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  • 1
    ISSN: 1432-0827
    Keywords: Prostaglandin E2 ; Long-term treatment ; Cancellous bone ; Bone formation ; Bone resorption ; Bone turnover ; Remodeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The effects of long-term prostaglandin E2 (PGE2) on cancellous bone in proximal tibial metaphysis were studied in 7-month-old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3, and 6 mg PGE2/kg/day and sacrificed after 60, 120, and 180 days. Histomorphometric analyses were performed on double fluorescent-labeled undecalcified bone specimens. After 60 days of treatment, PGE2 produced diffusely labeled trabecular bone area, increased trabecular bone area, eroded and labeled trabecular perimeter, mineral apposition rate, and bone formation rate at all dose levels when compared with age-matched controls. In rats given PGE2 for longer time periods (120 and 180 days), trabecular bone area, diffusely labeled trabecular bone area, labeled perimeter, mineral apposition, and bone formation rates were sustained at the elevated levels achieved earlier at 60-day treatment. The eroded perimeter continued to increase until 120 days, then plateau. The observation that continuous systemic PGE2 administration to adult male rats elevated metaphyseal cancellous bone mass to 3.5-fold of the control level within 60 days and maintained it for another 120 days indicates that the powerful skeletal anabolic effects of PGE2 can be sustained with continuous administration.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 36 (1984), S. 697-701 
    ISSN: 1432-0827
    Keywords: Endochondral osteogenesis ; Growth ; Pregnancy ; Lactation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The rates of endochondral bone elongation during pregnancy and lactation in rats have been studied. The rate of growth at the distal femoral epiphyseal growth plate was measured using fluorescent bone markers. Endochondral growth rates were substantially increased in pregnant animals when compared with age-matched, nonmated controls. There were also increases in growth plate thickness, hypertrophic cell lacunar height, and the calculated rate of cell production during pregnancy. At parturition, this growth trend was reversed and during lactation there were significant decreases in endochondral growth rates. There were also corresponding decreases in growth plate thickness, hypertrophic cell lacunar height, and the calculated rate of cartilage cell production. These results indicate that significant changes occur in maternal endochondral growth rates during the reproductive cycle in rats.
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  • 3
    ISSN: 1432-0827
    Keywords: Vitamin D ; Vitamin D deficiency ; Bone ; Cartilage ; Bone development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The role of vitamin D in early skeletal development was studied by measuring serum calcium and phosphorus, osseous tissue quantity and mineralization, and endochondral bone elongation in rat fetuses and pups from vitamin D-replete and vitamin D-deficient mothers. At the 20th day of pregnancy there was a slight, yet significant, increase in the amount of osteoid on trabecular bone surfaces in fetuses from vitamin D-deficient mothers. The fetal bones otherwise appeared normal in spite of severe skeletal changes in the vitamin D-deficient mothers. After parturition, the importance of vitamin D in skeletal development becomes progressively more obvious. Serum calcium levels were slightly, yet significantly, lower in vitamin D-deficient than in vitamin D-replete pups and these levels continued to fall in the vitamin D-deficient pups through lactation and after weaning. At 3 days postpartum, there was a small, yet significant, increase in the amount of osteoid on bone surfaces of the vitamin D-deficient pups. The relative amounts of osteoid in the vitamin D-deficient pups continued to increase through lactation and after weaning when compared with vitamin D-replete pups. By the 14th day of lactation and at later periods, there were significant reductions in metaphyseal mineralized tissues in the vitamin D-deficient pups when compared with the vitamin D-replete pups. At weaning and after weaning, there were substantial increases in growth plate thickness and decreases in longitudinal bone growth in the vitamin D-deficient pups when compared with the vitamin D-replete pups. The results from this study indicate that vitamin D does not appear to play a major role in fetal skeletal development. However, after birth, vitamin D becomes progressively more important with age for normal bone development, mineralization, and endochondral growth.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 32 (1980), S. 113-122 
    ISSN: 1432-0827
    Keywords: Rat ; Bone ; Metaphysis ; Quantitative ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The purpose of this work was to analyze the proximal tibial metaphysis of the 170 g rat in a quantitative histologic fashion which would allow some relation to tissue age to be established. Stained 3 µm thick tissue sections were analyzed with the aid of a Merz grid on an eyepiece reticule and a light microscope. Tissue mass and cell distribution were studied in all areas. The rate of change in tissue mass during aging of the metaphysis was calculated. Two regions of the metaphysis were identified. One, corresponding to the primary spongiosa, less than 4.45 days of age, is a region of high turnover of hard tissue and high numbers of osteoblasts and osteoprogenitor cells. The other, corresponding to the secondary spongiosa, is a region of relatively low net tissue turnover and low numbers of osteoblasts and osteoprogenitor cells. Osteoclasts were found relatively more uniformly distributed through the metaphysis than were osteoblasts and osteoprogenitor cells. The rate of bone formation in the primary spongiosa is 50 times that found in the Haversian bone of the rib of 5-year-old humans and about 500 times that found at the cortical-endosteal surface of ribs of 5-year-old humans. It is argued that both cell distribution and tissue distribution in the metaphysis support the concept that osteoblasts and osteoclasts, rather than osteocytes, are responsible for the maturation of the metaphysis. The inhomogeneous distribution of both cells and tissue in the metaphysis has definite meaning for the interpretation of findings concerning the incorporation of radionuclides into the skeleton.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 32 (1980), S. 123-133 
    ISSN: 1432-0827
    Keywords: Bone ; Cell kinetics ; Osteoprogenitor cell ; Migration ; Differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The purpose of this work was to provide further knowledge about bone cell kinetics in the metaphysis of the growing long bone. Seventy rats were sacrificed from 1 to 120 h after injection of tritiated thymidine. Autoradiographs of 3 µm thick sections of the proximal tibial metaphysis were studied in a manner which allowed evaluation of labeled cell nuclei as a function of increasing age of metaphyseal tissue. A cell cycle duration study for osteoprogenitor cells was done. Labeled osteoprogenitor cells and osteoblasts first appeared at 1 h post-injection. The great majority of all labeled osteoprogenitor cells and osteoblasts was found within 1 mm of the growth cartilage-metaphyseal junction (GCMJ) at all times, apparently migrating with the moving GCMJ. In contrast, labeled osteoclast nuclei first appeared at 24 h post-injection within 0.3 mm of the GCMJ and remained always with the area of bone surface with which they were first associated, even as the GCMJ migrated away. By 5 days post-injection, the source of new labeled osteoclast nuclei in the metaphysis near the GCMJ was depleted, whereas that for the osteoblasts remained. The existence of two kinetically different, as well as ultrastructurally different, members of the metaphyseal osteoprogenitor cells population is postulated. A cell cycle time of 39±18 h was found for the osteoprogenitor cell population, but has limited meaning. A schema for metaphyseal bone cell movements during longitudinal bone growth is presented.
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  • 6
    ISSN: 1432-0827
    Keywords: Vitamin D ; Vitamin D deficiency ; Bone ; Pregnancy ; Lactation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The effect of vitamin D on bone changes during the reproductive cycle in female rats has been investigated. One group of female rats was maintained on a vitamin D-deficient diet and another group on a vitamin D-replete diet from weaning. Both groups were mated with normal males and changes in their bones were determined histomorphometrically during pregnancy, lactation, and after weaning. All vitamin D-deficient rats had bone changes typical of rickets. Pregnancy caused significant reductions in mineralized tissue of trabecular and cortical bone in the vitamin D-deficient rats. Lactation caused further significant reductions in mineralized tissues of cortical and trabecular bone in both the vitamin D-deficient and vitamin D-replete animals, with the greatest changes seen at weaning. Some restoration of mineralized tissues occurred following weaning. There was an increase in tetracycline-labeled bone surface in the vitamin D-replete animals during lactation, likely due to an increase in bone formation rates. In the vitamin D-deficient animals during lactation, there was a decrease in tetracyclinelabeled bone surface, likely due to severely depressed bone mineralization. These results indicate that the mobilization of calcium from bone to maintain pregnancy and lactation occurs by a mechanism independent of vitamin D.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 145 (1967), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0827
    Keywords: Diphosphonate ; Bone ; Osteoclasts ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Male rats weighing 100 g were injected with vehicle (control group), 0.4 or 4.0 mg/kg/day of ethane-1-hydroxy-1,1-diphosphonate (EHDP). Beginning after 6 days of EHDP treatment all rats received six subcutaneous injections of3H-thymidine at 8 h intervals. The multiple labeling index of autoradiographically defined labeled cells was determined for the osteoprogenitor cells of the primary spongiosa of the proximal tibial metaphysis. The osteoclasts in the proximal tibial metaphysis were assayed for population parameters and incorporation of labeled nuclei at sequential intervals after the administration of3H-thymidine. After 6 days of EHDP pre-treatment the multiple labeling index of the osteoprogenitor cells was reduced with 4.0 mg/kg/day dose of EHDP. At the beginning of the experimental kinetic sampling period, after the 6 days of EHDP pre-treatment, EHDP treatment resulted in significant increases in the numbers of osteoclasts, nuclei per osteoclast profile, and total osteoclast nuclei. During the sampling period, the 4.0 mg/kg/day dose of EHDP caused further increases in the number of total osteoclasts. EHDP treatment caused a marked increase in the rate of incorporation and accumulation of3H-thymidine-labeled nuclei in osteoclasts. Thus, EHDP causes an accelerated rate of osteoclast production from precursor cells in spite of its ability to slow bone resorption. Although the origin of osteoclast nuclei is not clear, the kinetic data from this study suggests that osteoclast nuclei are not arising from osteoprogenitor cells or osteocytes in the EHDP-treated animals.
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  • 9
    ISSN: 1432-0827
    Keywords: Bone ; Diphosphonates ; Bone resorption ; Bone formation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Male rats weighing 100 g were assigned to groups and injected daily for 10 days with vehicle (control), 0.4, 2.0, 4.0, 10.0, or 20.0 mg/kg/day of ethane-1-hydroxy-1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl2MDP). The proximal tibial metaphysis and epiphysis were assayed for changes in percentage of hard tissue and bone formation parameters. From the data, information about hard tissue resorption was deduced. All doses of Cl2MDP and doses of 2.0 mg EHDP/kg/day and greater caused significant increases in percentage of hard tissues with Cl2MDP being more effective than similar doses of EHDP in decreasing bone resorption. Osteoclast population parameters were increased with all doses of both Cl2MDP and EHDP with Cl2MDP having a greater effect than similar doses of EHDP. Decreases in the proliferation of the osteoprogenitor pool parallel the decreases in osteoblasts and bone formation parameters. These decreases in osteoprogenitor pool proliferation do not account for the increases with diphosphonates in osteoclast population parameters.
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  • 10
    ISSN: 0899-0042
    Keywords: chiral pharmacokinetics ; rac-flurbiprofen ; rat ; bone pharmacodynamics ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The route of administration of the NSAID, flurbiprofen (sq vs. po) resulted in positive and negative results respectively with regard to enhanced cancellous and cortical bone accumulation in the immature rat. This pharmacokinetic study was an effort to understand the pharmacodynamic difference between the two routes of administration observed when the same dose range of drug, given as single daily doses, had been employed in both studies. Conventional chiral pharmacokinetics were evaluated in young rats. A significant difference was observed in the Tmax of the active (S)-enantiomer by both administration routes (sq 4 h and po 1 h). The bioavailability, as evaluated by AUCs favored the sq route as expected. The plasma concentrations over 18 h, at steady state, for one po dose group (0.5 mg/kg/day) fell well within the therapeutic window described by the 0.1 and 0.5 mg/kg sq doses which had demonstrated anabolic bone activity. Oral dosing had exhibited no significant bone activity. We conclude that the pharmacodynamic difference between routes of administration cannot be simply explained on a pahrmacokinetic basis. Consequently, experiments detailing the pharmacodynamics and pharmacokinetics of single and multiple dose administration of aryl-propionic acids in normal and osteopenic states need further pharmacologic study. © 1994 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
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