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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 3 - 3
11 Apr 2023
Kubo Y Fragoulis A Beckmann R Wolf M Nebelung S Wruck C Pufe T Jahr H
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Nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is key in maintaining redox homeostasis and the pathogenesis of osteoarthritis (OA) involves oxidative distress. We thus investigated whether Nrf2/ARE signaling may control expression of key chondrogenic differentiation and hyaline cartilage maintenance factor SOX9. In human C-28/I2 chondrocytes SOX9 expression was measured by RT–qPCR after shRNA-mediated knockdown of Nrf2 or its antagonist the Kelch-like erythroid cell-derived protein with cap “n” collar homology-associated protein 1 (Keap1). Putative ARE-binding sites in the proximal SOX9 promoter region were inactivated, cloned into pGL3, and co-transfected with phRL–TK for dual-luciferase assays to verify whether Nrf2 transcriptionally regulates SOX9. SOX9 promoter activity without and with Nrf2-inducer methysticin were analyzed. Sox9 expression in articular chondrocytes was correlated to cartilage thickness and degeneration in wild-type (WT) and Nrf2-knockout mice. Data were analyzed by one-way ANOVA, a Student's t-test, or Wilcoxon rank-sum test, according to the normal distribution. Statistical significance was set to p < 0.05. While Keap1-specific RNAi increased SOX9 expression, Nrf2-specific RNAi significantly decreased it. Putative ARE sites (ARE. 1. , ARE. 2. ) were identified in the SOX9 promoter region. ARE. 2. mutagenesis significantly reduced SOX9 promoter activity, while truncation of ARE. 1. did not. A functional ARE. 2. site was thus essential for methysticin-mediated induction of SOX9 promoter activity. Knee cartilage of young Nrf2-knockout mice further revealed significantly fewer Sox9-positive chondrocytes as compared to old Nrf2-knockout animals, which further showed thinner cartilage and more severe cartilage erosion. Our data suggest that SOX9 expression in articular cartilage is directly Nrf2-dependent and that pharmacological Nrf2 activation may hold potential to diminish age-dependent osteoarthritic changes in knee cartilage through improving protective SOX9 expression


Although remnant-preserved ACL reconstruction (ACLR) restores knee joint stability and dampens the problem of acute ACL rupture-induced knee pain, an increasing number of patients still develop post-traumatic osteoarthritis (PTOA) after 10 to 15 years of ACLR. We previously found that remnant-preserved ACLR with concomitant medial and lateral meniscus repair may not prevent cartilage degeneration and weaken muscle strength, while the clinical features of PTOA are not clear. We hypothesized that remnant-preserved ACLR with concomitant medial and lateral meniscus tears is related to early cartilage damage, worse function recovery, patient-reported outcomes (PROs) and delayed duration to return to sports. The aim is to evaluate the remnant-preserved ACLR with complicated meniscal injuries in predicting which patients are at higher risk of osteoarthritic changes, worse function and limited activities after ACLR for 12 months. Human ethical issue was approved by a committee from Xi'an Jiaotong University. 26 young and active patients (24 male, 2 female) with ACL injuries (Sherman type I and II) with concomitant medial and lateral meniscus within 2 months were included from January 2014 to March 2022. The average age of the ACLR+ meniscus repair was 26.77±1.52 (8 right, 5 left) and isolated ACLR control was 31.92±2.61 years old (7 left, 6 right). Remnant-preserved ACLR with a 5- to 6-strand hamstring tendon graft was operated on by the same sports medicine specialists. MRI CUBE-T. 2. scanning with 48 channels was conducted by a professional radiologist. The volume of the ACL graft was created through 3 dimensional MRI model (Mimics 19, Ann Arbor). Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS) was applied to score visible cartilage damage. IKDC 2000 score and VAS were assessed by two blinded researchers. Results were presented as mean± SEM of each group. The cross-sectional area and 3D volume of the ACL graft were greater in the remnant-preserved ACLR+meniscus group compared with isolated ACLR (p=0.01). It showed that ACLR+ meniscus group had early signs of joint damage and delayed meniscus healing regarding ACLOAS compared to control group (p=0.045). MRI CUBE-T. 2. prediction of radiographic cartilage degeneration was not obvious in both groups post remnant-preserved ACLR over 12 months (p>0.05). However, higher VAS scores, lower IKDC scores, and long-last joint swelling were reported in the ACLR+ meniscus repair group at the end of 12 months follow-up. Although remnant-preserved ACLR+ meniscus was able to maintain the restore the knee function, it showed delayed timing (>12 months) to return to play at the pre-injury stage, while no difference between the timing of returning to the normal daily routine of their ACLR knee compared to control (p=0.30). The cost of ACLR+ meniscus (average 10,520.76$) was higher than the control group (6,452.92$, p=0.018). Remnants-preserved ACLR with concomitant injured medial and lateral meniscus repair shows a higher risk of cartilage damage, greater cost, worse functional performance, and longer time for young male patients to return to sports after 12-month follow-up compared to isolated ACLR. Further evidence and long-term follow-up are needed to better understand the association between these results and the risk of development of PTOA in this patient cohort


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 57 - 57
1 Dec 2021
Gilbert S Boye J Mason D
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Abstract. INTRODUCTION. The mechanisms underlying abnormal joint mechanics are poorly understood despite it being a major risk factor for developing osteoarthritis. Glutamate signalling has been implicated in osteoarthritic bone changes and AMPA/kainate glutamate receptor (GluR) antagonists alleviate degeneration in rodent models of osteoarthritis. We investigated whether glutamate signalling molecules are mechanically regulated in a human, cell-based 3D model of bone. METHODS. Human Y201 MSC cells embedded in 3D type I collagen gels (0.05 × 106 cell/gel) differentiated to osteocytes were mechanically loaded in silicone plates (5000 µstrain, 10Hz, 3000 cycles) or not loaded (n=5/group). RNA extracted 1-hr post load was quantified by RTqPCR and RNAseq whole transcriptome analysis (NovaSeq S1 flow cell 2 × 100bp PE reads). Differentially expressed GluRs and glutamate transporters (GluTs) were identified using DEseq2 analysis on normalised count data. Genes were considered differentially expressed if >2 fold change and FDR p<0.05. RESULTS. Cells expressed mature osteocyte markers (E11, sclerostin, DMP-1). DEseq2 analysis, revealed 981 mechanically regulated genes. Mechanical loading upregulated kainate GluRs, GRIK2 (1.6 fold, p=0.024) and GRIK5 (4.2 fold, p=0.045); the NMDA GluR GRIN3B (3.25 fold, p=0.047) and the GluT SLC1A1 (3 fold, p=0.037). Conversely, AMPA GRIA3, NMDA GluRs GRIN2A&C, and the GluT SLC1A2 were down regulated by 50–60%, although not significant. Kainate GRIK3&4; AMPA GRIA2, NMDA GRIN1, and GluTs SLC1A6&A7 were not expressed in control or loaded osteocytes, whereas GluRs (GRIK1, GRIA1&4, GRIN2B&2D&3A) and GluT SLC1A3 were expressed but not regulated by mechanical loading. DISCUSSION. Mechanical loading of human osteocytes in 3D revealed that they regulated expression of glutamate receptors and transporters. This is consistent with our observation that mechanical perturbation after joint injury in rodent models of OA regulates glutamatergic signalling in the bone thus linking mechanical stimuli to inflammatory and nociceptive pathways mediated by glutamate receptors. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 95 - 95
1 Jul 2014
Florea C Malo M Rautiainen J Mäkelä J Nieminen M Jurvelin J Davidescu A Korhonen R
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Summary. In a rabbit model of early osteoarthritis, structural changes in femoral condyle cartilage were severer in the lateral compartment and preceded alterations in the underlying bone. In the medial compartment, altered bone properties occurred together with structural changes in cartilage. Introduction. Early osteoarthritic changes in cartilage have been previously studied through anterior cruciate ligament transection (ACLT) in rabbits. However, parallel changes in the structure of subchondral and trabecular bone at 4 weeks after ACLT are not known. Methods. Skeletally mature 14-month old New Zealand white rabbits (n=8) underwent ACLT in the left knee, while right knees were used as controls (CTRL). Femoral condyles (FCs) were harvested at 4 weeks after ACLT. INDENTATION TESTING. Stepwise stress-relaxation tests were performed on medial and lateral FC cartilage (100%/s ramp rate, 3×5% step, 15 min relaxation time). Sinusoidal loading was then applied (amplitude 4% of thickness, 1Hz, 4 cycles). Equilibrium (Eeq) and dynamic (Ed) moduli were derived from stress-relaxation and sinusoidal tests, respectively. STRUCTURAL ANALYSIS OF CARTILAGE. Polarised light microscopy (PLM) and digital densitometry (DD) were used to analyze the collagen orientation angle (COA) and proteoglycan content in the cartilage samples. STRUCTURAL ANALYSIS OF BONE. Distal compartments of FCs were scanned using a high-resolution µCT scanner (Skyscan 1172, Belgium) with an isotropic voxel size of 25 µm. µCT data were imported into Mimics (Materialise, Belgium) for segmentation. 2×2×4 mm. 3. volumes of interest (VOIs) were placed in weight-bearing regions of medial and lateral FCs. Subchondral bone plate thickness (Pt.Th), trabecular volume fraction (BV/TV), trabecular thickness (Tb.Th), structural model index (SMI) and trabecular separation (Tb.Sp) were calculated using the CTAnalyzer software (Skyscan) from the VOIs. STATISTICAL TESTS. Mixed linear model for cartilage parameters and Wilcoxon signed-rank test for bone parameters were used to compare ACLT and CTRL groups (p < 0.05). Results. In both lateral and medial FC compartments, Eeq was significantly smaller in ACLT than in CTRL cartilage. In the medial compartment, also Ed was significantly smaller in ACLT than in CTRL cartilage. As a result of ACLT, significant alterations in the COA extended deeper into cartilage in the lateral than medial compartment, while proteoglycan content was reduced significantly and similarly in both lateral and medial FC cartilages. After ACLT, Pt.Th was significantly reduced in the medial compartment, while no changes were observed in the lateral compartment. Furthermore, only in the medial compartment, both BV/TV and Tb.Th were significantly smaller in the ACLT compared to the CTRL group. Discussion. The study showed that disruption of the collagen architecture in the ACLT joint cartilage extended into the middle zone only in the lateral FC compartment. Instead, thinning of the subchondral bone plate combined with resorption of trabecular bone was observed only in the medial FC compartment. The former finding reflects early osteoarthritic changes, while the latter finding may be indicative of a diminished loading in the medial FC compartment, as caused by ACLT


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 83 - 83
1 Nov 2018
Flynn S O'Reilly M Feeley I Sheehan E
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Knee osteoarthritis is a common, debilitating condition. Intra articular corticosteroid injections are a commonly used non-operative treatment strategy. Intra articular hip injection with Ketorolac (an NSAID) has proven to be as efficacious as corticosteroids. No prior study compares the efficacy of Ketorolac relative to corticosteroids for relief of discomfort in knee osteoarthritis. The study design was a single centre double blinded RCT. Severity of osteoarthritic changes were graded on plain film weightbearing radiographs using the Kellgren and Lawrence system. Injection was with either 30mg Ketorolac or 40mg Methylprednisolone, given by intra-articular injection, in a syringe with 5mls 0.5% Marcaine. Pre-injection clinical outcomes were assessed using the Numerical Pain Score (NPS), WOMAC, and Oxford knee scores. Patients' NPS scores were assessed at Day 1 and Day 14 post-injection. An assessment of all clinical outcomes took place in clinic at six weeks. There were 72 participants (83 knees) in the study. No patients were lost to follow-up. Mean age was 62.66 years (Range 29–85). 42 knees received a corticosteroid injection, 41 a NSAID injection. Mean Kellgren and Lawrence score was 3.1. There was no significant difference in pre-injection clinical scores in either group. There was a significant improvement of NPS on Day 1 and 14 in both injection groups(p<0.05). These improved pain scores were sustained at 6 weeks in both groups. WOMAC and Oxford Knee Scores showed a statistically significant improvement in the corticosteroid group. WOMAC scores showed significant improvement in the NSAID group, however these improvements didn't achieve statistical significance using the Oxford Knee Score. Corticosteroid or NSAID injectate are a safe and effective non-operative treatment strategy in the patient with knee osteoarthritis. Ketorolac appears to provide effective medium-term improvement of pain and clinical scores. Further follow-up is recommended to investigate if this trend in sustained


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_2 | Pages 78 - 78
1 Jan 2017
Yasuda T Konishi H Morita Y Miyazaki Y Hayashi M Yamawaki Y Yoshimoto K Sueyoshi T Ota S Fujita S Onishi E Iwaki K Yamamoto H
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Medial meniscus tear has been proposed as a potential etiology of spontaneous osteonecrosis of the knee (SONK). Disruption of collagen fibers within the meniscus causes meniscal extrusion, which results in alteration in load distribution in the knee. A recent study has demonstrated high incidence of medial meniscus extrusion in the knee with SONK. Our purpose was to determine whether the extent of medial meniscus extrusion correlates with the severity of SONK in the medial femoral condyle. Anteroposterior and lateral knee radiographs were taken with the patients standing. Limb alignment was expressed as the femorotibial angle (FTA) obtained from the anteroposterior radiograph. The stage of progression of SONK was determined according to the radiological classification system described by Koshino. After measurement of anteroposterior, mediolateral, and superoinferior dimensions of the hypointense T1 signal intensity lesion of MRI, its ellipsoid volume was calculated with the three dimensions. Meniscal pathology (degeneration, tear, and extrusion) were also evaluated by MRI. Of the 18 knees with SONK, we found 5 knees at the radiological stage 2 lesions, 9 knees at the stage 3, and 4 knees at the stage 4. Whereas the ellipsoid volume of SONK lesion significantly increased with the stage progression, the volume was significantly greater at stage 4 than stage 2 or 3. All the 18 knees with SONK in the present study showed substantial extrusion (> 3mm) and degeneration of the medial meniscus. While medial meniscal extrusion increased with the stage progression, medial meniscus was significantly extruded at stage 3 or 4 compared with stage 2. A significant increase in FTA was found with the stage progression. FTA was significantly greater at stage 4 than stage 2 or 3. Multiple linear regression analysis revealed that medial meniscus extrusion and FTA were useful predictors of the volume of SONK lesion. This study has clearly shown a significant correlation between the extent of medial meniscus extrusion and the stage and volume of SONK lesion. Degeneration and tears of the medial meniscus in combination with extrusion may result in loss of hoop stress distribution in the medial compartment, which could increase the load in the medial femoral condyle. In addition to meniscal pathology, knee alignment can influence load distribution in the medial compartment biomechanically. Multiple linear regression analysis indicates that an increase in FTA concomitant with a greater extrusion of medial meniscus could result in greater lesion and advanced radiological stage of SONK. Taken together, alteration in compressive force transmission through the medial compartment by meniscus extrusion and varus alignment could develop subchondral insufficiency fractures in the medial femoral condyle, which is considered to be one of the main contributing factors to SONK development. There was high association of medial meniscus extrusion and FTA with the radiological stage and volume of SONK lesion. Increased loading in the medial femoral condyle with greater extrusion of medial meniscus and varus alignment may contribute to expansion and secondary osteoarthritic changes of SONK lesion


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 33 - 33
1 Aug 2013
Mthethwa J Hawkins A
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Magnetic resonance imaging (MRI) is a useful diagnostic tool in evaluating meniscus pathology in the knee. Data from available literature suggests sensitivity and specificity rates around 90% when compared to the gold standard findings at knee arthroscopy. We sought to evaluate the sensitivity, specificity and precision rate (positive predictive value) of MRI at diagnosing meniscus tears within our unit. A retrospective audit of a total of 79 MRI reports and arthroscopic findings spanning a one year period was carried out. There were 66 positive MRI reports and 13 negative reports. There were 6 false positives 4 false negatives when compared to arthroscopic findings. The sensitivity of MRI for detecting meniscus tears was 93.7% with 60 out of 64 tears detected. All 4 false negatives also had at least grade III osteoarthritic changes at arthroscopy. Specificity was rather low at 60% with MRI reporting 6 tears (false positives) out of 15 patients who had no tears found at arthroscopy. The positive predictive value (precision rate) of MRI detecting tears was 90.9%. This data shows that MRI in our unit has a comparable high sensitivity to that in various literature making it a useful tool at ruling out disease with a negative result in the clinical setting. A more useful parameter in the clinical setting is its high precision rate when faced with a positive result. However, its specificity is much lower than that in most published data. A total of 6 tears on MRI turned out not to be on arthroscopy meaning patients could have been subjected to an avoidable invasive procedure in the absence of any other indication. This highlights the importance of obtaining reports from experienced musculoskeletal radiologists and the need for surgeons to review MRI images and match them to clinical information prior to subjecting patients to surgery


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 12 | Pages 1710 - 1716
1 Dec 2010
Chia W Pan R Tseng F Chen Y Feng C Lee H Chang D Sytwu H

The patellofemoral joint is an important source of symptoms in osteoarthritis of the knee. We have used a newly designed surgical model of patellar strengthening to induce osteoarthritis in BALB/c mice and to establish markers by investigating the relationship between osteoarthritis and synovial levels of matrix metalloproteinases (MMPs). Osteoarthritis was induced by using this microsurgical technique under direct vision without involving the cavity of the knee. Degeneration of cartilage was assessed by the Mankin score and synovial tissue was used to determine the mRNA expression levels of MMPs. Irrigation fluid from the knee was used to measure the concentrations of MMP-3 and MMP-9. Analysis of cartilage degeneration was correlated with the levels of expression of MMP. After operation the patellofemoral joint showed evidence of mild osteoarthritis at eight weeks and further degenerative changes by 12 weeks. The level of synovial MMP-9 mRNA correlated with the Mankin score at eight weeks, but not at 12 weeks. The levels of MMP-2, MMP-3 and MMP-14 mRNA correlated with the Mankin score at 12 weeks. An increase in MMP-3 was observed from four weeks up to 16 weeks. MMP-9 was notably increased at eight weeks, but the concentration at 16 weeks had decreased to the level observed at four weeks. Our observations suggest that MMP-2, MMP-3 and MMP-14 could be used as markers of the progression of osteoarthritic change


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 328 - 328
1 Jul 2014
Hargrave-Thomas E Thambyah A McGlashan S Broom N
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Summary. Macroscopic grading, histologic grading, morphometry, mineral analysis, and mechanical testing were performed to better understand the changes that occur in the cartilage, calcified cartilage, and subchondral bone in early osteoarthritis. Introduction. The earliest changes in osteoarthritis (OA) remain poorly understood due to the difficulty in detecting OA before patients feel pain. We have published details of the mature bovine patella model showing the pre-OA state where no gross macroscopic changes are visible yet microstructural changes indicate very early degeneration. In this new study, we proceed to investigate this model further by more comprehensively quantifying the changes in articular cartilage (AC), zone of calcified cartilage (ZCC), and subchondral bone (SB) in pre and early OA. Methods. Patellae from mature cow were studied. Gross examination with India ink was used to classify macroscopic cartilage degeneration. Two groups were selected in this study: one with no visible surface degeneration (pre-OA) and the other with mild to moderate macroscopically visible surface degeneration (early OA). Histologic staining with Safranin O and Fast Green was analysed with two osteoarthritic scoring systems: Mankin and OOCHAS. Differential Interference Contrast (DIC) microscopy was used to quantify morphometric changes. Degree of mineralisation was analysed with energy dispersive X-ray spectroscopy (EDS) to quantify the calcium and phosphorus content of the mineralised tissues. Material properties of calcified cartilage and subchondral bone were tested macroscopically using 3 point bending. Results. In the early OA group, cartilage was fissured and showed matrix loss. In its hydrated state, average cartilage thickness was significantly greater (p<0.05) in the early OA group by 24% compared to pre-OA group. The early OA group showed an 88% increase in ZCC thickness. Early OA tissue was graded significantly higher in OOCHAS grading and structure scores, cellularity, and staining scores of Mankin grading but not in the tidemark integrity score. Pre-OA and early OA tissues showed no significant differences in ZCC or SB mineralisation although all samples showed an increase in the degree of mineralisation going from the upper to the deeper ZCC and SB. Macroscopic mechanical testing showed no significant differences in mechanical properties between pre-OA and early OA groups. However within groups, the ZCC was an order of magnitude less stiff than the SB. Micromechanical testing showed that deeper ZCC and SB were stiffer than their regions closer to the joint surface. Conclusions. Early osteoarthritic changes in the joint tissues produce macro-level cartilage degeneration as well as microstructural changes. The combination of mineralisation and mechanical data show that though calcified cartilage and subchondral bone have similar mineralisation profiles, their material properties are drastically different, suggesting that stiffness is not purely the result of the mineral phase


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_VIII | Pages 16 - 16
1 Mar 2012
Koo KH Ha YC Lee YK Yoo JJ Kim HJ
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Introduction. Advanced stage and a large area of necrotic bone are known risk factors for failure after transtrochanteric rotational osteotomy of the hip in patients with osteonecrosis. The purpose of this study was to determine whether there were other risk factors for failure of this osteotomy. Methods. One hundred and five patients (113 hips) underwent transtrochanteric anterior rotational osteotomy for femoral head osteonecrosis and were followed for a mean period of 51 months post-operatively. Radiographic failure was defined as secondary collapse or osteoarthritic change. Multivariate analysis with the use of a Cox proportional-hazards frailty model was performed to assess factors that influenced the secondary collapse and osteophyte formation. A Kaplan-Meier product-limit method was performed to estimate survival. Results. Secondary collapse occurred in twenty-seven hips (23.9%) and fourteen of these hips (12.4%) were converted to a total hip arthroplasty. At the most recent follow-up, Merle d'Aubigne and Postel hip scores ranged from 6 to 18 points (mean, 16 points). Multivariate analysis showed that the stage of necrosis (hazard ratio=3.28; 95% confidence interval=1.49-7.24), age of the patient (hazard ratio=1.08; 95% confidence interval=1.02-1.14), body mass index (hazard ratio=1.19; 95% confidence interval=1.03-1.38), and extent of necrosis (hazard ratio=1.08; 95% confidence interval=1.04-1.11) were associated with secondary collapse. Seven of eighty-six hips without collapse progressed to osteoarthritis. Survivorship with total hip arthroplasty and radiographic failure as endpoints was 63.4% (95% confidence interval=51.1%-75.7%) and survivorship with total hip arthroplasty, radiographic failure, and loss of follow-up as endpoints was 56.0% (95% confidence interval=44.6%-67.4%) at 110 months. Conclusion. Our study showed that age, body mass index, stage, and extent of osteonecrosis were determining factors for secondary collapse, subsequent unsatisfactory clinical results, and conversion to total hip arthroplasty. These factors should be considered in patient selection for the osteotomy


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 3 | Pages 428 - 436
1 Apr 2001
Lovász G Park SH Ebramzadeh E Benya PD Llinás A Bellyei Á Luck JV Sarmiento A

To investigate the effect of instability on the remodelling of a minor articular surface offset, we created a 0.5 mm coronal step-off of the medial femoral condyle in 12 New Zealand white rabbits and transected the anterior cruciate ligament (ACL). A control group of 12 rabbits had only ACL resection and the opposite knee was used as the non-operated control. The osteoarthritic changes at 6, 12 and 24 weeks after surgery were evaluated histologically. In addition, changes in the immunological detection of 3-B-3(-) and 7-D-4 chondroitin-6-sulphate epitopes were determined because of the previous association of such changes with repair of cartilage and early osteoarthritis. In the instability/step-off group there was rapidly progressing focal degeneration of cartilage on the high side of the defect, not seen in previous step-off studies in stable knees. The rest of the femoral condyles and the tibial plateaux of the instability/step-off group had moderate osteoarthritis similar to that of the instability group. 3-B-3(-) was detectable in the early and the intermediate stages of osteoarthritis but no staining was seen in the severely damaged cartilage zones. Immunoreactivity with 7-D-4 increased as degeneration progressed. Our findings have shown that even a minor surface offset may induce rapid degeneration of cartilage when the stability of the knee is compromised


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_VIII | Pages 23 - 23
1 Mar 2012
Nagoya S Okazaki S Tateda K Nagao M Wada T Kukita Y Kaya M Sasaki M Kosukegawa I Yamashita T
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Introduction. The purpose of this study was to evaluate the outcome of vascularized iliac bone grafting for idiopathic osteonecrosis of the femoral head. Methods. We reviewed the clinical and radiological results of 35 operations performed on 29 patients who had osteonecrosis of the femoral head (ONFH) in which a pedicle iliac bone grafting was performed for minimum follow-up of 10 years. The average age was 35 years (range, 17 to 62 years). According to the Japanese Orthopaedic Association classification for ONFH, there were 28 stage 2, 7 stage 3-A, 17 type C-1 hips, and 18 type C-2 hips. After a bone tunnel of 1.5 × 5 cm was made in the anterior aspect of the femoral head and curettage of necrotic lesion was performed, the pedicle bone with the deep circumflex iliac artery (DCIA) was inserted into the anterolateral portion of the femoral head. The average follow-up period was 13 years and 6 months. Weight bearing was not allowed for 2 months after the operation. Survival rate of the femoral head was calculated by Kaplan-Meier methods, and collapse of the femoral head and configuration of the femoral head was investigated at final follow-up. Results. Collapse of the femoral head occurred in 19 hip joints of 35 studied. Although only 16 of 28 stage 2 hips showed collapse, all 7 stage 3 hips collapsed. Four of 17 hips (24%) showed collapse in patients with type C-1 necrosis, whereas, 15 of 18 hips (83%) developed collapse in patients with type C-2 necrosis. When the bone graft was inserted in the anterolateral portion of the femoral head, the incidence of collapse was reduced. In patients without collapse for more than 12 years, osteoarthritic change was evident in 5 hips between 12 to 19 years after operation. Conclusion. In this study, we found that collapse of the femoral head occurred or progressed in almost half of our patients, and these findings allowed us to clarify the operative indications for DCIA pedicle bone graft. In patients with stage 3, DCIA pedicle bone graft could not prevent collapse of the femoral head. While 13 of 17 hips with type C-1 were prevented from collapse, only 3 of 18 with type C-2 did not show collapse. These results indicate that DCIA bone graft may be indicated for stage 2, type C-1 necrosis. However, technical demands of this surgery tend to make it a less routine application for the treatment of ONFH


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_VIII | Pages 39 - 39
1 Mar 2012
Kabata T Maeda T Tanaka K Yoshida H Kajino Y Horii T Yagishita SI Tomita K
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Introduction. The treatment of osteonecrosis of the femoral head (ONFH) in young and active patients remains a challenge. The purpose of this study was to determine and compare the clinical and radiographic results of the two different hip resurfacing systems; hemi-resurfacing and metal-on-metal total hip resurfacing in patients with ONFH. Methods. This study was a retrospective review of 20 patients with 30 hips who had ONFH and underwent hemi-resurfacing or total hip resurfacing between November 2002 and February 2006. We mainly performed hemi-resurfacing for early stage ONFH, and total hip resurfacing for advanced stages. Fifteen hips in 11 patients had a hemi-resurfacing component (Conserve, Wright Medical Co) with a mean age at operation of 50 years and an average follow-up of 5.5 years. Fifteen hips in 10 patients had a metal-on-metal total hip resurfacing component (Birmingham hip resurfacing, Smith & Nephew Co.) with a mean age at operation of 40 years and an average follow-up years. Results. The average postoperative Japanese Orthopaedic Association (JOA) hip scores were 86 points in hemi-resurfacing and 96 points in total hip resurfacing. The difference of pain score was a main factor to explain the difference of total JOA hip score in the two groups. Both implants were radiographically stable, but radiolucent lines around the metaphyseal stem were more frequent in total hip resurfacing. In hemi-resurfacing patients, ten of 15 hips had groin pain or groin discomfort and three hips were revised to total hip arthroplasties (THA) because of femoral neck fracture, acetabular protrusio, and osteoarthritic changes, respectively. In total hip resurfacing patients, there were no revisions and no groin pain observed. Conclusion. In the prosthetic treatment of young active patients with ONFH, it is theoretically desirable to choose an implant with a conservative design in anticipation of the future revision surgery. Hemi-resurfacing hip arthroplasty is the most conservative implant for the treatment of ONFH. However, the results of hemi-resurfacing in this study have been disappointing due to high revision rates and insufficient pain relief despite of the good implant stability. However, the pain relief and implant survivorship after total hip resurfacing were superior to the results of hemi-resurfacing, although the usages of the total hip resurfacing were for more advanced cases. These results suggest that total hip resurfacing was a more valuable treatment option for active patients with ONFH than hemi-resurfacing


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_VIII | Pages 45 - 45
1 Mar 2012
Kobayashi S Momose T Nakagawa H Shimodaira H Tanaka A Kodaira H Tensho K Saito N Takaoka K
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Introduction. The purpose of this study was to examine if Sugioka's transtrochanteric rotational osteotomy (TRO) of the femoral head could be a valid option in treating idiopathic osteonecrosis of the femoral head. Methods. Thirty-two TROs performed in 29 patients between 1985 and 2006 were studied. Patient age at operation ranged from 16 to 56 years (average, 36 years). Thirteen hips were in women and 19 hips in men. Height was 165 cm and weight 63 kg (Body Mass Index 23) on average. Risk factors were corticosteroid use in 18 hips and excessive alcohol consumption in 15 hips (2 of them had both backgrounds), while neither of them was found with 1 hip. Bilateral hips were affected in 19 patients and 3 of them underwent bilateral TROs sequentially. The femoral head was rotated anteriorly in 26 hips and posteriorly in 6 hips. For fixation of the osteotomy site, large femoral screws had been used till 1995 (Group 1, 9 hips), and since 1996 an AO angle plate or a compression hip screw has been used (Group 2, 13 hips). Since 2003, pre-operative planning was performed more meticulously and the distal part of the joint capsule was cut after osteotomy as described by Atsumi (Group 3, 10 hips). The average follow-up period was 6.5 years (range, 2 to 21 years). Results. The average Japanese Orthopaedic Association hip score was 55 points pre-operatively, 63 points at 1 year, and 61 points at the latest follow-up. With pain increase, re-collapse of the rotated femoral head, fracture of the proximal fragment, nonunion, trochanteric detachment, joint space narrowing, osteoarthritic changes, or infection as the endpoint, the survival rate was 58% at 1 year, 53% at 4 - 9 years. The endpoint developed in 14 hips (re-collapse of the rotated femoral head in 9, fracture of the proximal fragment in 3, joint space narrowing in 1, and infection in 1). The changes in the surgical techniques were suggested to have improved the 3-year survivorship: 25% in Group 1, 54% in Group 2, and 74% in Group 3. The 4- to 9-year survival of this procedure was 53%. The majority of the endpoints developed within the first year, which may suggest that most of them were surgery-related. Conclusion. This procedure requires precise and meticulous precautions in pre-operative planning, preservation of the posterior column vessels during surgery, capsulotomy, and after-treatment. With those precautions, this procedure could be a valid joint-reserving option in treating idiopathic osteonecrosis of the femoral head. TRO is a highly difficult procedure and should be performed only by surgeons who have full training


Bone & Joint Research
Vol. 6, Issue 2 | Pages 73 - 81
1 Feb 2017
Ishihara K Okazaki K Akiyama T Akasaki Y Nakashima Y

Objectives

Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts.

Methods

Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 130 - 138
1 Apr 2014
Shapiro F Connolly S Zurakowski D Flynn E Jaramillo D

Objectives

An experimental piglet model induces avascular necrosis (AVN) and deformation of the femoral head but its secondary effects on the developing acetabulum have not been studied. The aim of this study was to assess the development of secondary acetabular deformation following femoral head ischemia.

Methods

Intracapsular circumferential ligation at the base of the femoral neck and sectioning of the ligamentum teres were performed in three week old piglets. MRI was then used for qualitative and quantitative studies of the acetabula in operated and non-operated hips in eight piglets from 48 hours to eight weeks post-surgery. Specimen photographs and histological sections of the acetabula were done at the end of the study.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 11 | Pages 1528 - 1533
1 Nov 2007
Jeffcote B Nicholls R Schirm A Kuster MS

Achieving deep flexion after total knee replacement remains a challenge. In this study we compared the soft-tissue tension and tibiofemoral force in a mobile-bearing posterior cruciate ligament-sacrificing total knee replacement, using equal flexion and extension gaps, and with the gaps increased by 2 mm each. The tests were conducted during passive movement in five cadaver knees, and measurements of strain were made simultaneously in the collateral ligaments. The tibiofemoral force was measured using a customised mini-force plate in the tibial tray. Measurements of collateral ligament strain were not very sensitive to changes in the gap ratio, but tibiofemoral force measurements were. Tibiofemoral force was decreased by a mean of 40% (sd 10.7) after 90° of knee flexion when the flexion gap was increased by 2 mm. Increasing the extension gap by 2 mm affected the force only in full extension. Because increasing the range of flexion after total knee replacement beyond 110° is a widely-held goal, small increases in the flexion gap warrant further investigation.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 12 | Pages 1660 - 1665
1 Dec 2006
Surendran S Kim SH Jee BK Ahn SH Gopinathan P Han CW

We stably transfected early passage chondrocytes with an anti-apoptotic Bcl-2 gene in vitro using a retrovirus vector. Samples of articular cartilage were obtained from 11 patients with a mean age of 69 years (61 to 75) who were undergoing total knee replacement for osteoarthritis. The Bcl-2-gene-transfected chondrocytes were compared with non-transfected and lac-Z-gene-transfected chondrocytes, both of which were used as controls. All three groups of cultured chondrocytes were incubated with nitric oxide (NO) for ten days. Using the Trypan Blue exclusion assay, an enzyme-linked immunosorbent assay and flow cytometric analysis, we found that the number of apoptotic chondrocytes was significantly higher in the non-transfected and lac-Z-transfected groups than in the Bcl-2-transfected group (p < 0.05). The Bcl-2-transfected chondrocytes were protected from NO-induced impairment of proteoglycan synthesis.

We conclude that NO-induced chondrocyte death involves a mechanism which appears to be subject to regulation by an anti-apoptotic Bcl-2 gene. Therefore, Bcl-2 gene therapy may prove to be of therapeutic value in protecting human articular chondrocytes.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1392 - 1400
1 Oct 2008
Hayashi R Kondo E Tohyama H Saito T Yasuda K

We report the effects of local administration of osteogenic protein-1 on the biomechanical properties of the overstretched anterior cruciate ligament in an animal model. An injury in the anterior cruciate ligament was created in 45 rabbits. They were divided into three equal groups. In group 1, no treatment was applied, in group II, phosphate-buffered saline was applied around the injured ligament, and in group III, 12.5 μg of osteogenic protein-1 mixed with phosphate-buffered saline was applied around the injured ligament. A control group of 15 rabbits was assembled from randomly-selected injured knees from among the first three groups. Each rabbit was killed at 12 weeks.

The maximum load and stiffness of the anterior cruciate ligament was found to be significantly greater in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p = 0.025). The tensile strength and the tangent modulus of fascicles from the ligament were also significantly greater in group III than either group I (p = 0.002, p = 0.0174) or II (p = 0.005, p = 0.022).

The application of osteogenic protein-1 enhanced the healing in the injured anterior cruciate ligament, but compared with the control group the treated ligament remained lengthened. The administration of osteogenic protein-1 may have a therapeutic role in treating the overstretched anterior cruciate ligament.