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Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 445 - 445
1 Sep 2009
Stiehler M Stiehler C Overall R Foss M Besenbacher F Kruhøffer M Kassem M Günther K Bünger C
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Metallic implants are widely used in orthopedic, oral and maxillofacial surgery. Durable osseous fixation of an implant requires that osteoprogenitor cells attach and adhere to the implant, proliferate, differentiate into osteoblasts, and produce mineralized matrix. We previously observed that human mesenchymal stem cells (MSCs) adherent to smooth tantalum (Ta) surfaces demonstrated superior biocompatibility compared with titanium (Ti) coatings.

The aim of the present study was to investigate the interactions between MSCs and smooth surfaces of Ta and by means of whole-genome microarray technology.

Immortalized human mesenchymal stem cells were cultivated on smooth surfaces of Ti and Ta. Total RNA was extracted after culturing for 1, 2, 4, and 8 days and hybridized to Affymetrix whole-genome microarrays (N=16). Replicate arrays were averaged and the ratios of gene expression by MSCs cultivated on Ta versus Ti coating were calculated. Absolute fold differences were also calculated and lists of upregulated genes were generated. Moreover, gene Ontology (GO) annotation analysis of differentially regulated genes was performed.

For both Ta and Ti coatings, the vast majority of genes were upregulated after 4 d of cultivation. Genes upregulated by MSCs cultivated on Ta coating for 4 d were annotated to relevant GO terms. Ti-regulated GO annotation clusters were predominantly transcription-related. By using the K-means clustering algorithm, 10 clusters containing more than 5 genes were identified. Moreover, various genes related to osteogenesis and cell adhesion were upregulated by MSCs exposed to Ta surface.

Microarray analysis of MSCs exposed to smooth metallic surfaces of both Ta and Ti generally showed a huge increase in transcriptional activity after 4 d of cultivation. According to GO annotation analysis Ta coating may induce increased adhesion and earlier differentiation of MSCs compared to Ti surface making Ta a promising biocompatible material for bone implants.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 453 - 453
1 Oct 2006
Christensen F Videbaek T Soegaard R Hansen E Bünger C
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Introduction Circumferential fusion has become a common procedure in lumbar spinal fusion, both as a primary and salvage procedure. However, the claimed advantages of circumferential fusion over conventional posterolateral fusion lack scientific documentation. The aim of the present study was to analyse the long-term outcome; functional disability, pain and general health of circumferential lumbar fusion in comparison to instrumented posterolateral lumbar fusion.

Methods From April 1996 to November 1999 a total of 148 patients with severe chronic low back pain were randomly selected for either posterolateral lumbar fusion (titanium Cotrel-Dubousset) or circumferential lumbar fusion (instrumented posterolateral fusion with anterior intervertebral support by a Brantigan cage). The primary outcome measure was the Dallas Pain Questionnaire (DPQ). The secondary outcome measures were, the Oswestry Disability Index, the SF-36 instrument and the Low Back Pain Rating Scale. All measures assessed the end-point outcomes at 5–9 years postoperatively.

Results The available follow-up rate was 93%. The circumferential group showed a significantly better improvement (p< 0.05) in comparison to the posterolateral group with respect to all four DPQ categories: daily activities, work/leisure, anxiety/depression and social interest. The Oswestry Disability Index supported these results (p< 0.01) in the circumferential group where as no significant difference was found with respect to mental health compared to the posterolateral group. The circumferential group showed significantly less back pain (p< 0.05) in comparison to the posterolateral group. No significant difference was found regarding leg pain.

Discussion Circumferential lumbar fusion demands more extensive operative resources compared to posterolateral lumbar fusion. However, 5–9 years after surgery the circumferentially fused patients had a significantly improved outcome compared to posterolateral fusion alone. These new results underline the superiority of circumferential fusion in the complex pathology of the lumbar spine and are strongly supported in all validated questionnaires.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 307 - 307
1 May 2006
Drescher WR Li H Lundgaard A Bünger C Hansen E
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Introduction: In the pathogenesis of steroid-associated femoral head necrosis only intra- and extravascular factors have been discussed. This study investigated the effect of long term glucocorticoid treatment on contraction of intraosseous femoral head arteries in a porcine model.

Materials and Methods: From 24 immature female Danish Landrace pigs from 12 litters, 12 animals received 100 mg methylprednisolone daily for 3 months. Their 12 sister pigs served as controls and received no steroids. Resistance arteries (diameter approximately 250 μm) were isolated from the femoral head epiphyseal cancellous bone and mounted as ring preparations on a small vessel myograph for measurement of isometric force development.

Results: Increasing doses of endothelin-1 evoked significantly stronger vasoconstriction after 3 months of methylprednisolone treatment. The vasocontractory response to increasing doses of noradrenaline was not altered by the previous methylprednisolone treatment. After submaximal precontraction by noradrenaline, vasorelaxation by bradykinin was not altered by methylprednisolone treatment.

Discussion: The vasocontractory response of isolated intraosseous femoral head epiphyseal arteries to endothelin-1 after long term glucocorticoid treatment in the pig was enhanced. Enhanced contraction of FH lateral epiphyseal arteries can diminish femoral head blood flow as vessel diameter decreases. This may be a relevant cofactor in the early pathogenesis of steroid-associated femoral head necrosis.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_III | Pages 193 - 193
1 Mar 2003
Laursen M Christensen F Hansen E Høy K Gelineck J Niedermann B Helmig P Bünger C
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Introduction: In the attempt to improve fusion rates in spondylodesis surgery, focus has been applied on numerous factors, including surgical strategies, instrumentation-devices and –material, technical preparation of the fusion bed, stringency of radiological outcome criteria, patient-related factors such as age, sex, tobacco consumption, and severity of underlying pathology. In recent years the development of new techniques for exploring mechanisms in cellular and molecular biology have further directed focus toward more advanced biological techniques and considerations. To the authors’ knowledge, little or no attention has been focused on one of the basic and important factors in the attempt to achieve fusion, ie the impact of bone graft quantity placed at the fusion bed.

The aim of this study was to investigate the influence of autologous bone graft quantity in posterolateral instrumented spinal fusion (PLF) in respect to fusion rates.

Methods and results: A prospective clinical study in 76 patients, in which CD-instrumented posterolateral lumbar or lumbosacral spine fusion surgery was performed. The quantity of autologous bone graft applied at the fusion bed was recorded peroperatively. Spinal fusion rates were assessed by AP/lateral radiographs at one-year follow-up by two independent observers, according to our strict classification system. The impact of bone graft quantity, tobacco consumption, age and sex of the patients were analysed in respect to fusion-rates by logistic regression.

According to our classification “fusion” was seen in 76% of the patients, “non-union” in 12.7% and “doubtful”fusion in 11.3%. In “fusion” segments, the median amount of bone used was 24.4 (13–53) g and 14.7 (12.5–23.4) g in “non-union” segments. The “non-union” rate was 7.1% for non-smokers in contrast to 21.4% for patients who smoked during the first six post-operative months. The impact on fusion rates by graft quantity and cigarette smoking were significant, p< 0.006 respectively 0.035. Age and gender did not influence fusion rates. Thirty-three percent of patients with “non-union” had a corresponding failure of the implant.

Conclusions: The quantity of graft used at the fusion bed is critical for successful fusion. Based on the results presented here, we recommend a minimum of 24 g of autogenous bone graft at each intervention segment in auto-grafted posterolateral spinal spondylodesis surgery. In addition, this study underlines the importance of tobacco arrest, in at least the first six post-operative months. The data presented here strongly support the importance of quantifying or optimally standardising the amount of graft placed at each intervention segment.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_III | Pages 192 - 193
1 Mar 2003
Bünger C Hansen E Høy K Neumann P Niedermann B Lindblad B Helmig P Laursen M Christensen F
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Introduction: Lumbar spine fusion is now an evidence based treatment principle of low back pain. However, much controversy still exists on the choice of surgical technique. Since the source of pain may be located in the intervertebral disc, a disc removal seems logical. Instrumented and non-instrumented fusion as well as PLIF have failed to restore lumbar lordosis.

Aim: The aim of the present study was to study fusion rates, functional outcome, lumbar lordosis and complications in a RCT design using radiolucent cages and titanium instrumentation.

Materials and methods: 148 patients were bloc randomised to either PLF (72) or ALIF + PLF (76) from April 1996 to February 2000. Inclusion criteria were disc degeneration or spondylolisthesis groups 1 and 2; Age> 20 years and < 65 years. Life quality was assessed pre-operatively, one and two years post-operatively by Dallas Pain Questionnaires and by Back and Leg Pain rating scales from 0 to 10.

Results and discussion: A preliminary follow-up at one year post-op of 56 patients in each group showed no difference in admission or blood loss (921/1008 ml) and peroperative morbidity, although the operation time was significantly longer in the ALIF+ group (mean 219/344 minutes). Sagittal lordosis was restored and maintained in the ALIF+ group (p< 0.01), in contrast to the PLF group. There was no difference in functional outcome. Average back pain lasting 14 days scored 4.5 in each group, and leg pain 3.2 in the ALIF+ group versus 4 in the PLF group (NS). The re-operation rate was significantly higher in PLF after both one and two years with 9% refusion versus no refusion in the ALIF+ group. Global patient satisfaction was equal in both groups: 78% versus 76% at one year and at two years 75% versus 80% in PLF and ALIF+ groups.

Conclusion: ALIF+ fusion demands higher operative resources compared to PLF, however ALIF+ restores lordosis and provides the highest union rate and significantly fewer reoperations. A cost/effectiveness analysis after long-term follow-up may also favour the ALIF+ treatment due to improved lordosis and perhaps less degeneration of adjacent motion segments.