Effect of a Direct Thrombin Inhibitor Compared with Dalteparin and Unfractionated Heparin on Human Osteoblasts

Tobias Winkler*, Carsten Perka, Dörte Matziolis , Georg Matziolis
Center of Musculoskeletal Surgery, Berlin Brandenburg Center for Regenerative Medicine, Charité – Universitaetsmedizin Berlin, Germany

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© Winkler et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Center for Musculoskeletal Surgery, Charité – Universitätsmedizin Berlin, Department of Orthopaedics, Charitéplatz 1, D-10117 Berlin, Germany; Tel: +49 – 30 – 450 615109; Fax: +49 – 30 – 450 515922; E-mail:



Osteoporosis is a relevant problem after long term administration of unfractionated heparin (UFH) and low molecular weight heparin. Melagatran is a representative of a new group of direct thrombin inhibitors with comparable data in the prevention of thromboembolic events after orthopaedic surgery. The aim of our in vitro study was to investigate the effect of a direct thrombin inhibitor compared with dalteparin and UFH on human osteoblasts.

Materials and Methods:

Melagatran, dalteparin and UFH were added to primary osteoblast cultures in their therapeutic range and two decimal powers below and above. Cell number, protein synthesis, mitochondrial and alkaline phosphatase activity and collagen type I synthesis were evaluated.


Melagatran showed the least influence on protein synthesis and cell proliferation with a reduction of cell number to 83.5 ± 9% (p = 0.027) of the control group only in the highest investigated concentration after 15 days of incubation.

Mitochondrial and alkaline phosphatase activity and collagen type I synthesis in osteoblasts incubated with melagatran and dalteparin showed similar patterns. UFH showed the most pronounced influence on cellular metabolism.


Melagatran showed less inhibitory in vitro effects on human osteoblasts than dalteparin or UFH. The presented study gives first hints that direct thrombin inhibitors may help prevent heparin-induced negative effects on bone metabolism.

Keywords: Direct thrombin inhibitor, dalteparin, heparin, osteoblasts, osteoporosis.