Effects of Delta12-prostaglandin J2 on bone regeneration and growth factor expression in rats

OBJECTIVES: Cyclopentenone prostaglandins have been shown to promote osteoblast differentiation in vitro. The aim of this study was to examine in a rat model the effects of local delivery of Delta(12)-prostaglandin J(2) (Delta(12)-PGJ(2)) on new bone formation and growth factor expression in (i) cortical defects and (ii) around titanium implants. MATERIAL AND METHODS: Standardized transcortical defects were prepared bilaterally in the femur of 28 male Wistar rats. Ten microliters of Delta(12)-PGJ(2) at 4 concentrations (10(-9), 10(-7), 10(-5) and 10(-3) mol/l) in a collagen vehicle were delivered inside a half-cylindrical titanium chamber fixed over the defect. Contralateral defects served as vehicle controls. Ten days after surgery, the amount of new bone formation in the cortical defect area was determined by histomorphometry and expression of platelet-derived growth factor (PDGF)-A and -B, insulin-like growth factor (IGF)-I/II, bone morphogenetic protein (BMP)-2 and -6 was examined by immunohistochemistry. In an additional six rats, 24 titanium implants were inserted into the femur. Five microliters of carboxymethylcellulose alone (control) or with Delta(12)-PGJ(2) (10(-5) and 10(-3) mol/l) were delivered into surgically prepared beds prior to implant installation. RESULTS: Delta(12)-PGJ(2) (10(-5) and 10(-3) mol/l) significantly enhanced new bone formation (33%, P<0.05) compared with control cortical defects. Delivery of Delta(12)-PGJ(2) at 10(-3) mol/l significantly increased PDGF-A and -B and BMP-2 and -6 protein expression (P<0.05) compared with control defects. No significant difference was found in IGF-I/II expression compared with controls. Administration of Delta(12)-PGJ(2) also significantly increased endosteal new bone formation around implants compared with controls. CONCLUSION: Local delivery of Delta(12)-PGJ(2) promoted new bone formation in the cortical defect area and around titanium implants. Enhanced expression of BMP-2 and -6 as well as PDGF-A and -B may be involved in Delta(12)-PGJ(2)-induced new bone formation.

Cyclooxygenase-2 inhibition selectively attenuates bone morphogenetic protein-6 synthesis and bone formation during guided tissue regeneration in a rat model

OBJECTIVES: Bone formation during guided tissue regeneration is a tightly regulated process involving cells, extracellular matrix and growth factors. The aims of this study were (i) to examine the expression of cyclooxygenase-2 (COX-2) during bone regeneration and (ii) the effects of selective COX-2 inhibition on osseous regeneration and growth factor expression in the rodent femur model. MATERIAL AND METHODS: A standardized transcortical defect of 5 x 1.5 mm was prepared in the femur of 12 male rats and a closed half-cylindrical titanium chamber was placed over the defect. The expression of COX-2 and of platelet-derived growth factor-B (PDGF-B), bone morphogenetic protein-6 (BMP-6) and insulin-like growth factor-I/II (IGF-I/II) was analyzed at Days 3, 7, 21 and 28 semiquantitatively by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The effects of COX-2 inhibition by intraperitoneal injection of NS-398 (3 mg/kg/day) were analyzed in five additional animals sacrificed at Day 14. RESULTS: Histomorphometry revealed that new bone formation occurred in the cortical defect area as well as in the supracortical region, i.e. region within the chamber by Day 7 and increased through Day 28. Immunohistochemical evidence of COX-2 and PDGF-B levels were observed early (i.e. Day 3) and decreased rapidly by Day 7. BMP-6 expression was maximal at Day 3 and slowly declined by Day 28. In contrast, IGF-I/II expression gradually increased during the 28-day period. Systemic administration NS-398 caused a statistically significant reduction (P<0.05) in new bone formation (25-30%) and was associated with a statistically significant reduction in BMP-6 protein and mRNA expression (50% and 65% at P<0.05 and P<0.01, respectively). PDGF-B mRNA or protein expression was not affected by NS-398 treatment. CONCLUSION: COX-2 inhibition resulted in reduced BMP-6 expression and impaired osseous regeneration suggesting an important role for COX-2-induced signaling in BMP synthesis and new bone formation.

MRI characteristics and histology of bone marrow lesions in dogs with experimentally induced osteoarthritis

Signal changes within the bone marrow adjacent to osteoarthritic joints are commonly seen on magnetic resonance (MR) images in humans and in dogs. The histological nature of these lesions is poorly known. In this study, we describe the MR imaging of bone marrow lesions adjacent to the stifle joints of dogs with experimental osteoarthritis over 13 months. Histology of the proximal tibia at the end of the study was compared with the last MR imaging findings. In five adult dogs, the left cranial cruciate ligament was transected. Post-operatively, MR imaging was performed at 1, 2, 3, 4, 6, 8, and 13 months. Dogs were euthanised after 13 months and histological specimen of the proximal tibia were evaluated. Bone marrow edema like MR imaging signal changes were seen in every MR examination of all dogs in one or more locations of the proximal tibia and the distal femur. Lesions varied in size and location throughout the whole study with the exception of constantly seen lesions in the epiphyseal and metaphyseal region at the level of the tibial eminence. On histology, hematopoiesis and myxomatous transformation of the bone marrow and/or intertrabecular fibrosis without signs of bone marrow edema were consistent findings in the areas corresponding to the MR imaging signal changes. We conclude that within the bone marrow, zones of increased signal intensity on fat suppressed MR images do not necessarily represent edema but can be due to cellular infiltration. Contrary to humans, hematopoiesis is seen in bone marrow edema-like lesions in this canine model of osteoarthritis.

Evaluation of reparative cartilage after autologous chondrocyte implantation for osteochondritis dissecans: histology, biochemistry, and MR imaging

BACKGROUND: The aim of this study was to investigate the biochemical properties, histological and immunohistochemical appearance, and magnetic resonance (MR) imaging findings of reparative cartilage after autologous chondrocyte implantation (ACI) for osteochondritis dissecans (OCD). METHODS: Six patients (mean age 20.2 +/- 8.8 years; 13-35 years) who underwent ACI for full-thickness cartilage defects of the femoral condyle were studied. One year after the procedure, a second-look arthroscopic operation was performed with biopsy of reparative tissue. The International Cartilage Repair Society (ICRS) visual histological assessment scale was used for histological assessment. Biopsied tissue was immunohistochemically analyzed with the use of monoclonal antihuman collagen type I and monoclonal antihuman collagen type II primary antibodies. Glycosaminoglycan (GAG) concentrations in biopsied reparative cartilage samples were measured by high performance liquid chromatography (HPLC). MR imaging was performed with T1- and T2-weighted imaging and three-dimensional spoiled gradient-recalled (3D-SPGR) MR imaging. RESULTS: Four tissue samples were graded as having a mixed morphology of hyaline and fibrocartilage while the other two were graded as fibrocartilage. Average ICRS scores for each criterion were (I) 1.0 +/- 1.5; (II) 1.7 +/- 0.5; (III) 0.6 +/- 1.0; (IV) 3.0 +/- 0.0; (V) 1.8 +/- 1.5; and (VI) 2.5 +/- 1.2. Average total score was 10.7 +/- 2.8. On immunohistochemical analysis, the matrix from deep and middle layers of reparative cartilage stained positive for type II collagen; however, the surface layer did not stain well. The average GAG concentration in reparative cartilage was 76.6 +/- 4.2 microg/mg whereas that in normal cartilage was 108 +/- 11.2 microg/mg. Common complications observed on 3D-SPGR MR imaging were hypertrophy of grafted periosteum, edema-like signal in bone marrow, and incomplete repair of subchondral bone at the surgical site. Clinically, patients had significant improvements in Lysholm scores. CONCLUSIONS: In spite of a good clinical course, reparative cartilage after ACI had less GAG concentration and was inferior to healthy hyaline cartilage in histological and immunohistochemical appearance and on MRI findings.

Statistical shape analysis via principal factor analysis

Statistical shape analysis techniques commonly employed in the medical imaging community, such as active shape models or active appearance models, rely on principal component analysis (PCA) to decompose shape variability into a reduced set of interpretable components. In this paper we propose principal factor analysis (PFA) as an alternative and complementary tool to PCA providing a decomposition into modes of variation that can be more easily interpretable, while still being a linear efficient technique that performs dimensionality reduction (as opposed to independent component analysis, ICA). The key difference between PFA and PCA is that PFA models covariance between variables, rather than the total variance in the data. The added value of PFA is illustrated on 2D landmark data of corpora callosa outlines. Then, a study of the 3D shape variability of the human left femur is performed. Finally, we report results on vector-valued 3D deformation fields resulting from non-rigid registration of ventricles in MRI of the brain.

Hip arthroscopy after previous surgical hip dislocation for femoroacetabular impingement

PURPOSE: The purpose of this study was to examine whether arthroscopic adhesiolysis can relieve symptoms of patients with persistent pain after open surgical hip dislocation for femoroacetabular impingement syndrome without osseous or cartilaginous alterations. METHODS: This study comprised 16 consecutive patients (6 men and 10 women; mean age, 33.5 years [range, 19 to 60 years]) with persistent pain without osseous or cartilaginous alterations after surgical hip dislocation for the treatment of femoroacetabular impingement. At index surgery, all patients had osteochondroplasty of the head-neck junction and resection of the acetabular rim with reattachment of the labrum in 9 cases. All patients had preoperative magnetic resonance imaging-arthrogram and were treated with arthroscopy of the hip. RESULTS: At arthroscopy, all reattached labra were stable. In the cases without preservation of the labrum at the index operation, the joint capsule was attached at the level of the acetabular rim and synovitis was noticed. All patients had adhesions between the neck of the femur and joint capsule or between the labrum and capsule. In 3 patients the arthroscopic procedure was technically limited by massive thickening of the capsule. Overall, 81% of patients (13/16) showed less pain or were pain-free. The Merle d'Aubigné score improved from 13 points preoperatively to 16 points at the last follow-up. CONCLUSIONS: Persistent pain after surgical dislocation of the hip without evidence of cartilaginous and osseous alterations could result from intra-articular adhesions. Hip arthroscopy after previous surgery can be demanding because of scarring. If the adhesions can be released, good results can be achieved. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Kinematic biomechanical assessment of human articular cartilage transplants in the knee using 3-T MRI: an in vivo reproducibility study

The aims of this study were to examine the clinical feasibility and reproducibility of kinematic MR imaging with respect to changes in T (2) in the femoral condyle articular cartilage. We used a flexible knee coil, which allows acquisition of data in different positions from 40 degrees flexion to full extension during MR examinations. The reproducibility of T (2) measurements was evaluated for inter-rater and inter-individual variability and determined as a coefficient of variation (CV) for each volunteer and rater. Three different volunteers were measured twice and regions of interest (ROIs) were selected by three raters at different time points. To prove the clinical feasibility of this method, 20 subjects (10 patients and 10 age- and sex-matched volunteers) were enrolled in the study. Inter-rater variability ranged from 2 to 9 and from 2 to 10% in the deep and superficial zones, respectively. Mean inter-individual variability was 7% for both zones. Different T (2) values were observed in the superficial cartilage zone of patients compared with volunteers. Since repair tissue showed a different behavior in the contact zone compared with healthy cartilage, a possible marker for improved evaluation of repair tissue quality after matrix-associated autologous chondrocyte transplantation (MACT) may be available and may allow biomechanical assessment of cartilage transplants.

Femoroacetabular impingement: radiographic diagnosis- what the radiologist should know

OBJECTIVE: The purpose of this article is to show the important radiographic criteria that indicate the two types of femoroacetabular impingement: pincer and cam impingement. In addition, potential pitfalls in pelvic imaging concerning femoroacetabular impingement are shown. CONCLUSION: Femoroacetabular impingement is a major cause for early "primary" osteoarthritis of the hip. It can easily be recognized on conventional radiographs of the pelvis and the proximal femur.

High-volume FES-cycling partially reverses bone loss in people with chronic spinal cord injury

Spinal cord injury (SCI) leads to severe bone loss in the paralysed limbs and to a resulting increased fracture risk thereof. Since long bone fractures can lead to comorbidities and a reduction in quality of life, it is important to improve bone strength in people with chronic SCI. In this prospective longitudinal cohort study, we investigated whether functional electrical stimulation (FES) induced high-volume cycle training can partially reverse the loss of bone substance in the legs after chronic complete SCI. Eleven participants with motor-sensory complete SCI (mean age 41.9+/-7.5 years; 11.0+/-7.1 years post injury) were recruited. After an initial phase of 14+/-7 weeks of FES muscle conditioning, participants performed on average 3.7+/-0.6 FES-cycling sessions per week, of 58+/-5 min each, over 12 months at each individual's highest power output. Bone and muscle parameters were investigated in the legs by means of peripheral quantitative computed tomography before the muscle conditioning (t1), and after six (t2) and 12 months (t3) of high-volume FES-cycle training. After 12 months of FES-cycling, trabecular and total bone mineral density (BMD) as well as total cross-sectional area in the distal femoral epiphysis increased significantly by 14.4+/-21.1%, 7.0+/-10.8% and 1.2+/-1.5%, respectively. Bone parameters in the femoral shaft showed small but significant decreases, with a reduction of 0.4+/-0.4% in cortical BMD, 1.8+/-3.0% in bone mineral content, and 1.5+/-2.1% in cortical thickness. These decreases mainly occurred between t1 and t2. No significant changes were found in any of the measured bone parameters in the tibia. Muscle CSA at the thigh increased significantly by 35.5+/-18.3%, while fat CSA at the shank decreased by 16.7+/-12.3%. Our results indicate that high-volume FES-cycle training leads to site-specific skeletal changes in the paralysed limbs, with an increase in bone parameters at the actively loaded distal femur but not the passively loaded tibia. Thus, we conclude that high-volume FES-induced cycle training has clinical relevance as it can partially reverse bone loss and thus may reduce fracture risk at this fracture prone site.

AN EXPERIMENTAL STUDY OF PARTIAL LOW RISK DEPLOYMENT IN A FIXED VEHICLE ENVIRONMENT

This study will look at the passenger air bag (PAB) performance in a fix vehicle environment using Partial Low Risk Deployment (PLRD) as a strategy. This development will follow test methods against actual baseline vehicle data and Federal Motor Vehicle Safety Standards 208 (FMVSS 208). FMVSS 208 states that PAB compliance in vehicle crash testing can be met using one of three deployment methods. The primary method suppresses PAB deployment, with the use of a seat weight sensor or occupant classification sensor (OCS), for three-year old and six-year old occupants including the presence of a child seat. A second method, PLRD allows deployment on all size occupants suppressing only for the presents of a child seat. A third method is Low Risk Deployment (LRD) which allows PAB deployment in all conditions, all statures including any/all child seats. This study outlines a PLRD development solution for achieving FMVSS 208 performance. The results of this study should provide an option for system implementation including opportunities for system efficiency and other considerations. The objective is to achieve performance levels similar too or incrementally better than the baseline vehicles National Crash Assessment Program (NCAP) Star rating. In addition, to define systemic flexibility where restraint features can be added or removed while improving occupant performance consistency to the baseline. A certified vehicles’ air bag system will typically remain in production until the vehicle platform is redesigned. The strategy to enable the PLRD hypothesis will be to first match the baseline out of position occupant performance (OOP) for the three and six-year old requirements. Second, improve the 35mph belted 5th percentile female NCAP star rating over the baseline vehicle. Third establish an equivalent FMVSS 208 certification for the 25mph unbelted 50th percentile male. FMVSS 208 high-speed requirement defines the federal minimum crash performance required for meeting frontal vehicle crash-test compliance. The intent of NCAP 5-Star rating is to provide the consumer with information about crash protection, beyond what is required by federal law. In this study, two vehicles segments were used for testing to compare and contrast to their baseline vehicles performance. Case Study 1 (CS1) used a cross over vehicle platform and Case Study 2 (CS2) used a small vehicle segment platform as their baselines. In each case study, the restraints systems were from different restraint supplier manufactures and each case contained that suppliers approach to PLRD. CS1 incorporated a downsized twins shaped bag, a carryover inflator, standard vents, and a strategic positioned bag diffuser to help disperse the flow of gas to improve OOP. The twin shaped bag with two segregated sections (lobes) to enabled high-speed baseline performance correlation on the HYGE Sled. CS2 used an A-Symmetric (square shape) PAB with standard size vents, including a passive vent, to obtain OOP similar to the baseline. The A-Symmetric shape bag also helped to enabled high-speed baseline performance improvements in HYGE Sled testing in CS2. The anticipated CS1 baseline vehicle-pulse-index (VPI) target was in the range of 65-67. However, actual dynamic vehicle (barrier) testing was overshadowed with the highest crash pulse from the previous tested vehicles with a VPI of 71. The result from the 35mph NCAP Barrier test was a solid 4-Star (4.7 Star) respectfully. In CS2, the vehicle HYGE Sled development VPI range, from the baseline was 61-62 respectively. Actual NCAP test produced a chest deflection result of 26mm versus the anticipated baseline target of 12mm. The initial assessment of this condition was thought to be due to the vehicles significant VPI increase to 67. A subsequent root cause investigation confirmed a data integrity issue due to the instrumentation. In an effort to establish a true vehicle test data point a second NCAP test was performed but faced similar instrumentation issues. As a result, the chest deflect hit the target of 12.1mm; however a femur load spike, similar to the baseline, now skewed the results. With noted level of performance improvement in chest deflection, the NCAP star was assessed as directional for 5-Star capable performance. With an actual rating of 3-Star due to instrumentation, using data extrapolation raised the ratings to 5-Star. In both cases, no structural changes were made to the surrogate vehicle and the results in each case matched their perspective baseline vehicle platforms. These results proved the PLRD is viable for further development and production implementation.

Extended retinacular soft-tissue flap for intra-articular hip surgery: surgical technique, indications, and results of application

Osteotomies of the proximal femur for hip joint conditions are normally done at the intertrochanteric or subtrochanteric level. Intra-articular osteotomies would be more direct and therefore allow a more powerful correction with no or very little undesired side correction. However, concerns about the risk of vascular damage and osteonecrosis of the femoral head have so far basically excluded this technique from practical use. Based on detailed knowledge of the vascular anatomy of the proximal femur, an approach to safely dislocate the femoral head has been described and successfully performed. Experience as well as further studies of femoral head perfusion allowed a substantial extension of this approach, with subperiosteal exposure of the circumference of the femoral neck with constant intraoperative control of the blood supply to the head. Using the extended retinacular soft-tissue flap, four surgical techniques (relative neck lengthening, subcapital realignment in slipped capital femoral epiphysis, true femoral neck osteotomy, and femoral head reduction osteotomy) evolved or became safer with respect to perfusion of the femoral head. The extended retinacular soft-tissue flap offers the technical and biologic possibility for a new class of intra articular procedures. Although meticulous execution of the surgical steps is important, the procedures have a high level of safety for femoral head perfusion.

Hip MRI and its implications for surgery in osteoarthritis patients

Osteoarthritis (OA) of the hip joint stems from a combination of intrinsic factors, such as joint anatomy, and extrinsic factors, such as injuries, diseases, and load. Possible risk factors for OA are instability and impingement. Different surgical techniques, such as osteotomies of the pelvis and femur, surgical dislocation, and hip arthroscopy, are being performed to delay or halt OA. Success of salvage procedures of the hip depends on the existing cartilage and joint damage before surgery. The likelihood of therapy failure rises with advanced OA. For imaging of intra-articular hip pathology, MRI represents the best technique because it enables clinicians to directly visualize cartilage, it provides superior soft tissue contrast, and it offers the prospect of multidimensional imaging. However, opinions differ on the diagnostic efficacy of MRI and on the question of which MRI technique is most appropriate. This article gives an overview of the standard MRI techniques for diagnosis of hip OA and their implications for surgery.

Radiologische Diagnose des femoroazetabuläre Impingements [Radiological diagnosis of femoroacetabular impingement]

Femoroacetabular impingements (FAI) are due to an anatomical disproportion between the proximal femur and the acetabulum which causes premature wear of the joint surfaces. An operation is often necessary in order to relieve symptoms such as limited movement and pain as well as to prevent or slow down the degenerative process. The result is dependent on the preoperative status of the joint with poor results for advanced arthritis of the hip joint. This explains the necessity for an accurate diagnosis in order to recognize early stages of damage to the joint. The diagnosis of FAI includes clinical examination, X-ray examination and magnetic resonance imaging (MRI). The standard X-radiological examination for FAI is carried out using two X-ray images, an anterior-posterior view of the pelvis and a lateral view of the proximal femur, such as the cross-table lateral or Lauenstein projections. It is necessary that positioning criteria are adhered to in order to avoid distortion artifacts. MRI permits an examination of the pelvis on three levels and should also include radial planned sequences for improved representation of peripheral structures, such as the labrum and peripheral cartilage. The use of contrast medium for a direct MR arthrogram has proved to be advantageous particularly for representation of labrum damage. The data with respect to cartilage imaging are still unclear. Further developments in technology, such as biochemical-sensitive MRI applications, will be able to improve the diagnosis of the pelvis in the near future.