title: Effects of thromboprophylaxis on mesenchymal stromal cells during osteogenic differentiation: an in-vitro study comparing enoxaparin with rivaroxaban.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, Moorenstr. 5, 40225, Düsseldorf, Germany. hakan.pilge@med.uni-duesseldorf.de.
authors.forename: Hakan
authors.initials: H
authors.lastname: Pilge
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, Moorenstr. 5, 40225, Düsseldorf, Germany. julia.froebel@med.uni-duesseldorf.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Fröbel
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, Moorenstr. 5, 40225, Düsseldorf, Germany. silvia.mrotzek@uni-duesseldorf.de.
authors.forename: Silvia J
authors.initials: SJ
authors.lastname: Mrotzek
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, Moorenstr. 5, 40225, Düsseldorf, Germany. johannes.fischer@med.uni-duesseldorf.de.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Fischer
authors.affiliation: Department of Orthopaedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675, Munich, Germany. p_prodinger@hotmail.com.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Prodinger
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, Moorenstr. 5, 40225, Düsseldorf, Germany. christoph.zilkens@med.uni-duesseldorf.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Zilkens
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, Moorenstr. 5, 40225, Düsseldorf, Germany. bernd.bittersohl@med.uni-duesseldorf.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Bittersohl
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, Moorenstr. 5, 40225, Düsseldorf, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Krauspe
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000494:pharmacology*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D056990:Post-Exposure Prophylaxis; D000069552:Rivaroxaban / Q000494:pharmacology*
chemical_list: D017984:Enoxaparin; D005343:Fibrinolytic Agents; D000069552:Rivaroxaban