Effect of bisphosphonates on vascular calcification and bone metabolism in experimental renal failure.
Effect of bisphosphonates on vascular calcification and bone metabolism in experimental renal failure.
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DOI：
10.1038/ki.2008.646
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发表时间：
2009-03
影响因子：
19.6
通讯作者：
O'Neill, W. Charles
中科院分区：
文献类型：
--
作者：
Lomashvili, Koba A.;Monier-Faugere, Marie-Claude;Wang, Xiaonan;Malluche, Hartmut H.;O'Neill, W. Charles
虽然已知双膦酸盐可在体内防止内侧血管钙化，但其作用机制尚不清楚，尤其是它们是直接作用于血管还是通过抑制骨吸收间接作用于血管。为了确定这一点，我们研究了两种双膦酸盐对体外大鼠主动脉钙化和对肾衰竭大鼠在体主动脉钙化和骨代谢的影响。我们给高磷饮食的腺嘌呤诱导的肾功能衰竭的大鼠产生了血管钙化。每日服用依替磷酸二钠或帕米磷酸钠均可预防主动脉钙化，后者的效力是后者的100倍。主动脉钙化和骨形成同时减少，但骨吸收没有明显影响。在所有尿毒症大鼠中，主动脉钙含量与骨形成相关，但与骨吸收无关。双膦酸盐也抑制培养的大鼠主动脉的钙化，并阻止钙化前血管的进一步钙化，但不逆转其钙化。体外实验中，依替膦酸盐不改变成骨因子或钙化抑制因子的表达。因此，这些研究表明，双膦酸盐可以直接抑制尿毒症血管钙化，而不依赖于骨吸收。抑制主动脉钙化和骨矿化之间的相关性与防止羟基磷灰石形成等常见机制一致，提示双膦酸盐在不抑制尿毒症大鼠骨形成的情况下可能无法防止血管钙化。
Although it is known that bisphosphonates prevent medial vascular calcification in vivo, their mechanism of action remains unknown and, in particular, whether they act directly on the blood vessels or indirectly through inhibition of bone resorption. To determine this, we studied the effects of two bisphosphonates on calcification of rat aortas in vitro and on in vivo aortic calcification and bone metabolism in rats with renal failure. We produced vascular calcification in rats with adenine-induced renal failure fed a high-phosphate diet. Daily treatment with either etidronate or pamidronate prevented aortic calcification, with the latter being 100-fold more potent. Both aortic calcification and bone formation were reduced in parallel; however, bone resorption was not significantly affected. In all uremic rats, aortic calcium content correlated with bone formation but not with bone resorption. Bisphosphonates also inhibited calcification of rat aortas in culture and arrested further calcification of precalcified vessels but did not reverse their calcification. Expression of osteogenic factors or calcification inhibitors was not altered by etidronate in vitro. Hence, these studies show that bisphosphonates can directly inhibit uremic vascular calcification independent of bone resorption. The correlation between inhibition of aortic calcification and bone mineralization is consistent with a common mechanism such as the prevention of hydroxyapatite formation and suggests that bisphosphonates may not be able to prevent vascular calcification without inhibiting bone formation in uremic rats.
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影响因子：
2.9
作者：
Cogan, EB;Birrell, GB;Griffith, OH
通讯作者：
Griffith, OH
DOI：
10.1007/bf02547227
发表时间：
1973-01-01
期刊：
CALCIFIED TISSUE RESEARCH
影响因子：
--
作者：
JUNG, A;BISAZ, S;FLEISCH, H
通讯作者：
FLEISCH, H
DOI：
10.1016/0010-468x(81)90098-2
发表时间：
1981-01-01
期刊：
COMPUTER PROGRAMS IN BIOMEDICINE
影响因子：
--
作者：
MANAKA, RC;MALLUCHE, HH
通讯作者：
MALLUCHE, HH
影响因子：
13.6
作者：
Lomashvili, KA;Khawandi, W;O'Neill, WC
通讯作者：
O'Neill, WC
DOI：
10.1084/jem.192.4.463
发表时间：
2000-08-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Min H;Morony S;Sarosi I;Dunstan CR;Capparelli C;Scully S;Van G;Kaufman S;Kostenuik PJ;Lacey DL;Boyle WJ;Simonet WS
通讯作者：
Simonet WS