The Effect Of Low-Dosed Unfractioned And Low-Molecular-Weight Heparins On Bone Healing In Vivo

Abstract

Aim: To elucidate if low-dosed heparins (both unfractioned and low-molecular-weight) have a significantly negative effect on bone healing in vivo, as reported previously. While other studies applied higher doses, we used doses comparable to clinical application. Methods: Female rabbits received defined metaphyseal defects to their femora and were then subjected to daily injections of either saline solution, unfractioned low-dose heparin (UFH) or one of two different low-molecular-weight heparins for a period of 6 weeks. After scarification, the remaining osseous defects were histomorphometrically examined. Results: We found some indication, but no statistical evidence, that both UFH and two different LMWH appear to reduce bone healing compared to placebo after 6 weeks. In the placebo group, an average defect reduction of 50.7 % was observed. In the UFH group, the defects had reduced by 42,7 % on average, in the certoparine group by 42,7 % and in the dalteparin group by 47,9 %. Conclusion: As our results do not prove a significant reduction of bone healing in vivo at clinically relevant doses, we recommend to continue using a combined approach for clinical DVT prophylaxis, including daily s.c heparin administration, until full mobilization. LIST OF ABBREVIATIONS DVT Deep vein thrombosis LMWH Low molecular weight heparin UFH Unfractioned heparin IU International Unit, used to measure the anticoagulatory effect of a given heparin. Based on a WHO reference heparin derived from porcine intestinal mucosa. 1 mg of standard heparin contains ca. 170 IU (156).