Fracture vascularity and bone healing: A systematic review of the role of VEGF

Academic Dept of Trauma & Orthopaedics, Leeds Teaching Hospitals, University of Leeds, Leeds, UK.
Injury (Impact Factor: 2.14). 10/2008; 39 Suppl 2(Suppl 2):S45-57. DOI: 10.1016/S0020-1383(08)70015-9
Source: PubMed


Fracture healing constitutes a complex and delicate physiological process. Local vascularity at the site of the fracture has been identified as one of the most significant parameters influencing the healing procedure. VEGF is the most important component of the regeneration of the vascular system at the fracture site. The aim of this review is to determine the evidence supporting the direct role of VEGF in the enhancement of fracture healing and the possible clinical use of VEGF for non-unions. The literature search was performed via the internet using the Medline. The key words which were searched in the abstracts were the terms "VEGF", "angiogenesis", "fracture", "bone" and "healing". Twenty-five articles were relevant to the topic of interest. A total of 11 articles were excluded from our research due to non conformity of their content to the inclusion criteria. Evidence retrieved suggests that VEGF could be extremely valuable for the treatment of critical size bone defects and that VEGF could have a direct effect on osteoprogenitor cells, mainly by promoting the differentiation of osteoblasts and by increasing the mineralisation of the regenerated bone. The former observation could have very interesting repercussions for the field of non-unions and the latter for the field of osteoporosis.

Download full-text


Available from: Giorgio Maria Calori, Jun 11, 2014
1 Follower
307 Reads
  • Source
    • "The revascularization of the fracture and callus site is regulated by the angiopoietin-dependent pathway in which the first vascular ingrowth occurs from existing vessels from the periosteum. However, the main part of the revascularization is regulated by the VEGF pathway, which transforms the cartilaginous avascular matrix into vascularized osseous tissue [24]. In the transformation of soft into hard callus, the Wnt-protein family modulates the differentiation of MSCs into the osteoblastic lineage and later on the osteoblastic bone formation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the last 3 decades, scientific evidence advocates an association between traumatic brain injury (TBI) and accelerated fracture healing. Multiple clinical and preclinical studies have shown an enhanced callus formation and an increased callus volume in patients, respectively, rats with concomitant TBI. Over time, different substances (cytokines, hormones, etc.) were in focus to elucidate the relationship between TBI and fracture healing. Until now, the mechanism behind this relationship is not fully clarified and a consensus on which substance plays the key role could not be attained in the literature. In this review, we will give an overview of current concepts and opinions on this topic published in the last decade and both clinical and pathophysiological theories will be discussed.
    Mediators of Inflammation 04/2015; 2015:1-14. DOI:10.1155/2015/204842 · 3.24 Impact Factor
  • Source
    • "K. Joensuu et al. / Orthopaedics & Traumatology: Surgery & Research 101 (2015) 381–386 fracture healing [10] [11] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite recent advances in bone tissue engineering, efficient bone formation and vascularization remains a challenge for clinical applications. The aim of this study was to investigate if the osteoblastic differentiation of human mesenchymal stromal cells (MSCs) can be enhanced by co-culturing them with peripheral blood (PB) mononuclear cells (MNCs), with and without vascular endothelial growth factor (VEGF), a coupling factor of bone formation and angiogenesis. Human bone marrow (BM) derived MSCs were co-cultured with PB-MNCs in osteogenic medium with or without VEGF. Osteoblastic differentiation and mineral deposition were studied by staining for alkaline phosphatase (ALP), and von Kossa, respectively, and measurements for ALP activity and calcium concentration (Ca). Cell proliferation was assayed with Alamar blue. The mechanism(s) were further studied by Transwell(®) cell culture experiments. Both ALP and mineralization (von Kossa and Ca) were significantly higher in the MSC-MNC co-cultures compared to plain MSC cultures. VEGF alone had no effect on osteoblastic differentiation of MSCs, but further enhanced differentiation in co-culture settings. The mechanism was shown to require cell-cell contact between MSCs and MNCs and the factors contributing to further differentiation appear to be soluble. No differences were observed in cell proliferation. Our study demonstrates that the in vitro ALP activity and mineralization of human BM-MSCs is more efficient in the presence of PB-MNCs, and exogenously added VEGF further enhances the stimulatory effect. This indicates that PB-MNCs could be a potential cell source in development of co-culture systems for novel tissue engineering applications for enhanced bone healing. Level IV. Experimental research study. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    Orthopaedics & Traumatology Surgery & Research 03/2015; 101(3). DOI:10.1016/j.otsr.2015.01.014 · 1.26 Impact Factor
    • "The healing of fracture immediately initiates after fracture occurrence, and bone repair continues to restore its structural integrity.[1] However, because of inadequate fracture healing in a high number of bone fractures, the healing of fracture requires further treatment.[5] The measurement of enzymatic activity of the osteoblasts including bone alkaline phosphatase, or bone matrix component such as osteocalcin can be investigated for the bone healing process.[6] "
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to investigate the effects of the combination of vitex agnus castus extract, as a source of phytoestrogens, plus magnesium supplementation on osteogenic and angiogenic factors and callus formation in women with long bone fracture. In a double-blind randomized placebo controlled trial, 64 women with long bone fracture, 20-45 years old, were randomly allocated to receive 1) one Agnugol tablet (4 mg dried fruit extract of vitex agnus castus) plus 250 mg magnesium oxide (VAC + Mg group (n = 10)), 2) one Agnugol tablet plus placebo (VAC group (n = 15)), 3) placebo plus 250 mg magnesium oxide (Mg group (n = 12)), or 4) placebo plus placebo (placebo group (n = 14)) per day for 8 weeks. At baseline and endpoint of the trial, serum alkaline phosphatase, osteocalcin, and vascular endothelial growth factor (VEGF) were measured together with radiological bone assessment. There were no significant differences in the characteristic aspects of concern between the four groups at baseline. Despite the increased level of alkaline phosphatase in the VAC group (188.33 ± 16.27 to 240.40 ± 21.49, P = 0.05), administration of VAC + Mg could not increase alkaline phosphatase activity. However, treatment with VAC + Mg significantly enhanced the osteocalcin level. The serum concentration of VEGF was increased in the VAC group (269.04 ± 116.63 to 640.03 ± 240.16, P < 0.05). Callus formation in the VAC + Mg group was higher than the other groups but the differences between the four groups were not significant (P = 0.39). No relevant side effect was observed in patients in each group. Our results suggest that administration of vitex agnus castus plus magnesium may promote fracture healing. However, more studies need to further explore the roles of vitex agnus castus in fracture repair processes.
    Journal of research in medical sciences 01/2014; 19(1):1-7. · 0.65 Impact Factor
Show more