Search tips
Search criteria

Results 1-23 (23)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Subchondral bone influences chondrogenic differentiation and collagen production of human bone marrow-derived mesenchymal stem cells and articular chondrocytes 
Osteoarthritis (OA) is characterized by an imbalance in cartilage and underlying subchondral bone homeostasis. We hypothesized that signals from the subchondral bone may modulate production of matrix components, alter chondrogenic differentiation potential of cocultured bone marrow-derived mesenchymal stem cells (BMSC) and induce a phenotypic shift in differentiated OA chondrocytes.
We established a novel coculture model between BMSC, mixed cultures (BMSC and chondrocytes) and chondrocytes embedded in fibrin gel with OA and normal subchondral bone explants (OAB and NB). Tissues and cells were either derived from OA or trauma patients. In addition, we used adipose-derived stem cells (ASC) from liposuction. With gene expression analysis, biochemical assays, immunofluorescence and biomechanical tests we characterized the properties of newly generated extracellular matrix (ECM) from chondrocytes and chondrogenically differentiating BMSC cocultured with OAB or NB in comparison with monocultures (cultures without bone explants).
Overall, gene expression of collagens of OAB and NB cocultured cells was reduced compared to monocultures. Concomitantly, we observed significantly lower collagen I, II and III and glycosaminoglycan (GAG) production in OAB cocultured cell lysates. In parallel, we detected increased concentrations of soluble GAGs and basic fibroblast growth factor (bFGF), interleukin (IL)-6 and IL-8 in supernatants of OAB and NB cocultures mainly at early time points. IL-1ß concentration was increased in supernatants of OAB cocultures, but not in NB cocultures. Cell-free NB or OAB explants released different amounts of IL-1ß, bFGF and soluble GAG into cell culture supernatants. In comparison to cocultures, monocultures exhibited higher Young’s modulus and equilibrium modulus. Stimulation of monocultures with IL-1ß led to a downregulation of aggrecan (ACAN) gene expression and in general to induced matrix metalloprotease (MMP)2, MMP3 and MMP-13 gene expression while IL-6 and IL-8 stimulation partly reduced ACAN, MMP3 and MMP-13 gene expression.
Our results suggest an alteration of molecular composition and mechanical properties of the newly formed ECM in subchondral bone cocultures. We suggest that soluble factors, that is interleukins and bFGF, released in cocultures exert inhibitory effects on collagen and temporary effects on proteoglycan production, which finally results in a reduction of mechanical strength of newly formed fibrillar networks.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0453-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4209060  PMID: 25296561
2.  Melanocortin 1 Receptor-Signaling Deficiency Results in an Articular Cartilage Phenotype and Accelerates Pathogenesis of Surgically Induced Murine Osteoarthritis 
PLoS ONE  2014;9(9):e105858.
Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT–analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA-pathology. Our data suggest that MC1-signaling protects against cartilage degradation and subchondral bone sclerosis in OA indicating a beneficial role of the POMC system in joint pathophysiology.
PMCID: PMC4156302  PMID: 25191747
3.  Osteoarthritic cartilage explants affect extracellular matrix production and composition in cocultured bone marrow-derived mesenchymal stem cells and articular chondrocytes 
In the present study, we established a novel in vitro coculture model to evaluate the influence of osteoarthritis (OA) cartilage explants on the composition of newly produced matrix and chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs) and the phenotype of OA chondrocytes. In addition, we included a “tri-culture” model, whereby a mixture of BMSCs and chondrocytes was cultured on the surface of OA cartilage explants.
Gene expression analysis, protein and glycosaminoglycan (GAG) assays, dot-blot, immunofluorescence, and biomechanical tests were used to characterize the properties of newly generated extracellular matrix (ECM) from chondrocytes and chondrogenically differentiated BMSCs and a mix thereof. We compared articular cartilage explant cocultures with BMSCs, chondrocytes, and mixed cultures (chondrocytes and BMSCs 1:1) embedded in fibrin gels with fibrin gel-embedded cells cultured without cartilage explants (monocultures).
In general, co- and tri-cultured cell regimens exhibited reduced mRNA and protein levels of collagens I, II, III, and X in comparison with monocultures, whereas no changes in GAG synthesis were observed. All co- and tri-culture regimens tended to exhibit lower Young’s and equilibrium modulus compared with monocultures. In contrast, aggregate modulus and hydraulic permeability seemed to be higher in co- and tri-cultures. Supernatants of cocultures contained significant higher levels of interleukin-1 beta (IL-1β), IL-6, and IL-8. Stimulation of monocultures with IL-1β and IL-6 reduced collagen gene expression in BMSCs and mixed cultures in general but was often upregulated in chondrocytes at late culture time points. IL-8 stimulation affected BMSCs only.
Our results suggest an inhibitory effect of OA cartilage on the production of collagens. This indicates a distinct modulatory influence that affects the collagen composition of the de novo-produced ECM from co- and tri-cultured cells and leads to impaired mechanical and biochemical properties of the matrix because of an altered fibrillar network. We suggest that soluble factors, including IL-1β and IL-6, released from OA cartilage partly mediate these effects. Thus, neighbored OA cartilage provides inhibitory signals with respect to BMSCs’ chondrogenic differentiation and matrix composition, which need to be accounted for in future cell-based OA treatment strategies.
PMCID: PMC4097830  PMID: 24916039
4.  A minimally invasive approach for total hip arthroplasty does not diminish early post-operative outcome in obese patients: a prospective, randomised trial 
International Orthopaedics  2013;37(6):1013-1018.
The benefits of minimally invasive surgical techniques in total hip arthroplasty (THA) are well known, but concerns about applying those techniques in obese patients are controversial. We prospectively compared patients with increased body mass index (BMI ≥30) undergoing THA with normal weight patients.
A total of 134 patients admitted for unilateral THA were randomised to have surgery through either a transgluteal or a minimally invasive approach (MicroHip). In each group a BMI ≥30 was used to define obese patients. Pre- and early post-operative demographics, intraoperative data, baseline haematological values, hip function (Harris Hip Score, Oxford Hip Score) and quality of life (EQ-5D) were assessed with follow-up at three months.
Duration of surgery, blood loss, C-reactive protein levels, radiographic measurements and complication rates were comparable in all groups. There was a tendency for lower serum creatine kinase levels in the MicroHip group. Intraoperative fluoroscopic time and dose area products were significantly elevated in patients with a BMI exceeding 30 regardless of the approach used. Time points of mobilisation, length of hospital stay and functional outcome measurements were similar in the different weight groups.
Our data suggest that obese patients gain similar benefit from MicroHip THA as do non-obese patients. The results of this study should be further investigated to assess long-term survivorship.
PMCID: PMC3664165  PMID: 23446330
5.  Comparing navigation-based in vivo knee kinematics pre- and postoperatively between a cruciate-retaining and a cruciate-substituting implant 
International Orthopaedics  2013;37(3):407-414.
Individual physiological knee kinematics are highly variable in normal knees and are altered following cruciate-substituting (PS) and cruciate-retaining (CR) total knee arthroplasty (TKA). We wanted to know whether knee kinematics are different choosing two different knee designs, CR and PS TKA, during surgery using computer navigation.
For this purpose, 60 consecutive TKA were randomised, receiving either CR (37 patients) or PS TKA (23 patients). All patients underwent computer navigation, and kinematics were assessed prior to making any cuts or releases and after implantation. Outcome measures were relative rotation between femur and tibia, measured medial and lateral gaps and medial and lateral condylar lift-off.
We were not able to demonstrate a significant difference in femoral external rotation between either group prior to implantation (7.9° CR vs. 7.4° PS) or after implantation (9.0° CR vs. 11.3° PS), both groups showed femoral roll-back. It significantly increased pre- to postoperatively in PS TKA. In the CR group both gaps increased, the change of the medial gap was significantly attributable to medial release. In the PS group both gaps increased and the change of the medial and of the lateral gap was significant. Condylar lift-off was observed in the CR group during 20° and 60° of flexion.
This study did not reveal significant differences in navigation-based knee kinematics between CR and PS implants. Femoral roll-back was observed in both implant designs, but significantly increased pre- to postoperatively in PS TKA. A slight midflexion instability was observed in CR TKA. Intra-operative computer navigation can measure knee kinematics during surgery before and after TKR implantation and may assist surgeons to optimise knee kinematics or identify abnormal knee kinematics that could be corrected with ligament releases to improve the functional result of a TKR, whether it is a CR or PS design. Our intra-operative finding needs to be confirmed using fluoroscopic or radiographic 3D matching after complete recovery from surgery.
PMCID: PMC3580100  PMID: 23361937
6.  Arthrodesis of the talonavicular joint using angle-stable mini-plates: a prospective study 
International Orthopaedics  2012;36(12):2491-2494.
The talonavicular joint is a central connection of the human foot. Symptomatic talonavicular arthritis can be adequately addressed by isolated talonavicular fusion. However, non-union remains a relevant clinical challenge to the orthopaedic surgeon. The aim of this study was to analyse the clinicoradiological outcome of talonavicular fusion using angle-stable mini-plates.
We performed 30 talonavicular fusions in 30 patients (12 male, 18 female) with a mean age of 58.8 years (range, 22–74) between 2005 and 2007. Osseous joint fusion was achieved using mono- and multidirectional angle-stable mini-plates. The patients followed a standardised immobilisation and weight bearing protocol. The mean postoperative follow up was 15.8 months (6.1–23.8).
The American Orthopedic Foot and Ankle Society AOFAS score increased significantly from 31.7 (19–42) to 82.3 points (55–97) (p < 0.001). Neither age at operation nor gender influenced the score results significantly, while the aetiology of talonavicular degeneration showed a significant effect. Mean visual analogue scale (VAS) pain intensity (0–10) reduced from 8.6 to 1.7 (p < 0.001). Good or excellent results were achieved in 26 patients, while two patients reported fair and another two poor results. Complete osseous fusion was observed at a mean of 10.9 weeks (8–13) postoperatively.
For the treatment of talonavicular arthritis, the application of mono- and multidirectional angle-stable mini-plates provided a strong fixation that led to high union rates and good to excellent overall outcome.
PMCID: PMC3508057  PMID: 23052279
7.  Treatment of deep articular talus lesions by matrix associated autologous chondrocyte implantation—results at five years 
International Orthopaedics  2012;36(11):2279-2285.
Treatment of focal full-thickness chondral or osteochondral defects of the talus remains a challenge. The aim of this study was to evaluate the postoperative success and the long-term efficacy of matrix associated autologous chondrocyte implantation in these defects.
Matrix associated autologous chondrocyte implantation (MACI) was applied in 22 consecutive patients (mean age 23.9 years) with full-thickness chondral or osteochondral lesions of the talus. The average defect-size was 1.94 cm² (range 1–6). In case of osteochondritis dissecans (n = 13) an autologous bone graft was performed simultaneously. Follow-ups were routinely scheduled up to 63.5 (±7.4) months, consisting of clinical evaluation and magnetic resonance imaging.
The AOFAS score improved significantly from 70.1 to 87.9/92.6/93.5/95.0/95.5 and 95.3 points at three, six, 12, 24, 36 and 63.5 months, respectively. On a visual analogue scale, pain intensity decreased from 5.7 (±2.6) to 0.9 (±0.8) while subjective function increased from 5.3 (±2.3) to 8.9 (±0.9) at final follow-up (each p < 0.001). The Tegner score rose significantly from 2.4 (±1.2) to 4.7 (±0.6). The MOCART score improved from 62.6 (±19.4) at three months to 83.8 (±9.4) at final follow-up. No significant differences were found between lesions caused by osteochondritis dissecans or trauma and between first- or second-line treatments. For all scores, the most benefit was seen within the first 12 months with stable results afterwards. No major complications were noted.
Matrix associated autologous chondrocyte implantation is capable of significant and stable long-term improvement of pain and functional impairment caused by focal full-thickness chondral and osteochondral talus lesions.
PMCID: PMC3479272  PMID: 22885840
8.  Fluoroscopy-guided retrograde core drilling and cancellous bone grafting in osteochondral defects of the talus 
International Orthopaedics  2012;36(8):1635-1640.
In undetached osteochondral lesions (OCL) of the talus both revitalisation of the subchondral necrosis and cartilage preservation are essential. For these cases, we assess the results of minimally invasive retrograde core drilling and cancellous bone grafting.
Forty-one osteochondral lesions of the talus (12x grade I, 22x grade II and 7x grade III according to the Pritsch classification, defect sizes 7–14 mm) in 38 patients (mean age 33.2 years) treated by fluoroscopy-guided retrograde core drilling and autologous cancellous bone grafting were evaluated by clinical scores and MRI. The mean follow-up was 29.0 (±13) months.
The AOFAS score increased significantly from 47.3 (±15.3) to 80.8 (±18.6) points. Lesions with intact cartilage (grades I and II) had a tendency to superior results than grade III lesions (83.1 ± 17.3 vs. 69.4 ± 22.2 points, p = 0.07). First-line treatments and open distal tibial growth plates led to significantly better outcomes (each p < 0.05). Age, gender, BMI, time to follow-up, defect localisation or a traumatic origin did not influence the score results. On a visual analogue scale pain intensity reduced from 7.5 (±1.5) to 3.7 (±2.6) while subjective function increased from 4.6 (±2.0) to 8.2 (±2.3) (each p < 0.001). In MRI follow-ups, five of the 41 patients showed a complete bone remodelling. In two cases demarcation was detectable.
The technique reported is a highly effective therapeutic option in OCL of the talus with intact cartilage grades I and II. However, second-line treatments and grade III lesions with cracked cartilage surface can not be generally recommended for this procedure.
PMCID: PMC3535023  PMID: 22491802
9.  Accuracy of acetabular cup placement in computer-assisted, minimally-invasive THR in a lateral decubitus position 
International Orthopaedics  2010;35(6):809-815.
In a prospective and randomised clinical study, we implanted acetabular cups either by means of an image-free computer-navigation system (navigated group, n = 32) or by free-hand technique (freehand group n = 32, two drop-outs). Total hip replacement was conducted in the lateral position and through a minimally invasive anterior approach (MicroHip). The position of the component was determined postoperatively on CT scans of the pelvis using CT-planning software. We found an average inclination of 42.3° (range 32.7–50.6°; SD±3.8°) and an average anteversion of 24.5° (range 12.0–33.3°; SD±6.0°) in the computer-assisted study group and an average inclination of 37.9° (range 25.6–50.2°; SD±6.3°) and an average anteversion of 23.8° (range 5.6–46.9°; SD±10.1°) in the freehand group. The higher precision of computer navigation was indicated by the lower standard deviations. For both measurements we found a significant heterogeneity of variances (p < 0.05, Levene's test). The mean difference between the cup inclination/anteversion values displayed by computer navigation and the true cup position (CT control) was 0.37° (SD 3.26) and −5.61° (SD 6.48), respectively. We found a bias (underestimation) with regard to anteversion determined by the imageless computer navigation system. A bias for inclination was not found. Registration of the landmarks of the anterior pelvic plane in lateral position with undraped percutaneous methods leads to an error in cup anteversion, but not to an error in cup inclination. The bias we found is consistent with a correct registration of the anterosuperior iliac spine (ASIS) and with a registration of the symphysis 1 cm above the bone, corresponding to the less compressible overlying soft tissue in this region. There was no significant correlation between the bias and the thickness of soft tissue above the pubic tubercles. We suggest use of a percutaneous registration of ASIS and an invasive registration above the pubic tubercles when computer-assisted navigation is performed in minimally invasive THR in a lateral position.
PMCID: PMC3103965  PMID: 20495801
10.  The association between Femoral Tilt and impingement-free range-of-motion in total hip arthroplasty 
There is a complex interaction among acetabular component position and antetorsion of the femoral stem in determining the maximum, impingement-free prosthetic range-of-motion (ROM) in total hip arthroplasty (THA). By insertion into the femoral canal, stems of any geometry follow the natural anterior bow of the proximal femur, creating a sagittal Femoral Tilt (FT). We sought to study the incidence of FT as measured on postoperative computed tomography scans and its influence on impingement-free ROM in THA.
The incidence of the postoperative FT was evaluated on 40 computed tomography scans after cementless THA. With the help of a three-dimensional computer model of the hip, we then systematically analyzed the effects of FT on femoral antetorsion and its influence on calculations for a ROM maximized and impingement-free compliant stem/cup orientation.
The mean postoperative FT on CT scans was 5.7° ± 1.8°. In all tests, FT significantly influenced the antetorsion values. Re-calculating the compliant component positions according to the concept of combined anteversion with and without the influence of FT revealed that the zone of compliance could differ by more than 200%. For a 7° change in FT, the impingement-free cup position differed by 4° for inclination when the same antetorsion was used.
A range-of-motion optimized cup position in THA cannot be calculated based on antetorsion values alone. The FT has a significant impact on recommended cup positions within the concept of “femur first” or “combined anteversion”. Ignoring FT may pose an increased risk of impingement as well as dislocation.
PMCID: PMC3416712  PMID: 22559740
11.  Minimally invasive computer-navigated total hip arthroplasty, following the concept of femur first and combined anteversion: design of a blinded randomized controlled trial 
Impingement can be a serious complication after total hip arthroplasty (THA), and is one of the major causes of postoperative pain, dislocation, aseptic loosening, and implant breakage. Minimally invasive THA and computer-navigated surgery were introduced several years ago. We have developed a novel, computer-assisted operation method for THA following the concept of "femur first"/"combined anteversion", which incorporates various aspects of performing a functional optimization of the cup position, and comprehensively addresses range of motion (ROM) as well as cup containment and alignment parameters. Hence, the purpose of this study is to assess whether the artificial joint's ROM can be improved by this computer-assisted operation method. Second, the clinical and radiological outcome will be evaluated.
A registered patient- and observer-blinded randomized controlled trial will be conducted. Patients between the ages of 50 and 75 admitted for primary unilateral THA will be included. Patients will be randomly allocated to either receive minimally invasive computer-navigated "femur first" THA or the conventional minimally invasive THA procedure. Self-reported functional status and health-related quality of life (questionnaires) will be assessed both preoperatively and postoperatively. Perioperative complications will be registered. Radiographic evaluation will take place up to 6 weeks postoperatively with a computed tomography (CT) scan. Component position will be evaluated by an independent external institute on a 3D reconstruction of the femur/pelvis using image-processing software. Postoperative ROM will be calculated by an algorithm which automatically determines bony and prosthetic impingements.
In the past, computer navigation has improved the accuracy of component positioning. So far, there are only few objective data quantifying the risks and benefits of computer navigated THA. Therefore, this study has been designed to compare minimally invasive computer-navigated "femur first" THA with a conventional technique for minimally invasive THA. The results of this trial will be presented as soon as they become available.
Trial registration number
PMCID: PMC3180441  PMID: 21854588
12.  The oncofetal gene survivin is re-expressed in osteoarthritis and is required for chondrocyte proliferation in vitro 
Regulation of cell death and cell division are key processes during chondrogenesis and in cartilage homeostasis and pathology. The oncogene survivin is considered to be critical for the coordination of mitosis and maintenance of cell viability during embryonic development and in cancer, and is not detectable in most adult differentiated tissues and cells. We analyzed survivin expression in osteoarthritic cartilage and its function in primary human chondrocytes in vitro.
Survivin expression was analyzed by immunoblotting and quantitative real-time PCR. The localization was visualized by immunofluorescence. Survivin functions in vitro were investigated by transfection of a specific siRNA.
Survivin was expressed in human osteoarthritic cartilage, but was not detectable in macroscopically and microscopically unaffected cartilage of osteoarthritic knee joints. In primary human chondrocyte cultures, survivin was localized to heterogeneous subcellular compartments. Suppression of survivin resulted in inhibition of cell cycle progression and sensitization toward apoptotic stimuli in vitro.
The present study indicates a role for survivin in osteoarthritic cartilage and human chondrocytes. In vitro experiments indicated its involvement in cellular division and viability. Learning more about the functions of survivin in chondrocyte biology might further help toward understanding and modulating the complex processes of cartilage pathology and regeneration.
PMCID: PMC3141611  PMID: 21729321
apoptosis; chondrocyte; osteoarthritis; proliferation; survivin
13.  Leg Length and Offset Measures with a Pinless Femoral Reference Array during THA 
The bony fixation of reference marker arrays used for computer-assisted navigation during total hip arthroplasty (THA) theoretically involves the risk of fracture, infection, and/or pin loosening. We asked whether intraoperative assessment of leg length (LL) and offset (OS) changes would be accurate using a novel pinless femoral reference system in conjunction with an imageless measurement algorithm based on specific realignment of the relationship between a dynamic femoral and pelvis reference array. LL/OS measurements were recorded during THA in 17 cadaver specimen hips. Preoperatively and postoperatively, specimens were scanned using CT. Linear radiographic LL/OS changes were determined by two investigators using visible fiducial landmarks and image processing software. We found a high correlation of repeated measurements within and between (both 0.95 or greater) the two examiners who did the CT assessments. Pinless LL/OS values showed mean differences less than 1 mm and correlations when compared with CT measurements.
PMCID: PMC2882021  PMID: 19768517
14.  The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells in vitro 
BMC Cancer  2011;11:120.
Chondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro.
Resected chondrosarcoma specimens from which paraffin-embedded tissues could be extracted were available from 12 patients. In vitro experiments were performed in human chondrosarcoma cell lines SW1353 and Hs819.T. Immunohistochemistry, immunoblot, quantitative PCR, RNA interference, gene-overexpression and analyses of cell proliferation and apoptosis were performed.
Expression of survivin protein was detected in all chondrosarcoma specimens analyzed, while undetectable in adult human cartilage. RNA interference targeting survivin resulted in a G2/M-arrest of the cell cycle and led to increased rates of apoptosis in chondrosarcoma cells in vitro. Overexpression of survivin resulted in pronounced resistance to doxorubicin treatment.
These findings indicate that survivin plays a role in the pathogenesis and pronounced chemoresistance of high grade chondrosarcoma. Survivin antagonizing therapeutic strategies may lead to new treatment options in unresectable and metastasized chondrosarcoma.
PMCID: PMC3076263  PMID: 21457573
15.  Lifestyle factors and lumbar disc disease: results of a German multi-center case-control study (EPILIFT) 
Arthritis Research & Therapy  2010;12(5):R193.
In the large-scale case-control study EPILIFT, we investigated the dose-response relationship between lifestyle factors (weight, smoking amount, cumulative duration of different sports activities) and lumbar disc disease.
In four German study regions (Frankfurt am Main, Freiburg, Halle/Saale, Regensburg), 564 male and female patients with lumbar disc herniation and 351 patients with lumbar disc narrowing (chondrosis) aged 25 to 70 years were prospectively recruited. From the regional population registers, 901 population control subjects were randomly selected. In a structured personal interview, we enquired as to body weight at different ages, body height, cumulative smoking amount and cumulative duration of different sports activities. Confounders were selected according to biological plausibility and to the change-in-estimate criterion. Adjusted, gender-stratified odds ratios with 95% confidence intervals were calculated using unconditional logistic regression analysis.
The results of this case-control study reveal a positive association between weight and lumbar disc herniation as well as lumbar disc narrowing among men and women. A medium amount of pack-years was associated with lumbar disc herniation and narrowing in men and women. A non-significantly lowered risk of lumbar disc disease was found in men with high levels of cumulative body building and strength training.
According to our multi-center case-control study, body weight might be related to lumbar disc herniation as well as to lumbar disc narrowing. Further research should clarify the potential protective role of body building or strength training on lumbar disc disease.
PMCID: PMC2991029  PMID: 20955546
16.  Stem torsion in total hip replacement 
Acta Orthopaedica  2010;81(5):579-582.
Background and purpose
The clinical results of THR may be improved by correct femoral torsion. We evaluated the stem position by postoperative CT examination in 60 patients.
60 patients requiring total hip arthroplasty were prospectively enrolled in this study. Minimally invasive THR was performed (anterior approach) in a lateral decubitus position and each patient underwent a postoperative CT examination. The position of the stem was evaluated by an independent external institution.
Stem torsion ranged from –19° retrotorsion to 33° antetorsion. Normal antetorsion (i.e 10–15° according to Tönnis) was present in 5 of 60 patients, so the prevalence of abnormal stem antetorsion was 92% (95% CI: 82–97). We found a stem antetorsion outside the range of 0–25° in 21 of 60 hips. Women had a higher mean stem antetorsion (8.0° (SD 11)) than men (1.5° (SD 10)).
Postoperative stem antetorsion shows a high variability and is gender-related. We suggest precise assessment of stem antetorsion intraoperatively by means of computer navigation, preparing the femur first. In abnormal stem antetorsion, the cup position can be adjusted using a combined anteversion concept; alternatively, modular femoral components or stems with retroverted or anteverted necks (“retrostem”) could be used.
PMCID: PMC3214746  PMID: 20919811
17.  Leg axis correction with ConforMIS iForma™ (interpositional device) in unicompartmental arthritis of the knee 
International Orthopaedics  2008;33(4):955-960.
Degeneration of the meniscus and the articular cartilage in unicompartmental osteoarthritis of the knee results in progressive deformity of the leg axis. It is the aim of this study to evaluate if a leg axis correction can be achieved by implanting a customised metallic interpositional device for the knee (ConforMIS iForma™). Before and after implanting a ConforMIS iForma™ knee implant, a radiological analysis of the leg axis deviation in the frontal plane was performed prospectively in 27 patients by evaluating anteroposterior single-leg stance radiographs. We achieved a sufficient leg axis correction with an average correction of 3.8° and an averaged small under-adjustment of 0.9° by inserting the ConforMIS iForma™ interpositional knee implant. Apart from the primary treatment objective of articular surface restitution the ConforMIS iForma™ knee implant can be reliably used to correct axis deformity occurring with unicompartmental osteoarthritis of the knee.
PMCID: PMC2898985  PMID: 18563412
18.  Cell culture and passaging alters gene expression pattern and proliferation rate in rheumatoid arthritis synovial fibroblasts 
Rheumatoid arthritis synovial fibroblasts (RASF) are key players in synovial pathophysiology and are therefore examined extensively in various experimental approaches. We evaluated, whether passaging during culture and freezing has effects on gene expression and cell proliferation.
RASF were passaged for up to 8 passages. RNA was isolated after each passage and cDNA arrays were performed to evaluate the RNA expression pattern during passaging. In addition, doubling time of the cells was also measured.
From passages 2-4, mRNA expression did not change significantly. Gene expression in RASF started to change in passages 5-6 with 7-10% differentially expressed genes. After passages 7-8, more than 10% of the genes were differentially expressed. The doubling rate was constant for up to 5 passages and decreased after passages 6-8. After freezing, gene expression of the second passage is comparable to gene expression prior to freezing.
The results of this study show, that experiments, which examine gene expression of RASF and shall reflect or imitate an in vivo situation, should be limited to early culture passages to avoid cell culture effects. It is not necessary to stop culturing SF after a few passages, but to keep the problems of cell culture in mind to avoid false positive results. Especially, when large-scale screening methods on mRNA level are used. Of note, freezing does not affect gene expression substantially.
PMCID: PMC2911867  PMID: 20462438
19.  Navigated cup implantation in hip arthroplasty 
Acta Orthopaedica  2009;80(5):538-544.
Background and purpose Many studies have suggested that navigation-based implantation can improve cup positioning in total hip arthroplasty (THA). We conducted a systematic review and meta-analysis to compile the best available evidence, and to overcome potential shortcomings because of small sample sizes in individual studies.
Methods The search strategy covered the major medical databases from January 1976 through August 2007, as well as various publishers' databases. The internal validity of individual studies was evaluated independently by 3 reviewers. We used random-effects modeling to obtain mean differences in cup angulation and relative risk (RR) of cup positioning outside Lewinnek's safe zone.
Results Of 363 citations originally identified, 5 trials of moderate methodology enrolling a total of 400 patients were included in the analysis. Mean cup inclination and anteversion were not statistically significantly different between the conventional groups and the navigated groups. Navigation reduced the variability in cup positioning and the risk of placing the acetabular component beyond the safe zone (RR = 0.21, CI: 0.13–0.32).
Interpretation Based on the current literature, navigation is a reliable tool to optimize cup placement, and to minimize outliers. However, long-term outcomes and cost utility analyses are needed before conclusive statements can be drawn about the value of routine navigation in THA.
PMCID: PMC2823338  PMID: 19916685
20.  Cumulative occupational lumbar load and lumbar disc disease – results of a German multi-center case-control study (EPILIFT) 
The to date evidence for a dose-response relationship between physical workload and the development of lumbar disc diseases is limited. We therefore investigated the possible etiologic relevance of cumulative occupational lumbar load to lumbar disc diseases in a multi-center case-control study.
In four study regions in Germany (Frankfurt/Main, Freiburg, Halle/Saale, Regensburg), patients seeking medical care for pain associated with clinically and radiologically verified lumbar disc herniation (286 males, 278 females) or symptomatic lumbar disc narrowing (145 males, 206 females) were prospectively recruited. Population control subjects (453 males and 448 females) were drawn from the regional population registers. Cases and control subjects were between 25 and 70 years of age. In a structured personal interview, a complete occupational history was elicited to identify subjects with certain minimum workloads. On the basis of job task-specific supplementary surveys performed by technical experts, the situational lumbar load represented by the compressive force at the lumbosacral disc was determined via biomechanical model calculations for any working situation with object handling and load-intensive postures during the total working life. For this analysis, all manual handling of objects of about 5 kilograms or more and postures with trunk inclination of 20 degrees or more are included in the calculation of cumulative lumbar load. Confounder selection was based on biologic plausibility and on the change-in-estimate criterion. Odds ratios (OR) and 95% confidence intervals (CI) were calculated separately for men and women using unconditional logistic regression analysis, adjusted for age, region, and unemployment as major life event (in males) or psychosocial strain at work (in females), respectively. To further elucidate the contribution of past physical workload to the development of lumbar disc diseases, we performed lag-time analyses.
We found a positive dose-response relationship between cumulative occupational lumbar load and lumbar disc herniation as well as lumbar disc narrowing among men and women. Even past lumbar load seems to contribute to the risk of lumbar disc disease.
According to our study, cumulative physical workload is related to lumbar disc diseases among men and women.
PMCID: PMC2689164  PMID: 19422710
21.  A new short uncemented, proximally fixed anatomic femoral implant with a prominent lateral flare: design rationals and study design of an international clinical trial 
Anatomic short femoral prostheses with a prominent lateral flare have the potential to reduce stress-shielding in the femur through a more physiological stress distribution to the proximal femur. We present the design rationale of a new short uncemented, proximally fixed anatomic femoral implant and the study design of a prospective multi-centre trial to collect long-term patient outcome and radiographic follow up data.
A prospective surveillance study (trial registry NCT00208555) in four European centres (UK, Italy, Spain and Germany) with a follow up period of 15 years will be executed. The recruitment target is 200 subjects, patients between the ages of 18 and 70 admitted for primary cementless unilateral THA will be included. The primary objective is to evaluate the five-year survivorship of the new cementless short stem. The secondary objectives of this investigation are to evaluate the long term survivorship and the clinical performance of the implant, the impact on the subjects health related Quality of Life and the affect of the prosthesis on bone mineral density. Peri- and postoperative complications will be registered. Clinical and radiographic evaluation of prosthesis positioning will be done post-operatively and at 3, 6, 12, 24, 60, 120 and 180 months follow up.
Shortening of the distal stem can maximise bone and soft tissue conservation. New stem types have been designed to improve the limitations of traditional implants in primary THA. A new, uncemented femoral short stem is introduced in this paper. A long-term follow up study has been designed to verify stable fixation and to research into the clinical outcome. The results of this trial will be presented as soon as they become available.
PMCID: PMC2584636  PMID: 18983669
22.  Preemptive versus postoperative lumiracoxib for analgesia in ambulatory arthroscopic knee surgery 
Journal of pain research  2008;1:27-34.
We compared the efficacy and safety of preemptive vs postoperative dosing of lumiracoxib 400 mg in patients undergoing minor ambulatory arthroscopic knee surgery. Eligible patients were randomized to preemptive lumiracoxib, postoperative lumiracoxib, and placebo. The main efficacy parameter was pain intensity (PI) (0–100 mm visual analog scale) in the target knee upon movement, 2 hours after surgery. Other efficacy variables included PI in the target knee at rest and upon movement at 1, 3, 4, and 24 hours, time to first rescue medication intake. In the lumiracoxib preemptive and postoperative groups, the estimated treatment difference compared to placebo for primary endpoint was −4.0 (95% CI: −9, −1; p = 0.007) and −3.5 (95% CI: −8.5, 0; p = 0.052), respectively. There was no statistical significant difference between two active treatment groups (p = 0.602). Both preemptive and postoperative lumiracoxib resulted in significantly lower PI scores at rest and after movement at all time-points and no statistically significant difference was observed between the active treatments. Time to rescue medication intake was comparable for both active treatments. The proportion of adverse events was similar among all groups. We conclude that the efficacy of lumiracoxib 400 mg is not affected by the timing of administration (preemptive or postoperative).
PMCID: PMC3004612  PMID: 21197285
arthroscopy; arthroscopic knee surgery; lumiracoxib; NSAIDs; postoperative pain; preemptive dosing
23.  A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis 
Annals of the Rheumatic Diseases  2012;71(9):1454-1460.
To compare the effects of an intermediate molecular weight (MW) intra-articular hyaluronic acid (HA) with a low MW product on knee osteoarthritis (OA) symptoms.
Patients with symptomatic knee OA were enrolled inarandomised, controlled, double-blind, parallel-group, non-inferiority trial with the possibility to shift to superiority. Patients were randomised to GO-ON(MW 800–1500 kD, 25 mg/2.5 ml) or Hyalgan(MW 500–730 kD, 20 mg/2 ml) injected at 3-weekly intervals. The primary outcome was 6-month change in the WOMAC pain subscale (0–100 mm). Sample size was calculated on a non-inferiority margin of 9 mm, lower than the minimum perceptible clinical improvement. Secondary endpoints included OARSI-OMERACT responder rates
The intention-to-treat (ITT) and per-protocol (PP) populations consisted of 217 and 209 patients and 171 and 172 patients in the GO-ON and Hyalgan groups, respectively. ITT WOMAC pain of 47.5±1.0(SE) and 48.8±1.0 mm decreased by 22.9±1.4 mm with GO-ON and 18.4±1.5 mm with Hyalgan after 6 months. The primary analysis was conducted in the PP population followed by the ITT population.Mean (95% CI) differences in WOMAC pain change were 5.2 (0.9 to 9.6)mm and 4.5 (0.5 to 8.5)mm, respectively,favouring GO-ON, satisfying the claim for non-inferiority (lower limit>−9 mm) and for statistical superiority (95% CI all>0, p=0.021). Ahigher proportion of OARSI/OMERACT responders was observed with GO-ONthan with Hyalgan (73.3% vs58.4%, p=0.001). Both preparations were well tolerated.
Treatment with 3-weekly injections of intermediate MW HA may be superior to low MW HA on knee OA symptoms over 6 months, with similar safety.
PMCID: PMC3414228  PMID: 22294639

Results 1-23 (23)