Citations

ABSTRACT The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%–70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro‐inflammatory from their own senescence‐associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro‐inflammatory SASP of senescent human preadipocytes, caused them to become “senolytic‐resistant”. Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro‐inflammatory. In cell cultures, the 30%–70% of human senescent preadipocytes or human umbilical vein endothelial cells (HUVECs) that are senolytic‐resistant (to Dasatinib or Quercetin, respectively) had increased p16 INK4a , p21 CIP1 , senescence‐associated β‐galactosidase (SAβgal), γH2AX, and proliferative arrest similarly to the total SC population (comprising senolytic‐sensitive plus‐resistant SCs). However, the SASP of senolytic‐resistant SCs entailed less pro‐inflammatory/apoptotic factor production, induced less inflammation in non‐senescent cells, and was equivalent or richer in growth/fibrotic factors. Senolytic‐resistant SCs released less mitochondrial DNA (mtDNA) and more highly expressed the anti‐inflammatory immune evasion signal, glycoprotein non‐melanoma‐B (GPNMB). Transplanting senolytic‐resistant SCs intraperitoneally into younger mice caused less physical dysfunction than transplanting the total SC population. Because Ruxolitinib attenuates SC release of proapoptotic SASP factors, while pathogen‐associated molecular pattern factors (PAMPs) can amplify the release of these factors rapidly (acting as “senosensitizers”), senolytic‐resistant and senolytic‐sensitive SCs appear to be interconvertible.

Artificial intelligence (AI) is increasingly shaping pediatric spine care, leveraging its rapid advancements in healthcare to improve efficiency, accuracy, and disease understanding. Moreover, machine learning and deep learning excel at detecting complex patterns. This holds promise in processing spinal deformity data, with the potential to surpass traditional statistical methods in predictive accuracy. Challenges persist, however, including unclear clinical implementation guidelines, limited model transparency, and ethical concerns surrounding data privacy and bias. Small sample sizes and the need for larger, diverse datasets further complicate integration. In order to realize AI’s transformative potential in pediatric spine care, these critical obstacles must be addressed for effective and ethical clinical adoption. This review examines the role of AI through applications such as image sorting, surgical outcome prediction, forecasting of spinal curve progression, and vertebral volumetric analysis using deep reasoning. It also explores possible intraoperative contributions from AI, including robotics and optimized screw trajectory planning, and the potential of large language models in clinical practice.

ABSTRACT Femoroacetabular impingement (FAI) of the hip results from altered morphology of the proximal femur and/or acetabulum, creating abnormal contact between these structures during normal hip range of motion. The etiology of this structural phenotype is unknown. This study aimed to identify common single‐nucleotide variants (SNVs) among two families with seemingly heritable FAI. Additionally, this study examined biologic networks among proteins encoded by identified SNVs and surveyed the literature regarding the role of these proteins in musculoskeletal development. Methodologically, blood samples were collected from affected and unaffected members of two separate families with a pattern of heritable FAI. Exome sequencing identified SNVs, and a protein–protein interaction network assessment, in addition to a literature review, was performed to better understand the role of variant‐associated genes in musculoskeletal development. Results showed 33 and 43 variant‐associated genes affected in Family 1 and Family 2, respectively. Although no overlap in variant‐associated genes was found between families, network analysis showed that variant‐associated genes are functionally interconnected and are known to interact with each other. Furthermore, the variant‐associated genes are broadly associated with musculoskeletal development. Ultimately, genetic analysis of two families of multiple generations of FAI revealed variations in genes regulating musculoskeletal development, with several being critical local regulators of bone morphogenesis.

Background: Orthopaedic surgeons routinely delay surgical management of femoral neck fractures in patients taking direct oral anticoagulants (DOACs) to decrease perioperative bleeding and associated complications. However, this practice contradicts the principles of hip fracture management, as early surgery is associated with morbidity and mortality benefits. The purpose of this study was to quantify the association of DOAC use and perioperative outcomes in patients who underwent hemiarthroplasty (HA) or total hip arthroplasty (THA) for femoral neck fractures. We hypothesized that early surgical intervention on a patient taking a DOAC medication would not lead to worse perioperative outcomes. Methods: A retrospective cohort study was conducted on 2,833 patients who underwent primary THA or HA for femoral neck fractures between December 31, 2017, and January 29, 2024, across our hospital system. The patients taking a DOAC were divided into 3 groups based on the time since the last DOAC intake: 1 day, 2 days, and ≥3 days. Propensity matching was performed 1:1, accounting for age, sex, Elixhauser Comorbidity Index, preoperative chronic kidney disease stage, preoperative hemoglobin, body mass index, and hospital type. Subanalyses utilizing linear and conditional logistic regression models were performed to assess differences in outcomes between the groups that had a DOAC withheld and the control groups. Results: The mean age of all patients was 81 ± 10 years, 1,805 patients (64%) were women, and 207 patients (7%) were taking a DOAC prior to surgery. Despite comparable preoperative and postoperative hemoglobin levels between the groups that had a DOAC withheld and the control groups (all p > 0.05), the patients who had a DOAC withheld for 1 day were more likely to receive a postoperative blood transfusion (23.1% compared with 0%; p = 0.002). This difference in transfusion rate was not observed in other cohorts. There were no differences in medical complications, reoperation, discharge disposition, or mortality between the groups that had a DOAC withheld and the matched controls at any time point. Conclusions: Delaying surgical management due to DOAC medications may be unnecessary in patients undergoing arthroplasty for femoral neck fractures. Consideration should be given to adjusting transfusion triggers to reduce unwarranted blood transfusions in patients taking a DOAC. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Aims The use of jumbo femoral heads, defined as those with a diameter of ≥ 40 mm, in primary total hip arthroplasty (THA) has gained popularity, to mitigate dislocation. The aim of this study was to determine the risk of dislocation, implant survival, and clinical outcomes of a large cohort of primary THAs with jumbo femoral heads. Methods We conducted a retrospective analysis of 1,828 primary THAs with jumbo femoral heads, which were undertaken for osteoarthritis, in 1,578 patients between January 2000 and December 2022, at a single academic medical centre. The femoral head diameter was 40 mm in 1,584 THAs (87%) and 44 mm in 244 THAs (13%). The outer diameter of the acetabular component ranged from 52 mm to 72 mm in those with 40 mm heads, and from 54 mm to 78 mm in those with 44 mm heads. The types of bearing included ceramic-on-highly cross-linked polyethylene (1,229 THAs; 67%) and metal-on-polyethylene (599 THAs; 33%). Elevated liners were used in 472 THAs (26%) and 1,083 (59%) were lateralized. The most common operative approach was posterior (1,388 THAs; 76%). Outcomes of interest included the rate of dislocation, revision for dislocation, any revision, any reoperation, and the Harris Hip Score (HHS). The mean age of the patients at the time of THA was 64 years (8 to 94); 1,477 (81%) were male, and their mean BMI was 28 kg/m² (5 to 55). The mean follow-up was six years (2 to 14). Results The ten-year survival free of dislocation was 97% (95% CI 96 to 98; 97% for 40 mm heads (95% CI 95 to 98) and 99% for 44 mm heads (95% CI 97 to 100) (hazard ratio 3 (95% CI 1 to 14); p = 0.106)). The ten-year survival free of revision for dislocation was 99.6% (95% CI 99 to 100) (99.5% for 40 mm heads (95% CI 98 to 100) and 100% for 44 mm heads (p = 0.546)). The ten-year survival free of any revision and any reoperation was 95% (95% CI 94 to 97) and 93% (95% CI 91 to 95), respectively. There were no significant differences in survival free of any revision (p = 0.746) or any reoperation (p = 0.762) between the two groups. Conclusion In this large single-centre study of the use of jumbo femoral heads in primary THAs, the ten-year survival free of dislocation was 97%, with extremely few revisions for dislocation. These results highlight the potential for jumbo femoral heads to reduce the risk of dislocation and enhance implant longevity without compromising other clinical outcomes. Cite this article: Bone Joint J 2025;107-B(7):698–706.

Abstract Regenerative medicine is a rapidly advancing field, particularly within the field of physical medicine and rehabilitation. While orthobiologics are currently being used in clinical practice, there remains a need for high-quality clinical trials and translational research to standardize treatments and improve patient outcomes. Education is vital for streamlining development of evidence-based, practical, and effective treatments. In this article, we highlight the need for a 1-yr advanced fellowship in translational orthobiologics aiming to create a standardized core curriculum targeting physicians involved in treating musculoskeletal diseases. The fellowship’s objectives include advancing translational orthobiologics research, ethical considerations, and promoting effective communication regarding orthobiologic therapies. Such a program would serve as a foundation for physicians interested in conducting clinically oriented orthobiologics research for musculoskeletal disorders while improving the development of safe and effective therapeutics related to musculoskeletal disorders.

As artificial intelligence (AI) advances in healthcare, encompassing robust applications for the diagnosis and prognostication of musculoskeletal diseases, clinicians must increasingly understand the implications of machine learning and deep learning in their practice. This review article explores computer vision algorithms and patient-specific, multimodal prediction models; provides a simple framework to guide discussion on the limitations of AI model development; and introduces the field of generative AI.

Background: Although it is well established that the type of organism can be a risk factor for failure in patients with periprosthetic joint infection (PJI), no study to date has examined the impact of the number of positive cultures on treatment outcomes in patients undergoing 2-stage exchange. The purpose of this multicenter study was to determine the prognostic utility of multiple positive cultures at resection as a predictor of failure following reimplantation. Methods: This retrospective multicenter study identified 437 patients with chronic knee PJI who had undergone 2-stage exchange arthroplasty with a minimum of 1 year of follow-up following reimplantation. PJI was defined with use of the 2013 Musculoskeletal Infection Society (MSIS) criteria. Patients with culture-negative PJI were excluded (n = 138). Treatment failure was defined as either any reoperation for infection or PJI-related mortality. Multivariable regression controlling for risk factors for failure after a 2-stage arthroplasty was performed to determine whether ≥2 positive intraoperative cultures at resection can predict outcomes following reimplantation when compared with a single positive culture. Results: Two hundred and ninety-nine patients were included. At a mean follow-up of 6.2 ± 2.6 years, 48 patients (16.1%) experienced failure. Patients who had a failure were more likely to have had a longer interstage interval (p = 0.038) and were also more likely to have had ≥2 positive cultures at the time of resection arthroplasty (95.8% versus 75.3%; p = 0.001). On regression analysis, ≥2 positive cultures at resection was the only variable that was identified as a risk factor for failure following reimplantation in both the univariate (odds ratio [OR], 7.55 [95% CI, 2.24 to 47.0]; p = 0.006) and multivariable models (OR, 8.12 [95% CI, 2.31 to 51.9]; p = 0.005). Conclusions: This is the first study to examine the impact of the number of positive cultures on outcomes in patients with PJI. We found that the presence of ≥2 positive cultures at resection was an indicator of a poor prognosis and resulted in a greater than eightfold increase in the risk of treatment failure in patients undergoing a 2-stage exchange. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Abstract Morphological hip abnormalities (MHAs) significantly influence lifelong prognosis of the hip, contributing to early-onset osteoarthritis and impaired functionality. Developmental dysplasia of the hip (DDH) and femoroacetabular impingement (FAI) represent key pathologies, resulting from insufficient or excessive femoral head coverage, respectively. These abnormalities alter hip biomechanics, leading to structural damage, pain, and accelerated joint degeneration. Advances in genetic research have illuminated the interplay between genetics and mechanical loading in shaping hip morphology. Genes associated with osteoarthritis, DDH, and FAI include COL1A1, MMP13, and IL-6. Genes associated with FAI and osteoarthritis include ADAMTS4. Genes associated with DDH and osteoarthritis include FRZB, CX3CR1, ASPN, DKK1, PDRG1, GDF5, UQCC1, and TGF-β1. The mechanisms linking morphological derangements to symptomatic osteoarthritis remain incompletely understood. Multimodal approaches integrating imaging, biomechanics, and genetics may uncover distinct disease subtypes, enabling personalized interventions. Early detection of MHAs is critical in preventing early-onset osteoarthritis. Incorporating advanced imaging techniques, such as statistical shape modelling, can enhance the understanding of complex 3D hip morphologies and their progression to osteoarthritis. Future research should explore the genetic underpinnings of other morphologic hip conditions, including Slipped Capital Femoral Epiphysis and Legg–Calvé–Perthes disease, to refine preventive and therapeutic strategies. A comprehensive approach combining genetics, imaging, and clinical insights holds promise for mitigating the lifelong impact of MHAs.