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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. 104-B, Issue SUPP_14 | Pages 19 - 19
1 Dec 2022
Belvedere C Ruggeri M Berti L Ortolani M Durante S Miceli M Leardini A
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Biomedical imaging is essential in the diagnosis of musculoskeletal pathologies and postoperative evaluations. In this context, Cone-Beam technology-based Computed Tomography (CBCT) can make important contributions in orthopaedics. CBCT relies on divergent cone X-rays on the whole field of view and a rotating source-detector element to generate three-dimensional (3D) volumes. For the lower limb, they can allow acquisitions under real loading conditions, taking the name Weight-Bearing CBCT (WB-CBCT). Assessments at the foot, ankle, knee, and at the upper limb, can benefit from it in situations where loading is critical to understanding the interactions between anatomical structures. The present study reports 4 recent applications using WB-CBCT in an orthopaedic centre. Patient scans by WB-CBCT were collected for examinations of the lower limb in monopodal standing position. An initial volumetric reconstruction is obtained, and the DICOM file is segmented to obtain 3D bone models. A reference frame is then established on each bone model by virtual landmark palpation or principal component analysis. Based on the variance of the model point cloud, this analysis automatically calculates longitudinal, vertical and mid-lateral axes. Using the defined references, absolute or relative orientations of the bones can be calculated in 3D. In 19 diabetic patients, 3D reconstructed bone models of the foot under load were combined with plantar pressure measurement. Significant correlations were found between bone orientations, heights above the ground, and pressure values, revealing anatomic areas potentially prone to ulceration. In 4 patients enrolled for total ankle arthroplasty, preoperative 3D reconstructions were used for prosthetic design customization, allowing prosthesis-bone mismatch to be minimized. 20 knees with femoral ligament reconstruction were acquired with WB-CBCT and standard CT (in unloading). Bone reconstructions were used to assess congruency angle and patellar tilt and TT-TG. The values obtained show differences between loading and unloading, questioning what has been observed so far. Twenty flat feet were scanned before and after Grice surgery. WB-CBCT allowed characterization of the deformity and bone realignment after surgery, demonstrating the complexity and multi-planarity of the pathology. These applications show how a more complete and realistic 3D geometric characterization of the of lower limb bones is now possible in loading using WB-CBCT. This allows for more accurate diagnoses, surgical planning, and postoperative evaluations, even by automatisms. Other applications are in progress


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 67 - 67
1 Dec 2021
MacLeod A Belvedere C Fabbro GD Grassi A Nervuti G Leardini A Casonato A Zaffagnini S Gill H
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Abstract. Objectives. High tibial osteotomy for knee realignment is effective at relieving symptoms of knee osteoarthritis but the operation is surgically challenging. A new personalised treatment with simpler surgery using pre-operatively planned measurements from computed tomography (CT) imaging and 3D-printed implants and instrumentation has been designed and is undergoing clinical trial. The aim of this study was to evaluate the early clinical results of a preliminary pilot study evaluating the safety of this new personalised treatment. Methods. The single-centre prospective clinical trial is ongoing (IRCCS Istituto Ortopedico Rizzoli; IRB-0013355; ClinicalTrials.gov NCT04574570), with recruitment completed and all patients having received the novel custom surgical treatment. To preserve the completeness of the trial reporting, only surgical aspects were evaluated in the present study. Specifically, the length of the implanted osteosynthesis screws was considered, being determined pre-operatively eliminating intraoperative measurements, and examined post-operatively (n=7) using CT image processing (ScanIP, Synopsys) and surface distance mapping. The surgical time, patient discharge date and ease of wound closure were recorded for all patients (n=25). Results. Over the study period the average surgical time (skin incision to suture) reduced from 54 to 31 minutes (range: 17–62, n=25). It was noted that wound closure was easier than the conventional surgery due to the lower profile of the implant. Over seventy percent of patients were discharged day 2 post-op. The position, orientation and length of all screws matched the pre-operative configuration to within approximately 1mm. Conclusions. The early trial results are promising from a clinical perspective. It was evident that surgical time was saved because no intraoperative screw length measurements were required, and the use of custom instrumentation significantly reduced the surgical inventory. The reduced invasiveness and ease of surgery may contribute to faster patient recovery compared to conventional techniques. The full trial results will be reported later this year. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 22 - 22
1 Nov 2021
Belvedere C Leardini A Gill R Ruggeri M Fabbro GD Grassi A Durante S Zaffagnini S
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Introduction and Objective. Medial Knee Osteoarthritis (MKO) is associated with abnormal knee varism, this resulting in altered locomotion and abnormal loading at tibio-femoral condylar contacts. To prevent end-stage MKO, medial compartment decompression is selectively considered and, when required, executed via High Tibial Osteotomy (HTO). This is expected to restore normal knee alignment, load distribution and locomotion. In biomechanics, HTO efficacy may be investigated by a thorough analysis of the ground reaction forces (GRF), whose orientation with respect to patient-specific knee morphology should reflect knee misalignment. Although multi-instrumental assessments are feasible, a customized combination of medical imaging and gait analysis (GA), including GRF data, rarely is considered. The aim of this study was to report an original methodology merging Computed-Tomography (CT) with GA and GFR data in order to depict a realistic patient-specific representation of the knee loading status during motion before and after HTO. Materials and Methods. 25 MKO-affected patients were selected for HTO. All patients received pre-operative clinical scoring, and radiological/instrumental assessments; so far, these were also executed post-operatively at 6-month follow-up on 7 of these patients. State-of-the-art GA was performed during walking and more demanding motor tasks, like squatting, stair-climbing/descending, and chair-rising/sitting. An 8-camera motion capture system, combined with wireless electromyography, and force platforms for GRF tracking, was used together with an own established protocol. This marker-set was enlarged with 4 additional skin-based non-collinear markers, attached around the tibial-plateau rim. While still wearing these markers, all analyzed patients received full lower-limb X-ray in standing posture a CT scan of the knee in weight-bearing Subsequently, relevant DICOMs were segmented to reconstruct the morphological models of the proximal tibia and the additional reference markers, for a robust anatomical reference frame to be defined on the tibia. These marker trajectories during motion were then registered to the corresponding from CT-based 3D reconstruction. Relevant registration matrices then were used to report GRF data on the reconstructed tibial model. Intersection paths of GRF vectors with respect to the tibial-plateau plane were calculated, together with their centroids. Results. Pre-operative clinical and radiological scoring confirmed MKO and associated abnormal varism. The morphological characterization of GRF was successfully achieved pre- and post- HTO on patient-specific tibial plateau. Pre-operative GFR patterns and peaks, including those related to knee joint moments, were observed medially on the knee, as expected. In post-HTO, these resulted lateralized and much closer to the tibial plateau spine, as desired. In detail, when post- is compared to pre-op, the difference of the centroids were, on average, 54.6±18.1 mm (min÷max: 36.7÷72.8 mm) more lateral during walking and 52.5±28.5 mm (24.7÷87.6 mm) during stair climbing. When reported in % of the tibial plateau width, these values became 69.2±20.1 (46.1÷81.4) and 78.1±30.1 (43.4÷98.0), respectively. Post-op also clinical scores and GA revealed a considerable overall improvement, especially in functional performances. Conclusions. The reported novel approach allows a combination of motion data, including GFR, and tibial-plateau morphology. Relevant pre- and post-operative routine application offer a quantification of the effect of the original deformity and executed joint realignment, and an assistance for surgical planning in case of HTO as well as ideally in other orthopedic treatments


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 58 - 58
1 Mar 2021
Kinghorn A Bowd J Whatling G Wilson C Mason D Holt C
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Abstract. OBJECTIVES. Valgus high tibial osteotomy (HTO) represents an effective treatment for patients with medial compartment osteoarthritis (OA) in a varus knee. However, the mechanisms which cause this clinical improvement are unclear. Previous studies suggest a wider stance gait can reduce medial compartment loading via reduction in the external knee adduction moment (KAM); a measure implicated in progression of medial compartment OA. This study aimed to measure whether valgus HTO is associated with a postoperative increase in static stance width. METHODS. 32 patients, recruited in the Biomechanics and Bioengineering Centre Versus Arthritis HTO study, underwent valgus (medial opening wedge) HTO. Weightbearing pre- and post- operative radiographs were taken showing both lower limbs. The horizontal distance, measured from a fixed point on the right talus to the corresponding point on the left, was divided by the talus width to give a standardised “stance width” for each radiograph. The difference between pre- and post- operative stance width was compared for each patient using a paired sample t-test. RESULTS. Preoperatively, mean stance was 4.00 talar-widths but postoperatively this increased to 5.41. This mean increase of 1.42 talar-widths was statistically significant (p=0.001) and represents a mean proportional increase in stance width of 35.5% following HTO. Of the 32 patients, 23 showed increased stance width and 9 decreased (range −4.64 to 6.00 talar-widths). CONCLUSIONS. These findings indicate an association of frontal plane surgical realignment at the proximal tibia via a medial opening wedge HTO with an increased stance width on postoperative radiographs. Considering both wider stance gait and HTO have been shown to affect the progression of medial compartment OA, these results may explain one mechanism contributing to the efficacy of HTO surgery. However, the range of changes in stance width suggests significant variability in how patients adapt at a whole-limb and whole-body level following HTO. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 71 - 71
1 Mar 2021
Buddhdev P Vallim F Slattery D Balakumar J
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Abstract. Objective. To assess the prevalence of acetabular retroversion in patients presenting with Slipped Upper Femoral Epiphysis using both validated radiological signs and CT-angle measurements. Methods. A retrospective review of all cases involving surgical management for acute SUFE presenting to the Royal Children's Hospital, Melbourne were assessed from 2012–2018. Pre-operative plain radiographs were assessed for slip angle, validated radiological signs of retroversion (post wall/crossover/ischial spine sign) and standardised post-operative CT Scans were used to assess cranial and mid-acetabular version. Results. 116 SUFEs presented in 107 patients who underwent surgical intervention; 47 females and 60 boys, with an average age of 12.7 years (range 7.5–16.6 years). Complete radiological data was available for 91 patients (99 hips) with adequate axial CT imaging of both hips. 82% patients underwent pinning in situ (PIS) with subcapital realignment surgery (SRS) performed in 18% (slip angles >75°). Contralateral prophylactic hip PIS was performed in 72 patients (87%). On the slip side, 68% of patients had 1 or more radiological signs of retroversion in the slipped hip, with 60% on the contralateral side. The mean cranial and mid-acetabular version measurements were −8°(range −30 – 8°) and 10.5°(range −10 – 25°), respectively. Conclusions. Acetabular retroversion is rare in the normal population with studies reports ranging from 0–7%. This study showed an increased prevalence of 68% in SUFE patients, which is likely to be a primary anatomical abnormality, subsequently increasing the shear forces across the proximal femoral growth plate due to superior over-coverage. The resulting CAM lesion from SUFE in combination with the pincer lesion due to retroversion can lead to premature hip impingement and degeneration. Further larger studies are required to assess if acetabular retroversion is a true risk factor, and its role in helping guide management including prophylactic pinning. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 63 - 63
1 Dec 2020
Debnath A Dalal S Setia P Guro R Kotwal RS Chandratreya AP
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Introduction. Recurrent patellar dislocation is often reported in bilateral knees in young active individuals. The medial patellofemoral ligament (MPFL) tear is the attributable cause behind many of them and warrants reconstruction of the ligament to stabilize the patellofemoral joint. Besides, trochleoplasty and Fulkerson's osteotomy are some other procedures that are performed to treat this problem. This study aimed to compare the clinical and functional outcomes in a cohort of patients with single-stage bilateral realignment procedures vs staged procedures. Methods. It was a retrospective matched cohort study with prospectively collected data. A total of 36 patients (mean age-26.9 years, range 13 years to 47 years) with recurrent patellar dislocations, who underwent a surgical correction in both the knees, were divided into two matched groups (age, sex, follow-up, and type of procedure). Among them, 18 patients had surgeries in one knee done at least six months later than the other knee. The remaining 18 patients had surgical interventions for both knees done in a single stage. Lysholm, Kujala, Tegner, and subjective knee scores of both groups were compared and analyzed. The rate of complications and return to the theatre were noted in both groups. Results. With a mean follow-up of 7.3 years (2.0 years to 12.3 years), there was a significant improvement in PROMS observed in both the groups (p<0.05). No significant difference could be found between the two groups in terms of the Lysholm, Kujala, and subjective knee scores (p> 0.05). The rate of complication and the re-operation rate was comparable in both the groups (p>0.05). Conclusion. The outcomes of staged vs simultaneous surgeries for bilateral patellofemoral instability are comparable. Our results indicate that simultaneous bilateral surgical correction is safe. This can potentially be an option to reduce the surgical cost and perioperative morbidity. However, careful selection of cases, choice of the patient, and the scope of rehabilitation facilities are some of the other factors that should be considered


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 72 - 72
1 Dec 2020
PEHLIVANOGLU T BEYZADEOGLU T
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Introduction. Simultaneous correction of knee varus malalignment with medial open wedge high tibial osteotomy (MOWHTO) combined with anterior cruciate ligament (ACL) surgery aims to address symptomatic unicompartmental osteoarthritis in addition to restore knee stability in order to improve outcomes. The aim of this study is to present at least 5 years results of 32 patients who underwent simultaneous knee realignment osteotomy with ACL surgery. Methods. Patients with symptomatic instability due to chronic ACL deficiency or failed previous ACL surgery together with a varus malalignment of ≥6°, previous medial meniscectomy and symptomatic medial compartment pain who were treated with MOWHTO combined with ACL surgery were enrolled. ACL surgery was performed with the anatomical single bundle all-inside technique using TightRope. ®. RT (Arthrex, Naples, FL, USA) and MOWHTO using TomoFix. ®. medial high tibia plate (DePuy Synthes, Raynham, MA, USA) in all cases. Patients were evaluated preoperatively and at 6 months, 12 months and annually postoperatively using the Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS) and Euroqol's Visual Analogue Score (VAS) for pain. Results. 32 patients (22 men and 10 women) with a mean age of 41.2 years and mean BMI of 28.6 kg/m. 2. , underwent the combined procedures. Tibiofemoral neutral re-alignment was achieved in all patients with HTO. Complete subjective and objective scores have been obtained in 84.4% of patients with at least 5 years of follow-up (mean 8.7 years). An improvement in total KOOS of 27.1 points (p<0.003), OKS of 15.1 (p<0.003) and VAS for pain of 24.7 points (p<0.001) were detected. No ACL reconstruction failure was noted. Complications consisted of one superficial wound infection and one delayed union. Plate removal was needed in 20 (62.5%) patients due to pes anserinus pain. Conclusions. Simultaneous restoration of coronal knee axis by applying HTO and stability by ACL reconstruction/revision were reported to offer excellent improvement in early outcomes in patients with ACL rupture and symptomatic unicompartmental osteoarthritis. The combined procedure requires careful pre-operative planning and is therefore technically challenging. However, by restoring the neutral axis and providing stability, it represents a good joint preserving alternative to arthroplasty for active middle-aged patients


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 12 - 12
1 Nov 2018
Mason D
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Osteoarthritis (OA), characterised by pain, disability and joint degeneration, is common and has no cure. Prevalence of severe radiographic knee OA is 19% in over 45's and 50% in over 75's in the US and Europe. Abnormal joint loading, or injury, increase risk of OA. We have discovered that glutamatergic signalling is mechanically regulated and glutamate receptors (GluR) drive inflammation, degeneration and pain representing potential drug targets in osteoarthritic joints. Joints from OA and knee injured patients, and rodent models of arthritis, show increased synovial fluid glutamate concentrations and abundant GluR expression. Since AMPA/kainate GluRs regulate IL-6, a critical mediator of arthritic degeneration, we tested protective effects of the AMPA/KA GluR antagonist, NBQX in animal models of arthritis. In rodent antigen induced arthritis, and osteoarthritis (meniscal transection and anterior cruciate ligament rupture), NBQX reduced joint swelling, degeneration and pain, exceeding anti-degenerative effects of other drugs tested similarly. 3D osteocyte/osteoblast co-cultures and human bone samples taken from patients undergoing high tibial osteotomy joint realignment surgery, revealed underlying cellular mechanisms mediated by bone cells. Related drugs, already used in humans for epilepsy and migraine, represent a repurposing opportunity and are effective in our models of arthritis


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_2 | Pages 29 - 29
1 Jan 2019
Yao J Mengoni M Williams S Jones A
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Acetabular tissue damage is implicated in osteoarthritis (OA) and investigation of in situ acetabular soft tissues behaviour will improve understanding of tissue properties and interconnections. The study aim was to visualise acetabular soft tissues under load and to quantify displacements using computed tomography (CT) scans (XtremeCT, Scano Medical). A CT scan (resolution 82 μm) was performed on the disarticulated, unloaded porcine acetabulum. The femoral head was soaked in Sodium Iodide (NaI) solution and cling film wrapped to prevent transfer to the acetabular side. The joint was realigned, compressed using cable ties and re-scanned. The two images were down-sampled to 0.3 mm. Acetabular bone and soft tissues were segmented. Bony features were used to register the two background images, using Simpleware ScanIP 7.0 (Synopsys), to the same position and orientation (volume difference < 5%). Acetabular soft tissues displacements were measured by tracking the same points at the tissue edges on the two acetabular masks, along with difference in bone position as an additional error assessment. The use of radiopaque solution provided a clear contrast allowing separation of the femoral and acetabular soft tissues in the loaded image. The image registration process resulted in a difference in bone position in the areas of interest equivalent to image resolution (0.3 mm, a mean of 3 repeats by same user). A labral tip displacement of 1.7 mm and a cartilage thickness change from 1.5 mm unloaded to 0.9 mm loaded, were recorded. The combination of contrast enhancement, registration and focused local measurement was precise enough to reduce bone alignment error to that of image resolution and reveal local soft tissue displacements. These measurement methods can be used to develop models of soft tissues properties and behaviour, and therapy for hip tissue damage at early stage may be reviewed and optimised


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 263 - 263
1 Jul 2014
Imai K Ikoma K Gay R Hirano T Ozasa Y Chen Q An K Zhao C
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Summary Statement. ASTM therapy is commonly used to treat Achilles tendinopaty. However, there was no report to evaluate the biomechanical effects, especially the dynamic viscoelasticity. We have shown that ASTM treatment was biomechanically useful for chronic Achilles tendinopathy in an animal model. Introduction. Achilles tendinopathy is a common chronic overuse injury. Because Achilles tendon overuse injury takes place in sports and there has been a general increase in the popularity of sports activities, the number and incidence of Achilles tendon overuse injury has increased. Augmented Soft Tissue Mobilization (ASTM) therapy is a modification of traditional soft tissue mobilization and has been used to treat a variety of musculoskeletal disorders. ASTM therapy is thought to promote collagen fiber realignment and hasten tendon repair. It might also change the biomechanical behavior of the injured tendon, especially the dynamic viscoelasticity. The purpose of this study is to evaluate the effect of ASTM therapy in a rabbit model of Achilles tendinopathy by quantifying dynamic biomechanical properties and histologic features. Patients & Methods. The hind limbs of 12 rabbits were used, and 24 Achilles tendons were injected with collagenase to produce tendon injury. One hind limb of each animal was then randomly allocated to receive ASTM therapy, while the other received no treatment and served as a control. ASTM was performed on the Achilles tendon for 3 minutes on postoperative days 21, 24, 28, 31, 35, and 38. The Achilles tendons were harvested 10 days after the last treatment. Specimens were examined with dynamic viscoelasticity and light microscopy. Results. The mean±SD cross-sectional area for the treated and untreated tendons was 12.30±5.47 mm. 2. and 9.57±8.36 mm. 2. , respectively. The difference between the treated and untreated tendons was statistically significant (P<.01). At all dynamic loading frequencies, the storage modulus in the untreated tendons tended to be higher than that in the treated tendons. At 0.1 Hz and 10 Hz, in the untreated tendons was significantly higher than that in the treated tendons (P=.05). The loss modulus was significantly lower in the treated tendons than in the untreated tendons (P<.05). There was no significant difference in tan δ between the treated and untreated tendons. HE stain showed that the untreated tendon fiber was wavy and kinking and displayed a disordered collagen arrangement. In contrast, the tendon fiber was well aligned in the treated tendons. In the immunohistochemically stained specimens, the type III collagen showed higher color intensity in the untreated tendons than in the treated tendons. Discussion/Conclusion. We have shown that ASTM was a biomechanically useful treatment for chronic Achilles tendinopathy. Biomechanical and histologic data showed the treated Achilles tendons had better biomechanical function and histologic outcomes than the untreated tendons


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 99 - 99
1 Aug 2012
Whatling G Holt C Brakspear K Roberts H Watling D Kotwal R Wilson C Williams R Metcalfe A Sultan J Mason D
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BACKGROUND. High tibial Osteotomy (HTO) realigns the forces in the knee to slow the progression of osteoarthritis. This study relates the changes in knee joint biomechanics during level gait to glutamate signalling in the subchondral bone of patients pre and post HTO. Glutamate transmits mechanical signals in bone and activates glutamate receptors to influence inflammation, degeneration and nociception in arthritic joints. Thus glutamate signalling is a mechanism whereby mechanical load can directly modulate joint pathology and pain. METHODS. 3D motion analysis was used to assess level gait prior to HTO (n=5) and postoperatively (n=2). A biomechanical model of each subject was created in Visual3D (C-motion. Inc) and used for biomechanical analysis. Gene expression was analysed by RT-PCR from bone cores from anterior and posterior drill holes, subdivided according to medial or lateral proximal tibia from HTO patients (n=5). RESULTS. Knee adduction moment is a clinical marker of medial compartment loading. Pre-operatively the mean peak adduction moment was 3.8 ± 1.8 % body weight times height (BW.h). One subject maintained a consistent peak adduction moment pre (1.8 %BW.h) and post-operatively (1.9 %BW.h) with a reduction in the second moment peak. Another subjects peak adduction moment was significantly reduced from 6.7 %BW.h pre-operatively to 1.4 %BW.h postoperatively. GAPDH, osteocalcin, EAAT-1, EAAT1ex9skip, NR2A, KA1, OPG and RANKL mRNA expression was detected in HTO bone cores. In one patient, where HTO reduced medial compartment loading, differential expression of EAAT1ex9skip and KA1 was observed in pre and post HTO bone cores. CONCLUSION. Changes in knee adduction moments following HTO have been identified indicating altered medial compartmental loading. This is being investigated further in larger cohorts in a 5 year study. We have demonstrated that glutamate transporters and receptors are expressed in human subchondral bone and that glutamate transporter mRNA expression may vary after HTO surgery. In arthritis, glutamate concentrations in the synovial fluid are increased, activating receptors in joint tissues and nerves to influence pathology and nociception. Thus glutamatergic signals represent a direct mechanism linking mechanical loading through the joint to pathology and pain in human arthritis


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 37 - 37
1 May 2012
Kotwal RS Brakspear K Roberts H Wilson C Williams R Sultan J Mason DJ
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Glutamate is a neurotransmitter that transmits mechanical signals in bone (1) and activates glutamate receptors and transporters, in bone, cartilage, meniscus and synovium (2). Glutamate receptor activation influences inflammatory, degenerative and nociceptive pathways in arthritic joints (2). Thus glutamate signalling is a mechanism whereby mechanical load can directly influence joint pathology and pain. We have investigated components of glutamate signalling in the subchondral bone of patients with osteoarthritis to determine which are expressed and whether this varies in anatomical regions subject to different loads. Subchondral bone was sampled from tibial cuts derived from total knee arthroplasty (n=2, TKR, Kellgren Lawrence grade 3) and from tibial drill hole sites from high tibial osteotomy (n=5, HTO, KL grades 2 and 3) for osteoarthritis. RNA was extracted, reverse transcribed and RT-PCR performed for a housekeeping gene GAPDH, a glutamate transporters (EAAT-1, EAAT1ex9skip), glutamate receptors (NR2A and KA1), a bone matrix protein, osteocalcin, and signaling molecules (osteoprotegerin [OPG], RANKL). We found differential mRNA expression in different regions of subchondral bone. In one TKR patient, EAAT-1 expression was significantly reduced in the anterior zone versus the middle or posterior zones of the tibial plateau (ANOVA, p<0.001). HTO bone cores were subdivided medial/lateral and anterior/posterior. Good quality RNA was obtained from bone cores removed from drill holes during HTO surgery, with GAPDH, osteocalcin, EAAT-1, EAAT1ex9skip, NR2A, KA1, OPG and RANKL mRNA expression detected. In one patient, comparison of gene expression in bone cores obtained pre and post HTO revealed that EAAT1ex9skip was rarely detected in post-op bone whereas KA1 was rare in pre-op bone. This differential mRNA expression may be due to the altered loading through the joint caused by the osteotomy, although these on/off differences need to be quantified to confirm this. We have shown that glutamate transporters and receptors are expressed in human subchondral bone. Activation of these receptors and transporters by the increased synovial fluid concentrations of glutamate released in arthritis will influence pathological changes and nociception. In some patients, glutamate transporter mRNA expression appears to vary with anatomical location in bone, or after HTO surgery, consistent with our original discovery of this transporter as mechanically-regulated in bone (1). If glutamatergic signaling is mechanically regulated in the human knee, this will vary during arthritic disease progression and after joint realignment, providing a direct mechanism linking mechanical loading through the joint to pathology and pain in arthritis


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 10 | Pages 1460 - 1465
1 Oct 2010
Rauh PB Clancy WG Jasper LE Curl LA Belkoff S Moorman CT

We evaluated two reconstruction techniques for a simulated posterolateral corner injury on ten pairs of cadaver knees. Specimens were mounted at 30° and 90° of knee flexion to record external rotation and varus movement. Instability was created by transversely sectioning the lateral collateral ligament at its midpoint and the popliteus tendon was released at the lateral femoral condyle. The left knee was randomly assigned for reconstruction using either a combined or fibula-based treatment with the right knee receiving the other. After sectioning, laxity increased in all the specimens. Each technique restored external rotatory and varus stability at both flexion angles to levels similar to the intact condition. For the fibula-based reconstruction method, varus laxity at 30° of knee flexion did not differ from the intact state, but was significantly less than after the combined method.

Both the fibula-based and combined posterolateral reconstruction techniques are equally effective in restoring stability following the simulated injury.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 686 - 692
1 May 2007
Bolland BJRF New AMR Madabhushi SPG Oreffo ROC Dunlop DG

The complications of impaction bone grafting in revision hip replacement includes fracture of the femur and subsidence of the prosthesis. In this in vitro study we aimed to investigate whether the use of vibration, combined with a perforated tamp during the compaction of morsellised allograft would reduce peak loads and hoop strains in the femur as a surrogate marker of the risk of fracture and whether it would also improve graft compaction and prosthetic stability.

We found that the peak loads and hoop strains transmitted to the femoral cortex during graft compaction and subsidence of the stem in subsequent mechanical testing were reduced. This innovative technique has the potential to reduce the risk of intra-operative fracture and to improve graft compaction and therefore prosthetic stability.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 730 - 735
1 May 2005
Sharpe JR Ahmed SU Fleetcroft JP Martin R

In this study a combination of autologous chondrocyte implantation (ACI) and the osteochondral autograft transfer system (OATS) was used and evaluated as a treatment option for the repair of large areas of degenerative articular cartilage. We present the results at three years post-operatively. Osteochondral cores were used to restore the contour of articular cartilage in 13 patients with large lesions of the lateral femoral condyle (n = 5), medial femoral condyle (n = 7) and patella (n = 1). Autologous cultured chondrocytes were injected underneath a periosteal patch covering the cores. After one year, the patients had a significant improvement in their symptoms and after three years this level of improvement was maintained in ten of the 13 patients. Arthroscopic examination revealed that the osteochondral cores became well integrated with the surrounding cartilage. We conclude that the hybrid ACI/OATS technique provides a promising surgical approach for the treatment of patients with large degenerative osteochondral defects.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 721 - 729
1 May 2005
Yanai T Ishii T Chang F Ochiai N

We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel.

The histological scores were significantly higher in the groups with ACBMT collagen gel (p < 0.05). The area of regenerated soft tissue was smaller in the group allowed to bear weight (p < 0.05). These findings suggest that the repair of large defects of cartilage can be enhanced by joint distraction, collagen gel and ACBMT.