title: Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing.
abstract: OBJECTIVE
  Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing.
  
  
  METHODS
  We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation.
  
  
  RESULTS
  We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban.
  
  
  CONCLUSIONS
  Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro.Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95-100. DOI: 10.1302/2046-3758.53.2000595.
authors.affiliation: Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany Hakan.Pilge@med.uni-duesseldorf.de.
authors.forename: H
authors.initials: H
authors.lastname: Pilge
authors.affiliation: Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Fröbel
authors.affiliation: Clinic for Orthopedics and Sports Orthopedics, Technical University of Munich, 81675 Munich, Germany.
authors.forename: P M
authors.initials: PM
authors.lastname: Prodinger
authors.affiliation: Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors.forename: S J
authors.initials: SJ
authors.lastname: Mrotzek
authors.affiliation: Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors.forename: J C
authors.initials: JC
authors.lastname: Fischer
authors.affiliation: Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Zilkens
authors.affiliation: Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Bittersohl
authors.affiliation: Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Krauspe
keywords: bone healing; enoxaparin; human mesenchymal stromal cells (MSCs); low-molecular-weight heparins (LMWH); rivaroxaban