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.

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.

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.

[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.

[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).

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.

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.

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.

Isotachysterol-3 and 25-hydroxyisotachysterol-3: analogs of 1,25-dihydrox vitamin D3.

Isotachysterol(3), 25-hydroxyisotachysterol(3), and isovitamin D(3) have been synthesized and tested for biological activity. Like 1,25-dihydroxyvitamin D(3), isotachysterol(3) stimulates intestinal calcium transport and bone calcium mobilization in anephric rats, whereas 25-hydroxyvitamin D(3) does not. Although isovitamin D(3) is biologically active in normal rats it is inactive in anephric rats.

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.

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.

Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice.

INTRODUCTION: Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice. METHODS: Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were transplanted subcutaneously into immunocompetent mice (n=12). Undifferentiated MSC (group A) were compared with osteogenic-induced MSC (group B). Human-specific in situ hybridization and anti-vimentin staining was used to follow MSC after transplantation. Quantitative evaluation of lymphocytes and macrophages was performed as a measure of immunologic rejection. Unloaded scaffolds served as controls (group C). Specimens were harvested at 4 and 8 weeks. RESULTS: Undifferentiated BMSC and ASC were detected in the majority of cases after xenogenic transplantation (group A, a total of 22 out of 24 cases), while osteogenic-induced MSC (group B) could be detected in only three of 24 cases. Quantification of lymphocytes and macrophages revealed significantly higher cell numbers in group B compared with group A (P<0.05). DISCUSSION: Our results suggest that undifferentiated MSC are candidates for non-autologous cell transplantation, while osteogenic-induced MSC seem to be eliminated by the host's immune system. This observation seems independent of the origin of MSC and applies to BMSC and ASC.

Instant stem cell therapy: characterization and concentration of human mesenchymal stem cells in vitro.

In regenerative medicine, there is an approach to avoid expansion of the mesenchymal stem cell (MSC) before implantation. The aim of this study was to compare methods for instant MSC therapy by use of a portable, automatic and closed system centrifuge that allows for the concentration of MSCs. The main outcome measures were the amount of MSCs per millilitre of bone marrow (BM), clusters of differentiation (CD), proliferation and differentiation capacities of the MSC. A volume reduction protocol was compared to the traditional laboratory methods of isolation using a Ficoll gradient and native BM. Fifty millilitres of BM were obtained from haematologically healthy male Caucasians (n=10, age 8 to 49 years). The number of colony forming units-fibroblast (CFU-F)/ml BM was highest in the centrifuge volume reduction protocol, followed by the native BM (not significant), the centrifuge Ficoll (p=0.042) and the manual Ficoll procedure (p=0.001). The MSC of all groups could differentiate into the mesenchymal lineages without significant differences between the groups. The CD pattern was identical for all groups: CD13+; CD 44+; CD73 +; CD90+; CD105+; HLA-A,B,C+; CD14-; CD34-; CD45-; CD271-; HLA-DR-. In a further clinical pilot study (n=5) with 297 ml BM (SD 18.6), the volume reduction protocol concentrated the MSC by a factor of 14: there were 1.08 x 10(2) MSC/ml BM (standard deviation (SD) 1.02 x 10(2)) before concentration, 14.8 x 10(2) MSC/ ml BM (SD 12.4 x 10(2)) after concentration, and on average 296 x 10(2) MSC (SD 248.9 x 10(2), range 86.4-691.5 x 10(2)) were available for MSC therapy. The volume reduction protocol of the closed centrifuge allows for the highest concentration of the MSC, and therefore, is a promising candidate for instant stem cell therapy.

Total shoulder replacement in young and middle-aged patients with glenohumeral osteoarthritis.

Our aim in this prospective study was to evaluate the outcome of total shoulder replacement in the treatment of young and middle-aged active patients with primary glenohumeral osteoarthritis. We reviewed 21 patients (21 shoulders) with a mean age of 55 years (37 to 60). The mean follow-up was seven years (5 to 9). The same anatomical, third-generation, cemented implant had been used in all patients. All the patients were evaluated radiologically and clinically using the Constant and Murley score. No patients required revision. In one a tear of the supraspinatus tendon occurred. Overall, 20 patients (95%) were either very satisfied (n = 18) or satisfied (n = 2) with the outcome. Significant differences (p < 0.0001) were found for all categories of the Constant and Murley score pre- and post-operatively. The mean Constant and Murley score increased from 24.1 points (10 to 45) to 64.5 points (39 to 93), and the relative score from 30.4% (11% to 50%) to 83% (54% to 116%). No clinical or radiological signs of loosening of the implant were seen. For young and middle-aged patients with osteoarthritis, third-generation total shoulder replacement is a viable method of treatment with a low rate of complications and excellent results in the mid-term.

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.

VEGF producing bone marrow stromal cells (BMSC) enhance vascularization and resorption of a natural coral bone substitute.

Bone graft substitutes often exhibit poor bone regeneration in large defects because of inadequate vascularization. Studies have shown that if blood supply is compromised, application of osteogenic factors alone could not induce successful healing. This study was to evaluate the effects of vascular endothelial growth factor, which combined with a coralline scaffold, on vascularization, scaffold resorption and osteogenesis in a rabbit radius critical size defect model. The scaffold was either coated with a control-plasmid DNA (group 1), coated with VEGF-plasmid DNA (group 2), loaded with mesenchymal stem cells (BMSC) transfected with control plasmid (group 3) or with both stem cells and the VEGF plasmid (group 4). X-rays were taken every 4 weeks up to week 16, when animals were euthanized. The volume of new bone was measured by mu-CT scans and blood vessels were counted after anti-CD31 staining of endothelial cells. The results from the solitary VEGF- and VEGF-transfected cells (groups 2 and 4) demonstrated significantly enhanced vascularization, osteogenesis and resorption of the carrier when compared to the control group. The highest degree of osteogenesis was found when the carrier was loaded with BMSC (group 3), whereas VEGF-transfected cells led to the highest vascularization and fastest resorption of the bone substitute. Additionally, VEGF-transfected BMSC led to a more homogenous vascularization of the defect. The results indicate that VEGF can be a helpful factor to improve healing in large bone defects, in which bone substitutes will otherwise not be vascularized and replaced by fresh bone.

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.

Systemic regulation of angiogenesis and matrix degradation in bone regeneration--distraction osteogenesis compared to rigid fracture healing.

Aim of this study was the investigation of systemic biochemical regulation mechanisms of bone regeneration by angiogenic and matrix-degrading enzymes during distraction osteogenesis compared to rigid osteotomy bone healing. Serum samples of 10 otherwise healthy patients with callus distraction for lower limb-lengthening and 10 osteotomy patients undergoing elective axis correction have been collected prospectively in a standardized time schedule before and up to 6 months after the procedure. At the end of the individual investigation period, concentrations of metalloproteinases (MMP-9, -13), tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and the angiogenic factors angiogenin and VEGF have been detected by use of commercially available enzyme immunoassays. Results have been compared to our preliminary study on proMMP-1-3. In distraction osteogenesis, significantly elevated serum concentrations compared to baseline could be detected postoperatively for proMMP-1, MMP-9, TIMP-1, angiogenin and VEGF but not for proMMP-2, proMMP-3 or TIMP-2. In patients with rigid osteotomy healing, MMP-9, TIMP-1, TIMP-2, angiogenin and VEGF were significantly increased respectively. Comparison of both patient collectives revealed significantly higher increases of serum proMMP-1, VEGF and TIMP-1 in distraction patients during the lengthening period and significantly higher serum concentrations of TIMP-2 in late fracture healing period in osteotomy patients. Serum levels of MMP-13 were below the lowest standards, and therefore quantitative analysis was not possible. Bone regeneration in distraction osteogenesis and rigid osteotomy healing is accompanied by systemic increase of matrix-degrading and angiogenic factors in a certain time course and quantity. This might reflect biochemical regulation of local bone healing in the circulation. ProMMP-1, VEGF and TIMP-1 seem to be key regulatory factors during distraction osteogenesis.

[Diagnosis of stress fractures in adolescents]. / Diagnostik von Stressfrakturen bei Jugendlichen.

Stress fractures in adults are a well described and frequently observed overuse injury with good clinical outcome. In adolescents, stress fractures are very rare and there are only few studies devoted exclusively this type of injury in patients with immature skeletal system. Prognosis of stress fractures in adolescents mainly depends on early diagnosis and early initiated therapy. The object of the present study is to describe typical clinical symptoms as well as characteristic radiological findings in adolescent patients with stress fractures. Thirty-five patients with a total of 40 stress fractures affecting bone with the growth plates still open have been included in the present study. The average duration of follow-up was 4.7 years (standard deviation +/- 2.45, with a minimum follow of 12 months). The average age at occurrence was 12 years (SD +/- 4.31). At initial presentation, pain at exposure was declared as cardinal symptom in 19 of 40 cases, while pain at rest has been described in only 9 cases. An additional swelling has been noticed in 12 cases. Nevertheless, all patients described pain as their major complain. Conventional radiography was unconspicious in 12 of 40 cases; periost hypertrophy was found in 14 cases, while in further 14 cases a fracture line could be detected in conventional radiography. In all cases, in which a magnetic resonance imaging (MRI) has been conducted, changes in signal intensity were detected (including all cases of unconspicous x-ray). Our data indicate, that especially in young sportsmen with pain at exposure of the lower extremity, even if conventional radiography does not reveal abnormalities, MRI should be conducted to detect stress fractures of the juvenile skeletal system in early stages. Only if diagnosis is made early, consistent therapy can be applied as early as needed in order to achieve good clinical results.