Murray W J, Lindo V S, Kakkar V V, Melissari E
Thrombosis Research Institute, London, UK.
Blood Coagul Fibrinolysis. 1995 Apr;6(2):113-8. doi: 10.1097/00001721-199504000-00004.
To test whether heparin-induced osteoporosis is influenced by the molecular weight of heparin, 24 male rabbits received single daily subcutaneous injections of either physiological saline (controls, n = 5), low molecular weight heparin (LMWH, n = 7), conventional heparin (UFH, n = 7) or high molecular weight heparin (HMWH, n = 6). Heparin was administered in supratherapeutic daily dosages for 120 days (750 anti-FXa units/kg for 90 days and 1500 anti-FXa units/kg for another 30 days). Studied variables were: serial analysis of serum calcium, albumin, phosphate and alkaline phosphatase, measurement of the cortical thickness of the femur (radiographically), tibial and trabecular bone density (both by cross-sectional analysis) and femoral fragility. Observed changes in blood biochemistry associated with bone metabolism were not correlated to any of the treatments. Compared with the controls, a reduction in cortical and trabecular bone density was seen with UFH (P < 0.05) and HMWH (P < 0.01) but not with LMWH. Femoral fragility was also significantly increased (P < 0.002) by HMWH. In conclusion, LMWH did not cause toxic skeletal effects as opposed to HMWH which clearly did, and UFH which induced some osteoporotic changes.
为了测试肝素诱导的骨质疏松症是否受肝素分子量的影响，24只雄性兔子每日接受一次皮下注射，分别注射生理盐水（对照组，n = 5）、低分子量肝素（LMWH，n = 7）、普通肝素（UFH，n = 7）或高分子量肝素（HMWH，n = 6）。以超治疗剂量给予肝素，持续120天（90天为750抗Xa因子单位/千克，接下来30天为1500抗Xa因子单位/千克）。研究变量包括：血清钙、白蛋白、磷酸盐和碱性磷酸酶的系列分析，股骨皮质厚度的测量（通过X线摄影）、胫骨和小梁骨密度（均通过横断面分析）以及股骨脆性。观察到的与骨代谢相关的血液生化变化与任何一种治疗均无关联。与对照组相比，UFH（P < 0.05）和HMWH（P < 0.01）组出现皮质骨和小梁骨密度降低，而LMWH组未出现。HMWH还显著增加了股骨脆性（P < 0.002）。总之，与明显导致毒性骨骼效应的HMWH和诱导一些骨质疏松变化的UFH不同，LMWH未引起毒性骨骼效应。
