Post-traumatic Osteoarthritis Research Articles

Timing of cartilage articulation following impact injury affects the response of surface zone chondrocytes.

Post-traumatic osteoarthritis develops following an inciting injury to a joint and results in cartilage degeneration. Mechanical loading, including articulation, drives anabolic responses in cartilage clinically, in vivo, and in vitro. Tribological articulation, or sliding of cartilage on a glass counterface, has long been used as an in vitro tool to study cartilage tissue behavior. However, it is unclear if tribological articulation affects chondrocyte fate following injury, and if the timing of articulation impacts the resultant effect. The goal of this study was to investigate the effect of tribological articulation on injured cartilage tissue at two time points: (i) performed immediately after injury and (ii) 24 h after injury. Neonatal bovine femoral cartilage explants were injured using a rapid spring-loaded impactor and subsequently subjected to tribological articulation. Cell death due to impact injury was highest near the articular surface, suggesting a strain-dependent mechanism. Immediate articulation following injury mitigated cell death compared to injury alone or delayed articulation; markers for both general cell death and early-stage apoptosis were markedly decreased in the explants that were immediately slid. Interestingly, mitigation of cell death due to sliding was most predominant at the cartilage surface. Tribological articulation is known to create fluid flow within the tissue, predominantly at the articular surface, which could drive the protective response seen here. Altogether, this work shows that perturbations to the cellular environment immediately following cartilage injury significantly impact chondrocyte fate.

Healthy but not osteoarthritic human meniscus-derived matrix scaffolds promote meniscus repair

Meniscus tissue is commonly injured due to sports-related injuries and age-related degeneration and approximately 50% of individuals with a meniscus tear will develop post-traumatic osteoarthritis (PTOA). Given that the meniscus has limited healing potential, new therapeutic strategies are required to enhance meniscus repair. Porcine meniscus-derived matrix (MDM) scaffolds improve meniscus integrative repair, but sources of human meniscus tissue have not been investigated. Therefore, the objectives of this study were to generate healthy and osteoarthritic (OA) MDM scaffolds and to compare meniscus cellular responses and integrative repair. Meniscus cells showed high viability on both healthy and OA scaffolds. While DNA content was higher in cell-seeded OA scaffolds than cell-seeded healthy scaffolds, CCK-8, and both sGAG and collagen content were similar between scaffold types. After 28 days in an ex vivo meniscus defect model, healthy and OA scaffolds had similar DNA, sGAG, and collagen content. However, the shear strength of repair was reduced in defects containing OA scaffolds compared to healthy scaffolds. In conclusion, healthy human allograft tissue is a useful source for generating MDM scaffolds that can support cellular growth, ECM production, and ex vivo integrative repair of the meniscus, highlighting the potential suitability for tissue engineering approaches to improve meniscus repair.

Comparison of post-traumatic osteoarthritis mouse models

Comparison of post-traumatic osteoarthritis mouse models

IGF1 drives Wnt-induced joint damage and is a potential therapeutic target for osteoarthritis

Osteoarthritis is the most common joint disease and a global leading cause of pain and disability. Current treatment is limited to symptom relief, yet there is no disease-modifying therapy. Its multifactorial etiology includes excessive activation of Wnt signaling, but how Wnt causes joint destruction remains poorly understood. Here, we identify that Wnt signaling promotes the transcription of insulin-like growth factor 1 (IGF1) in articular chondrocytes and that IGF1 is a major driver of Wnt-induced joint damage. Male mice with cartilage-specific Igf1 deficiency are protected from Wnt-triggered joint disease. Mechanistically, Wnt-induced IGF1 transcription depends on β-catenin and binding of Wnt transcription factor TCF4 to the IGF1 gene promoter. In a clinically relevant mouse model of post-traumatic osteoarthritis, cartilage-specific deletion of Igf1 protects against the disease in male mice. IGF1 silencing in chondrocytes from patients with osteoarthritis restores a healthy molecular profile. Our findings reveal that reducing Wnt-induced IGF1 is a potential therapeutic strategy for osteoarthritis.

Osteoarthritis early-, mid- and late-stage progression in the rat medial meniscus transection model.

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.

Activation of Heme Metabolism Promotes Tissue Health After Intraarticular Injury or Surgical Exposure.

Posttraumatic osteoarthritis (PTOA) is a well-recognized public health burden without any disease modifying treatment. This occurs despite noted advances in surgical care in the past 50 years. Mitochondrial oxidative damage pathways initiate PTOA after severe injuries like intraarticular fracture that often require surgery and contribute to PTOA after less severe injuries that may or may not require surgery like meniscal injuries. When considering the mitochondrial and redox environment of the injured joint, we hypothesized that activation of heme metabolism, previously associated with healing in many settings, would cause prototypic mitochondrial reprogramming effects in cartilage ideally suited for use at the time of injury repair. Activation of heme metabolism can be accomplished through the gasotransmitter carbon monoxide (CO), which activates hemeoxygenase-1 (HO1) and subsequent heme metabolism. In this study, we employed unique carbon monoxide (CO)-containing foam (COF) to stimulate heme metabolism and restore chondrocyte oxygen metabolism in vitro and in vivo . Doxycycline-inducible, chondrocyte-specific HO1 overexpressing transgenic mice show similar mitochondrial reprogramming after induction compared to COF. CO is retained at least 24 h after COF injection into stifle joints and induces sustained increases in heme metabolism. Lastly, intraarticular injection of COF causes key redox outcomes without any adverse safety outcomes in rabbit stifle joints ex vivo and in vivo . We propose that activation of heme metabolism is an ideal adjuvant to trauma care that replenishes chondrocyte mitochondrial metabolism and restores redox homeostasis.

Ginger-derived nanovesicles attenuate osteoarthritis progression by inhibiting oxidative stress via the Nrf2 pathway.

Aim: Osteoarthritis (OA) is a common degenerative joint disease. Previous studies demonstrated ginger-derived exosome-like nanovesicles (GDN) showed therapeutic effects in degenerative diseases. However, it remains unknown whether GDN could alleviate OA progression.Materials & methods: In this study, GDN were obtained and characterized. Then we evaluated the effects of GDN in tert-butyl hydroperoxide (TBHP)-induced chondrocytes, posttraumatic OA rat model and ex vivo cultured human OA cartilage explants.Results: We demonstrated GDN promoted cartilage anabolism and alleviated oxidative stress in TBHP-induced chondrocytes and OA rat. Our results also showed GDN exhibited protective effects in cultured cartilage explants. Furthermore, we verified the Nrf2 pathway was associated with protective effects of GDN.Conclusion: Altogether, our findings demonstrated GDN hold great potential for OA treatment.

Cbx4 SUMOylates BRD4 to regulate the expression of inflammatory cytokines in post-traumatic osteoarthritis.

Brominated domain protein 4 (BRD4) is a chromatin reader known to exacerbate the inflammatory response in post-traumatic osteoarthritis (PTOA) by controlling the expression of inflammatory cytokines. However, the extent to which this regulatory effect is altered after BRD4 translation remains largely unknown. In this study, we showed that the E3 SUMO protein ligase CBX4 (Cbx4) is involved in the SUMO modification of BRD4 to affect its ability to control the expression of the proinflammatory genes IL-1β, TNF-α, and IL-6 in synovial fibroblasts. Specifically, Cbx4-mediated SUMOylation of K1111 lysine residues prevents the degradation of BRD4, thereby activating the transcriptional activities of the IL-1β, TNF-α and IL-6 genes, which depend on BRD4. SUMOylated BRD4 also recruits the multifunctional methyltransferase subunit TRM112-like protein (TRMT112) to further promote the processing of proinflammatory gene transcripts to eventually increase their expression. In vivo, treatment of PTOA with a Cbx4 inhibitor in rats was comparable to treatment with BRD4 inhibitors, indicating the importance of SUMOylation in controlling BRD4 to alleviate PTOA. Overall, this study is the first to identify Cbx4 as the enzyme responsible for the SUMO modification of BRD4 and highlights the central role of the Cbx4-BRD4 axis in exacerbating PTOA from the perspective of inflammation.

Knee joint pathology and efferent pathway dysfunction: Mapping muscle inhibition from motor cortex to muscle force

BackgroundDysfunction in efferent pathways after knee pathology is tied to long-term impairments in quadriceps and hamstrings muscle performance, daily function, and health-related quality of life. Understanding the underlying etiology is crucial for effective treatment and prevention of poor outcomes, such as post-traumatic osteoarthritis or joint replacement. ObjectivesTo synthesize recent evidence of efferent pathway dysfunction (i.e., motor cortex, motor units) among individuals with knee pathology. DesignCommentary. MethodWe summarize the current literature investigating the motor cortex, corticospinal tract, and motoneuron pool in individuals with three common knee pathologies: anterior cruciate ligament (ACL) injury, anterior knee pain (AKP), and knee osteoarthritis (OA). To offer a complete perspective, we draw from studies applying a range of neuroimaging and neurophysiologic techniques. ResultsAdaptations within the motor cortices, corticospinal tract, and motoneuron pool are present in those with knee pathology and underline impairments in quadriceps and hamstrings muscle function. Each pathology has evidence of altered motor system excitability and reduced volitional muscle activation and force-generating capacity, but few impairments were common across ACL injury, AKP, and OA studies. These findings underscore the central role of the motor cortex and motor unit behavior in the long-term outcomes of individuals with knee pathology. ConclusionsAdaptations in the efferent pathways underlie persistent muscle dysfunction across three common knee pathologies. This review provides an overview of these changes and summarizes key findings from neurophysiology and neuroimaging studies, offering direction for future research and clinical application in the rehabilitation of joint injuries.

Outcomes After Total Knee Arthroplasty in Patients With a History of Patella Fracture: A Propensity Score-Matched Analysis.

Posttraumatic osteoarthritis is a common indication for total knee arthroplasty (TKA). The purpose of this study was to evaluate the association between a history of patella fracture and postoperative complication rates after TKA. Patients diagnosed with a patella fracture before undergoing TKA were identified from a large national database and matched to a control cohort using propensity scoring. Rates of medical complications occurring within 90 days of TKA and surgery-related complications occurring within 1 year of TKA were compared using odds ratios. Healthcare utilization outcomes including 90-day emergency department (ED) presentation, hospital readmission, and total cost were also compared. Compared with a propensity-matched control cohort, TKA patients with a history of patella fracture had a lower incidence of pulmonary embolism (OR 0.74, P = 0.0442) and higher incidences of periprosthetic joint infection (OR 1.68, P < 0.0001), revision surgery (OR 1.84, P < 0.0001), dislocation (OR 1.61, P = 0.026), lysis of adhesions (OR 2.21, P = 0.0082), and wound disruption (OR 1.52, P < 0.0001). A history of patella fracture was also associated with an increased rate of ED presentation (OR 1.08, P = 0.0454) and increased total cost ($14,359 vs. $12,786, P = 0.0003). A history of patella fracture is associated with early surgery-related complications after TKA including periprosthetic joint infection, revision surgery, dislocation, lysis of adhesions, and wound disruption. Healthcare utilization is increased among these patients with higher rates of ED presentation and increased total cost. These findings allow for more accurate risk stratification and counseling of patients. III, Retrospective review.

ESC-sEVs alleviate non-early-stage osteoarthritis progression by rejuvenating senescent chondrocytes via FOXO1A-autophagy axis but not inducing apoptosis

Osteoarthritis (OA) is a common joint degenerative disease which currently lacks satisfactory disease-modifying treatments. Oxidative stress-mediated senescent chondrocytes accumulation is closely associated with OA progression, which abrogates cartilage metabolism homeostasis by secreting senescence-associated secretory phenotype (SASP) factors. Numerous studies suggested mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) have been regarded as promising candidates for OA therapy. However, MSC-sEVs were applied before the occurrence of cartilage degeneration or at early-stage OA, while in clinical practice, most OA patients who present with pain are already in non-early-stage. Recently, embryonic stem cells-derived sEVs (ESC-sEVs) have been reported to possess powerful anti-aging effects. However, whether ESC-sEVs could attenuate non-early-stage OA progression remains unknown. In this study, we demonstrated ESC-sEVs ameliorated senescent phenotype and cartilage destruction in both mechanical stress-induced non-early-stage posttraumatic OA and naturally aged mice. More importantly, we found ESC-sEVs alleviated senescent phenotype by rejuvenating aged chondrocytes but not inducing apoptosis. We also provided evidence that the FOXO1A-autophagy axis played an important role in the anti-aging effects of ESC-sEVs. To promote clinical translation, we confirmed ESC-sEVs reversed senescent phenotype in ex-vivo cultured human end-stage OA cartilage explants. Collectively, our findings reveal that ESC-sEVs-based therapy is of high translational value in non-early-stage OA treatment.

Cross-sectional study on the prevalence of post-traumatic osteoarthritis in young athletes

Background. Joint traumas often cause post-traumatic osteoarthritis (PTOA), especially in young high-impact athletes. PTOA is a primary cause of early-onset osteoarthritis, yet this group has a low diagnostic rate. The goal of this cross-sectional study is to investigate how common PTOA is in youth athletes and what risk factors they face. Methods. At Dehradun’s Shri Guru Ram Rai Institute of Medical and Health Sciences, 100 athletes aged 18-35-yearold participated in the study. Sports like athletics, cricket, football, rugby, and basketball added to the participant pool. Included criteria were joint trauma; excluded were congenital joint conditions or no traumatic osteoarthritis. Data collection included clinical exams, imaging (X-rays and MRI), and a detailed questionnaire about the athlete’s past, injuries, and rehabilitation. The main objective was PTOA incidence, while secondary outcomes assessed risk factors such sport, injury severity, and trauma duration. All statistical studies utilize logistic regression and Chi-square testing, with a significance level of p &lt; 0.05. Results. PTOA affected the knee (25%), ankle (18%), and hip (8%), with a total prevalence of 35%. The majority of PTOA patients had ligament tears, mostly ACLs. Football and rugby players had a 2.5-fold increased risk of PTOA. The risk was 3.1% higher for athletes with major injuries including fractures or dislocations. The time after the event also affected PTOA; damage older than five years was more likely. Conclusion. Results demonstrate that youth athletes often have ankle and knee PTOA. Early detection, prevention, and monitoring can reduce PTOA in this group. Identifying specific therapy to reduce joint injuries’ long-term effects requires more research.

A dynamically loaded ex vivo model to study neocartilage and integration in human cartilage repair.

Articular cartilage injuries in the knee can lead to post-traumatic osteoarthritis if untreated, causing debilitating problems later in life. Standard surgical treatments fail to ensure long lasting repair of damaged cartilage, often resulting in fibrotic tissue. While there is a vast amount of research into cartilage regeneration, integrating engineered implants with cartilage remains a challenge. As cartilage is a load bearing tissue, it is imperative to evaluate tissue repair strategies and their ability to integrate under mechanical loading. This work established a dynamically loaded ex vivo model of cartilage repair using human cartilage explants. The model was used to assess the efficacy of a stem cell therapy delivered in a bioadhesive hydrogel comprised of photocrosslinkable gelatin methacryloyl (GelMA) and microbial transglutaminase to repair the model defect. Extensive neocartilage production and integration were observed via histology and immunohistochemistry after 28days chondrogenic culture. Analysis of culture media allowed monitoring of glycosaminoglycan and type II collagen production over time. A mechanical assessment of integration via a push out test showed a 15-fold increase in push out strength over the culture duration. The model was successful in exhibiting robust chondrogenesis with transglutaminase or without, and under both culture conditions. The work also highlights several limitations of ex vivo models and challenges of working with bioreactors that must be overcome to increase their utility. This ex vivo model has the potential to delay the need for costly pre-clinical studies and provide a more nuanced assessment of cartilage repair strategies than is possible in vivo.

Effects of chronic ankle instability after grade I ankle sprain on the post-traumatic osteoarthritis

BackgroundUntreated acute ankle sprains often result in chronic ankle instability (CAI) and can ultimately lead to the development of post-traumatic osteoarthritis (PTOA). At present, a typical animal model of ankle instability in mice is established by transecting the ligaments around the ankle joint. This study aimed to establish a grade I acute ankle sprain animal model by rapid stretching of peri-ankle joint ligaments. Furthermore, we tried to explore the pathophysiological mechanism of ankle osteoarthritis.MethodsIn all, 18 male C57BL/6 J mice (7 weeks) were randomly divided into three groups: calcaneofibular ligament (CFL) laxity group, deltoid ligament (DL) laxity group, and SHAM group. One week after the surgical procedure, all mice were trained to run in the mouse rotation fatigue machine daily. The mice were tested on the balance beam before surgery and three days, 4 weeks, 8 weeks, and 12 weeks after surgery. Footprint analyses were performed on each mouse before surgery and 12 weeks after surgery. Micro-CT scanning was then performed to evaluate the degeneration of ankle joints and histological staining was performed to analyze and evaluate PTOA caused by ankle joint instability.ResultsAfter surgery, the mice in the CFL and DL laxity groups took longer to cross the balance beam and slipped more often than those in the SHAM group (p < 0.05). The step length and width in the CFL and DL laxity groups were significantly shorter and smaller than those in the SHAM group 12 weeks after surgery (p < 0.05). There was a significant increase in the bone volume fraction (BV/TV) in the CFL and DL laxity groups compared with the SHAM group (p < 0.05). Histological staining results suggested obvious signs of PTOA in the CFL and DL laxity groups.ConclusionsBased on CFL and DL laxity in a mouse ankle instability model, this study suggests that grade I ankle sprain can contribute to chronic ankle instability, impair motor coordination and balance, and eventually lead to PTOA of ankle with significant degeneration of its adjacent joints.

Omega-3 fatty acids protect cartilage from acute injurie by reducing the mechanical sensitivity of chondrocytes

Acute cartilage injuries, such as intra-articular fractures and blunt impacts, frequently result in chondrocyte death and extracellular matrix (ECM) degradation, significantly elevating the risk of post-traumatic osteoarthritis (PTOA). Despite advances in treatment, no effective therapies currently exist to fully cure PTOA or halt its progression. This study explores the protective effects of the dietary fatty acid eicosapentaenoic acid (EPA) on human primary chondrocytes (HPCs) and cartilage explants exposed to mechanical overload and blunt trauma. HPCs were isolated and subjected to mechanical stretching using BioFlex six-well culture plates, while cartilage explants were subjected to impact loading via a customized drop tower. EPA was incorporated into the culture medium, followed by assays to evaluate cell viability, calcium (Ca²⁺) influx, apoptosis, reactive oxygen species (ROS) levels, and collagen type II alpha (Col-2a) expression. EPA treatment markedly decreased chondrocyte mechanical sensitivity, as demonstrated by enhanced cell viability and reduced lactate dehydrogenase (LDH) release. Furthermore, EPA inhibited Piezo1 activation, leading to lower intracellular Ca²⁺ concentrations, decreased apoptosis, and diminished ROS levels. In cartilage explants, EPA improved chondrocyte viability, minimized structural damage, and sustained higher Col-2a expression compared to the blunt trauma group. These results indicate that EPA effectively shields chondrocytes and cartilage explants from mechanical overload-induced damage by inhibiting Piezo1 activation and mitigating Ca²⁺ influx, apoptosis, and oxidative stress. The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. Further research is warranted to assess the clinical applications of EPA and confirm its efficacy in larger animal models and human trials.

Comparative transcriptomic analysis of articular cartilage of post-traumatic osteoarthritis models.

Animal models of post-traumatic osteoarthritis (PTOA) recapitulate the pathological changes observed in human PTOA. Here, skeletally mature C57Bl6 mice were subjected to either rapid-onset non-surgical mechanical rupture of the anterior cruciate ligament (ACL) or to surgical destabilisation of the medial meniscus (DMM). Transcriptome profiling of micro-dissected cartilage at day7 or day42 following ACL or DMM procedure, respectively, showed that the two models were comparable and highly correlative. Gene ontology (GO) enrichment analysis identified similarly enriched pathways that were overrepresented by anabolic terms. To address the transcriptome changes more completely in the ACL model, we also performed small RNA sequencing, describing the first microRNA profile of this model. miR-199-5p was amongst the most abundant, yet differentially expressed, microRNAs, and its inhibition in primary human chondrocytes led to a transcriptome response that was comparable to that observed in both human 'OA damaged vs intact cartilage' and murine DMM cartilage datasets. We also experimentally verified CELSR1, GIT1, ECE1 and SOS2 as novel miR-199-5p targets. Together, these data support the use of the ACL rupture model as a non-invasive companion to the DMM model.

Loss of collagen content is localized near cartilage lesions on the day of injurious loading and intensified on day 12.

Joint injury can lead to articular cartilage damage, excessive inflammation, and post-traumatic osteoarthritis (PTOA). Collagen is an essential component for cartilage function, yet current literature has limited understanding of how biochemical and biomechanical factors contribute to collagen loss in injured cartilage. Our aim was to investigate spatially dependent changes in collagen content and collagen integrity of injured cartilage, with an explant model of early-stage PTOA. We subjected calf knee cartilage explants to combinations of injurious loading (INJ), interleukin-1α-challenge (IL) and physiological cyclic loading (CL). Using Fourier transform infrared microspectroscopy, collagen content (Amide I band) and collagen integrity (Amide II/1338 cm-1 ratio) were estimated on days 0 and 12 post-injury. We found that INJ led to lower collagen content near lesions compared to intact regions on day 0 (p < 0.001). On day 12, near-lesion collagen content was lower compared to day 0 (p < 0.05). Additionally, on day 12, INJ, IL, and INJ + IL groups exhibited lower collagen content along most of tissue depth compared to free-swelling control group (p < 0.05). CL groups showed higher collagen content along most of tissue depth compared to corresponding groups without CL (p < 0.05). Immunohistochemical analysis revealed higher MMP-1 and MMP-3 staining intensities localized within cell lacunae in INJ group compared to CTRL group on day 0. Our results suggest that INJ causes rapid loss of collagen content near lesions, which is intensified on day 12. Additionally, CL could mitigate the loss of collagen content at intact regions after 12 days.

Medial Meniscal Extrusion After Anterior Cruciate Ligament Reconstruction (ACLR) Associated With Meniscal Repair and Preoperative Extrusion.

The risk of post-traumatic osteoarthritis remains high even after anterior cruciate ligament reconstruction (ACLR). Medial meniscal extrusion (MME) is a valuable clinical sign as an early morphological change. This study aimed to analyze MME before and after ACLR and investigate the factors affecting postoperative MME. This study included patients who underwent anatomical double-bundle ACLR between January 2016 and July 2021. MME was measured using MRI preoperatively and one year postoperatively. The medial meniscus (MM) treatments were categorized into three groups: no MM injury and no repair (no injury/no repair (N/N)), MM injury but no repair (injury/no repair (I/N)), and MM injury and repair (injury/repair (I/R)). We investigated the factors influencing MME after ACLR using multiple linear regression analysis and compared MME before and after ACLR using paired t-tests. This study included 133 patients, of whom 90 (37 males and 53 females) were analyzed. The mean age of the patients at surgery was 27.5 years, and 41, 27, and 22 patients were assigned into N/N, I/N, and I/R groups, respectively. Preoperative MME (p<0.001) and I/R (p<0.001) had significant effects on postoperative MME in a regression analysis. Postoperative MME had greater effects than the preoperative MME in all cases (1.16 and 1.53 mm (p<0.01)) and in every MM treatment group (N/N: 1.02 and 1.32 mm (p<0.01), I/N: 1.16 and 1.44 mm (p<0.01), and I/R: 1.42 and 2.05 mm (p<0.001)). Larger preoperative MME and receiving MM repair were significantly associated with a larger MME after ACLR. Postoperative MME in ACLR patients was significantly greater than preoperative MME.

A mixed-methods approach exploring acceptability and feasibility of trials designed to test drugs targeting prevention of post-traumatic osteoarthritis after knee injury.

To explore key stakeholder views around feasibility and acceptability of trials seeking to prevent post-traumatic osteoarthritis (PTOA) following knee injury, and provide guidance for next steps in PTOA trial design. Healthcare professionals, clinicians, and/or researchers (HCP/Rs) were surveyed, and the data were presented at a congress workshop. A second and related survey was then developed for people with joint damage caused by knee injury and/or osteoarthritis (PJDs), who were approached by a UK Charity newsletter or Oxford involvement registry. Anonymized data were collected and analyzed in Qualtrics. Survey responses (n = 19 HCP/Rs, 39 PJDs) supported studies testing pharmacological agents preventing PTOA. All HCP/Rs and 30/31 (97%) PJDs supported the development of new treatments that improved or delayed knee symptoms and damage to knee structure. PJDs thought that improving structural knee damage was more important than knee symptoms. Both groups found studies more acceptable as expected future benefit and risk of PTOA increased. All drug delivery routes were acceptable. Workshop participants (around n = 60) reflected survey views. Discussions suggested that stratifying using molecular testing for likely drug response appeared to be more acceptable than using characteristics such as sex, age, and BMI. Our findings supported PTOA drug intervention studies, including situations where there is low risk of disease, no expected benefit of treatment, and frequent treatment administration. PJDs appeared less risk-averse than HCP/Rs. This work reinforces the benefits of consensus and involvement work in the co-creation of PTOA drug trial design. Involvement of key stakeholders, such as PJDs with different risks of OA and regulatory representatives, are critical for trial design success.

Survivorship and Functional Outcomes After Complex Primary Total Knee Arthroplasty With Contemporary Rotating-Hinge Implants

Background: Initial fixed-bearing hinge designs for primary total knee arthroplasty (TKA) had high rates of aseptic loosening. There are limited data on contemporary rotating-hinge implants. Purpose: We sought to determine survivorship and functional outcomes of contemporary rotating-hinge implants used in primary TKA. Methods: Retrospective review identified 54 primary rotating-hinge TKAs implanted in 49 patients from 2014 to 2018 at a single institution. Patients identified were 76% women, the mean body mass index was 29 kg/m2, the mean age was 65 years, and the mean follow-up was 3 years. The primary diagnosis for TKA in all cases was severe instability and ligamentous compromise. Secondary diagnoses included post-traumatic osteoarthritis (11, 20%), neurologic disease (10, 19%), inflammatory arthritis (10, 19%), connective tissue disease (3, 6%), valgus deformity (16, 30%), varus deformity (2, 4%), and recurvatum (2, 4%). Preoperative, postoperative (within 6 weeks), and most recent radiographs were reviewed. In this study, we collected preoperative, 1-year, and 2-year patient-reported outcome measures (PROMs) for patients with primary rotating-hinge TKA. Patient-reported outcome measures were prospectively collected, including the Knee Injury and Osteoarthritis Outcome Survey for Joint Replacement (KOOS JR) scores and the Mental (MCS) and Physical Component Scores (PCS) of the Veterans RAND 12-Item Health Survey (VR-12). Kaplan-Meier analysis was used to determine implant survivorship. Results: Reoperation was required in 6% (3/54); indications included periprosthetic joint infection (1), peripatellar fibrosis (1), and periprosthetic femur fracture (1). At both 2 and 5 years, survivorship free from all-cause reoperation was 95% and from revision for aseptic loosening was 100%. Mean KOOS JR scores increased from 47 preoperatively to 65 at 2 years postoperatively. On radiographic review, there were no progressive radiolucent lines consistent with aseptic loosening at final follow-up. Conclusion: The findings of this single-center, multi-surgeon retrospective case series on the use of rotating-hinge implants for primary TKA suggest excellent 2-year survivorship free from reoperation and no revisions for aseptic loosening. We report modest improvement in a variety of PROMs at 1-year and 2-year follow-up. Despite improvement, clinical outcomes were poor for a primary implant. Longer-term follow-up is required to monitor the durability of primary hinges.