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Archives of Orthopaedic and Trauma Surgery

Erschienen in:

01.07.2009 | Basic Science

The systemic angiogenic response during bone healing

verfasst von: Stefan Weiss, Gerald Zimmermann, Thomas Pufe, Deike Varoga, Philipp Henle

Erschienen in: Archives of Orthopaedic and Trauma Surgery | Ausgabe 7/2009

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Abstract

Introduction

Angiogenesis is known to be a critical and closely regulated step during bone formation and fracture healing driven by a complex interaction of various cytokines. Delays in bone healing or even nonunion might therefore be associated with altered concentrations of specific angiogenic factors. These alterations might in turn be reflected by changes in serum concentrations.

Method

To determine physiological time courses of angiogenic cytokines during fracture healing as well as possible changes associated with failed consolidation, we prospectively collected serum samples from patients who had sustained surgical treatment for a long bone fracture. Fifteen patients without fracture healing 4 months after surgery (nonunion group) were matched to a collective of 15 patients with successful healing (union group). Serum concentrations of angiogenin (ANG), angiopoietin 2 (Ang-2), basic fibroblast growth factor (bFGF), platelet derived growth factor AB (PDGF-AB), pleiotrophin (PTN) and vascular endothelial growth factor (VEGF) were measured using enzyme linked immunosorbent assays over a period of 24 weeks.

Results

Compared to reference values of healthy uninjured controls serum concentrations of VEGF, bFGF and PDGF were increased in both groups. Peak concentrations of these cytokines were reached during early fracture healing. Serum concentrations of bFGF and PDGF-AB were significantly higher in the union group at 2 and 4 weeks after the injury when compared to the nonunion group. Serum concentrations of ANG and Ang-2 declined steadily from the first measurement in normal healing fractures, while no significant changes over time could be detected for serum concentrations of these factures in nonunion patients. PTN serum levels increased asymptotically over the entire investigation in timely fracture healing while no such increase could be detected during delayed healing.

Conclusion

We conclude that fracture healing in human subjects is accompanied by distinct changes in systemic levels of specific angiogenic factors. Significant alterations of these physiologic changes in patients developing a fracture nonunion over time could be detected as early as 2 (bFGF) and 4 weeks (PDGF-AB) after initial trauma surgery.

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Titel: The systemic angiogenic response during bone healing
verfasst von: Stefan Weiss
Gerald Zimmermann
Thomas Pufe
Deike Varoga
Philipp Henle
Publikationsdatum: 01.07.2009
Verlag: Springer-Verlag
Erschienen in: Archives of Orthopaedic and Trauma Surgery / Ausgabe 7/2009
Print ISSN: 0936-8051
Elektronische ISSN: 1434-3916
DOI: https://doi.org/10.1007/s00402-008-0777-5

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