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Background: Posttraumatic osteoarthritis (PTOA) can be a crippling sequela of acetabular fracture (AF), and total hip arthroplasty (THA) is often necessary to alleviate the clinical progression of symptoms. The purpose of this study was to summarize the existing clinical evidence concerning the surgical management of AF with THA through meta-analyses., Methods: Databases were searched for articles published between 1995 and January 2022 that contained the keywords "acetabular," "fracture," "arthroplasty," and "osteoarthritis." Our study was registered in PROSPERO under number CRD42022314997., Results: We screened 3,125 studies and included data from 31 studies with 1,284 patients. The median patient age at the time of THA was 52 years and ranged from 19 to 94 years. The pooled overall survival rate was 88% [86%-90%, 95% confidence interval (CI)] and could reach 83% at ≥15-year follow-up. For the Harris Hip Score, we pooled 22 studies with an overall mean difference of 43.25 (40.40-46.10, 95% CI; P  < 0.001), indicating a large clinical effect. The pooled complications (incidence rates) across studies were: heterotopic ossification (22.53%), implant dislocation (4.66%), implant infection (3.44%), and iatrogenic nerve injury (1.07%)., Conclusion: THA in patients with PTOA following AF leads to significant improvement in symptoms and function at ≥15-year follow-up. Survival rates of implants free from re-operation or revision after THA decreased with follow-up time and could still reach 83% at ≥15-year follow-up. THA might be an effective therapeutic method for patients with PTOA due to AF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Yuan, Wang, Cai, Yang, Zheng, Zhao, Ma and Xu.)

Background: Biomarkers of cartilage turnover and joint metabolism have a potential use in detecting early degenerative changesafter a traumatic knee joint injury; however, no study has analyzed biomarkers before an anterior cruciate ligament (ACL) injuryand again after injury or in comparison with a similar group of uninjured controls.Hypothesis: Changes in serum biomarker levels and the ratio of cartilage degradation to synthesis, from baseline to follow-up,would be significantly different between ACL-injured patients and uninjured controls.Study Design: Case-control study; Level of evidence, 3.Methods: This case-control study was conducted to examine changes in serum biomarkers of cartilage turnover following ACLinjury in a young athletic population. Specifically, 2 markers for type II collagen and aggrecan synthesis (CPII and CS846, respectively)and 2 markers of types I and II degradation and type II degradation only (C1,2C and C2C, respectively) were studied. Preinjurybaseline serum samples and postinjury follow-up samples were obtained for 45 ACL-injured cases and 45 uninjuredcontrols matched for sex, age, height, and weight.Results: Results revealed significant decreases in C1,2C (P = .042) and C2C (P = .006) over time in the ACL-injured group whencompared with the controls. The change in serum concentrations of CS846 from baseline to follow-up was also significantly differentbetween the ACL-injured patients and uninjured controls (P = .002), as was the change between groups in the ratio ofC2C:CPII over time (P = .013). No preinjury differences in the ratio of C1,2C:CPII or C2C:CPII were observed between groups;however, postinjury differences were observed for both ratios.Conclusion: Changes in biomarker concentrations after an ACL injury suggest an alteration in cartilage turnover and joint metabolismin those sustaining ACL injuries compared with uninjured matched controls. [ABSTRACT FROM AUTHOR]

Disruption of the scapholunate ligament can cause a loss of normal scapholunate mechanics and eventually lead to osteoarthritis. Surgical reconstruction attempts to restore scapholunate relationship show improvement in functional outcomes, but postoperative effectiveness in restoring normal radio-carpal mechanics still remains a question. The objective of this study was to investigate the benefits of surgical repair by observing changes in contact mechanics on the cartilage surface before and after surgical treatment. Six patients with unilateral scapholunate dissociation were enrolled in the study, and displacement driven magnetic resonance image-based surface contact modeling was used to investigate normal, injured and postoperative radiocarpal mechanics. Model geometry was acquired from images of wrists taken in a relaxed position. Kinematics were acquired from image registration between the relaxed images, and images taken during functional loading. Results showed a trend for increase in radiocarpal contact parameters with injury. Peak and mean contact pressures significantly decreased after surgery in the radiolunate articulation and there were no significant differences between normal and postoperative wrists. Results indicated that surgical repair improves contact mechanics after injury and that contact mechanics can be surgically restored to be similar to normal. This study provides novel contact mechanics data on the effects of surgical repair after scapholunate ligament injury. With further work, it may be possible to more effectively differentiate between treatments and degenerative changes based on in vivo contact mechanics data. [ABSTRACT FROM AUTHOR]

The article discusses the role of anterior cruciate ligament(ACL) injury, which occurs in young, physically active persons, especially in women, under the age of 30 years because of early onset disability, to the development of posttraumatic knee osteoarthritis (PTOA). The risk factors associated with PTOA are meniscus status, chondral damage and the time interval between injury and surgical intervention. Certain prevention methods are mentioned.

Summary: Introduction: Vascular endothelial growth factor (VEGF) is detectable in later stages of human osteoarthritis (OA), but not in the healthy articular cartilage. Due to its capacity to increase matrix metalloproteinases and to decrease their inhibitors (tissue inhibitors of metalloproteinases or TIMPs) VEGF seems to play an important role in the development of osteoarthrosis. In late stages of osteoarthritis, invasion of blood vessels from the subchondral growth plate, synovitis with angiogenesis and osteophyte growth is observable. Several studies have revealed a central role for VEGF in all these phenomena. In order to investigate whether VEGF participates in early changes of OA or may even possess characteristics of a marker of OA, we developed an experimental posttraumatic OA New Zealand White rabbit animal model. Materials and methods: In four skeletally mature New Zealand White rabbits, OA was induced by joint instability after transsection of the anterior cruciate ligament in both knees. After eight weeks the animals were killed. OA was verified histologically using the Mankin scale. Expression of VEGF was detected by immunohistochemistry and RT-PCR. Proteoglycans were evaluated by using HE and safranin-O staining. Four non-surgically treated animals acted as a control. Results: The mean Mankin score was 5.11 (±2.14), corresponding to a moderate OA. VEGF and VEGF transcripts were detectable in the cartilage of early experimental posttraumatic OA rabbits. Control samples remained negative for VEGF mRNA and protein. Discussion: The results of this study are promising concerning the role of VEGF as a diagnostic marker. VEGF could further be participated in early changes of OA. A therapeutic approach by modulation of VEGF production could be a possibility for the future. [ABSTRACT FROM AUTHOR]

Abstract: Background: Regardless of the simple surgical technique, the success of the subtalar arthrodesis is limited by the rate of non-unions of the arthrodesis. The functional outcome of workers compensation is known to be poorer compared to patients without pending litigation. The aim of this study was to quantify the rate of non-unions and to determine risk factors leading to failure of the osseous consolidation after arthrodesis of the subtalar joint. The outcome assessed is a general health assessment with the SF-36 questionnaire and more illness specific with the AOFAS hindfoot score. Secondly, the influence of the health insurance status of the patients with or without worker''s compensation on the outcome was tested. Methods and results: The inclusive criterion was an arthrodesis of the subtalar joint with and without autologous cancellous bone grafting and screw osteosynthesis. This cohort study included the clinical course of 115 patients with posttraumatic osteoarthritis from 2000 to 2006. The average age of the patients (n =115) was 47±11.0 years, 83% of the treated patients were men. 68% of the patients suffered of secondary osteoarthritis after calcaneal fracture. The time interval from trauma to presenting at the physician due to therapy resistant pain was in the average 5.5±9.9 years. After primary arthrodesis (n =101) of the subtalar joint osseous consolidation was proved in 55% cases, consolidation was questionable in 21% and the rate of no consolidation with revision was remarkable high with 24%. The duration of osseous consolidation was proved by plain projection radiography or computer tomography and clinical reduction of pain. For primary arthrodesis osseous consolidation was reached after 6.4±6.3 month, after secondary arthrodesis osseous consolidation was reached after 9.4±13.1 month. After revision surgery 57% of the arthrodesis healed, 12% the osseous consolidation was questionable, and the failure rate was still 12%. Conclusion: The outcome measures of the patients with SF-36 and the more functional related AOFAS hindfoot score showed poor outcome rates after subtalar fusion in posttraumatic osteoarthritis. The AOFAS hindfoot score was 47±24 points after primary arthrodesis and 46±17 points after secondary arthrodesis of the subtalar joint. The patients regained their former ability to work only in 30% after fusion of the subtalar joint. If revision surgery was necessary 8% of the patients got back to their work prior to the injury. [Copyright &y& Elsevier]

Objective: To evaluate a possible beneficial effect of low-energy nuclear magnetic resonance (NMR) on cartilage in moderate and severe posttraumatic osteoarthrosis in the rabbit using a macroscopic and a histological grading system. Design: Following transection of the anterior cruciate ligament of both knees in 24 skeletally mature New Zealand White rabbits, we observed different stages of osteoarthrosis (OA) 6 and 12 weeks postoperatively. Animals were randomized into four groups: Group 1 (eight animals) was treated after 6 weeks by NMR (magnetic field: 20-40 G, interference field: 2.35 mT, 100 kHz; MBSTDevice, MedTec, Germany), with 1 h of treatment for seven consecutive days. Group 2 was treated in the same pattern after 12 weeks. The sham-operated groups 3 and 4 received no treatment. Seven days after the last treatment, OA was macroscopically graded and hyaline cartilage of the load bearing area was evaluated histologically according to the Mankin scale. Results: Macroscopically, there was less OA in group 1 ( p < 0.01), but did not reveal significance in group 2 ( p = 0.11) compared to the sham groups. There was no significant difference in the Mankin score in both of the treated groups compared to the control groups (group 1: p = 0.36; group 2: p = 0.81). Conclusions: The results showed some beneficial macroscopic effect in mild OA with less macroscopic OA signs in the treated animals but without a histological effect in the Mankin scale. There was no effect found in the pattern later OA. On behalf of these results, NMR for the treatment of posttraumatic OA cannot be recommended at this point of time. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this literature review is to systematically gather the highest level of available evidence on the long-term outcome after operatively treated ankle fractures in the English, German and Dutch literature. A search term with Boolean operators was constructed. The search was limited to humans and adults and the major databases were searched from 1966 to 2008 to identify studies relating to functional outcome, subjective outcome and radiographic evaluation at least 4 years after an operatively treated ankle fracture. Of the 42 initially relevant papers, 18 met our inclusion criteria. A total of 1822 fractures were identified. The mean sample-size weighted follow-up was 5.1 years. The initial number of patients that were included in the studies was 2724, which results in a long-term follow-up success rate of 66.9%. Regarding the fracture reduction we found 4 papers reporting on 106 fractures. Of the fractures that were classified according to Danis–Weber, 736 were eligible for correlation with the long-term outcome. In 442 fractures a comparison was possible between supination–external rotation stage 2 and 4 of the Lauge-Hansen classification. Only one study reported on the influence of initial cartilage lesions on the outcome. Regarding the involvement of the posterior malleolus, two studies reported on the long-term outcome. None of the studies addressed the influence of hindfoot varus or valgus on the long-term outcome after ankle fracture. Only 79.3% of the optimally reduced fractures show good to excellent long-term outcome. The Weber A type fractures do not show a better long-term outcome than Weber B type fractures. Recommendations for future research were formulated. [ABSTRACT FROM AUTHOR]

Symptomatic secondary osteoarthritis of the Lisfranc joints due to malunion following Lisfranc joint fracture dislocations or ligamentous lesions at the Lisfranc and innominate joint level generally lead to a painful functional loss and a substantial disturbance of the walking performance. Initially missed or inadequately addressed primary lesions still represent the major source of Lisfranc joint malunions. Neuro-osteoarthropathic disorders may also become manifest in the Lisfranc joint region and may be mistaken for truly posttraumatic consequences. Secondary osteoarthritis may be combined with typical multiplanar deformities. The concept of a corrective arthrodesis includes restoration of stable physiologic axes and length proportions of the foot columns. A standardized approach to analyze the clinical picture and corresponding pathomorphology and the transfer into a comprehensive surgical concept which respects the realignment of any component of deformity is a prerequisite for a good functional outcome and a high degree of patient satisfaction. A fusion limited to the medial three rays combined with a soft tissue release may be sufficient for a favorable outcome in the majority of cases and preserve the mobility of the two lateral rays. [ABSTRACT FROM AUTHOR]

Background: Impact injury to articular cartilage can lead to posttraumatic osteoarthritis. Hypotheses: This study tests the hypotheses that (1) chondrocyte injury occurs after impact at energies insufficient to fracture the cartilage surface, and that (2) cartilage injury patterns vary with impact energy, time after injury, and cartilage thickness. Study Design: Controlled laboratory study. Methods: Fresh bovine osteochondral cores were randomly divided into 5 groups: (1) control, (2) 0.35 J, (3) 0.71 J, (4) 1.07 J, and (5) 1.43 J impact energies. Cores were subjected to computer-controlled impact loading and full-thickness sections were then prepared and incubated in Dulbecco's Modified Eagle's Medium/F12 at 37°C. Adjacent sections were harvested 1 and 4 days after impact for viability staining and fluorescent imaging. The area of dead and living chondrocytes was quantified using custom image analysis software and reported as a percentage of total cartilage area. Results: The highest impact energy fractured the cartilage in all cores (1.43 J, n 5 17). Seventy-three percent and 64% of the osteochondral cores remained intact after lower energy impacts of 0.71 J and 1.07 J, respectively. At lower energy levels, fractured cores were thinner (P\.01) than those remaining intact. In cores remaining intact after impact injury, chondrocyte death increased with increasing impact energy (P\.05) and with greater time after impact (P\.05). A progressive increase in dead cells near the bone/cartilage interface and at the articular surface was observed. Conclusion: These data showing progressive chondrocyte death after impact injury at energies insufficient to fracture the cartilage surface demonstrate a potential need for early chondroprotective therapy. Clinical Relevance: These data show that efforts to reduce chondrocyte morbidity after joint injury may be a useful strategy to delay or prevent the onset of posttraumatic osteoarthritis. [ABSTRACT FROM AUTHOR]

The pathophysiology of posttraumatic osteoarthritis (PTOA) after intraarticular fractures is poorly understood. Pursuit of a better understanding of this disease is complicated by inability to accurately monitor its onset, progression and severity. Common radiographic methods used to assess PTOA do not provide sufficient image quality for precise cartilage measurements. Double-contrast multidetector computed tomography (MDCT) is an alternative method that may be useful, since it produces high-quality images in normal ankles. The purpose of this study was to assess this technique's performance in assessing cartilage maintenance in ankles with an intraarticular fracture. Thirty-six tibial plafond fractures were followed over two years, with 31 MDCTs being obtained four months after injury, and 22 MDCTs after two years. Unfortunately, clinical results with this technique were unreliable due to pathology (presumed arthrofibrosis) and technical problems (pooling of contrast). The arthrofibrosis that developed in many patients inhibited proper joint access and contrast infiltration, although high-quality images were obtained in 11 patients. In this patient subset, in which focal regions of cartilage degeneration could be visualized, thickness could be measured with a high degree of fidelity. While thus useful in selected instances, double-contrast MDCT was too unreliable to be recommended to assess these particular types of injuries. [ABSTRACT FROM AUTHOR]

Copyright of Obere Extremitat is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The treatment of tibial plafond fractures is challenging and often is complicated by the compromise of the anterior ankle soft-tissue envelope and a high degree of fracture comminution. Many of these injuries are nonreconstructable and posttraumatic osteoarthritis of the tibiotalar joint is unavoidable. These patients may benefit from a salvage procedure using a posterior blade plate fusion of the tibiotalar joint. This procedure avoids the compromised anterior ankle soft-tissue envelope and allows simultaneous reconstruction of the metaphyseal defect as well as fusion of the tibiotalar joint. Indications include the acute treatment of severely comminuted tibial plafond fractures that appear nonreconstructable, management of posttraumatic tibiotalar osteoarthritis that is associated with significant compromise of the anterior ankle soft tissue envelope, and salvage of distal metaphyseal nonunions or delayed unions that are associated with posttraumatic tibiotalar osteoarthritis. We suggest posterior blade plate fusion as a standard procedure for these patient populations. Further clinical trials are required to investigate the clinical long-term outcomes in these patients. [Copyright &y& Elsevier]

Introduction. An intact distal radioulnar joint (DRUJ) is essential for normal functioning of the upper limb. Osteoarthritis of the DRUJ often leads to ulnar wrist pain, limitation of forearm rotation and reduced grip strength, all of which limit activities of daily living. Once the joint is damaged, salvage procedures are recommended. Materials and methods. Between 1986 and 1996 a modified Sauvé-Kapandji procedure was performed in 117 patients with painfully limited forearm rotation and osteoarthritis of the distal radioulnar joint (DRUJ). Of the 117 patients, 73 women and 32 men, whose ages at operation ranged from 22 to 74 years (average 58 years), were retrospectively reviewed clinically and radiologically 8 years (range 5–12 years) after the operation. The DASH questionnaire was used with 53 patients, 43 patients were accepted for the study, and 10 were excluded. Results. Forearm rotation improved in all patients, ulnar wrist pain was reduced in 97% of the patients, and 9% had mild pain at the proximal ulnar stump. Grip strength improved from a preoperative mean of 38% to a postoperative mean of 55% compared with the contralateral side. The mean DASH score was 28 points (range 0–53 points). In all cases the arthrodesis fused within 8 weeks. The radiographs showed approximation between the proximal ulna stump and the radius compared with the preoperative situation in 74% of the patients. Conclusion. Our clinical and radiological findings suggest that the Sauvé-Kapandji procedure is indicated in symptomatic, non-reconstructable disorders of the DRUJ. The DASH questionnaire provides a general view of the functional outcome after the Sauvé-Kapandji procedure. The DASH questionnaire is very helpful in evaluating the effect of the Sauvé-Kapandji procedure on the entire upper limb. [ABSTRACT FROM AUTHOR]

Glenohumeral osteoarthritis has proven to be a major contributor to shoulder joint pain and dysfunction in the elderly. There are several conditions about the shoulder that contribute to the development of glenohumeral osteoarthritis, which includes traumatic injuries, rotator cuff pathology, glenohumeral instability, glenoid dysplasia, and osteonecrosis. When glenohumeral osteoarthritis pain is refractory to conservative treatment, intra-articular injections and surgery can be performed. The radiologist should be aware of the varying types of shoulder arthroplasties, what preoperative findings influence that decision and the expected postoperative appearance of the differing components., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient-specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro-inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage-synovial fluid-interface and decreased toward the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a partial recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease-modifying drug testing and rehabilitation strategies., (© 2021 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Lubricin, a glycoprotein encoded by the proteoglycan 4 (PRG4) gene, is an essential boundary lubricant that reduces friction between articular cartilage surfaces. The loss of lubricin subsequent to joint injury plays a role in the pathogenesis of posttraumatic osteoarthritis. In this study, we describe the development and evaluation of an adeno-associated virus (AAV)-based PRG4 gene therapy intended to restore lubricin in injured joints. The green fluorescent protein (GFP) gene was inserted the PRG4 gene to facilitate tracing the distribution of the transgene product (AAV-PRG4-GFP) in vivo . Transduction efficiency of AAV-PRG4-GFP was evaluated in joint cells, and the conditioned medium containing secreted PRG4-GFP was used for shear loading/friction and viability tests. In vivo transduction of joint tissues following intra-articular injection of AAV-PRG4-GFP was confirmed in the mouse stifle joint in a surgical model of destabilization of the medial meniscus (DMM), and chondroprotective activity was tested in a rabbit anterior cruciate ligament transection (ACLT) model. In vitro studies showed that PRG4-GFP has lubricin-like cartilage-binding and antifriction properties. Significant cytoprotective effects were seen when cartilage was soaked in PRG4-GFP before cyclic shear loading ( n  = 3). Polymerase chain reaction and confocal microscopy confirmed the presence of PRG4-GFP DNA and protein, respectively, in a mouse DMM ( n  = 3 per group). In the rabbit ACLT model, AAV-PRG4-GFP gene therapy enhanced lubricin expression ( p  = 0.001 vs. AAV-GFP: n  = 7-14) and protected the cartilage from degeneration ( p  = 0.014 vs. AAV-GFP: n  = 9-10) when treatments were administered immediately postoperation, but efficacy was lost when treatment was delayed for 2 weeks. AAV-PRG4-GFP gene therapy protected cartilage from degeneration in a rabbit ACLT model; however, data from the ACLT model suggest that early intervention is essential for efficacy.

Diabetes mellitus (DM) and osteoarthritis (OA) are commonly known metabolic diseases that affect a large segment of the world population. These two conditions share several risk factors such as obesity and aging; however, there is still no consensus regarding the direct role of DM on OA development and progression. Interestingly, both animal and human studies have yielded conflicting results, with some showing a significant role for DM in promoting OA, while others found no significant interactions between these conditions. In this review, we will discuss preclinical and clinical data that assessed the interaction between DM and OA. We will also discuss possible mechanisms associated with the effect of high glucose on the articular cartilage and chondrocytes. An emerging theme dominates the breath of published work in this area: most of the studies discussed in this review do not take into consideration the role of other factors such as the type of diabetes, age, biological sex, type of animal model, body mass index, and the use of pain medications when analyzing and interpreting data. Therefore, future studies should be more rigorous when designing experiments looking at DM and its effects on OA and should carefully account for these confounding factors, so that better approaches can be developed for monitoring and treating patients at risk of OA and DM. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Type 1 diabetes mellitus (T1DM) affects 9.5% of the population. T1DM is characterized by severe insulin deficiency that causes hyperglycemia and leads to several systemic effects. T1DM has been suggested as a risk factor for articular cartilage damage and loss, which could expedite the development of osteoarthritis (OA). OA represents a major public health challenge by affecting 300 million people globally, yet very little is known about the correlation between T1DM and OA. In addition, current studies that have looked at the interaction between diabetes mellitus and OA have reported conflicting results with some suggesting a positive correlation whereas others did not. In this study, we aimed to evaluate whether T1DM exacerbates the development of spontaneous OA or accelerates the progression of posttraumatic osteoarthritis (PTOA) after joint injury. Histological evaluation of T1DM and control joints determined that T1DM mice displayed cartilage degeneration measurements consistent with mild OA phenotypes. RNA sequencing analyses identified significantly upregulated genes in T1DM corresponding to matrix-degrading enzymes known to promote cartilage matrix degradation, suggesting a role of these enzymes in OA development. Next, we assessed whether preexisting T1DM influences PTOA development subsequent to trauma. At 6 weeks post-injury, T1DM injured joints displayed significantly less cartilage damage and joint degeneration than injured non-diabetic joints, suggesting a significant delay in PTOA disease progression. At the single-cell resolution, we identified increased number of cells expressing the chondrocyte markers Col2a1 , Acan , and Cytl1 in the T1DM injured group. Our findings demonstrate that T1DM can be a risk factor for OA but not for PTOA. This study provides the first account of single-cell resolution related to T1DM and the risk for OA and PTOA. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

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Background: After anterior cruciate ligament (ACL) reconstruction, patient-reported outcomes are improved 10 years post-surgery; however, cytokine concentrations remain elevated years after surgery with over 80% of those with combined ACL and meniscus injuries having posttraumatic osteoarthritis (PTOA) within 10-15 years. The purpose of this multicenter, randomized, placebo-controlled trial is to assess whether a 6-month course of oral montelukast after ACL reconstruction reduces systemic markers of inflammation and biochemical and imaging biomarkers of cartilage degradation., Methods: We will enroll 30 individuals undergoing primary ACL reconstruction to participate in this IRB-approved multicenter clinical trial. This trial will target those at greatest risk of a more rapid PTOA onset (age range 25-50 with concomitant meniscus injury). Patients will be randomly assigned to a group instructed to take 10 mg of montelukast daily for 6 months following ACL reconstruction or placebo. Patients will be assessed prior to surgery and 1, 6, and 12 months following surgery. To determine if montelukast alters systemic inflammation following surgery, we will compare systemic concentrations of prostaglandin E2, monocyte chemoattractant protein-1, and pro-inflammatory cytokines between groups. We will also compare degradative changes on magnetic resonance imaging (MRI) collected 1 and 12 months following surgery between groups with reductions in early biomarkers of cartilage degradation assessed with urinary biomarkers of type II collagen breakdown and bony remodeling., Discussion: There is a complex interplay between the pro-inflammatory intra-articular environment, underlying bone remodeling, and progressive cartilage degradation. PTOA affects multiple tissues and appears to be more similar to rheumatoid arthritis than osteoarthritis with respect to inflammation. There is currently no treatment to delay or prevent PTOA after ACL injury. Since there is a larger and more persistent inflammatory response after ACL reconstruction than the initial insult of injury, treatment may need to be initiated after surgery, sustained over a period of time, and target multiple mechanisms in order to successfully alter the disease process. This study will assess whether a 6-month postoperative course of oral montelukast affects multiple PTOA mechanisms. Because montelukast administration can be safely sustained for long durations and offers a low-cost treatment option, should it be proven effective in the current trial, these results can be immediately incorporated into clinical practice., Trial Registration: ClinicalTrials.gov NCT04572256 . Registered on October 1, 2020., (© 2022. The Author(s).)

Objective: A complex association exists between aberrant gait biomechanics and posttraumatic knee osteoarthritis (PTOA) development. Previous research has primarily focused on the link between peak loading during the loading phase of stance and joint tissue changes following anterior cruciate ligament reconstruction (ACLR). However, the associations between loading and cartilage composition at other portions of stance, including midstance and late stance, is unclear. The objective of this study was to explore associations between vertical ground reaction force (vGRF) at each 1% increment of stance phase and tibiofemoral articular cartilage magnetic resonance imaging (MRI) T1ρ relaxation times following ACLR., Design: Twenty-three individuals (47.82% female, 22.1 ±4.1 years old) with unilateral ACLR participated in a gait assessment and T1ρ MRI collection at 12.25 ± 0.61 months post-ACLR. T1ρ relaxation times were calculated for the articular cartilage of the weightbearing medial and lateral femoral (MFC, LFC) and tibial (MTC, LTC) condyles. Separate bivariate, Pearson product moment correlation coefficients ( r ) were used to estimate strength of associations between T1ρ MRI relaxation times in the medial and lateral tibiofemoral articular cartilage with vGRF across the entire stance phase., Results: Greater vGRF during midstance (46%-56% of stance phase) was associated with greater T1ρ MRI relaxation times in the MFC ( r ranging between 0.43 and 0.46)., Conclusions: Biomechanical gait profiles that include greater vGRF during midstance are associated with MRI estimates of lesser proteoglycan density in the MFC. Inability to unload the ACLR limb during midstance may be linked to joint tissue changes associated with PTOA development.

Objective: The primary aim was to determine differences in talocrural and subtalar joint (STJ) articular cartilage composition, using T1ρ magnetic resonance imaging (MRI) relaxation times, between limbs in individuals with unilateral chronic ankle instability (CAI) and compare with an uninjured control. Our secondary purpose was to determine the association between talocrural and STJ composition in limbs with and without CAI., Design: T1ρ MRI relaxation times were collected on 15 CAI (11 females, 21.13 ± 1.81 years, body mass index [BMI] = 23.96 ± 2.74 kg/m 2 ) and 15 uninjured control individuals (11 females, 21.07 ± 2.55 years, BMI = 24.59 ± 3.44 kg/m 2 ). Talocrural cartilage was segmented manually to identify the overall talar dome. The SJT cartilage was segmented manually to identify the anterior, medial, and posterior regions of interest consistent with STJ anatomical articulations. For each segmented area, a T1ρ relaxation time mean and variability value was calculated. Greater T1ρ relaxation times were interpreted as decreased proteoglycan content., Results: Individuals with CAI demonstrated a higher involved limb talocrural T1ρ mean and variability relative to their contralateral limb ( P < 0.05) and the healthy control limb ( P < 0.05). The CAI-involved limb also had a higher posterior STJ T1ρ mean relative to the healthy control limb ( P < 0.05). In healthy controls ( P < 0.05), but not the CAI-involved or contralateral limbs (p>0.05), talocrural and posterior STJ composition measures were positively associated., Conclusions: Individuals with CAI have lower proteoglycan content in both the talocrural and posterior STJ in their involved limbs relative to the contralateral and a healthy control limb. Cartilage composition findings may be consistent with the early development of posttraumatic osteoarthritis.

Objective: The current therapeutic strategy for posttraumatic osteoarthritis (PTOA) focuses on early intervention to attenuate disease progression, preserve joint function, and defer joint replacement timing. Sequential transcriptomic changes of articular cartilage in a rat model were investigated to explore the molecular mechanism in early PTOA progression., Design: Anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx)-induced PTOA model was applied on male Wistar rats. Articular cartilages were harvested at time 0 (naïve), 2 week, and 4 weeks after surgery. Affymetrix Rat genome 230 2.0 array was utilized to analyze the gene expression changes of articular cartilages., Results: We identified 849 differentially expressed genes (DEGs) at 2 weeks and 223 DEGs at 4 weeks post-ACLT + MMx surgery compared with time 0 (naïve group). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to gain further insights from these DEGs. 22 novel genes and 1 novel KEGG pathway (axon guidance) in cartilage degeneration of osteoarthritis were identified. Axon guidance molecules- Gnai1, Sema4d, Plxnb1 , and Srgap2 commonly dysregulated in PTOA progression. Gnai1 gene showed a concordant change in protein expression by immunohistochemistry staining., Conclusions: Our study identified 22 novel dysregulated genes and axon guidance pathway associated with articular cartilage degeneration in PTOA progression. These findings provide the potential candidates of biomarkers and therapeutic targets for further investigation.

Objective: To delineate the response of migrating chondrogenic progenitor cells (CPCs) that arose from the surface of mechanically injured articular cartilage to proinflammatory damage-associated-molecular-patterns (DAMPs)., Design: Bovine CPCs and non-CPC chondrocytes isolated from either impacted or scratched articular cartilage were studied. Those 2 types of cells were treated with mitochondrial DAMPs (MTDs; 10 nM fMLF and 10 µg/mL CpG DNA), or 10 nM HMGB1, or 10 ng/mL IL-1b for 24 hours. At the end of experiments, conditioned media and cell lysates were collected for analysis of expression levels of matrix metalloproteinases (MMPs), chemokines, and cytokines that are associated with cartilage degeneration with Western blotting and quantitative polymerase chain reaction. The difference of expression levels was compared by Welch's t -test., Results: Our data indicated that HMGB1 and MTDs remarkably upregulated pro-MMP-13 expression in CPCs. Compared with non-CPCs, CPCs expressed significantly more baseline mRNAs of MMP-13, CXCL12, and IL-6. MTDs greatly increased the expression of MMP-13 and IL-6 in CPCs by over 100-fold ( P < 0.001). MTDs also significantly increased IL-8 expression in CPCs to a similar extent ( P < 0.001). However, when IL-1b was present, CPCs expressed less MMP-3 and active MMP-13 proteins as well as less CCL2 and IL-6 than did non-CPCs., Conclusions: We concluded that CPCs were more sensitive than non-CPCs in response to DAMPs, especially MTDs. The proinflammatory nature of CPCs implied their critical role in the early phase of posttraumatic osteoarthritis development.

Objective: To evaluate the effect of intra-articular injection of autologous micronized adipose tissue (MAT) with ankle arthroscopic debridement in patients with advanced-stage posttraumatic osteoarthritis (PTOA) of ankle., Design: A retrospective cohort study investigating patients treated with arthroscopic debridement and autologous MAT injection for ankle PTOA was performed. Patients with Kellgren-Lawrence (KL) grade 3 to 4 were included. Visual analogue scale (VAS), Foot and Ankle Outcome Scores (FAOS), and patient satisfaction were evaluated., Results: A total of 19 patients (19 ankles) were included (KL grade 3, 8 patients; grade 4, 11 patients). At a mean follow-up time of 14.3 months (range, 7-23 months), the mean FAOS subscales for pain and quality of life significantly increased from 48.8 and 20.1 preoperatively to 61.1 and 30.1 ( P = 0.029 and 0.048, respectively). The mean VAS score significantly improved from 6.1 to 3.8 (P = 0.003) at final follow-up. A total of 10.5% (2/19) of patients were very satisfied, 31.6% (6/19) satisfied, 26.3% (5/19) neutral, 21.1% (4/19) unsatisfied, and 10.5% (2/19) very unsatisfied with their outcomes. The overall FAOS score demonstrated a significant difference in pre- to postoperative change with 14.8 for KL grade 3 and 5.9 for KL grade 4 ( P = 0.048)., Conclusions: Autologous MAT injection is a safe and potentially beneficial procedure for advanced-stage ankle PTOA as an adjunct to arthroscopic debridement, although more than one-third of patients were unsatisfied with the procedure. This procedure may be more beneficial for KL grade 3 patients than grade 4 patients. However, future investigations are necessary to define the role of MAT for ankle PTOA.

The knee joint is one of the most frequently injured joints in the body, and the resulting injury may often lead to the presence of a bloody effusion, or hemarthrosis. The acute management of this condition can have long-lasting implications, and may ultimately result in the early onset of osteoarthritis in this population. Heme, a breakdown product of erythrocytes, and associated pro-inflammatory mediators, are known to have deleterious interactions with cartilage and synovium. The presence of blood in a joint following injury can precipitate these effects and accelerate the degenerative changes in the joint. Currently, there is no consensus on the optimal management of a traumatic knee joint injury with a hemarthrosis. Nontraumatic hemarthosis, seen most commonly in hemophilia patients, has a set of established guidelines that does not routinely recommend drainage of the joint. This article presents a rationale for joint aspiration to minimize the harmful effects of blood following traumatic hemarthrosis.

Objectives: Osteoarthritis is a painful joint disease responsible for walking impairment. Its quantitative assessment by gait analysis in mice may be a relevant and noninvasive strategy to assess the disease severity. In this study, we aimed to determine the severity of osteoarthritis at the tissular and gait levels in unilateral and bilateral posttraumatic murine osteoarthritis., Methods: Twenty-four C57BL/6 male mice were randomly assigned to 3 groups ( n = 8/group): controls, unilateral surgery, and bilateral surgery. Posttraumatic osteoarthritis was induced unilaterally or bilaterally by destabilization of the medial meniscus. Gait analysis was performed weekly with the CatWalk TM XT system until the 16th week after surgery. After animal sacrifices, histological and micro-computed tomographic assessment was performed., Results: Operated knees showed a significant increase in the histological score compared with controls ( P < 0.001). Calcified anterior medial meniscal bone volume was higher on the ipsilateral side after unilateral destabilization of the medial meniscus ( P < 0.001) and on both sides after bilateral intervention ( P < 0.01). One week after surgery, the mice mean speed decreased significantly in both operated groups ( P < 0.001 and P < 0.05). In the unilateral group, a significant increase in the contralateral hind print area appeared from week 4 to week 16., Conclusions: While bilateral destabilization of the medial meniscus induced no detectable gait modification except 1 week after surgery, unilateral model was responsible for a gait disturbance on the contralateral side. Further studies are needed to better define the place of the CatWalk TM in the evaluation of mouse models of osteoarthritis.

Objective: Excessive articular loading, for example, an ankle sprain, may result in focal osteochondral damage, initiating a vicious degenerative process resulting in posttraumatic osteoarthritis (PTOA). Better understanding of this degenerative process would allow improving posttraumatic care with the aim to prevent PTOA. The primary objective of this study was to establish a drop-weight impact testing model with controllable, reproducible and quantitative axial impact loads to induce osteochondral damage in caprine tibiotalar joints. We aimed to induce osteochondral damage on microscale level of the tibiotalar joint without gross intra-articular fractures of the tibial plafond., Design: Fresh-frozen tibiotalar joints of mature goats were used as ex vivo articulating joint models. Specimens were axially impacted by a mass of 10.5 kg dropped from a height of 0.3 m, resulting in a speed of 2.4 m/s, an impact energy of 31.1 J and an impact impulse of 25.6 N·s. Potential osteochondral damage of the caprine tibiotalar joints was assessed using contrast-enhanced high-resolution micro-computed tomography (micro-CT). Subsequently, we performed quasi-static loading experiments to determine postimpact mechanical behavior of the tibiotalar joints., Results: Single axial impact loads with a mass of 15.5 kg dropped from 0.3 m, resulted in intra-articular fractures of the tibial plafond, where a mass of 10.55 kg dropped from 0.3 m did not result in any macroscopic damage. In addition, contrast-enhanced high-resolution micro-CT imaging neither reveal any acute microdamage (i.e., microcracks) of the subchondral bone nor any (micro)structural changes in articular cartilage. The Hexabrix content or voxel density (i.e., proteoglycan content of the articular cartilage) on micro-CT did not show any differences between intact and impacted specimens. However, quasi-static whole-tibiotalar-joint loading showed an altered biomechanical behavior after application of a single axial impact (i.e., increased hysteresis when compared with the intact or nonimpacted specimens)., Conclusions: Single axial impact loads did not induce osteochondral damage visible with high-resolution contrast-enhanced micro-CT. However, despite the lack of damage on macro- and even microscale, the single axial impact loads resulted in "invisible injuries" because of the observed changes in the whole-joint biomechanics of the caprine tibiotalar joints. Future research must focus on diagnostic tools for the detection of early changes in articular cartilage after a traumatic impact (i.e., ankle sprains or ankle fractures), as it is well known that this could result in PTOA.

Anterior cruciate ligament (ACL) injuries occur at a high frequency in the United States with approximately 400,000 ACL reconstructions being performed each year. While ACL reconstruction is our current gold standard of treatment, it does not restore joint motion, or prevent the premature development of posttraumatic osteoarthritis (PTOA) in many patients. Thus, new treatments for an ACL injury, which are less invasive and minimize patient morbidity, including cartilage damage, are highly desirable. We have used a tissue-engineered approach to stimulate ligament healing, to improve upon current treatment options. In this review, we describe and discuss our work moving a tissue engineering strategy from the concept to bench, preclinical, clinical trials and ultimately FDA 510(k) de Novo approval, providing clinicians and patients with a viable alternative to ACL reconstruction., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Traumatic injuries of the knee joint result in a wide variety of pathomechanisms, which contribute to the development of so-called posttraumatic osteoarthritis (PTOA). These pathogenetic processes include oxidative stress, excessive expression of catabolic enzymes, release of damage-associated molecular patterns (DAMPs), and synovial inflammation. The present review focuses on the underlying pathomechanisms of PTOA and in particular the behavior and fate of the surviving chondrocytes, comprising chondrocyte metabolism, regulated cell death, and phenotypical changes comprising hypertrophy and senescence. Moreover, possible therapeutic strategies, such as chondroanabolic stimulation, anti-oxidative and anti-inflammatory treatment, as well as novel therapeutic targets are discussed. [ABSTRACT FROM AUTHOR]

The roles that cytokines and matrix metalloproteinases play in the onset and progression of posttraumatic osteoarthritis (PTOA) remain a topic of debate. The study objective was to evaluate the concentrations of these inflammatory mediators during the development of mild to moderate PTOA in the porcine anterior cruciate ligament (ACL) surgical model. We hypothesized that there would be more animals with detectable mediators in the pigs that develop moderate PTOA (those receiving ACL reconstruction or untreated ACL transection) compared to those that develop mild PTOA (those receiving scaffold-enhanced ACL repair). 36 Yucatan minipigs underwent ACL transection and were randomized to: 1) no further treatment, 2) ACL reconstruction, or 3) scaffold-enhanced ACL repair. Synovial fluid samples were obtained pre-operatively, and at 1, 4, 12, 26 and 52 weeks post-operatively. The concentrations of inflammatory mediator in the synovial fluid samples were evaluated via multiplex assay. Macroscopic cartilage assessments were performed following euthanasia at 52 weeks. As found in prior studies, the repair group had significantly less cartilage damage than either the ACL transected or ACL reconstruction groups (P<.03). The presence and concentrations of the biomarkers were influenced by surgical group and time. In general, the concentrations of inflammatory mediators were higher in the repair group, which exhibited less cartilage damage than the other two treatment groups. While this finding disproved the hypotheses, these data suggest that the metabolic activity of the joints exhibiting less cartilage damage remained higher over the 52-week period than those that did not., Competing Interests: It should be noted that Dr. Murray is a founder, paid consultant and equity holder, Dr. Proffen is a paid consultant and equity holder, and Dr. Fleming is a founder of Miach Orthopaedics, Inc, which was formed to upscale production of a scaffold for ACL repair and is related to one of the ACL procedures described herein. Drs. Murray and Proffen maintain a conflict-of-interest management plan approved by Boston Children’s Hospital and Harvard Medical School. Dr. Fleming also maintains a conflict-of-interest management plan with Rhode Island Hospital with similar oversight., (AJTR Copyright © 2021.)

The purpose of this proof-of-concept study was to develop three-dimensional patient-specific mechanobiological knee joint models to simulate alterations in the fixed charged density (FCD) around cartilage lesions during the stance phase of the walking gait. Two patients with anterior cruciate ligament (ACL) reconstructed knees were imaged at 1 and 3 years after surgery. The magnetic resonance imaging (MRI) data were used for segmenting the knee geometries, including the cartilage lesions. Based on these geometries, finite element (FE) models were developed. The gait of the patients was obtained using a motion capture system. Musculoskeletal modeling was utilized to calculate knee joint contact and lower extremity muscle forces for the FE models. Finally, a cartilage adaptation algorithm was implemented in both FE models. In the algorithm, it was assumed that excessive maximum shear and deviatoric strains (calculated as the combination of principal strains), and fluid velocity, are responsible for the FCD loss. Changes in the longitudinal T 1ρ and T 2 relaxation times were postulated to be related to changes in the cartilage composition and were compared with the numerical predictions. In patient 1 model, both the excessive fluid velocity and strain caused the FCD loss primarily near the cartilage lesion. T 1ρ and T 2 relaxation times increased during the follow-up in the same location. In contrast, in patient 2 model, only the excessive fluid velocity led to a slight FCD loss near the lesion, where MRI parameters did not show evidence of alterations. Significance: This novel proof-of-concept study suggests mechanisms through which a local FCD loss might occur near cartilage lesions. In order to obtain statistical evidence for these findings, the method should be investigated with a larger cohort of subjects., (© 2020 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

With the exception of the relatively frequent fractures of the scaphoid bone, isolated fractures of individual carpal bones are rare. Because these injuries are uncommon and because of the complex anatomy and function of the carpus, treatment of carpal bone fractures can be challenging. Carpal bone fractures generally occur in young, sports active and professional patients, can be easily overlooked in plain radiographs and are frequently associated with ligamentous instability, neurovascular injuries and tendon lesions. Small posttraumatic alterations of the precisely aligned carpal structure can cause chronic pain and functional impairment. Therefore, if a wrist fracture is suspected a thorough clinical examination and appropriate differentiated imaging is always necessary, at the end of which a fracture can be excluded or an appropriate conservative or surgical treatment is initiated, with the aim of restoration of carpal anatomy and function.

Background: There is a high incidence of posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament (ACL) injury, and these injuries represent an enormous health care economic burden. In an effort to address this unmet clinical need, there has been increasing interest in cell-based therapies., Purpose: To establish a translational large animal model of PTOA and demonstrate the feasibility of intra-articular human cell-based interventions., Study Design: Descriptive laboratory study., Methods: Nine Yucatan mini-pigs underwent unilateral ACL transection and were monitored for up to 12 weeks after injury. Interleukin 1 beta (IL-1β) levels and collagen breakdown were evaluated longitudinally using enzyme-linked immunosorbent assays of synovial fluid, serum, and urine. Animals were euthanized at 4 weeks (n = 3) or 12 weeks (n = 3) after injury, and injured and uninjured limbs underwent magnetic resonance imaging (MRI) and histologic analysis. At 2 days after ACL injury, an additional 3 animals received an intra-articular injection of 10 7 human bone marrow-derived mesenchymal stem cells (hBM-MSCs) combined with a fibrin carrier. These cells were labeled with the luciferase reporter gene (hBM-MSCs-Luc) as well as fluorescent markers and intracellular iron nanoparticles. These animals were euthanized on day 0 (n = 1) or day 14 (n = 2) after injection. hBM-MSC-Luc viability and localization were assessed using ex vivo bioluminescence imaging, fluorescence imaging, and MRI., Results: PTOA was detected as early as 4 weeks after injury. At 12 weeks after injury, osteoarthritis could be detected grossly as well as on histologic analysis. Synovial fluid analysis showed elevation of IL-1β shortly after ACL injury, with subsequent resolution by 2 weeks after injury. Collagen type II protein fragments were elevated in the synovial fluid and serum after injury. hBM-MSCs-Luc were detected immediately after injection and at 2 weeks after injection using fluorescence imaging, MRI, and bioluminescence imaging., Conclusion: This study demonstrates the feasibility of reproducing the chondral changes, intra-articular cytokine alterations, and body fluid biomarker findings consistent with PTOA after ACL injury in a large animal model. Furthermore, we have demonstrated the ability of hBM-MSCs to survive and express transgene within the knee joint of porcine hosts without immunosuppression for at least 2 weeks., Clinical Relevance: This model holds great potential to significantly contribute to investigations focused on the development of cell-based therapies for human ACL injury-associated PTOA in the future (see Appendix Figure A1, available online).