Vidyadhar V Upasani, Christine L Farnsworth, Jason P Caffrey, Tony Olmert, Ian Brink, Phoebe Cain, Erin Mannen
{"title":"Defining the segmental tension generated in a vertebral body tethering system for scoliosis.","authors":"Vidyadhar V Upasani, Christine L Farnsworth, Jason P Caffrey, Tony Olmert, Ian Brink, Phoebe Cain, Erin Mannen","doi":"10.1002/jor.25995","DOIUrl":"https://doi.org/10.1002/jor.25995","url":null,"abstract":"<p><p>Vertebral body tethering (VBT) uses a flexible tether affixed across the curve convexity with tension applied at each segment to treat scoliosis. Intraoperative tether tension may be achieved directly with a counter-tensioner or with an extension spring tube. The purpose of this study was to quantify the force generated with and without the extension spring tube using current FDA-approved VBT instrumentation, to understand the variation between surgeons using the same instrumentation, and to define the force range that is generated intra-operatively. Using a benchtop mechanical testing setup to simulate a spinal segment, we affixed the tether and applied tension using a tensioner and counter-tensioner alone (method T1) or by adding an extension spring tube (method T2). Eight orthopedic surgeons used T1 and T2 at six tensioner settings, and one surgeon completed three trials. A two-way ANOVA with a Tukey's HSD post hoc test (p < 0.05) compared the tensioner methods and testing levels. Inter- and intra-rater reliabilities were calculated using intraclass correlation coefficients (ICCs). Methods T1 and T2 exhibited linear tension-setting relationships, with high determination coefficients (R<sup>2</sup> > 0.93). T2 consistently produced higher forces (increase of 62.1 N/setting), compared to T1 (increase of 50.6 N/setting, p < 0.05). Inter-rater reliability exhibited excellent agreement (ICC = 0.951 and 0.943 for T1 and T2, respectively), as did intra-rater reliability (ICC = 0.971).</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jay M. McKinney, Krishna A. Pucha, Fabrice C. Bernard, J. Brandon Dixon, Thanh N. Doan, Nick J. Willett
{"title":"Osteoarthritis early-, mid- and late-stage progression in the rat medial meniscus transection model","authors":"Jay M. McKinney, Krishna A. Pucha, Fabrice C. Bernard, J. Brandon Dixon, Thanh N. Doan, Nick J. Willett","doi":"10.1002/jor.25969","DOIUrl":"10.1002/jor.25969","url":null,"abstract":"<p>Osteoarthritis is a degenerative disease of synovial joints affecting all tissues, including articular cartilage and subchondral bone. Osteoarthritis animal models can recapitulate aspects of human disease progression and are used to test efficacy of drugs, biomaterials, and cell therapies. The rat medial meniscus transection (MMT) model is a surgically induced posttraumatic osteoarthritis model commonly used for preclinical therapeutic screening. We describe herein, the qualitative and quantitative changes to articular cartilage, subchondral bone, and formation of osteophytes at early-, mid-, and late-stages of osteoarthritis progression. Tibia of MMT-operated animals showed proteoglycan loss and fibrillation along articular cartilage surfaces as early as 3-weeks post-surgery. With contrast-enhanced micro-CT technique, quantitative, 3-dimensional analysis of the tibia showed that the articular cartilage thickened at 3- and 6-weeks post-surgery and decreased at 12-weeks post-surgery. This decreased cartilage thickness corresponded with increased lesions in the articular cartilage that led to its full degradation and exposing the subchondral bone layer. Further, subchondral bone thickening was significant at 6-weeks post-surgery and followed cartilage damage. Osteophytes were found as early as 3-weeks post-surgery and coincided with articular cartilage degradation. Cartilaginous osteophytes preceded mineralization, suggesting endochondral ossification. The rat MMT model has predominantly been used out to 3-weeks, and most studies determined the effect of therapies to delay or prevent the onset of osteoarthritis. We provide evidence that an extension of the rat MMT model out to 6- and 12-weeks more resembled severe phenotypes of human osteoarthritis. Thus, evaluating novel therapeutics at late-stage will be important for eventual clinical translation.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 1","pages":"102-116"},"PeriodicalIF":2.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25969","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martin Barylak, Sara L Arena, Stephanie H Carpentier, Robin M Queen
{"title":"Gait stability improves following unilateral total ankle arthroplasty.","authors":"Martin Barylak, Sara L Arena, Stephanie H Carpentier, Robin M Queen","doi":"10.1002/jor.25992","DOIUrl":"https://doi.org/10.1002/jor.25992","url":null,"abstract":"<p><p>End-stage ankle arthritis is often treated surgically by total ankle arthroplasty (TAA) due to its potential to improve gait through increased joint range of motion and reduce pain. However, TAA's effect on gait stability is not well understood. This study explores the impact of TAA on gait stability, measured by Margin of Stability (MoS), in 148 patients with end-stage ankle arthritis. Kinematic data were collected pre-operatively, at 1-year post-op, and at 2-years post-op and the MoS was determined at heel strike and midstance for the anteroposterior (MoS<sub>AP</sub>) and mediolateral (MoS<sub>ML</sub>) directions. A linear mixed effects model including gait speed as a factor was used to assess the effects of limb, session, and their interaction on outcome measures. A significant interaction (p < 0.002) between limb (surgical, nonsurgical) and session (pre-op, 1-year post-op, 2-years post-op) was identified for each MoS variable of interest. Cumulatively, our results suggest that the nonsurgical limb, MoS<sub>AP</sub> at heel strike and MoS<sub>ML</sub> at midstance improved (increased) as time from surgery increased. These results suggest patients developed a compensatory movement pattern to navigate surgical limb single support. TAA reduces this compensation improving side-to-side symmetry, while not fully restoring symmetry by 2-years post-op. These results indicate that TAA could improve gait stability in patients with end-stage ankle arthritis, but further work is needed to understand the impact of TAA on altering fall risk.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Niels Vanvelk, Karen L de Mesy Bentley, Michael H J Verhofstad, Willem-Jan Metsemakers, Thomas F Moriarty, Claudia Siverino
{"title":"Development of an ex vivo model to study Staphylococcus aureus invasion of the osteocyte lacuno-canalicular network.","authors":"Niels Vanvelk, Karen L de Mesy Bentley, Michael H J Verhofstad, Willem-Jan Metsemakers, Thomas F Moriarty, Claudia Siverino","doi":"10.1002/jor.25988","DOIUrl":"https://doi.org/10.1002/jor.25988","url":null,"abstract":"<p><p>Staphylococcus aureus has multiple mechanisms to evade the host's immune system and antibiotic treatment. One such mechanism is the invasion of the osteocyte lacuno-canalicular network (OLCN), which may be particularly important in recurrence of infection after debridement and antibiotic therapy. The aim of this study was to develop an ex vivo model to facilitate further study of S. aureus invasion of the OLCN and early-stage testing of antibacterial strategies against bacteria in this niche. The diameter of the canaliculi of non-infected human, sheep, and mouse bones was measured microscopically on Schmorl's picrothionin stained sections, showing a large overlap in canalicular diameter. S. aureus successfully invaded the OLCN in all species in vitro as revealed by presence in osteocyte lacunae in Brown and Brenn-stained sections and by scanning electron microscopy. Murine bones were then selected for further experiments, and titanium pins with either a wild-type or ΔPBP4 mutant S. aureus USA300 were placed trans-cortically and incubated for 2 weeks in tryptic soy broth. Wild-type S. aureus readily invaded the osteocyte lacunae in mouse bones while the ΔPBP4 showed a significantly lower invasion of the OLCN (p = 0.0005). Bone specimens were then treated with gentamicin, sitafloxacin, R14 bacteriophages, or left untreated. Gentamicin (p = 0.0027) and sitafloxacin (p = 0.0280) significantly reduced the proportion of S. aureus-occupied lacunae, whilst bacteriophage treatment had no effect. This study shows that S. aureus is able to invade the OLCN in an ex vivo model. This ex vivo model can be used for future early-stage studies before proceeding to in vivo studies.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Structural, compositional, and functional effects of blunt and sharp cartilage damage on the joint: A 9-month equine groove model study”","authors":"","doi":"10.1002/jor.25991","DOIUrl":"10.1002/jor.25991","url":null,"abstract":"<p>te Moller NCR, Mohammadi A, Plomp S, et al. Structural, compositional, and functional effects of blunt and sharp cartilage damage on the joint: A 9-month equine groove model study. J Orthop Res.2021;39:2363–2375.</p><p>In the supporting information document <i>jor24971-sup-0007-Supplementary_Material-EquineGrooveModel_12-2020.pdf</i>, on page 22, the Supplementary data set is mentioned: “Data generated by this research and used for analysis in the current paper, will be made available from data repository.” The link to this data set was missing. The data can be accessed via the link below:</p><p>https://public.yoda.uu.nl/dgk/UU01/0TO6PE.html</p><p>And has the following persistent identifier:</p><p>doi:10.24416/UU01-0TO6PE</p><p>We apologize for the delay.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 1","pages":"238"},"PeriodicalIF":2.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessing postural stability in flatfoot using a time-in-boundary method during single-leg standing.","authors":"Paul S Sung, Dongchul Lee","doi":"10.1002/jor.25987","DOIUrl":"https://doi.org/10.1002/jor.25987","url":null,"abstract":"<p><p>Flatfoot, a foot deformity characterized by the collapse of the arch, significantly impacts an individual's balance and stability. This study explored postural adjustments and sway excursions in individuals with and without flatfoot using the Time-in-Boundary method. This method assessed relative stability by exploring various center of pressure radius thresholds during three trials of single-leg stance. We observed significant interactions in threshold levels (F = 4.37, p = 0.04) and normalized relative stable times (F = 7.64, p = 0.01), particularly in the initial trials. Initially, the flatfoot group showed marked decreases in stable times at 10 mm, 15 mm, and 20 mm thresholds, which expanded to 25 mm and 30 mm in subsequent trials. Despite a significant decrease in stability at the 30 mm threshold in early trials, participants exhibited improved stability control as trials progressed. This enhancement likely reflects a combination of a learning effect and an increased understanding of the task requirements, underscoring the adaptability of postural control systems to the biomechanical challenges posed by flatfoot. The Time-in-Boundary method has proven to be an effective tool for clinicians to assess postural control, playing a vital role in developing customized rehabilitation strategies for individuals with flatfoot.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Suramin enhances proliferation, migration, and tendon gene expression of human supraspinatus tenocytes.","authors":"Shih-Hao Huang, Chih-Chien Wang, Po-Chih Shen, Zi-Miao Liu, Shu-Jung Chen, Yin-Chun Tien, Cheng-Chang Lu","doi":"10.1002/jor.25990","DOIUrl":"https://doi.org/10.1002/jor.25990","url":null,"abstract":"<p><p>Rotator cuff tendinopathy is a common musculoskeletal disorder with limited pharmacological treatment strategies. This study aimed to investigate tenocytes' functional in vitro response from a ruptured supraspinatus tendon to suramin administration and to elucidate whether suramin can enhance tendon repair and modulate the inflammatory response to injury. Tenocytes were obtained from human supraspinatus tendons (n = 6). We investigated the effect of suramin on LPS-induced inflammatory responses and the underlying molecular mechanisms in THP-1 macrophages. Suramin enhanced the proliferation, cell viability, and migration of tenocytes. It also increased the protein expression of PCNA and Ki-67. Suramin-treated tenocytes exhibited increased expression of COL1A1, COL3A1, TNC, SCX, and VEGF. Suramin significantly reduced LPS-induced iNOS, COX2 synthesis, inflammatory cytokine TNF-α production, and inflammatory signaling by influencing the NF-κB pathways in THP-1 cells. Our results suggest that suramin holds great promise as a therapeutic option for treating rotator cuff tendinopathy.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Do Weon Lee, Hyuk-Soo Han, Du Hyun Ro, Yong Seuk Lee
{"title":"Development of the machine learning model that is highly validated and easily applicable to predict radiographic knee osteoarthritis progression","authors":"Do Weon Lee, Hyuk-Soo Han, Du Hyun Ro, Yong Seuk Lee","doi":"10.1002/jor.25982","DOIUrl":"10.1002/jor.25982","url":null,"abstract":"<p>Many models using the aid of artificial intelligence have been recently proposed to predict the progression of knee osteoarthritis. However, previous models have not been properly validated with an external data set or have reported poor predictive performances. Therefore, the purpose of this study was to design a machine learning model for knee osteoarthritis progression, focusing on high validation quality and clinical applicability. A retrospective analysis was conducted on prospectively collected data, using the Osteoarthritis Initiative data set (5966 knees) for model development and the Multicenter Osteoarthritis Study data set (3392 knees) for validation. The analysis aimed to predict Kellgren–Lawrence grade (KLG) progression over 4–5 years in knees with initial KLG of 0, 1, or 2. Possible predictors included demographics, comorbidities, history of meniscectomy, gait speed, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and radiological findings. The Random Forest algorithm was employed for the predictive model development. Baseline KLG, contralateral knee osteoarthritis, lateral joint space narrowing (JSN) grade, BMI, medial JSN grade, and total WOMAC score were six features selected for the model in descending order of importance. Odds ratios of baseline KLG, contralateral knee osteoarthritis, and lateral JSN grade were 1.76, 2.59, and 4.74, respectively (all <i>p</i> < 0.001). The area-under-the-curve of the ROC curve in the validation set was 0.76 with an accuracy of 0.68 and an F1-score of 0.56. The progression of knee osteoarthritis in 4 ~ 5 years could be well-predicted using easily available variables. This simple and validated model may aid surgeons in knee osteoarthritis patient management.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 1","pages":"128-138"},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily K Bliven, Anita Fung, Alexander Baker, Ingmar Fleps, Stephen J Ferguson, Pierre Guy, Benedikt Helgason, Peter A Cripton
{"title":"How accurately do finite element models predict the fall impact response of ex vivo specimens augmented by prophylactic intramedullary nailing?","authors":"Emily K Bliven, Anita Fung, Alexander Baker, Ingmar Fleps, Stephen J Ferguson, Pierre Guy, Benedikt Helgason, Peter A Cripton","doi":"10.1002/jor.25984","DOIUrl":"https://doi.org/10.1002/jor.25984","url":null,"abstract":"<p><p>Hip fracture prevention approaches like prophylactic augmentation devices have been proposed to strengthen the femur and prevent hip fracture in a fall scenario. The aim of this study was to validate the finite element model (FEM) of specimens augmented by prophylactic intramedullary nailing in a simulated sideways fall impact against ex vivo experimental data. A dynamic inertia-driven sideways fall simulator was used to test six cadaveric specimens (3 females, 3 males, age 63-83 years) prophylactically implanted with an intramedullary nailing system used to augment the femur. Impact force measurements, pelvic deformation, effective pelvic stiffness, and fracture outcomes were compared between the ex vivo experiments and the FEMs. The FEMs over-predicted the effective pelvic stiffness for most specimens and showed variability in terms of under- and over-predicting peak impact force and pelvis compression depending on the specimen. A significant correlation was found for time to peak impact force when comparing ex vivo and FEM data. No femoral fractures were found in the ex vivo experiments, but two specimens sustained pelvic fractures. These two pelvis fractures were correctly identified by the FEMs, but the FEMs made three additional false-positive fracture identifications. These validation results highlight current limitations of these sideways fall impact models specific to the inclusion of an orthopaedic implant. These FEMs present a conservative strategy for fracture prediction in future applications. Further evaluation of the modelling approaches used for the bone-implant interface is recommended for modelling augmented specimens, alongside the importance of maintaining well-controlled experimental conditions.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gilbert Smolyak, Andrew Rodenhouse, Anne E C Nichols, Constantinos Ketonis, Alayna E Loiselle
{"title":"Pharmacological antagonism of Ccr2+ cell recruitment to facilitate regenerative tendon healing.","authors":"Gilbert Smolyak, Andrew Rodenhouse, Anne E C Nichols, Constantinos Ketonis, Alayna E Loiselle","doi":"10.1002/jor.25986","DOIUrl":"10.1002/jor.25986","url":null,"abstract":"<p><p>Successful tendon healing requires sufficient deposition and remodeling of new extracellular matrix at the site of injury, with this process mediating in part through fibroblast activation via communication with macrophages. Moreover, resolution of healing requires clearance or reversion of activated cells, with chronic interactions with persistent macrophages impairing resolution and facilitating the conversion to fibrotic healing. As such, modulation of the macrophage environment represents an important translational target to improve the tendon healing process. Circulating monocytes are recruited to sites of tissue injury, including the tendon, via upregulation of cytokines including Ccl2, which facilitates recruitment of Ccr2<sup>+</sup> macrophages to the healing tendon. Our prior work has demonstrated that Ccr2<sup>-/-</sup> can modulate fibroblast activation and myofibroblast differentiation. However, this approach lacked temporal control and resulted in healing impairments. Thus, in the current study we have leveraged a Ccr2 antagonist to blunt macrophage recruitment to the healing tendon in a time-dependent manner. We first tested the effects of Ccr2 antagonism during the acute inflammatory phase and found that this had no effect on the healing process. In contrast, Ccr2 antagonism during the early proliferative/granulation tissue period resulted in significant improvements in mechanical properties of the healing tendon. Collectively, these data demonstrate the temporally distinct impacts of modulating Ccr2<sup>+</sup> cell recruitment and Ccr2 antagonism during tendon healing and highlight the translational potential of transient Ccr2 antagonism to improve the tendon healing process.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}