[Fixed angle carbon fiber reinforced polymer composite plate for treatment of distal radius fractures : Pilot study on clinical applications]. / Winkelstabile karbonverstärkte Polymerkompositplatte zur Versorgung einer distalen Radiusfraktur : Pilotstudie zur klinischen Anwendung.

BACKGROUND: The clinical implementation of a new carbon-fiber-reinforced polyetheretherketon (PEEK) plate for distal radius fractures might offer advantageous properties over the conventional metallic devices. This includes similar elastic modulus to cortical bone, radiolucency, low artifacts on MRI scans and the lack of metal allergies. OBJECTIVE: The aim of this study was to evaluate the clinical results at 6-week and 12-month follow-up using either a new fixed angle (monoaxial) PEEK plate system or a fixed angle (polyaxial) titanium plate. METHODES: We included 26 patients (mean age 59.3) with displaced fractures of the distal radius (all AO types). Radiological and functional outcomes were measured prospectively at a 6-week and 12 month follow-up. RESULTS: We documented no cases of hardware breakage or significant loss of the surgically achieved fracture reduction with the usage oft the new PEEK device. Operating time was 101.0 min using PEEK versus 109.3 min in titanium plates, recorded times were including preparation, draping, and postoperative processing (ns, p 0.156). At the 6-week follow up the PEEK plate showed a trend for better range of motion and functional results (DASH-score, Mayo-wrist score, VAS) with no statistical significance. Results of 12 month follow up with PEEK showed comparable results with corresponding studies examining titanium plate after this period. CONCLUSION: First experience with PEEK plate osteosynthesis demonstrate quick clinical implementation with good clinical outcome and the advantage of excellent postoperative radiological assessment. At early follow-up PEEK even showed a trend for improved functional results.

Comparison of intraoperative flat panel imaging and postoperative plain radiography for the detection of intraarticular screw displacement in volar distal radius plate ostheosynthesis.

OBJECTIVES: To investigate if intraoperative 3D flat panel imaging improves the detection of radiocarpal intraarticular screw misplacement (RCSM) in comparison to standard postoperative x-ray. METHODS: In a study on cadaver specimens, we evaluated the sensitivity and specificity to detect RCSM using X-ray, intraoperative 3D-fluoroscopy as well as the digital volume tomography. The gold standard reference was computed tomography. RESULTS: Sensitivity for the detection of RCSM for X-ray was 58% and specificity 88%. For DVT, the sensitivity to detect RCSM was 88% and the specificity 53%. For 3D-fluoroscopy, the sensitivity for RCSM was 68% and specificity 95%. When combining the methods, the best performance was found, when combining the two intraoperative imaging methods, with a resulting sensitivity of 88% and a specificity of 73%. CONCLUSIONS: Intraoperative 3D fluoroscopy and digital volume tomography appear to be at least as sensitive and specific to detect RCSM than the regular postoperative radiography in two planes. However, especially discrete screw misplacements can be missed with either method. LEVEL OF EVIDENCE: Level IV. Diagnostic device study.

[Knee joint infections]. / Das infizierte Kniegelenk.

Knee joint infection represents an emergency case at every age. Joint infection occurs frequently after trauma or joint surgery. The infection can be caused by numerous bacteria, viruses, or yeasts; however, Staphylococcus aureus is identified as the cause in 85-95 % of joint infections. Early treatment is important for patient outcome. In addition to synovectomy and therapeutic arthroscopy, antibiotic therapy is essential and should be started after sample recovery.

Platelet-released growth factors can accelerate tenocyte proliferation and activate the anti-oxidant response element.

Little is know about the pathophysiology of acute and degenerative tendon injuries. Although most lesions are uncomplicated, treatment is long and unsatisfactory in a considerable number of cases. Besides the common growth factors that were shown to be relevant for tendon integrity more recently protection against oxidative stress was shown to promote tendon healing. To improve tendon regeneration, many have advocated the use of platelet-rich plasma (PRP), a thrombocyte concentrate that can serve as an autologous source of growth factors. In this study, we investigated the effect of platelet-released growth factors (PRGF) on tenocytes. Tenocytes were isolated from the Achilles tendon of postnatal rats. Tenocyte cell cultures were stimulated with PRGF. We used a CyQuant assay and WST assay to analyse tendon cell growth and viability in different concentrations of PRGF. Migration and proliferation of cells grown in PRGF were assessed by a scratch test. A dual-luciferase assay was used to demonstrate the activation of the anti-oxidant response element (ARE) in tenocytes. A positive effect of PRGF could be shown on tendon cell growth and migratory capacity. PRGF activated the Nrf2-ARE pathway in a dose-dependent manner. Here, we provide evidence of a biological effect of PRGF on tenocytes by the promotion of tenocyte growth and activation of the Nrf2-ARE pathway. This is a novel aspect of the action of platelet concentrates on tendon growth.

[Patella dislocation]. / Patellaluxation.

The patella dislocation is defined as a non-recurring or recurrent dislocation of the patella from the patella surface of the femur. In general the patella dislocates in the lateral direction. Patella dislocations are subdivided in congenital, habitual or traumatic dislocations. Furthermore patella dislocations are differentiated in recurrent and chronic dislocations. Etiology of patella dislocations is not consistent and can be due to genu valgum, patella dysplasia or patella alta etc. Frequently the patella reposes spontaneously after dislocation. Besides examination of the knee, x-ray and magnetic resonance tomography belong to clinical diagnostics of the knee joint. Decision between conservative and operative therapy is addicted to accompanying injuries like fractures or ligamental injuries.

[Mass sports improves proprioception and reduces valgus stress on the female knee joint]. / Breitensport verbessert die Propriozeption und beugt Valgusstress im Kniegelenk der Frau vor.

AIM: ACL rupture is more common in females than in males. The injury can result in chondral and meniscal damage or chronic instability. Most often ACL rupture occurs during landing after throwing and jumping in ball sports. Many studies have reported on incidence, mechanism of injury and predisposing factors in professional athletes. In contrast, we have investigated the impact of mass sports on predisposing factors for the female ACL rupture. METHOD: In an empirical analytical study leg-axis dynamics, proprioception and foot load of 44 women participating either in regular mass sports or in no sports were investigated by video analysis and on the Biodex-Stability Platform. RESULTS: Our study demonstrates that mass sports improves proprioception of the knee joint. Non-sportive subjects had an increased valgus leg axis during landing in comparison with mass sport participants. CONCLUSION: Here, we show to the best of our knowledge for the first time that moderate sports activity has a positive effect on predisposing factors of the female ACL rupture. We conclude that prevention programmes focussed on jumping and proprioception can lower the incidence of female ACL ruptures.

The antimicrobial peptide HBD-2 and the Toll-like receptors-2 and -4 are induced in synovial membranes in case of septic arthritis.

Septic arthritis is frequently observed especially in immune-compromised or chronically diseased patients and leads to functional impairment due to tissue destruction. Recently, production of antimicrobial peptides (AMP) was observed in articular cartilage after exposure to bacteria. This report examines the role of synoviocyte-derived AMPs in innate defense mechanisms of articular joints. Samples of healthy, low-grade synovialitis and septic synovial membranes were assessed for the expression of human beta-defensin-2 (HBD-2) and Toll-like receptor-2 and -4 (TLR) by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). A stable synoviocyte line (K4IM) was used for in vitro experiments and assayed for endogenous HBD-2 and TLR production after exposure to inflammatory cytokines or bacterial supernatants by reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, Western blot, ELISA, and dual luciferase assay. Healthy human synovial membranes and cultured synoviocytes are able to produce HBD-2 and TLR-1-5 at basal expression levels. Samples of bacteria-colonized synovial membranes produce higher levels of HBD-2 when compared with samples of healthy tissues. K4IM synoviocytes exposed to Staphylococcus aureus, Pseudomonas aeruginosa, or proinflammatory cytokines demonstrated a clear HBD-2 transcription and protein induction. TLR-2 and -4 are known to have a critical role in the recognition of gram-positive and gram-negative bacteria in epithelia and are induced in mesenchymal synoviocytes after bacterial exposure on transcription and on protein level. This report demonstrates an unappreciated role of synovial membranes: samples of septic synovial membranes and cultured synoviocytes exposed to bacteria produce increased amounts of the AMP HBD-2 and the bacteria recognition receptors TLR-2 and -4. The induction of anti-inflammatory pathways in infected synoviocytes suggests involvement in intra-articular defense mechanisms.

Osteoblasts participate in the innate immunity of the bone by producing human beta defensin-3.

Gram-positive bacterial bone infections are an important cause of morbidity particularly in immunocompromised patients. Antimicrobial peptides (AP) are effectors of the innate immune system and directly kill microorganisms in the first hours after microbial infection. The aim of the present investigation was to study the expression and regulation of gram-positive specialized human beta-defensin-3 (HBD-3) in bone. Samples of healthy and osteomyelitic human bone were assessed for the expression of HBD-3. Using primary and immortalized osteoblasts (SAOS-2 cells), release and regulation of HBD-3 was evaluated after exposure to Staphylococcus aureus supernatant and/or corticosteroids using PCR, immunohistochemistry, Western blot and ELISA. To determine the role of toll-like-receptors-2 and -4 (TLR-2/-4), shRNA was used to downregulate TLRs. An osteomyelitis mouse model was created performed to investigate the release of murine beta-defensins using immunohistochemistry and RT-PCR. Cultured osteoblasts and human bone produce HBD-3 under standard conditions. The release increases within hours of bacterial supernatant exposure in cultured osteoblasts. This observation was not made in chronically infected bone samples. The shRNA-technology revealed the necessity of TLR-2 and -4 in HBD-3 induction in osteoblasts. Blocking protein synthesis with cycloheximide showed that the rapid release of HBD-3 is not dependent on a translational de novo synthesis and is not affected by glucocorticoids. The murine osteomyelitis model confirmed the in vivo release uptake of mouse beta-defensins-4 (MBD-4) in bone. This report shows the bacterial induction of HBD-3 via TLR-2 and -4 in osteoblasts and suggests a central role of antimicrobial peptides in the prevention of bacterial bone infection. The rapid and effective induction of HBD-3 in osteoblasts incubated with conditioned media from bacteria is more likely a result of a rapid secretion of preformed HBD-3 by osteoblasts rather than a result of enhanced biosynthesis. The increased incidence of gram-positive bacterial bone infection in patients with regular intake of glucocorticoids does not seem to be caused by a deranged HBD-3 release in osteoblasts.

The role of human beta-defensin-2 in bone.

Osteomyelitis often causes functional impairment due to tissue destruction. This report demonstrates a novel previously unappreciated role of osteoblasts. Samples of osteomyelitic bone and bacterially challenged osteoblasts produce increased amounts of antimicrobial peptides in order to combat bacterial bone infection. An osteomyelitis mouse model confirmed the osseous induction of the murine homologue of human beta-defensin-2, suggesting a central role in the prevention of bacterial bone infection. Antimicrobial peptides are effectors of the innate defence system and play a key role in host protection at cellular surfaces. Some of them are produced constitutively, whereas others are induced during infection. Human beta-defensins represent a major subclass of antimicrobial peptides and act as a first line of defence through their broad spectrum of potent antimicrobial activity. The aim of the present in-vitro and in-vivo investigations was to study the expression and regulation of human beta-defensin-2 in the case of bacterial bone infection and to analyse the effects of immunosuppressive drugs on bone-derived antimicrobial peptide expression. Samples of healthy human bone, osteomyelitic bone and cultured osteoblasts (hFOB cells) were assessed for the expression of human beta-defensin-2. Regulation of human beta-defensin-2 was studied in hFOB cells after exposure to bacterial supernatants, proinflammatory cytokines and immunosuppressive drugs (glucocorticoids and methotrexate) and was assayed by enzyme-linked immunosorbent assay. An osteomyelitis mouse model was performed to demonstrate the regulation of the murine homologue of human beta-defensin-2, named murine beta-defensin-3, by real-time reverse transcription-polymerase chain reaction and immunohistochemistry. Healthy human bone and cultured osteoblasts are able to produce human beta-defensin-2 under standard conditions. Samples of infected bone produce higher levels of endogenous antibiotics, such as human beta-defensin-2, when compared with samples of healthy bone. A clear induction of human beta-defensin-2 was observed after exposure of cultured osteoblasts to gram-positive bacteria or proinflammatory cytokines. Additional treatment with glucocorticoids or methotrexate prevented bacteria-mediated antimicrobial peptide induction in cultured osteoblasts. The osteomyelitis mouse model demonstrated transcriptional upregulation of the murine homologue of human beta-defensin-2, namely murine beta-defensin-3, in bone after intraosseous contamination of the tibia. Human and murine bone have the ability to produce broad-spectrum endogenous antibiotics when challenged by micro-organisms in vitro and in vivo. Immunosuppressive drugs, such as glucocorticoids or methotrexate, may increase the susceptibility to bone infection by decreasing antimicrobial peptide expression levels in case of microbial challenge. The induction of human beta-defensin-2 following bacterial contact suggests a central role of antimicrobial peptides in the prevention of bacterial bone infection.

[Malalignment of the tibia--comparative investigation of three stabilization procedures by clinical analysis and radiological measuring techniques]. / Vergleichende Untersuchung von drei Stabilisationsverfahren bei Unterschenkelschaftfraktur durch klinische Analyse und radiologische Messtechniken.

INTRODUCTION: Malalignment after osteosynthetic stabilization of lower leg fractures is still a common problem for trauma surgeons. The aim of the present study was to evaluate the incidence of torsional and varus- or valgus-malalignment of the lower leg subsequent to osteosynthetic stabilization techniques such as reamed nailing, unreamed nailing and tibial plating. METHODS: 70 patients with 73 fractures of the lower leg were included in the study. The fractures were treated consecutively in 37 cases with an unreamed nail (UTN), in 21 cases with a reamed nail and 15 cases were stabilized with a plate. During clinical follow-up after 5.7 years each patient was analyzed for malalignment of the lower leg with a CT-Scan and a dual-energy X-ray absorptiometry (DXA) analysis. RESULTS: Multi-level CT-scans revealed a significant rotational malalignment in 16.4 % of patients. Interestingly, all misaligned cases were treated with a nail (9.6 % UTN, 6.8 % reamed nail). Varus- or valgus-malalignment was detected in 5.4 % of cases all of whom had been treated with an intramedullary nail. CONCLUSIONS: Malalignment is still a common problem after osteosynthetic stabilization of lower leg fractures, whereby the majority of these cases can be expected after intramedullary nailing. Rotational malalignment can be detected by CT-Scans, whereas DXA analysis is a reliable procedure to diagnose varus- or valgus-malalignment after osteosynthetic stabilization of lower leg fractures.

Influence of estradiol on vascular endothelial growth factor expression in bone: a study in Göttingen miniature pigs and human osteoblasts.

Ovariectomy (OVX) in animal models is an accepted method to simulate postmenopausal osteoprosis. Vascular endothelial growth factor (VEGF) has been recently shown to play an important role during endochondral bone formation, hypertrophic cartilage remodeling, ossification, and angiogenesis. We hypothesized that reduced VEGF expression in bone contributes to OVX-induced bone loss and tested it in a miniature pig model and in vitro using human osteoblasts. Seventeen primiparous sows (Göttingen miniature pigs) were allocated to two experimental groups when they were 30 months old: a control group (n = 9) and an OVX group (n = 8). After 15 months, VEGF levels in lumbar vertebrae were measured by enzyme-linked immunosorbent assay and verified by Western blot analysis. VEGF and its receptor (VEGFR) were localized by immunohistochemistry. Expression of VEGF mRNA was analyzed by real-time reverse-transcription polymerase chain reaction. Differently sulfated glycosaminoglycans were localized in subchondral bone histochemically. Osteoblasts were immunopositive for VEGF. VEGF concentration in the vertebra was 27% lower in OVX miniature pigs. VEGFR-2 could be immunostained on osteoblasts. VEGF mRNA and protein were detectable in the lumbar vertebrae of all animals. In subchondral trabecular bone of OVX animals, significantly more islands of mineralized cartilage containing chondroitin 4- and 6-sulfate or keratan sulfate occurred compared to the control group. The occurrence of remnants of mineralized cartilage in subchondral bone of the OVX group may be caused by a delayed bone turnover due to low VEGF levels. In vitro experiments revealed an increase of VEGF in the supernatant of osteoblasts after incubation with estradiol. In conclusion, estrogen seems to be a key factor for regulation of VEGF expression in bone. Loss of VEGF due to menopause may be a reason for reduction of bone density.

TLR-2-mediated induction of vascular endothelial growth factor (VEGF) in cartilage in septic joint disease.

Bacterial arthritis is a progressive joint disease which includes rapid destruction of articular cartilage even after clearance of the causal factor. The resulting post-infectious arthropathy is mainly characterized by self-perpetuating joint destruction and extensive angiogenesis in the emerging pannus-like synovial membrane, but the underlying molecular mechanisms of the bacteria-initiated process remain incompletely understood. This study was conducted to elucidate the expression and regulation of angiogenic and cartilage-destructive vascular endothelial growth factor (VEGF) in septic arthritis. For that purpose, aspirates of synovial fluid from patients with pyogenic arthritis were examined for VEGF levels by ELISA. In vitro studies with primary and immortalized chondrocytes were performed to determine whether Gram-positive and Gram-negative bacteria induce VEGF expression, by using real-time RT-PCR, ELISA, and immunohistochemistry. Activation of the transcription factor AP-1 was assessed by EMSA experiments. The necessity of the Toll-like receptor-2 (TLR-2), ERK-1/-2, and AP-1 pathway for infectious VEGF induction in chondrocytes was examined by using specific blocking reagents. ELISA experiments revealed that aspirates of synovial fluid from patients with pyogenic arthritis contain elevated levels of VEGF. The in vitro results confirmed the transcriptional induction of VEGF in chondrocytes after bacterial challenge by real-time RT-PCR, ELISA, and immunohistochemistry. This activation was mediated by a TLR-2-, ERK-1/-2-, and AP-1-dependent pathway. The findings demonstrate the expression of Toll-like receptors on mesenchymal articular chondrocytes and reveal TLR-2-mediated VEGF induction in human chondrocytes after Gram-positive bacterial sensing. Since VEGF is a potent angiogenic and tissue remodelling factor, evidence that Toll-like receptors contribute to destructive arthropathy after microbial joint infection is provided. VEGF may be a therapeutic target in the future for the prevention of post-infectious cartilage degradation in articular joints.

Expression and regulation of human beta-defensin-2 in osteoarthritic cartilage.

Defensins are antibiotic peptides that are involved in host defence at epithelial and mesenchymal surfaces. Previous studies have shown the induction of human beta-defensin-3 (HBD-3) in osteoarthritic joints, suggesting that these molecules have functions in addition to their ability to kill microbes. The aim of this study was to investigate the production of a further human beta-defensin, named HBD-2, in osteoarthritis (OA) and to determine its regulation by inflammatory cytokines. Healthy and osteoarthritic cartilage was assessed for HBD-2 expression by RT-PCR, immunohistochemistry, and ELISA. C28/I2 chondrocytes, primary chondrocytes, and cartilage explants were cultured for in vitro studies. After 24 h of stimulation with tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or IL-6, real-time RT-PCR and ELISA experiments were performed to evaluate the effect of these cytokines on the production of HBD-2. In contrast to healthy cartilage, HBD-2 expression was identified in most of the OA samples examined (eight of ten). Cytokines that are potentially involved in the pathogenesis of OA, namely TNF-alpha, IL-1, and IL-6, were transcriptional inducers of HBD-2 in cultured chondrocytes and cartilage explants in vitro, as measured by real-time RT-PCR and ELISA. These results illustrate the induction of HBD-2 in osteoarthritic cartilage and suggest that it is a further factor in the pathogenesis of OA. However, further studies are required to elucidate the role played by HBD-2 in osteoarthritic cartilage.