Andrea Meurer

Cell viability, osteoblast differentiation, and gene expression are altered in human osteoblasts from hypertrophic fracture non-unions

Recent studies have provided evidence that the number and proliferation capacity of bone marrow-derived mesenchymal stem cells, as well as the number of osteoprogenitor cells are reduced in patients with fracture non-unions. For fracture non-unions that do not heal after appropriate surgical intervention, the question arises as to what extent systemic cellular dysfunctions should be considered as being pathogenetic factors. For this purpose, we have examined the hypothesis that the cell function of osteoblasts isolated from patients with fracture non-unions may differ from those of normal control individuals in an identical and controlled in vitro situation. We analyzed the osteoblast cell viability, formation of alkaline phosphatase-positive (CFU-ALP) and mineralization-positive (CFU-M) colony forming units, as well as global differences of gene expression in osteoblasts from patients with fracture non-unions and from control individuals. We found that cell viability and CFU-M-formation were significantly reduced in non-union osteoblasts. This was accompanied by significant differences in osteoblast gene expression as revealed by Affymetrix-microarray analysis and RT-PCR. We identified a set of significantly down-regulated factors in non-union osteoblasts that are involved in regulation of osteoblast proliferation and differentiation processes (canonical Wnt-, IGF-, TGF-beta-, and FGF-signaling pathways). The results of the present study strongly support the hypothesis that cell viability, differentiation, and gene expression of osteoblasts may be altered in patients who develop recurrent and recalcitrant fracture non-unions. Proteins involved in Wnt-, IGF, TGF-beta-, and FGF-signaling pathways may be of particular interest and may unveil new potential therapies.

Unilateral hip osteoarthritis: The effect of compensation strategies and anatomic measurements on frontal plane joint loading†

In order to reduce pain caused by the affected hip joint, unilateral hip osteoarthritis patients (HOAP) adopt characteristic gait patterns. However, it is unknown if the knee and hip joint loading in the non‐affected (limbnon‐affected) and the affected (limbaffected) limb differ from healthy controls (HC) and which gait parameters correlate with potential abnormal joint loading. Instrumented 3D‐gait analysis was performed on 18 HOAP and 18 sex, age, and height matched HC. The limbnon‐affected showed greater first and second peak external hip adduction moments (first HAM: +15%, p = 0.014; second HAM: +15%, p = 0.021, respectively), than seen in HC. In contrast, the second peak external knee adduction moment (KAM) in the limbaffected is reduced by about 23% and 30% compared to the limbnon‐affected and HC, respectively. Furthermore, our patients showed characteristic gait compensation strategies including reduced peak vertical forces (pvF), a greater foot progression angle (FPA), and reduced knee range of motion (ROM) in the limbaffected. The limbaffected was 5.6 ± 3.8 mm shorter than the limbnon‐affected. Results of stepwise regression analyses showed that increased first pvF explain 16% of first HAM alterations, whereas knee ROM and FPA explain 39% of second KAM alterations. We therefore expect an increased rate of progression of OA in the hip joint of the limbnon‐affected and suggest that the shift in the medial‐to‐lateral knee joint load distribution may impact the rate of progression of OA in the limbaffected. The level of evidence is III.

Abnormal loading of the hip and knee joints in unilateral hip osteoarthritis persists two years after total hip replacement: JOINT LOADING AFTER HIP REPLACEMENT

A total hip replacement (THR) is a common and routine procedure to reduce pain and restore normal activity. Gait analysis can provide insights into functional characteristics and dynamic joint loading situation not identifiable by clinical examination or static radiographic measures. The present prospective longitudinal study tested whether 2 years after surgery a THR would restore dynamic loading of the knee and hip joints in the frontal plane to normal. Instrumented gait analysis was performed shortly before surgery and approximately 2 years after THR on 15 unilateral hip osteoarthritis (OA) patients. 15 asymptomatic matched individuals were recruited as healthy controls. Results showed that abnormal joint loading persisted 2 years after THR. The 2nd external knee adduction moment in terminal stance in the affected (−34%, p = 0.002, d = 1.22) and non‐affected limb (−25%, p = 0.035, d = 0.81) was lower compared to controls and thus indicated a shift in the knee joint load distribution from medial to lateral. A correlation analysis revealed that a smaller hip range of motion explained 46% of 2nd knee adduction moment alterations. In contrast, the 2nd external hip adduction moment in terminal stance was postoperatively higher in the affected (+22%, p = 0.007, d = 1.04) and non‐affected limb (+22%, p = 0.005, d = 1.05). Here, 51% of 2nd hip adduction moment alterations can be explained with a greater hip adduction angle. Patients with a THR may therefore be at higher risk for abnormal joint loading and thus for the development of OA in other joints of the lower extremities.

Effect of lumbar spinal fusion surgery on the association of self-report measures with objective measures of physical function

BACKGROUND Self-report measures are used to evaluate surgery outcome but are not necessarily indicative of actual disabilities. RESEARCH QUESTION The aim of the present study was to determine the association between self-report assessments of quality of life and objective measures of function in patients with symptomatic lumbar degenerative disease. Additionally, we evaluated the effect of lumbar spinal fusion surgery on this relationship. METHODS Before and 6 month after surgery 26 patients completed self-report questionnaires and assessments of 3D gait analysis and trunk range of motion (ROM) during standing. RESULTS Before surgery, questionnaires were not correlated with any of the gait parameters and with only 2 trunk ROM parameters. Six month after surgery, the questionnaires showed 12 significant correlations with gait parameters and 19 with trunk ROM parameters. A better Oswestry Disability Index (ODI) (r = 0.464, p = .026), EQ-5D (r = -0.440, p = .036), and EQ VAS (r = -0.472, p = .023) score were correlated with a reduced anterior thorax tilt during walking. Maximum forward flexion of the trunk during standing was correlated with a better EQ-5D (r = 0.684, p = .001) and ODI (r = -0.560, p = .008) score as well as with reduced pain scores. SIGNIFICANCE The lack of association between self-reported questionnaires and objective measures of function before surgery was likely due to psychological distress, correlating with emotional and cognitive function rather than true functional capacities. The influence of these psychological factors might be reduced after surgery due to a reduction of low back pain. To obtain an accurate assessment of impairment, there is a need to evaluate function by measuring objective physiologic parameters that are unsusceptible to voluntary or affective influences.

O 089 - Influence of the femoral offset on hip and knee joint loading following primary total hip replacement for unilateral osteoarthritis

Abnormal loading in the knee and hip joints persist 2 years after total hip replacement (THR) [1], which may result in an increased wear of the artificial hip joint as well as an increased progression of osteoarthritis (OA) in other lower extremity joints. The femoral offset (FO) is one of the important perioperative parameters in THR. The question arises whether FO has an effect on dynamic joint loading and thus can explain gait abnormalities.

Using the Oxford Foot Model to determine the association between objective measures of foot function and results of the AOFAS Ankle-Hindfoot Scale and the Foot Function Index: a prospective gait analysis study in Germany

Objective After cross-cultural adaption for the German translation of the Ankle-Hindfoot Scale of the American Orthopaedic Foot and Ankle Society (AOFAS-AHS) and agreement analysis with the Foot Function Index (FFI-D), the following gait analysis study using the Oxford Foot Model (OFM) was carried out to show which of the two scores better correlates with objective gait dysfunction. Design and participants Results of the AOFAS-AHS and FFI-D, as well as data from three-dimensional gait analysis were collected from 20 patients with mild to severe ankle and hindfoot pathologies. Kinematic and kinetic gait data were correlated with the results of the total AOFAS scale and FFI-D as well as the results of those items representing hindfoot function in the AOFAS-AHS assessment. With respect to the foot disorders in our patients (osteoarthritis and prearthritic conditions), we correlated the total range of motion (ROM) in the ankle and subtalar joints as identified by the OFM with values identified during clinical examination ‘translated’ into score values. Furthermore, reduced walking speed, reduced step length and reduced maximum ankle power generation during push-off were taken into account and correlated to gait abnormalities described in the scores. An analysis of correlations with CIs between the FFI-D and the AOFAS-AHS items and the gait parameters was performed by means of the Jonckheere-Terpstra test; furthermore, exploratory factor analysis was applied to identify common information structures and thereby redundancy in the FFI-D and the AOFAS-AHS items. Results Objective findings for hindfoot disorders, namely a reduced ROM, in the ankle and subtalar joints, respectively, as well as reduced ankle power generation during push-off, showed a better correlation with the AOFAS-AHS total score—as well as AOFAS-AHS items representing ROM in the ankle, subtalar joints and gait function—compared with the FFI-D score. Factor analysis, however, could not identify FFI-D items consistently related to these three indicator parameters (pain, disability and function) found in the AOFAS-AHS. Furthermore, factor analysis did not support stratification of the FFI-D into two subscales. Conclusions The AOFAS-AHS showed a good agreement with objective gait parameters and is therefore better suited to evaluate disability and functional limitations of patients suffering from foot and ankle pathologies compared with the FFI-D.

Congenital Bone Disorders

The term congenital bone disorder describes alterations in typical combination that present themselves at one or multiple parts of the skeletal system. Osteogenesis imperfecta (OI) is a genetic heterogeneous group of bone disorders. In case of diaphyseal fractures, telescopic rods are fixed in the proximal and distal epiphyses of the long bones. The design allows that the rods grow with the bone. These rods dramatically reduced the number of operations needed for one child. But complications like the cutting out of the nail or bowing of the bone around the nail can occur in any method of treatment due to the nature of the disease. Fibrous dysplasia is a non-hereditary, benign tumorous bone disorder, in which normal bone is displaced by fibrous bone. Surgical approaches include removing the affected intraosseous lesion and filling this cavity with autologous or allogenic bone material. Depending on the extent of the fibrous dysplasia, one also has to consider stabilizing the bone by intramedullary rods. Hypophosphatasie is a rare autosomal recessive disease, which presents mainly in a hypomineralization of the bone and the teeth. Intramedullary rodding can be performed once there are symptomatic fractures. The entry portal of the femur is situated at the tip of the greater trochanter. For the tibia, the entry portal is situated at the tibia tuberosity. The entry point should be exactly in the center of the medullary canal in the anteroposterior view. For the humerus, the ideal entry point is situated medial to the greater tuberosity, which is lateral to the axis of the medullary canal in the anteroposterior view and in line with the axis in the lateral view. Rod migration and telescoping are the two most frequent complications.

Anatomische und physiologische Grundlagen der Elektromyographie

Zum grundsatzlichen Verstandnis der Entstehung eines Elektromyogramms und zur Ablichatzung der Moglichkeiten und Grenzen der aus ihm gewinnbaren Information sind einige Grundkenntnisse der Muskelphysiologie erforderlich, die im Folgenden zusammenfassend dargestellt werden.

Kompensationsmechanismen und Veränderungen im Muskelaktivitätsbild beim Gang mit simulierter Beinlängendifferenz

Eine Beinlangendifferenz ist eine in der tagliehen klinisehen Routine haufig beobaehtete Erseheinung. Ungefahr 80% aller Mensehen haben, oft unbemerkt, in den unteren Extremitaten eine Langendifferenz von bis zu 1 cm. Zahlreiche Sekundarerkrankungen werden als Folge hiervon besehrieben, z. B. Spondylarthrosen, Coxa saltans sowie Coxarthrosen. Eine mogliche Beteiligung an der Genese einer Lumbalskoliose ist bis heute nicht endgultig ausgesehIossen [61]. Insbesondere weisen aueh Patienten mit einer Coxarthrose aufgrund zerstorter Gelenkstrukturen eine Beinlangendifferenz auf. Bei der Gelenkersatzoperation gelingt der Ausgleich aus operationsteehnisehen Grunden nieht immer vollstandig, sodass eine kleinere Beinlangendifferenz aueh bei postoperativen Coxarthrosepatienten ein haufiger Befund ist. Neben den biomeehanisehen Auswirkungen einer Beinlangendifferenz auf die Korperstatik beim aufreehten Stand sind insbesondere aueh Auswirkungen auf die Dynamik der Gehbewegung mit entspreehenden Veranderungen im Aktivitatsverlauf der beteiligten Muskeln zu erwarten. Aus der Kenntnis solcher Veranderungen konnen Rucksehlusse auf veranderte Belastungsverhaltnisse im Muskuloskelettalsystem gezogen werden.

Die Muskelfunktion im Gang gesunder Probanden verschiedener Altersklassen

Die menschliche Gehbewegung war in der Vergangenheit der Gegenstand einer Vielzahl von theoretischen und experimentellen Untersuchungen. Von seiner grundsatzlichen physikalischen Charakteristik ist der Gang die Bewegung eines mechanischen Systems, des menschlichen Korpers, aufgrund einer koordiniert wirkenden Vielfalt von korperinneren und auf den Korper von ausen einwirkenden Kraften. Eine vollstandige, geschlossene Beschreibung dieses Phanomens in allen seinen physikalischen und biologischen Aspekten ist wegen der Komplexitat des menschlichen Bewegungsapparates praktisch nicht moglich. Je nach Ausgangspunkt der jeweiligen Fragestellung konnen deshalb jeweils nur einzelne, ausgewahlte Aspekte des Ganges untersucht und dargestellt werden.