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01.12.2016 | Research article | Ausgabe 1/2016 Open Access

BMC Musculoskeletal Disorders 1/2016

Effects of thromboprophylaxis on mesenchymal stromal cells during osteogenic differentiation: an in-vitro study comparing enoxaparin with rivaroxaban

BMC Musculoskeletal Disorders > Ausgabe 1/2016
Hakan Pilge, Julia Fröbel, Silvia J. Mrotzek, Johannes C. Fischer, Peter M. Prodinger, Christoph Zilkens, Bernd Bittersohl, Rüdiger Krauspe
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12891-016-0966-2) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

HP and JF designed the study and wrote the manuscript. SM helped to design the study and wrote the manuscript. JF carried out the flow cytometric analysis, BB helped to write and helped to draft the manuscript, CZ performed the statistical analysis, PP participated in the design of the study and helped to perform the statistical analysis, RK helped to draft the manuscript. All authors read and approved the final manuscript.



Low-molecular-weight heparins (e.g. Enoxaparin) are widely used to prevent venous thromboembolism after orthopaedic surgery, but there are reports about serious side effects including reduction in bone density and strength. In recent years new oral antithrombotic drugs (e.g. direct Factor Xa-inhibitor, Rivaroxaban) have been used to prevent venous thromboembolism. However, there is lack of information on the effects of these new drugs on human mesenchymal stromal cells during osteogenic differentiation and, therefore, effects during postoperative bone healing.


We evaluated the effects of Rivaroxaban and Enoxaparin on the proliferation, mRNA and surface receptor expression as well as differentiation capacity of primary human mesenchymal stromal cells during their osteogenic differentiation.


Enoxaparin, but not Rivaroxaban treatment significantly increased human mesenchymal stromal cell (hMSC) proliferation during the first week of osteogenic differentiation while suppressing osteogenic marker genes, surface receptor expression and calcification.


This is the first paper to demonstrate that Rivaroxaban had no significant influence on hMSC differentiation towards the osteogenic lineage, indicating a less affected bone healing process compared with Enoxaparin in vitro. Based on these findings Rivaroxaban seems to be superior to Enoxaparin in early stages of bone healing in vitro.
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