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Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims. The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice. Methods. Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro. Results. The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 (Ccn2) in WT mouse cells. Conclusion. Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis. Cite this article: Bone Joint Res 2024;13(7):321–331


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XL | Pages 69 - 69
1 Sep 2012
Hirokawa S Fukunaga M Tsukamoto M Akiyama T Horikawa E Mawatari M
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The objective of this study is to determine the knee joint forces when rising from a kneeling position. We have developed a new type of knee prosthesis which is capable of attaining Japanese style sitting. To run the simulations and experiments needed to assess the performance of this prosthesis, it is necessary to know what forces act on the knee during deep flexion. Because these data are lacking, we created a 2D mathematical model of the lower leg to help determine knee joint forces during deep flexion. Healthy subjects of ten males (age of 25±4years, height of 170.3±9.1cm, and weight of 67.0±22.2kg) and five females (25±3years, 161±7.1cm, 47.7±6.2kg) participated in the experiment. Ground reaction force and joints angles were measured using a force plate and a motion recording system respectively. The collected data were entered into our mathematical model, and the muscle forces and the knee joint forces were calculated. To verify our model, we first used it to run simulation of middle and high flexions of the knee joint. In vivo data for these actions are available in the literature, and the results from our simulation were in good agreement with these data. We then collected the data and run simulation when rising from a kneeling position under the conditions shown in Fig. 1. They were a) double leg rising (both legs are aligned) without using the arms, b) ditto but using the arms, c) single leg rising (legs are in the front and the rear respectively) without using the arms, and d) ditto but using the arms. We obtained the following results. The statistics of the maximum values on the single knee joint for each condition were; a) Fmax=5.1±0.4 [BW: (force on the knee joint)/(body weight)] at knee flexion angle of Q=140±8°, b) Fmax=3.2±0.9[BW] at Q=90±10°, c) Fmax-d=5.4±0.5[BW] at Qd=62±20° for the dominant leg and Fmax-s=3.0±0.5[BW] at Qs=138±6° for the supporting leg respectively, and d) Fmax-d=3.9±1.5[BW] at Qd=70±17° for the dominant, and Fmax-s=2.1±0.5 [BW] at Qs=130±11° for the supporting. We may conclude that the single leg rising should be recommended since the maximum knee joint force did not become large as long as the knee was at deep flexion. The values introduced in this study could be used to assess the strength of the knee prosthesis at deep flexion. To obtain more realistic values of the joint forces, it is necessary to determine the ratio of the forces exerted by the mono-articular and the bi-articular joint muscles


Bone & Joint Research
Vol. 12, Issue 4 | Pages 285 - 293
17 Apr 2023
Chevalier A Vermue H Pringels L Herregodts S Duquesne K Victor J Loccufier M

Aims. The goal was to evaluate tibiofemoral knee joint kinematics during stair descent, by simulating the full stair descent motion in vitro. The knee joint kinematics were evaluated for two types of knee implants: bi-cruciate retaining and bi-cruciate stabilized. It was hypothesized that the bi-cruciate retaining implant better approximates native kinematics. Methods. The in vitro study included 20 specimens which were tested during a full stair descent with physiological muscle forces in a dynamic knee rig. Laxity envelopes were measured by applying external loading conditions in varus/valgus and internal/external direction. Results. The laxity results show that both implants are capable of mimicking the native internal/external-laxity during the controlled lowering phase. The kinematic results show that the bi-cruciate retaining implant tends to approximate the native condition better compared to bi-cruciate stabilized implant. This is valid for the internal/external rotation and the anteroposterior translation during all phases of the stair descent, and for the compression-distraction of the knee joint during swing and controlled lowering phase. Conclusion. The results show a better approximation of the native kinematics by the bi-cruciate retaining knee implant compared to the bi-cruciate stabilized knee implant for internal/external rotation and anteroposterior translation. Whether this will result in better patient outcomes remains to be investigated. Cite this article: Bone Joint Res 2023;12(4):285–293


Bone & Joint Open
Vol. 5, Issue 9 | Pages 785 - 792
19 Sep 2024
Clement RGE Wong SJ Hall A Howie SEM Simpson AHRW

Aims. The aims of this study were to: 1) report on a cohort of skeletally mature patients with native hip and knee septic arthritis over a 14-year period; 2) to determine the rate of joint failure in patients who had experienced an episode of hip or knee septic arthritis; and 3) to assess the outcome following septic arthritis relative to the infecting organism, whether those patients infected by Staphylococcus aureus would be more likely to have adverse outcomes than those infected by other organisms. Methods. All microbiological samples from joint aspirations between March 2000 and December 2014 at our institution were reviewed in order to identify cases of culture-proven septic arthritis. Cases in children (aged < 16 years) and prosthetic joints were excluded. Data were abstracted on age at diagnosis, sex, joint affected (hip or knee), type of organisms isolated, cause of septic arthritis, comorbidities within the Charlson Comorbidity Index (CCI), details of treatment, and outcome. Results. A total of 142 patients were confirmed to have had an episode of septic arthritis in a native hip (n = 17) or knee joint (n = 125). S. aureus accounted for 57.7% of all hip and knee joint infections. There were 13 inpatient deaths attributed to septic arthritis. The median age of the patients who died was 77.5 (46.9 to 92.2) and their median age-adjusted CCI was 8 (6 to 12). A failure of the joint occurred in 26 knees (21%) and nine hips (53%). Of the knee joints infected by S. aureus (n = 71), 23 knees (32%) went into failure of joint, whereas of those infected by other organisms (n = 54), only three knees (6%) failed. Conclusion. Based on our study findings, hip and knee septic arthritis long-term outcomes were substantially worse than their immediate outcome suggested. Failure of knee joint is 6.1 times more likely to occur in those infected with S. aureus. Cite this article: Bone Jt Open 2024;5(9):785–792


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 102 - 102
1 Nov 2021
Forriol F
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The knee joint has also a periarticular adipose tissue, which is known as Hoffa's fat pad (IPFP). IPFP has a dual function in the joint it reduces the concentration of Nitric Oxide, the release of glycosaminoglycans and the expression of MMP1 in the cartilage, but it also contains MSC and macrophages. Our hypothesis is that synovial fluid contains elements, not all of which are understood, which act as messengers and alter the “homeostasis” of the knee and the metabolism of all the cellular components of the joint, including the MSC of Hoffa's fat pad, thus making them another piece in the puzzle as far as OA of the knee is concerned. The IPFP of 37 patients with OA and 36 patients with ACL rupture were analyzed. Isolation, primary culture, and a functional and proteomic study of MSCs from IPFP were performed. Our results show that OA of the knee, in its more severe phases, also affects the MSC's of IPFP, which is a new actor in the OA degenerative process and which can contribute to the origin, onset and progression of the disease. A differential protein profile between OA and ACL patients were identified. Infrapatellar pad should be regarded as an adipose tissue with its own characteristics and it´s also able to produce and excrete important inflammatory mediators directly into the knee joint


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_13 | Pages 80 - 80
7 Aug 2023
Liu A Qian K Dorzi R Alabdullah M Anand S Maher N Kingsbury S Conaghan P Xie S
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Abstract. Introduction. Knee braces are limited to providing passive support. There is currently no brace available providing both continuous monitoring and active robot-assisted movements of the knee joint. This project aimed to develop a wearable intelligent motorised robotic knee brace to support and monitor rehabilitation for a range of knee conditions including post-surgical rehabilitation. This brace can be used at home providing ambulatory continuous passive movement obviating the need for hospital admissions. Methodology. A wearable sensing system monitoring knee range of motion was developed to provide remote feedback to clinicians and real-time guidance for patients. A prototype of an exoskeleton providing dynamic motion assistance was developed to help patients complete their exercise goals and strengthen their muscles. The accuracy and reliability of those functions were validated in human participants during exercises including knee flexion/extension (FE) in bed and in chair, sit-to-stand and stand-to-sit. Results. The knee FE measurement from the sensing system showed high accuracy (correlation coefficient of 0.99°) in human participants. The real-time FE data during exercises showed that the desired exoskeleton rotation fitted well with the participant's knee rotation. This indicated the exoskeleton could coordinate with the participant's knee motion by providing consistent motion assistance. The development of user interfaces to provide feedback is currently underway. Conclusion. A wearable robotic knee brace to monitor and support knee rehabilitation exercises was successfully developed. Further development of this device with the use of artificial intelligence has the potential to aid patient rehabilitation in a variety of knee conditions


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 97 - 97
11 Apr 2023
Milakovic L Dandois F Fehervary H Scheys L
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This study aims to create a novel computational workflow for frontal plane laxity evaluation which combines a rigid body knee joint model with a non-linear implicit finite-element model wherein collateral ligaments are anisotropically modelled using subject-specific, experimentally calibrated Holzpfel-Gasser-Ogden (HGO) models. The framework was developed based on CT and MRI data of three cadaveric post-TKA knees. Bones were segmented from CT-scans and modelled as rigid bodies in a multibody dynamics simulation software (MSC Adams/view, MSC Software, USA). Medial collateral and lateral collateral ligaments were segmented based on MRI-scans and are modelled as finite elements using the HGO model in Abaqus (Simulia, USA). All specimens were submitted varus/valgus loading (0-10Nm) while being rigidly fixed on a testing bench to prevent knee flexion. In subsequent computer simulations of the experimental testing, rigid bodies kinematics and the associated soft-tissue force response were computed at each time step. Ligament properties were optimised using a gradient descent approach by minimising the error between the experimental and simulation-based kinematic response to the applied varus/valgus loads. For comparison, a second model was defined wherein collateral ligaments were modelled as nonlinear no-compression spring elements using the Blankevoort formulation. Models with subject-specific, experimentally calibrated HGO representations of the collateral ligaments demonstrated smaller root mean square errors in terms of kinematics (0.7900° +/− 0.4081°) than models integrating a Blankevoort representation (1.4704° +/− 0.8007°). A novel computational workflow integrating subject-specific, experimentally calibrated HGO predicted post-TKA frontal-plane knee joint laxity with clinically applicable accuracy. Generally, errors in terms of tibial rotation were higher and might be further reduced by increasing the interaction nodes between the rigid body model and the finite element software. Future work should investigate the accuracy of resulting models for simulating unseen activities of daily living


Bone & Joint Research
Vol. 12, Issue 4 | Pages 259 - 273
6 Apr 2023
Lu R Wang Y Qu Y Wang S Peng C You H Zhu W Chen A

Aims. Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism. Methods. In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results. DHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion. We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment. Cite this article: Bone Joint Res 2023;12(4):259–273


Bone & Joint Research
Vol. 8, Issue 11 | Pages 509 - 517
1 Nov 2019
Kang K Koh Y Park K Choi C Jung M Shin J Kim S

Objectives. The aim of this study was to investigate the biomechanical effect of the anterolateral ligament (ALL), anterior cruciate ligament (ACL), or both ALL and ACL on kinematics under dynamic loading conditions using dynamic simulation subject-specific knee models. Methods. Five subject-specific musculoskeletal models were validated with computationally predicted muscle activation, electromyography data, and previous experimental data to analyze effects of the ALL and ACL on knee kinematics under gait and squat loading conditions. Results. Anterior translation (AT) significantly increased with deficiency of the ACL, ALL, or both structures under gait cycle loading. Internal rotation (IR) significantly increased with deficiency of both the ACL and ALL under gait and squat loading conditions. However, the deficiency of ALL was not significant in the increase of AT, but it was significant in the increase of IR under the squat loading condition. Conclusion. The results of this study confirm that the ALL is an important lateral knee structure for knee joint stability. The ALL is a secondary stabilizer relative to the ACL under simulated gait and squat loading conditions. Cite this article: Bone Joint Res 2019;8:509–517


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 58 - 58
11 Apr 2023
Jansen M Salzlechner C Barnes E DiFranco M Custers R Watt F Vincent T Lafeber F Mastbergen S
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Knee joint distraction (KJD) has been associated with clinical and structural improvement and synovial fluid (SF) marker changes. However, structural changes have not yet been shown satisfactorily in regular care, since radiographic acquisition was not fully standardized. AI-based modules have shown great potential to reduce reading time, increase inter-reader agreement and therefore function as a tool for treatment outcome assessment. The objective was to analyse structural changes after KJD in patients using this AI-based measurement method, and relate these changes to clinical outcome and SF markers. 20 knee OA patients (<65 years old) were included in this study. KJD treatment was performed using an external fixation device, providing 5 mm distraction for 6 weeks. SF was aspirated before, during and immediately after treatment. Weight-bearing antero-posterior knee radiographs and WOMAC questionnaires were collected before and ~one year after treatment. Radiographs were analysed with the Knee Osteoarthritis Labelling Assistant (KOALA, IB Lab GmbH, Vienna, Austria), and 10 pre-defined biomarker levels in SF were measured by immunoassay. Radiographic one-year changes were analysed and linear regression was used to calculate associations between changes in standardized joint space width (JSW) and WOMAC, and changes in JSW and SF markers. After treatment, radiographs showed an improvement in Kellgren-Lawrence grade in 7 of 16 patients that could be evaluated; 3 showed a worsening. Joint space narrowing scores and continuous JSW measures improved especially medially. A greater improvement in JSW was significantly associated with a greater improvement in WOMAC pain (β=0.64;p=0.020). A greater increase in MCP1 (β=0.67;p=0.033) and lower increase in TGFβ1 (β=-0.787;p=0.007) were associated with JSW improvement. Despite the small number of patients, also in regular care KJD treatment shows joint repair as measured automatically on radiographs, significantly associated with certain SF marker change and even with clinical outcome


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 149 - 149
4 Apr 2023
Killen B Willems M Hoang H Verschueren S Jonkers I
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The aim of this research was to determine biomechanical markers which differentiate medial knee osteoarthritis (OA) patients who do and do not show structural progression over a 2-year period. A cohort of 36 subjects was selected from a longitudinal study (Meireles et al 2017) using Kellgren-Lawrence (KL) scores at baseline and 2-year follow-up. The cohort consisted of 10 healthy controls (HC) (KL=0 at both time points), 15 medial knee OA non-progressors (NPKOA) (KL≥1 at baseline and no change over 2 years), and 11 medial knee OA progressors (PKOA) (KL≥1 at baseline and increase of ≥1 over 2 years). 3D integrated motion capture data from three walking trials were processed through a musculoskeletal modelling framework (Smith et al 2016) to estimate knee joint loading parameters (i.e., magnitude of mean contact pressure, and centre of pressure (COP)). Parameters at first and second peak were extracted and compared between groups using Kruskal-Wallis and Mann-Whitney tests. Higher magnitudes were observed in PKOA vs NPKOA, and PKOA vs HC groups at both time points. Additionally, a posterior (1st and 2nd peak), and lateral (2nd peak) shift in medial compartment COP was shown between PKOA and NPKOA, and PKOA and HC subjects. Interestingly, in the studied parameters, no differences were observed between NPKOA and HC groups. Significantly higher magnitude, and a more posterior and lateral COP was observed between PKOA and NPKOA patients. These differences, combined with an absence of difference between NPKOA and HC suggest structural OA progression is driven by a combination of altered loading magnitude and location. These results may serve as guidelines for targeted gait retraining rehabilitation to slow or stop knee OA progression whereby shifting COP anterior and medial and reducing magnitude by ~22% may shift patients from a PKOA to a NPKOA trajectory


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_7 | Pages 61 - 61
1 Jul 2022
Wang D Willinger L Athwal K Williams A Amis A
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Abstract. Background. Little scientific evidence is available regarding the effect of knee joint line obliquity (JLO). Methods. 10 fresh-frozen human cadaveric knees were axially loaded to 1500 N in a materials testing machine with the joint line tilted 0, 4, 8, and 12 degrees varus and valgus, at 0, and 20 degrees of knee flexion. The mechanical compression axis was aligned to the centre of the tibial plateau. Contact pressures / areas were recorded by sensors inserted between the tibia and femur below the menisci. Changes in relative femoral and tibial position in the coronal plane were obtained by an optical tracking system. Results. medial and lateral JLO caused significant tibiofemoral subluxation and pressure distribution changes. Medial (varus) JLO caused the femur to sublux medially down the coronal slope of the tibial plateau, and vice versa for lateral (valgus) downslopes (P=0.01). Areas of peak pressure moved 12 mm and 8 mm across the medial and lateral condyles, onto the ‘downhill’ meniscus and the ‘uphill’ tibial spine. Changes in JLO had only small effects on maximum contact pressures. Conclusion. A change of JLO during load bearing caused significant mediolateral tibiofemoral subluxation. The femur slid down the slope of the tibial plateau to abut the tibial eminence and also to rest on the downhill meniscus. Clinical Relevance. These results provide important information for understanding the consequences of creating coronal JLO and for clinical practice in terms of osteotomy planning regarding the effect on JLO


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_1 | Pages 42 - 42
1 Feb 2020
Innocenti B Bori E Paszicsnyek T
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INTRODUCTION. Applying the proper amount of tension to knees collateral ligaments during surgery is a prerequisite to achieve optimal performance after TKA. It must be taken into account that lower values of ligament tension could lead to an instable joint while higher values could induce over-tensioning thus leading to problems at later follow-up: a “functional stability” must then be defined and achieved to guarantee the best results. In this study, an experimental cadaveric activity was performed to measure the minimum tension required to achieve functional stability in the knee joint. METHODS. Ten cadaveric knee specimens were investigated; each femur and tibia was fixed with polyurethane foam in specific designed 3D-printed fixtures and clamped to a loading frame. A constant displacement rate of 0.05 mm/s was applied to the femoral clamp in order to achieve joint stability and the relative force was measured by the machine: the lowest force guaranteeing joint stability was then determined to be the one corresponding to the slope change in the force/displacement curve, representing the activation of the elastic region of both collateral ligaments. The force span between the slack region and the found point was considered to be the tension required to reach the functional stability of the joint. This methodology was applied on intact knee, after ACL-resection and after further PCL-resection in order to simulate the knee behavior in CR and PS implants. The test was performed at 0, 30, 60 and 90° of flexion using a specifically designed device. Each configuration was analyzed three times for the sake of repeatability. RESULTS. Results demonstrated that an overall tension of 40–50N is sufficient to reach stability in native knee with intact cruciate ligaments. Similar values appear to be sufficient in an ACL-resected knee, while higher tension is required (up to 60N) for stability after ACL and PCL resection. Moreover, the tension required for stabilization was slightly higher at 60° of flexion compared to the one required at the other angles, reflecting thus the mid-flection instability behavior. DISCUSSION AND CONCLUSIONS. The results are in agreement to other experimental studies. 1,2. and show that the tensions necessary to stabilize a knee joint in different ligament conditions are way lower than the ones usually applied via tensioners nowadays. To reach functional stability, surgeons should consider such results intraoperatively to avoid laxity, mid-flexion instability or ligament over-tension


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 4 - 4
2 Jan 2024
Han S Yoo Y Choi H Lee K Korhonen R Esrafilian A
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It is known that the gait dynamics of elderly substantially differs from that of young people. However, it has not been well studied how this age-related gait dynamics affects the knee biomechanics, e.g., cartilage mechanical response. In this study, we investigated how aging affects knee biomechanics in a female population using subject-specific computational models.

Two female subjects (ages of 23 and 69) with no musculoskeletal disorders were recruited. Korea National Institute for Bioethics Policy Review Board approved the study. Participants walked at a self-selected speed (SWS), 110% of SWS, and 120% of SWS on 10 m flat ground. Three-dimensional marker trajectories and ground reaction forces (Motion Analysis, USA), and lower limbs’ muscle activities were measured (EMG, Noraxon USA). Knee cartilage and menisci geometries were obtained from subjects’ magnetic resonance images (3T, GE Health Care). An EMG-assisted musculoskeletal finite element modeling workflow was used to estimate knee cartilage tissue mechanics in walking trials. Knee cartilage and menisci were modeled using a transversely isotropic poroviscoelastic material model.

Walking speed in SWS, 110%, and 120% of SWS were 1.38 m/s, 1.51 m/s, and 1.65 m/s for the young, and 1.21 m/s, 1.34 m/s and 1.46 m/s for the elderly, respectively. The maximum tensile stress in the elderly tibial cartilage was ~25%, ~33%, and ~32% lower than the young at SWS, 110%, and 120% of SWS, respectively. These preliminary results suggest that the cartilage in the elderly may not have enough stimulation even at 20% increases in walking speed, which may be one reason for tissue degeneration. To enhance these findings, further study with more subjects and different genders will investigate how age-related gait dynamics affects knee biomechanics.

Acknowledgments: Australian NHMRC Ideas Grant (APP2001734), KITECH (JE220006)


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 122 - 122
1 Mar 2021
Teunissen M Popov-Celeketic J Coeleveld K Meij BP Lafeber F Tryfonidou MA Mastbergen SC
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Knee joint distraction (KJD) is a joint-preserving treatment strategy for severe osteoarthritis (OA) that provides long-term clinical and structural improvement. Data from both human trials and animal models indicate clear cartilage regeneration from 6 months and onwards post-KJD. However, recent work showed that during distraction, the balance between catabolic and anabolic indicators is directed towards catabolism, as indicated by collagen type 2 markers, proteoglycan (PG) turnover and a catabolic transcription profile [unpublished data]. The focus of this study was to investigate the cartilage directly and 10 weeks after joint distraction in order to elucidate the shift from a catabolic to an anabolic cartilage state. Knee OA was induced bilaterally in 8 dogs according to the groove model. After 10 weeks of OA induction, all 8 animals received right knee joint distraction, employing the left knee as an OA control. After 8 weeks of distraction, 4 dogs were euthanized and after 10 weeks of follow-up the 4 other dogs. Macroscopic cartilage degeneration and synovial tissue inflammation was assessed using the OARSI canine scoring system. PG content was determined spectrometrically using Alcian Blue dye solution and the synthesis of newly formed PGs was determined using . 35. SO. 4. 2-. as a tracer, as was described before. Directly after KJD, macroscopic cartilage damage of the right tibial plateau was higher compared to the left OA control (OARSI score: 1.7±0.2 vs 0.6±0.3; p < 0.001). 10 weeks post-KJD this difference persisted (OARSI score: 1.4± 0.6 vs 0.6±0.3; p = 0.05). Directly after KJD, there was no difference in synovial inflammation between KJD and OA control (OARSI score: 1.4±0.5). At 10 weeks synovial inflammation increased significantly in the distracted knee (OARSI score: 2.1±0.3 vs 1.4±0.5; p < 0.05). Biochemical analysis of the tibia cartilage directly after KJD revealed a lower PG content (20.1±10.3 mg/g vs 23.7±11.7 mg/g). At 10 weeks post-KJD this difference in PG content was less (24.8±6.8 mg/g vs 25.4±7.8 mg/g). The PG synthesis rate directly after KJD appeared significantly lower vs. OA (1.4±0.6 nmol/h.g vs 5.9±4.4 nmol/h.g; p < 0.001)). However, 10 weeks post-KJD this difference was not detected (3.7±1.2 nmol/h.g vs 2.9±0.8 nmol/h.g), and the synthesis rate in the distracted knee was increased compared to directly after distraction (p < 0.01). Further in-depth investigation of the material is ongoing; these first results suggest that the shift from a catabolic to an anabolic state occurs within the first weeks after joint distraction, mostly reflected in the biochemical changes. As such, the post-distraction period seems to be essential in identifying key-players that support intrinsic cartilage repair


Bone & Joint Research
Vol. 12, Issue 12 | Pages 702 - 711
1 Dec 2023
Xue Y Zhou L Wang J

Aims

Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA.

Methods

First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 353 - 361
10 Jul 2024
Gardete-Hartmann S Mitterer JA Sebastian S Frank BJH Simon S Huber S Löw M Sommer I Prinz M Halabi M Hofstaetter JG

Aims. This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool. Methods. Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures. Results. The JI panel detected microorganisms in 7/48 (14.5%) and 15/67 (22.4%) cases related to UNCs and SPCs, respectively, but not in cases of UPCs. The correlation between JI panel detection and infection classification criteria for early/late acute and chronic PJI was 46.6%, 73%, and 40%, respectively. Overall, the JI panel identified 12.6% additional microorganisms and three new species. The JI panel pathogen identification showed a sensitivity and specificity of 41.4% (95% confidence interval (CI) 33.7 to 49.5) and 91.1% (95% CI 84.7 to 94.9), respectively. In total, 19/195 (9.7%) could have been managed differently and more accurately upon JI panel evaluation. Conclusion. Despite its microbial limitation, JI panel demonstrated clinical usefulness by complementing the traditional methods based on multiple cultures, particularly in PJI with unclear microbiological results. Cite this article: Bone Joint Res 2024;13(7):353–361


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 4 - 4
1 Dec 2021
J⊘rgensen AR Hanberg P Bue M Thomassen MB J⊘rgensen N Stilling M
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Aim. This study evaluated target tissue concentrations of double dose cefuroxime administered intravenously as either one 15 min infusion of 3,000 mg (Group 1) or two single 15 min infusions of 1,500 mg administered 4 h apart (Group 2). Method. Sixteen pigs were randomised into two groups of eight. Cortical and cancellous bone, synovial fluid of the knee joint and subcutaneous adipose tissue concentrations were measured based on sampling via microdialysis. Plasma samples were collected as a reference. Comparison of the groups was based on time with concentrations above relevant minimal inhibitory concentrations (fT>MIC) of 4 μg/mL. Results. The mean time fT>MIC (4 μg/mL) across compartments was longer for Group 2 (280–394 min) than for Group 1 (207–253 min) (p<0.01). Cortical bone showed a tendency towards longer fT>MIC (4 μg/mL) in Group 2 (280 min) than in Group 1 (207 min) (p=0.053). Within 50 min after administration, the mean concentration of 4 μg/mL was reached in all compartments for both groups. The mean concentrations decreased below 4 μg/mL after approximately 4 h (Group 1) and 3 h (Group 2) from initiation of administration (time zero). Conclusions. During an 8 h interval, double-dose cefuroxime administered as 2 × 1,500 mg with a 4 h interval provides longer time above MIC breakpoint for Staphylococcus aureus (4 μg/mL) than a single bolus of 3,000 mg cefuroxime. To maintain sufficient tissue concentrations during longer surgeries, re-administration of cefuroxime (1,500 mg) should be considered 3 h after the first administration


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 441 - 441
1 Dec 2013
Murase K Tsutsumi S Takai S Yoshino N
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The contact condition in the human knee joint must play important roles especially in dynamic loading situations where the loads transfer in the knee. In this study, the impact stress propagations through the inside of the knee joint were simulated using the three-dimensional finite element analysis (FEA). And the differences in the stress distribution were investigated between the intact knee and the total replacement condition. The finite element (FE) models of an intact human knee joint and a total replaced knee joint were constructed with high shape fidelity. The intact model included the cortical bone, cancellous bone, articular cartilage, bone marrow, and meniscus. And the total replacement knee FE model, which is consisted of the artificial femoral and tibial components were also prepared to compare the impact propagations with the intact model (Figure 1). Impact load were applied to the proximal femur of the FE models under the same conditions as those of the weight-drop experiments with the knee joint specimens. The FEA results showed that the impact stress propagated to the tibia through the knee joint for several milliseconds. The values and the time dependent change of the compressive strain on the cortical surface had good agreement with the experimental results. The compressive stress mainly propageted at the medial side, with 1.0 MPa at 1.2 milliseconds. Especially, the impact stress propagated not only in the cortical surface area which has hard material property but also in the soft cancellous bone region inside the knee joint. The mass density of the cancellous bone has similar to that of the cortical bone, and thus the role of the load bearing in the cancellous area must be much increasing under the impact condition. In the total replacement model, concentration of the impact compressive stress was observed with 2.8 MPa at the tibial region, while not under the normal intact conditions (Figure 2). Since the total replacement model is formed of different materials and the impact propagations were inhibited by the interfacial condition, such as sliding or debonding, it is considered that the contact condition between such materials have a great effect on the stress propagation


The Bone & Joint Journal
Vol. 99-B, Issue 1 | Pages 51 - 58
1 Jan 2017
van der Woude JAD Wiegant K van Heerwaarden RJ Spruijt S Emans PJ Mastbergen SC Lafeber FPJG

Aims. Knee joint distraction (KJD) is a relatively new, knee-joint preserving procedure with the goal of delaying total knee arthroplasty (TKA) in young and middle-aged patients. We present a randomised controlled trial comparing the two. Patients and Methods. The 60 patients ≤ 65 years with end-stage knee osteoarthritis were randomised to either KJD (n = 20) or TKA (n = 40). Outcomes were assessed at baseline, three, six, nine, and 12 months. In the KJD group, the joint space width (JSW) was radiologically assessed, representing a surrogate marker of cartilage thickness. Results. In total 56 patients completed their allocated treatment (TKA = 36, KJD = 20). All patient reported outcome measures improved significantly over one year (p < 0.02) in both groups. At one year, the TKA group showed a greater improvement in only one of the 16 patient-related outcome measures assessed (p = 0.034). Outcome Measures in Rheumatology-Osteoarthritis Research Society International clinical response was 83% after TKA and 80% after KJD. A total of 12 patients (60%) in the KJD group sustained pin track infections. In the KJD group both mean minimum (0.9 mm, standard deviation (. sd. ) 1.1) and mean JSW (1.2 mm, . sd. 1.1) increased significantly (p = 0.004 and p = 0.0003). Conclusion. In relatively young patients with end-stage knee osteoarthritis, KJD did not demonstrate inferiority of outcomes at one year when compared with TKA. However, there is a high incidence of pin track infection associated with KJD. Cite this article: Bone Joint J 2017;99-B:51–8