than that of the controls and was negatively correlated with age in the latter. There was also a positive correlation between MWT and TBV in the controls but not in the osteoporotics. Sigmaf, in days, showed a tendency to decline with age in the control biopsies and was further decreased in the osteoporotic patients. These results suggest that a major contribution to the negative skeletal balance existing in both primary osteoporosis and physiological osteopenia is a decrease in bone formation, caused by a reduction in the life span of the osteoblastic population at the basic multicellular unit (BMU) level.
    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: 1433-2965
    Keywords: Bone fluoride content ; Bone remodeling ; Fluoride ; Histomorphometry ; Lambs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The evolution of bone changes induced by fluoride after the end of exposure was investigated in lambs. Sodium fluoride (NaF) was given orally at a dose of 3.5 mg/kg per day to 14 animals for 120 days. A group of 7 control and 7 treated lambs was slaughtered at the end of NaF administration (T120) and another group 120 days after the end of NaF exposure (T240). At T120, the bone fluoride content (BFC) was very significantly increased in treated animals. The histomorphometric analysis confirmed that fluoride induces an increase in bone formation (the osteoid perimeter and area were 3-fold and 4.5-fold higher respectively in treated than in control animals). The number of osteoblasts was significantly augmented. Serum osteocalcin level was twice as high in treated animals compared with controls. The bone formation rate at the tissue level (BFR) doubled after treatment, but the apposition rate (Aj.AR) was half that in the control group. The mineralization lag time (Mlt) was 120 days in treated animals compared with 42 days in controls. At T240, BFC had decreased by 50% compared with the level at T120, but it was still significantly higher than in controls. The osteoid and osteoblastic parameters were 2 and 1.3 times higher than in control animals. BFR remained significantly increased in treated animals, but Aj.AR and Mlt were similar in control and treated animals. In conclusion, after 4 months of NaF exposure fluoride induced an increase in osteoblast natality and bone formation at the tissue level, associated with a toxic effect at the individual cell level. Four months after the end of NaF exposure, positive effects on bone formation were still present but the evidence of cellular toxicity had disappeared.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    ISSN: 1434-9949
    Keywords: Ossein-Hydroxyapatite Compound ; Bone Remodeling ; Biochemistry ; Histomorphometry ; Ewe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ossein-hydroxyapatite compound (OHC) is a protein-mineral complex derived from bovine bone. Its effects on bone remodeling were studied in old ewes which have seasonal variations in bone remodeling. Seven animals received 200 mg OHC/kg b.w./day for 90 days from July to September. The control group consisted of 7 untreated animals followed for the same period of time. OHC was administered through a fistula into the fourth stomach. A significant decrease of bone histomorphometric parameter values was noted in controls at the end of the experiment, due to seasonal variations: the cancellous eroded perimeter decreased by 45%, the osteoblastic perimeter by 60% and the bone formation rate at the cell level by 20%. In contrast, in the treated-group, these parameters tended to increase or did not change. In conclusion, counteracting the significant seasonal reduction of bone remodeling in ewes, OHC seems able to stimulate directly or indirectly bone metabolism, especially when osteoblast activity is reduced and may partly prevent the seasonal reduction of bone turnover.
    Type of Medium: Electronic Resource
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