Effect of alendronate on cultured normal human osteoblasts

Effect of alendronate on cultured normal human osteoblasts
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DOI:
10.1016/s8756-3282(97)00270-6
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发表时间:
1998-03-01
期刊:
影响因子:
4.1
通讯作者:
Aubía, J
Aubía, J
中科院分区:
医学2区
文献类型:
--
作者:
García-Moreno, C;Serrano, S;Aubía, J

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阿仑膦酸盐是一种氨基二膦酸盐,具有强效抗重吸收作用,似乎不会干扰骨矿化,甚至能够通过尚未完全了解的机制增加绝经后妇女的骨密度。本研究旨在评估阿仑膦酸盐对正常人成骨细胞生理学各个方面的直接影响。测试了宽浓度范围(10(-1)至10(-12)mol/L)的阿仑膦酸盐对正常人成骨细胞的细胞活力、增殖、胶原合成和矿物质沉积能力的体外作用。在有或没有胎牛血清的情况下,在培养48和96 h时检测阿仑膦酸钠的作用。在体外,阿仑膦酸钠在浓度等于或高于10(-4)mol/L时影响成骨细胞的活力,在浓度等于或高于10(-3)mol/L时,在培养物中没有观察到活细胞,在体外,浓度在10(-5)和10(-12)mol/L之间的阿仑膦酸钠对正常人成骨细胞的增殖能力没有任何影响,这是通过两种不同的技术测定的:(1)氚化胸苷掺入DNA和(2)细胞计数。正常人成骨细胞的胶原合成在与补充有胎牛血清的阿仑膦酸盐孵育后显示出降低的趋势,这种降低仅在培养96小时后才具有统计学显著性;最后,在等于或低于10(-5)mol/L的浓度下,在体外观察到阿仑膦酸钠对正常人成骨细胞的钙沉积没有影响。总之,本研究表明,阿仑膦酸钠在体外不影响成骨细胞的活力、增殖,和正常人成骨细胞的矿物质存款能力,在其抑制破骨细胞的再吸收能力的50%的浓度下,该药物的报告为2 × 10(-9)mol/L,(C)1998由Elsevier Science Inc. All rights reserved.
Alendronate is an aminobisphosphonate with a potent antireabsorptive action that does not appear to interfere with bone mineralization, and is even able to increase bone mineral density in osteoporotic postmenopausal women through a still not fully understood mechanism, This study was conducted to assess the direct effect of alendronate on diverse aspects of normal human osteoblast physiology, For that purpose, the in vitro effect of a wide range of concentrations (from 10(-1) to 10(-12) mol/L) of alendronate on cell viability, proliferation, collagen synthesis, and the mineral-depositing capacity of normal human osteoblasts was tested. Alendronate effects were examined at 48 and 96 h of culture in the presence or absence of fetal calf serum, In vitro alendronate affected osteoblast viability at concentrations equal to or higher than 10(-4) mol/L, At concentrations equal to or higher than 10(-3) mol/L, no viable cells were observed in cultures, In vitro alendronate at concentrations between 10(-5) and 10(-12) mol/L did not have any effect on the proliferative capacity of normal human osteoblasts determined by two different techniques: (1) tritiated thymidine incorporation to DNA and (2) cell counting, Collagen synthesis by normal human osteoblasts showed a tendency to decrease following incubation with alendronate supplemented with fetal calf serum, This decrease was only statistically significant after 96 h of culture; however, a dose-response effect could not he documented, Finally, no effect of alendronate was observed on calcium deposition in vitro by normal human osteoblasts at concentrations equal to or lower than 10(-5) mol/L, In conclusion, the present study shows that alendronate in vitro does not affect viability, proliferation, and mineral deposit capacity of normal human osteoblasts at the concentration at which it inhibits by 50 % the resorptive capacity of osteoclasts that for this drug has been reported as 2 x 10(-9) mol/L, (C) 1998 by Elsevier Science Inc. All rights reserved.