Monteggia fractures: analysis of patient-reported outcome measurements in correlation with ulnar fracture localization.

BACKGROUND: Monteggia fractures and Monteggia-like lesions result after severe trauma and have high complication rates. Preliminary biomechanical studies suggested a correlation between ulnar fracture localization and clinical result. OBJECTIVES: Key objective was to evaluate whether the site of the ulnar fracture can be correlated to clinical outcome after open reduction and internal stabilization. METHODS: In a retrospective, monocentric study 35 patients who underwent surgical treatment after suffering a Monteggia injury or Monteggia-like lesion were included. Fractures were classified according to Bado and Jupiter, the site of the fracture location at the proximal ulna and regarding the potential accompanying ligamentary injury. In a follow-up examination validated patient-reported outcome measures and functional parameters were evaluated. Furthermore, treatment strategy and complications were analysed. RESULTS: Mean patient age was 51.9 years (± 18.0). 69% were females (n = 24). Follow-up took place after 50.5 months (± 22.1). Fractures were classified according to Bado (I:2, II:27, III:4, IV:2). Bado II-fractures were further classified according to Jupiter (A:7, B:16, C:3, D:1). Cases were divided into subgroups depending upon the distance of the ulnar fracture site in respect to its distal endpoint (A: < 7 cm and B: > 7 cm). Average overall MEPS was 84.1 (± 19.0). Oxford elbow score and DASH were 37.2 (± 10.5) and 20.4 (± 20.5). Average extension capability reached - 7° (± 7.5). Mean flexion was 134.8° (± 19.7). Average pain according to visual analogue scale was 1.6 (± 1.9). We found no differences between the subgroups regarding the PROMs. Subgroup A displayed a worse extension capability (p = 0.027) and patients were significantly older (p < 0.01). Comparing patients with and without fracture of the radial head, we observed no differences. Patients with an accompanying injury of the coronoid process displayed higher pain levels (p = 0.011), a worse functionality (p = 0.027) and overall lower scoring in PROM. CONCLUSION: The presented results suggest that in Monteggia fractures and Monteggia-like lesions, the localization of the ulna fracture can give a hint for its postoperative outcome. However, we could not confirm the hypothesis of an increasing instability in ulnar fractures located further distally (high severity of the potential ligamentous injury). Intraarticular fractures or injuries with a close relation to the joint have a worse prognosis, especially if the coronoid process is injured. Trial registration Registration was done with ClinicalTrials.gov under NCT05325268.

Cytotoxicity of drugs injected into joints in orthopaedics.

OBJECTIVES: Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro. METHODS: Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed. RESULTS: Using LA or GC, especially triamcinolone acetonide, a dilution of 1:100 resulted in only a moderate reduction of viability, while a dilution of 1:10 showed significantly fewer cell counts. TA and CA reduced viability significantly at a dilution of 1:2. Higher dilutions did not affect viability. Notably, HA showed no effects of cytotoxicity in all drug dilutions. CONCLUSION: The toxicity of common intra-articular injectable drugs, assessed by cell viability, is mainly dependent on the dilution of the drug being tested. LA are particularly toxic, whereas HA did not affect cell viability.Cite this article: P. Busse, C. Vater, M. Stiehler, J. Nowotny, P. Kasten, H. Bretschneider, S. B. Goodman, M. Gelinsky, S. Zwingenberger. Cytotoxicity of drugs injected into joints in orthopaedics. Bone Joint Res 2019;8:41-48. DOI: 10.1302/2046-3758.82.BJR-2018-0099.R1.

Prospective randomized controlled trial in the treatment of lateral epicondylitis with a new dynamic wrist orthosis.

BACKGROUND: In the treatment of lateral epicondylitis (LE), the role of a new dynamic wrist orthosis is unclear. PATIENTS AND METHODS: Patients suffering from a LE longer than 3 months were multicentrically and prospectively randomized into a physiotherapeutic group (PT group) and in a physiotherapy group plus wrist orthosis (PT + O group). Physiotherapy consisted of daily eccentric strengthening exercises under initial professional supervision. Inclusion criteria were a Placzek score greater than 4. Exclusion criteria were previous surgery, rheumatic arthritis, elbow instability, radicular symptoms, higher-grade extensor tendon rupture, or cervical osteoarthritis. The clinical evaluation was performed after 12 weeks and 12 months. The Patient-Rated Tennis Elbow Evaluation (PRTEE) scale, Placzek Score, the pain rating (VAS), range of motion and the Subjective Elbow Score were evaluated. RESULTS: Of the initially 61 patients, 31 were followed up after 12 weeks and 22 after 12 months. Twenty-nine patients (43%) were male, the mean age was 46, and 44 patients (66%) had the right elbow involved. At 12 weeks, there was a pain reduction on the VAS in both groups (PT + O: 6.5-3.7 [p = .001]; PT: 4.7-4.1 [p = .468]), albeit it was only significant for the PT + O group. At 12 months, reduction was significant in both groups (PT + O: 1.1 [p = .000]; PT: 1.3 [p = .000]). The painless maximum hand strength in kg improved in both groups significant after 3 and 12 months. The Placzek score was reduced from 8.25 to 3.5 [p = .001] after 12 weeks for the PT + O group and from 8.1 to 3.8 [p = .000] in the PT group, as well as after 12 months in the PT + O group to 0 [p = .000] and in the PT group to 2.0 [p = .000]. The PRTEE improved in both groups after 12 weeks (PT + O: 52.8--31.3 [p = .002]; PT: 48.6-37.6 [p = .185]) and 12 months (PT + O: 16.15 [p = .000]; PT: 16.6 [p = .000]), although the reduction at 12 weeks was not significant for the PT group. CONCLUSION: The elbow orthosis appears to accelerate the healing process with respect to the PRTEE and pain on the VAS (12 weeks follow-up), although there is an adjustment after 12 months in both groups and a significant improvement of symptoms is achieved in all endpoints.

Novel fiber-based pure chitosan scaffold for tendon augmentation: biomechanical and cell biological evaluation.

One possibility to improve the mechanical properties after tendon ruptures is augmentation with a scaffold. Based on wet spinning technology, chitosan fibres were processed to a novel pure high-grade multifilament yarn with reproducible quality. The fibres were braided to obtain a 3D tendon scaffold. The CS fibres and scaffolds were evaluated biomechanically and compared to human supraspinatus (SSP) tendons. For the cytobiological characterization, in vitro cell culture experiments with human mesenchymal stem cells (hMSC) were performed. Three types of 3D circular braided scaffolds were fabricated. Significantly, higher ultimate stress values were measured for scaffold with larger filament yarn, compared to scaffold with smaller filament yarn. During cultivation over 28 days, the cells showed in dependence of isolation method and/or donor a doubling or tripling of the cell number or even a six-fold increase on the CS scaffold, which was comparable to the control (polystyrene) or in the case of cells obtained from human biceps tendon even higher proliferation rates. After 14 days, the scaffold surface was covered homogeneously with a cell layer. In summary, the present work demonstrates that braided chitosan scaffolds constitute a straightforward approach for designing tendon analogues, maintaining important flexibility in scaffold design and providing favourable mechanical properties of the resulting construct.

Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU).

BACKGROUND: Autologous chondrocyte implantation (ACI) is an established and well-accepted procedure for the treatment of localised full-thickness cartilage defects of the knee. METHODS: The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning therapeutic consequences of primary cartilage lesions and the suitable indication for ACI. RESULTS: Based on best available scientific evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than three to four square centimetres; in the case of young and active sports patients at 2.5cm(2), while advanced degenerative joint disease needs to be considered as the most important contraindication. CONCLUSION: The present review gives a concise overview on important scientific background and the results of clinical studies and discusses the advantages and disadvantages of ACI. LEVEL OF EVIDENCE: Non-systematic Review.

Feasibility of an exercise programme in elderly patients undergoing allogeneic stem cell transplantation - a pilot study.

It has been demonstrated that physical exercise benefits younger patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). We designed a prospective pilot study investigating whether elderly patients (>60 years) would also be able to participate in such a programme. It consisted of physiotherapist-supervised alternating endurance and resistance workouts on 6 of 7 days a week. Sixteen consecutive patients undergoing allo-HSCT were enrolled into the study. The median age was 64.5 years. Twelve patients participated in the programme until the time of discharge (75%) from the transplant unit. Therefore, the predefined criteria regarding feasibility were met. The reason for drop out was transplantation associated mortality in all patients (n = 4). Adherence was very good with a median of 85% attended training sessions. No adverse events were recorded. The endurance capacity dropped by 7% and lower extremity strength improved by 2% over time. Quality of life decreased during the study period, with global health being significantly worse at the time of discharge. In conclusion, a combined and intensified strength and endurance exercise programme is feasible and safe in a population of elderly patients undergoing allo-HSCT. Further research should focus on exploring effect sizes of such an intervention by conducting randomised controlled trials.

Can reverse shoulder arthroplasty in post-traumatic revision surgery restore the ability to perform activities of daily living?

BACKGROUND: Failed shoulder arthroplasty and failed internal fixation in fractures of the proximal humerus can benefit from implantation of a reverse total shoulder arthroplasty (RSA). While there is some evidence that RSA can improve function regarding range of motion (ROM), pain, satisfaction, and strength, there is sparse data how this translates into activities of daily living (ADLs). A marker-based 3D video motion analysis system has recently been designed that can measure changes of ROM in dynamic movements in every plane. The hypothesis was that a gain of maximum ROM also translates into the ability to perform ADLs and into a significant increase of ROM in ADLs. MATERIALS AND METHODS: Six consecutive patients (5 women, 1 man; 2× failed arthroplasty, 4× failed open reduction and internal fixation) who received RSA were examined the day before and 1 year after shoulder replacement. A 3D motion analysis system using a novel upper extremity model measured active maximum values and ROM in four ADLs. RESULTS: Comparing the pre- to the 1-year postoperative status, RSA resulted in a significant increase in mean maximum values for active flexion (humerus to thorax) of 37° (S.D. ±23°), from 50 to 87° [P=0.005], and for active abduction averaging of 17° (S.D. ±13°), from 52 to 69° [P=0.027]. The extension decreased significantly by about 8° (S.D. ±16°), from a mean of 39 to 31° [P=0.009]. For active adduction and internal and external rotation, there were trends for improvements, but no significant changes. Only three additional tasks of the ADL (out of 13/24 preoperatively) could be performed after revision surgery. Comparing the preoperative to the postoperative ROM in the ADLs in flexion/extension, ROM improved significantly in one ("tying an apron") of four ADLs. There were no significant changes in the abduction/adduction and internal/external rotation in any ADLs. CONCLUSION: RSA in revision cases significantly improved maximum active flexion and abduction, but decreased extension in this series. However, the patients were only able to use this greater ROM to their benefit in one of four ADLs.

Comparative study of elbow disorders in young high-performance gymnasts.

The study aimed to investigate the prognosis of osteochondral affection (e.g., osteochondritis dissecans (OCD), cartilage lesions, fractures and bone edema in the elbows of high-performance gymnasts (n=30) compared to prognosis results with athletes not undergoing excessive stress on the upper extremity (n=29). The study also tested a novel isotropic 3D-FSE-sequence (CUBE) technique as an early diagnostic modality. Standard protocol was used to conduct the MRI examinations, which were then compared to results from the CUBE - sequence. The gymnast group (p=0.012) presented a significantly higher prevalence of complaints in the elbow joint compared to the other athlete group. Furthermore, osteochondral lesions in MRIs appeared more frequently in the group of gymnasts (n=10, 33%, p=0.033), including 7 cases (23%) of OCD. In the control athlete group 2 asymptomatic cases of OCD and one case of bone edema were detected. The MRI investigation with the CUBE - sequence showed similar results as the standard MRI protocol in terms of the diagnosis sensitivity. The current study indicates that juvenile gymnasts are at a higher risk for osteochondral lesions of the elbow than athletes without excessive stress on the upper extremities.

[Scapulothoracic dysbalance in overhead athletes. Causes and therapy strategies]. / Skapulothorakale Dysbalancen bei Überkopfsportlern. Ursachen und Therapiestrategien.

BACKGROUND: A key element for movement of the arm is the position and motion of the scapula. A stable basis for efficient arm function is only possible if the scapula makes three dimensional movements coordinated with the upper arm. AIM: This article presents a discussion of causes, diagnosis and therapy options for scapular dyskinesis. MATERIAL AND METHODS: The article is based on a literature search in the PubMed database and taking own experience into account. RESULTS: Soft tissue and bony injuries, muscle insufficiency and dysbalance can alter the position and function of the scapula. This pathological position and motion is called scapular dyskinesis. This clinically presents as a prominent medial border and malrotation (lacking external rotation and posterior tilt) of the scapula when raising the arm. The clinical examination includes a visual inspection followed by clinical tests of the scapula at rest and during movement. Specific exercises of the musculature surrounding the scapula and specific techniques for schooling the senses for positioning and movement can harmonize the sequence of movements and restore the dynamic scapular stability. CONCLUSION: A conservative stepwise and stage-adapted exercise program can be used to treat scapular dyskinesis with good results.

Prevalence of low back pain in adolescent athletes - an epidemiological investigation.

Low back pain (LBP) is a common symptom in the populations of western countries, and adolescent athletes seem to be prone to LBP. The main objective of this study was to analyze the point (LBP within the last 48 h), 1-year (LBP within the last 12 months) and lifetime (LBP within the entire life) prevalence rates of LBP in adolescent athletes participating in various sports. We also assessed the characteristics of LBP and its association with potential risk factors. To this end, 272 competitive adolescent athletes involved in 31 different sports (158 males, 113 females, 15.4 ± 2.0 years, body mass index [BMI] 20.3 ± 2.4 kg/m(2)) were enrolled in a 10-month prospective clinical trial that included a questionnaire and physical examination. We found a point prevalence of 14%, a 1-year prevalence of 57%, and a lifetime prevalence of 66% for LBP. The mean age of first appearance of LBP was 13.1 ± 2.0 years. The lifetime prevalence was significantly higher in volleyball than in biathletes (74.3 vs. 45.7%, p = 0.015). Our findings confirm that LBP is a common symptom in adolescent athletes; LBP prevalence correlates with sports participation and individual competitive level. Adolescent athletes with LBP should receive a thorough diagnostic work-up and adapt training and technique correspondingly when indicated.

[Post-treatment rehabilitation after autologous chondrocyte implantation: State of the art and recommendations of the Clinical Tissue Regeneration Study Group of the German Society for Accident Surgery and the German Society for Orthopedics and Orthopedic Surgery]. / Nachbehandlung bei der autologen Chondrozytentransplantation: Eine Bestandsaufnahme und Empfehlung der AG Klinische Geweberegeneration der DGU/DGOOC.

BACKGROUND: Over the course of the past two decades autologous chondrocyte implantation (ACI) has become an important surgical technique for treating large cartilage defects. The original method using a periostal flap has been improved by using cell-seeded scaffolds for implantation, the matrix-based autologous chondrocyte implantation (mb-ACI) procedure. MATERIAL AND METHODS: Uniform nationwide guidelines for post-ACI rehabilitation do not exist. A survey was conducted among the members of the clinical tissue regeneration study group concerning the current rehabilitation protocols and the members of the study group published recommendations for postoperative rehabilitation and treatment after ACI based on the results of this survey. RESULTS: There was agreement on fundamentals concerning a location-specific rehabilitation protocol (femoral condyle vs. patellofemoral joint). With regard to weight bearing and range of motion a variety of different protocols exist. Similar to this total agreement on the role of magnetic resonance imaging (MRI) for postsurgical care was found but again a great variety of different protocols exist. CONCLUSIONS: This manuscript summarizes the recommendations of the members of the German clinical tissue regeneration study group on postsurgical rehabilitation and MRI assessment after ACI (level IVb/EBM).

[Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group "Tissue Regeneration" of the German Society of Orthopaedic Surgery and Traumatology (DGOU)]. / Stellenwert der autologen Chondrozytentransplantation (ACT) in der Behandlung von Knorpelschäden des Kniegelenks - Empfehlungen der AG Klinische Geweberegeneration der DGOU.

Autologous chondrocyte transplantation/implantation (ACT/ACI) is an established and recognised procedure for the treatment of localised full-thickness cartilage defects of the knee. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning potential consequences of primary cartilage lesions and the suitable indication for ACI. Based on current evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than 3-4 cm2; in the case of young and active sports patients at 2.5 cm2. Advanced degenerative joint disease is the single most important contraindication. The review gives a concise overview on important scientific background, the results of clinical studies and discusses advantages and disadvantages of ACI.

Comparison of platelet-rich plasma and VEGF-transfected mesenchymal stem cells on vascularization and bone formation in a critical-size bone defect.

Both platelet-rich plasma (PRP) and vascular endothelial growth factor (VEGF) can promote regeneration. The aim of this study was to compare the effects of these two elements on bone formation and vascularization in combination with bone marrow stromal cells (BMSC) in a critical-size bone defect in rabbits. The critical-size defects of the radius were filled with: (1) a calcium-deficient hydroxyapatite (CDHA) scaffold + phVEGF(165)-transfected BMSC (VEGF group), (2) CDHA and PRP, or (3) CDHA, autogenous BMSC, and PRP. As controls served: (4) the CDHA scaffold alone and (5) the CDHA scaffold and autogenous BMSC. The volume of new bone was measured by means of micro-CT scans, and vascularization was assessed in histology after 16 weeks. Bone formation was higher in the PRP + CDHA, BMSC + CDHA, and PRP + BMSC + CDHA groups than in the VEGF group (p < 0.05). VEGF transfection significantly promoted vascularization of the scaffolds in contrast to BMSC and PRP (p < 0.05), but was similar to the result of the CDHA + PRP + BMSC group. The results show that VEGF-transfected BMSC as well as the combination of PRP and BMSC improve vascularization, but bone healing was better with the combination of BMSC and PRP than with VEGF-transfected BMSC. Expression of VEGF in BMSC as a single growth factor does not seem to be as effective for bone formation as expanded BMSC alone or PRP which contains a mixture of growth factors.

Pressurisation leads to better cement penetration into the glenoid bone: a cadaveric study.

The aim of this study was to compare a third-generation cementing procedure for glenoid components with a new technique for cement pressurisation. In 20 pairs of scapulae, 20 keeled and 20 pegged glenoid components were implanted using either a third-generation cementing technique (group 1) or a new pressuriser (group 2). Cement penetration was measured by three-dimensional (3D) analysis of micro-CT scans. The mean 3D depth of penetration of the cement was significantly greater in group 2 (p < 0.001). The mean thickness of the cement mantle for keeled glenoids was 2.50 mm (2.0 to 3.3) in group 1 and 5.18 mm (4.4 to 6.1) in group 2, and for pegged glenoids it was 1.72 mm (0.9 to 2.3) in group 1 and 5.63 mm (3.6 to 6.4) in group 2. A cement mantle < 2 mm was detected less frequently in group 2 (p < 0.001). Using the cement pressuriser the proportion of cement mantles < 2 mm was significantly reduced compared with the third-generation cementing technique.

Prediction of in vivo bone forming potency of bone marrow-derived human mesenchymal stem cells.

Human mesenchymal stem cells (MSC) have attracted much attention for tissue regeneration including repair of non-healing bone defects. Heterogeneity of MSC cultures and considerable donor variability however, still preclude standardised production of MSC and point on functional deficits for some human MSC populations. We aimed to identify functional correlates of donor-dependency of bone formation in order to develop a potency assay predicting the therapeutic capacity of human MSC before clinical transplantation. MSC from 29 donors were characterised in vitro and results were correlated to bone formation potency in a beta-tricalcium-phosphate (ß-TCP)-scaffold after subcutaneous implantation into immunocompromised mice. In contrast to osteogenic in vitro differentiation parameters, a doubling time below 43.23 hours allowed to predict ectopic bone formation at high sensitivity (81.8%) and specificity (100%). Enriched conditions adapted from embryonic stem cell expansion rescued bone formation of inferior MSC populations while growth arrest of potent MSC by mitomycin C abolished bone formation, establishing a causal relationship between neo-bone formation and growth. Gene expression profiling confirmed a key role for proliferation status for the bone forming ability suggesting that a rate limiting anabolism and open chromatin determined and predicted the therapeutic potency of culture-expanded MSC. Proliferation-based potency testing and switch to enriched expansion conditions may pave the way for standardised production of MSC for bone repair.

Mid-term survivorship analysis of a shoulder replacement with a keeled glenoid and a modern cementing technique.

We have investigated the mid-term outcome of total shoulder replacement using a keeled cemented glenoid component and a modern cementing technique with regard to the causes of failure and loosening of the components. Between 1997 and 2003 we performed 96 total shoulder replacements on 88 patients, 24 men and 64 women with a mean age of 69.7 years (31 to 82). The minimum follow-up was five years and at the time of review 87 shoulders (77 patients) were examined at a mean follow-up of 89.1 months (60 to 127). Cumulative survival curves were generated with re-operations (accomplished and planned), survivorship of the proshesis, loosening of the glenoid (defined as tilt > 5 degrees or subsidence > 5 mm), the presence of radiolucent lines and a Constant score of < 30 as the endpoints. There were two re-operations not involving revision of the implants and the survival rate of the prosthesis was 100.0% for the follow-up period, with an absolute Constant score of > 30 as the endpoint the survival rate was 98%. Radiological glenoid loosening was 9% after five years, and 33% after nine years. There was an incidence of 8% of radiolucent lines in more than three of six zones in the immediate post-operative period, of 37.0% after the first year which increased to 87.0% after nine years. There was no correlation between the score of Boileau and the total Constant score at the latest follow-up, but there was correlation between glenoid loosening and pain (p = 0.001). We found that total shoulder replacement had an excellent mid-term survivorship and clinical outcome. The surgical and cementing techniques were related to the decrease in radiolucent lines around the glenoid compared with earlier studies. One concern, however, was the fact that radiolucent lines increased over time and there was a rate of glenoid loosening of 9% after five years and 33% after nine years. This suggests that the design of the glenoid component, and the implantation and cementing techniques may need further improvement.

[Novel software-based and validated evaluation method for objective quantification of bone regeneration in experimental bone defects]. / Eine neue objektivierte und validierte Methode zur Quantifizierung der Knochenneubildung in Tiermodellen auf Basis eines frei verfügbaren Bildbearbeitungsprogramms.

AIM: The quantification of newly formed bone in experimental defect models is a problem in various experimental set-ups. Several methods have been described to evaluate and quantify the regeneration of newly formed bone in various animal models. Most methods only describe the amount of regenerated tissue on a semi-quantitative level, the results significantly depend on the subjective rating of the observer and such evaluation methods have not been validated in terms of objectivity and reliability. The aim of the present study was to introduce a novel evaluation method for the accurate quantification of bone regeneration on digital X-ray images using a freely available digital image software analysis programme (GIMP, GNU General Public Licence). METHODS: The method introduced here contains 5 steps: standardisation of size and colour, determination of range of interest (ROI), defining different qualities of mineralisation, pixel analysis with histogram function, similar to the Hondsfield index, and quantification. In order to evaluate the objectivity and reliability, the quantification method was compared to semi-quantitative scores described by Mosheiff and Werntz for inter- and intraobserver variability. Six observers were asked to determine bone regeneration in 16 X-ray images of 2 different animal models. In order to describe intraobserver variability, the evaluation was repeated after a period of 4 weeks. Statistical analysis including determination of intra- and interobserver variability (Bland-Altman coefficient of reproduction) was performed using SAS software. RESULTS: For both experimental set-ups analysed in this project (rabbit and sheep bone defects), the objectivity was significantly higher in the GIMP-based evaluation compared to the evaluation according to Mosheiff and Werntz using the Bland-Altman coefficient (rabbit: GIMP: 0.095, Mosheiff: 0.272, Werntz: 0.283; sheep: GIMP: 0.098, Mosheiff: 0.658, Werntz: 0.668). Analogous results were obtained for reliability (rabbit: GIMP: 0.086, Mosheiff: 0.221, Werntz: 0.385; sheep: GIMP: 0.102, Mosheiff: 0.339, Werntz: 0.623). CONCLUSION: This quantification method introduced here has proved to be a reliable and "easy-to-use" tool in order to perform objective quantification of bone regeneration in 2 different experimental set-ups. It offers a more detailed and quantitative way for precise determination of regenerated tissue and is characterised by higher objectivity and reliability compared to other semi-quantitative evaluation methods. The objectivity seems to be independent of the animal model to which the method is applied.

[Perspectives of clinical stem cell therapy in the treatment of musculoskeletal diseases in Germany]. / Perspektiven klinischer mesenchymaler Stammzelltherapie bei muskuloskeletalen Erkrankungen in Deutschland.

AIM: The treatment of large bone defects remains a challenge for the orthopaedic surgeon. Regenerative therapies with the use of mesenchymal stem cells (MSC) may provide an alternative to autogenous bone transplantation, callus distraction or the use of allografts. MATERIAL AND METHODS: On the occasion of an expert workshop of the German Society for Orthopaedic and Trauma Surgery, a literature search regarding studies with the use of MSC was performed to evaluate its potential for future clinical studies. Furthermore, the legislative requirements were examined. RESULTS: Various in vitro and animal studies showed the benefit of MSC in bone regeneration. However, there are sparse data from clinical studies. Due to recent legislative changes there are several regulatory demands to meet if clinical studies are performed with MSC. CONCLUSIONS: For further evaluation of the role of MSC in the treatment of bone defects there is a need for clinical trials. The current paper provides some assistance for the successful application for clinical trials with MSC. Planning and performance of these studies may require early consultation with the regulatory authorities and cooperation of research centres in order to obtain authorisation for the evaluation of MSC. Preclinical data have to be obtained according to good laboratory practice with equivalent protocols that will be used in the clinical trials. In the latter the implementation of the guidelines for good clinical practice are mandatory.

Transplantation of human mesenchymal stem cells in a non-autogenous setting for bone regeneration in a rabbit critical-size defect model.

Human mesenchymal stem cells (hMSC) represent an attractive cell population for tissue engineering purposes. Furthermore, hMSC are described as immune privileged, and non-autogenous application seems possible. The current study examines the regeneration potential of hMSC after xenogenic transplantation compared with autogenous rabbit MSC in a critical-size bone defect. After isolation, hMSC and rabbit MSC were seeded on calcium-deficient hydroxyapatite (CDHA) and transplanted into a radial critical-size defect of New Zealand white rabbits. Defects were filled with a CDHA scaffold seeded with autogenous rabbit MSC, CDHA seeded with xenogenic hMSC or unseeded CDHA. An empty defect served as control group. Animals were sacrificed after 3 months. Evaluation was performed using radiography, micro-computed tomography (micro-CT) and histology. In addition, a non-destructive four-point-bending test was performed in order to evaluate biomechanical stiffness. While autogenous MSC seeded on CDHA led to increased healing of critical-size bone defects from radiological (micro-CT; p = 0.009) and histological (p = 0.048) perspectives compared with unloaded CDHA, it was not possible to demonstrate analogous effects for the xenogenic transplantation of hMSC. The xenogenic treatment group displayed inferior results in all parameters compared with the autogenous MSC treatment group (histology p = 0.041; micro-CT p = 0.006; biomechanical testing p = 0.017). Nevertheless, no local or systemic inflammatory response resulting from xenogenic transplantation was observed. While previous papers suggest the use of non-autogenous hMSC cells for tissue engineering purposes, the present results show inferior clinical results from transplantation of hMSC in a xenogenic setting compared with autogenous MSC.

Humeral head resurfacing for fixed anterior glenohumeral dislocation.

The purpose of this prospective study was to describe cementless humeral surface replacement arthroplasty (CHSRA) as a bone preserving treatment option for patients with fixed anterior glenohumeral dislocation. Ten patients with post-traumatic fixed anterior glenohumeral dislocation underwent CHSRA with a mean follow-up of 24 months. All patients were evaluated clinically using the Constant score and with radiographs in two planes. There were two reoperations: one patient developed glenoid erosion and was revised and in another case redislocation occurred. Clinical or radiographical signs of implant loosening were not found. The humeral head centred in the glenoid in nine out of ten cases radiographically. The Constant score increased from 20 points preoperatively to 61 points postoperatively (p < 0.007). CHSRA is a viable treatment option for elderly patients with fixed anterior glenohumeral dislocation and bone defects of the humeral head. Good clinical results and a moderate complication rate were found in the short term.