Tibial bone defect prediction based on preoperative artefact-reduced CT imaging is superior to standard radiograph assessment.

PURPOSE: The purpose of this study was to evaluate the accuracy of preoperative CT-based Anderson Orthopaedic Research Institute (AORI)-grading and to correlate Computed tomography (CT)-based volumetric defect measurements with intraoperative AORI findings. METHODS: 99 patients undergoing revision total knee arthroplasty (rTKA) with preoperative CT-images were identified in an institutional revision registry. CT-image segmentation with 3D-Slicer Software was used to create 3D tibial bone defects which were then graded according to the AORI-classification. The AORI classification categorizes tibial defects into three types: Type I has healthy cortical and cancellous bone near the joint line, Type II involves metaphyseal bone loss affecting one or both condyles, and Type III indicates deficient metaphyseal bone with distal defects and potential damage to the patellar tendon and collateral ligament attachments. These 3D-CT gradings were compared to preoperative X-ray and intraoperative AORI grading. The Friedman test was used to investigate differences between AORI values of each measurement method. Volumetric 3D-bone defect measurements were used to investigate the relationship between AORI classification and volumetric defect size in the three anatomic zones of the tibia. RESULTS: Substantial agreements between preoperative 3D-CT AORI and intraoperative AORI (kappa = 0.663; P < 0.01) and fair agreements between preoperative X-ray AORI and intraoperative AORI grading (kappa = 0.304; P < 0.01) were found. Moderate correlations between volume of remaining bone and intraoperative AORI grading were found in epiphysis (rS = - 0.529; P < 0.001), metaphysis (rS = - 0.557; P < 0.001) and diaphysis (rS = - 0.421; P < 0.001). Small volumetric differences between AORI I vs. AORI II defects and relatively large differences between AORI II and AORI III defects in each zone were detected. CONCLUSION: Tibial bone defect prediction based on preoperative 3D-CT segmentation showed a substantial agreement with intraoperative findings and is superior to standard radiograph assessment. The relatively small difference in defect volume between AORI I, IIa and IIb suggests that updated CT-based classifications might hold benefits for the planning of rTKA. LEVEL OF EVIDENCE: Retrospective Cohort Study; III.

Influence of implantation of a total hip endoprosthesis on the ipsilateral leg alignment: the effect of sex and dysplasia of the hip.

INTRODUCTION: Differences in leg and hip morphology exist between sexes and developmental hip dysplasia is known to alter proximal femoral morphology. The purpose of this study was to determine whether existing differences in leg alignment due to sex or developmental hip dysplasia have an effect on changes in leg alignment after total hip arthroplasty. MATERIALS AND METHODS: 30 hip osteoarthritis patients underwent biplanar full-length radiography in the standing position preoperatively and 3 months after total hip arthroplasty. Differences in leg alignment between men and women and between patients with primary hip osteoarthritis and patients with developmental dysplasia before and after surgery were tested using a general linear model for repeated measures. RESULTS: Implantation of a hip prosthesis had no differential effect on ipsilateral leg alignment in patients with hip osteoarthritis due to dysplasia and in patients with primary hip osteoarthritis. However, patients with hip osteoarthritis due to dysplasia had a 2.1° higher valgus both before and after surgery. After total hip arthroplasty, women had a significantly greater increase in varus angle (1.6° vs. 0°) and femoral offset (10.5 vs. 4.6 mm) compared with men. Because the change in acetabular offset was smaller (2.2 vs. 6.2 mm), the global femoral offset was only increased in women. Femoral torsion was constant for men (15.0° and 16.5°), whereas femoral torsion was significantly reduced in women (19.9° and 13.2°). CONCLUSIONS: Hip arthroplasty has a greater effect on leg axis in women than in men. The axial leg alignment of women could change from a natural valgus to a varus alignment. Therefore, surgeons should consider the effects of total hip arthroplasty on leg alignment in patients with hip osteoarthritis. Whether these changes in leg alignment are also clinically relevant and lead to premature medial or lateral knee osteoarthritis should be investigated in future work. TRIAL REGISTRATION: This study was registered with DRKS (German Clinical Trials Register) under the number DRKS00015053. Registered 1st of August 2018.

Correlation between Adrenoceptor Expression and Clinical Parameters in Degenerated Lumbar Intervertebral Discs.

Despite advanced knowledge of the cellular and biomechanical processes of intervertebral disc degeneration (IVDD), the trigger and underlying mechanisms remain unclear. Since the sympathetic nervous system (SNS) has been shown to exhibit catabolic effects in osteoarthritis pathogenesis, it is attractive to speculate that it also influences IVDD. Therefore, we explored the adrenoceptor (AR) expression profile in human IVDs and correlated it with clinical parameters of patients. IVD samples were collected from n = 43 patients undergoing lumbar spinal fusion surgery. AR gene expression was analyzed by semi-quantitative polymerase chain reaction. Clinical parameters as well as radiological Pfirrmann and Modic classification were collected and correlated with AR expression levels. In total human IVD homogenates α1A-, α1B-, α2A-, α2B-, α2C-, ß1- and ß2-AR genes were expressed. Expression of α1A- (r = 0.439), α2A- (r = 0.346) and ß2-AR (r = 0.409) showed a positive and significant correlation with Pfirrmann grade. α1A-AR expression was significantly decreased in IVD tissue of patients with adjacent segment disease (p = 0.041). The results of this study indicate that a relationship between IVDD and AR expression exists. Thus, the SNS and its neurotransmitters might play a role in IVDD pathogenesis. The knowledge of differential AR expression in different etiologies could contribute to the development of new therapeutic approaches for IVDD.

Generation of Matrix Degradation Products Using an In Vitro MMP Cleavage Assay.

Matrix metalloproteinases (MMPs) play crucial roles in tissue homeostasis and pathologies by remodeling the extracellular matrix. Previous studies have demonstrated the biological activities of MMP-derived cleavage products. Furthermore, specific fragments can serve as biomarkers. Therefore, an in vitro cleavage assay to identify substrates and characterize cleavage patterns could provide important insight in disease-relevant mechanisms and the identification of novel biomarkers. In the pathogenesis of osteoarthritis (OA), MMP-2, -8, -9 and -13 are of vital importance. However, it is unclear which protease can cleave which matrix component. To address this question, we established an in vitro cleavage assay using recombinantly expressed MMPs and the two cartilage matrix components, COMP and thrombospondin-4. We found a time- and concentration-dependent degradation and an MMP-specific cleavage pattern for both proteins. Cleavage products can now be enriched and purified to investigate their biological activity. To verify the in vivo relevance, we compared the in vitro cleavage patterns with serum and synovial fluid from OA patients and could indeed detect fragments of similar size in the human samples. The cleavage assay can be adapted to other MMPs and substrates, making it a valuable tool for many research fields.

[Scheuermann's disease]. / Morbus Scheuermann.

Scheuermann's disease represents the second most common deformity of the growing spine after the various forms of scoliosis. In cases of early diagnosis and mild kyphotic deformity conservative treatment with a brace and physiotherapy shows very good results; however, in cases of neurologic deficits, curve progression despite conservative treatment and increasing pain symptoms with a Stagnara angle of more than 70-75°, surgical treatment is meaningful. The surgical strategy can include posterior spondylodesis with prior anterior release or posterior instrumentation with posterior column osteotomy depending on the surgeon's experience. The choice of the extent of the operation with the vertebrae to be instrumented and including the straightening method should be oriented to the avoidance of complications, such as proximal or distal junctional kyphosis.

Total Hip Arthroplasty Revision Surgery: Impact of Morbidity on Perioperative Outcomes.

BACKGROUND: Primary and revision total hip arthroplasty (THA) is increasingly performed in patients with high comorbidity burden. Its predominantly negative effects on outcomes are well understood in primary THA; however, the effects of morbidity on revision THA are unknown. Since revision procedures account for about 10% of the total surgical volume, we set out to investigate the effects of physical health status on perioperative outcomes in this setting. METHODS: We queried our prospectively collected institutional database for patients who underwent revision THA at our institution (Orthopedic University Hospital Friedrichsheim, Frankfurt) between 2007 and 2011. Patients were classified according to American Society of Anesthesiologists (ASA) category and number of comorbidities. Subsequently, their impact on perioperative parameters was analyzed. RESULTS: Our database revealed 294 cases of revision THA during the study period. Patients preoperatively classified as ASA 3 and 4 showed significantly higher rates of intraoperative and postoperative complications, transfusions, prolonged intensive care unit (ICU) stay, and total length of stay (LOS) compared to patients classified as ASA 1 and 2. Similarly, patients with >3 comorbidities presented with significantly elevated postoperative complications, ICU stay, and LOS. Particularly, preoperative cardiac diseases were associated with increased blood loss, transfusions, duration of surgery, postoperative complications, ICU stay, LOS, and re-revisions. CONCLUSION: Poor physical health condition is associated with negative perioperative outcomes in revision THA. Especially cardiac comorbidities are linked to unfavorable outcomes, which have important implications for assessment of perioperative risk.

Accuracy of Preoperative Templating in Total Hip Arthroplasty With Special Focus on Stem Morphology: A Randomized Comparison Between Common Digital and Three-Dimensional Planning Using Biplanar Radiographs.

BACKGROUND: Accurate preoperative planning is a key component of successful total hip arthroplasty (THA). The purpose of the present study was to compare the accuracy and reliability of three-dimensional (hipEOS) and common digital two-dimensional (TraumaCad) templating with special focus on stem morphology. METHODS: 51 patients undergoing THA were randomized to two groups. Preoperative planning was performed on 23 patients with hipEOS (3D) and on 28 patients with TraumaCad (2D) planning software. Planning results were compared with the implanted component size. Inter- and intraobserver reliability as well as planning accuracy of both planning methods with special focus on straight and short stem design were recorded. RESULTS: Intraobserver reliability of both planning methods was good for component planning (ICC2,1: 0.835-0.967). Interobserver ICC2,1 for stem and cup planning were higher for 3D templating (3D ICC2,1: 0.906-0.918 vs. 2D ICC2,1: 0.835-0.843). Total stem and cup size predictions were within 2 sizes for 3D and within 3 sizes for 2D planning. Comparing short stem planning accuracy of both planning methods, absolute difference between implanted and planned component size was significantly lower in 3D planning (P = .029). There was no significant difference in straight stem (P = .935) and cup (P = .954) planning accuracy. CONCLUSION: Our findings suggest that 3D templating with hipEOS software has a good overall reliability and may have a better planning accuracy of short stem prostheses than digital templating with TraumaCad software. Assuming that the number of implanted short stem prostheses will further increase in coming years, a more precise planning with 3D technique can contribute to improve surgery outcome.

COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis.

Osteoarthritis (OA) is a slow-progressing joint disease, leading to the degradation and remodeling of the cartilage extracellular matrix (ECM). The usually quiescent chondrocytes become reactivated and accumulate in cell clusters, become hypertrophic, and intensively produce not only degrading enzymes, but also ECM proteins, like the cartilage oligomeric matrix protein (COMP) and thrombospondin-4 (TSP-4). To date, the functional roles of these newly synthesized proteins in articular cartilage are still elusive. Therefore, we analyzed the involvement of both proteins in OA specific processes in in vitro studies, using porcine chondrocytes, isolated from femoral condyles. The effect of COMP and TSP-4 on chondrocyte migration was investigated in transwell assays and their potential to modulate the chondrocyte phenotype, protein synthesis and matrix formation by immunofluorescence staining and immunoblot. Our results demonstrate that COMP could attract chondrocytes and may contribute to a repopulation of damaged cartilage areas, while TSP-4 did not affect this process. In contrast, both proteins similarly promoted the synthesis and matrix formation of collagen II, IX, XII and proteoglycans, but inhibited that of collagen I and X, resulting in a stabilized chondrocyte phenotype. These data suggest that COMP and TSP-4 activate mechanisms to protect and repair the ECM in articular cartilage.

Anti-Inflammatory Effects of Endogenously Released Adenosine in Synovial Cells of Osteoarthritis and Rheumatoid Arthritis Patients.

Exogenous adenosine and its metabolite inosine exert anti-inflammatory effects in synoviocytes of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. We analyzed whether these cells are able to synthesize adenosine/inosine and which adenosine receptors (ARs) contribute to anti-inflammatory effects. The functionality of synthesizing enzymes and ARs was tested using agonists/antagonists. Both OA and RA cells expressed CD39 (converts ATP to AMP), CD73 (converts AMP to adenosine), ADA (converts adenosine to inosine), ENT1/2 (adenosine transporters), all AR subtypes (A1, A2A, A2B and A3) and synthesized predominantly adenosine. The CD73 inhibitor AMPCP significantly increased IL-6 and decreased IL-10 in both cell types, while TNF only increased in RA cells. The ADA inhibitor DAA significantly reduced IL-6 and induced IL-10 in both OA and RA cells. The A2AAR agonist CGS 21680 significantly inhibited IL-6 and induced TNF and IL-10 only in RA, while the A2BAR agonist BAY 60-6583 had the same effect in both OA and RA. Taken together, OA and RA synoviocytes express the complete enzymatic machinery to synthesize adenosine/inosine; however, mainly adenosine is responsible for the anti- (IL-6 and IL-10) or pro-inflammatory (TNF) effects mediated by A2A- and A2BAR. Stimulating CD39/CD73 with simultaneous ADA blockage in addition to TNF inhibition might represent a promising therapeutic strategy.

[Axial deformities of the lower extremity in the frontal plane : From physiological development to pathological and possible long-term consequences]. / Achsdeformitäten der unteren Extremität in der Frontalebene : Von der physiologischen Entwicklung zum Pathologischen und zu möglichen Langzeitfolgen.

BACKGROUND: From birth to the end of growth, leg axes undergo physiological changes. Congenital, idiopathic or secondary deformities of the lower extremities are considered as a pre-arthrosis. A detailed clinical examination is of primary importance. On the basis of the established preventive examinations, predominantly asymptomatic deformities can be distinguished from age-typical physiological axis deviations at an early stage. THERAPY: There is a variety of conservative and surgical therapy options. In most cases, the spontaneous course of development can be waited for, depending on the deformity and the associated restrictions. It is important to recognize the right time for an intervention. Usually, surgical interventions are necessary, including guided growth by permanent and partial arrest of the growth plate or osteotomies. The aim is to restore the anatomical axial alignment and thus prevent the development of osteoarthritis. A missed intervention often leads to an early endoprosthetic replacement in adulthood.

[Dynamic analysis of joint loading due to leg axis deformity in the frontal plane : Relevance of instrumented gait analysis]. / Dynamische Analyse der Gelenkbelastung bei Beinachsendeformitäten in der Frontalebene : Stellenwert der instrumentellen Ganganalyse.

BACKGROUND: Instrumented 3D gait analysis (IGA) has been established for the functional evaluation of orthopedic diseases. It can provide valuable additional information beyond conventional static radiographic diagnostics and, thus, contributes to treatment decisions and a successful surgical outcome. Regarding the assessment of leg axis deformities IGA is currently only used in a few specialized centers. PRACTICE: This article describes the methods used by IGA and shows its benefit for the treatment of leg axis deformities of the knee in the frontal plane. In particular, the calculation of dynamic joint loads provides important insights regarding the development of degenerative joint deformities in the knee joint and, thus, complements the static assessment of the leg axis. A new treatment algorithm for guided growth intervention in children and adolescents by temporary epiphysiodesis is presented. IGA can be particularly useful for clinical decision-making in borderline cases. If there is a discrepancy between the static leg axis and dynamic knee joint loading, IGA can reveal potential compensatory mechanisms during walking.

[Prevalence and predictors of rebound deformity in the frontal plane : A literature review]. / Häufigkeit und Prädiktoren für einen Rebound nach operativer Achskorrektur in der Frontalebene : Eine Literaturübersicht.

The present literature review presents the current state of the art on the prevalence and causes of the rebound phenomenon after successful correction of leg axis deformity using temporary epiphysiodesis in children and adolescents. A total of 20 studies was included by three independent reviewers. The validity of most studies regarding the rebound incidence is limited by a non-standardized follow-up after plate removal, heterogeneous patient groups with a small number of cases, and missing information on the definition of rebound. The rebound incidence in studies without fundamental limitations in study design is on an average about 50% and underlines the clinical relevance of the topic. Only four studies reported reasons or risk factors for the occurrence of a rebound. In particular, a young age at the beginning of treatment with high residual growth potential after implant removal represents an increased rebound risk, which can be minimized by appropriate overcorrection of the leg axis.

[Nonfusion procedures in pediatric scoliosis]. / Nonfusionsverfahren bei kindlichen Skoliosen.

The treatment of early onset scoliosis (EOS) in children is a complex and demanding challenge in the treatment of spinal deformities. Conservative treatment with physiotherapy is indicated in mild forms with a Cobb angle from 10° and additionally a corset treatment with a Cobb angle of more than 20°. After exhaustion of the conservative measures or a progression of spinal scoliosis of 10° or deformities of more than 35°, a surgical approach should be considered in order to prevent respiratory insufficiency as well as severe postural and thoracic deformities. In situations where growth is still ongoing fusion operations can lead to stunted growth, a crankshaft phenomenon or degeneration of alignment. Meaningful alternatives to a fusion are so-called growing rods as a distraction-based nonfusion technique, e.g. traditional growing rods (TGR) and magnetically controlled growing rods (MCGR) or as a further method a vertical expandable prosthetic titanium rib (VEPTR) device. The advantages and disadvantages of each operative procedure must be considered with respect to the risk profile of each patient and the experience of the surgeon in order to guarantee the best possible treatment.

Implementation of an anaemia walk-in clinic: Feasibility and preliminary data from the Orthopedic University Hospital.

BACKGROUND: Approximately one in three patients suffers from preoperative anaemia. Even though haemoglobin is measured before surgery, anaemia management is not implemented in every hospital. OBJECTIVE: Here, we demonstrate the implementation of an anaemia walk-in clinic at an Orthopedic University Hospital. To improve the diagnosis of iron deficiency (ID), we examined whether reticulocyte haemoglobin (Ret-He) could be a useful additional parameter. MATERIAL AND METHODS: In August 2019, an anaemia walk-in clinic was established. Between September and December 2019, major orthopaedic surgical patients were screened for preoperative anaemia. The primary endpoint was the incidence of preoperative anaemia. Secondary endpoints included Ret-He level, red blood cell (RBC) transfusion rate, in-hospital length of stay and anaemia at hospital discharge. RESULTS: A total of 104 patients were screened for anaemia. Preoperative anaemia rate was 20.6%. Intravenous iron was supplemented in 23 patients. Transfusion of RBC units per patient (1.7 ± 1.2 vs. 0.2 ± 0.9; p = 0.004) and hospital length of stay (13.1 ± 4.8 days vs. 10.6 ± 5.1 days; p = 0.068) was increased in anaemic patients compared to non-anaemic patients. Ret-He values were significantly lower in patients with ID anaemia (33.3 pg [28.6-40.2 pg]) compared to patients with ID (35.3 pg [28.9-38.6 pg]; p = 0.015) or patients without anaemia (35.4 pg [30.2-39.4 pg]; p = 0.001). CONCLUSION: Preoperative anaemia is common in orthopaedic patients. Our results proved the feasibility of an anaemia walk-in clinic to manage preoperative anaemia. Furthermore, our analysis supports the use of Ret-He as an additional parameter for the diagnosis of ID in surgical patients.

Norepinephrine Inhibits the Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells via ß2-Adrenoceptor-Mediated ERK1/2 and PKA Phosphorylation.

Bone marrow-derived mesenchymal stem cells (BMSCs) represent an alternative to chondrocytes to support cartilage regeneration in osteoarthritis (OA). The sympathetic neurotransmitter norepinephrine (NE) has been shown to inhibit their chondrogenic potential; however, their proliferation capacity under NE influence has not been studied yet. Therefore, we used BMSCs obtained from trauma and OA donors and compared the expression of adrenergic receptors (AR). Then, BMSCs from both donor groups were treated with NE, as well as with combinations of NE and α1-, α2- or ß1/2-AR antagonists (doxazosin, yohimbine or propranolol). Activation of AR-coupled signaling was investigated by analyzing ERK1/2 and protein kinase A (PKA) phosphorylation. A similar but not identical subset of ARs was expressed in trauma (α2B-, α2C- and ß2-AR) and OA BMSCs (α2A-, α2B-, and ß2-AR). NE in high concentrations inhibited the proliferation of both trauma and OA BMCSs significantly. NE in low concentrations did not influence proliferation. ERK1/2 as well as PKA were activated after NE treatment in both BMSC types. These effects were abolished only by propranolol. Our results demonstrate that NE inhibits the proliferation and accordingly lowers the regenerative capacity of human BMSCs likely via ß2-AR-mediated ERK1/2 and PKA phosphorylation. Therefore, targeting ß2-AR-signaling might provide novel OA therapeutic options.

Adrenoceptor Expression during Intervertebral Disc Degeneration.

Healthy and degenerating intervertebral discs (IVDs) are innervated by sympathetic nerves, however, adrenoceptor (AR) expression and functionality have never been investigated systematically. Therefore, AR gene expression was analyzed in both tissue and isolated cells from degenerated human IVDs. Furthermore, human IVD samples and spine sections of wildtype mice (WT) and of a mouse line that develops spontaneous IVD degeneration (IVDD, in SM/J mice) were stained for ARs and extracellular matrix (ECM) components. In IVD homogenates and cells α1a-, α1b-, α2a-, α2b-, α2c-, ß1-, and ß2-AR genes were expressed. In human sections, ß2-AR was detectable, and its localization parallels with ECM alterations. Similarly, in IVDs of WT mice, only ß2-AR was expressed, and in IVDs of SM/J mice, ß2AR expression was stronger accompanied by increased collagen II, collagen XII, decorin as well as decreased cartilage oligomeric matrix protein expression. In addition, norepinephrine stimulation of isolated human IVD cells induced intracellular signaling via ERK1/2 and PKA. For the first time, the existence and functionality of ARs were demonstrated in IVD tissue samples, suggesting that the sympathicus might play a role in IVDD. Further studies will address relevant cellular mechanisms and thereby help to develop novel therapeutic options for IVDD.

Are changes in radiological leg alignment and femoral parameters after total hip replacement responsible for joint loading during gait?

BACKGROUND: Gait kinematics after total hip replacement only partly explain the differences in the joint moments in the frontal plane between hip osteoarthritis patients after hip replacement and healthy controls. The goal of this study was to determine if total hip replacement surgery affects radiological leg alignment (Hip-Knee-Shaft-Angle, femoral offset, Neck-Shaft-Angle and varus/valgus alignment) and which of these parameters can explain the joint moments, additionally to the gait kinematics. METHODS: 22 unilateral hip osteoarthritis patients who were scheduled for total hip replacement were included in the study. Preoperatively and 1 year postoperatively all patients had biplanar radiographic examinations and 3D gait analysis. RESULTS: The operated leg showed significantly (P < 0.05) more varus (1.1°) as well as a larger femoral offset (+ 8 mm) and a larger Hip-Knee-Shaft-Angle (+ 1.3°) after total hip replacement; however no significant differences in the joint moments in the frontal plane compared to healthy controls were found. The hip moment (first half of stance) and the knee moments (first and second half of stance) were mostly determined by the varus/valgus alignment (29% and respectively 36% and 35%). The combination with a kinematic parameter (knee range of motion, foot progression angle) increased the predictive value for the knee moments. CONCLUSION: In our patient group the joint moments after total hip replacement did not differ from healthy controls, whereas radiological leg alignment parameters changed significantly after the total hip replacement. A combination of these radiological leg parameters, especially the varus alignment, and the deviating kinematics explain the joint moments in the frontal plane during gait after total hip replacement surgery. For surgeons it is important not to create too much of a structural varus alignment by implanting the new hip joint as varus alignment can increase the knee adduction moment and the risk for osteoarthritis of the medial knee compartment. TRIAL REGISTRATION: This study was retrospectively registered with DRKS (German Clinical Trials Register) under the number DRKS00015053. Registered 1st of August 2018.

Influence of Hip Geometry Reconstruction on Frontal Plane Hip and Knee Joint Moments During Walking Following Primary Total Hip Replacement.

BACKGROUND: Following total hip replacement (THR), hip geometry reconstruction parameters such as the femoral offset (FO) correlate with hip stability and wear. The purpose of this study is to determine the relationship between hip geometry parameters and knee and hip joint loading during walking. METHODS: Forty-one patients were examined before and a minimum of 1 year after primary THR. Pearson correlation coefficient (r) was performed to identify relationships between radiographic parameters and gait data. In addition, we divided patients into 2 groups according to the restoration of the FO (within ±5 mm vs more than 5 mm increment). RESULTS: The FO and global offset (GO) showed a positive correlation with the first (r = 0.469, P = .002; r = 0.542, P < .001) and second (r = 0.365, P = .019; r = 0.484, P = .001) knee adduction moment (KAM). The neck-shaft angle revealed a negative correlation with the first hip adduction moment (r = -0.375, P = .047). The reconstruction of FO with an increment of more than 5 mm was associated with a significant higher first KAM (+16%, P = .045) compared to the restored group. CONCLUSION: Our findings suggest that abnormal hip and knee joint loading during walking after THR have a biomechanical background originating from hip geometry reconstruction. Patients with a high FO/GO were more likely to have an increased KAM during walking or vice versa. Surgeons need to be aware that an accurate control of FO, GO, and neck-shaft angle restoration in THR has an impact on hip and knee joint loading that may influence degenerative changes of the knee and higher wear of the artificial hip joint, respectively.

Role of Norepinephrine in IL-1ß-Induced Chondrocyte Dedifferentiation under Physioxia.

As part of the pathogenesis of osteoarthritis (OA), chondrocytes lose their phenotype and become hypertrophic, or dedifferentiate, mainly driven by interleukin-1ß (IL-1ß). The contribution of other factors to the dedifferentiation process is not completely understood. Recent studies suggested a dose-dependent role for the sympathetic neurotransmitter norepinephrine (NE) in OA chondrocyte metabolism. Therefore, the aim of this study was to analyze the contribution of NE (10-8 M, 10-6 M) to human articular OA chondrocyte dedifferentiation in the absence or presence of IL-1ß (0.5 ng/mL). Here, we demonstrate that OA chondrocytes express α2A-, α2C- and ß2-adrenoceptors (AR) and show the characteristic shift towards a fibroblast-like shape at day 7 in physioxic monolayer culture. NE alone did not affect morphology but, in combination with IL-1ß, markedly accelerated this shift. Moderate glycosaminoglycan (GAG) staining was observed in untreated and NE-treated cells, while IL-1ß strongly decreased GAG deposition. IL-1ß alone or in combination with NE decreased SOX9, type II collagen, COMP, and aggrecan, and induced MMP13 and ADAMTS4 gene expression, indicating an accelerated dedifferentiation. NE alone did not influence gene expression and did not modulate IL-1ß-mediated effects. In conclusion, these results indicate that low-grade inflammation exerts a dominant effect on chondrocyte dedifferentiation and should be targeted early in OA therapy.

The Expression of Thrombospondin-4 Correlates with Disease Severity in Osteoarthritic Knee Cartilage.

Osteoarthritis (OA) is a progressive joint disease characterized by a continuous degradation of the cartilage extracellular matrix (ECM). The expression of the extracellular glycoprotein thrombospondin-4 (TSP-4) is known to be increased in injured tissues and involved in matrix remodeling, but its role in articular cartilage and, in particular, in OA remains elusive. In the present study, we analyzed the expression and localization of TSP-4 in healthy and OA knee cartilage by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and immunoblot. We found that TSP-4 protein expression is increased in OA and that expression levels correlate with OA severity. TSP-4 was not regulated at the transcriptional level but we detected changes in the anchorage of TSP-4 in the altered ECM using sequential protein extraction. We were also able to detect pentameric and fragmented TSP-4 in the serum of both healthy controls and OA patients. Here, the total protein amount was not significantly different but we identified specific degradation products that were more abundant in sera of OA patients. Future studies will reveal if these fragments have the potential to serve as OA-specific biomarkers.