Joint instability leads to long-term alterations to knee synovium and osteoarthritis in a rabbit model.

OBJECTIVES: Joint instability is believed to promote early osteoarthritic changes in the knee. Inflammatory reactions are associated with cartilage degradation in osteoarthritis (OA) but their possible synergistic or additive effects remain largely unexplored. The goal of the present study was to investigate the in vivo effects of Botulinum Toxin A (BTX-A) induced joint instability on intraarticular alterations in an otherwise intact rabbit knee joint model. METHODS: Ten 1-year-old female New Zealand White rabbits (average 5.7 kg, range 4.8-6.6 kg) were randomly assigned to receive three monthly unilateral intramuscular injections of BTX-A (experimental group), or no treatment (control group). After 90 days, all knees were analyzed for specific mRNA levels using RT-qPCR. The synovium and cartilage tissue was assessed for histological alterations using the OARSI scoring system. RESULTS: Cartilage and synovial histology showed significant higher OARSI scores in the BTX-A group animals compared to the untreated controls and contralateral limbs. There were no differences between the untreated control and the contralateral experimental limbs. Gene expression showed significant elevations for collagen I, collagen III, nitric oxide, TGF-ß, IL-1 and IL-6 compared to the healthy controls. CONCLUSION: BTX-A induced joint instability in a muscle weakness model uniquely leads to alterations in gene expression and histological changes in the synovial membranes and cartilage in otherwise intact knee joints. These results lead to the conclusion that joint instability may promote an inflammatory intraarticular milieu, thereby contributing to the development of OA.

Tissue engineering approaches to degenerative disc disease--a meta-analysis of controlled animal trials.

OBJECTIVE: The objective of this systematic review was to assess cell/biomaterial treatments of degenerative disc disease in controlled animal trails. The primary endpoints were restoration of disc height and T2 signal intensity. METHOD: PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) were searched for studies reporting on the use of tissue engineering treatments (cells/biomaterials/cells and biomaterials) for degenerative disc disease treatments in a controlled trial. Publication bias was assessed graphically using funnel plots and Egger's regression. Data were grouped by follow-up duration - early (<4 weeks), intermediate (4-12 weeks) and late (>12 weeks), and weighted mean differences (WMD) were calculated using DerSimonian-Laird Random Effect models. RESULTS: Thirteen papers, published between 2004 and 2011, were included in this study. In comparison with the injured disc, all three treatments showed a positive effect in disc height, but none of the treatments restored disc height compared to the healthy disc. Overall, there seemed to be a better effect on disc height restoration for the treatment with cells and biomaterials. None of the treatments could achieve the same T2 signal intensity as the healthy disc, and compared to the injured disc, only the treatment with cells and biomaterials showed consistently better results. CONCLUSION: Treatment of an injured/degenerating disc with cells, cells plus biomaterial or biomaterial alone has a potential for at least a partial regeneration of the disc. However, so far, none of the treatments is able to effectively restore the properties of a healthy disc.

Effectiveness of autologous chondrocyte implantation in cartilage repair of the knee: a systematic review of controlled trials.

OBJECTIVE: The relative differences in effectiveness of subchondral stimulation, osteochondral grafts, and autologous chondrocyte implantation (ACI) are still unclear. It is the objective of this study to systematically review the literature on ACI compared to other treatments by clinical outcome and the quality of the repair tissue, including an assessment of the validity of these findings. METHOD: The online databases PubMed, EMBASE, Cochrane Controlled Trial Register, CENTRAL, CINAHL, and BioMed were searched. Controlled trials comparing ACI with other methods of cartilage repair or placebo were included. Data on clinical outcome and the quality of the repair tissue was abstracted in duplicate. Study validity was assessed by individual components (randomization, blinded outcome assessment, sample size, attrition, percentage biopsies). RESULTS: Nine studies were included. The internal validity of most of these studies was poor. Studies comparing ACI with subchondral stimulation have a higher quality and show no differences in clinical outcomes, but suggest better results in tissue quality. The high quality evidence comparing ACI with osteochondral grafts shows better clinical outcomes and higher tissue quality after ACI. CONCLUSION: Among the included studies there is much inconsistency in methodological quality and findings. Regardless of these problems, the absolute differences between groups are fairly small, thus raising questions about their clinical importance. Future studies will be needed to answer the question of benefits of ACI compared to other treatments, and could profit from addressing and avoiding the problems seen in this group. Finally conclusions concerning long-term effects are still difficult.

Microfracture for the treatment of cartilage defects in the knee joint - A golden standard?

The evidence for the effectiveness of the microfracture procedure is largely derived from case series and few randomized trials. Clinical outcomes improve with microfracture for the most part, but in some studies these effects are not sustained. The quality of cartilage repair following microfracture is variable and inconsistent due to unknown reasons. Younger patients have better clinical outcomes and quality of cartilage repair than older patients. When lesion location was shown to affect microfracture outcome, patients with lesions of the femoral condyle have the best clinical improvements and quality of cartilage repair compared with patients who had lesions in other areas. Patients with smaller lesions have better clinical improvement than patients with larger lesions. The necessity of long postoperative CPM and restricted weight bearing is widely accepted but not completely supported by solid data. Maybe new developments like the scaffold augmented microfracture(6) will show even more consistent clinical and biological results as well as faster rehabilitation for the treatment of small to medium sized cartilage defects in younger individuals. All in all there is limited evidence that micro fracture should be accepted as gold standard for the treatment of cartilage lesions in the knee joint. There is no study available which compares empty controls or non-surgical treatment/physiotherapy with microfracture. According to the literature there is even evidence for self regeneration of cartilage lesions. The natural history of damaged cartilage seems to be written e.g. by inflammatory processes, genetic predisposition and other factors. Possibly that explains the large variety of the clinical outcome after micro fracture and possibly the standard tools for evaluation of new technologies (randomized controlled trials, case series, etc.) are not sufficient (anymore). Future technologies will be evaluated by big data from international registries for earlier detection of safety issues, for detection of subtle but crucial co-factors for failure and osteoarthritis as well as for lower financial burdens affecting industry and healthcare systems likewise.

[Association between Hindfoot Alignment and Localisation of Osteochondral Lesions of the Talus]. / Zusammenhang der Rückfußachse mit der Lokalisation von osteochondralen Läsionen am Talus.

BACKGROUND: Osteochondral lesions (OCL) of the talus show a distinct distribution pattern. Vascular, metabolic, idiopathic, and biomechanical factors have been proposed as influencing factors. However, the association of hindfoot alignment and the location of talar OCL is not known. MATERIALS AND METHODS: In 22 patients undergoing autologous osteochondral transplantation for OCL of the talus we collected preoperative data on radiographic hindfoot alignment and clinical performance using the AOFAS score and the VAS for pain. The inter-observer reliability between two investigators was calculated. The association between hindfoot alignment and OCL location was statistically assessed. RESULTS: The preoperative AOFAS score was 64.1 ± 13.9 points and the VAS 5.1 ± 1.4. The mean measurement difference between the two observers was less than 0.5 degrees and the reliability of the measurements was good with a high association (κ = 0.83). Surprisingly, the location of the OCL of the talus was independent from hindfoot alignment (p = 0.766). CONCLUSION: In our study the hindfoot alignment showed no association with the location of OCL of the talus. Hence, hindfoot alignment per se does not correlate with the localisation of talar OCL.

[Evidence-based treatment of combined rotator cuff and SLAP lesions]. / Evidenzbasierte Behandlung der kombinierten Rotatorenmanschetten- und SLAP-Läsion.

PURPOSE: In the face of improved radiological and arthroscopic techniques the diagnosis and treatment of SLAP lesions has recently gained much interest. Originally described as an (isolated) injury of the overhead athlete, it was only recently that the association of SLAP and rotator cuff defects was described in up to 40 % of cases. This study addresses the question of the evidence-based treatment of such frequent, combined lesions. METHODS: Based on a systematic review of the online databases PubMed, EMBASE, CINAHL and Cochrane Library we identified clinical studies on the treatment of combined SLAP and rotator cuff lesions. Study quality was assessed using levels of evidence and a modified Jadad score. Clinical outcome was assessed through scores and range of motion assessments. RESULTS: We included 7 studies of 374 patients with a mean age of 53 ± 11 years followed for 35 ± 13 months. Combined lesions have a significant negative effect on isolated rotator cuff or SLAP repair. Patients older than 45 years of age had a significantly better clinical result after biceps tenotomy than SLAP repair with concomitant rotator cuff repair. Biceps tenotomy plus rotator cuff repair showed significantly better range of motion for flexion and rotation than SLAP plus rotator cuff repair. CONCLUSION: The frequent combination of SLAP and rotator cuff injury should be considered during assessment and informed consent of shoulder patients. While young patients and isolated SLAP lesions show excellent clinical results after elective repair, combined lesions should be treated with biceps tenotomy and/or debridement plus rotator cuff repair in patients older than 45 years.

[Evidence-based therapy for cartilage lesions in the knee - regenerative treatment options]. / Evidenzbasierte Knorpeltherapie im Kniegelenk - regenerative Behandlungsoptionen.

BACKGROUND: The treatment of cartilage defects has seen a shift from replacement to regeneration in the last few years. The rationale behind this development is the improvement in the quality-of-care for the growing segment of young patients who are prone to arthroplasty complications because of their specific characteristics - young age, high level of activity, high demand for functionality. These days, two of the most popular regenerative treatments are microfracture and autologous chondrocyte implantation (ACI). Although these new options show promising results, no final algorithm for the treatment of cartilage lesions has been established as yet. MATERIALS AND METHODS: The objective of this review is to describe and compare these two treatment options and to present an evidence-based treatment algorithm for focal cartilage defects. RESULTS: Microfracture is a cost-effective, arthroscopic one-stage procedure, in which by drilling of the subchondral plate, mesenchymal stem cells from the bone marrow migrate into the defect and rebuild the cartilage. ACI is a two-stage procedure in which first chondrocytes are harvested, expanded in cell culture and in a second open procedure reimplanted into the cartilage defect. Microfracture is usually used for focal cartilage defects < 4 cm2, the treated defect size of the ACI seems to have a wider range. The effectiveness of these two treatments has been shown in long-term longitudinal studies, where microfracture showed improvement in up to 95 % of patients, whereas 92 % of the patients in a 2-9 year period of follow-up after ACI showed improvements, respectively. The successful outcome of the treatment depends on multiple factors such as the location of the defect, cell differentiation and proliferation, concomitant problems, and the age of the patient. Associated complications and disadvantages of the two different applications are, for the microfracture patient, a poor tissue differentation or a formation of an intra-lesional osteophyte, and for the ACI patient, periosteal hypertrophy and the need for two procedures in ACI. Only a few studies provide detailed and evidence-based information on a comparative assessment. These studies, however, are showing widely similar clinical outcomes but better histological results for ACI, which are likely to translate into better long-term outcomes. CONCLUSIONS: Although evidence-based studies comparing microfracture and ACI have not found significant differences in the clinical outcome, the literature does show that choosing the treatment based on the size and characteristics of the osteochondral lesion might be beneficial. The American Association of Orthopedic Surgeons suggest that contained lesions < 4 cm2 should be treated by microfracture, lesions bigger than that by ACI.

[Introduction to methods of economic modelling: a primer for orthopaedic surgeons and traumatologists]. / Eine Einführung in Methoden der ökonomischen. Evaluation für Orthopäden und Unfallchirurgen.

AIM: Health economics and cost-efficiency are ubiquitously present issues in present day orthopaedic surgery. These subjects, however, are almost exclusively dealt with by economists and policy makers, while medical professionals rarely take part, quite often because of insufficient methodological knowledge. This report presents the basics of economic evaluation to orthopaedic surgeons to facilitate informed discussion. METHOD: This text reviews the basic methodology of economic evaluation and pertinent findings for orthopaedic surgery. RESULTS: Economic evaluation combines costs and consequences of medical treatments. Partial analyses study costs only, while complete studies include different parameters of consequence. Cost-effectiveness analysis sets cost and effectiveness in natural metrics in relation, while cost-utility analyses present consequences as quality-adjusted life years. Cost-benefit analyses translate both costs and consequences into money value and thus produce a net benefit. Orthopaedic research focuses mainly on cost-utility analyses, yet their number and quality, despite both have been rising over the last years, are mostly insufficient to come to unequivocal conclusions or to produce clear recommendations. CONCLUSION: The trend for an increasing demand for economic evaluations in orthopaedic surgery will continue unabated. Both patients and medical professionals would benefit if orthopaedic surgeons received instruction in economic evaluations in order to be able to take part in such studies or to meaningfully discuss such matters.

[Outcomes after minimally invasive total knee replacement--a meta-analysis]. / Ergebnisse nach minimalinvasivem Knieersatz - eine Metaanalyse.

AIM: A systematic review of randomised controlled trials reporting on the comparison of minimally invasive total knee replacement and standard incision technique was carried out. METHOD: Online searches were performed in Medline, CINAHL, EMBASE, and the Cochrane Controlled Trials Register. Data concerning the endpoints postoperative pain, function, complications, and implant position were extracted in duplicate and pooled using fixed and random effects models. RESULTS: Weighted mean differences for postoperative pain showed 1.4 (95 % CI 1.8 to 1.0, p = 0.014) point better results for MIS. For function, standardised mean differences were calculated and showed better results for MIS, too (0.6 points, 95 % CI 0.03 to 1.12, p = 0.038). There were no significant differences in complication rates (OR 1.3, 95 % CI 0.6 to 2.9, p = 0.477) and implant position. Meta-regression showed no influence of navigation on any of the endpoints. CONCLUSION: Minimally invasive total knee replacement showed better postoperative pain and function without any differences in complication rates or implant position.

[Clinical applicability of evidence-based orthopedics--a cross-sectional study of the quality of orthopedic evidence]. / Die klinische Anwendbarkeit evidenzbasierter Orthopädie--Eine Querschnittsstudie der Qualität der Evidenz orthopädischer Studien.

INTRODUCTION: The demand to routinely apply evidence-based methods in orthopedic surgery increases steadily. In order to do so, however, the validity and reliability of the "evidence" has to be scrutinized. AIM: The object of this study was to assess the quality of the most recent orthopedic evidence and to determine variables that have an influence on quality. METHOD: All 2006 controlled trials from orthopedic journals with high impact factors were analysed in a cross-sectional study. A score based on the CONSORT statement was used to assess study quality. Selected variables were tested for their influence on the quality of the study. RESULTS: Two independent blinded observers reviewed 126 studies. The overall quality was moderate to high. The most neglected parameters were power analysis, intention-to-treat, and concealment. The participation of a methodologically trained investigator increases study quality significantly. There was no difference in study quality irrespective of whether or not there was statistically significant result. CONCLUSION: Using our quality score we were able show fairly good results for recent orthopedic studies. The most frequently neglected issues in orthopedic research are blinding, power analysis, and intention-to-treat. This may distort the results of clinical investigations considerably and, especially, lack of concealment causes false-positive findings. Our data show furthermore that participation of a methodologist significantly increases quality of the study and consequently strengthens the reliability of results.

[Tissue engineering in orthopaedic surgery--clinical effectiveness and cost effectiveness of autologous chondrocyte transplantation]. / Tissue Engineering in der Orthopädischen Chirurgie--Klinischer Effekt und Kosten-Nutzen-Analyse der autologen Chondrozytentransplantation im Kurz- und Langzeitmodell.

BACKGROUND: Tissue engineering applications are spreading in orthopaedic surgery. The best known example is autologous chondrocyte transplantation (ACT). The objective of this work is to compare ACT with alternative treatment options concerning long-term effects and cost-effectiveness. MATERIAL AND METHODS: Data on clinical effectiveness, long-term effects, and cost-effectiveness are systematically reviewed. Due to the high clinical and statistical heterogeneity between studies a descriptive analysis has been done. RESULTS: 6 randomised controlled studies have assessed the effectiveness of ACT compared with microfrature or mosaic plasty. 4 studies report on no or only insignificant differences - one recently presented 5-year results - whereas 2 studies observed better results with ACT. Long-term results are good throughout, but the high quality of the regenerative tissue is a clear advantage of ACT. Cost-effectiveness models support ACT for the longevity of its results and thus relatively lower costs in the long-term. CONCLUSION: ACT is an expensive and complex procedure. In direct comparison with alternative treatments ACT produces results at least as good in the short-term, and most likely better in the long-term due to the high quality repair tissue. Thus higher initial costs are compensated for with time.

[Minimally invasive hip replacement--a meta-analysis]. / Der minimalinvasive Hüftersatz - eine Metaanalyse.

AIM: A systematic review of randomized controlled trials reporting on the comparison of minimally invasive THA and standard incision technique. METHOD: An online search in Medline, CINAHL,EMBASE, and the Cochrane Controlled Trials Register was performed. Data concerning the endpoints duration of procedure, blood loss,complications, and Harris Hip Score (HHS) were extracted and pooled using a random effects model. RESULTS: 8 Studies observing a total of 917 patients(481 MIS, 436 Std.) were included. The weighted mean difference in duration of the procedures was 4 min, which is not significant(p = 0.21). There was significantly less blood loss in the mini group (p < 0.001). The difference in increases in HHS of averagely 4.14 pts. was only borderline significant (p = 0.06). The complication odds ratio showed no significance (p = 0.71). CONCLUSION: There is only a marginal difference between these techniques. The minimally invasive total hip replacement is a variance of the standard procedure with better cosmesis. Differences in postoperative rehabilitation, however,are not within the scope of this study.