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A patellar luxation and concomitant cranial cruciate ligament rupture is a common pathology in dogs. Diagnosis is based on clinical evidence of a patellar luxation and stifle joint instability. However, diagnostic imaging is required to assess the number of skeletal deformities and signs of instability. Surgical options include both soft tissue and osseous techniques, although, in most cases, a combination of multiple procedures is necessary to correct the patellar luxation and restore the stifle joint stability. Complication rates are generally low, but can include reluxation and implant-associated complications. This article describes the patellar luxation and cranial cruciate ligament rupture signs in dogs, including the clinical presentation and diagnosis, and discusses current treatment options.

Background: Stifle osteoarthritis (OA) lesions are most common in the medial femorotibial (MFT) compartment. Their characterisation and mapping will inform equine veterinarians towards an accurate diagnosis of OA., Objectives: Investigate and map micro-CT (μCT) changes in the hyaline articular cartilage (HAC) in the medial femoral condyle (MFC) and medial tibial plateau (MTP)., Study Design: Ex vivo cadaveric., Methods: Stifles (n = 7 OA and 17 control [CO]) were retrieved from a tissue bank. The MFC and MFT were imaged with μCT. Regions of interest (ROIs) were cranial (MFCcr; MTPcr) and caudal (MFCca; MTPca) sites. In each ROI, μCT images were scored for HAC fibrillation, surface mineralisation and for the presence of high-density mineralised protrusions (HDMP). The lesions were mapped, and site-matched histology was performed., Results: The microstructure of healthy and abnormal HAC was discernible on μCT images and confirmed with histology. HAC fibrillation was more prevalent (p = 0.019) in the MFCcr of the OA group (n = 7/7, 100%) when compared with the CO group (n = 7/17, 41%). Score 1 HAC surface mineralisation was more prevalent (p = 0.038) in the OA MFCca (n = 4/7, 57%) when compared with the CO group (n = 2/17, 12%). HDMP were heterogenous and hyperdense mineralised material protruding into the HAC and were more frequent (p = 0.033) in MFCs (n = 12/24, 50%) compared with MTPs (n = 5/24, 20%). Score 3 HDMPs were also more prevalent (p = 0.003) in the MFCcr (n = 7/24, 29%) compared with MFCca (n = 0/24, 0%) and in MFCs (n = 7/24, 29%) compared with MTPs (n = 3/24, 12.5%) (p = 0.046)., Main Limitations: Clinical history was not available for all specimens., Conclusions: Equine HDMP and HAC surface mineralisation are imaged for the first time in the MFT joint. HAC fibrillation and erosion and HDMP are more frequent in the cranial aspect of the MFC. μCT images of OA in equine stifle joints provide a novel perspective of lesions and improve understanding of OA., (© 2024 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

A patellar luxation and concomitant cranial cruciate ligament rupture is a common pathology in dogs. Diagnosis is based on clinical evidence of a patellar luxation and stifle joint instability. However, diagnostic imaging is required to assess the number of skeletal deformities and signs of instability. Surgical options include both soft tissue and osseous techniques, although, in most cases, a combination of multiple procedures is necessary to correct the patellar luxation and restore the stifle joint stability. Complication rates are generally low, but can include reluxation and implant-associated complications. This article describes the patellar luxation and cranial cruciate ligament rupture signs in dogs, including the clinical presentation and diagnosis, and discusses current treatment options. [ABSTRACT FROM AUTHOR]

Concomitant cranial cruciate ligament rupture (CCLR) is a common complication in small breed dogs with patellar luxation (PL) with an elusive pathogenesis. Surgical treatment is available and commonly includes remodelling osteotomies. While these modern techniques have shown good functional results, access is limited due to the high costs for owners and the need for special surgical equipment. The objectives of the study were to evaluate the frequency and risk factors for concomitant CCLR in small breed dogs with PL. To study the outcome and complications of the combination of the Wedge recession osteotomy (WR) and Tibial tuberosity transposition (TT) with a Fascia over-the-top (OT) or a Capsular and fascial imbrication technique (CFI) for the simultaneous treatment of PL and concomitant CCLR. A retrospective study is presented here. The signalment, body weight, luxation grade and direction, affected side, bilateral or unilateral PL, CCLR and meniscal status were analysed. The surgical treatment for PL and concomitant CCLR, outcome and complications were investigated. Of 233 small breed dogs with PL, 52 (22.31%) had a concomitant CCLR. Maltese dogs were more likely to have concomitant CCLR. The mean age for the dogs with PL only was 5.32 years, which was significantly younger than the mean age of dogs with PL and concomitant CCLR (7.39 years). Overweight dogs with PL were prone to develop concomitant CCLR. Surgical stabilisation with a combination of WR, TT and OT or CFI had excellent or good results in 86.63% of the cases, while 16.67% of the cases developed complications. In conclusion, PL and concomitant CCL ruptures can be managed successfully by performing a combination of WR, TT and OT or CFI. The outcomes and complication rates are comparable to remodelling osteotomies. Moreover, these techniques are less expensive and can be performed with standard surgical equipment. These findings should be beneficial for clinical diagnosis, client education and treatment.

This retrospective case series reports on French bulldogs diagnosed with patellar maltracking without patellar luxation. We describe clinical presentation, joint exploration, and surgical treatment with patellar groove replacement to alleviate maltracking in the first attempt. Three French bulldogs were included. Clinical presentation was similar in all cases, with intermittent skipping lameness of 1 hind limb, absence of patellar luxation, and patellar maltracking. Joint exploration revealed abnormal conflict between the patella and medial ridge of the trochlea, with secondary severe erosion of articular cartilages of both patella and medial ridge of the trochlea. Patellar groove replacement was completed without perioperative or postoperative complications. Follow-up results and owner satisfaction were excellent in all cases. Patellar maltracking should be included as a differential diagnosis for stifle lameness in French bulldogs. Patellar groove replacement should be considered to alleviate maltracking associated with secondary severe patellofemoral erosion. Key clinical message: Patellar maltracking seems to be a misdiagnosed component of patellar luxation in the dog, particularly in the French bulldog. Patellar groove replacement may be a first-attempt surgical treatment to alleviate the maltracking., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Objective: To explain the relationship between cartilage erosion and medial patellar luxation (MPL) and to identify risk factors in dogs., Methods: A retrospective review was conducted on 90 dogs (103 stifles) surgically treated for MPL between January 2006 and March 2024. Data collected included signalment, side of operated stifle, patellar luxation grade, symptom duration, and lameness score. Cartilage erosion was evaluated for extent and location on the patella and femoral trochlea. Statistical analyses were conducted to identify risk factors., Results: The prevalence of cartilage erosion of the patella and femoral trochlea was 47.6% (49/103) and 54.4% (56/103), respectively, increasing with a higher grade of patellar luxation. Lesions were most prevalent in the distolateral patella and proximomedial trochlea, with generalized lesions more prevalent in grade IV. The extent of both lesions was significantly associated with age, patellar luxation grade, and symptom duration, while body weight significantly correlated only with the cartilage erosion of the patella. No significant correlation was observed with sex, side of operated stifle, or lameness score., Conclusions: Many patients with MPL exhibited cartilage erosion in the patellofemoral joint, likely due to biomechanical mechanisms. Surgery can be indicated for patients with MPL, as it may prevent cartilage erosion while improving patellofemoral alignment and gait. When selecting surgical candidates, it is important to consider risk factors, such as patellar luxation grade, body weight, age, and symptom duration., Clinical Relevance: Early surgical treatment is recommended, especially for dogs with higher body weight and higher grade of MPL, to prevent cartilage erosion and secondary osteoarthritis.

A 7-year-old female spayed Bernese Mountain dog was presented for evaluation of hematuria. Incidentally, a right stifle sarcoma was diagnosed via cytology, which raised concern for histiocytic sarcoma (given the patient's signalment) versus another joint-associated sarcoma. Histopathology and immunohistochemistry revealed a CD18-negative, non-histiocytic origin cell population. Findings were consistent with a joint-associated grade II soft tissue sarcoma (STS). The patient's hematuria was progressive over 5 months, and urinary bladder transitional cell carcinoma (TCC) was diagnosed via cystoscopy and histopathology. An enlarged right medial iliac lymph node was identified on routine restaging via abdominal ultrasound 3 months later. Cytology of the lymph node revealed a markedly pleomorphic cell population, again raising concern for histiocytic sarcoma (HS). Other differentials included an anaplastic metastatic population from the joint-associated STS or the TCC. Immunocytochemistry revealed a cytokeratin-positive, CD18-, CD204-, and vimentin-negative cell population, consistent with a carcinoma. DNA was extracted from cytology slides to sequence cells for BRAF mutation status. Sequencing revealed a homozygous V596E (transcript ENSCAFT00845055173.1) BRAF mutation, consistent with the known biology of TCC. In neither case was HS truly present in this patient, but immunocytochemistry provided information that helped to optimize the patient's chemotherapy recommendations., (© 2024 The Authors. Veterinary Clinical Pathology published by Wiley Periodicals LLC on behalf of American Society for Veterinary Clinical Pathology.)

Osteoarthritis is one of the most common diseases in veterinary medicine. There are various causes for joints developing OA, with some of them being well investigated, while others are still a matter of speculation. In this retrospective study we examined the prevalence of OA in the shoulder, elbow, hip and stifle joints in a clinic population of dogs older than 8 years, which were presented mostly due to orthopaedic complaints. Dogs were included in the study if one or more of the aforementioned joints was included in the radiographs. Radiographs were reviewed by three different observers and graded by severity. Prevalence of OA was 39.2%, 57.4%, 35.9% and 36.4% for the shoulder, elbow, hip and stifle, respectively. There was no correlation between higher grades of OA and weight as well as age, but significantly higher prevalence of OA in heavier groups when grouped for weight. Sex and castration status did not affect presence of OA. As most of the examined joints were free of OA, radiographic findings suggestive of OA should not be considered normal in senescent dogs., Competing Interests: Declaration of Competing Interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Concomitant cranial cruciate ligament rupture (CCLR) is a common complication in small breed dogs with patellar luxation (PL) with an elusive pathogenesis. Surgical treatment is available and commonly includes remodelling osteotomies. While these modern techniques have shown good functional results, access is limited due to the high costs for owners and the need for special surgical equipment. The objectives of the study were to evaluate the frequency and risk factors for concomitant CCLR in small breed dogs with PL. To study the outcome and complications of the combination of the Wedge recession osteotomy (WR) and Tibial tuberosity transposition (TT) with a Fascia over-the-top (OT) or a Capsular and fascial imbrication technique (CFI) for the simultaneous treatment of PL and concomitant CCLR. A retrospective study is presented here. The signalment, body weight, luxation grade and direction, affected side, bilateral or unilateral PL, CCLR and meniscal status were analysed. The surgical treatment for PL and concomitant CCLR, outcome and complications were investigated. Of 233 small breed dogs with PL, 52 (22.31%) had a concomitant CCLR. Maltese dogs were more likely to have concomitant CCLR. The mean age for the dogs with PL only was 5.32 years, which was significantly younger than the mean age of dogs with PL and concomitant CCLR (7.39 years). Overweight dogs with PL were prone to develop concomitant CCLR. Surgical stabilisation with a combination of WR, TT and OT or CFI had excellent or good results in 86.63% of the cases, while 16.67% of the cases developed complications. In conclusion, PL and concomitant CCL ruptures can be managed successfully by performing a combination of WR, TT and OT or CFI. The outcomes and complication rates are comparable to remodelling osteotomies. Moreover, these techniques are less expensive and can be performed with standard surgical equipment. These findings should be beneficial for clinical diagnosis, client education and treatment. [ABSTRACT FROM AUTHOR]

Concomitant cranial cruciate ligament rupture (CCLR) is a common complication in small breed dogs with patellar luxation (PL) with an elusive pathogenesis. Surgical treatment is available and commonly includes remodelling osteotomies. While these modern techniques have shown good functional results, access is limited due to the high costs for owners and the need for special surgical equipment. The objectives of the study were to evaluate the frequency and risk factors for concomitant CCLR in small breed dogs with PL. To study the outcome and complications of the combination of the Wedge recession osteotomy (WR) and Tibial tuberosity transposition (TT) with a Fascia over-the-top (OT) or a Capsular and fascial imbrication technique (CFI) for the simultaneous treatment of PL and concomitant CCLR. A retrospective study is presented here. The signalment, body weight, luxation grade and direction, affected side, bilateral or unilateral PL, CCLR and meniscal status were analysed. The surgical treatment for PL and concomitant CCLR, outcome and complications were investigated. Of 233 small breed dogs with PL, 52 (22.31%) had a concomitant CCLR. Maltese dogs were more likely to have concomitant CCLR. The mean age for the dogs with PL only was 5.32 years, which was significantly younger than the mean age of dogs with PL and concomitant CCLR (7.39 years). Overweight dogs with PL were prone to develop concomitant CCLR. Surgical stabilisation with a combination of WR, TT and OT or CFI had excellent or good results in 86.63% of the cases, while 16.67% of the cases developed complications. In conclusion, PL and concomitant CCL ruptures can be managed successfully by performing a combination of WR, TT and OT or CFI. The outcomes and complication rates are comparable to remodelling osteotomies. Moreover, these techniques are less expensive and can be performed with standard surgical equipment. These findings should be beneficial for clinical diagnosis, client education and treatment. [ABSTRACT FROM AUTHOR]

A 2-year-old neutered male bullmastiff dog was presented with chronic left hind limb lameness. Physical examination revealed left stifle effusion and medial buttress without cranial tibial thrust. Radiographs showed joint effusion and new bone formation at the patella apex. Magnetic resonance imaging showed increased synovial fluid, widening of the joint space, abnormal infrapatellar fat body and thinning of the cranial cruciate ligament. Synoviocentesis and cytologic evaluation of synovial fluid revealed marked mononuclear inflammation with abundant fatty tissue, suggesting synovial lipomatosis in conjunction with the imaging findings. The disease was confirmed histologically after sampling the lesion during arthrotomy. Synovial lipomatosis, characterized by extensive synovial adipose tissue proliferation of the synovial membrane, is a rare "tumor-like" disorder that usually affects the stifle. Although the etiology remains unclear, joint trauma, inflammation, instability, and lipid abnormalities have been proposed as causes. Inflammatory factors may promote synoviocyte and adipocyte hyperplasia that perpetuate the process. Surgical removal may be suggested to eliminate triggers and prevent future recurrences. The report provides the first cytological description of adipocytes in synovial fluid associated with the diagnosis of synovial lipomatosis in dogs. This case report underscores the potential effectiveness of cytologic analysis of synovial fluid smears, in combination with magnetic resonance imaging (MRI), for diagnosing this condition and reducing complications associated with arthrotomy for sampling purposes. Additionally, the case highlights that synovial lipomatosis should be considered as a potential differential diagnosis for synovial masses in dogs. Further cases are needed to validate these observations in veterinary medicine., (© 2024 The Authors. Veterinary Clinical Pathology published by Wiley Periodicals LLC on behalf of American Society for Veterinary Clinical Pathology.)

Objective: To compare palpation and ultrasound scores of effusion of the medial femorotibial and femoropatellar joints of horses., Animals: 40 horses (80 stifles) were evaluated over a 12-week period., Methods: Horses > 1 year of age without history of stifle disease were enrolled from September to December 2022. Palpation of right and left medial femorotibial and femoropatellar joint compartments was performed. Amount of effusion was scored by a board-certified large animal surgeon, a third-year large animal surgery resident, and an equine sports medicine intern. Effusion of right and left medial femorotibial and femoropatellar joints was quantified with ultrasound by a board-certified equine sports medicine and rehabilitation clinician. Amount of effusion on palpation and ultrasound was graded as none-mild (1), moderate (2), or severe (3). A 2-way intraclass correlation coefficient evaluated interrater reliability of palpation scores. The Spearman rank correlation determined association between palpation and ultrasound scores., Results: Interrater reliability for palpation of effusion was poor between all observers for all joint compartments. No significant correlation was identified between palpation and ultrasound scores for any joint compartment for any observer., Clinical Relevance: Clinicians often rely on palpation of joint effusion as an indication of stifle pathology. We found interrater reliability to be poor for palpation scores, indicating low agreement for palpation of joint effusion between clinicians within our group. No correlation was found between palpation and ultrasound scores for joint effusion, indicating that clinicians should not rely on palpation alone to quantify joint effusion of the medial femorotibial and femoropatellar joints.

Background: Subchondral lucencies (SCLs) in the distal aspect of the medial femoral condyle (MFC) of young Thoroughbred horses are a source of controversy on presale radiographs. There is limited scientific evidence regarding the risk of progression and impact on future racing performance., Objectives: To (1) identify the prevalence of MFC SCLs on sales repository radiographs in yearling and 2-year-old Thoroughbreds; (2) identify any association between grade of MFC SCL and future racing performance and (3) monitor changes in MFC SCL grades between yearling and 2-year-old sales., Study Design: Prospective cohort study., Methods: Radiographs were obtained with consignor permission from a 2016 yearling sale and five 2017 2-year-old sales. Stifle radiographs were evaluated and MFC SCLs graded on a scale of 0-3. Axial MFC lucencies were recorded separately. Maximum MFC grades per horse were analysed for associations with racing performance outcomes, adjusted for sex, to the end of the horses' 4-year-old racing year. Analysis was via logistic, negative binomial or linear regression as appropriate, with the threshold for significance set at α = 0.05., Results: Radiographs from 2508 yearlings (5016 stifles) and 436 2-year-olds (872 stifles) were included in the study. MFC SCLs of grades 1-3 were observed in 242 (9.65%) yearlings and 49 (11.2%) 2-year-olds. Bilateral MFC SCLs of grades 1-3 were observed in 54 (2.2%) yearlings and 12 (2.8%) 2-year-olds. Grade 1 MFC SCLs in yearlings either remained unchanged (14/31), progressed to a grade 2 (6/31) or resolved (11/31) by the 2-year-old sale. Grade 2 MFC SCLs in yearlings remained unchanged (6/10), progressed to a grade 3 (2/10) or improved to a grade 1 (2/10). Yearlings with a grade 3 MFC SCL had a 78% probability of starting a race (95% confidence interval [CI] 58.2-89.6%), compared with an 84% probability of racing for grade 0 yearlings (95% CI 82.7-85.8%). Six of the seven yearlings with axial MFC lucencies raced., Main Limitations: This study may underestimate the prevalence of severe lesions in the general yearling population of U.S. Thoroughbreds. However, the convenience sample used is representative of the population of interest at sales. The study design could not address exclusions prior to sale., Conclusions: Grade 1 MFC SCLs are the most common type seen in yearling and 2-year-old sales horses. The majority of yearling grade 1 MFC SCLs resolved or remained static by 2-year-old sales. It was also possible for grade 2 and 3 MFC SCLs to improve one grade between sales. Fewer sales yearlings with a grade 3 MFC SCL raced, but in those that did race there was no evidence of worse performance compared to unaffected peers. Axial MFC lucencies did not affect racing performance., (© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Objective: To describe cases with caudal cruciate ligament (CdCL) avulsion fragments diagnosed based on computed tomography (CT) examination and report on arthroscopic fragment removal., Animals: Four Warmblood horses with hindlimb lameness and osseous fragments located in the caudal medial femorotibial joint (mFTJ)., Study Design: Short case series., Methods: CT and arthroscopic evaluation of the caudal mFTJ were performed. The caudal mFTJ and the insertion of the CdCL on the tibia were assessed and removal of the avulsion fragments was attempted in three horses using a cranial intercondylar approach., Results: The fragment was not accessible via caudomedial approaches in one horse. A cranial intercondylar approach was used in three horses, allowing removal of the intra-articular fragment in two horses, and removal of two-thirds of the proximal fragment in the last horse. Acute, profuse, arterial bleeding occurred in this horse during surgery with transient postoperative soft tissue swelling. Comorbidities included medial femoral condyle cartilage defects (3), cranial cruciate ligament lesions (2), and medial collateral ligament lesions (2). Horses were followed up for 16 months (median, range 11-28 months), at which point all were back in ridden exercise; owners' satisfaction was good., Conclusion: CT examination confirmed the diagnosis and allowed evaluation of the stifle joint for comorbidities. A cranial intercondylar arthroscopic approach facilitated the removal of CdCL insertional avulsion fragments, although not always complete., Clinical Significance: A cranial intercondylar approach can allow access to CdCL avulsion fragments, but complications and incomplete removal remain possible., (© 2023 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Objective:  The aim of this study was to describe the arthroscopic changes to the caudal cruciate ligament (CdCL) in dogs with cranial cruciate ligament disease., Study Design:  Arthroscopic video recordings ( n  = 117) of the stifle with cranial cruciate ligament disease were reviewed. The extent of CdCL tearing was described. Signalment, palpable stifle stability and the presence of a meniscal tear were recorded. Pathology of the synovial joint and the synovium overlying the CdCL were scored at two time points.Two-way interactions were investigated ( p  < 0.05). Univariate analysis and a Wald test ( p  < 0.20) were performed. Factors were retained with a Wald test p  < 0.05 or if a confounder, then a changing model coefficient >15%. A weighted kappa statistic was used to evaluate intraobserver agreement., Results:  Caudal cruciate ligament tearing was identified in 94% of stifles. Longitudinal tearing (76%) was the most common type of damage (45% partial, 31% full thickness). Synovitis was present in all joints and changes to the synovium overlying the CdCL were less frequently identified (67%).Synovitis was associated with the degree to CdCL tearing. Synovitis overlying the CdCL was associated with lower body weight and lower CdCL damage., Conclusion:  Caudal cruciate ligament damage is common in dogs with cranial cruciate ligament disease and longitudinal tearing was the most common injury identified. Severity of joint pouch synovitis was positively correlated with the degree of CdCL damage and the portion of the CdCL not exposed to the synovium was unaffected. These findings suggest synovitis is likely a contributor to CdCL injury., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective:  The main aim of this study was to compare the accuracy of stifle exploratory using either a stifle distractor (SD method) or a combination of Hohmann and Senn retractors (HS method) for diagnosing canine medial meniscal tears in cranial cruciate ligament-deficient stifles., Study Design:  Fifteen pairs of canine cadaveric pelvic limbs were used and cranial cruciate ligament were transected in all stifles. Paired limbs were then randomly assigned to one of five groups based on the tears created in the caudal pole of the medial meniscus: no tear, peripheral detachment, or a variation in three vertical longitudinal tears. A craniomedial mini-arthrotomy was performed by two observers and diagnosis of the medial meniscal status was made utilizing the HS and SD methods. Correct diagnosis of the meniscal tear was compared for both methods and observers., Results:  Correct diagnoses were made using the HS and SD methods in 24/30 and 24/30 cases for observer 1 respectively; and in 17/30 and 19/30 cases for observer 2 respectively. There was no significant difference in the correct diagnosis of meniscal tears within each observer between the two methods., Conclusion:  Both HS and SD methods have equal accuracy for the diagnosis of canine medial meniscal pathology for a board-certified surgeon. Unassisted surgeons using the SD method for the evaluation of the medial meniscus are at no diagnostic disadvantage compared with assisted surgeons utilizing the HS method., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To report the findings and long-term outcome of 76 sport horses with meniscal injury., Study Design: Retrospective case series., Animals: Seventy-six horses with 93 meniscal injuries in 85 stifles., Methods: Medical records of sport horses diagnosed with meniscal injury during arthroscopy were reviewed. Owner follow up was obtained via telephone interview ≥1.5 years postoperatively. Preoperative and intraoperative findings, and postoperative treatments, were analyzed for potential association with return to athletic performance., Results: The medial meniscus was involved in 82.8% of cases, with grade 1 injuries diagnosed in 76.3% of menisci. Overall, 85.5% of horses returned to athletic performance, with 40% returning to their previous level. The grade of meniscal injury was associated with long-term outcome (P = .023). The presence of preoperative radiographic abnormalities (P = .259) or additional joint pathology (P = 1.00) was not associated with long-term outcomes. Fifty-nine stifles were treated with an orthobiologic: autologous conditioned serum, platelet-rich plasma, or marrow-derived mesenchymal stem cells. There was no association between the use of any orthobiologic and long-term outcome (P = .394)., Conclusion: This is the first report on long-term outcome of sport horses with meniscal injuries following arthroscopic surgery. Overall, the long-term prognosis was fair, with 40% of horses returning to their previous level of use. Severity of the meniscal injury was a prognostic indicator for return to work. The presence of radiographic abnormalities or additional joint pathology, or the use of orthobiologics, was not associated with long-term outcome., Clinical Significance: These findings can help in prognostication for sport horses with meniscal injuries., (© 2022 American College of Veterinary Surgeons.)

Posttraumatic osteoarthritis (PTOA) can develop after an injury to the knee. Previous studies have indicated that an intra-articular (IA) injection of the potent glucocorticoid dexamethasone (DEX) may significantly prevent induction of PTOA. The aim of the present study was to investigate the effectiveness of a single IA injection of hyaluronic acid (HA), alone and in combination with DEX following a localized intra-articular injury as a PTOA-preventing treatment option. An established rabbit model of surgical injury consisting of dual intra-articular (IA) drill holes in a non-cartilaginous area of the femoral notch near the origin of the anterior cruciate ligament (ACL) to allow for bleeding into the joint space was used. Immediately following surgery, subjects were treated with HA, HA + DEX, or received no treatment. An uninjured control group was used for comparison (N = 5/group). Rabbits were sacrificed and investigated at 9 weeks post-injury. At 9 weeks post-injury, there was a significant protective capacity of the single IA treatment of DEX + HA on the histological grade of the synovial tissue, and some variable location-specific effects of HA alone and HA + DEX interactions on cartilage damage. Thus, it is possible that co-treatment with HA may interfere with the effectiveness of the DEX. In vitro friction testing indicated that DEX did not interfere with the lubricating ability of HA or synovial fluid on cartilage. These results suggest that a single IA administration of HA in combination with DEX following an IA injury is not recommended for inhibition of PTOA progression in this model., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA., (© 2021. The Author(s).)

Objective: To explore how systemic factors that modify knee osteoarthritis risk are connected to 'whole-joint' structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics., Methods: Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age (n = 9-13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group., Results: High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1,412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1β and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites., Conclusion: Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure., (Published by Elsevier Ltd.)

Objective: Metabolic dysfunction can cause IL-1β mediated activation of the innate immune system, which could have important implications for the therapeutic efficacy of IL-1β neutralizing drugs as treatment for OA in the context of metabolic syndrome (MetS). In the present study, we investigated whether early treatment with a single dose of IL-1β blocking antibodies could prevent Western diet (WD) induced changes to systemic monocyte populations and their cytokine secretion profile and herewith modulate collagenase induced osteoarthritis (CiOA) pathology., Methods: CiOA was induced in female C57Bl/6 mice fed either a standard diet (SD) or WD and treated with a single dose of either polyclonal anti-IL-1β antibodies or control. Monocyte subsets and granulocytes in bone marrow and blood were analyzed with flow cytometry, and cytokine expression by bone marrow cells was analyzed using qPCR. Synovial cellularity, cartilage damage and osteophyte formation were assessed on histology., Results: WD feeding of C57Bl/6 mice led to increased serum levels of low-density lipoprotein (LDL) and innate immune activation in the form of an increased number of Ly6C high cells in bone marrow and blood and increased cytokine expression of IL-6 and TNF-α by bone marrow cells. The increase in monocyte number and activity was ameliorated by anti-IL-1β treatment. However, anti-IL-1β treatment did not significantly affect synovial lining thickness, cartilage damage and ectopic bone formation during WD feeding., Conclusions: Single-dose systemic anti-IL-1β treatment prevented WD-induced innate immune activation during early stage CiOA in C57Bl/6 mice, but did not ameliorate joint pathology., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To determine whether osteoarthritis (OA) pain characteristics and mechanistic pathways in pre-clinical models are phenotype-specific., Design: Male 11-week-old C57BL6 mice had unilateral medial-meniscal-destabilization (DMM) or antigen-induced-arthritis (AIA), vs sham-surgery/immunised-controls (Sham/Im-CT). Pain behaviour (allodynia, mechanical- and thermal-hyperalgesia, hindlimb static weight-bearing, stride-length) and lumbar dorsal root ganglia (DRG) gene-expression were measured at baseline, day-3, week-1/-2/-4/-8/-16, and pain-behaviour:gene-expression:joint-pathology associations investigated., Results: DMM and AIA induced structural OA defined by progressively increasing cartilage erosion, subchondral bone sclerosis and osteophyte size and maturation. All pain-behaviours were modified, with model-specific differences in severity and temporal pattern. Tactile allodynia developed acutely in both models and persisted to week-16. During early-OA (wk4-8) there was; reduced right hindlimb weight-bearing in AIA; thermal-hyperalgesia and reduced stride-length in DMM. During chronic-OA (wk12-16); mechanical-hyperalgesia and reduced right hindlimb weight-bearing were observed in DMM only. There were no associations in either model between different pain-behaviour outcomes. A coordinated DRG-expression profile was observed in sham and Im-CT for all 11 genes tested, but not in AIA and DMM. At wk-16 despite equivalent joint pathology, changes in DRG-expression (Calca, Trpa1, Trpv1, Trpv4) were observed only in DMM. In AIA mechanical-hyperalgesia was associated with Trpv1 (r = -0.79) and Il1b (r = 0.53). In DMM stride-length was associated with Calca, Tac1, Trpv1, Trpv2, Trpv4 and Adamts5 (r = 0.4-0.57). DRG gene-expression change was correlated with subchondral-bone sclerosis in DMM, and cartilage damage in AIA. Positive pain-behaviour:joint-pathology associations were only present in AIA - for synovitis, subchondral-bone resorption, chondrocyte-hypertrophy and cartilage damage., Conclusion: Pain and peripheral sensory neuronal responses are OA-phenotype-specific with distinct pathology:pain-outcome:molecular-mechanism relationships., (Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Xian-Xiong-Gu-Kang is composed of Epimedium brevicornu, Ligusticum chuanxiong, Radix clematidis, Cinnamomum cassia, and Fructus xanthii. It is used to treat numbness and pain of limbs. In this study, we developed a method to simultaneously quantify 11 components of Xian-Xiong-Gu-Kang (icarrin, epimedin A, epimedin B, epimedin C, icariside II, chlorogenic acid, ligustilide, senkyunolide A, senkyunolide I, ferulic acid, and cinnamic acid) in rat plasma using ultra-performance liquid chromatography coupled with quadrupole linear ion trap mass spectrometry. Chromatographic separation was performed on an ACQUITY UPLC BEH C18 column using gradient elution with a mobile phase comprising acetonitrile and 0.05% (v/v) formic acid aqueous solution. Mass spectrometry detection was performed using positive and negative electrospray ionization in the multiple reaction monitoring mode. The calibration curves of the 11 constituents were linear, with correlation coefficients > 0.99. The intra- and interday accuracy and precision values were within ±15.0%. The extraction recoveries of the 11 constituents and two internal standards were between 66.05 and 105.40%, and the matrix effects were between 86.74 and 112.86%. Using this method, the pharmacokinetic features of the 11 constituents were elucidated in the plasma of osteoarthritic rats after oral administration of the Xian-Xiong-Gu-Kang extract., (© 2021 Wiley-VCH GmbH.)

Background: Stifle joint diseases (SJD) are common in dogs and include a variety of diagnoses. The objective of the study was to provide an overview of the epidemiology of SJD in insured dogs., Methods: An historical single cohort study of dogs insured in Agria Pet Insurance (2011-2016) in Sweden was performed. Incidence and relative risk (RR) of SJD was calculated for the whole dog population and for subgroups divided by breed, breed group and sex., Results: The study population included almost 600,000 insured dogs (>1.7 million dog-years). Ninety-three different stifle joint diagnoses were reported in 9624 dogs, and the most common were cruciate ligament rupture and patellar luxation. The incidence of SJD was 55.4 cases per 10,000 dog-years at risk. Bulldog and boerboel had the highest RR of SJD. The breeds that accounted for the highest proportion of all SJD claimed dogs were mixed breed and Labrador retriever. Female dogs had a slightly increased RR compared with male dogs (RR 1.06, p = 0.006). The incidence increased yearly during the observation period., Conclusion: The study demonstrates breed-specific differences in incidence of SJD in dogs, which may be of importance for breeders, dog owners and veterinarians., (© 2021 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Objective: While the prevalence of radiographic and symptomatic osteoarthritis (OA) is higher in women, male mice are more frequently used in animal experiments to explore its pathogenesis or drug efficacy. In this study, we examined whether sexual dimorphism affects pain and joint degeneration in destabilization of the medial meniscus (DMM) mouse model., Methods: DMM or sham surgery was performed on the knee of male and female C57BL/6 mice. Joint damage was assessed by safranin O staining and scored using the Osteoarthritis Research Society International (OARSI) scoring system. Von Frey hair, incapacitance, and rotarod tests were conducted to measure joint pain. The analgesic effect of capsazepine (CPZ), a TRPV1 antagonist, was compared between male and female mice., Results: Histology and OARSI scoring analysis showed that cartilage degeneration developed, and progressed in both male and female DMM groups, however, damage was less severe in females at the late stage of OA. Pain behavior, as measured by mechanical allodynia, was displayed for longer in male DMM mice compared to females. Incapacitance data showed that CPZ significantly reduced DMM-induced pain in male mice but not in female mice. Immunofluorescence microscopy analysis demonstrated that DMM surgery increased the expression of TRPV1 in both female and male dorsal root ganglion (DRG). Injection of CPZ significantly suppressed TRPV1 expression in the DRG of male mice only., Conclusion: Joint damage develops comparably in both female and male mice after DMM although it progresses less in females. There was a subtle sex difference in pain behaviors and analgesic efficacy of a TRPV1 antagonist, which was accompanied by a differential regulation of TPRV1., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To compare the Osteoarthritis Research Society International (OARSI) and Articular Cartilage Structure (ACS) grading schemes applied to multiple and single sections, along with additional histologic measures, in two mouse models of Osteoarthritis (OA)., Methods: Six coronal histologic stifle joint sections were collected from 40 C57BL/6J mice, including aged mice with spontaneous OA (approximately 18 months of age; n = 15) and young (12-week-old) mice that either underwent destabilization of the medial meniscus (DMM) surgery (n = 15) or sham surgery (n = 10). Sections were evaluated with the standard OARSI (0-6) scheme, a modified OARSI scheme, the ACS (0-12) scheme, histomorphometry of cartilage and bone, and scoring of osteophytes (0-3) and synovial hyperplasia (0-3). Principal components analysis (PCA) was used to determine the features explaining the greatest variability among the sections., Results: The grading schemes performed similarly when applied to a single mid-coronal section or six total coronal sections per joint. OARSI grading produced similar results when applied to hematoxylin and eosin or toluidine blue-stained sections. Aged mice had higher severity scores in the LTP than DMM mice (mid-coronal OARSI grade aged = 2.3 and DMM = 1.1, p = 0.0006; ACS grade aged = 4.1 and DMM = 1.6, p = 0.0024). PCA resulted in retention of four factors that accounted for 78.4% of the total variance. Factor 1 (36.4%) included the OARSI grade, ACS grade, Toluidine blue grade, articular cartilage area and thickness and the osteophyte grade., Conclusions: Grading of a single mid-coronal section using either the OARSI or ACS schemes combined with osteophyte and histomorphometric measures can consistently define OA severity in mice., (Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective:  The aim of this study was to determine the trochlear sulcus depth of three common brachycephalic breeds at risk of medial patellar luxation., Study Design:  Retrospective blinded clinical study using a previously validated ratio (T/P) of maximal trochlear sulcus depth (T) and maximal patellar craniocaudal thickness (P) measured on computed tomography, to assess trochlear sulcus depth in Pugs, French Bulldogs and English Bulldogs without clinical patellar luxation. The effect of breed on T/P was assessed using one-way linear regression models., Results:  The mean T/P was affected by breed ( p  < 0.001). There was significant difference between Pugs (0.45) and French Bulldogs (0.38) and between Pugs and English Bulldogs (0.4). There was no significant difference between Pugs and previously published data for non-brachycephalic and mixed breed dogs (0.46) ( p  = 0.39). Mean T/P was significantly reduced in the brachycephalic dog breeds combined compared with the previously published data ( p  < 0.001)., Conclusion:  The trochlear sulcus varies by breed and was more shallow in French and English Bulldogs than Pugs, hence a shallow sulcus may be a breed-driven characteristic. The three breeds assessed are at risk of patellar luxation but sulcus depth did not directly correlate with previously published risk factors-the contribution of sulcus depth to the aetiopathogenesis of patellar luxation remains unclear. Trochlear recession to achieve patellar coverage of 50% may be excessive considering maximal breed normal depth., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To report the preoperative evaluation, treatment with transarticular elastic external skeletal fixation (ESF), and outcome of a dog with bilateral medial patellar luxation (MPL) and stifle rotational deformity., Animal: One nonambulatory, 2.5-month-old, 7.5-kg mixed-breed intact female dog., Study Design: Case report METHODS: Complex pelvic limb deformities were assessed with physical examination and computed tomography (CT) and characterized as bilateral grade 4 MPL and 90° internal rotation of the tibia in relation to the femur. Three-dimensional imaging and bone models were used to quantify the deformity and rehearse surgical correction. Transarticular elastic chains between ESF pins in the femur and tibia were used to gradually correct stifle rotational malalignment on each pelvic limb. Soft tissue releases, imbrication, and a transphyseal staple were used to correct the patellar luxation (PL) and femoral varus. The dog was reevaluated for 1 year postoperatively., Results: Short- and long-term management included intensive physical rehabilitation to increase pelvic limb strength and function. Surgical treatment resulted in resolution of the PL and neutral stifle alignment. The dog was able to ambulate with persistent decreased range of motion of the stifle., Conclusion: Transarticular elastic chains and femoral physeal stapling improved the function of a dog with severe bone deformities and PL in a growing dog., (© 2020 American College of Veterinary Surgeons.)

Osteoarthritis (OA) is one of the major causes of chronic pain in dogs. However, the pathogenesis of OA has not been fully understood in dogs. The objective of this study was to comprehensively investigate the mRNA expression levels of proinflammatory cytokines, inflammatory mediators, nerve growth factor and its receptor, and matrix metalloproteinases in the synovium of dogs with spontaneous OA as well as to elucidate their relationships with the severity of synovitis. Dogs that were diagnosed with stifle OA on the basis of radiographic findings were included, and the degree of synovitis was observed using stifle arthroscopy. The dogs were assigned to two different groups depending on their synovitis scores: the low-grade group (score of 1 or 2; n = 8) and high-grade group (score of 3 to 5; n = 18). The dogs showing no evidence of orthopedic disease were included in the control group (n = 6). Synovial tissue samples were collected from the sites at which synovitis scores were assessed using arthroscopy. Total RNA was extracted from the collected synovial tissue, and cDNA was synthesized. Subsequently, RT-qPCR were performed using canine-specific primer sets for IL1B, IL6, CXCL8, TNF, TGFB1, PTGS2, PTGES, MMP3, MMP13, NGF, NTRK1, and PTGER4. Expression levels of IL1B, IL6, CXCL8, and MMP13 were significantly higher in the high-grade group than in the control group. In addition, expression levels of IL1B, CXCL8, TNF, and PTGS2 were significantly higher in the high-grade group than in the low-grade group. Expression levels of IL1B, IL6, CXCL8, TNF, PTGS2, and PTGER4 showed significant positive correlation with synovitis score. In conclusion, all mRNA expression levels in the synovial membrane varied according to the degree of synovitis in dogs with spontaneous OA. Thus, this study may partially elucidate the pathogenesis of synovitis in dogs with spontaneous OA., Competing Interests: No conflict of interest.

Objective: Lipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the formation of prostaglandin D 2 (PGD 2 ), which has important roles in inflammation and cartilage metabolism. We undertook this study to investigate the role of L-PGDS in the pathogenesis of osteoarthritis (OA) using an experimental mouse model., Methods: Experimental OA was induced in wild-type (WT) and L-PGDS-deficient (L-PGDS -/- ) mice (n = 10 per genotype) by destabilization of the medial meniscus (DMM). Cartilage degradation was evaluated by histology. The expression of matrix metalloproteinase 13 (MMP-13) and ADAMTS-5 was assessed by immunohistochemistry. Bone changes were determined by micro-computed tomography. Cartilage explants from L-PGDS -/- and WT mice (n = 6 per genotype) were treated with interleukin-1α (IL-1α) ex vivo in order to evaluate proteoglycan degradation. Moreover, the effect of intraarticular injection of a recombinant adeno-associated virus type 2/5 (rAAV2/5) encoding L-PGDS on OA progression was evaluated in WT mice (n = 9 per group)., Results: Compared to WT mice, L-PGDS -/- mice had exacerbated cartilage degradation and enhanced expression of MMP-13 and ADAMTS-5 (P < 0.05). Furthermore, L-PGDS -/- mice displayed increased synovitis and subchondral bone changes (P < 0.05). Cartilage explants from L-PGDS -/- mice showed enhanced proteoglycan degradation following treatment with IL-1α (P < 0.05). Intraarticular injection of rAAV2/5 encoding L-PGDS attenuated the severity of DMM-induced OA-like changes in WT mice (P < 0.05). The L-PGDS level was increased in OA tissues of WT mice (P < 0.05)., Conclusion: Collectively, these findings suggest a protective role of L-PGDS in OA, and therefore enhancing levels of L-PGDS may constitute a promising therapeutic strategy., (© 2020, American College of Rheumatology.)

Objective: The present study aimed to evaluate the effectiveness of photobiomodulation therapy by light-emitting diode on osteoarthritis treatment in the knees of rats., Design: Twenty male Wistar rats were randomly assigned into two experimental groups: OAC: animals subjected to induction of osteoarthritis, without therapeutic intervention and the group OAL: animals subjected to induction of osteoarthritis treated with light-emitting diode photobiomodulation therapy (850 nm, 200 mW, 6 J)., Results: The results of gait analysis showed no statistical difference between the groups. The histological findings showed that the OAL group presented abnormal chondrocyte orientation, yet with less irregularities along fibrillation and the joint tissue. Thus, it presented a lower degenerative process when evaluated by the Osteoarthritis Research Society International. Likewise, in the immunohistochemical analysis, the OAL group showed higher collagen 2 and transforming growth factor β immunoexpression when compared with the OAC group., Conclusions: Given the above, it is possible to suggest that the photobiomodulation therapy by light-emitting diode had positive effects on the expression of extracellular matrix proteins responsible for synthesis of articular tissue.

Objectives: Pharmacological options for treating osteoarthritis (OA) are limited and alternative treatments are required. Given the clinical data indicating that granulocyte macrophage-colony stimulating factor (GM-CSF) may be a therapeutic target in human OA, we evaluated different treatment regimens with a neutralizing anti-GM-CSF monoclonal antibody (mAb) in an experimental OA model to determine their effectiveness on amelioration of pain and disease., Methods: The collagenase-induced osteoarthritis (CiOA) model was induced in C57BL/6 mice, followed by different treatment regimens of anti-GM-CSF mAb or isotype control. Anti-CCL17 mAb treatment was also administered continually during the late stage of CiOA. Pain-related behavior (change in weight distribution of hind limbs), and disease (cartilage damage and osteophyte size) were assessed., Results: Blocking GM-CSF only during early synovitis in CiOA prevented pain and disease development. Once OA pain was established, regardless of the treatment regimen, anti-GM-CSF mAb treatment rapidly and efficiently ameliorated it; however, unless the treatment was continued, pain returned and disease progressed. Continual late stage blockade of GM-CSF was able to ameliorate pain (between-group difference: -6.567; 95% confidence interval (CI): -10.12, -3.011) and suppress cartilage damage (P = 0.0317, 95% CI: -1.75, -0.0556). Continual late stage blockade of CCL17 showed similar effects on pain and disease development., Conclusions: Early and short-term GM-CSF neutralization is effective at preventing CiOA pain and disease development but, once pain is evident, continual GM-CSF blockade is required to prevent pain from returning and to suppress disease progression in mice. These data reinforce the potential benefits of anti-GM-CSF (and anti-CCL17) mAb therapy in OA and should inform further clinical trials., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Chemokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) have been shown to cause monocyte and natural killer cell chemotaxis and polymorphonuclear cell chemotaxis, respectively. Additionally, MCP-1 signalling has been implicated in modulating pain. Elevated synovial fluid concentrations of MCP-1 and IL-8 have been demonstrated in humans with osteoarthritis, but currently there are no studies evaluating synovial MCP-1 or IL-8 concentrations in dogs. Additionally, there are no canine studies evaluating the correlation between these chemokines and caregiver perceived pain and mobility, as measured by the clinical metrology instrument, Liverpool Osteoarthritis in Dogs. This study documented elevated synovial fluid concentrations of IL-8 and MCP-1 in the stifle of dogs with secondary osteoarthritis compared with normal stifles. However, this study found no correlation between MCP-1 or IL-8 and Liverpool Osteoarthritis in Dogs or radiographic severity of osteoarthritis., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptors (FGFRs) are key regulatory factors in osteoarthritis (OA). HMWTg mice overexpress the high molecular weight FGF2 isoforms (HMWFGF2) in osteoblast lineage and phenocopy both Hyp mice (which overexpress the HMWFGF2 isoforms in osteoblasts and osteocytes) and humans with X-linked hypophosphatemia (XLH). We previously reported that, similar to Hyp mice and XLH subjects who develop OA, HMWTg mice also develop an OA phenotype associated with increased degradative enzymes and increased FGFR1 compared with VectorTg mice. Therefore, in this study, we examined whether in vivo treatment with the FGFR tyrosine kinase inhibitor NVP-BGJ398 (BGJ) would modulate development of the OA phenotype in knee joints of HMWTg mice. VectorTg and HMWTg mice (21 days of age) were treated with vehicle or BGJ for 13 weeks. Micro-computed tomography images revealed irregular shape and thinning of the subchondral bone with decreased trabecular number and thickness within the epiphyses of vehicle-treated HMWTg knees, which was partially rescued following BGJ treatment. Articular cartilage thickness was decreased in vehicle-treated HMWTg mice, and was restored to the cartilage thickness of VectorTg mice in the BGJ-treated HMWTg group. Increased OA degradative enzymes present in HMWTg vehicle-treated joints decreased after BGJ treatment. OA in HMWTg mice was associated with increased Wnt signaling that was rescued by BGJ treatment. This study demonstrates that overexpression of the HMWFGF2 isoforms in preosteoblasts results in osteoarthropathy that can be partially rescued by FGFR inhibitor via reduction in activated Wnt signaling., (© Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Objective: To determine the predictive value of meniscal click for specific meniscal tear morphology., Study Design: Prospective cohort., Animals: Client-owned dogs (104) with cranial cruciate ligament (CCL) deficiency treated with stifle arthroscopy (111)., Methods: All stifles underwent a standardized examination for meniscal click before anesthesia (EBA) and during anesthesia (EDA). Presence or absence of a medial meniscal tear and diagnosis of tear morphology were confirmed with arthroscopic examination., Results: Complete CCL tears were noted in 93 dogs, and incompetent partial tears were noted in 18 dogs. Medial meniscal tears were noted in 40.5% (55/111) of dogs, including bucket handle tears (BHT) in 65.6% (36/55) of tears. Frays of the lateral meniscus were noted in 6.3% of dogs (7/111). Examination for meniscal click before anesthesia was 38% sensitive and 94.5% specific, and EDA was 38% sensitive and 98.2% specific for all meniscal tear morphologies. Positive meniscal click at EBA was associated with a meniscal BHT but not with a meniscal non-BHT (P < .0001 and P = .3515, respectively). Positive meniscal click at EDA was associated with a meniscal BHT but not with a meniscal non-BHT (P < .0001 and P = .1909, respectively)., Conclusion: A meniscal click is more commonly associated with a meniscal BHT than with a non-BHT., Clinical Significance: Meniscal tear morphology influences the presence or absence of meniscal click. Because of the high incidence of meniscal disease, this study provides evidence to support joint exploration in the treatment of CCL disease., (© 2019 The American College of Veterinary Surgeons.)

Insulin-like growth factor-I (IGF-I) is anabolic for cartilage and important for cartilage integrity, which might suggest a connection between IGF-I and osteoarthritis (OA) development. However, the results of studies performed so far are conflicting, and we aimed to clarify the role of endocrine IGF-I in rodent OA. Male mice with inducible inactivation of circulating, liver-derived IGF-I (LI-IGF-I -/- mice, serum IGF-I reduced by ~80%) were used. Experimental OA was induced in young adult LI-IGF-I -/- and control mice by destabilization of the medial meniscus (DMM); age-related OA was also evaluated in 1-yr-old mice. DMM-operated LI-IGF-I -/- mice had thinner lateral subchondral bone plate in tibia compared with control mice, whereas osteophyte volume and articular cartilage damage were unaffected at the medial side of the DMM knee. However, the control mice but not the LI-IGF-I -/- mice also developed mild OA on the lateral side of the DMM knee compared with the unoperated knee. One-year-old LI-IGF-I -/- mice had lower mid-diaphyseal cortical bone area than the 1-yr-old control mice, whereas analyses of joint tissues displayed smaller osteophyte volume and thicker calcified cartilage than the control mice. There was no difference in OA severity in the articular cartilage between old LI-IGF-I -/- and control mice. Our study is the first to investigate whether there is an association between circulating IGF-I and OA in mice. We conclude that, although there is an ~80% reduction of circulating IGF-I and a decrease in cortical bone in male LI-IGF-I -/- mice, cartilage damage is clearly not intensified and may instead be slightly reduced.

Objective: To determine the ability to reduce iatrogenic cartilage injury (IACI) during canine stifle arthroscopy by using a silicone arthroscope cannula guard., Study Design: Ex vivo canine cadaver experimental study., Animals: Paired canine stifles from 14 cadavers (≥20 kg)., Methods: Stifles (N = 28) were assigned to unguarded traditional or silicone-guarded arthroscopy. Stifle arthroscopy and full joint exploration with meniscal probing was performed by a second-year surgery resident (I.C.) in fourteen canine cadavers, alternating between left and right stifles for guarded vs unguarded arthroscopy. After arthroscopy, stifles were disarticulated, and india ink assay was performed to identify IACI. Total IACI number, lesion length and area, duration of procedure, and procedure difficulty score were recorded for each stifle., Results: Unguarded arthroscopy resulted in more total IACI per joint (unguarded 5.2 ± 3.0, guarded 2.4 ± 1.4; P = .02), larger IACI area (unguarded 5.2 ± 4.2 mm 2 , guarded 2.3 ± 1.5 mm 2 ; P = .02), and IACI length (unguarded 13.6 ± 6.9 mm, guarded 8.6 ± 5.9 mm; P = .03). No difference was identified in duration of procedure (unguarded 11.8 ± 5.2 minutes, guarded 13.8 ± 4.3 minutes; P = .79) or procedure difficulty score (unguarded 1.7 ± 0.6, guarded 1.6 ± 0.6 P = .73)., Conclusion: Silicone-guarded arthroscope cannulas decreased IACI number and size during canine cadaveric stifle arthroscopy without increasing duration of procedure or surgical difficulty., Clinical Significance: Silicone-guarded arthroscope cannulas may be safer than traditional cannulas for novice veterinary surgeons performing stifle arthroscopy., (© 2019 The American College of Veterinary Surgeons.)

Purpose: To evaluate if synovial inflammation and hypervascularization are present in a dog model of knee osteoarthritis and can be detected on conventional magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), contrast-enhanced magnetic resonance imaging (CE-MRI), and quantitative digital subtraction angiography (Q-DSA) imaging., Materials and Methods: Six dogs underwent MRI and angiography of both knees before and 12 weeks after right knee anterior cruciate ligament injury. Synovial vascularity was evaluated on CE-MRI, DCE-MRI, and Q-DSA by 2 independent observers. Synovial inflammation and vascularity were histologically scored independently. Cartilage lesions and osteophytes were analyzed macroscopically, and cartilage volumetry was analyzed by MRI. Vascularity and osteoarthritis markers on imaging were compared before and after osteoarthritis generation, and between the osteoarthritis model and the control knee, using linear mixed models accounting for within-dog correlation., Results: In all knees, baseline imaging showed no abnormalities. Control knees did not develop significant osteoarthritis changes, synovial inflammation, or hypervascularization. In osteoarthritis knees, mean synovial enhancement score on CE-MR imaging increased by 13.1 ± 0.59 (P < .0001); mean synovial inflammation variable increased from 47.33 ± 18.61 to 407.97 ± 18.61 on DCE-MR imaging (P < .0001); and area under the curve on Q-DSA increased by 1058.58 ± 199.08 (P = .0043). Synovial inflammation, hypervascularization, and osteophyte formations were present in all osteoarthritis knees. Histology scores showed strong correlation with CE-MR imaging findings (Spearman correlation coefficient [SCC] = 0.742; P = .0002) and Q-DSA findings (SCC = 0.763; P < .0001) and weak correlation with DCE-MR imaging (SCC = -0.345; P = .329). Moderate correlation was found between CE-MR imaging and DSA findings (SCC = 0.536; P = .0004)., Conclusions: In this early-stage knee osteoarthritis dog model, synovial inflammation and hypervascularization were found on imaging and confirmed by histology., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine the effect of the circadian gene Clock on posttranscriptional function and pro-inflammatory mechanisms in osteoarthritis (OA)., Methods: The cartilage from Clock mutant mice was assessed using histology, (OA) score, and real-time polymerase chain reaction (PCR) quantification of key pro-inflammatory genes. Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) translocation, posttranslational state and expression levels during day and night conditions were assessed using immunoblot and IP. The regulation of transcription by Clock in cartilage tissue was assessed by using chromatin immunoprecipitation (ChIP) and luciferase assays. Total acetylation level and pattern over 24 h were quantified using immunoblot and real-time PCR. Finally, the effects of exogenous Clock nanoparticle treatment were quantified by histology and immunoblot., Results: The Clock mutation significantly promoted the degradation of cartilage and the expression of the key pro-inflammatory mediators, IL-1β, IL-6 and MCP-1. The Clock mutation significantly promoted NFκB nuclear translocation. The circadian protein CLOCK positively regulates NFκB at the transcriptional level by binding the E-box domain. The Clock mutation significantly inhibited the total lysine acetylation level in cartilage and inhibited NFκB acetylation at the Lys310 residue but promoted phosphorylation at the Ser276 residue. The forced expression of Clock in vivo inhibited NFκB activation by increasing acetylation and decreasing phosphorylation levels and by decreasing cartilage damage and inflammation., Conclusions: This study demonstrates the mutation of Clock promotes inflammatory activity by mediating the posttranscriptional regulation of NFκB in OA pathogenesis., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine biomechanical effects of knee cartilage defect perimeter morphology based on cartilage strain and opposing subchondral bone contact., Design: Articular cartilage defects were created in 5 bovine femoral condyles: group 1, 45° inner bevel with 8-mm rim; group 2, vertical with 8-mm rim; and group 3, 45° outer bevel with 8-mm base. Samples were placed into a custom-machined micro-computed tomography tube and subjected to 800 N of axial loading. DICOM data were used to calculate cartilage thickness 4 and 6 mm from the center, distance between tibial cartilage surface and femoral subchondral bone, and contact width between tibial cartilage and subchondral bone. Strain 4 mm from the center and both absolute and change in distance (mm) to subchondral bone were compared between groups 1 and 2 using paired t tests. Strain at 6 mm and distance changed, loaded distance, and contact width (mm) were compared between groups using the Friedman test with post hoc analysis using Wilcoxon signed rank test., Results: No significant differences in rim strain were noted between groups 1 and 2 at 4 mm ( P = 0.10) and between groups 1, 2, and 3 at 6 mm ( P = 0.247) from the defect center. The loaded distance was significantly different between groups 1 and 3 ( P = 0.013). No significant change in distance to the subchondral bone was found between groups ( P = 0.156). The difference in subchondral bone contact area approached but did not reach significance ( P = 0.074)., Conclusion: When debriding focal articular cartilage defects, establishment of an inner bevel decreases tissue deformation and contact with opposing subchondral bone.

The suitability of near-infrared spectroscopy (NIRS) for non-destructive measurement of cartilage thickness was compared with the gold standard needle indentation. A combination of NIRS and biomechanical indentation (NIRS-B) was used to address the influence of varying loads routinely applied for hand-guided NIRS during real-life surgery on the accuracy of NIRS-based thickness prediction. NIRS-B was performed under three different loading conditions in 40 osteochondral cylinders from the load-bearing area of the medial and lateral femur condyle of 20 cadaver joints (left stifle joints; female Merino sheep; 6.1 ± 0.6 years, mean ± standard error of the mean). The cartilage thickness measured by needle indentation within the region analyzed by NIRS-B was then compared with cartilage thickness prediction based on NIRS spectral data using partial least squares regression. NIRS-B repeat measurements yielded highly reproducible values concerning force and absorbance. Separate or combined models for the three loading conditions (the latter simulating load-independent measurements) resulted in models with optimized quality parameters (e.g., coefficients of determination R 2 between 92.3 and 94.7) and a prediction accuracy of < 0.1 mm. NIRS appears well suited to determine cartilage thickness (possibly in a hand-guided, load-independent fashion), as shown by high reproducibility in repeat measurements and excellent reliability compared with tissue-destructive needle indentation. This may provide the basis for non-destructive, intra-operative assessment of cartilage status quo and fine-tuning of repair procedures.

Objective: To determine the effect of tibial rotation on radiographic tibial plateau angle (TPA) measurement in normal and cranial cruciate ligament (CrCL)-deficient stifles., Study Design: Cadaveric study., Sample Population: Five pairs of canine cadaver hind limbs with no stifle osteoarthritis., Methods: Mediolateral radiographs of each specimen were obtained at 0°, 10°, 20°, and 30° of internal and external rotation of the tibia with both intact and transected CrCL. Two Kirschner wires were placed at the cranial and caudal landmarks of the tibial plateau, and the 0° views were imaged again, representing the anatomic TPA. Five observers measured the TPA twice on all images. Measurements were compared by using a mixed-model ANOVA. Intraobserver and interobserver variability were evaluated by using the coefficient of variation., Results: Tibial plateau angle did not differ among the anatomic, CrCL-intact, and CrCL-deficient 0° views or between the CrCL-intact and CrCL-deficient views at the various tibial rotations. The only difference detected was between CrCL-intact stifles radiographed at 0° and external rotation (range, 1.16°-1.6°; P = .016, P = .001, and P < .001). Tibial rotation, CrCL transection, and their interaction all failed to influence intraobserver and interobserver variability (P > .05)., Conclusion: In CrCL-deficient stifles, tibial rotation of up to 30° internally and externally did not result in clinically relevant changes in TPA measurements., Clinical Significance: The TPA can be successfully measured with up to 30° of internal and external tibial rotation in CrCL-deficient stifles with no osteoarthritic changes., (© 2019 The American College of Veterinary Surgeons.)

CASE DESCRIPTION A 12-year-old mixed-breed mare (horse 1) and 6-year-old Friesian gelding (horse 2) were examined for chronic lameness associated with the stifle joint. CLINICAL FINDINGS Lameness examination revealed effusion of the right (horse 1) or left (horse 2) femoropatellar and medial femorotibial joints and grade 3/5 (horse 1) or 4/5 (horse 2) lameness. A diagnosis of cranial cruciate ligament (CCL) injury with associated mineralization and avulsion (horse 1) or mineralization alone (horse 2) was facilitated in both horses with a caudomedial-craniolateral oblique radiographic view obtained 45° medial to the caudocranial line, which highlighted the origin of the ligament on the caudoaxial aspect of the lateral femoral condyle within the intercondylar fossa. These lesions were subsequently confirmed via CT. TREATMENT AND OUTCOME Arthroscopy of the medial and lateral femorotibial joints was performed for horse 1 and revealed the osseous fragment associated with the CCL, but the fragment could not be removed. Horse 2 was euthanized while anesthetized following CT owing to the poor prognosis. CONCLUSIONS AND CLINICAL RELEVANCE Radiography is typically the first imaging modality attempted for horses with CCL injury, particularly outside the hospital setting. A 45° caudomedial-craniolateral oblique radiographic view may aid in diagnosis of CCL injury when avulsion or mineralization is present. Although this view is not commonly included in the typical radiographic series for imaging of the stifle joint in horses, it should be considered when CCL injury is suspected.

Objective: To assess the relationship between histologic degeneration of cranial cruciate ligaments (CCLs) and severity of synovitis and ligament vascularity., Sample: CCL and synovium from 59 stifle joints (53 dogs)., Procedures: CCL and synovium specimens were obtained from stifle joints of juvenile (15 joints; 12 dogs) and adult (25 joints; 22 dogs) dogs with intact CCLs and dogs with CCL rupture (rCCL; 19 joints; 19 dogs). Vascular density and degenerative changes of the CCL core region and severity of synovitis were semiquantitatively evaluated. Relationships were analyzed by use of a random effects model to account for correlated specimens., Results: Mean ± SD modified Bonar scores (scale, 0 to 9) of adults (4.85 ± 0.44) and dogs with rCCL (5.69 ± 0.49) were significantly higher than scores of juveniles (1.13 ± 0.55). Vascularity scores (scale, 0 to 3) were significantly higher for juveniles (3.00 ± 0.24) than for adults (1.53 ± 0.27) and dogs with rCCL (0.78 ± 0.23). Synovitis scores were not significantly different among groups. There was a significant negative relationship between modified Bonar scores and vascularity scores for juveniles and adults and for adults and dogs with rCCL when controlling for age, but there was not a significant relationship between modified Bonar scores and synovitis scores. There was a significant relationship between modified Bonar scores and body weight of adults., Conclusions and Clinical Relevance: Poor blood supply to the core region could be an important underlying condition for spontaneous degeneration of the CCL in at-risk dogs.

Knee ligaments and tendons are collagen-rich viscoelastic connective tissues that provide vital mechanical stabilization and support to the knee joint. Deterioration of ligaments has an adverse effect on the health of the knee and can eventually lead to ligament rupture and osteoarthritis. In this study, the feasibility of near infrared spectroscopy (NIRS) was, for the first time, tested for evaluation of ligament and tendon mechanical properties by performing measurements on bovine stifle joint ligament (N = 40) and patellar tendon (N = 10) samples. The mechanical properties of the samples were determined using a uniaxial tensile testing protocol. Partial least squares regression models were then developed to determine if morphological, viscoelastic, and quasi-static properties of the samples could be predicted from the NIR spectra. Best performance of NIRS in predicting mechanical properties was observed for toughness at yield point (median [Formula: see text], median normalized [Formula: see text]), toughness at failure point (median [Formula: see text], median normalized [Formula: see text]), and the ultimate strength of the ligament/tendon (median [Formula: see text], median normalized [Formula: see text]). Thus, we show that NIRS is capable of estimating ligament and tendon biomechanical properties, especially in parameters related to tissue failure. We believe this method could substantially enhance the currently limited arthroscopic evaluation of ligaments and tendons.

Objective: Gene therapy holds great promise for the treatment of osteoarthritis (OA) because a single intraarticular injection can lead to long-term expression of therapeutic proteins within the joint. This study was undertaken to investigate the use of a helper-dependent adenovirus (HDAd)-mediated intraarticular gene therapy approach for long-term expression of interleukin-1 receptor antagonist (IL-1Ra) as sustained symptomatic and disease-modifying therapy for OA., Methods: In mouse models of OA, efficacy of HDAd-IL-1Ra was evaluated by histologic analysis, micro-computed tomography (micro-CT), and hot plate analysis. In a horse OA model, safety and efficacy of HDAd-IL-1Ra were evaluated by blood chemistry, analyses of synovial fluid, synovial membrane, and cartilage, and gross pathology and lameness assessments., Results: In skeletally immature mice, HDAd-IL-1Ra prevented development of cartilage damage, osteophytes, and synovitis. In skeletally immature and mature mice, treatment with HDAd-interleukin-1 receptor antagonist post-OA induction resulted in improved-albeit not significantly-cartilage status assessed histologically and significantly increased cartilage volume, cartilage surface, and bone surface covered by cartilage as assessed by micro-CT. Fewer osteophytes were observed in HDAd-IL-1Ra-treated skeletally immature mice. Synovitis was not affected in skeletally immature or mature mice. HDAd-IL-1Ra protected against disease-induced thermal hyperalgesia in skeletally mature mice. In the horse OA model, HDAd-IL-1Ra therapy significantly improved lameness parameters, indicating efficient symptomatic treatment. Moreover, macroscopically and histologically assessed cartilage and synovial membrane parameters were significantly improved, suggesting disease-modifying efficacy., Conclusion: These data from OA models in small and large animals demonstrated safe symptomatic and disease-modifying treatment with an HDAd-expressing IL-1Ra. Furthermore, this study establishes HDAd as a vector for joint gene therapy., (© 2018, American College of Rheumatology.)

Objective: To determine the influence of methods of joint inspection during tibial plateau leveling osteotomy (TPLO) on radiographic appearance of the patellar tendon., Study Design: Retrospective study., Animals: Client-owned dogs (191) treated with TPLO (199)., Methods: Data collected from medical records included signalment, weight, duration of anesthesia and surgery, preoperative and postoperative tibial plateau angle (TPA), cranial cruciate ligament status, meniscal status, and meniscal treatment. Method of joint inspection was recorded as (1) arthroscopy (AR), (2) craniomedial parapatellar arthrotomy (CrMA), or (3) caudomedial arthrotomy (CdMA). The radiographic thickness of the patellar tendon (PTT) was measured preoperatively and at 8-12 weeks postoperatively. Radiographic signs of patellar tendonitis were graded as 0-2 on the basis of the severity of changes., Results: Thirty-nine dogs (41 stifles) underwent AR, 86 dogs (87 stifles) underwent CrMA, and 70 dogs (71 stifles) underwent CdMA. Durations of surgery (P < .001) and anesthesia (P < .001) were longer when joints were inspected by AR than by arthrotomies. PTT was greater after AR than after CrMA (P = .004) and CdMA (P < .001). The proportion of dogs with grade 1 or grade 2 PTT was greater after AR (78.04%) than after CrMA (52.87%, P = .0065) and CdMA (28.17%, P < .001)., Conclusion: The PTT was thicker 8-12 weeks after TPLO when stifles were inspected arthroscopically rather than via arthrotomies., Clinical Significance: The method of stifle exploration during TPLO influences the postoperative radiographic appearance of the patellar tendon and may contribute to patellar tendinopathy., (© 2018 The American College of Veterinary Surgeons.)

Two related female snow leopards ( Panthera uncia) were diagnosed with osteochondritis dissecans of the lateral femoral condyle via radiographs and computed tomography. Lesions were either bilateral (Patient 1) or unilateral (Patient 2). Surgical treatment was performed using an osteochondral autograft transfer system following cartilage flap removal. After a 6-wk recovery period, both animals had a markedly improved gait with mild pelvic limb stiffness. Patient 1 developed intermittent lameness 9 mo postsurgery and Patient 2 had mild lameness 3 yr postsurgery. Because of recurrent lameness, both animals were treated with platelet-rich plasma intra-articular injections and oral gabapentin (Patient 1) or oral meloxicam (Patient 2). Full incorporation of autografts was confirmed with computed tomography (both patients) and arthroscopy (Patient 1 only). Osteochondritis dissecans has been previously reported in snow leopards and these cases represent the first reported use of osteochondral autograft repair and platelet-rich plasma to treat the condition.