title: Heparin induces mobilization of osteoprotegerin into the circulation.
abstract: 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 lowmolecular-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.
authors.affiliation: Center for Atherothrombotic Research in Tromsø (CART), Department of Medicine, Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway. anders.vik@fagmed.uit.no
authors.forename: Anders
authors.initials: A
authors.lastname: Vik
authors.forename: Ellen
authors.initials: E
authors.lastname: Brodin
authors.forename: Baldur
authors.initials: B
authors.lastname: Sveinbjørnsson
authors.forename: John-Bjarne
authors.initials: JB
authors.lastname: Hansen
mesh_terms: D000328:Adult; D001775:Blood Circulation; D004333:Drug Administration Routes; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000139:chemically induced; D053244:Osteoprotegerin / Q000097:blood* / Q000493:pharmacokinetics; D010599:Pharmacokinetics
chemical_list: D006495:Heparin, Low-Molecular-Weight; D053244:Osteoprotegerin; D006493:Heparin