Bone defects and nonunions—What role does

Injury, Int. J. Care Injured 41 (2010) 553–554
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Injury
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Editorial
Bone defects and nonunions—What role does vascularity play in ﬁlling the gap?
Bone defects and nonunions impose a tremendous cost on
society. The average cost for patients suffering nonunions equates
to about 25.000 USD.26 Although bone loss is known to cause
longer periods of treatment, higher complication rates and
associated hospital costs, the information on this condition is
surprisingly sparse.
Clinicians are aware that certain biological conditions have to be
respected to ensure effective treatment of bone loss.4,15,18–22,9,27 The
quality of the soft tissue envelope is crucial and close cooperation
between orthopaedic trauma surgeons and plastic surgeons is
required to allow for a high standard of care. The presence of
adequate blood supply to the affected limb is of paramount importance to any plans of reconstruction. In preparation for surgery, large
nutrient vessels are routinely assessed for the feasibility to place a
free ﬂap. In contrast, smaller vessels, or even the microvascular
supply, are not examined on a routine basis (Table 1).
Historically, plastic surgeons have therefore focussed upon the
quality of soft tissue coverage while orthopaedic trauma surgeons
treated the bone lesion and research was purely assessing bone
grafting or techniques to ﬁll in the bony gap. Thus, orthopaedic
surgeons used distraction osteogenesis, autologous bone grafting,
heterologous bone grafting, or ﬁlled the void using bone matrices.
These were combined with growth factors, osteogenic cells or a
combination of the above. The interaction with basic researchers to
improve clinical outcomes has been limited. Cancedda et al. broke
this rule and performed one of the few available studies that
looked at ﬁlling large bone defects. Nevertheless, the number of
clinical studies determining the ingrowth of large bone grafts is
limited.4 More recently, Masquelet and coworkers have also
initiated a cooperation with basic researchers to assess why their
method of temporary implantation of one cement causes the
growth of a well vascularised membrane. According to their
ﬁndings, both the osseous conditions and the vascularity are of
pivotal importance to ensure adequate ingrowth of bone.
Masquelet and Begue were also the ﬁrst to describe a technique
focussing on improvement of the surrounding small vessel
vascularity.15 According to the histological studies, temporary
ﬁlling of the gap with bone cement induces the development of a
well vascularised membrane. This membrane appears to have
excellent nourishing abilities even for large grafts. Moreover, these
grafts appear to function even in the aftermath of osteomyelitis,
provided that the active infection has been cured. Animal studies
have supported the clinical experience, but to date, only one large
case series has been published.15
Among the local conditions under which the vascularity can be
improved are local tissue factors. The diamond concept clearly
0020–1383/$ – see front matter ß 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.injury.2010.04.001
Table 1
Causes for bone loss.26.
documents the importance of a well-balanced system of cellular
components, mechanics, and host factors (Fig. 1).
Numerous animal studies demonstrated the pivotal role of
vascular endothelial growth factor (VEGF).20–22,9 It appears that
these factors are important in generating a microenvironment that
facilitates bone growth. Regulation of bone growth appears to be
dependant on interactions between various hormones and VEGF.
Among these, estradiol and corticoid derivates have been
examined. The crucial role of angiogenetic factors such as VEGF
is supported by the model described by Parﬁtt (Fig. 2).18
He describes the coupling of osteoblasts and osteoclasts in basic
multicellular units (BMU’s). The centre of a BMU is formed
by capillary endothelial cells. Angiogenetic factor (VEGF) is a
mediator for the recruitment of endothelial cells. Following their
Editorial / Injury, Int. J. Care Injured 41 (2010) 553–554
554
Fig. 1. Diamond concept of bone generation, according to Ref. 19.
Fig. 2. VEGF can be immunostained in osteoblasts of a basic multicellular units
(BMUs). In the centre of the BMU are endothelial cells detectable (arrow heads).
Bar = 10 mm.
recruitment, endothelial cells undergo a time-dependent gene
switch that promotes bone remodelling. Likewise, endothelial cells
may act as a source to release mitogens for osteoblasts. In addition,
they appear to be capable of inhibiting or regulating osteoclast
activity.27 Recent studies revealed that other angiogenetic factors
such as pleiotropin (PTN) may also participate in fracture
healing.19 Clinical studies clearly document that decreased serum
levels of PTN are associated with malunion and nonunion in
addition to the factors described before.24,17,2,14,11,10
Future research should aim at a close cooperation between
basic researchers and clinicians in order to undermine the clinical
ﬁndings.1,3,12,13,5–8,25,16,23
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H.C. Pape*
Dept. of Orthopaedics/Trauma, University of Aachen Med. Ctr. 30
Pauwels Street, Aachen 52074, Germany
Th. Pufe
Dept. of Anatomy, University of Aachen Med. Ctr., 30 Pauwels Street,
Aachen 52074, Germany
*Corresponding
author. Tel.: +1 412 605 3219;
fax: +1 412 687 0802
E-mail address: [email protected] (H.C. Pape)

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