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Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra) on human osteoblasts in vitro


Handschin, A E; Trentz, O A; Hoerstrup, S P; Kock, H J; Wanner, G A; Trentz, O (2005). Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra) on human osteoblasts in vitro. British Journal of Surgery, 92(2):177-183.

Abstract

BACKGROUND: The prolonged administration of heparin for prevention and treatment of venous thromboembolism has been associated with a risk of heparin-induced osteoporosis. Fondaparinux is a new antithrombotic drug that specifically inhibits factor Xa. Because of the known interactions of other antithrombotic agents with bone remodelling, the effects of fondaparinux on human osteoblasts were analysed in vitro. METHODS: Primary human osteoblast cell cultures were incubated with either the low molecular weight heparin dalteparin at concentrations of 30, 300 and 900 microg/ml or with fondaparinux at concentrations of 25, 50, 100, 150, 200 and 250 microg/ml. Cellular proliferation rate and protein synthesis were measured. Expression of genes encoding osteocalcin, collagen type I and alkaline phosphatase was examined by reverse transcriptase-polymerase chain reaction. RESULTS: Incubation with dalteparin led to a significant, dose-dependent inhibition of osteoblast proliferation, inhibition of protein synthesis, and inhibited expression of phenotype markers (osteocalcin and alkaline phosphatase genes) after 3 and 7 days. No inhibitory effects were observed in the fondaparinux-treated cells. CONCLUSION: Fondaparinux did not inhibit osteoblast proliferation in vitro and may reduce the risk of heparin-induced osteoporosis associated with long-term heparin administration.

BACKGROUND: The prolonged administration of heparin for prevention and treatment of venous thromboembolism has been associated with a risk of heparin-induced osteoporosis. Fondaparinux is a new antithrombotic drug that specifically inhibits factor Xa. Because of the known interactions of other antithrombotic agents with bone remodelling, the effects of fondaparinux on human osteoblasts were analysed in vitro. METHODS: Primary human osteoblast cell cultures were incubated with either the low molecular weight heparin dalteparin at concentrations of 30, 300 and 900 microg/ml or with fondaparinux at concentrations of 25, 50, 100, 150, 200 and 250 microg/ml. Cellular proliferation rate and protein synthesis were measured. Expression of genes encoding osteocalcin, collagen type I and alkaline phosphatase was examined by reverse transcriptase-polymerase chain reaction. RESULTS: Incubation with dalteparin led to a significant, dose-dependent inhibition of osteoblast proliferation, inhibition of protein synthesis, and inhibited expression of phenotype markers (osteocalcin and alkaline phosphatase genes) after 3 and 7 days. No inhibitory effects were observed in the fondaparinux-treated cells. CONCLUSION: Fondaparinux did not inhibit osteoblast proliferation in vitro and may reduce the risk of heparin-induced osteoporosis associated with long-term heparin administration.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2005
Deposited On:23 Mar 2010 10:13
Last Modified:05 Apr 2016 13:53
Publisher:Wiley-Blackwell
ISSN:0007-1323
Publisher DOI:10.1002/bjs.4809
PubMed ID:15584059

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