Heparin induces mobilization of osteoprotegerin into the circulation

 

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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.

• References

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