Tributyltin chloride induces chondrocyte damage through the activation of NLRP3­mediated inflammation and pyroptosis.

Tributyltin chloride (TBTC) is known to have effects and mechanisms in various diseases; however, whether TBTC is detrimental to joints and causes osteoarthritis (OA), as well as its underlying mechanism, has not yet been fully elucidated. The present study explored the effects of TBTC on rat chondrocytes, as well as on mouse OA. The toxicity of TBTC toward rat chondrocytes was detected using a lactate dehydrogenase (LDH) leakage assay and cell viability was evaluated using the Cell Counting Kit­8 assay. The results showed that TBTC decreased the viability of rat chondrocytes and increased the LDH leakage rate in a concentration­dependent manner. Moreover, compared with in the control group, TBTC increased the expression levels of interleukin (IL)­1ß, IL­18, matrix metalloproteinase (MMP)­1, MMP­13, NLR family pyrin domain containing 3 (NLRP3), caspase­1, PYD and CARD domain containing, and gasdermin D in chondrocytes. Furthermore, knockdown of NLRP3 reversed the TBTC­induced increases in LDH leakage and NLRP3 inflammasome­associated protein levels. In vivo, TBTC exacerbated cartilage tissue damage in mice from the OA group, as evidenced by the attenuation of safranin O staining. In conclusion, TBTC may aggravate OA in mice by promoting chondrocyte damage and inducing pyroptosis through the activation of NLRP3 and caspase­1 signaling. The present study demonstrated that TBTC can cause significant damage to the articular cartilage; therefore, TBTC contamination should be strictly monitored.

cGAS-STING pathway in pathogenesis and treatment of osteoarthritis and rheumatoid arthritis.

Osteoarthritis (OA) and Rheumatoid Arthritis (RA) are significant health concerns with notable prevalence and economic impact. RA, affecting 0.5% to 1.0% of the global population, leads to chronic joint damage and comorbidities. OA, primarily afflicting the elderly, results in joint degradation and severe pain. Both conditions incur substantial healthcare expenses and productivity losses. The cGAS-STING pathway, consisting of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), is a crucial component of mammalian immunity. This pathway is responsible for detecting foreign DNA, particularly double-stranded DNA (dsDNA), triggering innate immune defense responses. When cGAS recognizes dsDNA, it catalyzes the synthesis of cyclic GMP-AMP (cGAMP), which then binds to and activates STING. Activated STING, in turn, initiates downstream signaling events leading to the production of interferons and other immune mediators. The cGAS-STING pathway is essential for defending against viral infections and maintaining cellular balance. Dysregulation of this pathway has been implicated in various inflammatory diseases, including arthritis, making it a target for potential therapeutic interventions. Understanding the intricate molecular signaling network of cGAS-STING in these arthritis forms offers potential avenues for targeted therapies. Addressing these challenges through improved early detection, comprehensive management, and interventions targeting the cGAS-STING pathway is crucial for alleviating the impact of OA and RA on individuals and healthcare systems. This review offers an up-to-date comprehension of the cGAS-STING pathway's role in the development and therapeutic approaches for these arthritis types.

The role of YAP/TAZ on joint and arthritis.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common forms of arthritis with undefined etiology and pathogenesis. Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ), which act as sensors for cellular mechanical and inflammatory cues, have been identified as crucial players in the regulation of joint homeostasis. Current studies also reveal a significant association between YAP/TAZ and the pathogenesis of OA and RA. The objective of this review is to elucidate the impact of YAP/TAZ on different joint tissues and to provide inspiration for further studying the potential therapeutic implications of YAP/TAZ on arthritis. Databases, such as PubMed, Cochran Library, and Embase, were searched for all available studies during the past two decades, with keywords "YAP," "TAZ," "OA," and "RA."

Ankle Cartilage: Chondral and Osteochondral Lesions: A Further Dive into the Incidence, Terminology, and the Cartilage Cascade.

The current concepts thoroughly highlight the ankle cartilage cascade focusing on the different stages and the different etiologic factors that can introduce a patient into the cascade. Moreover, the authors will provide the reader with a comprehensive overview of the types of lesions that may present as symptomatic, asymptomatic, and dangerous for progression into osteoarthritis, and the authors supply the reader with considerations and directions for future clinical implications and scientific endeavors.

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Runt-related transcription factor (RUNX1) is a transcription factor closely involved in hematopoiesis. RUNX1 gene mutation plays an essential pathogenic role in the initiation and development of hematological tumors, especially in acute myeloid leukemia. Recent studies have shown that RUNX1 is also involved in the regulation of bone development and the pathological progression of bone-related diseases. RUNX1 promotes the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts and modulates the maturation and extracellular matrix formation of chondrocytes. The expression of RUNX1 in mesenchymal stem cells, chondrocytes, and osteoblasts is of great significance for maintaining normal bone development and the mass and quality of bones. RUNX1 also inhibits the differentiation and bone resorptive activities of osteoclasts, which may be influenced by sexual dimorphism. In addition, RUNX1 deficiency contributes to the pathogenesis of osteoarthritis, delayed fracture healing, and osteoporosis, which was revealed by the RUNX1 conditional knockout modeling in mice. However, the roles of RUNX1 in regulating the hypertrophic differentiation of chondrocytes, the sexual dimorphism of activities of osteoclasts, as well as bone loss in diabetes mellitus, senescence, infection, chronic inflammation, etc, are still not fully understood. This review provides a systematic summary of the research progress concerning RUNX1 in the field of bone biology, offering new ideas for using RUNX1 as a potential target for bone related diseases, especially osteoarthritis, delayed fracture healing, and osteoporosis.

Hypobaric hypoxia aggravates osteoarthritis via the alteration of the oxygen environment and bone remodeling in the subchondral zone.

A high prevalence of osteoarthritis (OA) has been observed among individuals living at high altitudes, and hypobaric hypoxia (HH) can cause bone mass and strength deterioration. However, the effect of HH on OA remains unclear. In this study, we aimed to explore the impact of HH on OA and its potential mechanisms. A rat knee OA model was established by surgery, and the rats were bred in an HH chamber simulating a high-altitude environment. Micro-computed tomography (Micro-CT), histological analysis, and RNA sequencing were performed to evaluate the effects of HH on OA in vivo. A hypoxic co-culture model of osteoclasts and osteoblasts was also established to determine their effects on chondrogenesis in vitro. Cartilage degeneration significantly worsened in the HH-OA group compared to that in the normoxia-OA (N-OA) group, 4 weeks after surgery. Micro-CT analysis revealed more deteriorated bone mass in the HH-OA group than in the N-OA group. Decreased hypoxia levels in the cartilage and enhanced hypoxia levels in the subchondral bone were observed in the HH-OA group. Furthermore, chondrocytes cultured in a conditioned medium from the hypoxic co-culture model showed decreased anabolism and extracellular matrix compared to those in the normoxic model. RNA sequencing analysis of the subchondral bone indicated that the glycolytic signaling pathway was highly activated in the HH-OA group. HH-related OA progression was associated with alterations in the oxygen environment and bone remodeling in the subchondral zone, which provided new insights into the pathogenesis of OA.

Molecular biomarker approaches to prevention of post-traumatic osteoarthritis.

Up to 50% of individuals develop post-traumatic osteoarthritis (PTOA) within 10 years following knee-joint injuries such as anterior cruciate ligament rupture or acute meniscal tear. Lower-extremity PTOA prevalence is estimated to account for ≥12% of all symptomatic osteoarthritis (OA), or approximately 5.6 million cases in the USA. With knowledge of the inciting event, it might be possible to 'catch PTOA in the act' with sensitive imaging and soluble biomarkers and thereby prevent OA sequelae by early intervention. Existing biomarker data in the joint-injury literature can provide insights into the pathogenesis and early risk trajectory related to PTOA and can help to elucidate a research agenda for preventing or slowing the onset of PTOA. Non-traumatic OA and PTOA have many clinical, radiological and genetic similarities, and efforts to understand early risk trajectories in PTOA might therefore contribute to the identification and classification of early non-traumatic OA, which is the most prevalent form of OA.

Coronal vertical fracture of vertebral body following minimally invasive lateral lumbar interbody fusion: risk factor analysis in consecutive case series.

BACKGROUND: To investigate the incidence and risk factors of coronal vertical vertebral body fracture (CV-VBF) during lateral lumbar interbody fusion (LLIF) for degenerative lumbar disease. METHODS: Clinical data, including age, sex, body mass index, and bone mineral density, were reviewed. Radiological assessments, such as facet joint arthrosis, intervertebral disc motion, index disc height, and cage profiles, were conducted. Posterior instrumentation was performed using either a single or staged procedure after LLIF. Demographic and surgical data were compared between patients with and without VBF. RESULTS: Out of 273 patients (552 levels), 7 (2.6%) experienced CV-VBF. Among the 552 levels, VBF occured in 7 levels (1.3%). All VBF cases developed intraoperatively during LLIF, with no instances caused by cage subsidence during the follow-up period. Sagittal motion in segments adjacent to VBF was smaller than in others (4.6° ± 2.6° versus 6.5° ± 3.9°, P = 0.031). The average grade of facet arthrosis was 2.5 ± 0.7, indicating severe facet arthrosis. All fractures developed due to oblique placement of a trial or cage into the index disc space, leading to a nutcracker effect. These factors were not related to bone quality. CONCLUSIONS: CV-VBF after LLIF occurred in 2.6% of patients, accounting for 1.3% of all LLIF levels. A potential risk factor for VBF involves the nutcracker-impinging effect due to the oblique placement of a cage. Thorough preoperative evaluations and surgical procedures are needed to avoid VBF when considering LLIF in patients with less mobile spine.

The role of targeting glucose metabolism in chondrocytes in the pathogenesis and therapeutic mechanisms of osteoarthritis: a narrative review.

Osteoarthritis (OA) is a common degenerative joint disease that can affect almost any joint, mainly resulting in joint dysfunction and pain. Worldwide, OA affects more than 240 million people and is one of the leading causes of activity limitation in adults. However, the pathogenesis of OA remains elusive, resulting in the lack of well-established clinical treatment strategies. Recently, energy metabolism alterations have provided new insights into the pathogenesis of OA. Accumulating evidence indicates that glucose metabolism plays a key role in maintaining cartilage homeostasis. Disorders of glucose metabolism can lead to chondrocyte hypertrophy and extracellular matrix degradation, and promote the occurrence and development of OA. This article systematically summarizes the regulatory effects of different enzymes and factors related to glucose metabolism in OA, as well as the mechanism and potential of various substances in the treatment of OA by affecting glucose metabolism. This provides a theoretical basis for a better understanding of the mechanism of OA progression and the development of optimal prevention and treatment strategies.

Hnrnpk protects against osteoarthritis through targeting WWC1 mRNA and inhibiting Hippo signaling pathway.

Osteoarthritis (OA) is an age-related or post-traumatic degenerative whole joint disease characterized by the rupture of articular cartilage homeostasis, the regulatory mechanisms of which remain elusive. This study identifies the essential role of heterogeneous nuclear ribonucleoprotein K (hnRNPK) in maintaining articular cartilage homeostasis. Hnrnpk expression is markedly downregulated in human and mice OA cartilage. The deletion of Hnrnpk effectively accelerates the development of post-traumatic and age-dependent OA in mice. Mechanistically, the KH1 and KH2 domain of Hnrnpk bind and degrade the mRNA of WWC1. Hnrnpk deletion increases WWC1 expression, which in turn leads to the activation of Hippo signaling and ultimately aggravates OA. In particular, intra-articular injection of LPA and adeno-associated virus serotype 5 expressing WWC1 RNA interference ameliorates cartilage degeneration induced by Hnrnpk deletion, and intra-articular injection of adeno-associated virus serotype 5 expressing Hnrnpk protects against OA. Collectively, this study reveals the critical roles of Hnrnpk in inhibiting OA development through WWC1-dependent downregulation of Hippo signaling in chondrocytes and defines a potential target for the prevention and treatment of OA.

Bone deformity in sports-related elbow osteoarthritis: influence of osteochondritis dissecans of the capitellum-a cross-sectional study.

INTRODUCTION: Sports activity can cause elbow osteoarthritis, which subsequently induces bone deformity. Osteochondritis dissecans (OCD) of the capitellum develops defects of articular surfaces and can exacerbate bone deformity. This study aimed to investigate whether OCD exacerbates deformities in sports-related elbow osteoarthritis. MATERIALS AND METHODS: Twenty-one patients who underwent bilateral computed tomography preoperatively followed by surgery for sports-related elbow osteoarthritis were included. Patients were divided into two groups according to the presence or absence of an OCD history: OCD + (n = 6) and OCD- (n = 15). Bilateral three-dimensional bone models of the humerus, ulna, and radius were created using computed tomography data, and bone deformities were extracted by subtracting healthy mirror models from the affected models using a Boolean operation. Bone deformities were divided into 22 regions in the 3 bones. The volume of the deformity was estimated by correlating the anteroposterior and lateral diameters of the OCD and by comparing the two groups. RESULTS: The anteroposterior diameter of the OCD correlated with the articular surface of the medial trochlear notch, whereas the lateral diameter correlated with the whole ulna, medial gutter of the ulna, whole radius, and lateral side of the radial head. The deformities were 2.2 times larger in the whole humerus, 1.9 times larger in the whole ulna, and 3.0 times larger in the whole radius in the OCD + group than in the OCD- group. The deformities were significantly larger in the OCD + group than in the OCD- group in the radial fossa, posterior capitellum, medial gutter, and lateral gutter in the humerus, medial gutter in the ulna, and lateral, anterior, and posterior sides of the radial head. CONCLUSION: Larger OCD exacerbated deformity in elbow OA, and the presence of OCD exacerbated deformities in sports-related elbow OA. These results demonstrate the highlight of preventing OCD progression.

Genetically inspired organoids prevent joint degeneration and alleviate chondrocyte senescence via Col11a1-HIF1α-mediated glycolysis-OXPHOS metabolism shift.

INTRODUCTION: Developmental dysplasia of hip (DDH) is a hip joint disorder leading to subsequent osteoarthritis. Previous studies suggested collagen XI alpha 1 (COL11A1) as a potential gene in hip dysplasia and chondrocyte degeneration. However, no genetic association has reported COL11A1-related cellular therapy as treatment of DDH and joint degeneration. METHODS AND RESULTS: We report identified genetic association between COL11A1 locus and DDH with genome-wide association study (GWAS). Further exome sequencing for familial DDH patients was conducted in different populations to identify potential pathogenic Col11A1 variants for familiar DDH. Further studies demonstrated involvement of COL11A1 expression was down-regulated in femoral head cartilage of DDH patients and Col11a1-KO mice with induced DDH. Col11a1-KO mice demonstrated aggravated joint degeneration and severe OA phenotype. To explore the underlying mechanism of Col11a1 in cartilage and DDH development, we generated scRNA-seq profiles for DDH and Col11a1-KO cartilage, demonstrating disrupted chondrocyte homeostasis and cellular senescence caused by Col11a1-HIF1α-mediated glycolysis-OXPHOS shift in chondrocytes. Genetically and biologically inspired, we further fabricated an intra-articular injection therapy to preventing cartilage degeneration by generating a Col11a1-over-expressed (OE) SMSC mini-organoids. Col11a1-OE organoids demonstrated superior chondrogenesis and ameliorated cartilage degeneration in DDH mice via regulating cellular senescence by up-regulated Col11a1/HIF1α-mediated glycolysis in chondrocytes. CONCLUSION: We reported association between COL11A1 loci and DDH with GWAS and exome sequencing. Further studies demonstrated involvement of COL11A1 in DDH patients and Col11a1-KO mice. ScRNA-seq for DDH and Col11a1-KO cartilage demonstrated disrupted chondrocyte homeostasis and cellular senescence caused by Col11a1-HIF1α-mediated glycolysis-OXPHOS shift in chondrocytes. Genetically and biologically inspired, an intra-articular injection therapy was fabricated to prevent cartilage degeneration with Col11a1-OE SMSC organoids. Col11a1-OE organoids ameliorated cartilage degeneration in DDH mice via regulating cellular senescence by up-regulated Col11a1/HIF1α-mediated glycolysis in chondrocytes.

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice.

BACKGROUND: Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression. PURPOSE: To evaluate the therapeutic effects of systemic and topical TXA treatment on the progression of posttraumatic OA in the knee of mice. STUDY DESIGN: Controlled laboratory study. METHODS: OA was induced via anterior cruciate ligament (ACL) transection on the right knee of female mice. Mice were treated with TXA or vehicle intraperitoneally daily or intra-articularly weekly for 4 weeks, starting on the day of surgery. Articular cartilage degeneration, synovitis, bone erosion, and osteophyte formation were scored histologically. Micro-computed tomography evaluation was conducted to measure the subchondral bone microstructure and osteophyte volume. Cartilage thickness and bone remodeling were assessed histomorphometrically. RESULTS: Both systemic and topical TXA treatment significantly reduced cartilage degeneration, synovitis, and bone erosion scores and increased the ratio of hyaline to calcified cartilage thickness in posttraumatic OA. Systemic TXA reversed ACL transection-induced subchondral bone loss and osteophyte formation, whereas topical treatment had no effect. Systemic TXA decreased the number and surface area of osteoclasts, whereas those of osteoblasts were not affected. No effect of topical TXA on osteoblast or osteoclast parameters was observed. CONCLUSION: Both systemic and topical TXA exerted protective effects on the progression of posttraumatic OA. Drug repurposing of TXA may, therefore, be useful for the prevention or treatment of posttraumatic OA, particularly after ACL surgery. CLINICAL RELEVANCE: TXA might be beneficial in patients with posttraumatic OA of the knee.

Nanoparticle-based inhibition of vascular endothelial growth factor receptors alleviates osteoarthritis pain and cartilage damage.

Osteoarthritis (OA) is characterized by cartilage damage, inflammation, and pain. Vascular endothelial growth factor receptors (VEGFRs) have been associated with OA severity, suggesting that inhibitors targeting these receptors alleviate pain (via VEGFR1) or cartilage degeneration (via VEGFR2). We have developed a nanoparticle-based formulation of pazopanib (Votrient), an FDA-approved anticancer drug that targets both VEGFR1 and VEGFR2 (Nano-PAZII). We demonstrate that a single intraarticular injection of Nano-PAZII can effectively reduce joint pain for a prolonged time without substantial side effects in two different preclinical OA rodent models involving either surgical (upon partial medial meniscectomy) or nonsurgical induction (with monoiodoacetate). The injection of Nano-PAZII blocks VEGFR1 and relieves OA pain by suppressing sensory neuronal ingrowth into the knee synovium and neuronal plasticity in the dorsal root ganglia and spinal cord. Simultaneously, the inhibition of VEGFR2 reduces cartilage degeneration. These findings provide a mechanism-based disease-modifying drug strategy that addresses both pain symptoms and cartilage loss in OA.

Is occupational noise associated with arthritis? Cross-sectional evidence from US population.

BACKGROUND: The impact of occupational noise exposure on various diseases, including ear and cardiovascular diseases, has been studied extensively. Nevertheless, the connection between osteoarthritis (OA) and rheumatoid arthritis (RA) and occupational noise exposure remains largely unexplored in real-world scenarios. This study assessed the association between occupational noise exposure and the prevalence of two types of arthritis. METHODS: This study used database data from 2005 to 2012 and 2015-March 2020 from the prepandemic National Health and Nutrition Examination Survey (NHANES) related to occupational noise exposure and arthritis. Multivariate logistic regression analysis was used to estimate the association between occupational noise exposure and RA/OA, adjusting for age, gender, race, education level, marital status, the ratio of family income to poverty, trouble sleeping, smoking status, alcohol consumption, diabetes, hypertension, body mass index (BMI), metabolic equivalents (METs), and thyroid disease. RESULTS: This study included 11,053 participants. Multivariate logistic regression analysis demonstrated that previous exposure to occupational noise was positively associated with self-reported RA (OR = 1.43, 95% CI = 1.18-1.73) and OA (OR = 1.25, 95% CI = 1.07-1.46). Compared to individuals without a history of occupational noise exposure, those with an exposure duration of 1 year or greater exhibited higher odds of prevalent RA, though there was no apparent exposure response relationship for noise exposure durations longer than 1 year. The results of our subgroup analyses showed a significant interaction between age and occupational noise exposure on the odds of self-reported prevalent OA. CONCLUSIONS: Our findings suggest an association between occupational noise exposure and the prevalence of RA and OA. Nevertheless, further clinical and basic research is warranted to better explore their associations.

Sirtuin 4 (Sirt4) downregulation contributes to chondrocyte senescence and osteoarthritis via mediating mitochondrial dysfunction.

Chondrocyte senescence has recently been proposed as a key pathogenic mechanism in the etiology of osteoarthritis (OA). Nevertheless, the precise molecular mechanisms underlying chondrocyte senescence remain poorly understood. To address this knowledge gap, we conducted an investigation into the involvement of Sirtuin 4 (Sirt4) in chondrocyte senescence. Our experimental findings revealed a downregulation of Sirt4 expression in TBHP-induced senescent chondrocytes in vitro, as well as in mouse OA cartilage. Additionally, we observed that the knockdown of Sirt4 in chondrocytes promoted cellular senescence and cartilage degradation, while the overexpression of Sirt4 protected the cells against TBHP-mediated senescence of chondrocytes and cartilage degradation. Moreover, our findings revealed elevated levels of reactive oxygen species (ROS), abnormal mitochondrial morphology, compromised mitochondrial membrane potential, and reduced ATP production in Sirt4 knockdown chondrocytes, indicative of mitochondrial dysfunction. Conversely, Sirt4 overexpression successfully mitigated TBHP-induced mitochondrial dysfunction. Further analysis revealed that Sirt4 downregulation impaired the cellular capacity to eliminate damaged mitochondria by inhibiting Pink1 in chondrocytes, thereby enhancing the accumulation of ROS and facilitating chondrocyte senescence. Notably, the overexpression of Pink1 counteracted the effects of Sirt4 knockdown on mitochondrial dysfunction. Importantly, our study demonstrated the promise of gene therapy employing a lentiviral vector encoding mouse Sirt4, as it successfully preserved the integrity of articular cartilage in mouse models of OA. In conclusion, our findings provide compelling evidence that the overexpression of Sirt4 enhances mitophagy, restores mitochondrial function, and protects against chondrocyte senescence, thereby offering a novel therapeutic target and potential strategy for the treatment of OA.

Synovial-tissue resident macrophages play proinflammatory functions in the pathogenesis of RA while maintaining the phenotypes in the steady state.

Synovial tissue-resident macrophages (STRMs) maintain normal joint homeostasis in a steady state. However, it is unclear whether STRMs still play homeostatic roles or change the functions in the joint of rheumatoid arthritis (RA), where infiltrating peripheral blood monocyte-derived macrophages (PBMoMs) play proinflammatory roles. In the present study, we examined changes in the phenotypes and functions of STRMs in response to RA-related stimuli in vitro. STRMs were prepared from non-inflammatory osteoarthritis (OA) joint synovium, which is histologically indistinguishable from normal joint synovium. PBMoMs were prepared and used for comparison. After stimulation with plate-bound IgG, which mimics anti-citrullinated protein antibody immunocomplex formed in RA joints, or with combinations of RA-related inflammatory mediators, namely tumor necrosis factor-α (TNF-α) and prostaglandin E2 or interferon-γ, PBMoMs downregulated surface markers and genes associated with anti-inflammatory macrophages, and upregulated cytokine and marker genes of proinflammatory macrophages in RA. On the other hand, STRMs hardly changed the expression of surface molecules and marker genes but altered the pattern of cytokine gene expression after stimulation like PBMoMs. Furthermore, in vitro stimulated STRMs promote proinflammatory functions of cocultured synovial fibroblasts. Thus, STRMs might play proinflammatory roles in RA joints, while maintaining their phenotypes in the steady state.

The clinical characteristics, managements, and outcomes of acute myocardial infarction in osteoarthritis patients; a cross-sectional analysis of 6.5 million patients.

OBJECTIVES: The prevalence of osteoarthritis (OA) and cardiovascular disease are increasing and both conditions share similar risk factors. We investigated the association between OA and receipt of invasive managements and clinical outcomes in patients with acute myocardial infarction (AMI). METHODS: Using the National Inpatient Sample, adjusted binary logistic regression determined the association between OA and each outcome variable. RESULTS: Of 6,561,940 AMI hospitalizations, 6.3% had OA. OA patients were older and more likely to be female. OA was associated with a decreased odds of coronary angiography (adjusted odds ratio 0.91; 95% confidence interval 0.90, 0.92), PCI (0.87; 0.87, 0.88), and coronary artery bypass grafting (0.98; 0.97, 1.00). OA was associated with a decreased odds of adverse outcomes (in-hospital mortality: 0.68; 0.67, 0.69; major acute cardiovascular and cerebrovascular events: 0.71; 0.70, 0.72; all-cause bleeding: 0.76; 0.74, 0.77; and stroke/TIA: 0.84; 0.82, 0.87). CONCLUSIONS: This study of a representative sample of the US population highlights that OA patients are less likely to be offered invasive interventions following AMI. OA was also associated with better outcomes post-AMI, possibly attributed to a misclassification bias where unwell patients with OA were less likely to receive an OA code because codes for serious illness took precedence.

A New Method for Creating Impact-Induced Intra-Articular Fractures in a Rabbit Model Induces Severe Post-Traumatic Osteoarthritis.

OBJECTIVES: The objective of this work was to develop a model of intra-articular fracture (IAF) in a rabbit and document the speed and severity of degenerative joint changes after fracture fixation. METHODS: With Institutional Animal Care & Use Committee approval, impact-induced IAFs were created in the distal tibia of 16 New Zealand White rabbits. Fractures were fixed with a plate and screws. Pain and function were monitored at regular postoperative intervals with limb loading analysis. Twelve or 26 weeks after fracture, animals were euthanized for histological assessment of cartilage degeneration and micro-computed tomography analysis of bone histomorphometry. RESULTS: Eleven animals successfully completed the study. Maximum foot force in the fractured limb was 41% ± 21% lower than preoperative values ( P = 0.006) 12 weeks after fracture and remained 25% ± 13% lower ( P = 0.081) after 26 weeks. Cortical bone mineral density in micro-computed tomography images was 34% ± 13% lower 12 weeks after fracture ( P < 0.001) and remained (42% ± 8%) lower 26 weeks after fracture ( P < 0.001). Twelve weeks after fracture, Mankin scores of cartilage degeneration were significantly higher in the medial talus ( P = 0.007), lateral talus ( P < 0.001), medial tibia ( P = 0.017), and lateral tibia ( P = 0.002) of the fractured limb compared with the uninjured contralateral limb. Average Mankin scores in the talus increased from 12 to 26 weeks (5.9 ± 0.9 to 9.4 ± 0.4; P < 0.001 lateral; 5.4 ± 1.8 to 7.8 ± 2.0; P = 0.043 medial), indicating substantial and progressive joint degeneration. CONCLUSIONS: The ankle joint of the New Zealand White rabbit provides the smallest available model of impact-induced IAF that can be treated with clinically relevant techniques and replicates key features of healing and degeneration found in human patients.

Outcomes and Return-to-Sports Rates in Patients With Borderline Hip Dysplasia After Periacetabular Osteotomy: A Case Series With 5-Year Follow-up.

BACKGROUND: The optimal surgical approach in patients with borderline hip dysplasia (BHD) remains controversial. Both hip arthroscopy and periacetabular osteotomy (PAO) are commonly employed in this patient population. Those who participate in sports want to resume and maintain sports activities after surgery, and the ability to do so plays an important role in the choice of a treatment method. To our knowledge, no previous study has assessed return-to-sports rates and activity levels in patients with BHD after PAO. PURPOSE: To assess return-to-sports rates and postoperative activity levels as measured by the University of California, Los Angeles (UCLA), activity scale as well as patient-reported outcome measures. Also to assess changes in sports activity both qualitatively and quantitatively as well as underlying reasons for these changes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We conducted a retrospective analysis of prospectively collected data from 55 hips in 52 patients with BHD who underwent PAO between January 2015 and June 2017. Return-to-sports rates, UCLA activity scores, International Hip Outcome Tool-12 scores, Subjective Hip Value scores, Hip disability and Osteoarthritis Outcome Score subscores, sports practiced, frequency and duration of sports activity, and postoperative changes as well as underlying reasons were recorded. RESULTS: The mean follow-up was 62.8 ± 9.0 months. The return-to-sports rate among preoperatively active patients was 92.5%. Most patients resumed sports activity after 6 months (50%) or after 3 to 6 months (37.5%). The UCLA activity score improved significantly (from 5.2 ± 2.4 to 7.0 ± 1.8; P < .001). The International Hip Outcome Tool-12, Subjective Hip Value, and Hip disability and Osteoarthritis Outcome Score scores also improved significantly (all, P < .001). Changes in sports activity occurred in 34.5% of cases after PAO. Significantly more patients engaged in low-impact sports postoperatively. Participation in high-impact sports did not decrease significantly. Reasons for changes were both hip related and non-hip related. Quantitatively, patients were able to significantly increase both the frequency (P = .007) and duration (P = .007) of sports activity. CONCLUSION: The return-to-sports rate in patients with BHD after PAO was high at over 92%. Most patients returned to sports after a period of 6 months or 3 to 6 months. Overall, activity levels and hip function improved after PAO. A number of patients adjusted their sports activity after PAO. Although more patients engaged in low-impact sports, participation in high-impact sports was maintained postoperatively. The results of this study may help both patients and orthopaedic surgeons in deciding on the best surgical procedure in the setting of BHD.