低分子肝素和标准肝素对胎鼠头颅钙流失的影响。
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肖内西SG，杨E，德尚P，赫什J
低分子肝素和标准肝素对胎鼠头颅钙流失的影响。
《血》1995 Aug 15;86(4):1368-73。
- PubMed ID
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7632944 (PubMed视图］
- 摘要
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骨质疏松症是长期使用肝素的公认并发症。然而，肝素影响骨代谢的机制尚不清楚。我们在这里报道，未分离的肝素刺激骨吸收过程，低分子肝素(LMWHs)，依诺肝素，fragmin, logiparin和ardeparin产生的钙损失明显低于未分离的肝素。为了评估骨钙流失，我们量化了45Ca在胎鼠颅骨培养基中的释放量。加入未分离肝素或低分子肝素均可增加45Ca的释放，并呈剂量依赖性;但要获得与未分离肝素相当的效果，低分子肝素浓度需要高出50倍以上。因此，在浓度>或= 2微克/mL (0.35 anti-Xa单位/mL)时，未分离的肝素刺激45Ca释放1.53 +/- 0.06倍。添加10(-7)mol/L甲状旁腺激素(PTH)或10(-6)mol/L 1,25二羟基维生素D3 (1,25 Vit D3)后，45Ca的释放也有类似程度的增加。与未分离的肝素相比，在观察到最大同位素释放之前，低分子肝素浓度>或= 100微克/mL(>或= 14.0抗xa单位/mL)是必需的。在远高于治疗水平的浓度下，LMWHs仅刺激了1.25 /+- 0.01倍的45Ca释放。 Heparins with high and low antithrombin III affinities stimulated 45Ca release equally well. Both size and sulfation were found to be major determinants of heparin's ability to promote isotope release. Thus, the ability of defined heparin fragments to stimulate 45Ca release correlated with their molecular weight, and after N-desulfation the ability of heparin to induce isotope release was greatly diminished. Dermatan sulfate had no effect on 45Ca release. We conclude that size and sulfation are major determinants of heparin's ability to promote bone resorption and that the risk of heparin-induced osteoporosis may be reduced by the use of LMWH preparations.