Bone & Joint Research最新文献

{"title":"Antimicrobial-laden PerOssal beads display in vitro inhibition and killing of extensively drug-resistant Gram-negative bacteria associated with conflict wounds in Ukraine.","authors":"Henry Adam Claireaux, Edward J A Douglas, Scott J C Pallett, Luke S P Moore, Matthew K O'Shea, Olena V Moshynets, Julian R Jones, Arul Ramasamy, Andrew M Edwards","doi":"10.1302/2046-3758.158.BJR-2026-0211.R1","DOIUrl":"https://doi.org/10.1302/2046-3758.158.BJR-2026-0211.R1","url":null,"abstract":"<p><strong>Aims: </strong>Open fractures sustained in contemporary conflict are associated with high-energy transfer, contamination with resistant bacteria, and delays to surgical care, resulting in high rates of infection. Similar conditions occur in civilian disasters, where crush injuries and overwhelmed healthcare systems prolong the interval to surgical wound excision. Prophylactic systemic antimicrobial regimens may be ineffective due to antimicrobial resistance or limited bioavailability in bone and joint tissues. Local antimicrobial delivery can provide higher drug concentrations within the wound, which may be sufficient to overcome resistance. This route is established in bone and joint infection, although evidence in conflict trauma is lacking. We evaluated the in vitro activity of antimicrobial-laden PerOssal hydroxyapatite and calcium sulphate beads.</p><p><strong>Methods: </strong>Bacterial isolates from Ukraine isolated from contaminated traumatic wounds were tested, including extensively drug-resistant (XDR) <i>Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa</i>, and <i>Escherichia coli</i>. The antimicrobial effects of antimicrobial-laden PerOssal beads were assessed by zone-of-inhibition testing and time-kill analysis.</p><p><strong>Results: </strong>All Gram-negative isolates from Ukraine were resistant to gentamicin, tobramycin, co-amoxiclav, cefazolin, and ciprofloxacin, with minimum inhibitory concentrations (MICs) exceeding European Committee on Animicrobial Susceptibility Testing (EUCAST) breakpoints. PerOssal beads laden with gentamicin, tobramycin, or cefazolin were weakly growth inhibitory. However, gentamicin-rifampicin in combination achieved consistent broad-spectrum bacterial inhibition and killing, while co-amoxiclav-loaded beads inhibited the growth of all bacterial strains.</p><p><strong>Conclusion: </strong>Antimicrobial-laden PerOssal hydroxyapatite and calcium sulphate beads displayed in vitro inhibition and killing of XDR Gram-negative bacteria associated with contaminated traumatic wounds. Early local antimicrobial delivery may reduce infection risk following heavily contaminated open fractures, particularly when surgical wound excision is delayed. This may be relevant to both modern conflict and civilian disaster settings. Further work is required to determine the effectiveness of this approach in vivo.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"1055-1066"},"PeriodicalIF":5.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting AHNAK ameliorates osteonecrosis of the femoral head and affects adipogenic pathways involving Smad/PPARγ.","authors":"Mei-Feng Chen, Chih-Chien Hu, Yi-Min Hsiao, Pei-Heng Jiang, Yung-Heng Hsu, Chia-Yun Wu, Steve W N Ueng, Yuhan Chang","doi":"10.1302/2046-3758.158.BJR-2025-0304.R2","DOIUrl":"https://doi.org/10.1302/2046-3758.158.BJR-2025-0304.R2","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to investigate the role of AHNAK in patients with osteonecrosis of the femoral head (ONFH) and its association with bone adipogenesis. Non-traumatic ONFH, primarily driven by steroid use and alcohol consumption, results in an imbalance between osteogenesis and adipogenesis. Understanding the function of AHNAK under ischaemic stress may help identify novel therapeutic targets for ONFH.</p><p><strong>Methods: </strong>Bone tissues from 19 ONFH patients and 15 control patients were analyzed using proteomics, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence (IF). A steroid-induced ONFH mouse model and an ischaemia-mimicking in vitro model using MC3T3-E1 preosteoblasts were employed to examine AHNAK expression and function. AHNAK knockdown was performed using short hairpin RNA (shRNA) to assess its regulatory effects on adipogenic markers and Smad/PPARγ/C/EBPα signalling.</p><p><strong>Results: </strong>AHNAK expression was significantly upregulated in bone tissues of ONFH patients and in femoral heads of steroid-induced ONFH mice. This was accompanied by reduced osteocyte numbers and increased adipogenesis, as indicated by elevated perilipin 1 (PLIN1) expression. In vitro, ischaemic stress induced AHNAK and PLIN1 expression, whereas AHNAK knockdown reversed these effects and suppressed Smad1/5 phosphorylation and PPARγ activation. C/EBPα expression remained unchanged, suggesting a selective role of AHNAK in modulating the Smad/PPARγ axis during adipogenesis.</p><p><strong>Conclusion: </strong>AHNAK is a critical mediator of ischaemia-induced adipogenesis in ONFH through activation of the Smad/PPARγ signalling pathway, promoting the differentiation of preosteoblasts into adipocytes. Targeting AHNAK may offer a novel therapeutic strategy to reduce bone loss and marrow fat accumulation in ONFH, particularly in cases associated with steroids or metabolic dysfunction. Further studies are warranted to validate AHNAK as a clinical target.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"1042-1054"},"PeriodicalIF":5.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo quantification of polyethylene wear in total ankle arthroplasty : a longitudinal study using weightbearing CT.","authors":"Francois Lintz, Alessio Bernasconi, Wolfram Grün, Enrico Pozzessere, Emily Luo, Pierre-Henri Vermorel, Albert Anastasio, Mark Easley, Kristian Buedts, Cesar de Cesar Netto","doi":"10.1302/2046-3758.158.BJR-2026-0005.R2","DOIUrl":"https://doi.org/10.1302/2046-3758.158.BJR-2026-0005.R2","url":null,"abstract":"<p><strong>Aims: </strong>In vivo assessment of polyethylene (PE) wear in total ankle arthroplasty (TAA) relies on approximation using 2D metal interspace height (2D-MIH) loss on weightbearing radiographs. Weightbearing CT (WBCT), combined with distance mapping, may improve quantification of PE wear over time using 3D metal interspace volume (3D-MIV) loss. This study aimed to assess 3D-MIV with successive WBCT scans. We hypothesized that WBCT based 3D-MIV would enable longitudinal quantification of PE wear and identify predictors.</p><p><strong>Methods: </strong>This retrospective study included 29 ankles from 28 TAA patients (16 men, mean age 57.9 years (SD 10.5), BMI 26.3 kg/m² (SD 4.1)) who had WBCT scans at minimum two-year intervals. Patients aged below 18 years, and those with trauma or surgical procedures affecting ankle alignment between scans, were excluded. Demographic data, implant types, and clinical outcomes were extracted. 3D-MIV was measured after segmentation of individual bones and prosthetic components. Annualized approximated wear rates were calculated. Correlations and multivariate regression analyses were used to identify predictors.</p><p><strong>Results: </strong>Mean follow-up between scans was 58.7 months (SD 17.9). Mean 3D-MIV decreased from 3.92 mL (SD 1.17) initially to 3.86 mL (SD 1.11) (p = 0.015). Yearly 3D-MIV loss was -11.34 mm³/year (SD 19.62). Correlations existed between 3D-MIV loss and coronal plane rotation (ρ = -0.58, p < 0.001), mediolateral translation (ρ = -0.52, p = 0.004, superoinferior translation (ρ = 0.56, p = 0.002) and BMI ≥ 27 kg/m² (p = 0.037). Multivariate regression identified coronal plane alignment (<i>β</i> = -3.66, 95% CI -7.31 to -0.01), p = 0.049) and mediolateral translation (<i>β</i> = -9.97, 95% CI -18.48 to -1.45), p = 0.024) as predictors of 3D-MIV loss.</p><p><strong>Conclusion: </strong>Using a WBCT-based approach, this study enabled longitudinal in vivo quantification of PE wear in TAA. Wear rates (~11.3 mm³/year) aligned with prior estimates, and the method correctly identified anticipated predictors of increased wear.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"1033-1041"},"PeriodicalIF":5.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piezo1 drives fibroblast activation in epidural fibrotic remodelling via the ET-1/HIF-1α pathway.","authors":"Yue Huang, Zeyuan Song, Xiaojie Mei, Youpeng Zhao, Tao Zhu, Mohan Shi, Jinpeng Sun, Mingshun Zhang, Tao Wu, Jun Liu","doi":"10.1302/2046-3758.158.BJR-2025-0662.R1","DOIUrl":"10.1302/2046-3758.158.BJR-2025-0662.R1","url":null,"abstract":"<p><strong>Aims: </strong>Epidural fibrosis is a major cause of failed back surgery syndrome following laminectomy. While previous studies have focused primarily on the early phases of scar formation, fibrotic remodelling remains poorly understood. This study aimed to investigate the interaction between collagen accumulation and fibroblasts during the remodelling phase of epidural fibrosis.</p><p><strong>Methods: </strong>In this study, a 3D collagen encapsulation model was used to simulate mechanical stress. Fibrotic and mechanosensitive pathway-related molecules were analyzed to assess fibroblast activation, and specific pharmacological inhibitors were applied to verify the proposed mechanism. Additionally, a mouse laminectomy model was used to evaluate the therapeutic effect of Piezo1 blockade on epidural fibrosis.</p><p><strong>Results: </strong>We found that collagen fibres encapsulate fibroblasts during the stage of scar remodelling. In vitro, collagen may activate the transforming growth factor beta-1 (TGF-β1)/Smad3 pathway in fibroblasts, which is mediated by the Piezo1 and hypoxia-inducible factor 1-alpha (HIF-1α) signalling pathways. This process establishes a positive feedback loop between collagen accumulation and fibroblast activation. Furthermore, we demonstrated that Piezo1-mediated activation of HIF-1α occurs through calcium ion influx and stabilization of endothelin-1 (ET-1). More importantly, blocking the activation of Piezo1 attenuated fibrosis progression in a mouse model of laminectomy.</p><p><strong>Conclusion: </strong>These results highlight the critical role of the Piezo1/ET-1/HIF-1α pathway in epidural fibrotic remodelling. Targeting Piezo1 may offer a promising therapeutic strategy for alleviating epidural fibrosis and improving outcomes after spinal surgery.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"1017-1032"},"PeriodicalIF":5.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13477817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel diagnostic technology rapidly detects the presence of infection and defines antimicrobial sensitivities in organisms typical for joint infection.","authors":"Isabelle L Cochrane, Roselline Gabriella Gunarto, Frank Alexander Schildberg, Dieter Christian Wirtz, Robert J H Hammond, Phillip J Walmsley","doi":"10.1302/2046-3758.158.BJR-2025-0581.R1","DOIUrl":"https://doi.org/10.1302/2046-3758.158.BJR-2025-0581.R1","url":null,"abstract":"<p><strong>Aims: </strong>Infective arthritis is rare, but serious. Timely treatment with appropriate antimicrobial therapy is potentially life- and limb-saving, but our ability to deliver this is limited by current laboratory practices, which confer a delay of several days before antimicrobial sensitivities are available. We propose a novel diagnostic modality, the Scattered Light Integrating Collector (SLIC), which monitors bacterial growth in real time, allowing a diagnosis of infection to be made in minutes, and antimicrobial sensitivities to be delivered in under an hour.</p><p><strong>Methods: </strong>We collated data previously collected on SLIC relating to laboratory strains of <i>Staphylococcus aureus 25923</i> and <i>methicillin-resistant S. aureus</i> (MRSA) <i>29213</i>. Liquid cultures of the two organisms, with varying dilutions of target antibiotics, were compared in SLIC against positive (no antibiotic) and negative (no bacteria) controls. Three key measurements were derived: time to positivity (TTP - the timepoint at which significant bacterial growth was confirmed), time to sensitivities (TTS - the timepoint of statistically significant growth inhibition conferred by antibiotics vs the positive control), and IC50 (50% growth suppression relative to control).</p><p><strong>Results: </strong>TTP for <i>S. aureus</i> and MRSA was two minutes and 2.2 minutes, respectively. <i>S. aureus</i> was sensitive to gentamicin, with a minimum TTS of one minute, and IC50 achieved in under 19 minutes for all doses. Similarly, <i>S. aureus</i> susceptibility to vancomycin was established, with a minimum TTS of three minutes, and IC50 achieved in under 55 minutes for all but the lowest dose. MRSA was sensitive to rifampicin, with IC50 achieved in 16.5 minutes. Despite all tested antibiotics achieving TTS in under 30 minutes, only rifampicin achieved the criterion IC50 to declare susceptibility.</p><p><strong>Conclusion: </strong>SLIC rapidly determines the presence of infection and characterizes antimicrobial susceptibilities in organisms typical for joint infection.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"1005-1016"},"PeriodicalIF":5.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13472738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro evaluation of vancomycin-loaded Marlex mesh against staphylococci isolated from periprosthetic joint infection.","authors":"Mona Mustafa Hellou, Melissa J Karau, Sergio F Guarin Perez, Diego J Restrepo, Jay Mandrekar, Nicholas A Bedard, Robin Patel, Matthew P Abdel","doi":"10.1302/2046-3758.158.BJR-2025-0522.R2","DOIUrl":"10.1302/2046-3758.158.BJR-2025-0522.R2","url":null,"abstract":"<p><strong>Aims: </strong>Extensor mechanism disruption is a major complication following total knee arthroplasty, with treatment often consisting of extensor mechanism reconstruction utilizing monofilament polypropylene mesh (Marlex mesh, C. R. Bard, Inc). Infection following this procedure is devastating, often resulting in revision surgery and mesh removal, with permanent limb dysfunction. This study evaluated the in vitro ability of vancomycin-loaded polypropylene mesh to inhibit growth of isolates of three <i>Staphylococcus</i> species from patients with periprosthetic joint infection.</p><p><strong>Methods: </strong>The mesh was prepared in two configurations - single-layer and eight-layer - and soaked for ten minutes in either sterile water (control) or vancomycin solution (50 mg/ml), after which the mesh was placed on tryptic soy agar plates inoculated with staphylococci and incubated at 37°C for 18 to 24 hours. Zones of inhibition were measured daily over seven days, with mesh transferred to freshly inoculated plates daily. Testing was performed in triplicate, with experiments repeated three times for each bacterial isolate. A total of 30 clinical isolates were tested (five methicillin-susceptible <i>Staphylococcus epidermidis</i>, five methicillin-resistant <i>S. epidermidis</i>, ten methicillin-resistant <i>Staphylococcus aureus</i>, and ten <i>Staphylococcus lugdunensis</i>).</p><p><strong>Results: </strong>Across all species, the eight-layer vancomycin-loaded mesh produced statistically significantly larger median zones of inhibition than the single-layer mesh. The antibacterial activity of the eight-layer mesh persisted through to day 7, while the single-layer mesh showed reduced activity by days 4 to 5.</p><p><strong>Conclusion: </strong>Compared with single-layer vancomycin-loaded mesh, multilayer vancomycin-loaded mesh, which mimics clinical application, provides enhanced and sustained antibacterial activity in vitro.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"998-1004"},"PeriodicalIF":5.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13467363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a human osteocyte model to reveal mechanisms of chronic Staphylococcus epidermidis bone and joint infections.","authors":"Claudia Siverino, Qi Sun, Lucian Bogdan Solomon, Thomas Fintan Moriarty, Gerald J Atkins","doi":"10.1302/2046-3758.158.BJR-2025-0681.R1","DOIUrl":"10.1302/2046-3758.158.BJR-2025-0681.R1","url":null,"abstract":"<p><strong>Aims: </strong>Chronic bone and joint infections caused by <i>Staphylococcus epidermidis</i> can be difficult to treat and are prone to recurrence. In this study, established human osteoblast- and osteocyte-like cell line models were used in vitro to investigate the intracellular persistence of <i>S. epidermidis</i> as a potential mechanism for infection persistence.</p><p><strong>Methods: </strong>The SaOS2 human osteosarcoma cell line was differentiated into osteoblast-like (SaOS2-OB) and osteocyte-like (SaOS2-OY) stages and infected with four <i>S. epidermidis</i> strains at varying multiplicities of infection. Susceptibilities to lysostaphin, a known bacteriolytic enzyme, and a panel of antibiotics were determined to identify an antimicrobial capable of clearing extracellular bacteria while preserving intracellular bacterial viability. Bacterial survival and number were quantified by colony-forming unit and droplet digital polymerase chain reaction (PCR), while host gene expression was analyzed by real-time PCR.</p><p><strong>Results: </strong>Lysostaphin was ineffective against all four <i>S. epidermidis</i> strains, while 10 × minimal bactericidal concentration levofloxacin consistently eliminated extracellular but not intracellular bacteria. Intracellular <i>S. epidermidis</i> at multiplicities of infection of 1,000 persisted in SaOS2-OY for 14 days at 10 × minimal bactericidal concentration levofloxacin, while it was cleared within five days in SaOS2-OB cells. Droplet digital PCR genome copy analysis identified a higher number of bacteria than conventional culture, indicating more accurate counting and a transition of the intracellular bacteria to a non-culturable state. Proinflammatory and bone remodelling responses by both bone cell types were evident upon infection, with increased messenger RNA levels of <i>CCL5</i>, <i>CXCL6</i>, <i>CXCL10</i>, <i>SOST</i>, receptor activator of nuclear factor kappa-B ligand (<i>RANKL</i>), and matrix metalloproteinase 13 (<i>MMP13</i>).</p><p><strong>Conclusion: </strong>We report the first model of intracellular <i>S. epidermidis</i> persistence in osteocyte-like cells, which provides a robust platform for mechanistic studies of chronic bone and joint infections and the preclinical screening of novel therapeutics targeting intracellular bacteria.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"987-997"},"PeriodicalIF":5.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bone histological approach to distinguish periprosthetic joint infection from aseptic osteolysis in revision joint replacement.","authors":"Dzenita Muratovic, Ryan D Quarrington, Dongqing Yang, Masakazu Kogawa, Renjy Nelson, Boopalan Ramasamy, Lucian Bogdan Solomon, Gerald J Atkins","doi":"10.1302/2046-3758.158.BJR-2025-0605.R2","DOIUrl":"10.1302/2046-3758.158.BJR-2025-0605.R2","url":null,"abstract":"<p><strong>Aims: </strong>Accurate differentiation between periprosthetic joint infection (PJI) and aseptic osteolysis (AO) remains a major clinical challenge in revision joint arthroplasty. We examined bone biopsies for alterations in bone matrix integrity and the osteocyte lacunocanalicular network in order to differentiate between these pathologies.</p><p><strong>Methods: </strong>Bone biopsies were taken from areas of osteolysis in patients who underwent revision arthroplasty for either PJI, diagnosed according to 2018 International Consensus Meeting criteria, or AO. Controls were obtained during primary arthroplasty. Biopsies were assessed histologically by Masson's trichrome, silver and RGB trichrome staining, and for osteocyte lacunocanalicular characteristics. The diagnostic potential of histological measures was investigated using univariate area under the receiver operating characteristic curve (AUROC) analysis.</p><p><strong>Results: </strong>RGB trichrome staining was most effective for revealing both bone matrix and lacunocanalicular features. Osteocyte lacunar area and circularity were increased in PJI relative to both AO and Control bone. PJI bone exhibited reduced canalicular density compared to AO (p < 0.001), and shorter, narrower canaliculi than AO and Controls. Predictive univariate modelling revealed that all histological parameters measured except lacunar area were potentially diagnostic for PJI. Degraded bone matrix differentially predicted PJI (AUROC = 0.875, 88% sensitivity, 80% specificity) and AO (AUROC = 0.733, 63% sensitivity, 76% specificity), as did lacunar circularity (PJI: AUROC = 0.903, 75% sensitivity, 96% specificity; AO: AUROC = 0.797, 69% sensitivity, 84% specificity). Canalicular area fraction, length, and width all predicted PJI (AUROCs = 0.915, 0.982, 0.883), with canalicular length yielding 94% sensitivity and 100% specificity. Canalicular density differentially predicted PJI (AUROC = 0.770, 69% sensitivity, 80% specificity) and AO (AUROC = 0.757, 88% sensitivity, 60% specificity).</p><p><strong>Conclusion: </strong>Histological assessment of bone matrix degradation and the osteocyte lacunocanalicular network reveals new potential diagnostic markers for PJI to support clinical decision-making and provides novel measures for distinguishing PJI from AO, which may be particularly useful in cases of low-grade and chronic infections. Based on these findings, larger confirmatory studies are warranted.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"973-986"},"PeriodicalIF":5.5,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient acute kidney injury following femoral fracture in mice : the role of sympathetic activation.","authors":"Katharina Oßwald, Hannah Herbst, Sandra Dieterich, Elizabeth Rosado Balmayor, Anita Ignatius, Markus Huber-Lang, Melanie Haffner-Luntzer, Rebecca Halbgebauer","doi":"10.1302/2046-3758.158.BJR-2025-0760.R1","DOIUrl":"10.1302/2046-3758.158.BJR-2025-0760.R1","url":null,"abstract":"<p><strong>Aims: </strong>Femoral shaft fractures are commonly associated with high-energy trauma, and affect individuals of all ages. Kidney dysfunction frequently complicates fracture healing, and trauma-related acute kidney injury (TRAKI) elevates the risk of adverse outcomes. The mechanisms of post-fracture kidney injury, particularly the involvement of sympathetic activation, remain poorly understood. We aimed to define the impact of femoral fracture on the kidney and investigate mechanistically the potential contribution of sympathetic activation.</p><p><strong>Methods: </strong>A total of 46 female C57BL/6J mice were subjected to femoral shaft fracture and external fixation, and received daily treatment for three days with either phentolamine, propranolol, or butoxamine. They were analyzed early (at day 1) and late at day 21 post-fracture. Renal function was assessed via blood urea nitrogen measurement, while kidney injury was evaluated using histology and gene expression analysis.</p><p><strong>Results: </strong>While renal function remained within the physiological range, animals with fracture revealed signs of kidney damage one day after fracture, reflected by increased expression of kidney damage markers and oxidative stress indicators and histopathological changes. Cellular inflammation and proliferation were induced upon fracture but did not cause long-term fibrosis. By 21 days, these effects were no longer detectable, suggesting transient TRAKI. Adrenergic receptor (AR) blockade experiments clearly indicated a sympathetic contribution to this temporal renal response. α-AR-mediated effects in particular modulated the kidneys' response to oxidative stress, as phentolamine treatment reduced early oxidative stress markers. Furthermore, immune activation was only detected upon propranolol application. However, none of the treatments provided a sustained protective effect. Rather, a mixed outcome was observed in different aspects of TRAKI.</p><p><strong>Conclusion: </strong>Taken together, femoral fractures in mice can induce transient mild kidney injury, local cellular damage, and inflammation, while maintaining renal function. Adrenergic signalling appears to contribute to TRAKI development, which warrants further mechanistic investigation.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"961-972"},"PeriodicalIF":5.5,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A target-based population pharmacokinetic and pharmacodynamic analysis for intra-articular dosing regimen optimization of vancomycin in patients with periprosthetic joint infections.","authors":"Wenyuan Liu, Wei-Jun Wang, Manzhen Ding, Minghao Zhang, Lu Lin, Shiguang Lai, Qing Jiang, Ruijuan Xu","doi":"10.1302/2046-3758.158.BJR-2025-0536.R2","DOIUrl":"10.1302/2046-3758.158.BJR-2025-0536.R2","url":null,"abstract":"<p><strong>Aims: </strong>Although intra-articular vancomycin has demonstrated satisfactory outcomes for periprosthetic joint infection (PJI), dose and dosing frequency remain largely empirical. This study aimed to develop a target-based population pharmacokinetics (PK) model to predict local vancomycin exposure, and to evaluate the efficacy and safety of various regimens in patients with PJI.</p><p><strong>Methods: </strong>Patients with PJI who received intravenous (IV) infusion or intra-articular injection of vancomycin were included. Population PK analysis was performed using nonlinear mixed effects modelling. Monte Carlo simulations were used to assess pharmacodynamic target attainment against <i>Staphylococcus</i> species, and to evaluate vancomycin-associated safety risks.</p><p><strong>Results: </strong>A total of 450 plasma and synovial fluid samples from 161 patients with PJI were analyzed. The pharmacokinetics of vancomycin in synovial fluid were best described by a two-compartment joint model linked to a central plasma compartment. Creatinine clearancesignificantly affected systemic clearance, while age influenced the penetration from synovial fluid to the central compartment. Simulations suggested that intra-articular dosing of 500 mg once daily was sufficient for targets against <i>Staphylococcus aureus</i> and <i>Staphylococcus epidermidis</i>, whereas other coagulase-negative staphylococci required more intensive regimens, including 250 or 500 mg every 12 hours or 1,000 mg once daily. For patients with severe renal impairment, intra-articular administration alone provided adequate systemic exposure, and concomitant IV administration was not recommended.</p><p><strong>Conclusion: </strong>The intra-articular population PK model accurately characterized vancomycin concentrations in plasma and synovial fluid, supporting optimized intra-articular dosing regimens in patients with PJI according to renal function and age.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"951-960"},"PeriodicalIF":5.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}