Although bone morphogenetic protein 2 (BMP-2) has been FDA-approved for spinal fusion for decades, its disadvantages of promoting osteoclast-based bone resorption and suboptimal carrier (absorbable collagen sponge) leading to premature release of the protein limit its clinical applications. Our recent study showed an excellent effect on bone regeneration when BMP-2 and zoledronic acid (ZA) were co-delivered based on a calcium sulphate/hydroxyapatite (CaS/HA) scaffold in a rat critical-size femoral defect model. Therefore, the aim of this study was to evaluate whether local application of BMP-2 and ZA released from a CaS/HA scaffold is favorable for spinal fusion. We hypothesized that CaS/HA mediated controlled co-delivery of rhBMP-2 and ZA could show an improved effect in spinal fusion over BMP-2 alone. 120, 8-week-old male Wistar rats (protocol no. 25-5131/474/38) were randomly divided into six groups in this study (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, CaS/HA + BMP-2 + local ZA). A posterolateral spinal fusion at L4 to L5 was performed bilaterally by implanting group-dependent scaffolds. At 3 weeks and 6 weeks, 10 animals per group were euthanized for µCT, histological staining, or mechanical testing. µCT and histological results showed that the CaS/HA + BMP-2 + local ZA group significantly promoted bone regeneration than other treated groups. Biomechanical testing showed breaking force in CaS/HA + BMP + local ZA group was significantly higher than other groups at 6 weeks. In conclusion, the CaS/HA-based biomaterial functionalized with bioactive molecules rhBMP-2 and ZA enhanced bone formation and concomitant spinal fusion outcome

Acknowledgements: Many thanks to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology).

A novel EP4 selective agonist (KMN-159) was developed [1] and has been proven that it can act as an osteopromotive factor to repair critical-size femoral bone defects in rats at a dose-dependent manner [2]. Based on its osteopromotive properties, we hypothesized that KMN-159 could also aid in bone formation for spinal fusion. Therefore, the aim of this study was to investigate its spinal fusion effect in a dorsolateral spinal fusion model in rats. This study was performed on 192, 10-week-old male Wistar rats. The rats were randomized into 8 groups (n = 12 per group): 1) SHAM (negative control), 2) MCM (scaffold only), 3) MCM + 20 µg BMP-2 (positive control), 4-8) MCM + 0.2, 2, 20, 200 or 2000 µg KMN-159. A posterolateral intertransverse process spinal fusion at L4 to L5 was performed bilaterally by implanting group dependent scaffolds (see above) or left empty in the SHAM group (protocol no. 25-5131/474/38). Animals were euthanized after 3 weeks and 6 weeks for µCT and biomechanical testing analysis. The results showed that KMN-159 promoted new bone formation in a dose-dependent manner at 3 weeks and 6 weeks as verified by µCT. The biomechanical testing showed that the dose of 20, 200 and 2000 µg KMN-159 groups obtained comparable strength with BMP-2 group, which higher than SHAM, MCM and lower doses of 0.2 and 2 µg KMN-159 groups. In conclusion, KMN-159 could be a potential replacement of BMP-2 as a novel osteopromotive factor for spinal fusion.

Acknowledgements: We are grateful to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology).

Aims

Periprosthetic fracture is a significant complication of total hip and knee arthroplasty. This study aimed to describe the survival of patients sustaining periprosthetic femoral fractures and compare this with that of the general population, as well as to identify the factors that influence survival.

Introduction

A review of the literature showed a discrepancy between biomechanical and clinical studies on fracture fixation failure in patients with poor bone quality.

The objective of the present study is to assess the influence of local bone status on complications after surgical treatment of proximal humerus fractures.

Introduction

Primary malign tumors and solitary metastatic lesions of the thoracic and thoracolumbar spine are indications for radical en bloc resections. Extracompartimental tumor infiltration makes the achievement of adequate oncological resection more difficult and requires an extension of the resection margins. We present a retrospective clinical study of patients that underwent chest wall resection in combination with vertebrectomy due to sarcomas and solitary metastases for assessing the clinical outcome especially focusing on onco-surgical results.

Introduction: Total en bloc spondylectomy (TES) as the only radical treatment option for sarcoma and solitary metastases of the spine was shown to markedly minimize local recurrences, improve patient quality of life and substantially increase overall survival rates. This study analyzes the onco-surgical results after multilevel thoracolumbar TES and reconstruction with a carbon composite vertebral body replacement system (CC-VBR) in a collective of patients.

Methods: 26 patients (14f/12m; age 52±14y) treated with thoracolumbar multilevel TES (10x2, 12x3, 3x4, 1x5 segments) for spinal sarcomas (n=16), solitary metastases (n=5) and aggressive primary tumors (n=5) were retrospectively investigated. According to the classification system of Tomita et al. all patients were surgically staged as type 6 (multisegmental/extracom-partimental). Defect reconstruction (14 thoracic, 6 thoraco-lumbar and 6 lumbar) were performed with posterior stabilization and a CC-VBR. Patient charts and the current clinical follow-up results were analyzed for histopathological tumor type, pre- and postoperative data (symptoms, duration of surgery, blood loss, complications, intensive care, adjuvant therapies etc.) and course of disease. Latest radiographs and CT-scans were analyzed at follow up. Oncological status was evaluated using cumulative disease specific and metastases-free survival analysis.

Results: With a mean follow up (100%) of 18 (4–44) months 24 patients (92%) were postoperatively ambulatory without any support. Postoperative neurological deficits were seen in two patient (8%). Wide resection margins were attained in 9, marginal in 17 patients. Depending on tumor biology/grading and/or resections margins an adjuvant therapy (radiation/chemotherapy) was performed in 18 (69%) patients. Local recurrence was found in two patient (8%). 19 (73%) patients showed no evidence of disease, 3 were alive with disease while 2 died of disease at 10 and 27 months postoperatively.

Conclusion: In selected patients with multisegmental spinal tumor involvement oncological sufficient resections can be reached by multilevel TES. Although the surgical procedure is challenging and the patient’s stress is considerable our encouraging midterm results together with the low complication rate clearly favour and legitimate this technique. However, treatment success strongly depends on adjuvant therapies. Reconstruction with a CC-VBR showed low complication rates, promising biomechanical characteristics, increased volume for bone grafting and lower artefact rates in follow-up MR- and CT-imaging.

Introduction: Total en bloc spondylectomy (TES) as the only radical treatment option for sarcoma and solitary metastases of the spine was shown to markedly minimize local recurrences, improve patient quality of life and substantially increase overall survival rates. Due to surgical difficulty of TES and complex biomechanical demands in defect reconstruction multisegmental tumor involvement of the spine has long been considered as a palliative situation, exceeding the limits of surgical feasibility. Thus, multilevel resections reports are very rare. For the first time, this study analyzes the onco-surgical results after multilevel thoracolumbar TES and reconstruction with a carbon composite vertebral body replacement system (CC-VBR) in a collective of patients.

Methods: 18 patients (9f/9m; age 52±14y) treated with thoracolumbar multilevel TES (6x2, 9x3, 3x4 segments) for spinal sarcomas (n=9), solitary metastases (n=5) and aggressive primary tumors (n=3) were retrospectively investigated. According to the classification system of Tomita et al. all patients were surgically staged as type 6 (multisegmental/extracompartimental). Defect reconstruction (11 thoracic, 3 thoracolumbar and 4 lumbar) were performed with posterior stabilization and a CC-VBR. Patient charts and the current clinical follow-up results were analyzed for histopathological tumor type, pre- and postoperative data (symptoms, duration of surgery, blood loss, complications, intensive care, adjuvant therapies etc.) and course of disease. Latest radiographs and CT-scans were analyzed at follow up. Oncological status was evaluated using cumulative disease specific and metastases-free survival analysis.

Results: With a mean follow up (100%) of 18 (4–44) months 17 patients (94%) were postoperatively ambulatory without any support. Postoperative neurological deficits were seen in one patient (6%). Wide resection margins were attained in 7, marginal in 11 patients. Depending on tumor biology/grading and/or resections margins an adjuvant therapy (radiation/chemotherapy) was performed in 12 (67%) patients. Local recurrence was found in one patient (6%). 13 (72%) patients showed no evidence of disease, 3 were alive with disease while 2 died of disease at 10 and 27 months postoperatively.

Conclusion: In selected patients with multisegmental spinal tumor involvement oncological sufficient resections can be reached by multilevel TES. Although the surgical procedure is challenging and the patient’s stress is considerable our encouraging midterm results together with the low complication rate clearly favour and legitimate this technique. However, treatment success strongly depends on adjuvant therapies. Reconstruction with a CC-VBR showed low complication rates, promising biomechanical characteristics, increased volume for bone grafting and lower artefact rates in follow-up MR- and CT-imaging.

A major pathway of closed soft-tissue injury is failure of microvascular perfusion combined with a persistently enhanced inflammatory response. We therefore tested the hypothesis that hypertonic hydroxyethyl starch (HS/HES) effectively restores microcirculation and reduces leukocyte adherence after closed soft-tissue injury. We induced closed soft-tissue injury in the hindlimbs of 14 male isoflurane-anaesthetised rats. Seven traumatised animals received 7.5% sodium chloride-6% HS/HES and seven isovolaemic 0.9% saline (NS). Six non-injured animals did not receive any additional fluid and acted as a control group. The microcirculation of the extensor digitorum longus muscle (EDL) was quantitatively analysed two hours after trauma using intravital microscopy and laser Doppler flowmetry, i.e. erythrocyte flux. Oedema was assessed by the wet-to-dry-weight ratio of the EDL.

In NS-treated animals closed soft-tissue injury resulted in massive reduction of functional capillary density (FCD) and a marked increase in microvascular permeability and leukocyte-endothelial cell interaction as compared with the control group. By contrast, HS/HES was effective in restoring the FCD to 94% of values found in the control group. In addition, leukocyte rolling decreased almost to control levels and leukocyte adherence was found to be reduced by ~50%. Erythrocyte flux in NS-treated animals decreased to 90 ± 8% (mean sem), whereas values in the HS/HES group significantly increased to 137 ± 3% compared with the baseline flux. Oedema in the HS/HES group (1.06 ± 0.02) was significantly decreased compared with the NS-group (1.12 ± 0.01).

HS/HES effectively restores nutritive perfusion, decreases leukocyte adherence, improves endothelial integrity and attenuates oedema, thereby restricting tissue damage evolving secondary to closed soft-tissue injury. It appears to be an effective intervention, supporting nutritional blood flow by reducing trauma-induced microvascular dysfunction.