Abstract
BackgroundLow-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.MethodsWe 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.ResultsEnoxaparin, 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-0966-2) contains supplementary material, which is available to authorized users.
Highlights
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 the context of venous thromboembolism (VTE) prophylaxis, reports show that long-term therapy with heparin and low-molecular-weight heparins (LMWH) for the prevention of VTE following major orthopaedic surgery has an adverse effect on bone, with an increase in fractures and osteoporosis having been reported [4,5,6,7]
Solayar et al showed that Enoxaparin treatment caused the down-regulation of osteoblast function that was associated with reduced mRNA expression of bone markers such as osteocalcin, Runx2 and bone-morphogenetic protein 2 (BMP2) in mature osteoblasts [19]
Summary
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. There is lack of information on the effects of these new drugs on human mesenchymal stromal cells during osteogenic differentiation and, effects during postoperative bone healing. Following general and orthopaedic surgery, thromboprophylaxis is essential to avoid venous thromboembolism (VTE). Current treatment options for prevention include heparin and low-molecular-weight heparins (LMWHs). The risk of developing VTE after major lower extremity orthopaedic surgery is between 40. Studies report that long-term administration negatively affect postoperative bone healing, increase the risk of fracture and of developing osteoporosis [4,5,6,7]
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