Heparin induces mobilization of osteoprotegerin into the circulation

Anders Vik; Ellen Brodin; Baldur Sveinbjörnsson; John-Bjarne Hansen

doi:10.1160/TH06-11-0671

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(01): 148-154
DOI: 10.1160/TH06-11-0671

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Heparin induces mobilization of osteoprotegerin into the circulation

Authors

Anders Vik

¹Center for Atherothrombotic Research in Tromsö (CART), Department of Medicine, Institute of Clinical Medicine, University of Tromsö, Tromsö, Norway
Ellen Brodin

¹Center for Atherothrombotic Research in Tromsö (CART), Department of Medicine, Institute of Clinical Medicine, University of Tromsö, Tromsö, Norway
Baldur Sveinbjörnsson

²Department of Experimental Pathology, Institute of Medical Biology, University of Tromsö, Tromsö, Norway
John-Bjarne Hansen

¹Center for Atherothrombotic Research in Tromsö (CART), Department of Medicine, Institute of Clinical Medicine, University of Tromsö, Tromsö, Norway

Abstract

Summary

Heparin treatment may induce osteoporosis by an unknown mechanism. Osteoprotegerin (OPG), a glycoprotein with a heparin-binding site, is a decoy receptor for RANKL which is responsible for osteoclast development.The objective was to investigate the effect of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH; dalteparin) on plasma levels of OPG.Twenty-two male students were allocated to the following treatment regimens; A) one bolus of 5,000 IU UFH iv followed by infusion of 450 IU/kg/24 h for 72 hours (n=7), B) sc administration of LMWH (200 IU/kg) once daily for 72 hours (n=8), C) sc administration of 100 IU/kg LMWH once (n=8), D) sc administration of 250 IU/kg UFH once (n=7), E) control infusion of saline for 12 hours (n=7). UFH boluses of 5,000 IU were given 4 and 24 hours after cessation of regimens A and B. Bolus injection of UFH iv caused a prompt increase in plasma OPG from 0.68 ng/ml (SD=0.09) to 1.13 ng/ml (SD=0.30) (p=0.003) which declined during the continuous UFH infusion and reached baseline values after 8 hours (regime A). Similar increases in plasma OPG was obtained by repeated UFH boluses after cessation of treatment. Subcutaneous administration of LMWH (200 IU/kg) caused a modest, but significant (p=0.002) increase in plasma OPG similar to the mobilization by 250 IU/kg UFH sc, but the LMWH treatment caused a three-fold higher anti-Xa activity (p<0.001). We conclude that UFH causes a more pronounced vascular mobilization of OPG than LMWH, indicating that UFH has a higher affinity for OPG than LMWH.

Keywords

UFH - LMWH - dalteparin - osteoprotegerin - osteoporosis

Full Text

References

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