The influence of low molecular weight heparin on the expression of osteogenic growth factors in human fracture healing

Int Orthop. 2012 May;36(5):1095-8. doi: 10.1007/s00264-011-1392-6. Epub 2011 Oct 29.


Purpose: Anticoagulant therapy with low molecular weight heparins (LMWH) and mechanical compression is considered the gold standard for the prevention of thrombosis. However, evidence exists that LMWHs impair bone metabolism. The aim of this study was therefore to analyse alterations in the expression of M-CSF, VEGF and TGF-ß1 after treatment with enoxaparin in patients with long bone fracture to investigate the effect of LMWH on human fracture healing.

Methods: A total of 81 patients with long bone fractures were included in the study and divided into two groups. One group comprised patients who received enoxaparin and the other group, patients who did not receive enoxaparin postoperatively. Growth factor levels were analysed in patients' serum and different groups were retrospectively compared.

Results: M-CSF serum concentrations were found to be significantly higher only at 48 weeks after surgery in enoxaparin. Mean overall VEGF serum concentration was higher in patients with enoxaparin. TGF-β1 serum concentrations were higher at 48 weeks after surgery in patients with enoxaparin.

Conclusion: This is the first comparative systemic measurement of M-CSF, VEGF and TGF-ß1 serum levels in patients with and without enoxaparin after long bone fracture. Significant differences of the expression of the growth factors after enoxaparin therapy were only observed at week 48 after surgery for M-CSF and TGF-ß1.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / pharmacology*
  • Enoxaparin / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Fracture Healing / drug effects*
  • Fractures, Bone / metabolism
  • Fractures, Bone / physiopathology*
  • Humans
  • Macrophage Colony-Stimulating Factor / blood*
  • Male
  • Middle Aged
  • Transforming Growth Factor beta1 / blood*
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Endothelial Growth Factor A / blood*
  • Young Adult


  • Anticoagulants
  • Enoxaparin
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • Macrophage Colony-Stimulating Factor