Götz Röderer

BMP‐2, BMP‐4, and PDGF‐bb stimulate chemotactic migration of primary human mesenchymal progenitor cells

For bone development, remodeling, and repair; the recruitment of mesenchymal progenitor cells (MPC) and their differentiation to osteoblasts is mandatory. The process of migration is believed to be regulated in part by growth factors stored within the bone matrix and released by bone resorption. In this study, primary human MPCs and to osteoblasts differentiated progenitor cells were examined for chemotaxis in response to human basic fibroblast growth factor (rhbFGF), human transforming growth factor beta 1 (rhTGF‐β1), human platelet derived growth factor bb (rhPDGF‐bb), human bone morphogenetic protein‐2 (rhBMP‐2), and recombinant bone morphogenetic protein‐4 of Xenopus laevis (rxBMP‐4) from 0.001 to 1.0 ng/ml each. The results of migration were expressed as a chemotactic index (CI). Migration of primary human progenitor cells was stimulated by rhBMP‐2, rxBMP‐4, and rhPDGF‐bb in a dose‐dependent manner. The increase of CI was up to 3.5‐fold for rhBMP‐2, 3.6‐fold for rxBMP‐4, and up to 22‐fold for rhPDGF‐bb, whereas rhTGF‐β1 and rhbFGF did not stimulate cell migration in the concentration range tested. In contrast differentiated progenitor cells behave similar to primary human osteoblasts. RhBMP‐2, rhPDGF‐bb, and rhTGF‐β1 stimulated the migration from 2.2 to 2.4‐fold each, while rxBMP‐4 and rhbFGF reached only a CI of 1.7–1.6. The effect of rhBMP‐2, rxBMP‐4, and rhPDGF‐bb as chemoattractive proteins for primary human MPC, including the change in response to growth factors after differentiation suggests a functional role for recruitment of MPCs during bone development and remodeling, as well as fracture healing. J. Cell. Biochem. 87:305‐312, 2002.

Clinical Results for Minimally Invasive Locked Plating of Proximal Humerus Fractures

Objectives: To describe the minimally invasive treatment of fractures of the proximal humerus using the Non-Contact-Bridging (NCB) plate. The system allows secondary locking of screws to the plate with a locking cap and polyaxial (30° radius) screw placement. Design: Prospective cohort study. Setting: University Level I trauma center. Patients: Fifty-four patients with unstable fractures of the proximal humerus. Intervention: Minimal anterolateral acromial approach to the proximal humerus, percutaneous fracture reduction, and minimally invasive application of the NCB plate. Main Outcome Measurements: Constant Score and radiologic follow-up (anteroposterior and transscapular). Visual Analog Scale for subjective evaluation of pain and function. Results: After 17 months, the average Constant Score was 66.8 points (87% of the age- and sex-related normal values). Implant-related complications (plate impingement, screw perforation into the glenohumeral joint, loosening of screws) occurred in nine cases (17%). The rate of avascular necrosis was low (5.5%) and no cases of nonunion were seen. Conclusions: The effectiveness of the NCB is similar to other published methods of treatment for fractures of the proximal humerus and potentially provides a less invasive option for this problem. Complication rates and functional outcome in this series are comparable to the literature. An important factor in this technique is the process of percutaneous fracture reduction. The NCB plate is suitable for both a minimally invasive technique or standard open reduction and internal fixation through a deltopectoral approach; the surgeon must decide which approach is best for each particular fracture pattern and should be comfortable with both techniques.

Second generation locked plating of proximal humerus fractures—A prospective multicentre observational study

Surgical treatment of most displaced proximal humerus fractures is challenging due to osteoporosis. Locking plates are intended to provide superior mechanical stability. In a prospective multicentre study 131 patients were treated with second generation locked plating (NCB-PH, Zimmer, Inc.). The open procedure (n = 78) was performed using a deltopectoral approach; the minimally invasive technique (n = 53) involved percutaneous reduction and an anterolateral deltoid split approach. Clinical and radiological follow-up was obtained. Improvement in function (ROM) was statistically significant. Fracture type (AO) had the most significant impact on the incidence of complications. The most frequent complications detected were intra-articular screw perforation (15%) and secondary displacement (8%). Complication rate and functional outcome of the NCB-PH are comparable to reports in the literature. Not all problems are likely to be solved by this new generation of implants, i.e. secondary dislocation still occurred in 8% of our patients.

Minimally invasive application of the non-contact-bridging (NCB) plate to the proximal humerus: an anatomical study.

Objectives: To describe a minimal anterolateral acromial approach for minimally invasive (MI) treatment of fractures of the proximal humerus (PH) with the Non-Contact-Bridging (NCB) plate. Design: 1) Cadaver study and 2) clinical case series. Setting: 1) University Institute of Anatomy and the 2) University Level I trauma center. Specimens/Patients: 1) Ten fresh frozen human humeri and 2) 22 patients with 22 isolated proximal humeral fractures. Intervention: 1) Minimal anterolateral acromial approach with MI application of the NCB-PH plate followed by dissection of the axillary nerve and 2) MI fracture fixation using this approach and technique of plate insertion. Main Outcome Measures: 1) Integrity of the axillary nerve and evaluation of its relationship to the implant, and 2) early postoperative functional results. Results: In the cadaver study, the nerve directly crossed over the percutaneously inserted plate in all the arms. The nerve then divided into two branches anterior to the plate in eight arms and divided into two branches directly over the plate in two arms. One branch of the axillary nerve in one arm was injured. In the clinical case series, no intraoperative complications relating to the approach or the implant occurred. No symptoms of axillary nerve lesion have been detected so far in the early follow-up. Conclusions The minimal anterolateral acromial approach is suitable for MI technique to apply the NCB-PH. The relationship of the axillary nerve to the plate is anatomically close. We recommend that strict bone contact be maintained during plate insertion and that screw insertion complies with the guidelines provided for this technique. In a small clinical cases series, the plate and screws were inserted in accordance with these guidelines and no axillary nerve lesions have yet been detected.

Biomechanical in vitro assessment of screw augmentation in locked plating of proximal humerus fractures

INTRODUCTION Proximal humerus fracture fixation can be difficult because of osteoporosis making it difficult to achieve stable implant anchorage in the weak bone stock even when using locking plates. This may cause implant failure requiring revision surgery. Cement augmentation has, in principle, been shown to improve stability. The aim of this study was to investigate whether augmentation of particular screws of a locking plate aimed at a region of low bone quality is effective in improving stability in a proximal humerus fracture model. MATERIALS AND METHODS Twelve paired human humerus specimens were included. Quantitative computed tomography was performed to determine bone mineral density (BMD). Local bone quality in the direction of the six proximal screws of a standard locking plate (PHILOS, Synthes) was assessed using mechanical means (DensiProbe™). A three-part fracture model with a metaphyseal defect was simulated and fixed with the plate. Within each pair of humeri the two screws aimed at the region of the lowest bone quality according to the DensiProbe™ were augmented in a randomised manner. For augmentation, 0.5 ml of bone cement was injected in a screw with multiple outlets at its tip under fluoroscopic control. A cyclic varus-bending test with increasing upper load magnitude was performed until failure of the screw-bone fixation. RESULTS The augmented group withstood significantly more load cycles. The correlation of BMD with load cycles until failure and BMD with paired difference in load cycles to failure showed that augmentation could compensate for a low BMD. DISCUSSION AND CONCLUSION The results demonstrate that augmentation of screws in locked plating in a proximal humerus fracture model is effective in improving primary stability in a cyclic varus-bending test. The augmentation of two particular screws aimed at a region of low bone quality within the humeral head was almost as effective as four screws with twice the amount of bone cement. Screw augmentation combined with a knowledge of the local bone quality could be more effective in enhancing the primary stability of a proximal humerus locking plate because the effect of augmentation can be exploited more effectively limiting it to the degree required.

[The Non-Contact Bridging Plate. A new fixed-angle device for the minimally-invasive treatment of fractures of the proximal humerus--technique and preliminary results].

Background. Fractures of the proximal humerus are common in elderly patients, especially in osteoporotic bone. Requirements for surgical treatment are high primary stability to allow early functional physiotherapy. The Non-Contact Bridging (NCB®) Plate for the proximal humerus (PH) is a new head locking system for treating fractures of the proximal humerus which allows minimally invasive surgery (MIS). Methods. In this contribution, the implant and technique are described, as well as the analysis of the first clinical results after 61

Delayed bone healing following high tibial osteotomy related to increased implant stiffness in locked plating.

INTRODUCTION Asymmetrical callus formation and incomplete bone formation underneath stiff locking plates have been reported recently in clinical and experimental fracture healing studies. After similar effects were observed in the outcome of high tibial osteotomy (HTO) patients, a retrospective study was performed to quantify the frequency and level of such incomplete healing cases. MATERIAL AND METHODS Twenty-three patients treated with medial open wedge HTO and locking plate (Tomofix™) for posttraumatic or congenital genu varum were investigated. No bone grafts were applied to fill the osteotomy gap. The median correction angle was 8° (5-18°). Elective hardware removal was performed after a median of 19.5 months (12-58 months) following an uneventful clinical course. The most recent postoperative X-ray available (median 21 months; 13-56 months) was evaluated for consolidation of the osteotomy. We performed an in vitro biomechanical experiment using the same HTO on a loaded cadaver knee joint to compare interfragmentary movements (IFMs) when using regular locking screws with the Tomofix™ plate and screws that enabled dynamic stabilisation of this plate. RESULTS Fifteen patients (65%) displayed incomplete consolidation of the osteotomy underneath the locking plate (10.9% of the osteotomy length) and cortical deficiency. The time to implant removal for these patients of 27 months was longer than the 21 months for the patients with a complete osteotomy gap healing. The biomechanical experiment demonstrated that very low IFMs and corresponding interfragmentary strain occur underneath the plate when using regular locking screws. Replacement with dynamic screws resulted in an increased IFM. DISCUSSION AND CONCLUSIONS These results support the hypothesis that low bone formation underneath locking plates is induced by increased stiffness. This high stiffness situation could be altered by replacing the standard screws with dynamic screws which allow for a movement of 0.35mm perpendicular to the screw axis. This resulted in an approximately threefold increase in the IFM and may be a potential concept to avoid incomplete bone healing under stiff plate fixations.

Where do locking screws purchase in the humeral head

INTRODUCTION One of the limiting factors in finding the best osteosynthesis approach in proximal humerus fractures is the current lack of information on the properties of the cancellous bone regions engaged by the implants fixing the epiphysis. The aim of this study is to assess the densitometric and mechanical characteristics of these regions when using a proximal humerus locking plate (PHLP). MATERIALS AND METHODS Nineteen PHLPs were mounted on cadaveric humeri using only their three most distal screws. Subsequently, the plates were removed and the bones were scanned using high-resolution peripheral quantitative computed tomography. Bone mineral density (BMD) was determined in the intact proximal epiphysis and in the exact locations where the six proximal screws would have been positioned concluding the instrumentation. Each plate was then repositioned on its bone and a minimally destructive local torque measurement was performed in the same six locations. A statistical analysis was performed to detect significant differences in the investigated parameters between screw positions, and to test the ability of local torque values to discriminate the bone mineral density of the entire humeral head (BMD(TOT)). RESULTS Novel data about the cancellous bone engaged by the screws of a PHLP are provided. Different epiphyseal locations showed statistically significant different properties. A local torque measurement was a good predictor of the BMD(TOT). CONCLUSION Position and direction of the epiphyseal screws on a locking implant are determinant to engage bone regions with significantly better bone quality. A breakaway torque measurement in a given screw position can distinguish between humeral heads with different densitometric properties.

Mechanical Assessment of Local Bone Quality to Predict Failure of Locked Plating in a Proximal Humerus Fracture Model

The importance of osteoporosis in proximal humerus fractures is well recognized. However, the local distribution of bone quality in the humeral head may also have a significant effect because it remains unclear in what quality of bone screws of standard implants purchase. The goal of this study was to investigate whether the failure of proximal humerus locked plating can be predicted by the DensiProbe (ARI, Davos, Switzerland). A 2-part fracture with metaphyseal impaction was simulated in 12 fresh-frozen human cadaveric humeri. Using the DensiProbe, local bone quality was determined in the humeral head in the course of 6 proximal screws of a standard locking plate (Philos; Synthes GmbH, Solothurn, Switzerland). Cyclic mechanical testing with increasing axial loading until failure was performed. Bone mineral density (BMD) significantly correlated with cycles until failure. Head migration significantly increased between 1000 and 2000 loading cycles and significantly correlated with BMD after 3000 cycles. DensiProbe peak torque in all screw positions and their respective mean torque correlated significantly with the BMD values. In 3 positions, the peak torque significantly correlated with cycles to failure; here BMD significantly influenced mechanical stability. The validity of the DensiProbe was proven by the correlation between its peak torque measurements and BMD. The correlation between the peak torque and cycles to failure revealed the potential of the DensiProbe to predict the failure of locked plating in vitro. This method provides information about local bone quality, potentially making it suitable for intraoperative use by allowing the surgeon to take measures to improve stability.

Electrophysiological Assessment of the Deltoid Muscle after Minimally Invasive Treatment of Proximal Humerus Fractures - A Clinical Observation

The minimal anterolateral acromial approach offers a less invasive access to the proximal humerus. Functional impairment following this procedure may be caused by paresis of the deltoid muscle as a result of iatrogenic injury to the axillary nerve. It was addressed whether electromyography (EMG) of the deltoid muscle gives evidence for an axillary nerve lesion in association with the minimal anterolateral acromial approach. Twenty-three patients (14 men, 9 women; average age 58 years) with proximal humerus fractures were included in this clinical observation. Follow-up was performed 6 weeks (6w), 6 months (6m) and 12 months (12m) postoperatively. EMG changes indicating either lesion of the axillary nerve or direct muscle trauma were distinguished in “acute”, “chronic” and “combined” and semi quantified in “slight”, “moderate” and “severe”. Patients were examined clinically (standard neurological examination and Constant Score). Three cases of incomplete axillary nerve lesion with limited functional impairment were detected. Subclinical EMG signs of neural impairment of the deltoid muscle were observed frequently (6w, N = 8; 6m, N = 8; 12m, N = 7). Functional outcome did not show an association with EMG. Most patients presented with subclinical and most likely trauma- related neurogenic lesions of the deltoid muscle following the anterolateral acromial approach. Despite the fact that the axillary nerve does not function normally following this less-invasive approach for fixation of proximal humerus fractures, this does not appear to affect the clinical outcome. Prospective studies with larger sample sizes are required to determine the effect of axillary nerve retraction in the more commonly used deltopectoral approach.