Fachbereich Veterinärmedizin



    Osteointegration verschiedener vorgefüllter Titan-Mesh-Cages mit osteoinduktiven Materialien zur Verbesserung der Spondylodese der Halswirbelsäule Bio- Cage IX (2011)

    Dettmann, Sonja (WE 12)
    Berlin: Mensch und Buch Verlag, 2011 — VI, 223 Seiten
    ISBN: 978-3-86387-003-4
    URL (Volltext): http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000024647
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    +49 30 838 62450

    Abstract / Zusammenfassung

    The fusion of vertebral segments is an established treatment for degenerative diseases of the cervical spine. For decades the autologous tricortical iliac crest bone graft has been used as gold standard (Banwart et al., 1995). The increased incidence of implant failure with kyphothic malposition and moving led to the increased use of intervertebral cages augmented with cancellous bone. These metallic and plastic implants are introduced via a ventral surgical access in an intervertebral disc space in order to prevent the collapse associated with kyphosis of the cervical spine and stenosis of the exit openings for the spinal nerves (foramina intervertebralia), (Korovessis et al., 2006).
    Emphasis of spondylodesis research is placed on improving surgical procedures and implants used. Further, it aims at acceleration of spondylodesis to increase biomechanical stability and at the development of alternatives for the use of autologous bone grafts to avoid relevant removal morbidity (Park and An, 2009).
    In this in vivo study the use of an intervertebral box-design cage made of titanium (Syncage-C) augmented with a combination of different osteoinductive or osteoconductive bone replacement materials was investigated. The groups “unfilled cage” and “cage augmented with TricOs” were used as controls. The objective of the study was the examination of the transferability of the results of other orthopedically studies in the animal model (permission 152/1997, 09/2000, 139/2000, 191/2003, 185/2004, cantonal veterinary office Zurich, Switzerland) to the use in intervertebral spondylodesis. It was expected that the results are at least comparable with the use of autologous bone.
    For this purpose forty-eight two year old merino-mix female sheeps underwent a standardized procedure of discectomy of C3 / C4 and were, divided into the following randomised groups, by means of implantation of a cage fused.
    Group 3 and 12 (n 3, 12 = 8) served as control groups, which received either unfilled cages (group 12) or TricOs-granules augmented implants (group 3).
    Group 9, 10, 11, 15 served as study-groups (n 9, 10, 11, 15 = 8), who`s implanted cages were augmented with TricOs and the parathormone in four different concentrations (1,0; 0,4; 0,7; 0,2 mg / ml) covalently bound to the substrate fibrin.
    Twelve weeks after operation euthanasia of the animals took place followed by histological, immunohistological and histomorphometrical evaluation of the vertebral segment.
    In addition, the quantitatively calculated absolute areas of bone and TricOs are used to establish the fusion score, the density of osteoclasts and the vascular density. The histological appearance of all groups is comparable, only the control group “unfilled cage” differs because of the absence of TricOs-granules.
    On the one hand, by analyzing the results of the descriptive histology and fusion score after the twelve weeks of lifetime the desired complete vertebral bone fusion of C3 / C4 could not be detected. On the other hand, the use of an iliac crest graft achieved a solid spinal fusion from 88 up to 97% (Bohlmann et al., 1993; Brodke and Zdeblick, 1992; De Palma et al., 1972). A conclusive scientific evidence of at least equivalent results by use of the analysed bone substitution material has not been achieved.
    The TricOs-particles, surrounded by bone, cartilage and connective tissue, dominates the disc, with the exception of the dorsal region.
    The incomplete degradation of the TricOs-particles conforms to the results of a study from Katthagen and Mittelmeier (Katthagen and Mittelmeier, 1984). In the present study the TricOs- particles were additionally neither completely sourrounded by bone nor integrated in the intervertebral space. In these areas a significant high density of osteoclasts was detected, which was significantly higher in the cranial and caudal regions of study group 15 than in the control groups. The osteoinductive effect was established by formation of new bone such as described in an other source (Nizard, 1981) as well as its osteoconductivity as support matrix for the local use of the osteoinductive parathormone (Franch et al., 2006).
    There is a mainly light inflammatory reaction in direct contact to TricOs- granules and the titanium implant, whereas severe cases are only occasionally detected. This confirms the expected extent of inflammation described in literature (Bauer, 2007; Kandziora et al., 2002 a, b, c). All histological preparations are characterized by a generally high vascular density with the significantly greatest value for control group 3 “TricOs”. Occurrence of hypervascularisation validate, in addition to the osteoconductivity of the bone substitute TricOs, an inflammatory reaction associated with high hydrostatic stress (Lacroix and Prendergast, 2002; Loboa et al., 2001). To obtain excellent results during bone formation besides the osteoconductive ceramic, a combination of osteoinductive components like PTH and fibrin, as in this study, should be employed (Arrighi et al., 2009).
    By comparison between the six groups there are significant differences for the areas of bone, mineralized bone, undifferentiated connective tissue, cartilage, TricOs-granules and absolute connective tissue. The control group “unfilled cage” is characterized by the significant greatest bone area within the intervertebral disc space.
    Several studies obtained by use of an unfilled cage made of titanium to reach vertebral fusion in humans good clinical results without the complications associated with extraction of an Iliac crest graft (Lange et al., 2000; Schröder et al., 2007; Krayenbühl et al., 2008). An inhomogeneous group distribution was determined for the measured areas of cartilage, TricOs and connective tissue.
    On the other hand the measured areas of cartilage, TricOs, absolute connective tissue show inhomogeneous differences between the groups.
    Spondylodesis, stimulated by the unfilled cage, is comparable, but no de-novo-synthesis of cartilage has taken place. This control group formed practically no cartilage. But chondral ossification is necessary to achieve optimal process during fracture healing (Schiedt, 1955).
    Differentiation between already existing and newly formed bone following discectomy was not possible. Therefore used toluidine blue staining preparations of the controlgroup “unfilled cage” were unfortunately not rateable. This is in contrast to the results of a study carried out by Arrighi et al. where the toluidine blue staining is successful used to differentiate newly formed bone (Arrighi et al., 2009).
    This study in sheep revealed, that this material for bone replacement, despite outstanding of establishment of the optimum concentration of parathormone, is a composition of active ingredients, which accelerate the osteointegration and de-novo-synthesis of bone independent of the patients morbidity.