Functional results after oncological scapula resections.

INTRODUCTION: Tumors of the scapula are rare representing only 1.6%-2.8% of all skeletal tumor localizations. Wide resection of these tumors is often necessary, and their anatomic location is the most decisive factor for the extent of the resection. Because of the importance of the shoulder girdle for all daily activities, such resections can have major functional consequences. However, only few reports with small numbers of cases are found in the literature. PATIENTS AND METHODS: We retrospectively evaluated 31 consecutive patients with scapular tumors treated surgically for aggressive benign or malignant tumors of the scapula. Patients who had received curettage only were excluded. Four of these 31 patients were lost to follow-up. In 7 of the remaining 27 patients, a total scapulectomy had to be performed, whereas all others received a partial resection. In 1 case, a partial resection and replantation after irradiation was performed. Musculoskeletal Tumor Society Scoring System (MSTS) and Toronto Extremity Salvage Score (TESS) scores were evaluated postoperatively at the time of their follow-up. RESULTS: In 16 men and 11 women, the median age was 46.2 years and the tumor entities were heterogeneous. The median follow-up time was 71 months. Three patients died during follow-up due to their tumor and 1 due to cardiac disease. We found significantly better functional results in the group with incomplete scapula resections as opposed to the scapulectomy group. We did not see a significant functional difference between the patients with benign and those with malignant lesions. Both the MSTS score with median 83.3% (range between 23% and 100%) and the TESS score with 81.6% (ranging from 20.4% to 100%) were at a satisfactory level. The preservation of the supraspinatus muscle was shown to be advantageous for better shoulder function, and younger patients also tended to have better postoperative results. CONCLUSION: The resection of scapular tumors may lead to a significant functional disability of the shoulder girdle and the affected arm in many cases. However, this is represented neither in the MSTS or TESS score nor in the overall acceptance of the patients. Only 1 patient, an artisan, had to change his job. In total, the clinical results are quite good in short- and long-term follow-up. The score results were comparable to other studies.

Osteogenic Differentiation of Human Adipose-Derived Stem Cells Seeded on a Biomimetic Spongiosa-like Scaffold: Bone Morphogenetic Protein-2 Delivery by Overexpressing Fascia.

Human adipose-derived stem cells (hADSCs) have the capacity for osteogenic differentiation and, in combination with suitable biomaterials and growth factors, the regeneration of bone defects. In order to differentiate hADSCs into the osteogenic lineage, bone morphogenetic proteins (BMPs) have been proven to be highly effective, especially when expressed locally by route of gene transfer, providing a constant stimulus over an extended period of time. However, the creation of genetically modified hADSCs is laborious and time-consuming, which hinders clinical translation of the approach. Instead, expedited single-surgery gene therapy strategies must be developed. Therefore, in an in vitro experiment, we evaluated a novel growth factor delivery system, comprising adenoviral BMP-2 transduced fascia tissue in terms of BMP-2 release kinetics and osteogenic effects, on hADSCs seeded on an innovative biomimetic spongiosa-like scaffold. As compared to direct BMP-2 transduction of hADSCs or addition of recombinant BMP-2, overexpressing fascia provided a more uniform, constant level of BMP-2 over 30 days. Despite considerably higher BMP-2 peak levels in the comparison groups, delivery by overexpressing fascia led to a strong osteogenic response of hADSCs. The use of BMP-2 transduced fascia in combination with hADSCs may evolve into an expedited single-surgery gene transfer approach to bone repair.

Impact of femoro-tibial size combinations and TKA design on kinematics.

INTRODUCTION: The variability in patients' femoral and tibial anatomy requires to use different tibia component sizes with the same femoral component size. These size combinations are allowed by manufacturers, but the clinical impact remains unclear. Therefore, the goals of our study were to investigate whether combining different sizes has an impact on the kinematics for two well-established knee systems and to compare these systems' kinematics to the native kinematics. MATERIALS AND METHODS: Six fresh frozen knee specimens were tested in a force controlled knee rig before and after implantation of a cruciate retaining (CR) and a posterior-stabilized (PS) implant. Femoro-tibial kinematics were recorded using a ultrasonic-based motion analysis system while performing a loaded squat from 30° to 130°. In each knee, the original best fit inlay was then replaced by different inlays simulating a smaller or bigger tibia component. The kinematics obtained with the simulated sizes were compared to the original inlay kinematics using descriptive statistics. RESULTS: For all size combinations, the difference to the original kinematics reached an average of 1.3 ± 3.3 mm in translation and - 0.1 ± 1.2° in rotation with the CR implant. With the PS implant, the average differences reached 0.4 ± 2.7 mm and  - 0.2 ± 0.8°. Among all knees, no size combination consistently resulted in significantly different kinematics. Each knee showed a singular kinematic pattern. For both knee systems, the rotation was smaller than in the native knee, but the direction of the rotation was preserved. The PS showed more rollback and the CR less rollback than the native knee. CONCLUSION: TKA systems designed with a constant tibio-femoral congruency among size combinations should enable to combine different sizes without having substantial impact on the kinematics. The rotational pattern was preserved by both TKA systems, while the rollback could only be maintained by the PS design.

Osteoinduction within adipose tissue fragments by heterodimeric bone morphogenetic Proteins-2/6 and -2/7 versus homodimeric bone morphogenetic protein-2: Therapeutic implications for bone regeneration.

BACKGROUND: Fragments of subcutaneous adipose tissue that have been genetically modified to express bone morphogenetic protein-2 (BMP-2) regenerate large segmental osseous lesions in rodents. Gene-activated adipose tissue can be implanted into osseous defects without prior cell extraction and cell culture. The present study aimed to explore whether the heterodimers BMP-2/6 or BMP-2/7 exceed the osteoinductive effect of BMP-2 on adipose tissue. METHODS: In an in vitro tissue culture system, freshly harvested rat subcutaneous adipose tissue was cultivated in the presence of either BMP-2 or BMP-2/6 or BMP-2/7 at a high (200 ng/ml) and low (50 ng/ml) concentration. Gene expression analysis as well as histological and immunohistochemical methods were applied to test for osteoinduction. RESULTS: A concentration of 200 ng/ml of homodimeric BMP-2 induced osteogenic differentiation most potently, showing more calcification and a higher expression level of bone markers than both concentrations of BMP-2/6 or -2/7. A concentration of 50 ng/ml of BMP-2 was a significantly stronger osteogenic inducer than both concentrations of BMP-2/6 and the low concentration of BMP-2/7. The most potent heterodimeric driver of osteoinduction was BMP-2/7 at a high concentration, demonstrating effects similar to those of BMP-2 at a low concentration. CONCLUSIONS: Homodimeric BMP-2 evoked osteoinduction within adipose tissue more potently and at a lower concentration than heterodimeric BMP-2/6 or BMP-2/7. This result agrees well with the fact that it might be easier to translate adipose grafts activated by homodimeric BMP-2 clinically. Preclinical in vivo gene transfer studies are necessary to confirm the results of the present study.

Effects of a medical second opinion programme on patients' decision for or against knee arthroplasty and their satisfaction with the programme.

BACKGROUND: German social legislation gives patients the right to obtain a second opinion before elective surgery and defines quality criteria for reimbursement by statutory health insurances. However, the effects of second opinions before elective surgery are largely unknown. The aim of this study was to evaluate the effects of a second opinion programme in patients recommended for knee arthroplasty. METHODS: The largest statutory health insurance funds in Bavaria offered patients who had been recommended to have knee arthroplasty the opportunity to partake in a second opinion programme which consisted of an in person presentation to an experienced knee surgeon. In this cohort study, consecutive patients from this second opinion programme who signed informed consent were included from 07/10/2016 to 14/02/2020. Data were collected before and after the second opinion visit. RESULTS: A total of 141 (66%) of 215 patients who presented for a second opinion participated in the evaluation study. The second opinion physician recommended knee arthroplasty to 40% of the patients, later knee arthroplasty if the conditions worsened to 40%, and no knee arthroplasty to 20%. After receiving the second opinion 28 of 56 (41%) undecided patients preferred knee arthroplasty, 14 no knee arthroplasty, 14 remained undecided. Four of 46 patients with a preference for "arthroplasty" changed their decision to "no arthroplasty", five of 35 patients from "no arthroplasty" to "arthroplasty". The patients were more confident in their decision according to the decision confidence scale (before: 5.4 ± 3.0; after: 7.8 ± 2.5; p < 0.001). They rated their satisfaction with the second opinion programme with a mean grade of 1.35 (± 0.60) (best:1; worst:6). Logistic regression analyses showed that the recommendation of the second opinion physician for joint arthroplasty was associated with the guideline criteria radiological severity of osteoarthritis (p = 0.001) and knee-joint-specific quality of life (p = 0.041). CONCLUSION: The second opinion of an experienced knee surgeon frequently deviates from the initial recommendation for knee arthroplasty. The association of guideline criteria to the second recommendation suggests a high quality of the second opinion. From the patient perspective, the second opinion reduces uncertainties in their treatment decision.

Ceramic Coating in Cemented Primary Total Knee Arthroplasty is Not Associated With Decreased Risk of Revision due to Early Prosthetic Joint Infection.

BACKGROUND: Prosthetic joint infection (PJI) is one of the most frequent and devastating causes of short-term revision total knee arthroplasty (TKA). In vitro evidence suggests ceramic surfaces demonstrate resistance to biofilm, but the clinical effect of bearing surface modifications on the risk of PJI remains unclear. This premier registry-based study examines the influence of ceramic bearing surface coatings on the outcome in cemented primary TKA. METHODS: In total, 117,660 cemented primary TKAs in patients with primary osteoarthritis recorded in the German arthroplasty registry since 2012 were followed up for a maximum of 3 years. The primary endpoint was risk of revision for PJI on ceramic coated and uncoated cobalt-chromium-molybdenum femoral components. Propensity score matching for age, gender, obesity, diabetes mellitus, depression and Elixhauser comorbidity index, and substratification on common design twins with and without coating was performed. RESULTS: In total, 4637 TKAs (85.1% female) with a ceramic-coated femoral component were identified, 42 had been revised for PJI and 122 for other reasons at 3 years. No survival advantage due to the risk of revision for PJI could be determined for ceramic-coated components. Revision for all other reasons demonstrated a significant higher rate for TKAs with ceramic-coated components. However, the results of this were confounded by a strong prevalence (20.7% vs 0.3%) of metal sensitivity in the ceramic-coated group. CONCLUSION: No evidence of reduced risk for PJI due to ceramic-coated implants in cemented primary TKA was found. Further analysis for revision reasons other than PJI is required.

Short versus conventional stem in cementless total hip arthroplasty : An evidence-based approach with registry data of mid-term survival.

BACKGROUND: Short-stemmed total hip arthroplasty (THA) is well established and gaining popularity in Germany. The perception that short stems may predispose to primary instability in the femur has resulted in a more thorough follow-up of younger patient cohorts than the typical uncemented THA population. To address this issue, an evidence-based approach is presented for a retrospective mid-term survival analysis of a large registry-based cohort in primary cementless THA comparing short stems with a matched group of conventional stems. MATERIAL AND METHODS: Propensity score matching (PSM, see Infobox 1) was used on 131,580 primary cementless THAs fulfilling the inclusion criteria performed between November 2012 and September 2019 and the cumulative probability of revision (CPR) of short and conventional stems for any reason, for reasons excluding prosthetic joint infection (PJI), and due to PJI were compared. RESULTS: After PSM at 1:1 balanced groups of 17,526 short stems and of 17,526 conventional stems were achieved demonstrating no significant difference for CPR for any reason and for reasons excluding PJI. Matched CPR for any reason was 2.9% (95% confidence interval, CI, 2.4-3.5%) 5 years after primary THA in the short stem and 3.1% (95% CI 2.7-3.4%) in the conventional stem group. The CPR excluding PJI was 2.2% (95% CI 1.7-2.7%) vs. 2.1% (95% CI 1.8-2.4%). In contrast, the incidence of PJI was statistically significant lower for short stems. CONCLUSION: For the considered period, there was no statistically significant survival difference in uncemented THA between comparison groups but a lower incidence for PJI in short-stem THA. Further analyses of registry data are required to rule out range of indications and late mechanical failure of short stems.

Synergistic interaction of hTGF-ß3 with hBMP-6 promotes articular cartilage formation in chitosan scaffolds with hADSCs: implications for regenerative medicine.

BACKGROUND: Human TGF-ß3 has been used in many studies to induce genes coding for typical cartilage matrix components and accelerate chondrogenic differentiation, making it the standard constituent in most cultivation media used for the assessment of chondrogenesis associated with various stem cell types on carrier matrices. However, in vivo data suggests that TGF-ß3 and its other isoforms also induce endochondral and intramembranous osteogenesis in non-primate species to other mammals. Based on previously demonstrated improved articular cartilage induction by a using hTGF-ß3 and hBMP-6 together on hADSC cultures and the interaction of TGF- ß with matrix in vivo, the present study investigates the interaction of a chitosan scaffold as polyanionic polysaccharide with both growth factors. The study analyzes the difference between chondrogenic differentiation that leads to stable hyaline cartilage and the endochondral ossification route that ends in hypertrophy by extending the usual panel of investigated gene expression and stringent employment of quantitative PCR. RESULTS: By assessing the viability, proliferation, matrix formation and gene expression patterns it is shown that hTGF-ß3 + hBMP-6 promotes improved hyaline articular cartilage formation in a chitosan scaffold in which ACAN with Col2A1 and not Col1A1 nor Col10A1 where highly expressed both at a transcriptional and translational level. Inversely, hTGF-ß3 alone tended towards endochondral bone formation showing according protein and gene expression patterns. CONCLUSION: These findings demonstrate that clinical therapies should consider using hTGF-ß3 + hBMP-6 in articular cartilage regeneration therapies as the synergistic interaction of these morphogens seems to ensure and maintain proper hyaline articular cartilage matrix formation counteracting degeneration to fibrous tissue or ossification. These effects are produced by interaction of the growth factors with the polysaccharide matrix.

Varus or valgus positioning of the tibial component of a unicompartmental fixed-bearing knee arthroplasty does not increase wear.

PURPOSE: Higher revision rates were shown in varus- or valgus-positioned tibias in unicompartmental knee arthroplasty (UKA), but more than 15% of UKA prostheses are implanted with more than 5° of varus or valgus. This study aimed to analyze the wear rate in UKA when implanting the tibial component in either varus or valgus position versus a neutral placement at 90° to the tibial anatomical axis. The study hypothesized that a 5° varus or valgus positioning of the tibial plateau will generate less wear compared to a neutral alignment. METHODS: Wear was experimentally analyzed on a medial anatomical fixed-bearing unicompartmental knee prosthesis (Univation, Aesculap, Germany) in vitro with a customized, four-station, servohydraulic knee wear simulator, reproducing the walking cycle. The forces, loading and range of motion were applied as specified in the ISO 14243-1:2002, 5 million cycles were analyzed. The tibial components of the medial prostheses were inserted in a neutral position, with 5° varus, and 5° valgus (n = 3, each group). RESULTS: The wear rate decreased significantly with a 5° varus positioning (6.30 ± 1.38 mg/million cycles) and a 5° valgus positioning (4.96 ± 2.47 mg/million cycles) compared to the neutral position (12.16 ± 1.26 mg/million cycles) (p < 0.01 for the varus and the valgus position). The wear area on the inlay was slightly reduced in the varus and valgus group. CONCLUSION: A varus or valgus "malpositioning" up to 5° will not lead to an increased wear. Wear was even less because of the reduced articulating contact area between the inlay and the femur. A slight varus positioning of the tibial component (parallel to the anatomical joint line) positioning can be advocated from a point of wear. LEVEL OF EVIDENCE: Experimental study.

The effect of autologous Achilles bursal tissue implants in tendon-to-bone healing of rotator cuff tears in rats.

BACKGROUND: The aim of this study was to investigate the influence of autologous bursal tissue derived from the Achilles bursa on tendon-to-bone healing after rotator cuff tear repair in a rat model. METHODS: A total of 136 Sprague-Dawley rats were randomly assigned to either an untreated or a bursal tissue application group or biomechanical testing and histologic testing after rotator cuff repair. After separating the supraspinatus tendon close to the greater tuberosity, the tendon was reattached either unaltered or with a bursal tissue interposition sewn onto the interface. Immunohistologic analysis was performed 1 and 7 weeks after supraspinatus tendon reinsertion. Biomechanical testing of the tendon occurred 6 and 7 weeks after reinsertion. RESULTS: Immunohistologic results demonstrated a significantly higher percentage of Type II collagen (P = .04) after 1 and 7 weeks in the tendon-to-bone interface using autologous bursal tissue in comparison to control specimens. The bursa group showed a significantly higher collagen I to III quotient (P = .03) at 1 week after surgery in comparison to the 7-week postsurgery bursa groups and controls. Biomechanical assessment showed that overall tendon stiffness (P = .002) and the tendon viscoelasticity in the bursa group (P = .003) was significantly improved after 6 and 7 weeks. There was no significant difference (P = .55) in force to failure between the bursa group and the control group after 6 and 7 weeks. CONCLUSION: Autologous bursal tissue derived from the Achilles bursa and implanted to the tendon-to-bone interface after rotator cuff repair facilitates a faster healing response to re-establish the biologic and biomechanical integrity of the rotator cuff in rats.

[Influence of institutional experience on results in hip and knee total arthroplasty : An analysis from the German arthroplasty registry (EPRD)]. / Einfluss der institutionellen Erfahrung auf die Ergebnisse in Hüft- und Knietotalendoprothetik : Eine Analyse aus dem Endoprothesenregister Deutschland (EPRD).

BACKGROUND: The German Arthroplasty Registry, EPRD, has the ability to examine early factors influencing the probability of failure of total hip arthroplasty (THA) and knee arthroplasty (TKA). The study analyses the influence of the overall experience of a hospital, as well as the change in supplier on the revision rate. MATERIALS AND METHODS: A total of 164,903 cementless THA and 155,577 cemented TKA were in follow-up from 656 hospitals from 2012 to 2019. The number of arthroplasties performed per hospital per year was used as a surrogate parameter for institutional experience. This number was subdivided into 250, 251-500 and more than 500 for hip and knee per year and the overall revision rate was analysed. Additionally, the effects of the change of a major supplier of implant systems to a hospital were analysed. At least 70% of the documented implant components for each calendar quarter were used in that hospital to define the company as a major supplier. RESULTS: The overall revision rate for THA was 3.9% for hospitals with up to 250 arthroplasties per year, 3.3% for hospitals with 251-500 arthroplasties per year and 2.9% for hospitals performing over 500 surgeries per year (p < 0.0001). The revision rate for TKA was also significantly different between the three groups with 3.4, 3.3 and 2.7% (p < 0.0001). Changing the supplier of implant systems also showed a significant increase of the revision rate (p < 0.0001 for THA, p = 0.02 for TKA). CONCLUSION: The institutional experience significantly influences short-term results in terms of the revision rate of hip and knee arthroplasty. Changing the implant system even in an experienced hospital has a major impact on the early revision rate and, therefore, needs careful transition.

[Realistic preclinical finite element simulation in knee and hip replacements]. / Realitätsnahe Finite-Elemente-Simulation in der präklinischen Testung von Knie- und Hüftimplantaten.

BACKGROUND: In the process of developing an implant, computer simulation involving finite element (FE) methods allows the early identification of design-related issues, thus reducing the development process to a minimum. In addition, the FE simulation is used for selecting testing combinations in order to provide the relevant authority with proof of a "worst-case" construct scenario for the subsequent experimental fatigue test. RESULTS: Research studies with FE simulations show that implant positioning may affect mechanical loads under certain circumstances and, therefore, influence the preclinical evaluation of the prostheses. DISCUSSION: Although the FE simulation currently contributes significantly to preclinical testing, a standardization of the calculation models allowing comparability of results is lacking. Furthermore, the development of new dynamic and realistic models is necessary in order to identify complex damage modes that currently cannot be reproduced experimentally. When considering everyday clinical life in particular, models that can reproduce intraoperative kinematic changes and the resulting incorrect loads of the implant, as well as address these problems by changing the position or design of the prosthesis, are necessary and would help in future.

Osteoinduction within BMP-2 transduced muscle tissue fragments with and without a fascia layer: implications for bone tissue engineering.

Bone can be engineered in vivo by implantation of gene-activated muscle tissue fragments. This expedited approach may be further improved by use of muscle tissue with attached fascia. The aim of this in vitro study was to provide an in depth comparison of the osteogenic differentiation capacity of muscle alone and muscle with fascia after BMP-2 transduction. Skeletal muscle tissue from rats was cut into pieces with and without a fascia layer on the surface. Adenoviral BMP-2 or GFP vectors were used for transduction. Osteogenic differentiation within the tissue fragments was evaluated and compared by qRT-PCR, alizarin red S staining, histomorphometry and immunohistology. Transduction efficiency and level of transgene expression were higher for muscle with fascia than muscle alone. Transduction with BMP-2 led to a significant upregulation of bone marker genes, proteins, and calcium deposition in both groups. Interestingly, histological evaluation revealed that osteoinduction did not occur within the fascia layer itself. The upregulation of bone marker genes in muscle with fascia was significantly lower after 2 weeks but similar after 4 weeks of in vitro culture in comparison to muscle alone. The fascia layer led to higher transduction efficiency and enhanced BMP-2 expression. Despite fascia's lower capacity for osteogenic differentiation, muscle implants may benefit from the fascia layer by the improved ability to deliver BMP-2. The presented data may contribute to the development of a novel, cost-effective, single-surgery bone engineering technology and encourage the evaluation of the osteoregenerative potential of muscle with fascia in an animal model.

Accuracy of a non-invasive CT-based measuring technique for cement penetration depth in human tibial UKA.

BACKGROUND: Aseptic loosening of the tibial component remains a major cause of failure in unicompartmental knee arthroplasty (UKA) and may be related to micro-motion at the cement-bone interface due to insufficient cement penetration depth. Cement penetration is therefore taken as an indicator of solid fixation strength and primary stability. However, its non-invasive clinical assessment remains difficult in vivo as conventional x-ray is prone to distortion and CT-scans (computed tomography) are difficult to assess due to metal artifacts. The purpose of this study was to develop and validate a reliable in vivo measuring technique of cement penetration depth in human tibial UKA. METHODS: In an experimental setting, twelve UKA were implanted in fresh-frozen human cadaver knees using a minimal-invasive medial approach. Cement penetration depth was then measured via 1) virtual 3D-models based on metal artifact reduced CT-scans and 2) histological evaluation of nine serial cross-section cuts through the implant-cement-bone-interface. Subsequently, a concordance analysis between the two measuring techniques was conducted. RESULTS: The average cement penetration depth was 1) 2.20 mm (SD 0.30 mm) measured on metal artifact reduced CT-scans and 2) 2.21 mm (SD = 0.42) measured on serial cuts (p = 0.956). The mean difference between both techniques was 0.01 mm (SD 0.31 mm) and the Person correlation coefficient was r = 0.686 (p = 0.014). All differences were within the upper and lower limit of agreement. There was no evidence of any significant proportional bias between both techniques (p = 0.182). CONCLUSIONS: CT-based non-invasive measurement of cement penetration depth delivers reliable results in measuring the penetration depth in tibial UKA. Thereby, it enables clinicians and researchers to assess the cement penetration for in vivo diagnostics in the clinical setting as well as in vitro biomechanical research with subsequent application of load to failure on the implant-cement-bone-interface.

Survival and prognostic factors in conventional G1 chondrosarcoma.

BACKGROUND: Chondrosarcoma is the second most frequent malignant bone tumor. Grade I chondrosarcoma (syn.: atypical cartilaginous tumor) is classified as an intermediately and locally aggressive neoplasm and typically is treated less aggressively (i.e., by intralesional curettage). Does the data regarding local recurrence (LR) and metastatic disease justify this? METHODS: From 1982 to 2014, 37 consecutive patients with G1 chondrosarcoma had been resected or curetted. The margin was defined as R0 (wide resection) or R1 (marginal resection). All patients were followed for evidence of local recurrence or metastatic disease. Overall and recurrence-free survival were calculated, and various potentially prognostic factors were evaluated. RESULTS: In 23 patients (62%), the tumor was widely (R0) resected, whereas in 14 patients, (38%) the resection was marginal (R1). Overall survival was 97% after 5 years, 92% after 10 years, and 67% after 20 years. Five-year local recurrence-free survival was 96%. Ten-year local recurrence-free survival was 83%. Local recurrence-free survival showed a significant correlation to margin status but no correlation to location or age. None of the patients with local recurrence died during the follow-up. One patient had metastatic disease at initial presentation, and a further five patients developed metastatic disease during follow-up. Metastatic disease proofed to be a highly significant factor for survival but was not correlated to local recurrence. CONCLUSIONS: There was no significant correlation between the outcome and the primary tumor location. Marginal resection was a risk factor for LR, but there was no significant difference in the overall survival in patients with or without LR. Metastatic disease (16%) was more common than expected from the literature and a significant predictor for poor overall survival.

Aneurysmal bone cyst: results of an off label treatment with Denosumab.

BACKGROUND: The treatment of aneurysmal bone cysts (ABCs) has evolved and less invasive methods have been tried. Denosumab is a monoclonal antibody which inhibits osteoclasts. It has been shown to be effective in giant cell tumour of bone (GCT) of bone and hence promises some effect also in ABC. We report on 6 patients treated with Denosumab and compare our results to the cases already published. METHODS: Data of 6 patients with ABCs and patients whose treatment included Denosumab were retrospectively analyzed. Denosumab was used at a dose of 120 mg on days 1, 8, 15 and 29, and every 4 weeks thereafter. In some of these patients the dose was reduced at the end of the treatment. Clinical and radiological responses were evaluated. RESULTS: In 4 female and 2 male patients with a mean age of 17 years (range: 6-30 years) the lesions were located in the sacrum (2), in distal radius, distal femur, talus and pelvis. One of the sacral lesions healed after 12 months and has stayed stable for 3 years since. The second patient received 2 years of therapy with recalcification, but recurred 1 year later and is under renewed therapy. The pelvic lesion improved but recurred. This patient has a 13-years history of intermittent therapy including surgery, two pregnancies and remains in a stable situation. The lesion of the talus did not improve with Denosumab after surgery and was complicated by destruction of the ankle joint with osteoarthritis. Recurrent lesions of the distal femur and the distal radius, previously treated by curettage and bone grafting healed under Denosumab and have remained stable for 2 and 3 years, respectively. One case of severe hypercalcemia was observed in a 7-year old child 6 months after discontinuation of Denosumab. CONCLUSION: Denosumab provides a treatment option for ABCs in anatomically critical locations. Adjuvant application might reduce the rate of local recurrence. In young patients, severe rebound hypercalcemia months after discontinuation of Denosumab may occur.

TKA design-integrated trochlea groove rotation reduces patellofemoral pressure.

PURPOSE: Total knee arthroplasty (TKA) leaves 11-25% of the patients unsatisfied, and patellofemoral joint pain is one cause. This study aimed to compare the differences between kinematics and load transfer in the same knee with axial internal/external rotation of the femoral component (CoRo) versus a separate axial internal/external trochlear groove rotation (TrRo) which is included in the TKA trochlea design. METHODS: A validated weight-bearing finite element model with modifications of the TKA axial femoral component rotation (CoRo) and a modified trochlear rotation (TrRo) was calculated and analysed. RESULTS: Compared to the neutrally implanted TKA at 105° of flexion, a 6° external rotation of the trochlear groove reduced the retropatellar stress by 7%, whereas a 3° internal trochlear groove rotation increased the retropatellar stress by 7%. With femoral component rotation, the tibia inlay stress of 6.7 MPa at 60° of flexion was two times higher both with a 3° internal component rotation and a 6° external rotation. CONCLUSION: These results demonstrate in the tested TKA design that a trochlear groove rotation can reduce retropatellar stress. Additionally, during the TKA operation, the surgeon should be aware of the significant influence of axial femoral component rotation on mechanical inlay stress during flexion and of the fact that even small changes in the patellofemoral joint may influence the tibiofemoral joint. These results support that an external rotation of the femoral component should be preferred in TKA to avoid anterior knee pain. Furthermore, new developed TKA designs should integrate an externally rotated trochlea groove.

Induction of Articular Chondrogenesis by Chitosan/Hyaluronic-Acid-Based Biomimetic Matrices Using Human Adipose-Derived Stem Cells.

Cartilage repair using tissue engineering is the most advanced clinical application in regenerative medicine, yet available solutions remain unsuccessful in reconstructing native cartilage in its proprietary form and function. Previous investigations have suggested that the combination of specific bioactive elements combined with a natural polymer could generate carrier matrices that enhance activities of seeded stem cells and possibly induce the desired matrix formation. The present study sought to clarify this by assessing whether a chitosan-hyaluronic-acid-based biomimetic matrix in conjunction with adipose-derived stem cells could support articular hyaline cartilage formation in relation to a standard chitosan-based construct. By assessing cellular development, matrix formation, and key gene/protein expressions during in vitro cultivation utilizing quantitative gene and immunofluorescent assays, results showed that chitosan with hyaluronic acid provides a suitable environment that supports stem cell differentiation towards cartilage matrix producing chondrocytes. However, on the molecular gene expression level, it has become apparent that, without combinations of morphogens, in the chondrogenic medium, hyaluronic acid with chitosan has a very limited capacity to stimulate and maintain stem cells in an articular chondrogenic state, suggesting that cocktails of various growth factors are one of the key features to regenerate articular cartilage, clinically.

The effects of radiosynoviorthesis in pigmented villonodular synovitis of the knee.

INTRODUCTION: Tenosynovial giant-cell tumor also known as pigmented villonodular synovitis (PVS) is a benign but aggressive synovial proliferative disease most often affecting the knee joint. The mainstay of therapy is surgical resection. Due to a high rate of local recurrence, radiosynoviorthesis (RSO) is used as an adjuvant method in many cases. The aim of this study was to compare local recurrence (LR) rates after surgical synovectomy with and without adjuvant RSO. MATERIALS AND METHODS: From 1996 to 2014, 37 surgical interventions were performed in 32 patients with diffuse pigmented villonodular synovitis of the knee. All patients underwent open synovectomy. Adjuvant radiosynoviorthesis (RSO) was applied in 26 cases, the control group consists of 11 cases without RSO. RESULTS: 9 (24%) lesions recurred within a median of 19 months after surgery. Of those 9 recurrences, 3 (17%) were seen in primary disease, 6 (32%) in already recurring cases (n.s.). In 26 RSO treated patients 6 (23%) recurred, in 11 patients of the control group, 3 (27%) recurred (n.s.). CONCLUSIONS: RSO is effective in PVS as also shown in some smaller reports in the literature. But surgery is still the mainstay of therapy. RSO is not a method of compensating for an insufficient surgical approach, but it may reduce the high rate of LR in patients with large and even recurrent diffuse forms of the disease.

Bone morphogenetic protein-2 is a stronger inducer of osteogenesis within muscle tissue than heterodimeric bone morphogenetic protein-2/6 and -2/7: Implications for expedited gene-enhanced bone repair.

BACKGROUND: Bone morphogenetic protein (BMP)-2 gene-activated muscle tissue fragments can regenerate large bone defects in preclinical animal models. The use of tissue fragments instead of isolated cells expedites gene-enhanced tissue engineering and may increase the possibility of clinical translation. The present in vitro study investigated whether the osteoinductive effect of BMP-2 on muscle tissue fragments can be enhanced using the heterodimers BMP-2/6 or BMP-2/7. METHODS: Skeletal muscle tissue fragments from rats were cultured in vitro for up to 20 days in normal medium, osteogenic medium or osteogenic medium supplemented with either a low (50 ng/ml) or high (200 ng/ml) concentration of recombinant human BMP-2, BMP-2/6 or BMP-2/7. Osteoinduction was evaluated by a quantitative reverse transcriptase-polymerase chain reaction, Alizarin red S staining, immunohistology and histomorphometry. RESULTS: Interestingly, BMP-2 was a significantly stronger inducer of osteogenic differentiation within muscle tissue than both heterodimers. Even the low concentration of BMP-2 elicited significantly higher levels of calcium deposition, bone-specific gene expression and protein production than the high concentration of both heterodimers. At the high concentration, BMP-2/7 had a significantly stronger osteogenic effect on muscle than BMP-2/6. CONCLUSIONS: The homodimer BMP-2 induced osteoblastogenesis in muscle faster, at a lower concentration and with a higher potency than the heterodimers BMP-2/6 or BMP-2/7. The findings of this in vitro study encourage bone repair by muscle implants in combination with BMP-2 single growth factor delivery, which might be beneficial with respect to clinical translation.