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Early diagnosis of post‐traumatic osteoarthritis (PTOA) is critical for designing better treatments before the degradation becomes irreversible. We utilized multimodal high‐resolution imaging to investigate early‐stage deterioration in articular cartilage and the subchondral bone plate from a sub‐critical impact to the knee joint, which initiates PTOA. The knee joints of 12 adult rabbits were mechanically impacted once on the femoral articular surface to initiate deterioration. At 2‐ and 14‐week post‐impact surgery, cartilage‐bone blocks were harvested from the impact region in the animals (N = 6 each). These blocks were assessed for deterioration using polarized light microscopy (PLM), microcomputed tomography (μCT), and biochemical analysis. Statistically significant changes were noted in the impact tissues across the calcified zone (CZ) at 14 weeks post‐impact: the optical retardation values in the CZ of impact cartilage had a drop of 29.0% at 14 weeks, while the calcium concentration in the CZ of impact cartilage also had a significant drop at 14 weeks. A significant reduction of 6.3% in bone mineral density (BMD) was noted in the subchondral bone plate of the impact samples at 14 weeks. At 2 weeks post‐impact, only minor, non‐significant changes were measured. Furthermore, the impact knees after 14 weeks had greater structural changes compared with the 2‐week impact knees, indicating progressive degradation over time. The findings of this study facilitated a connection between mineralization alterations and the early deterioration of knee cartilage after a mechanical injury. In a broader context, these findings can be beneficial in improving clinical strategies to manage joint injuries. [ABSTRACT FROM AUTHOR]

To investigate the effect of unilateral anterior cruciate ligament (ACL) injury on cartilage thickness and composition, specifically laminar transverse relaxation time (T2) by magnetic resonance imaging (MRI), in younger and older participants and to compare within-person side differences in these parameters between ACL-injured and healthy controls. Quantitative double-echo steady-state 3 Tesla MRI-sequences were acquired in both knees of 85 participants in four groups: 20–30 years: healthy, HEA 20–30 , n = 24; ACL-injured, ACL 20–30 , n = 23; 40–60 years: healthy, HEA 40–60 , n = 24; ACL-injured, ACL 40–60 , n = 14 (ACL injury 2–10 years prior to study inclusion). Weight-bearing femorotibial cartilages were manually segmented; cartilage T2 and thickness were computed using custom software. Mean and side differences in subregional cartilage thickness, superficial and deep cartilage T2 were compared within and between groups using non-parametric statistics. Cartilage thickness did not differ within or between groups. Only the side difference in medial femorotibial cartilage thickness was greater in ACL 20–30 than in HEA 20–30. Deep zone T2 was longer in the ACL-injured than in the contralateral uninjured knees and than in healthy controls, especially in the lateral compartment. Most ACL-injured participants had side differences in femorotibial deep zone T2 above the threshold derived from controls. In the ACL-injured knee, early compositional differences in femorotibial cartilage (T2) appear to occur in the deep zone and precede cartilage thickness loss. These results suggest that monitoring laminar T2 after ACL injury may be useful in diagnosing and monitoring early articular cartilage changes. [ABSTRACT FROM AUTHOR]

Background: End-stage post-traumatic osteoarthritis of the ankle joint may require arthrodesis if conservative treatment fails and a decision against total ankle replacement is made. We aimed to compare the sex-specific differences in outcomes and objectify them using validated specific scores. Methods: Between 2010 and 2021, 221 patients underwent ankle arthrodesis at our institution, including 143 men (MAA) and 78 women (FAA). In addition to demographic data, the aetiology of osteoarthritis, the Foot Function Index (FFI-D), the Olerud-Molander Score (OMAS), and the Short Form-12 questionnaire (SF-12) were collected in this monocentric study. The mean follow-up time was 5.8 years. End-stage osteoarthritis was mostly due to ankle fractures as a result of sprains, falls, and road traffic accidents. Results: Post-operatively, the mean FFI-D for pain was 17.3 (MAA: 14.7; FAA 22.2) and 43.9 for function (MAA: 41.1; FAA 49.5); the mean OMAS was 58.2; and the mean SF-12 physical component score was 42.5. Women achieved significantly worse results in all scores; only the mental component summary of the SF-12 did not differ between the sexes (p > 0.05). Approximately 34% of women stated that the result in terms of gait pattern was worse than expected (MAA 16.1%; p < 0.05). Again, significantly more men stated that the result was better than expected (MAA: 48.3%; FAA: 31.5%, p < 0.05). Conclusions: The fact that the clinical results were significantly worse in women after ankle arthrodesis should be considered when determining the indication. However, the expectations of men and women also need to be individually adjusted. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a heterogeneous disease. The objective was to compare differences in underlying cellular mechanisms and endogenous repair pathways between synovial fluid (SF) from male and female participants with different injuries to improve the current understanding of the pathophysiology of downstream post-traumatic osteoarthritis (PTOA). SF from n = 33 knee arthroscopy patients between 18 and 70 years with no prior knee injuries was obtained pre-procedure and injury pathology assigned post-procedure. SF was extracted and analyzed via liquid chromatography-mass spectrometry metabolomic profiling to examine differences in metabolism between injury pathologies (ligament, meniscal, and combined ligament and meniscal) and patient sex. Samples were pooled and underwent secondary fragmentation to identify metabolites. Different knee injuries uniquely altered SF metabolites and downstream pathways including amino acid, lipid, and inflammatory-associated metabolic pathways. Notably, sexual dimorphic metabolic phenotypes were examined between males and females and within injury pathology. Cervonyl carnitine and other identified metabolites differed in concentrations between sexes. These results suggest that different injuries and patient sex are associated with distinct metabolic phenotypes. Considering these phenotypic associations, a greater understanding of metabolic mechanisms associated with specific injuries, sex, and PTOA development may yield data regarding how endogenous repair pathways differ between male and female injury types. Ongoing metabolomic analysis of SF in injured male and female patients can be performed to monitor PTOA development and progression. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA's natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males. A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2 weeks, and 6 weeks post-surgery (129 biospecimens in total). High-throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre-surgery versus 2 and 6 weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed. Levels of 46 miRNAs were increased at 2 weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2 weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2 weeks (log 2 -fold-change 0.71, 95%CI 0.22,1.20) and 6 weeks (log 2 -fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2 weeks (log 2 -fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6 weeks (log 2 -fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2 weeks post-surgery in females compared to males: L-leucine (−1.44, 95%CI −1.75,−1.13), g-guanidinobutyrate (−1.27, 95%CI 1.54,−0.99), creatinine (−1.17, 95%CI −1.44,−0.90), 2-methylbutyrylcarnitine (−1.76, 95%CI −2.17,−1.35), and leu-pro (−1.13, 95%CI −1.44,−0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males. MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a disease with sex-dependent prevalence and severity in both human and animal models. We sought to elucidate sex differences in synovitis, mechanical sensitization, structural damage, bone remodeling, and the synovial transcriptome in the anterior cruciate ligament rupture (ACLR) mouse model of post-traumatic OA (PTOA). Male and female 12-week-old C57/BL6J mice were randomized to Sham or noninvasive ACLR with harvests at 7d or 28d post-ACLR (n = 9 per sex in each group – Sham, 7d ACLR, 28d ACLR). Knee hyperalgesia, mechanical allodynia, and intra-articular matrix metalloproteinase (MMP) activity (via intravital imaging) were measured longitudinally. Trabecular and subchondral bone (SCB) remodeling and osteophyte formation were assessed by µCT. Histological scoring of PTOA, synovitis, and anti-MMP13 immunostaining were performed. Na V 1.8-Cre;tdTomato mice were used to document localization and sprouting of nociceptors. Bulk RNA-seq of synovium in Sham, 7d, and 28d post-ACLR, and contralateral joints (n = 6 per group per sex) assessed injury-induced and sex-dependent gene expression. Male mice exhibited more severe joint damage at 7d and 28d and more severe synovitis at 28d, accompanied by 19% greater MMP activity, 8% lower knee hyperalgesia threshold, and 43% lower hindpaw withdrawal threshold in injured limbs compared to female injured limbs. Females had injury-induced catabolic responses in trabecular and SCB, whereas males exhibited 133% greater normalized osteophyte volume relative to females and sclerotic remodeling of trabecular and SCB. Na V 1.8+ nociceptor sprouting in SCB and medial synovium was induced by injury and comparable between sexes. RNA-seq of synovium demonstrated similar injury-induced transcriptomic programs between the sexes at 7d, but only female mice exhibited a transcriptomic signature indicative of synovial inflammatory resolution by 28d, whereas males had persistent pro-inflammatory, pro-fibrotic, pro-neurogenic, and pro-angiogenic gene expression. Male mice exhibited more severe overall joint damage and pain behavior after ACLR, which was associated with persistent activation of synovial inflammatory, fibrotic, and neuroangiogenic processes, implicating persistent synovitis in driving sex differences in murine PTOA. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament (ACL) injuries are associated with a risk of post-traumatic osteoarthritis due to chondral damage. Magnetic resonance imaging (MRI) techniques provide excellent visualization and assessment of cartilage and can detect subtle and early chondral damage. This is often preceding clinical and radiographic post-traumatic osteoarthritis. Hypothesis: Morphologic and quantitative MRI techniques can assess early and progressive degenerative chondral changes after acute ACL injury. Study Design: Prospective longitudinal cohort. Level of Evidence: Level 3. Methods: Sixty-five participants with acute unilateral ACL injuries underwent bilateral knee MRI scans within 1 month of injury. Fifty-seven participants presented at 6 months, while 54 were evaluated at 12 months. MRI morphologic evaluation using a modified Noyes score assessed cartilage signal alteration, chondral damage, and subchondral bone status. Quantitative T1ρ and T2 mapping at standardized anatomic locations in both knees was assessed. Participant-reported outcomes at follow-up time points were recorded. Results: Baseline Noyes scores of MRI detectable cartilage damage were highest in the injured knee lateral tibial plateau (mean 2.5, standard error (SE) 0.20, P < 0.01), followed by lateral femoral condyle (mean 2.1, SE 0.18, P < 0.01), which progressed after 1 year. Longitudinal prolongation at 12 months in the injured knees was significant for T1ρ affecting the medial and lateral femoral condyles (P < 0.01) and trochlea (P < 0.01), whereas T2 values were prolonged for medial and lateral femoral condyles (P < 0.01) and trochlea (P < 0.01). The contralateral noninjured knees also demonstrated T1ρ and T2 prolongation in the medial and lateral compartment chondral subdivisions. Progressive chondral damage occurred despite improved patient-reported outcomes. Conclusion: After ACL injury, initial and sustained chondral damage predominantly affects the lateral tibiofemoral compartment, but longitudinal chondral degeneration also occurred in other compartments of the injured and contralateral knee. Clinical Relevance: Early identification of chondral degeneration post-ACL injury using morphological and quantitative MRI techniques could enable interventions to be implemented early to prevent or delay PTOA. [ABSTRACT FROM AUTHOR]

Aims: 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. Methods: 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. Results: 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. Conclusion: 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. Cite this article: Bone Joint Res 2024;13(9):513–524.

Abstract Background Untreated 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. Methods In 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. Results After 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

Abstract Background End-stage post-traumatic osteoarthritis of the ankle joint may require arthrodesis if conservative treatment fails and a decision against total ankle replacement is made. We aimed to compare the sex-specific differences in outcomes and objectify them using validated specific scores. Methods Between 2010 and 2021, 221 patients underwent ankle arthrodesis at our institution, including 143 men (MAA) and 78 women (FAA). In addition to demographic data, the aetiology of osteoarthritis, the Foot Function Index (FFI-D), the Olerud-Molander Score (OMAS), and the Short Form-12 questionnaire (SF-12) were collected in this monocentric study. The mean follow-up time was 5.8 years. End-stage osteoarthritis was mostly due to ankle fractures as a result of sprains, falls, and road traffic accidents. Results Post-operatively, the mean FFI-D for pain was 17.3 (MAA: 14.7; FAA 22.2) and 43.9 for function (MAA: 41.1; FAA 49.5); the mean OMAS was 58.2; and the mean SF-12 physical component score was 42.5. Women achieved significantly worse results in all scores; only the mental component summary of the SF-12 did not differ between the sexes (p > 0.05). Approximately 34% of women stated that the result in terms of gait pattern was worse than expected (MAA 16.1%; p

The ArmeD SerVices TrAuma RehabilitatioN OutComE (ADVANCE) study is investigating long-term combat-injury outcomes; this sub-study aims to understand the association of osteoarthritis (OA) biomarkers with knee radiographic OA (rOA), pain and function in this high-risk population for post-traumatic OA. ADVANCE compares combat-injured participants with age, rank, deployment and job-role frequency-matched uninjured participants. Post-injury immunoassay-measured serum biomarkers, knee radiographs, Knee Injury and Osteoarthritis Outcome Scale, and six-minute walk tests are reported. The primary analysis, adjusted for age, body mass, socioeconomic status, and ethnicity, was to determine any differences in biomarkers between those with/without combat injury, rOA and pain. Secondary analyses were performed to compare post-traumatic/idiopathic OA, painful/painfree rOA and injury patterns. A total of 1145 male participants were recruited, aged 34.1 ± 5.4, 8.9 ± 2.2 years post-injury (n = 579 trauma-exposed, of which, traumatic-amputation n = 161) or deployment (n = 566 matched). Cartilage oligomeric matrix protein (COMP) was significantly higher in the combat-injured group compared to uninjured (p = 0.01). Notably, COMP was significantly lower in the traumatic-amputation group compared to non-amputees (p < 0.001), decreasing relative to number of amputations (p < 0.001). Leptin was higher (p = 0.005) and adiponectin lower (p = 0.017) in those with v without knee pain, associated with an increased risk of 22% and 17% for pain, and 46% and 34% for painful rOA, respectively. There were no significant differences between trauma-exposed and unexposed participants with rOA. The most notable findings of this large, unique study are the similarities between those with rOA regardless of trauma-exposure, the injury-pattern and traumatic-amputation-associated differences in COMP, and the relationship between adipokines and pain. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) injury, particularly in increasingly young and active adolescents, continues to pose a clinical challenge with re-injury rates reported as high as 30%. Evidence also suggests that current standard-of-care ACL reconstruction (ACLR) does not mitigate post-traumatic osteoarthritis (PTOA) risk. Bridge- enhanced ACL restoration (BEAR) is a recently developed and tested ACL surgery that promotes primary healing of the native ACL with excellent early results. BEAR has shown to reduce signs of early PTOA compared to ACLR in an animal model. Here, we describe a theoretical framework related to re-innervation that can clarify why the outcomes of ACLR and BEAR surgeries differ. We also discuss how ongoing and new challenges in determining return-to-sport readiness following the competing surgeries may differ, and how emerging imaging tools and measures of neuromuscular function may aid in clinical decision-making to decrease the likelihood of re-injury and PTOA risk. [ABSTRACT FROM AUTHOR]

Post-traumatic osteoarthritis of the ankle (PTOA) is frequently observed following a debilitating consequence of intra-articular ankle fractures. Numerous risk factors contribute to the pathogenesis of PTOA, including articular incongruity, joint malalignment, and concomitant soft tissue damage. Despite attempts to restore joint anatomy and manage soft tissues to avoid long-term complications after intra-articular ankle fractures, the incidence of PTOA remains markedly elevated. Inflammatory processes triggered by intra-articular ankle fractures have emerged as potential instigators that expedite the progression of PTOA. Injury to the articular cartilage and subchondral bone may lead to the release of inflammatory mediators, which can contribute to cartilage degradation and bone resorption. This study provides a narrative review on the current knowledge concerning the association between inflammation and the development of PTOA following intra-articular ankle fractures. We also discuss novel therapeutic agents that target inflammatory pathways to impede the progression of post-traumatic osteoarthritis after intra-articular ankle fractures. These medication and interventions were summarized within this review article. [ABSTRACT FROM AUTHOR]

The aim of the study – to identify the factors associated with the development of chronic post-traumatic pain (CPTP) in patients with knee joint (KJ) injury.Materials and methods. The study group consisted of 136 patients (51.5% women, age 38.7±12.4 years) who suffered a KJ injury with damage to the anterior cruciate ligament and/or menisci. The inclusion criterion was the presence of pain in KJ ≥4 on a numerical rating scale (NRS 0–10) for at least 1 month after injury. Surgical intervention (plastic surgery of the anterior cruciate ligament, meniscus suture, meniscus resection, combined operations) was performed immediately after injury in 48.5% of patients. The incidence of CPTP was assessed (persistence of pain during movement ≥4 on NRS after 3 and 6 months of follow-up) and factors related to the development of CPTP. All patients were recommended to use orthoses of KJ, physical therapy and taking nonsteroidal anti-inflammatory drugs in the “on-demand” mode. Results. CPTP was detected after 3 months in 33.1%, and after 6 months in 32.4% of patients. Surgical treatment did not affect the development of CPTP: odds ratio (OR) – 1.241, 95% confidence interval (95% CI): 0.775–1.986 (p=0.474). The risk of CPTP after 6 months was statistically significantly higher in women, persons with a high body mass index (≥30 kg/m2), initially severe pain (≥7 on NRS), in the presence of initial signs of depression and anxiety (HADS (Hospital Anxiety and Depression Scale) ≥8) and highly probable central sensitization (CSI (Central Sensitization Inventory) ≥40): OR=2,152, 95% CI: 1,383–3,348 (p=0,002); OR=1,243, 95% CI: 1,054–1,465 (p=0,05); OR=3,567, 95% CI: 1,717–5,708 (p=0,001); OR=2,330, 95% CI: 1,070–5,726 (p=0.0044); OR=2,446, 95% CI: 1,220–4,905 (p=0,016); OR=2,584, 95% CI: 1,101–8,133 (p=0.043), respectively.

Abstract Objective Muscle wasting frequently occurs following joint trauma. Previous research has demonstrated that joint distraction in combination with treadmill exercise (TRE) can mitigate intra-articular inflammation and cartilage damage, consequently delaying the advancement of post-traumatic osteoarthritis (PTOA). However, the precise mechanism underlying this phenomenon remains unclear. Hence, the purpose of this study was to examine whether the mechanism by which TRE following joint distraction delays the progression of PTOA involves the activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), as well as its impact on muscle wasting. Methods Quadriceps samples were collected from patients with osteoarthritis (OA) and normal patients with distal femoral fractures, and the expression of PGC-1α was measured. The hinged external fixator was implanted in the rabbit PTOA model. One week after surgery, a PGC-1α agonist or inhibitor was administered for 4 weeks prior to TRE. Western blot analysis was performed to detect the expression of PGC-1α and Muscle atrophy gene 1 (Atrogin-1). We employed the enzyme-linked immunosorbent assay (ELISA) technique to examine pro-inflammatory factors. Additionally, we utilized quantitative real-time polymerase chain reaction (qRT-PCR) to analyze genes associated with cartilage regeneration. Synovial inflammation and cartilage damage were evaluated through hematoxylin-eosin staining. Furthermore, we employed Masson’s trichrome staining and Alcian blue staining to analyze cartilage damage. Results The decreased expression of PGC-1α in skeletal muscle in patients with OA is correlated with the severity of OA. In the rabbit PTOA model, TRE following joint distraction inhibited the expressions of muscle wasting genes, including Atrogin-1 and muscle ring finger 1 (MuRF1), as well as inflammatory factors such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in skeletal muscle, potentially through the activation of PGC-1α. Concurrently, the production of IL-1β, IL-6, TNF-α, nitric oxide (NO), and malondialdehyde (MDA) in the synovial fluid was down-regulated, while the expression of type II collagen (Col2a1), Aggrecan (AGN), SRY-box 9 (SOX9) in the cartilage, and superoxide dismutase (SOD) in the synovial fluid was up-regulated. Additionally, histological staining results demonstrated that TRE after joint distraction reduced cartilage degeneration, leading to a significant decrease in OARSI scores.TRE following joint distraction could activate PGC-1α, inhibit Atrogin-1 expression in skeletal muscle, and reduce C-telopeptides of type II collagen (CTX-II) in the blood compared to joint distraction alone. Conclusion Following joint distraction, TRE might promote the activation of PGC-1α in skeletal muscle during PTOA progression to exert anti-inflammatory effects in skeletal muscle and joint cavity, thereby inhibiting muscle wasting and promoting cartilage regeneration, making it a potential therapeutic intervention for treating PTOA.

Objective: Muscle wasting frequently occurs following joint trauma. Previous research has demonstrated that joint distraction in combination with treadmill exercise (TRE) can mitigate intra-articular inflammation and cartilage damage, consequently delaying the advancement of post-traumatic osteoarthritis (PTOA). However, the precise mechanism underlying this phenomenon remains unclear. Hence, the purpose of this study was to examine whether the mechanism by which TRE following joint distraction delays the progression of PTOA involves the activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), as well as its impact on muscle wasting. Methods: Quadriceps samples were collected from patients with osteoarthritis (OA) and normal patients with distal femoral fractures, and the expression of PGC-1α was measured. The hinged external fixator was implanted in the rabbit PTOA model. One week after surgery, a PGC-1α agonist or inhibitor was administered for 4 weeks prior to TRE. Western blot analysis was performed to detect the expression of PGC-1α and Muscle atrophy gene 1 (Atrogin-1). We employed the enzyme-linked immunosorbent assay (ELISA) technique to examine pro-inflammatory factors. Additionally, we utilized quantitative real-time polymerase chain reaction (qRT-PCR) to analyze genes associated with cartilage regeneration. Synovial inflammation and cartilage damage were evaluated through hematoxylin-eosin staining. Furthermore, we employed Masson's trichrome staining and Alcian blue staining to analyze cartilage damage. Results: The decreased expression of PGC-1α in skeletal muscle in patients with OA is correlated with the severity of OA. In the rabbit PTOA model, TRE following joint distraction inhibited the expressions of muscle wasting genes, including Atrogin-1 and muscle ring finger 1 (MuRF1), as well as inflammatory factors such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in skeletal muscle, potentially through the activation of PGC-1α. Concurrently, the production of IL-1β, IL-6, TNF-α, nitric oxide (NO), and malondialdehyde (MDA) in the synovial fluid was down-regulated, while the expression of type II collagen (Col2a1), Aggrecan (AGN), SRY-box 9 (SOX9) in the cartilage, and superoxide dismutase (SOD) in the synovial fluid was up-regulated. Additionally, histological staining results demonstrated that TRE after joint distraction reduced cartilage degeneration, leading to a significant decrease in OARSI scores.TRE following joint distraction could activate PGC-1α, inhibit Atrogin-1 expression in skeletal muscle, and reduce C-telopeptides of type II collagen (CTX-II) in the blood compared to joint distraction alone. Conclusion: Following joint distraction, TRE might promote the activation of PGC-1α in skeletal muscle during PTOA progression to exert anti-inflammatory effects in skeletal muscle and joint cavity, thereby inhibiting muscle wasting and promoting cartilage regeneration, making it a potential therapeutic intervention for treating PTOA. [ABSTRACT FROM AUTHOR]

Objectives: Osteoarthritis is an inflammatory and degenerative disorder characterized by the degradation of the extracellular matrix. It commences with injuries to the knee that activate inflammatory pathways. Trauma may predispose to osteoarthritis, called post-traumatic osteoarthritis (PTOA). The disease is diagnosed in the later stages with (KL grade>2) as seen by X-ray; measuring the biomarkers present in the body fluids holds significant promise for the early detection and evaluation of PTOA. The study aimed to establish the role of inflammatory and collagen markers such as serum interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-β1), and urine C-terminal cross-linked telopeptide of type II collagen (CTX-II) in the diagnosis of early post-traumatic osteoarthritis of the knee. Methods: This case-control study was conducted among 80 participants, of which 40 were apparently healthy individuals, and 40 were cases with a history of trauma to the knee joint in the past ten to 12 weeks. Baseline characteristics, body mass index (BMI), Visual Analog Score (VAS), and Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) were collected from all the participants. X-ray and MRI were done in the cases. Serum IL-6 and TGF-β1, and urine CTX-II were analyzed by ELISA. Statistical analysis was done with SPSS version 16. A P value ≤ 0.05 was considered statistically significant. Results: The mean serum IL-6, TGF-β1, and urine CTX-II levels were significantly higher in cases than in controls, with P values of 0.025, 0.033, and 0.040 respectively. IL-6 showed correlations with age, WOMAC score, and urine CTX-II values. TGF-β1 showed a positive correlation with VAS. Conclusion: Individuals with previous knee joint trauma exhibited notably elevated serum IL-6, TGF-β1, and urine CTXII levels. Among the three biomarkers, IL-6 seemed to be a potential biomarker of early post-traumatic osteoarthritis in patients with knee injuries. [ABSTRACT FROM AUTHOR]

Background: Patients with complex proximal tibial plateau fractures (TPFs) tend to overestimate the prognosis of their injury, potentially due to factors such as a limited understanding, optimism, and the influence of the pain intensity. Understanding the reasons behind this misperception is crucial for healthcare providers to effectively communicate with patients and establish realistic expectations for treatment outcomes. The purpose of this study was to analyze the outcomes of TPFs, with a particular focus on patient-reported outcome measures concerning functional recovery, pain levels, and overall satisfaction with treatment. The authors aim to provide valuable insights into the realistic expectations and potential limitations that patients may encounter during their recovery journey. Methods: In this retrospective single-center study, all surgically treated TPFs between January 2014 and December 2019 with a minimum follow-up of 12 months were included. Several patient-reported outcome measures were obtained, including the International Knee documentation Committee Score (IKDC), Lyholm score, Tegner score, and visual analog scale (VAS) for pain. Fractures were classified according to Schatzker, and then subgrouped into simple (Schatzker I–III) and complex (Schatzker IV–VI) fractures. Results: A total of 54 patients (mean age 51.1 ± 11.9 years, 59.3% female) with a mean follow-up time of 3.9 years were included. Schatzker II fractures were present in 48% (n = 26) of the cases, with Schatzker III in 6% (n = 3), Schatzker IV fractures in 6% (n = 3), and Schatker VI fractures in 41% (n = 22) of the cases. All outcome scores showed a significant improvement between the first year after surgery and the last follow-up (mean: 3.9 years). Simple fractures showed significantly lower patient-reported outcomes when compared to the preinjury state; however, good to excellent results were observed. Patient-reported outcomes of complex fractures showed no significant changes in the study period with good to excellent results. When it comes to the Lysholm score, there were no significant differences in the outcome between simple and complex fractures. Furthermore, there was a return-to-sports rate of 100%, with high rates of changing sporting activity in 25% (simple fractures) and 45% in complex fractures. Conclusions: The data from this study showed that both simple and complex tibial plateau fractures show favorable outcomes at the midterm follow-up, and that injury severity does not correlate with worse results. While patients may tend to overestimate the recovery speed, this research highlights the importance of long-term follow-up, demonstrating a substantial improvement between one year post-surgery and the final evaluation. Return-to-sports rates were high, with adjustments needed for certain activities. However, patients should recognize the need to shift to lower-impact sports and the lengthy recovery process. [ABSTRACT FROM AUTHOR]

Post-traumatic Osteoarthritis (PTOA) results from traumatic joint injuries (such as an ACL rupture). Mechanical impact and an immediate synovial inflammatory response can result in joint tissue degradation and longer-term progression to PTOA. Astronauts are susceptible to increased exercise-related joint injuries leading to altered musculoskeletal physiology, further escalated due to microgravity and increased exposure to ionizing radiation. We applied a human Cartilage-Bone-Synovium (CBS) coculture model to test the potential of low-dose dexamethasone (Dex) and IGF-1 in ameliorating PTOA-like degeneration on Earth and the International Space Station-National Laboratory (ISS-NL, ISS for short). CBS cocultures were established using osteochondral plugs (CB) subjected to compressive impact injury (INJ) followed by coculture with synovium (S) explants. Study groups consisted of control (CB); disease [CBS + INJ]; treatment [CBS + INJ + Dex + IGF-1]; and drugsafety [CB + Dex + IGF-1]. Outcome measures included cell viability, altered matrix glycosaminoglycans (GAG) and collagens, multiplex-ELISA quantification of released cytokines, histopathology, and metabolomic and proteomic analyses of spent media. A 21-day study on ISS-NL explored PTOA-like pathogenesis and treatment in microgravity. Tissue cards for study groups were cultured in custombuilt culture chambers within multi-use variable-g platforms (MVPs). A marked upregulation in the release of inflammatory cytokines and tissue-GAG loss was observed in CBS + INJ groups in space and ground controls utilizing tissues from the same donors, similar to that reported in a previous multi-donor study on Earth; these changes were partly ameliorated by Dex + IGF-1, but with donor variability. Metabolomic and proteomic analyses revealed an array of distinct differences between metabolites/proteins released to the medium in Space versus on Earth. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the clinical efficacy of ankle arthrodesis with different internal fixation methods in the treatment of post-traumatic osteoarthritis. We collected 85 patients with post-traumatic osteoarthritis who underwent different ankle arthrodesis between December 2015 and December 2020. The operation performance, complication rate, hindfoot alignment, talus tilt angle, visual analogue scale (VAS), and American Orthopedic Foot and Ankle Society (AOFAS) score were preoperatively and postoperatively evaluated. In an anterior approach, the locking plate-fixation exhibited a similarity in operation time, incision length, postoperative drainage, bone fusion, hindfoot alignment, and talus tilt angle with fibula support compression screw-fixation, but it was better in increasing postoperative AOFAS. The locking plate-fixation in the anterior approach had lower operation time, incision length, and postoperative drainage than that in the lateral approach. In addition, the lateral locking plate combined with posterolateral compression screw fixation (LLPPCSF) presented shorter bone fusion time, higher AOFAS score, and lower complication rate than either plate- or screw-fixation alone. Lateral locking plate fixation was better than fibula support compression screw fixation in relieving postoperative pain. Anterior locking plate fixation was more time-saving and less invasiveness than lateral locking plate fixation, but its application was limited in low degree of ankle deformation. LLPPCSF was the most effective in improving bone fusion and postoperative pain, considering an optimal option for the treatment of post-traumatic osteoarthritis. [ABSTRACT FROM AUTHOR]

Degradation of articular cartilage (AC) due to injury to the knee joint may initiate post-traumatic osteoarthritis (PTOA). Failure to diagnose the onset of the disease at an early stage makes the cure ineffective for PTOA. This study investigated the consequences of a mechanical injury to the knee in a rabbit model using microscopic magnetic resonance imaging (µMRI) at high resolution. A mechanical injury was induced to the knee joints of 12 rabbits. Cartilage blocks were extracted from the non-impacted and impacted knee joints after 2 and 14 weeks post-impact. The specimens were studied using µMRI T2 relaxation and inductively coupled plasma analysis to determine the early degradation of the articular cartilage. The data established a connection between T2 relaxation time and the early progression of knee PTOA after an impact injury. T2 values were found to be higher in the impacted cartilage at both 2 and 14 weeks, in particular, T2–55° values in the impacted samples displayed a significant rise of 6.93% after 2 weeks and 20.02% after 14 weeks. Lower glycosaminoglycan measurement and higher water content in the impacted cartilage confirmed the µMRI results. This µMRI T2 study was able to detect cartilage damage in the impacted knees. In addition, greater degradation in the affected knees at 14 weeks than at 2 weeks indicated the progressive nature of cartilage deterioration over time. The µMRI results were in accord with the biochemical analysis, indicating the detection of early structural damage in the cartilage. [ABSTRACT FROM AUTHOR]

The importance of mechanical loading and its relationship to orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA) is beginning to receive attention. This review explores the current efficacy of orthobiologic interventions, notably platelet-rich plasma (PRP), bone marrow aspirate (BMA), and mesenchymal stem/stromal cells (MSCs), in combating PTOA drawing from a comprehensive review of both preclinical animal models and human clinical studies. This review suggests why mechanical joint loading, such as running, might improve outcomes in PTOA management in conjunction with orthiobiologic administration. Accumulating evidence underscores the influence of mechanical loading on chondrocyte behavior and its pivotal role in PTOA pathogenesis. Dynamic loading has been identified as a key factor for optimal articular cartilage (AC) health and function, offering the potential to slow down or even reverse PTOA progression. We hypothesize that integrating the activation of mechanotransduction pathways with orthobiologic treatment strategies may hold a key to mitigating or even preventing PTOA development. Specific loading patterns incorporating exercise and physical activity for optimal joint health remain to be defined, particularly in the clinical setting following joint trauma.

Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.

Rapid joint clearance of small molecule drugs is the major limitation of current clinical approaches to osteoarthritis and its subtypes, including post-traumatic osteoarthritis (PTOA). Particulate systems such as nano/microtechnology could provide a potential avenue for improved joint retention of small molecule drugs. One drug of interest for PTOA treatment is flavopiridol, which inhibits cyclin-dependent kinase 9 (CDK9). Herein, polylactide-co-glycolide microparticles encapsulating flavopiridol were formulated, characterized, and evaluated as a strategy to mitigate PTOA-associated inflammation through the inhibition of CDK9. Characterization of the microparticles, including the drug loading, hydrodynamic diameter, stability, and release profile was performed. The mean hydrodynamic diameter of flavopiridol particles was ∼15 µm, indicating good syringeability and low potential for phagocytosis. The microparticles showed no cytotoxicity in-vitro, and drug activity was maintained after encapsulation, even after prolonged exposure to high temperatures (60 °C). Flavopiridol-loaded microparticles or blank (unloaded) microparticles were administered by intraarticular injection in a rat knee injury model of PTOA. We observed significant joint retention of flavopiridol microparticles compared to the soluble flavopiridol, confirming the sustained release behavior of the particles. Matrix metalloprotease (MMP) activity, an indicator of joint inflammation, was significantly reduced by flavopiridol microparticles 3 days post-injury. Histopathological analysis showed that flavopiridol microparticles reduced PTOA severity 28 days post-injury. Taken altogether, this work demonstrates a promising biomaterial platform for sustained small molecule drug delivery to the joint space as a therapeutic measure for post-traumatic osteoarthritis. STATEMENT OF SIGNIFICANCE: Post-traumatic osteoarthritis (PTOA) begins with the deterioration of subchondral bone and cartilage after acute injuries. In spite of the prevalence of PTOA and its associated financial and psychological burdens, therapeutic measures remain elusive. A number of small molecule drugs are now under investigation to replace FDA-approved palliative measures, including cyclin-dependent kinase 9 (CDK9) inhibitors which work by targeting early inflammatory programming after injury. However, the short half-life of these drugs is a major hurdle to their success. Here, we show that biomaterial encapsulation of Flavopiridol (CDK9 inhibitor) in poly (lactic-co-glycolic acid) microparticles is a promising route for direct delivery and improved drug retention time in the knee joint. Moreover, administration of the flavopiridol microparticles reduced the severity of PTOA.

Abstract Background and aim Post-traumatic osteoarthritis (PTOA) is a subtype of osteoarthritis (OA). Exercise may produce and release the myokine irisin through muscle fiber contraction. However, the effect of exercise-promoted irisin production on the internal interactions of the muscle–bone unit in PTOA studies remains unclear. Methods Eighteen 8-week-old Sprague–Dawley (SD) rats were randomly divided into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). The PTOA model was established by transection of anterior cruciate ligament (ACLT) and destabilization of medial meniscus (DMM). After 4 weeks of modeling, the PTOA/TW group underwent treadmill exercise (15 m/min, 30 min/d, 5 d/ week, 8 weeks), and the other two groups were free to move in the cage. Evaluation and correlation analysis of muscle, cartilage, subchondral bone and serological indexes were performed after euthanasia. Results Eight weeks of treadmill exercise effectively alleviated the trauma-induced OA phenotype, thereby maintaining cartilage and subchondral bone integrity in PTOA, and reducing quadriceps atrophy and myofibril degradation. Exercise reversed the down-regulated expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and fibronectin type III structural domain protein 5 (FNDC5) in muscle tissue of PTOA rats, and increased the blood irisin level, and the irisin level was positively correlated with the expression of PGC-1α and FNDC5. In addition, correlation analysis showed that irisin metabolism level was strongly negatively correlated with Osteoarthritis Research Society International (OARSI) and subchondral bone loss, indicating that irisin may be involved in cartilage biology and PTOA-related changes in cartilage and subchondral bone. Moreover, the metabolic level of irisin was strongly negatively correlated with muscle fiber cross-sectional area (CSA), Atrogin-1 and muscle ring-finger protein-1(MuRF-1) expression, suggesting that irisin may alleviate muscle atrophy through autocrine action. Conclusion Treadmill exercise can alleviate the atrophy and degeneration of muscle fibers in PTOA rats, reduce the degradation of muscle fibrin, promote the expression of serum irisin, and alleviate the degeneration of articular cartilage and subchondral bone loss in PTOA rats. These results indicate that treadmill exercise can affect the process of PTOA by promoting the expression of myokine irisin in rat muscle–bone unit.

In this review, we discuss the interaction of mechanical factors influencing knee osteoarthritis (KOA) and post-traumatic osteoarthritis (PTOA) pathogenesis. Emphasizing the importance of mechanotransduction within inflammatory responses, we discuss its capacity for being utilized and harnessed within the context of prevention and rehabilitation of osteoarthritis (OA). Additionally, we introduce a discussion on the Goldilocks zone, which describes the necessity of maintaining a balance of adequate, but not excessive mechanical loading to maintain proper knee joint health. Expanding beyond these, we synthesize findings from current literature that explore the biomechanical loading of various rehabilitation exercises, in hopes of aiding future recommendations for physicians managing KOA and PTOA and athletic training staff strategically planning athlete loads to mitigate the risk of joint injury. The integration of these concepts provides a multifactorial analysis of the contributing factors of KOA and PTOA, in order to spur further research and illuminate the potential of utilizing the body's own physiological responses to mechanical stimuli in the management of OA. [ABSTRACT FROM AUTHOR]

Elbow joint injuries are common and can cause secondary degenerative changes in the joint. Combined traumatic injury therapy in the setting of an underlying degenerative joint change requires and especially good understanding of the injury mechanisms and the degeneration and an appropriate treatment and rehabilitation strategy development. In the absence of an appropriate treatment, these impairments can lead to permanent functional limitations and disability. The aim is to present effects of implementing a multimodal rehabilitation, of a patient with traumatic elbow joint injury, combined with secondary post-traumatic osteoarthritis, and rehabilitation program including Deep Oscillation®, ice block therapy and special therapeutic exercises applied. Materials and Methods: The multimodal rehabilitation program was performed as outpatient in a 39-year-old patient referred for physical therapy by an orthopaedist, 4 weeks post left elbow injury. The patient reported a history of joint surgically treated trauma, at the age of 12. Radiologically, arthritic posttraumatic changes were manifested. Presently complaining of limited flextion and inability to fully extend the elbow joint, pain acompaning movement in the medial epicondyle area, difficult daily living, and self-care activities. The intervention includes: “Ice Block” cryotherapy, a set of therapeutic exercises tailored to the degree of disability and Deep Oscillation® with a handheld applicator (120-180Hz 5-7min; 14-30Hz 3-5min; 85Hz 3-5min) for 8 days. To determine rehabilitation potential, the following assessment methods were used: the Disabilities of the Arm, Shoulder, and Hand (DASH) to assess upper limb function, centimetry to measure joint circumference, the range of joint motion, the manual muscle test (MMT). The patient's symptoms were assessed in the period before and immediately after therapy. Results: Reduction in subjective and objective symptomatology was observed: DASH score from moderate-severe 54.5 to mild impairment 29.5; left elbow joint centimetry from 44.7cm to 42.5cm; goniometry S/0°-5°-95° to S/0°-0°-125°; RLUJ/60°-0°-55° to R/75°-0°-65°; reduced muscular imbalance, improved functional activity and ADL. Conclusion: The application of Deep Oscillation® treatment in combination with cryotherapy and therapeutic exercises effectively reduces pain symptomatology, swelling and stiffness of the elbow joint and reduces functional limitations (DASH score) in the specific patient after elbow injury on the background of a secondary post-traumatic osteoarthritis. In order to better verify the effects of the applied multimodal rehabilitation program in combined pathology of post-traumatic injuries in degeneratively altered elbow joint, it is necessary to continue research with more patients with a similar pathology. [ABSTRACT FROM AUTHOR]

Background and aim: Post-traumatic osteoarthritis (PTOA) is a subtype of osteoarthritis (OA). Exercise may produce and release the myokine irisin through muscle fiber contraction. However, the effect of exercise-promoted irisin production on the internal interactions of the muscle–bone unit in PTOA studies remains unclear. Methods: Eighteen 8-week-old Sprague–Dawley (SD) rats were randomly divided into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). The PTOA model was established by transection of anterior cruciate ligament (ACLT) and destabilization of medial meniscus (DMM). After 4 weeks of modeling, the PTOA/TW group underwent treadmill exercise (15 m/min, 30 min/d, 5 d/ week, 8 weeks), and the other two groups were free to move in the cage. Evaluation and correlation analysis of muscle, cartilage, subchondral bone and serological indexes were performed after euthanasia. Results: Eight weeks of treadmill exercise effectively alleviated the trauma-induced OA phenotype, thereby maintaining cartilage and subchondral bone integrity in PTOA, and reducing quadriceps atrophy and myofibril degradation. Exercise reversed the down-regulated expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and fibronectin type III structural domain protein 5 (FNDC5) in muscle tissue of PTOA rats, and increased the blood irisin level, and the irisin level was positively correlated with the expression of PGC-1α and FNDC5. In addition, correlation analysis showed that irisin metabolism level was strongly negatively correlated with Osteoarthritis Research Society International (OARSI) and subchondral bone loss, indicating that irisin may be involved in cartilage biology and PTOA-related changes in cartilage and subchondral bone. Moreover, the metabolic level of irisin was strongly negatively correlated with muscle fiber cross-sectional area (CSA), Atrogin-1 and muscle ring-finger protein-1(MuRF-1) expression, suggesting that irisin may alleviate muscle atrophy through autocrine action. Conclusion: Treadmill exercise can alleviate the atrophy and degeneration of muscle fibers in PTOA rats, reduce the degradation of muscle fibrin, promote the expression of serum irisin, and alleviate the degeneration of articular cartilage and subchondral bone loss in PTOA rats. These results indicate that treadmill exercise can affect the process of PTOA by promoting the expression of myokine irisin in rat muscle–bone unit. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess whether articular cartilage changes in an equine model of post‐traumatic osteoarthritis (PTOA), induced by surgical creation of standard (blunt) grooves, and very subtle sharp grooves, could be detected with ex vivo T1 relaxation time mapping utilizing three‐dimensional (3D) readout sequence with zero echo time. Grooves were made on the articular surfaces of the middle carpal and radiocarpal joints of nine mature Shetland ponies and osteochondral samples were harvested at 39 weeks after being euthanized under respective ethical permissions. T1 relaxation times of the samples (n = 8 + 8 for experimental and n = 12 for contralateral controls) were measured with a variable flip angle 3D multiband‐sweep imaging with Fourier transform sequence. Equilibrium and instantaneous Young's moduli and proteoglycan (PG) content from OD of Safranin‐O‐stained histological sections were measured and utilized as reference parameters for the T1 relaxation times. T1 relaxation time was significantly (p < 0.05) increased in both groove areas, particularly in the blunt grooves, compared with control samples, with the largest changes observed in the superficial half of the cartilage. T1 relaxation times correlated weakly (Rs ≈ 0.33) with equilibrium modulus and PG content (Rs ≈ 0.21). T1 relaxation time in the superficial articular cartilage is sensitive to changes induced by the blunt grooves but not to the much subtler sharp grooves, at the 39‐week timepoint post‐injury. These findings support that T1 relaxation time has potential in detection of mild PTOA, albeit the most subtle changes could not be detected. [ABSTRACT FROM AUTHOR]

Post-traumatic osteoarthritis (PTOA), a disorder of the synovium, subchondral bone, and cartilage that affects the entire joint, constitutes approximately 12% of all cases of symptomatic osteoarthritis. This review summarizes the pathogenetic mechanisms that underlie the positive influence of chondroitin sulphates (CSs) on PTOA as means of preventive and therapeutic treatment. Mechanisms of PTOA development involve chondrocytes undergoing various forms of cell death (apoptosis, pyroptosis, necroptosis, ferroptosis and/or necrosis). Chondroitin sulphates are a class of glycosaminoglycans that improve the structure and function of cartilage and subchondral bone, which is associated with their ability to decrease the activation of NF-κB and p38 MAPK, and up-regulate Nrf2. Standardized small fish extract (SSFE) is an example of the drugs that can attenuate NF-κB-mediated systemic inflammation, potentially helping to reduce joint inflammation and cartilage degradation, improve joint function, and alleviate pain and disability in patients with these conditions.

Abstract Background The predictors of post-traumatic osteoarthritis (PTOA) in patients with transverse acetabular fractures (TAFs) following open reduction internal fixation (ORIF) remain unclear. This study aimed to investigate the risk factors for PTOA in TAFs after ORIF. Methods Data of TAF patients receiving ORIF were collected from January 2012 and February 2021. Patients suffered PTOA were classified as the osteoarthritis group (OG), while those without PTOA were classified as the non- osteoarthritis group (NG) with a minimum follow-up of 2 years. PTOA was diagnosed according to Tönnis OA classification during the period of follow-up. Univariate analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analyses were used to evaluate demographics, injury-related characteristics, perioperative and post-discharge information. Results Three hundred and eleven TAF patients were analyzed in this study, including 261 males and 50 females, with a mean age of 40.4 years (range 18 to 64 years). The incidence of PTOA was 29.6% (92 of 311) during the mean follow-up of 36.8 months (range 24 to 70 months). Several factors of PTOA were found using univariate analysis, including transverse fracture associated with posterior wall acetabular fracture (TPW-AF, p = 0.002), acetabular roof fracture (ARF, p = 0.001), femoral head lesion (FHL, p = 0.016), longer time from injury to surgery (TIS, p＜0.001) and physical work after surgery (PWAS, p＜0.001). Logistic regression analysis showed that TPW-AF (p = 0.007, OR = 2.610, 95%CI: 1.302–5.232), ARF (p = 0.001, OR = 2.887, 95%CI: 1.512–5.512), FHL (p = 0.005, OR = 2.302, 95%CI: 1.283–4.131), TIS (p

ObjectivePost-traumatic osteoarthritis (PTOA) is a degenerative joint disease initiated by injury. Early phase (0-7 days) treatments often include rest (unloading) and anti-inflammatory medications, but how those early interventions impact PTOA progression is unknown. We hypothesized that early unloading and anti-inflammatory treatment would diminish joint inflammation and slow PTOA progression.DesignMice were injured with non-invasive ACL rupture followed by hindlimb unloading (HLU) or normal cage activity (ground control: GC) for 7 days, after which all mice were allowed normal cage activity. HLU and GC mice were treated with daily celecoxib (CXB; 10 mg/kg IP) or vehicle. Protease activity was evaluated using in vivo fluorescence imaging, osteophyte formation and epiphyseal trabecular bone were quantified using micro-computed tomography, and synovitis and articular cartilage were evaluated using whole-joint histology at 7, 14, 21, and 28 days post-injury.ResultsHLU significantly reduced protease activity (-22-30% compared to GC) and synovitis (-24-50% relative to GC) at day 7 post-injury (during unloading), but these differences were not maintained at later timepoints. Similarly, trabecular bone volume was partially preserved in HLU mice at during unloading (-14-15% BV/TV for HLU mice, -21-22% for GC mice relative to uninjured), but these differences were not maintained during reloading. Osteophyte volume was reduced by both HLU and CXB, but there was not an additive effect of these treatments (HLU: -46%, CXB: -30%, HLU + CXB: -35% relative to vehicle GC at day 28).ConclusionsThese data suggest that early unloading following joint injury can reduce inflammation and potentially slow PTOA progression.

Abstract Background The estimated prevalence of post-traumatic osteoarthritis (PTOA) is 10–12% and in this study 12.4%. Different knee and hip injuries have been identified as risk factors for PTOA, but there is no consensus regarding the most painful and disabling injuries. Identifying these injuries might help in the prevention of PTOA. Additionally, patients with PTOA have a higher risk for complications after arthroplasty than patients with primary OA, perhaps due to differences in the profile and comorbidity that might help to explain the difference. This work aims 1) to identify the most common past injuries associated with the most painful and disabling PTOA cases in non-athlete patients and 2) to compare the comorbidities and characteristics between PTOA and primary OA. Methods Retrospective hospital-based cohort study with 1290 participants with joint complaints or who received arthroplasty. Medical records included demographic information, diagnosis, medication, smoking, alcohol history and comorbidities. Data from January 2012 orthopaedic consults till December 2019 was reviewed and had the type and date of injury, pain score by the numerical rating scale and walking disability. Odds Ratio (OR) and 95% confidence intervals are presented. Results There were 641 cases with primary OA (65% females) and 104 with PTOA (61% males). Patients with PTOA were 7.5 years younger (P

Injuries cause a systemic neurohumoral and behavioral response of the body, aimed at restoring damaged tissues and correcting biomechanical disorders. However, in many cases, full-fledged repair is impossible – traumatic injury, inflammation that occurs against its background, and degenerative processes (fibrosis, neoangiogenesis, heterotopic ossification) lead to severe structural changes and a progressive decrease in functional ability. The most common complications of trauma include chronic post-traumatic pain and post-traumatic osteoarthritis (PTOA). These complications are interrelated – pain (accompanied by stiffness and dysfunction) that occurs in 10–50% of people who have suffered a joint injury may indicate the formation of early (pre-radiological) stages of PTOA. The development of typical structural changes in PTOA is observed 10–15 years after a knee injury (in >30% of patients). PTOA of large joints is more aggressive, often accompanied by synovitis, and requires arthroplasty on average 10–15 years earlier than primary osteoarthritis. Early diagnosis of PTOA is based on the analysis of the dynamics of clinical manifestations (primarily post-traumatic pain), visualization of early changes in the structure of the joint (magnetic resonance imaging), as well as the study of the level of biomarkers of inflammation and osteochondral destruction. As additional risk factors for PTOA, genetic features are considered that determine the chronicity of inflammation, pain, and impaired repair of cartilage and bone tissue.

Introduction: Post-traumatic osteoarthritis (PTOA) develops following traumatic articular insult. One model system used to study the progression and treatment of PTOA is the destabilization of the medial meniscus (DMM) as first described by Glasson et al performed in mini-pigs. Miniature pigs are less available, more expensive, and have synovial fluid sampling limitations, limiting the availability of osteoarthritis biomarkers compared to domestic pigs. Objectives: The following technical note details stepwise procedures and animal welfare strategies for the use of Yorkshire pigs as a large animal PTOA model. Methods: The following technical note details stepwise procedures to perform peroperative saphenous nerve block, DMM, and subsequent postoperative management in Yorkshire pigs as a large animal PTOA model. Results: At 4 weeks post-operatively, all pigs develop mild-moderate PTOA based on postmortem joint dissections. Conclusions: This technical note provides further details on the arthrotomy approach to destabilize the medial meniscus of domestic pigs as a model of PTOA.

Objective: To develop an imaging mass cytometry method for identifying complex cell phenotypes, inter-cellular interactions, and population changes in the synovium and infrapatellar fat pad (IFP) of the mouse knee following a non-invasive compression injury. Design: Fifteen male C57BL/6 mice were fed a high-fat diet for 8 weeks prior to random assignment to sham, 0.88 ​mm, or 1.7 ​mm knee compression displacement at 24 weeks of age. 2-weeks after loading, limbs were prepared for histologic and imaging mass cytometry analysis, focusing on myeloid immune cell populations in the synovium and IFP. Results: 1.7 ​mm compression caused anterior cruciate ligament (ACL) rupture, development of post-traumatic osteoarthritis, and a 2- to 3-fold increase in cellularity of synovium and IFP tissues compared to sham or 0.88 ​mm compression. Imaging mass cytometry identified 11 myeloid cell subpopulations in synovium and 7 in IFP, of which approximately half were elevated 2 weeks after ACL injury in association with the vasculature. Notably, two monocyte/macrophage subpopulations and an MHC IIhi population were elevated 2-weeks post-injury in the synovium but not IFP. Vascular and immune cell interactions were particularly diverse in the synovium, incorporating 8 unique combinations of 5 myeloid cell populations, including a monocyte/macrophage population, an MHC IIhi population, and 3 different undefined F4/80+ myeloid populations. Conclusions: Developing an imaging mass cytometry method for the mouse enabled us to identify a diverse array of synovial and IFP vascular-associated myeloid cell subpopulations. These subpopulations were differentially elevated in synovial and IFP tissues 2-weeks post injury, providing new details on tissue-specific immune regulation.

Post-traumatic OA (PTOA) can occur within 5 years after a significant injury and is a valuable paradigm for identifying biomarkers. This systematic review aims to summarise published literature in human studies on the associations of known serum and synovial fluid biomarkers at least a year from injury to structural, symptomatic changes and underlying PTOA processes.A systematic review was performed using PRISMA guidelines, prospectively registered on PROSPERO (CRD42022371838), for all ‘wet’ biomarkers a year or more post-injury in 18–45-year-old participants. Three independent reviewers screened search results, extracted data, and performed risk of bias assessments (Newcastle-Ottawa Scale). Study heterogeneity meant a narrative synthesis was undertaken, utilising SWiM guidelines.952 studies were identified, 664 remaining after deduplication. Following first-round screening, 53 studies underwent second-round screening against pre-determined criteria. Eight studies, with 879 participants (49 ​% male), were included, measuring serum (n ​= ​7), synovial fluid (SF, n ​= ​6), or both (n ​= ​5). The pooled participant mean age was 29.1 (±4). 51 biomarkers were studied (serum ​= ​38, SF ​= ​13), with no correlation between paired serum and SF samples. One serum biomarker, cartilage oligomeric matrix protein (COMP), and four SF biomarkers, interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF), and COMP, were measured in multiple studies.Associations were described between 11 biomarkers related to catabolism (n ​= ​4), anabolism (n ​= ​2), inflammation (n ​= ​4) and non-coding RNA (n ​= ​1), with OA imaging changes (X-ray and MRI), pain, quality of life and function. Widespread differences in study design and methodology prevented meta-analysis, and evidence was generally weak. A unified approach is required before widespread research and clinical biomarker use.

Interposition arthroplasty of the elbow is often preferred in young patients compared with implant total elbow arthroplasty. However, research comparing outcomes based on diagnosis in patients with post-traumatic osteoarthritis (PTOA) and inflammatory arthritis following interposition arthroplasty is sparse. Therefore, the purpose of this study was to compare outcomes and complication rates following interposition arthroplasty in patients with PTOA and inflammatory arthritis. A systematic review was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The PubMed, Embase, and Web of Science databases were queried from inception to December 31, 2021. The search generated 189 total studies, of which 122 were unique. Original studies on interposition arthroplasty of the elbow in the setting of post-traumatic or inflammatory arthritis in patients aged <65 years were included. Six studies that were suitable for inclusion were identified. The query yielded 110 elbows, of which 85 had received a diagnosis of PTOA and 25, inflammatory arthritis. The cumulative complication rate following the index procedure was 38.4%. The complication rate in patients with PTOA was 41.2% compared with 11.7% in those with inflammatory arthritis. Furthermore, the cumulative reoperation rate was 23.5%. The reoperation rates in PTOA and inflammatory arthritis patients were 25.0% and 17.6%, respectively. The average preoperative Mayo Elbow Performance Index pain score was 11.0, which improved to 26.3 postoperatively. The mean preoperative and postoperative pain scores for the PTOA patients were 4.3 and 30.0, respectively. For the inflammatory arthritis patients, the preoperative pain score was 0 and the postoperative pain score was 45. The overall mean preoperative Mayo Elbow Performance Index functional score was 41.5, improving to 74.0 after the procedure. This study found that interposition arthroplasty is associated with a 38.4% complication rate and 23.5% reoperation rate, in addition to positive improvements in pain and function. In patients aged <65 years, interposition arthroplasty may be considered in those unwilling to undergo implant arthroplasty. [ABSTRACT FROM AUTHOR]

BACKGROUND: As a disease that greatly affects the quality of life of patients, ankle osteoarthritis has been paid more and more attention. The clinical and experimental research of ankle osteoarthritis is not as complete as that of knee joint, and there is a lack of systematic review on animal models. OBJECTIVE: To explore the methods and characteristics of experimental models of ankle osteoarthritis, and to provide theoretical basis for the improvement of experimental research of ankle osteoarthritis. METHODS: Using the search terms of “ankle joint, osteoarthritis, animal models, post-traumatic osteoarthritis”, CNKI, WANFANG Data Platform, VIP, PubMed, and Embase databases from 2009 to 2022 were searched. Totally 49 articles were included for systematic review. RESULTS AND CONCLUSION: (1) In the animal model of ankle osteoarthritis, the modeling methods for traumatic arthritis include chronic ankle instability model and intra-articular fracture model. Noninvasive animal models include intraarticular drug injection-induced models, cartilage atrophy models, joint senescence models, and spontaneous osteoarthritis models in specific strains of osteoarthritis susceptible species. (2) Although the incidence of traumatic ankle osteoarthritis is high, the research on ankle osteoarthritis is quite limited compared with knee osteoarthritis. Due to the differences in structure and characteristics between ankle joint and knee joint, the research results of knee joint are not completely applicable to ankle joint. The study of its animal model is more conducive to the in-depth exploration of the blind area of the current research. [ABSTRACT FROM AUTHOR]

Background: The predictors of post-traumatic osteoarthritis (PTOA) in patients with transverse acetabular fractures (TAFs) following open reduction internal fixation (ORIF) remain unclear. This study aimed to investigate the risk factors for PTOA in TAFs after ORIF. Methods: Data of TAF patients receiving ORIF were collected from January 2012 and February 2021. Patients suffered PTOA were classified as the osteoarthritis group (OG), while those without PTOA were classified as the non- osteoarthritis group (NG) with a minimum follow-up of 2 years. PTOA was diagnosed according to Tönnis OA classification during the period of follow-up. Univariate analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analyses were used to evaluate demographics, injury-related characteristics, perioperative and post-discharge information. Results: Three hundred and eleven TAF patients were analyzed in this study, including 261 males and 50 females, with a mean age of 40.4 years (range 18 to 64 years). The incidence of PTOA was 29.6% (92 of 311) during the mean follow-up of 36.8 months (range 24 to 70 months). Several factors of PTOA were found using univariate analysis, including transverse fracture associated with posterior wall acetabular fracture (TPW-AF, p = 0.002), acetabular roof fracture (ARF, p = 0.001), femoral head lesion (FHL, p = 0.016), longer time from injury to surgery (TIS, p＜0.001) and physical work after surgery (PWAS, p＜0.001). Logistic regression analysis showed that TPW-AF (p = 0.007, OR = 2.610, 95%CI: 1.302–5.232), ARF (p = 0.001, OR = 2.887, 95%CI: 1.512–5.512), FHL (p = 0.005, OR = 2.302, 95%CI: 1.283–4.131), TIS (p<0.0001, OR = 1.294, 95%CI: 1.192–1.405) and PWAS (p<0.0001, 3.198, 95%CI: 1.765–5.797) were independent risk factors of PTOA. Furthermore, ROC curve analysis indicated 11.5 days as the cut-off values to predict PTOA. Conclusions: Our findings identified that TPW-AF, ARF, FHL, TIS and PWAS were independent risk factors for PTOA in patients with TAFs following ORIF. It can help orthopedic surgeons to take early individualized interventions to reduce its incidence. [ABSTRACT FROM AUTHOR]

The development of post-traumatic osteoarthrosis after tibial plateau fracture (TPF) is multifactorial and can only be partially influenced by surgical treatment. There is no standardized method for assessing pre- and postoperative knee joint laxity. Data on the incidence of postoperative laxity after TPF are limited. The purpose of this study was to quantify postoperative laxity of the knee joint after TPF. Fifty-four patients (mean age 51 ± 11.9 years) were included in this study. There was a significant increase in anterior–posterior translation in 78.0% and internal rotation in 78.9% in the injured knee when compared to the healthy knee. Simple fractures showed no significant difference in laxity compared to complex fractures. When preoperative ligament damage and/or meniscal lesions were present and surgically treated by refixation and/or bracing, patients showed higher instability when compared to patients without preoperative ligament and/or meniscal damage. Patients with surgically treated TPF demonstrate measurable knee joint laxity at a minimum of 1 year postoperatively. Fracture types have no influence on postoperative laxity. This emphasizes the importance of recognizing TPF as a multifaceted injury involving both complex fractures and damage to multiple ligaments and soft tissue structures, which may require further surgical intervention after osteosynthesis. [ABSTRACT FROM AUTHOR]

Intra-articular fractures (IAF) result in significant and prolonged inflammation, increasing the chances of developing post-traumatic osteoarthritis (PTOA). Interleukin-one beta (IL-1β) and Tumor Necrosis Factor-alpha (TNF-α) are key inflammatory factors shown to be involved in osteochondral degradation following IAF. As such, use of targeted biologics such as Infliximab (INX), a TNF-α inhibitor, and Anakinra (ANR), an interleukin-one (IL-1) receptor antagonist (IL1RA), may protect against PTOA by damping the inflammatory response to IAF and reducing osteochondral degradation. To test this hypothesis, IAFs were induced in the hindlimb knee joints of rats treated with INX at 10 mg/kg/day, ANR at 100 g/kg/day, or saline (vehicle control) by subcutaneous infusion for a period of two weeks and healing was evaluated at 8-weeks post injury. Serum and synovial fluid (SF) were analyzed for soluble factors. In-vivo microcomputed tomography (µCT) scans assessed bone mineral density and bone morphometry measurements. Cationic CA4+ agent assessed articular cartilage composition via ex vivo µCT. Scoring according to the Osteoarthritis Research Society International (OARSI) guidelines was performed on stained histologic tibia sections at the 56-day endpoint on a 0–6 scale. Systemically, ANR reduced many pro-inflammatory cytokines and reduced osteochondral degradation markers Cross Linked C-Telopeptide Of Type II (CTXII, p < 0.05) and tartrate-resistant acid phosphatase (TRAP, p < 0.05). ANR treatment resulted in increased chemokines; macrophage-chemotractant protein-1 (MCP-1), MPC-3, macrophage inhibitory protein 2 (MIP2) with a concomitant decrease in proinflammatory interleukin-17A (IL17A) at 14 days post-injury within the SF. Microcomputed tomography (µCT) at 56 days post-injury revealed ANR Treatment decreased epiphyseal degree of anisotropy (DA) (p < 0.05) relative to saline. No differences were found with OARSI scoring but contrast-enhanced µCT revealed a reduction in glycosaminoglycan content with ANR treatment. These findings suggest targeted cytokine inhibition, specifically IL-1 signaling, as a monotherapy has minimal utility for improving IAF healing outcomes but may have utility for promoting a more permissive inflammatory environment that would allow more potent disease modifying osteoarthritis drugs to mitigate the progression of PTOA after IAF. [ABSTRACT FROM AUTHOR]

Post-traumatic osteoarthritis (PTOA), a disorder of the synovium, subchondral bone, and cartilage that affects the entire joint, constitutes approximately 12% of all cases of symptomatic osteoarthritis. This review summarizes the pathogenetic mechanisms that underlie the positive influence of chondroitin sulphates (CSs) on PTOA as means of preventive and therapeutic treatment. Mechanisms of PTOA development involve chondrocytes undergoing various forms of cell death (apoptosis, pyroptosis, necroptosis, ferroptosis and/or necrosis). Chondroitin sulphates are a class of glycosaminoglycans that improve the structure and function of cartilage and subchondral bone, which is associated with their ability to decrease the activation of NF-κB and p38 MAPK, and up-regulate Nrf2. Standardized small fish extract (SSFE) is an example of the drugs that can attenuate NF-κB-mediated systemic inflammation, potentially helping to reduce joint inflammation and cartilage degradation, improve joint function, and alleviate pain and disability in patients with these conditions. [ABSTRACT FROM AUTHOR]

Background: Posterolateral rotatory instability (PLRI) is the most frequent form of both acute and chronic elbow instability. It is due to mechanical incompetence of the lateral collateral ligament. O’Driscoll et al described treatment of this instability by autologous reconstruction of the lateral ulnar collateral ligament. The aim of our study was to evaluate the medium and long-term clinical, functional and radiological results of patients who were surgically treated for PLRI by this technique. We hypothesized that such ligament reconstruction restores a functional joint complex and durably stabilizes the elbow and limits the long-term risk of osteoarthritis. Methods: All patients treated for symptomatic PLRI by ligament reconstruction since January 1995 and who had a minimum follow-up of 36 months were retrospectively included. Results: Thirty-two patients (32 elbows) underwent clinical and radiological evaluation with a mean follow-up of 112 months (range, 36-265 months). The success rate of the procedure was 97% with one patient requiring revision reconstruction. Twenty-four patients (75%) were free from pain. Pain was significantly greater in patients with associated lesions (P = .03) and those with morbid obesity (body mass index ≥40) (P = .03). Twenty-nine (91%) patients had resumed their previous activities. Twenty-eight patients (87%) were satisfied or very satisfied. The mean Mayo Clinic score was 96/100 and the QuickDash 14.7/100. Two patients (6%) with accompanying lesions developed severe osteoarthritis. Conclusion: Elbow ligament reconstruction by the technique of O’Driscoll et al effectively restores stability and limits progression to osteoarthritis in the long term. The only failure in our series was due to several technical errors. Patients who had dislocation with associated lesions or morbid obesity are at risk of poorer functional results.

ObjectiveJoint injury rapidly induces expression of primary response genes (PRGs), which activate a cascade of secondary genes that destroy joint tissues and initiate post-traumatic osteoarthritis (PTOA). Bromodomain-containing-protein-4 (Brd4) and cyclin-dependent-kinase-9 (CDK9) cooperatively control the rate-limiting step of PRG transactivation, including pro-inflammatory genes. This study investigated whether Brd4 and CDK9 inhibitors suppress inflammation and prevent PTOA development in vitro and in a mouse PTOA model.MethodsThe effects of Brd4 and CDK9 inhibitors (JQ1 and Flavopiridol) on PRG and associated secondary damage were rigorously tested in different settings. Short-term effects of inflammatory stimuli (IL-1β, IL-6, TNF) on human chondrocyte PRG expression were assessed by RT-PCR and microarray after 5-h. We quantified glycosaminoglycan release from IL-1β-treated bovine cartilage explants after 3-6 days, and osteoarthritic changes in mice after ACL-rupture using RT-PCR (2-24hrs), in vivo imaging of MMP activity (24hrs), AFM-nanoindentation (3-7days), and histology (3days-4wks).ResultsFlavopiridol and JQ1 inhibitors act synergistically, and a combination of both almost completely prevented the activation of most IL-1β-induced PRGs in vitro by microarray analysis, and prevented IL-1β-induced glycosaminoglycan release from cartilage explants. Mice given the drug combination showed reduced IL-1β and IL-6 expression, less in vivo MMP activity, and lower synovitis (1.5 vs 4.9) and OARSI scores (2.8 vs 6.0) than untreated mice with ACL-rupture.ConclusionsJQ1 and Flavopiridol work synergistically to reduce injury response after joint trauma, suggesting that targeting Brd4 and/or CDK9 could be a viable strategy for PTOA prevention and treatment of early OA.

Post-traumatic osteoarthritis of the ankle (PTOA) is frequently observed following a debilitating consequence of intra-articular ankle fractures. Numerous risk factors contribute to the pathogenesis of PTOA, including articular incongruity, joint malalignment, and concomitant soft tissue damage. Despite attempts to restore joint anatomy and manage soft tissues to avoid long-term complications after intra-articular ankle fractures, the incidence of PTOA remains markedly elevated. Inflammatory processes triggered by intra-articular ankle fractures have emerged as potential instigators that expedite the progression of PTOA. Injury to the articular cartilage and subchondral bone may lead to the release of inflammatory mediators, which can contribute to cartilage degradation and bone resorption. This study provides a narrative review on the current knowledge concerning the association between inflammation and the development of PTOA following intra-articular ankle fractures. We also discuss novel therapeutic agents that target inflammatory pathways to impede the progression of post-traumatic osteoarthritis after intra-articular ankle fractures. These medication and interventions were summarized within this review article.