[What can we learn in future from the data of the German Arthroplasty Registry (EPRD) in comparison to other registries?]. / Welcher Zusatznutzen ergibt sich in Zukunft aus den Daten des EPRD im Vergleich zu anderen Registern?

The German Arthroplasty Registry (EPRD) was founded in 2010 and has been in full operation since 2014. Previous attempts at a systematic data collection of elective and non-elective knee and hip replacement in Germany failed mainly because of the long-term lack of funding. The EPRD is an interdisciplinary collaborative partnership between the German Association of Orthopedics and Orthopedic Surgery (DGOOC), all implant manufacturers of the German Medical Technology Association (BVMed), health insurers (AOK and the Association of Additional Healthcare Insurance) and hospitals (German Hospital Federation). As part of this cooperation a worldwide unique implant database has been set up, which includes all relevant components and a detailed description of implant specifications. This implant library enables a detailed evaluation of implant survival, revision rates and possible inferior implant performance of knee and hip replacements in Germany. At the end of 2015 the EPRD encompassed over 200,000 registered operations. Due to the high number of hip and knee arthroplasties in Germany with many different implants from different manufacturers there will be a rapid growth of data that are available for a national and also international comparison of the results.

[Early detection of systematic defects by endoprostheses registries]. / Frühzeitige Detektion systematischer Schadensfälle durch Endoprothesenregister.

BACKGROUND: The burden of revision of the 210,000 total hip and the 146,000 total knee arthroplasties performed in Germany every year is 10.9% and 7.9%, respectively. Since the probability of revisions could be cut in half by the implementation of a national joint registry in Sweden, several other countries have also established national joint registries. Nevertheless, these registries were not able to detect the failure of some implant systems, which resulted in thousands of patients who had received implants being recalled later on. OBJECTIVES: We aimed to identify the methods that are currently used for statistical analyses in joint registries and which could be used to implement an early warning system. MATERIALS AND METHODS: We analyzed the available reports of national joint registries regarding the methods used for the early detection of implants that perform less efficiently than expected. The methods identified are described and evaluated if they are suitable for being used in a national joint registry. RESULTS: While most of the identified national joint registries use the Kaplan-Meier method for analyzing implant survival, there was little agreement regarding the methods used for the early detection of implants that perform less efficiently than expected. Methods identified included revision rate per 100 component years, variants of statistical process control (SPC), cumulative sums (CUSUM) and funnel plots. CONCLUSION: Currently, there are no standardized methods for the early detection of inferior implants that are used by the established national joint registries. Most of the statistical methods that could be identified were either not used at all or only in a very limited number of registries. The value of these methods still needs to be established. It appears probable that the statistical methods for early detection have to be developed further in order to identify a possible inferior performance of implants at an earlier point in time. This is necessary in order to avoid that thousands of patients are again treated with implants which are associated with an increased revision rate.

Pigmented villo-nodular synovitis and giant-cell tumor of tendon sheaths: a binational retrospective study.

AIM: Pigmented villonodular synovitis is rare. Thus, we initiated a retrospective multi-center study regarding symptoms, location, type of disease, type of surgery, number of recurrences, use of adjuvant therapies and functional outcome. RESULTS: Ten centers contributed. Data from 173 patients were sampled. The disease was seen predominantly in joints, less frequently in tendon sheaths and bursae. Patients with articular lesions suffered mainly from the diffuse type. In tendon sheaths, the relation "diffuse versus nodular" was nearly 50 % each, in bursae most often the nodular type was found. Anatomically, mostly the knee was affected. Institutions with more than 20 patients had a lower rate of recurrence than those with less than 20 cases. Regarding the knee, there were less recurrences in joints treated with open synovectomy than in those treated arthroscopically. CONCLUSIONS: Since the rate of recurrence has been rather high, the use of adjuvant treatments (radiosynoviorthesis or radiotherapy) is recommended. In our study, the rate of their application was quite low. Patients who received an adjuvant therapy after primary surgery did not show any recurrence. In 14 % of patients in whom an adjuvant therapy had been used, after at least one recurrence, further recurrences were observed. Functional results were excellent in 84 % of patients. LEVEL OF EVIDENCE: Prognostic multi-center study, Level III.

[Synovialitis of the arthrofibrotic type: criteria of a new synovialitis type for the diagnosis of arthrofibrosis]. / Synovialitis vom arthrofibrotischen Typ: Kriterien eines neuen Synovialitis-Typus für die Diagnose der Arthrofibrose.

After rheumatologic conservative medical therapy has been exhausted in degenerative and inflammatory joint diseases, arthroplastic operations are an important option to restore quality of life. Endoprosthesis-associated arthrofibrosis is a severe fibrosing disease of the synovial membrane after endoprosthetic operations. Neither the morphological substrate nor histopathological criteria have been described. The aim was to describe the histopathological substrate of arthrofibrosis and to define histological and immunohistochemical criteria of arthrofibrosis on the basis of tissue samples derived from revision. In histopathological analyses arthrofibrosis revealed a synovialitis with varying fibrosis, without detectable ossification and without minimal wear particle reaction (so-called synovialitis of arthrofibrotic type, SAT). A 3-stage grading was determined based on the cellular density of the fibrous tissue (fibroblast cellularity). In 191 cases with SAT, grade 1 was found in 24.1 % (n = 46), grade 2 was found in 51.8 % (n = 99) and grade 3 was found in 24.1 % (n = 46). The control group consisted of 29 cases with synovialitis of indifferent type (type IV membrane). If SAT grades 2 and 3 are summed together, i.e. the distance between the fibroblasts was less than two cell lengths, the difference of the fibroblast cellularity compared with the type IV membrane was significant (p < 0.001). Above SAT grade 2 the diagnosis of arthrofibrosis could be made with a sensitivity 0.7592 and specificity 0.8276. The SM-alpha-actin cytoplasmic positivity of fibroblasts indicates a myofibroblast phenotype and the ß-catenin positivity suggests a resemblance to fibromatosis or a keloid-like process. In the quantitative evaluation of the ß-catenin positive fibroblasts, there was a significant difference (p < 0.001) between type IV membrane and SAT. A threshold value of 20 beta-catenin positive cells per microscopic high power field (HPF) was determined, which represents in conjunction with the clinical information a new histopathological diagnosis component (sensitivity 0.720, specificity 0.867).

[Revised consensus classification. Histopathological classification of diseases associated with joint endoprostheses]. / Erweiterte Konsensusklassifikation. Histopathologische Klassifikation von Gelenkendoprothesen-assoziierten Erkrankungen.

The revised classification of the periprosthetic membrane (synovial-like interface membrane SLIM) encompasses all pathological alterations which can occur as a result of endoprosthetic replacement of major joints and lead to a reduction in durability of prostheses. This also includes the established consensus classification of SLIM by which aseptic and septic prosthetic loosening can be subdivided into four histological types and histopathological criteria for additional pathologies: endoprosthesis-associated arthrofibrosis, immunological/allergic alterations and osseous pathologies. This revision represents the foundation for the histopathological diagnostics of the total spectrum of diseases associated with joint prostheses, is a suitable basis for a standardized diagnostic procedure and etiological clarification of endoprosthesis failure and also as a data standard for endprosthesis registers, in particular for registers based on routine data (e.g. German endoprosthesis register).

Tumor risk by tissue engineering: cartilaginous differentiation of mesenchymal stem cells reduces tumor growth.

OBJECTIVE: Implantation of autologous chondrocytes (AC) is a promising option for the treatment of cartilage defects, but problems with cell harvesting, dedifferentiation, or the donor age limit the clinical outcome. Mesenchymal stem cells (MSC) gain much interest because of their simple isolation and multipotential differentiation capacity along with their immunosuppressive properties. The latter might introduce tumor manifestation. The influence of undifferentiated and chondrogenically differentiated MSC or AC on tumor growth and metastasis formation was investigated in a murine melanoma model. METHODS: Allogeneic melanoma cells and either syngeneic MSC (C3H10T1/2, transduced with enhanced green fluorescent protein gene) or AC were co-injected at a distance of 3 cm into the contra lateral groins of five mice/group, and evaluated macroscopically and histologically after 4 weeks. RESULTS: Undifferentiated MSC migrated to the tumor site and induced strong tumor growth and metastasis formation. Even avital MSC promoted tumor growth and spreading, but insignificantly without detectable MSC at the tumor site. Chondrogenically differentiated MSC did not migrate and had a significantly lower impact on tumor growth and spreading; AC had no measurable influence on melanoma cells. CONCLUSIONS: Our data suggest that differentiation of MSC reduces MSC-dependent promotion of latent tumors and that native AC do not introduce any increased risk of tumor growth. The question of how far MSC should be differentiated prior to clinical application should be addressed in further studies.

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.

Ibandronate treatment reverses glucocorticoid-induced loss of bone mineral density and strength in minipigs.

The Göttingen minipig is one of the few large animal models that show glucocorticoid (GC)-induced bone loss. We investigated whether GC-induced loss of bone mineral density (BMD) and bone strength in minipigs can be recovered by treatment with the bisphosphonate ibandronate (IBN). 40 primiparous sows were allocated to 4 groups when they were 30 months old: GC treatment for 8 months (GC8), for 15 months (GC15), GC treatment for 15 months plus IBN treatment for months 8-15 (GC&IBN), and a control group without GC treatment. Prednisolone was given at a daily oral dose of 1 mg/kg body weight for 8 weeks and thereafter 0.5 mg/kg body weight. IBN was administered intramuscularly and intermittently with an integral dose of 2.0 mg/kg body weight. BMD of the lumbar spine (L1-3) was assessed in vivo by Quantitative Computed Tomography (QCT) at months 0, 8, and 15. Blood and urine samples were obtained every 2-3 months. After sacrificing the animals lumbar vertebrae L4 were tested mechanically (Young's modulus and ultimate stress). Histomorphometry was performed on L2 and mineral content determined in ashed specimens of T12 and L4. In the GC&IBN group, the GC associated losses in BMD of -10.5%+/-1.9% (mean+/-standard error of the mean, p<0.001) during the first 8 months were more than recovered during the following 7 months of IBN treatment (+14.8%+/-1.2%, p<0.0001). This increase was significantly larger (p<0.0001) than the insignificant +2.1%+/-1.2% change in group GC15. At month 15, the difference between groups GC&IBN and GC15 was 22% (p<0.01) for BMD, 48% (p<0.05) for Young's modulus, and 31% (p<0.14) for ultimate stress; bone-specific alkaline phosphatase showed trends to lower values (p<0.2) while deoxypyridinoline was comparable. This minipig study demonstrates that GC-induced impairment of bone strength can be effectively and consistently treated by IBN. GC&IBN associated alterations in BMD and bone turnover markers can be monitored in vivo using QCT of the spine and by biochemical analyses, reflecting the changes in bone strength.

Comparing ultrasound measurements of neonatal hips using the methods of Graf and Terjesen.

In a prospective study, 232 neonates were examined sonographically using the methods of Graf and Terjesen. In order to determine the reproducibility of the methods, 50 hips were evaluated by two skilled examiners. In an inter-observer study, five physicians and five medical students evaluated 24 images, which were evaluated on ten occasions at two-weekly intervals by one of the authors. Statistical evaluation used the Bland-Altman approach. The neonates (110 females, 122 males) were less than four days old. The mean alpha angle was 62.4 degrees and mean femoral head cover was 55.4%. According to Graf's method, 1.3% of hips were pathological, compared with 4.1% according to Terjesen. Spearman's correlation coefficient between femoral head cover and alpha angles was 0.552. The Bland-Altman approach shows greater variation for femoral head cover than for alpha, if measured by experienced examiners. The Bland-Altman approach shows almost equal reproducibility for alpha and femoral head cover in the inter-observer test, but better repeatability for alpha in the intra-observer test. The Graf results relate better than Terjesen's to the well-known frequency of 1% to 2% hip dysplasia in the European population. Kappa statistics indicate a fair agreement between the two methods. Inter-observer evaluation shows an equal reproducibility of both methods, whereas intra-observer tests reveal better repeatability with Graf's method.

Combination of reduced oxygen tension and intermittent hydrostatic pressure: a useful tool in articular cartilage tissue engineering.

Cartilage cells are normally studied under atmospheric pressure conditions and without loading. However, since cartilage exists in a condition of reduced oxygen and intermittent hydrostatic pressure we hypothesized lower partial oxygen pressures (PO2) and different intermittent hydrostatic pressures (IHP) would increase articular chondrocyte proliferation and matrix production and to stabilize chondrocyte phenotype in vitro. Monolayers of adult bovine articular chondrocytes were cultured under 5% or 21% PO2 in combination with IHP (0.2 MPa amplitude, frequencies 5/5s = 0.1 Hz, 30/2 or 2/30 min on/off loading). We measured proliferation (3H-thymidine incorporation) and collagen secretion (protein-binding assay, collagen type II-ELISA and immunocytochemical staining of pericellular collagen types I, II and IX). Reduced PO2 stimulated proliferation and collagen type II and IX secretion of chondrocytes in comparison to 21% PO2. Additionally, collagen type I expression was delayed by low PO2, indicating a stabilization of the cell phenotype. IHP 5/5s and 30/2 min inhibited proliferation but increased collagen secretion (pericellular collagen type IX was decreased). IHP 30/2 min delayed first expression of collagen type I. In contrast, IHP 2/30 min increased proliferation, but lowered collagen expression. All stimulating or inhibiting effects of PO2 and IHP were additive and vice versa. Reduced PO2 and different settings of IHP increased proliferation, collagen secretion, and phenotype stability of chondrocytes. The oxygen- and IHP-induced effects were additive, suggesting that a combination of these parameters might be a useful tool in cartilage tissue engineering.

Evaluation of water content by spatially resolved transverse relaxation times of human articular cartilage.

Non-invasive assessment of cartilage properties, specifically water content, could prove helpful in the diagnosis of early degenerative joint diseases. Transverse relaxation times T(2) of human articular cartilage (34 cartilage slices of three donors) were measured on a pixel-by-pixel basis in a clinical whole body MR system in vitro. In vivo feasibility to measure quantitative T(2) maps was shown for human patellar cartilage. The relaxation times of cartilage with collagen in the radial zone oriented perpendicular to the magnetic field increased from approximately 10 ms near the bone to approximately 60 ms near the articular surface. Cartilage water content of the tibial plateau and femoral condyles could be determined from the correlation with T(2) (R(2) = 0.71) with an error of approximately 2 wt.%. In vivo, directional variation would need to be considered. If confirmed in vivo, T(2) measurements could potentially serve as a non-invasive tool for the evaluation of the status and distribution of water content in articular cartilage.

[The femoropatellar gliding motion during active knee stretching. Imaging using motion-triggered MR tomography]. / Die femoropatellare Gleitbewegung während aktiver Kniestreckung. Darstellung mit bewegungsgetriggerter MR-Tomographie.

By means of motion-triggered MRT it has been possible for the first time to demonstrate movements in the patello-femoral joint by means of MRT. Patello-femoral movement was studied during active extension of the knee between 30 degrees flexion and complete extension. The knees of 5 normal females and 7 normal males were studied together with 2 women with recurrent lateral patellar luxation. In normal women there was an average 16 degrees (10 to 18 degrees), in men an average of 12 degrees (10 to 14 degrees) of lateralisation of the patella during complete extension of the knee. In 1 patient there was 10 degrees medial displacement of the patella before extension. In 2 knees with recurrent lateral subluxation there was a 20 and 24 degrees displacement of the patella.

[MR arthrography of the labrum acetabulare--a radiological-anatomical correlation in 20 cadaveric hips]. / MR-Arthrographie des Labrum acetabulare--radiologisch-anatomische Korrelation an 20 Leichenhüften.

PURPOSE: To investigate frequency of acetabular labral lesions in elderly hip joints, and to determine sensitivity and specificity of MR arthrography (MRa) for the detection of these abnormalities. MATERIALS AND METHODS: Twenty cadaveric hip joints were examined by MRa. For MRa, 15 ml of a solution of iodinated contrast solution (Solutrast 300) and Gd-DTPA (100:1) were injected under fluoroscopic guidance. MR imaging was performed on a 1.5 T MR scanner (Vision, Siemens; FOV 16 cm, matrix 256 x 256, fat-suppressed 3D-FLASH). Multiplanar image reconstructions were done perpendicular to the acetabulum in the oblique-coronal, oblique-axial, and radial planes. The labral specimens were examined macroscopically. RESULTS: In 12/20 hips (60%), a labral lesion was found on pathologic examination. In 7 specimens, the labrum was partially or completely detached in the weight-bearing superior region. One flap-like variant of the labrum was seen; in 4 hip joints, the labrum was degenerated (one cystic degeneration). Pathologic findings were confirmed by MRa in 8/12 specimens (sensitivity 67%). All degenerated labra were correctly diagnosed on MRa. Three small labral detachments and the flap-like variant were misinterpreted as being normal. There were no false positive findings (specificity 100%). The accuracy was 80%. Labral lesions were seen in 6/8 and in 6/12 of hips with and without osteoarthritis, respectively. CONCLUSION: MRa is well suited to delineate the acetabular labrum and to diagnose labral abnormalities. Detection of small labral detachments and anatomic variants is difficult and requires some experience. Labral lesions are correlated to osteoarthritis of the hip, but may be frequently seen in the elderly without underlying osteoarthritis.

Magnetic resonance arthrography of the acetabular labrum. Macroscopic and histological correlation in 20 cadavers.

We studied the sensitivity and specificity of magnetic resonance arthrography (MRa) for the diagnosis of lesions of the acetabular labrum in 20 cadaver hips. The MRa results were compared with macroscopic and histological findings. We found that the labrum could be satisfactorily delineated by MRa and that large detachments could be identified satisfactorily. The diagnosis of small detachments and degeneration of the labrum was less reliable.

Survival analysis of hips treated with flexion osteotomy for femoral head necrosis.

The treatment of osteonecrosis of the femoral head (FHN) is controversial. It mainly occurs in young patients in whom total hip replacement is best avoided because of an increased risk of revision. The objective of this long-term follow-up study was to evaluate the outcome of intertrochanteric flexion osteotomy as a hip joint preserving operation for FHN. Over a 19-year period we carried out 70 intertrochanteric flexion osteotomies for FHN in 64 patients. The mean follow-up was 10.4 years (3.0 to 20.3). The overall mean Harris hip score increased from 51 points preoperatively to 71 points postoperatively. Six patients (9%) developed early postoperative complications. A total of 19 hips (27%) underwent total hip arthroplasty at a mean of 8.7 years after osteotomy. The five-year survival rate was 90%. Survival rates of hips in Ficat stage 2 were higher than those in stages 3 or 4. Hips with a preoperative necrotic angle of <200 degrees had a better survival probability than those with a necrotic angle >200 degrees. Our findings suggest that flexion osteotomy is a safe and effective procedure in Ficat stage 2 and 3 FHN, preferably with a necrotic angle of <200 degrees.

Little league shoulder syndrome in an adolescent cricket player.

The first case of little league shoulder syndrome in a cricket player is reported. The condition has been reported in baseball pitchers and is characterised by a proximal humeral epiphyseolysis.

Immunohistochemical detection of estrogen receptor alpha in articular chondrocytes from cows, pigs and humans: in situ and in vitro results.

Clinical observations suggest that estrogens are involved in the pathogenesis of postmenopausal osteoarthritis, but only little is known about the influence of these hormones on articular cartilage cells. The effect of estradiol is mediated by estrogen receptors alpha and beta. The goal of the present study was to search for estrogen receptor alpha in articular tissue from cows, pigs and humans by immunohistochemistry to form a basis for in vitro studies. In addition, we also tried to detect estrogen receptor alpha in cultivated articular chondrocytes from cows and bulls under certain culture conditions. Estrogen receptor alpha is detected by the use of antibody 13H2 in articular chondrocytes from cows, bulls, pigs and humans. Chondrocytes are physiologically exposed to reduced oxygen tension. In isolated articular chondrocytes from cows and bulls incubated either with 21% O2 or with 5% O2 positive cells were also found. These positive results therefore encourage testing the influence of estradiol on cultivated articular cartilage cells in these species under different culture conditions.

The arterial supply of the lesser metatarsal heads: a vascular injection study in human cadavers.

The possibility of avascular changes of the metatarsal heads following forefoot surgery has been previously documented. The aim of this study was to investigate the arterial supply of the lesser metatarsal heads with regard to osteotomies of these bones. We used epoxy resin injections and a modified Spalteholz technique in human cadaveric specimens to demonstrate the intraosseous and extraosseous blood supply of the lesser metatarsals. The metatarsal heads had two arterial sources: 1. The dorsal metatarsal arteries, which arose from the dorsalis pedis artery, and 2. The plantar metatarsal arteries, which are branches of the posterior tibial artery. These two vessels typically anastomosed at two sites about the metatarsal heads, forming a vascular ring and provided an extensive extraosseous arterial network around the metatarsal heads. Small arterial branches of this network run distally on the metatarsal cortex to enter the bone of the metatarsal head. The nutrient arteries traversed the cortex of the metaphysis close to the capsular and ligamentous insertions to provide multiple branches for the supply of the subchondral bone. Extensive capsular stripping during metatarsal head osteotomies results in damage to the medial and lateral head vessels.