Modern Radiological Postoperative Diagnostics of the Hip Joint in Children and Adults.

UNLABELLED: The assessment of bone healing and loosening of endoprosthesis material was long the primary indication for postoperative projection radiography and CT imaging of the hip joint following trauma and endoprosthesis implantation. With the increasing number of joint-preserving surgery, e. g. of surgical hip luxation and hip arthroscopy for the treatment of femoroacetabular impingement (FAI), high-resolution imaging of intra-articular pathologies before and after surgery has become increasingly important. In this review article, diagnostic imaging of the hip joint is presented following common trauma surgery and orthopedic surgery interventions. The imaging modalities of projection radiography, CT and MRI including direct MR-arthrography are discussed with regard to their diagnostic capability in the postoperative assessment of the hip joint. Among others topics, imaging is discussed following hip arthroplasty, following surgical hip luxation and arthroscopic interventions for the treatment of FAI, as well as following core decompression for avascular necrosis of the femoral head. Moreover, orthopedic interventions of the hip joint in children and adolescents are presented and the dedicated reporting of postoperative imaging is outlined. KEY POINTS: • Consolidation of osteotomies and position of implants should be assessed in postoperative imaging. • MRI is useful for confirming correct articulation after treatment of congenital hip dislocation. • Radiologically assessable complications after total hip replacement are inlay wear, loosening, dislocation, periarticular ossifications and infection. • MRI can detect and classify pseudotumours in cases of metal-metal pairing after total hip replacement.

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.

[Symptomatic bilateral soft tissue tumor of the breast wall]. / Symptomatischer bilateraler Weichteiltumor der Brustwand.

A 54-year-old woman presented with progressive swelling of the right scapula as well as motion-dependent pain. The medical history revealed a polyglandular autoimmune syndrome and lumbar disc degeneration. The magnetic resonance imaging (MRI) scan showed a bilateral well-defined muscle isointense space-occupying lesion situated between the scapula, rib cage and thoracic muscles with homogeneous contrast enhancement. The constellation is indicative of a elastofibroma dorsi, a rare mesenchymal tumor often appearing bilaterally.

Autologous capping during resection arthroplasty of the hip in patients with cerebral palsy.

In patients with severe quadriplegic cerebral palsy and painful hip dislocation proximal femoral resection arthroplasty can reduce pain, but the risk of heterotopic ossification is significant. We present a surgical technique of autologous capping of the femoral stump in order to reduce this risk, using the resected femoral head as the graft. A retrospective study of 31 patients (43 hips) who had undergone proximal femoral resection arthroplasty with (29 hips) and without autologous capping (14 hips) was undertaken. Heterotopic ossification was less frequent in patients with autologous capping, and a more predictable pattern of bony overgrowth was found. For a selected group of non-ambulatory patients with long-standing painful dislocation of the hip, we recommend femoral resection arthroplasty over more complicated reconstructive operations. The risk of heterotopic ossification, which is a major disadvantage of this operation, is reduced by autologous capping.

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.

Delayed administration of adenoviral BMP-2 vector improves the formation of bone in osseous defects.

The direct, local, administration of adenovirus carrying human BMP-2 cDNA (Ad.BMP-2) heals critical-sized femoral bone defects in rabbit and rat models. However, the outcome is suboptimal and the technology needs to provide a more reliable and uniform outcome. To this end, we investigated whether the timing of Ad.BMP-2 administration influenced the formation of mineralized tissue within the defect. Critical-sized defects were created in the femora of 28 Sprague-Dawley rats. Animals were injected intralesionally with a single, percutaneous injection of Ad.BMP-2 (4 x 10(8) plaque-forming units) either intraoperatively (day 0) or 24 h (day 1), 5 days or 10 days after surgery. The femora were evaluated 8 weeks after surgery by X-ray, microcomputed tomography, dual-energy X-ray absorptiometry and biomechanical testing. The incidence of radiological union was markedly increased when administration of Ad.BMP-2 was delayed until days 5 and 10, at which point 86% of the defects healed. These time points also provided greater bone mineral content within the defect site and improved the average mechanical strength of the healed bone. Thus, delaying the injection of Ad.BMP-2 until 5 or 10 days after surgery enables a greater percentage of critical-sized, segmental defects to achieve radiological union, producing a repair tissue with enhanced mineralization and greater mechanical strength.

Direct adenoviral transfer of bone morphogenetic protein-2 cDNA enhances fracture healing in osteoporotic sheep.

Osteoporosis, a major public health burden, is associated with increased fracture risk. Fracture healing in osteoporosis is delayed, with reduced callus formation and impaired biomechanical properties of newly formed bone leading to high risk of fixation failure. Adenoviral gene transfer of bone morphogenetic protein-2 (BMP-2) has been shown to enhance fracture healing. This study evaluated the ability of gene transfer to enhance bone healing in osteoporosis. An established sheep model of osteoporosis with well-characterized alterations in fracture healing was used. Osteotomies were created surgically in the tibias of adult female sheep and monitored for 8 weeks, using radiographic, biomechanical, and histological methods. For pilot experiments, primary ovine osteoblasts and mesenchymal stem cells were transduced with a recombinant adenovirus carrying BMP-2 cDNA (Ad.BMP-2). Large increases in alkaline phosphatase production and mineralization confirmed the ability of human BMP-2 to stimulate osteoblastic differentiation in sheep. In vivo bending stiffness measurements during fracture healing as well as ex vivo torsional stiffness measurements demonstrated stiffer callus tissue after treatment with Ad.BMP-2. The differences were found mainly in the early fracture-healing period. Computed tomography demonstrated that animals receiving the BMP-2 cDNA had larger cross-sectional callus area and higher callus density. Histological examination of the tibias confirmed enhanced callus formation. Direct, local adenoviral delivery of an osteogenic gene thus led to enhanced healing of fractures in an ovine model of osteoporosis. These promising data encourage the further development of genetic approaches to enhance bone healing in patients suffering osteoporosis-associated fractures.

Effect of BMP-2 gene transfer on bone healing in sheep.

Critical size defects of bone and delayed fracture healing due to metabolic disorders are still problems in orthopaedic surgery. Adenoviral vectors encoding bone morphogenetic protein-2 (Ad.BMP-2) have been used to stimulate bone formation in small animals. The present study evaluated the use of direct adenoviral gene transfer for inducing bone formation in a large animal. Standardized iliac crest defects were created surgically on both sides of the pelvic bone of white mountain sheep. The efficiency of gene transfer was evaluated using recombinant adenoviruses carrying the cDNA for luciferase. High levels of transgene expression, restricted to the site of injection, were found for the 1st week. Transgene expression then fell considerably, but could still be detected for up to 5 weeks. To investigate the effect on bone healing, Ad.BMP-2 (10(11) particles in 200 mul saline) was unilaterally injected into iliac crest defects and into tibial osteotomies. The contralateral defects remained untreated to evaluate possible systemic effects. The controls were treated with saline solution. Bone formation within the defect, assessed by micro-computed tomography (CT) measurement at 8 weeks, and callus formation after osteotomy were significantly reduced following direct application of Ad.BMP-2. The retardation compared to untreated control animals was additionally found at the contralateral iliac crest indicating a systemic inhibitory effect. Histological analysis confirmed the CT measurement and showed an increased number of inflammatory cells within both defects. Antibodies against the adenovirus and the transgene product were detected in all treated animals. These data show a systemic retardation of bone formation following a single local injection of Ad.BMP-2 in sheep. This finding stands in contrast to the data obtained from small animal models. Further studies are needed to determine the contribution of the immune response to these results, and whether a lower dose of Ad.BMP-2 would be advantageous.

The potential of gene therapy for fracture healing in osteoporosis.

Osteoporosis-associated fractures impair a patient's function and quality of life and represent one of the major public health burdens. Demographic changes predict a dramatic increase in osteoporotic fractures. Experimental data have shown that osteoporosis impairs fracture healing. Clinical observations demonstrate high failure rates of implant fixation in osteoporosis. The reduced healing capacity, including impaired bone formation, in osteoporotic humans might be due to defects in mesenchymal stem cells that lead to reduced proliferation and osteoblastic differentiation. Growth factors show remarkable promise as agents that can improve the healing of bone or increase the proliferation and differentiation capacities of mesenchymal stem cells. Their clinical utility is limited by delivery problems. The attraction of gene-transfer approaches is the unique ability to deliver authentically processed gene products to precise anatomical locations at therapeutic levels for sustained periods of time. Unlike the treatment of chronic diseases, it is neither necessary nor desirable for transgene expression to persist beyond the few weeks or months needed to achieve healing. This review presents different approaches of gene therapy to enhance fracture healing and summarizes the promising results of preclinical studies. It focuses on applications of this new technique to fracture healing in osteoporosis. In our opinion, these applications represent some of the few examples in which gene therapy has a good chance of early clinical success.