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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


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293


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


Bone & Joint Research
Vol. 6, Issue 6 | Pages 376 - 384
1 Jun 2017
Stentz-Olesen K Nielsen ET De Raedt S Jørgensen PB Sørensen OG Kaptein BL Andersen MS Stilling M

Objectives. Static radiostereometric analysis (RSA) using implanted markers is considered the most accurate system for the evaluation of prosthesis migration. By using CT bone models instead of markers, combined with a dynamic RSA system, a non-invasive measurement of joint movement is enabled. This method is more accurate than current 3D skin marker-based tracking systems. The purpose of this study was to evaluate the accuracy of the CT model method for measuring knee joint kinematics in static and dynamic RSA using the marker method as the benchmark. Methods. Bone models were created from CT scans, and tantalum beads were implanted into the tibia and femur of eight human cadaver knees. Each specimen was secured in a fixture, static and dynamic stereoradiographs were recorded, and the bone models and marker models were fitted to the stereoradiographs. Results. Results showed a mean difference between the two methods in all six degrees of freedom for static RSA to be within -0.10 mm/° and 0.08 mm/° with a 95% limit of agreement (LoA) ranging from ± 0.49 to 1.26. Dynamic RSA had a slightly larger range in mean difference of -0.23 mm/° to 0.16 mm/° with LoA ranging from ± 0.75 to 1.50. Conclusions. In a laboratory-controlled setting, the CT model method combined with dynamic RSA may be an alternative to previous marker-based methods for kinematic analyses. Cite this article: K. Stentz-Olesen, E. T. Nielsen, S. De Raedt, P. B. Jørgensen, O. G. Sørensen, B. L. Kaptein, M. S. Andersen, M. Stilling. Validation of static and dynamic radiostereometric analysis of the knee joint using bone models from CT data. Bone Joint Res 2017;6:376–384. DOI: 10.1302/2046-3758.66.BJR-2016-0113.R3


Bone & Joint Research
Vol. 5, Issue 7 | Pages 280 - 286
1 Jul 2016
Ozkurt B Sen T Cankaya D Kendir S Basarır K Tabak Y

Objectives. The purpose of this study was to develop an accurate, reliable and easily applicable method for determining the anatomical location of the joint line during revision knee arthroplasty. Methods. The transepicondylar width (TEW), the perpendicular distance between the medial and lateral epicondyles and the distal articular surfaces (DMAD, DLAD) and the distance between the medial and lateral epicondyles and the posterior articular surfaces (PMAD, DLAD) were measured in 40 knees from 20 formalin-fixed adult cadavers (11 male and nine female; mean age at death 56.9 years, . sd. 9.4; 34 to 69). The ratios of the DMAD, PMAD, DLAD and PLAD to TEW were calculated. Results. The mean TEW, DMAD, PMAD, DLAD and PLAD were 82.76 mm (standard deviation (. sd. ) 7.74), 28.95 mm (. sd. 3.3), 28.57 mm (. sd. 3), 23.97 mm (. sd. 3.27) and 24.42 mm (. sd. 3.14), respectively. The ratios between the TEW and the articular distances (DMAD/TEW, DLAD/TEW, PMAD/TEW and PLAD/TEW) were calculated and their means were 0.35 (. sd. 0.02), 0.34 (. sd. 0.02), 0.28 (. sd. 0.03) and 0.29 (. sd. 0.03), respectively. Conclusion. This method provides a simple, reproducible and reliable technique enabling accurate anatomical joint line restoration during revision total knee arthroplasty. Cite this article: B. Ozkurt, T. Sen, D. Cankaya, S. Kendir, K. Basarır, Y. Tabak. The medial and lateral epicondyle as a reliable landmark for intra-operative joint line determination in revision knee arthroplasty. Bone Joint Res 2016;5:280–286. DOI: 10.1302/2046-3758.57.BJR-2016-0002.R1


Bone & Joint Research
Vol. 5, Issue 11 | Pages 552 - 559
1 Nov 2016
Kang K Koh Y Son J Kwon O Baek C Jung SH Park KK

Objectives. Malrotation of the femoral component can result in post-operative complications in total knee arthroplasty (TKA), including patellar maltracking. Therefore, we used computational simulation to investigate the influence of femoral malrotation on contact stresses on the polyethylene (PE) insert and on the patellar button as well as on the forces on the collateral ligaments. Materials and Methods. Validated finite element (FE) models, for internal and external malrotations from 0° to 10° with regard to the neutral position, were developed to evaluate the effect of malrotation on the femoral component in TKA. Femoral malrotation in TKA on the knee joint was simulated in walking stance-phase gait and squat loading conditions. Results. Contact stress on the medial side of the PE insert increased with internal femoral malrotation and decreased with external femoral malrotation in both stance-phase gait and squat loading conditions. There was an opposite trend in the lateral side of the PE insert case. Contact stress on the patellar button increased with internal femoral malrotation and decreased with external femoral malrotation in both stance-phase gait and squat loading conditions. In particular, contact stress on the patellar button increased by 98% with internal malrotation of 10° in the squat loading condition. The force on the medial collateral ligament (MCL) and the lateral collateral ligament (LCL) increased with internal and external femoral malrotations, respectively. Conclusions. These findings provide support for orthopaedic surgeons to determine a more accurate femoral component alignment in order to reduce post-operative PE problems. Cite this article: K-T. Kang, Y-G. Koh, J. Son, O-R. Kwon, C. Baek, S. H. Jung, K. K. Park. Measuring the effect of femoral malrotation on knee joint biomechanics for total knee arthroplasty using computational simulation. Bone Joint Res 2016;5:552–559. DOI: 10.1302/2046-3758.511.BJR-2016-0107.R1


Bone & Joint Research
Vol. 3, Issue 3 | Pages 82 - 88
1 Mar 2014
Abdel MP Morrey ME Barlow JD Grill DE Kolbert CP An KN Steinmann SP Morrey BF Sanchez-Sotelo J

Objectives. The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model. Methods. A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively. Results. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection. . Conclusions. In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82–8


Objectives. The lack of effective treatment for cartilage defects has prompted investigations using tissue engineering techniques for their regeneration and repair. The success of tissue-engineered repair of cartilage may depend on the rapid and efficient adhesion of transplanted cells to a scaffold. Our aim in this study was to repair full-thickness defects in articular cartilage in the weight-bearing area of a porcine model, and to investigate whether the CD44 monoclonal antibody biotin-avidin (CBA) binding technique could provide satisfactory tissue-engineered cartilage. Methods. Cartilage defects were created in the load-bearing region of the lateral femoral condyle of mini-type pigs. The defects were repaired with traditional tissue-engineered cartilage, tissue-engineered cartilage constructed with the biotin-avidin (BA) technique, tissue-engineered cartilage constructed with the CBA technique and with autologous cartilage. The biomechanical properties, Western blot assay, histological findings and immunohistochemical staining were explored. Results. The CBA group showed similar results to the autologous group in biomechanical properties, Moran’s criteria, histological tests and Wakitani histological scoring. Conclusions. These results suggest that tissue-engineered cartilage constructed using the CBA technique could be used effectively to repair cartilage defects in the weight-bearing area of joints. Cite this article: H. Lin, J. Zhou, L. Cao, H. R. Wang, J. Dong, Z. R. Chen. Tissue-engineered cartilage constructed by a biotin-conjugated anti-CD44 avidin binding technique for the repairing of cartilage defects in the weight-bearing area of knee joints in pigs. Bone Joint Res 2017;6:–295. DOI: 10.1302/2046-3758.65.BJR-2016-0277


Bone & Joint Research
Vol. 5, Issue 8 | Pages 320 - 327
1 Aug 2016
van IJsseldijk EA Valstar ER Stoel BC Nelissen RGHH Baka N van’t Klooster R Kaptein BL

Objectives. An important measure for the diagnosis and monitoring of knee osteoarthritis is the minimum joint space width (mJSW). This requires accurate alignment of the x-ray beam with the tibial plateau, which may not be accomplished in practice. We investigate the feasibility of a new mJSW measurement method from stereo radiographs using 3D statistical shape models (SSM) and evaluate its sensitivity to changes in the mJSW and its robustness to variations in patient positioning and bone geometry. Materials and Methods. A validation study was performed using five cadaver specimens. The actual mJSW was varied and images were acquired with variation in the cadaver positioning. For comparison purposes, the mJSW was also assessed from plain radiographs. To study the influence of SSM model accuracy, the 3D mJSW measurement was repeated with models from the actual bones, obtained from CT scans. Results. The SSM-based measurement method was more robust (consistent output for a wide range of input data/consistent output under varying measurement circumstances) than the conventional 2D method, showing that the 3D reconstruction indeed reduces the influence of patient positioning. However, the SSM-based method showed comparable sensitivity to changes in the mJSW with respect to the conventional method. The CT-based measurement was more accurate than the SSM-based measurement (smallest detectable differences 0.55 mm versus 0. 82 mm, respectively). Conclusion. The proposed measurement method is not a substitute for the conventional 2D measurement due to limitations in the SSM model accuracy. However, further improvement of the model accuracy and optimisation technique can be obtained. Combined with the promising options for applications using quantitative information on bone morphology, SSM based 3D reconstructions of natural knees are attractive for further development. Cite this article: E. A. van IJsseldijk, E. R. Valstar, B. C. Stoel, R. G. H. H. Nelissen, N. Baka, R. van’t Klooster, B. L. Kaptein. Three dimensional measurement of minimum joint space width in the knee from stereo radiographs using statistical shape models. Bone Joint Res 2016;320–327. DOI: 10.1302/2046-3758.58.2000626


Bone & Joint Research
Vol. 2, Issue 11 | Pages 233 - 237
1 Nov 2013
Russell DF Deakin AH Fogg QA Picard F

Objectives. We performed in vitro validation of a non-invasive skin-mounted system that could allow quantification of anteroposterior (AP) laxity in the outpatient setting. Methods. A total of 12 cadaveric lower limbs were tested with a commercial image-free navigation system using trackers secured by bone screws. We then tested a non-invasive fabric-strap system. The lower limb was secured at 10° intervals from 0° to 60° of knee flexion and 100 N of force was applied perpendicular to the tibia. Acceptable coefficient of repeatability (CR) and limits of agreement (LOA) of 3 mm were set based on diagnostic criteria for anterior cruciate ligament (ACL) insufficiency. Results. Reliability and precision within the individual invasive and non-invasive systems was acceptable throughout the range of flexion tested (intra-class correlation coefficient 0.88, CR 1.6 mm). Agreement between the two systems was acceptable measuring AP laxity between full extension and 40° knee flexion (LOA 2.9 mm). Beyond 40° of flexion, agreement between the systems was unacceptable (LOA > 3 mm). Conclusions. These results indicate that from full knee extension to 40° flexion, non-invasive navigation-based quantification of AP tibial translation is as accurate as the standard validated commercial system, particularly in the clinically and functionally important range of 20° to 30° knee flexion. This could be useful in diagnosis and post-operative evaluation of ACL pathology. Cite this article: Bone Joint Res 2013;2:233–7


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 Research
Vol. 13, Issue 9 | Pages 485 - 496
13 Sep 2024
Postolka B Taylor WR Fucentese SF List R Schütz P

Aims. This study aimed to analyze kinematics and kinetics of the tibiofemoral joint in healthy subjects with valgus, neutral, and varus limb alignment throughout multiple gait activities using dynamic videofluoroscopy. Methods. Five subjects with valgus, 12 with neutral, and ten with varus limb alignment were assessed during multiple complete cycles of level walking, downhill walking, and stair descent using a combination of dynamic videofluoroscopy, ground reaction force plates, and optical motion capture. Following 2D/3D registration, tibiofemoral kinematics and kinetics were compared between the three limb alignment groups. Results. No significant differences for the rotational or translational patterns between the different limb alignment groups were found for level walking, downhill walking, or stair descent. Neutral and varus aligned subjects showed a mean centre of rotation located on the medial condyle for the loaded stance phase of all three gait activities. Valgus alignment, however, resulted in a centrally located centre of rotation for level and downhill walking, but a more medial centre of rotation during stair descent. Knee adduction/abduction moments were significantly influenced by limb alignment, with an increasing knee adduction moment from valgus through neutral to varus. Conclusion. Limb alignment was not reflected in the condylar kinematics, but did significantly affect the knee adduction moment. Variations in frontal plane limb alignment seem not to be a main modulator of condylar kinematics. The presented data provide insights into the influence of anatomical parameters on tibiofemoral kinematics and kinetics towards enhancing clinical decision-making and surgical restoration of natural knee joint motion and loading. Cite this article: Bone Joint Res 2024;13(9):485–496


Bone & Joint Research
Vol. 13, Issue 4 | Pages 149 - 156
4 Apr 2024
Rajamäki A Lehtovirta L Niemeläinen M Reito A Parkkinen J Peräniemi S Vepsäläinen J Eskelinen A

Aims. Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium. Methods. Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia. Results. Median metal concentrations were as follows: cobalt: 0.69 μg/g (interquartile range (IQR) 0.10 to 6.10); chromium: 1.1 μg/g (IQR 0.27 to 4.10); and titanium: 1.6 μg/g (IQR 0.90 to 4.07). Moderate ALVAL scores were found in 30% (n = 39) of the revised knees. There were ten patients with an ALVAL score of 6 or more who were revised for suspected periprosthetic joint infection (PJI), aseptic loosening, or osteolysis. R2 varied between 0.269 and 0.369 for the ordinal regression models. The most important variables were model type, indication for revision, and cobalt and chromium in the ordinal regression models. Conclusion. We found that metal particles released from the knee prosthesis can accumulate in the periprosthetic tissues. Several patients revised for suspected culture-negative PJI had features of an ALVAL reaction, which is a novel finding. Therefore, ALVAL-type reactions can also be found around knee prostheses, but they are mostly mild and less common than those found around metal-on-metal prostheses. Cite this article: Bone Joint Res 2024;13(4):149–156


Bone & Joint Research
Vol. 11, Issue 8 | Pages 575 - 584
17 Aug 2022
Stoddart JC Garner A Tuncer M Cobb JP van Arkel RJ

Aims. The aim of this study was to determine the risk of tibial eminence avulsion intraoperatively for bi-unicondylar knee arthroplasty (Bi-UKA), with consideration of the effect of implant positioning, overstuffing, and sex, compared to the risk for isolated medial unicondylar knee arthroplasty (UKA-M) and bicruciate-retaining total knee arthroplasty (BCR-TKA). Methods. Two experimentally validated finite element models of tibia were implanted with UKA-M, Bi-UKA, and BCR-TKA. Intraoperative loads were applied through the condyles, anterior cruciate ligament (ACL), medial collateral ligament (MCL), and lateral collateral ligament (LCL), and the risk of fracture (ROF) was evaluated in the spine as the ratio of the 95. th. percentile maximum principal elastic strains over the tensile yield strain of proximal tibial bone. Results. Peak tensile strains occurred on the anterior portion of the medial sagittal cut in all simulations. Lateral translation of the medial implant in Bi-UKA had the largest increase in ROF of any of the implant positions (43%). Overstuffing the joint by 2 mm had a much larger effect, resulting in a six-fold increase in ROF. Bi-UKA had ~10% increased ROF compared to UKA-M for both the male and female models, although the smaller, less dense female model had a 1.4 times greater ROF compared to the male model. Removal of anterior bone akin to BCR-TKA doubled ROF compared to Bi-UKA. Conclusion. Tibial eminence avulsion fracture has a similar risk associated with Bi-UKA to UKA-M. The risk is higher for smaller and less dense tibiae. To minimize risk, it is most important to avoid overstuffing the joint, followed by correctly positioning the medial implant, taking care not to narrow the bone island anteriorly. Cite this article: Bone Joint Res 2022;11(8):575–584


Bone & Joint Research
Vol. 12, Issue 5 | Pages 313 - 320
8 May 2023
Saiki Y Kabata T Ojima T Kajino Y Kubo N Tsuchiya H

Aims. We aimed to assess the reliability and validity of OpenPose, a posture estimation algorithm, for measurement of knee range of motion after total knee arthroplasty (TKA), in comparison to radiography and goniometry. Methods. In this prospective observational study, we analyzed 35 primary TKAs (24 patients) for knee osteoarthritis. We measured the knee angles in flexion and extension using OpenPose, radiography, and goniometry. We assessed the test-retest reliability of each method using intraclass correlation coefficient (1,1). We evaluated the ability to estimate other measurement values from the OpenPose value using linear regression analysis. We used intraclass correlation coefficients (2,1) and Bland–Altman analyses to evaluate the agreement and error between radiography and the other measurements. Results. OpenPose had excellent test-retest reliability (intraclass correlation coefficient (1,1) = 1.000). The R. 2. of all regression models indicated large correlations (0.747 to 0.927). In the flexion position, the intraclass correlation coefficients (2,1) of OpenPose indicated excellent agreement (0.953) with radiography. In the extension position, the intraclass correlation coefficients (2,1) indicated good agreement of OpenPose and radiography (0.815) and moderate agreement of goniometry with radiography (0.593). OpenPose had no systematic error in the flexion position, and a 2.3° fixed error in the extension position, compared to radiography. Conclusion. OpenPose is a reliable and valid tool for measuring flexion and extension positions after TKA. It has better accuracy than goniometry, especially in the extension position. Accurate measurement values can be obtained with low error, high reproducibility, and no contact, independent of the examiner’s skills. Cite this article: Bone Joint Res 2023;12(5):313–320


Bone & Joint Research
Vol. 12, Issue 1 | Pages 58 - 71
17 Jan 2023
Dagneaux L Limberg AK Owen AR Bettencourt JW Dudakovic A Bayram B Gades NM Sanchez-Sotelo J Berry DJ van Wijnen A Morrey ME Abdel MP

Aims. As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods. Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71


Bone & Joint Research
Vol. 13, Issue 7 | Pages 342 - 352
9 Jul 2024
Cheng J Jhan S Chen P Hsu S Wang C Moya D Wu Y Huang C Chou W Wu K

Aims. To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods. The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm. 2. , 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results. In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-β, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion. ESWT promoted the effect of TGF-β/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model. Cite this article: Bone Joint Res 2024;13(7):342–352


Bone & Joint Research
Vol. 13, Issue 5 | Pages 226 - 236
9 May 2024
Jürgens-Lahnstein JH Petersen ET Rytter S Madsen F Søballe K Stilling M

Aims. Micromotion of the polyethylene (PE) inlay may contribute to backside PE wear in addition to articulate wear of total knee arthroplasty (TKA). Using radiostereometric analysis (RSA) with tantalum beads in the PE inlay, we evaluated PE micromotion and its relationship to PE wear. Methods. A total of 23 patients with a mean age of 83 years (77 to 91), were available from a RSA study on cemented TKA with Maxim tibial components (Zimmer Biomet). PE inlay migration, PE wear, tibial component migration, and the anatomical knee axis were evaluated on weightbearing stereoradiographs. PE inlay wear was measured as the deepest penetration of the femoral component into the PE inlay. Results. At mean six years’ follow-up, the PE wear rate was 0.08 mm/year (95% confidence interval 0.06 to 0.09 mm/year). PE inlay external rotation was below the precision limit and did not influence PE wear. Varus knee alignment did not influence PE wear (p = 0.874), but increased tibial component total translation (p = 0.041). Conclusion. The PE inlay was well fixed and there was no relationship between PE stability and PE wear. The PE wear rate was low and similar in the medial and lateral compartments. Varus knee alignment did not influence PE wear. Cite this article: Bone Joint Res 2024;13(5):226–236


Bone & Joint Research
Vol. 13, Issue 2 | Pages 66 - 82
5 Feb 2024
Zhao D Zeng L Liang G Luo M Pan J Dou Y Lin F Huang H Yang W Liu J

Aims. This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results. A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion. The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets. Cite this article: Bone Joint Res 2024;13(2):66–82


Bone & Joint Research
Vol. 12, Issue 10 | Pages 624 - 635
4 Oct 2023
Harrison CJ Plessen CY Liegl G Rodrigues JN Sabah SA Beard DJ Fischer F

Aims. To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health. Methods. Patient-reported outcome measure (PROM) data measuring knee health were obtained from the NHS PROMs dataset and Total or Partial Knee Arthroplasty Trial (TOPKAT). Assumptions for common scale modelling were tested. A graded response model (fitted to OKS item responses in the NHS PROMs dataset) was used as an anchor to calibrate paired HAAS items from the TOPKAT dataset. Information curves for the combined OKS-HAAS model were plotted. Bland-Altman analysis was used to compare common scale scores derived from OKS and HAAS items. A conversion table was developed to map between HAAS, OKS, and the common scale. Results. We included 3,329 response sets from 528 patients undergoing knee arthroplasty. These generally met the assumptions of unidimensionality, monotonicity, local independence, and measurement invariance. The HAAS items provided more information than OKS items at high levels of knee health. Combining both instruments resulted in higher test-level information than either instrument alone. The mean error between common scale scores derived from the OKS and HAAS was 0.29 logits. Conclusion. The common scale allowed more precise measurement of knee health than use of either the OKS or HAAS individually. These techniques for mapping PROM instruments may be useful for the standardization of outcome reporting, and pooling results across studies that use either PROM in individual-patient meta-analysis. Cite this article: Bone Joint Res 2023;12(10):624–635