Outcome of surgical correction of medial patellar luxation in dogs weighing less than 10 kg.

BACKGROUND: Various trochleoplasty techniques, including trochlear wedge recession (TWR) and trochlear block recession (TBR), are used to treat dogs with medial patellar luxation (MPL). However, the objective outcomes of these surgical procedures are underreported. METHODS: Medical records were obtained for dogs weighing less than 10 kg that underwent either TWR or TBR and tibial tuberosity transposition to address grade I-III MPL. Long-term (at least 1 year after the last procedure) follow-up included orthopaedic and radiographic examinations, such as osteoarthritis score (OAS), ground reaction force (GRF) analysis and canine brief pain inventory (CBPI). RESULTS: Overall, 20 dogs (26 stifles) were followed up in the long term. Minor postoperative complications, medial patellar reluxation (MPR) and intermittent lameness occurred in 46.15%, 19.23% and 15% of the dogs, respectively. MPR occurred only in TWR-treated stifles, while mean OAS increased in all groups. Using the CBPI, the owners perceived an excellent or very good outcome in 95% of dogs. LIMITATIONS: The limitations of the study include its retrospective observational nature, a lack of randomisation and a small sample size. CONCLUSION: Surgical treatment resulted in a favourable outcome. GRF analysis could detect subtle differences in weight bearing in dogs treated for MPL, which might not be apparent clinically. There might be a higher risk for reluxation for TWR. However, a larger-scale prospective study would be required to find which treatment is superior.

Quantitative sensory testing in canine musculoskeletal pain: Findings from a systematic review, meta-analysis feasibility assessment, and limitations.

Quantitative sensory testing (QST) allows the study of pain mechanisms, patient phenotyping, and response to therapy. The goals of this study were to conduct a systematic review of the use of QST in dogs with musculoskeletal disease including osteoarthritis (OA), and to assess, by means of a meta-analysis, the ability of QST to differentiate affected dogs from healthy controls. The study protocol was registered; three bibliographic databases were screened. Studies involving QST in healthy dogs and those with musculoskeletal disease were included. Data were extracted using a standardized form. Assessment of quality and risk of bias were performed using the CAMARADES critical assessment tool. Twenty-nine articles met the inclusion criteria [systematic review (n = 11); meta-analysis (n = 28)]. In the systematic review, ten studies performed static QST: mechanical [punctate tactile (n = 6); mechanical pressure (n = 5)]; thermal [cold (n = 3); hot (n = 4)]; electrical (n = 1); and one study performed dynamic QST [conditioned pain modulation (n = 1)]. Most studies were of good scientific quality and showed low to moderate risk of bias. A meta-analysis was not possible due to numerous and severe issues of heterogeneity of data among studies. Methods to reduce risk of bias and use of reporting guidelines are some of the most needed improvements in QST research in dogs. Standardization of QST methodology is urgently needed in future studies to allow for data synthesis and a clear understanding of the sensory phenotype of dogs with and without chronic pain including OA.

Pulsed shortwave electromagnetic field therapy increases quality of life in canines with symptoms of osteoarthritics.

BACKGROUND: Joint stiffness, lameness and reduced activity levels are common inflammatory responses observed in canines and have significant impact on quality of life (QOL). The symptoms are often ascribed to osteoarthritis (OA), for which the standard treatment is systemic anti-inflammatories, but pharmacologic intervention can have significant short-term and long-term side effects. OBJECTIVES: Test the efficacy of a Food and Drug Administration (FDA)-cleared pulsed shortwave therapy (PSWT) device as a means to modulate vagus nerve activity and initiate a systemic anti-inflammatory response to determine its ability to improve functionality and the QOL of canines with inflammatory symptoms commonly associated with OA. METHODS: A randomized, double-blinded, placebo-controlled 14-day study of 60 dogs with a presumptive prior diagnosis of OA in at least one limb joint. Two outcomes assessing changes in the dog's QOL and functionality were measured: subjectively determined changes in eight behaviours associated with discomfort and objectively determined changes in passive range of motion (PROM). The device was secured near the cervico-thoracic region of the dog's spine. PROM measures were taken at baseline and at the end of study. Behavioural measures were taken daily. RESULTS: Forty-nine animals completed the study. No negative side effects were reported. Average subjective discomfort scores for the treatment group (N = 26) were reduced from 3.74 to 2.10 (44%), compared to no improvement in the placebo group (N = 23) over the study period (p = 0.0001). Average PROM scores increased by 5.51 (4.59-6.23) degrees relative to the placebo group (p < 0.01). Ninety-six per cent of the treatment group showed either increased PROM or improved behavioural changes or both, compared to 4% for the placebo group (p < 0.01). Most changes occurred within the first 8 days of treatment. CONCLUSIONS: PSWT applied at the level of the cervico-thoracic spine to target the vagus nerve may have the potential to improve QOL in dogs manifesting behaviours commonly associated with OA.

Spatial working memory in a disappearing object task is impaired in female but not male dogs with chronic osteoarthritis.

Chronic pain in humans is associated with impaired working memory but it is not known whether this is the case in long-lived companion animals, such as dogs, who are especially vulnerable to developing age-related chronic pain conditions. Pain-related impairment of cognitive function could have detrimental effects on an animal's ability to engage with its owners and environment or to respond to training or novel situations, which may in turn affect its quality of life. This study compared the performance of 20 dogs with chronic pain from osteoarthritis and 21 healthy control dogs in a disappearing object task of spatial working memory. Female neutered osteoarthritic dogs, but not male neutered osteoarthritic dogs, were found to have lower predicted probabilities of successfully performing the task compared to control dogs of the same sex. In addition, as memory retention interval in the task increased, osteoarthritic dogs showed a steeper decline in working memory performance than control dogs. This suggests that the effects of osteoarthritis, and potentially other pain-related conditions, on cognitive function are more clearly revealed in tasks that present a greater cognitive load. Our finding that chronic pain from osteoarthritis may be associated with impaired working memory in dogs parallels results from studies of human chronic pain disorders. That female dogs may be particularly prone to these effects warrants further investigation.

Prevalence of radiographic appendicular osteoarthritis and associated clinical signs in young dogs.

This study aimed to determine the prevalence of osteoarthritis (OA) and associated clinical signs in young dogs. Owners of dogs aged 8 months-4 years from a single practice, were contacted in random order, to participate in a general health screen. Clinical and orthopedic examinations were performed. Each joint was scored for pain reactions (0-4). Orthogonal radiographs of all joints were made under sedation. Each joint was scored for radiographic OA (rOA) severity on an 11-point scale. Clinical OA (cOA) was defined as an overlap of rOA and joint pain in ≥ 1 joint. Owners completed OA questionnaires. The owners of 123 dogs agreed to participate. Overall, 39.8% (49/123) of dogs had rOA in ≥ 1 joint, and 16.3% (20/123) or 23.6% (29/123) dogs had cOA, depending on the cut-off value of joint pain; moderate (2), or mild (1), respectively. Owners of dogs with cOA observed signs of impairment in approximately 30% of cases. Only 2 dogs with cOA were receiving OA pain management. The most commonly affected joints in descending order of frequency were elbow, hip, tarsus, and stifle. Radiographically visible OA is common in young dogs, and 40-60% of dogs with rOA had cOA. However, OA-pain appears underdiagnosed and undertreated in young dogs.

Comparative study of 1H-NMR metabolomic profile of canine synovial fluid in patients affected by four progressive stages of spontaneous osteoarthritis.

The study aimed to assess the metabolomic profile of the synovial fluid (SF) of dogs affected by spontaneous osteoarthritis (OA) and compare any differences based on disease progression. Sixty client-owned dogs affected by spontaneous OA underwent clinical, radiographic, and cytologic evaluations to confirm the diagnosis. The affected joints were divided into four study groups based on the Kallgreen-Lawrence classification: OA1 (mild), OA2 (moderate), OA3 (severe), and OA4 (extremely severe/deforming). The osteoarthritic joint's SF was subjected to cytologic examination and 1H-NMR analysis. The metabolomic profiles of the study groups' SF samples were statistically compared using one-way ANOVA. Sixty osteoarthritic joints (45 stifles, 10 shoulders and 5 elbows) were included in the study. Fourteen, 28, and 18 joints were included in the OA1, OA2, and OA3 groups, respectively (0 joints in the OA4 group). Metabolomic analysis identified 48 metabolites, five of which were significantly different between study groups: Mannose and betaine were elevated in the OA1 group compared with the OA2 group, and the 2-hydroxyisobutyrate concentration decreased with OA progression; in contrast, isoleucine was less concentrated in mild vs. moderate OA, and lactate increased in severe OA. This study identified different 1H-NMR metabolomic profiles of canine SF in patients with progressive degrees of spontaneous OA, suggesting 1H-NMR metabolomic analysis as a potential alternative method for monitoring OA progression. In addition, the results suggest the therapeutic potentials of the metabolomic pathways that involve mannose, betaine, 2-hydroxyisobutyrate, isoleucine, and lactate.

microRNAs are differentially expressed in equine plasma of horses with osteoarthritis and osteochondritis dissecans versus control horses.

Osteoarthritis (OA) is a leading cause of lameness in horses with no effective disease-modifying treatment and challenging early diagnosis. OA is considered a disease of the joint involving the articular cartilage, subchondral bone, synovial membrane, and ligaments. Osteochondritis dissecans (OCD) is a joint disease consisting of focal defects in the osteochondral unit which may progress to OA later in life. MicroRNAs (miRNAs) have been recognized as small non-coding RNAs that regulate a variety of biological processes and have been detected in biological fluids. MiRNAs are currently investigated for their utility as biomarkers and druggable targets for a variety of diseases. The current study hypothesizes that miRNA profiles can be used to actively monitor joint health and differences in miRNA profiles will be found in healthy vs diseased joints and that differences will be detectable in blood plasma of tested horses. Five horses with OA, OCD, and 4 controls (C) had blood plasma and synovial fluid collected. Total RNA, including miRNA was isolated before generating miRNA libraries from the plasma of the horses. Libraries were sequenced at the Schroeder Arthritis Institute (Toronto). Differential expression analysis was done using DESeq2 and validated using ddPCR. KEGG pathway analysis was done using mirPath v.3 (Diana Tools). 57 differentially expressed miRNAs were identified in OA vs C plasma, 45 differentially expressed miRNAs in OC vs C plasma, and 21 differentially expressed miRNAs in OA vs OCD plasma. Notably, miR-140-5p expression was observed to be elevated in OA synovial fluid suggesting that miR-140-5p may serve as a protective marker early on to attenuate OA progression. KEGG pathway analysis of differentially expressed plasma miRNAs showed relationships with glycan degradation, glycosaminoglycan degradation, and hippo signaling pathway. Interestingly, ddPCR was unable to validate the NGS data suggesting that isomiRs may play an integral role in miRNA expression when assessed using NGS technologies.

A missed opportunity: A scoping review of the effect of sex and age on osteoarthritis using large animal models.

OBJECTIVE: The objective was to critically analyze the published literature accounting for sex differences and skeletal age (open vs. closed physis) in preclinical animal models of OA, including the disaggregation of data by sex and skeletal maturity when data is generated from combined sex and/or multi-aged cohorts without proper confounding. METHOD: A scoping literature review of PubMed, Web of Science, EMBASE, and SCOPUS was performed for studies evaluating the effect of sex and age in experimental studies and clinical trials utilizing preclinical large animal models of OA. RESULTS: A total of 9727 papers were identified in large animal (dog, pig, sheep, goat, horse) models for preclinical OA research, of which 238 ex vivo and/or in vivo studies disclosed model type, animal species, sex, and skeletal age sufficient to analyze their effect on outcomes. Dogs, followed by pigs, sheep, and horses, were the most commonly used models. A paucity of preclinical studies evaluated the effect of sex and age in large animal models of naturally occurring or experimentally induced OA: 26 total studies reported some kind of analysis of the effects of sex or age, with 4 studies discussing the effects of sex only, 11 studies discussing the effects of age only, and 11 studies analyzing both the effects of age and sex. CONCLUSION: Fundamental to translational research, OARSI is uniquely positioned to develop recommendations for conducting preclinical studies using large animal models of OA that consider biological mechanisms linked to sex chromosomes, skeletal age, castration, and gonadal hormones affecting OA pathophysiology and treatment response.

Effect of intra-articular platelet-rich plasma or hyaluronic acid on limb function recovery in dogs with TPLO for cranial cruciate ligament rupture: a randomised controlled trial.

OBJECTIVES: This study aimed to investigate the recovery of limb function following a single intra-articular injection of platelet-rich plasma or hyaluronic acid in dogs with cranial cruciate ligament rupture treated with tibial plateau levelling osteotomy compared to dogs receiving no injection intraoperatively. MATERIALS AND METHODS: Sixty-two dogs with cranial cruciate ligament rupture, body weights of 20 to 40 kg, and no other orthopaedic conditions were enrolled in this prospective, randomised, double-blind, controlled study at the small animal clinic at LMU Munich. All dogs underwent tibial plateau levelling osteotomy. Based on random allocation, they received either a single intra-articular injection of platelet-rich plasma, hyaluronic acid or no injection intraoperatively. Gait analysis, clinical examinations, radiography of the stifle joint for osteoarthritis progression and two validated owner questionnaires were compared among groups at three timepoints postoperatively (6 weeks, 3 and 6 months). Limb function was primarily assessed by measuring the ground reaction forces. RESULTS: At all times postoperatively, no differences were observed among groups regarding clinical examinations, osteoarthritis score values, ground reaction forces or owner questionnaires. All dogs showed significant improvement in limb function clinically, in all ground reaction forces and in the validated questionnaires. Osteoarthritis progressed minimally during rechecks in all dogs regardless of the additional injection or not. CLINICAL SIGNIFICANCE: All dogs treated with tibial plateau levelling osteotomy for cranial cruciate ligament rupture showed improvements in limb function. No additive effect on faster recovery was demonstrated with the additional intra-articular injection of platelet-rich plasma or hyaluronic acid. Addition of platelet-rich plasma/hyaluronic acid injections during tibial plateau levelling osteotomy is unnecessary considering the lack of benefit observed up to 6 months postoperatively.

Magnetic collars improve owner-reported pain scores in dogs with osteoarthritis in a blinded crossover study.

OBJECTIVE: To investigate changes in owner-reported pain, interference of pain on function, and quality of life (QOL) in dogs with clinically suspected osteoarthritis when wearing a collar containing a static magnet. ANIMALS: 16 dogs over 5 years old weighing between 10 and 40 kg with a clinical diagnosis of osteoarthritis and on stable treatment. METHODS: A prospective, blinded crossover study in which dogs wore a collar containing a static magnet or placebo for two 4-week study arms separated by a 2-week washout period. Clients completed the Canine Brief Pain Inventory prior to collar placement and then weekly throughout each arm. Changes in QOL, pain severity, and pain interference scores from the beginning to the end of these arms and changes between the arms were calculated and analyzed using Wilcoxon signed rank tests. RESULTS: 40% of included dogs were on stable doses of NSAIDs. The pain severity scores (PSS), pain interference scores (PIS), and QOL scores were not significantly different at the start of the arms. There was no significant change in PSS or PIS from the start to end of the placebo arms (median changes, 0 and -0.1). Both PSS and PIS reduced significantly during the magnet arms (median changes, -1.0 and -1.2, respectively). The QOL scores did not change significantly in either arm (median changes, 0 and 0). CLINICAL RELEVANCE: This preliminary study suggests that magnetic collars reduce owner-reported pain severity and pain interference on function in dogs with clinically suspected osteoarthritis, and further, larger investigations are now warranted.

Evaluation of subchondral bone cysts in canine elbows with radiographic osteoarthritis secondary to elbow dysplasia.

OBJECTIVE: To investigate whether subchondral bone cysts (SBCs) were present in dogs with radiographic elbow osteoarthritis (OA) and to investigate their relationship with radiographic OA severity. STUDY DESIGN: Retrospective cross-sectional study. SAMPLE POPULATION: Thirty-eight Labrador retrievers (total of 76 elbows). METHODS: Elbow computed tomography (CT) images of 18 young (≤2 years old) and 20 old (>2 years old) Labrador retrievers, which presented for elbow-associated lameness, were reviewed. Radiographic elbow OA was graded into four groups based on the largest osteophyte size on CT. The presence, number, and maximum diameter of SBCs were determined. RESULTS: Subchondral bone cysts were only identified in elbows with osteophytic new bone formation. The number and size of SBCs were associated with radiographic OA severity (p < .001 and p = .041 respectively). Specifically, the rate at which SBCs were present increased for both moderate and severe OA in comparison with the mild OA (moderate OA RR = 2.46, 95% CI 2.08-2.92, p < .001; severe OA RR = 5.60, 95% CI 4.79-6.55, p < .001). For dogs with severe OA, there was an increased likelihood that their SBCs were larger than SBCs from dogs with mild OA (OR = 1.056, 95% CI 1.012-1.101, p = .012). No SBCs were observed in elbows without radiographic evidence of OA. CONCLUSION: Subchondral bone cysts were identified as a feature of radiographic elbow osteoarthritis in Labrador retrievers, and their number and size were indicative of the presence and severity of radiographic elbow OA. CLINICAL SIGNIFICANCE: Subchondral bone cysts are a potential imaging biomarker for quantitative assessment for canine OA.

Quantifying the Stress in Stress Radiographs to Determine Sufficient Laxity of the Coxofemoral Joint: A Canine Hip Dysplasia Cadaveric Study.

OBJECTIVE: While it has been known for a long time that laxity in the hip joint is the primary cause of degenerative changes later on in canine hip dysplasia, limited data are available on the fundamental characteristics that define the procedure used to quantify this. The aim of this study was to evaluate the force-laxity relation to assess the repeatability of repeated cycles of stress on the hip joint and determine the force necessary tomeasure a sufficient proportion of laxity present in hip joints. MATERIALS AND METHODS: Thirty-four canine cadavers underwent a radiographic protocol including stress radiographs with increasing force using the Vezzoni modified Badertscher distension measuring device (VMBDmD). Three dogs underwent five repeat examinations. The laxity index (LI) and osteoarthritis were scored. RESULTS AND CONCLUSION: The curves and the maximal LI (LImax) were not significantly influenced by osteoarthritis, weight, gender, and side. The position of the VMBDmD influenced the curve but not the LImax. The force-laxity curve itself and the LImax were repeatable, which indicated that it did not cause permanent damage to the joint and also confirmed the practicability of the procedure. Ninety percent of hip joints reached sufficient laxity at a force of 95.32 N, which is realistically achievable. Further studies are necessary before extrapolating these results to patients and to further enlighten the biomechanics of stress radiographs.

Therapeutic applications of canine platelets and their derivatives: a narrative review.

Platelets contain a multitude of growth factors and play a crucial role in physiological processes such as thrombogenesis, tissue repair, and angiogenesis. As a result, platelet-derived products have significant potential for efficient utilization in the realm of regenerative medicine due to their therapeutic and biological attributes. Numerous studies have already substantiated the therapeutic viability of platelets in various canine ailments. The existing literature indicates a substantial surge in the clinical application of canine platelets, positioning platelet-derived products as a viable alternative to conventional therapeutic agents. Platelet concentrates, including platelet-rich plasma and platelet-rich fibrin are commonly used as a therapeutic modality in clinical cases. These therapeutic derivatives exhibit effectiveness in tissue regeneration and can serve as complementary therapies. Notably, they offer a cost-effective and easily accessible therapeutic option, which has demonstrated its benefits in chronic inflammatory disorders such as osteoarthritis and tendinitis, ophthalmic conditions, wound healing, and mandibular injuries in canine patients. The broad spectrum of therapeutic effects displayed by platelets is providing researchers with novel perspectives for crafting therapeutic models in future investigations. This review centers on exploring the therapeutic potential of canine platelets across diverse disorders. Further exploration into platelet products, encompassing their preparation and applicability in canine medicine, is imperative. These inquiries hold the promise of unveiling fresh horizons for the domain of regenerative medicine.

Current evidence for non-pharmaceutical, non-surgical treatments of canine osteoarthritis.

Osteoarthritis is a progressive degenerative disease process that affects a significant proportion of the canine population, impacting these animals' quality of life. Currently, there is no cure and treatment consists of managing the clinical signs of pain and reduced mobility. There are many treatments for canine osteoarthritis and in this review we discuss the evidence base behind non-pharmaceutical, non-surgical treatments of this disease. These treatments include weight management, nutraceuticals, acupuncture, physiotherapies such as therapeutic exercise, hydrotherapy as well as other therapeutic modalities including photobiomodulation therapy, electromagnetic field therapy and others.

GenPup-M: A novel validated owner-reported clinical metrology instrument for detecting early mobility changes in dogs.

OBJECTIVE: To use a previously validated veterinary clinical examination sheet, Liverpool Osteoarthritis in Dogs (LOAD) questionnaire, combined with kinetic and kinematic gait analysis in dogs with/without mobility problems to demonstrate the capacity of a novel clinical metrology instrument ("GenPup-M") to detect canine mobility impairments. DESIGN: Quantitative study. ANIMALS: 62 dogs (31 with mobility impairments and 31 without mobility impairments). PROCEDURE: The dogs' clinical history was obtained from owners and all dogs underwent a validated orthopaedic clinical examination. Mobility impairments were diagnosed in the mobility impaired group based on clinical history and orthopaedic examination. Owners were asked to complete GenPup-M along with a previously validated mobility questionnaire (Liverpool Osteoarthritis in Dogs (LOAD)) to identify construct validity. As a test of criterion validity, the correlation between instrument scores and the overall clinical examination scores, along with force-platform obtained peak vertical forces (PVF) were calculated. GenPup-M underwent internal consistency and factor analysis. Spatiotemporal parameters were calculated for dogs with/without mobility impairments to define the gait differences between these two groups. RESULTS: Principal Component Analysis identified GenPup-M had two components with Eigenvalues >1 ("stiffness/ease of movement" and "willingness to be active/exercise"). Cronbach's α was used to test internal consistency of GenPup-M and was found to be "good" (0.87). There was a strong, positive correlation between GenPup-M and LOAD responses (r2 = 0.69, p<0.001) highlighting construct validity. Criterion validity was also shown when comparing GenPup-M to clinical examination scores (r2 = 0.74, p<0.001) and PVF (r2 = 0.43, p<0.001). Quantitative canine gait analysis showed that there were statistically significant differences between peak vertical forces (PVF) of mobility impaired and non-mobility impaired dogs (p<0.05). Analyses of PVF showed that non-mobility impaired dogs more evenly distributed their weight across all thoracic and pelvic limbs when compared to mobility impaired dogs. There were also consistent findings that mobility impaired dogs moved slower than non-mobility impaired dogs. CONCLUSION AND CLINICAL RELEVANCE: GenPup-M is a clinical metrology instrument (CMI) that can be completed by dog owners to detect all mobility impairments, including those that are early in onset, indicating the versatility of GenPup-M to assess dogs with and without mobility impairments. Results of the study found that GenPup-M positively correlated with all three objective measures of canine mobility and consequently showed criterion and construct validity. Owner-reported CMIs such as GenPup-M allow non-invasive scoring systems which veterinary surgeons and owners can use to allow communication and longitudinal assessment of a dog's mobility. It is anticipated that GenPup-M will be used by owners at yearly vaccinations/health checks, allowing identification of any subtle mobility changes, and enabling early intervention.

Evaluation of the hoof centre-of-pressure path in horses affected by chronic osteoarthritic pain.

INTRODUCTION: The Centre of Pressure (COP) is the single point summarising all forces transferred to the hoof during the stance phase of a stride. COP path (COPp) is the trajectory that COP follows from footstrike to lift-off. Aim of the present study was to characterize the COP and COPp in horses affected by osteoarthritis and chronic lameness. MATERIALS AND METHODS: Seventeen adult horses with a diagnosis of osteoarthritis and single limb chronic lameness were recruited. The COP was recorded using a wireless pressure measuring system (TekScan®) with sensors taped to the hooves (either fore- or hind limb, depending on lameness location). The COPp coordinates were further processed. Procrustes analysis was performed to assess the variability of single strides COPp and average COPp among strides, gaits, and limbs by calculating Procrustes distances (D-values). A linear mixed-effects model was run to analyse D-values differences for lame and sound limbs. Additionally, average COPp D-values and COPp hoofprint shape indices were compared for lame and sound limbs with the Signed Rank Test. RESULTS: At walk and trot the single-stride COPp D-values were significantly lower in lame than in sound limbs (marginal effects p<0.001). Analysis of the average COPp D-values confirmed that each hoof COPp is highly consistent with itself over subsequent trials but is different from the contralateral. COPp and hoofprint shape indices did not differ between sound and lame limbs. Footstrike and lift-off within the hoofprint showed that most horses had lateral footstrike and lift-off, independently of the lameness location. CONCLUSION: Our findings are in line with previous observations that COPp are highly repetitive and characteristic for each horse and limb. There seems to be a further decrease in COPp variability in the presence of a painful limb pathology.

Pro-Inflammatory Cytokine Priming and Purification Method Modulate the Impact of Exosomes Derived from Equine Bone Marrow Mesenchymal Stromal Cells on Equine Articular Chondrocytes.

Osteoarthritis (OA) is a widespread osteoarticular pathology characterized by progressive hyaline cartilage degradation, exposing horses to impaired well-being, premature career termination, alongside substantial financial losses for horse owners. Among the new therapeutic strategies for OA, using mesenchymal stromal cell (MSC)-derived exosomes (MSC-exos) appears to be a promising option for conveying MSC therapeutic potential, yet avoiding the limitations inherent to cell therapy. Here, we first purified and characterized exosomes from MSCs by membrane affinity capture (MAC) and size-exclusion chromatography (SEC). We showed that intact MSC-exos are indeed internalized by equine articular chondrocytes (eACs), and then evaluated their functionality on cartilaginous organoids. Compared to SEC, mRNA and protein expression profiles revealed that MAC-exos induced a greater improvement of eAC-neosynthesized hyaline-like matrix by modulating collagen levels, increasing PCNA, and decreasing Htra1 synthesis. However, because the MAC elution buffer induced unexpected effects on eACs, an ultrafiltration step was included to the isolation protocol. Finally, exosomes from MSCs primed with equine pro-inflammatory cytokines (IL-1ß, TNF-α, or IFN-γ) further improved the eAC hyaline-like phenotype, particularly IL-1ß and TNF-α. Altogether, these findings indicate the importance of the exosome purification method and further demonstrate the potential of pro-inflammatory priming in the enhancement of the therapeutic value of MSC-exos for equine OA treatment.

A prospective, randomized, double-blind, placebo-controlled multisite, parallel-group field study in dogs with osteoarthritis conducted in the United States of America evaluating bedinvetmab, a canine anti-nerve growth factor monoclonal antibody.

OBJECTIVE: Bedinvetmab, a fully canine anti-nerve growth factor monoclonal antibody, was evaluated in dogs for control of osteoarthritis-related pain in a study conducted to support registration in the USA. STUDY DESIGN: Randomized, double-blind, placebo-controlled, multicenter, parallel-group study. ANIMALS: General practice client-owned dogs with osteoarthritis (n = 272). METHODS: Dogs were block randomized 1:1 to placebo (saline, n = 137) or bedinvetmab (n = 135; 0.5-1.0 mg kg-1) administered subcutaneously, once monthly. The primary end point, day 28 Canine Brief Pain Inventory (CBPI) treatment success (TS), required pain severity score (PSS; 0-10) decrease ≥1 and pain interference score (PIS; 0-10) decrease ≥ 2. CBPI TS rates [and number needed to treat (NNT)], change in scores [and standardized effect size (ES)], change in quality of life (QoL) and bedinvetmab half-life were calculated. RESULTS: Significant (p < 0.05) improvement with bedinvetmab over placebo occurred (days 28, 42, 56, 84) for CBPI TS. Of cases evaluable for day 28 CBPI TS (placebo, n = 131; bedinvetmab, n = 128), success rates were 36.6% and 47.4%, respectively (p = 0.0410) (NNT, 9.3; PSS and PIS ES, 0.3). CBPI TS increased after the second dose in both groups, plateaued for bedinvetmab at day 42 and decreased for placebo beginning day 84. Day 84 NNT (4.3), PSS (0.4) and PIS (0.5) showed continued improvement with monthly dosing. After the first dose, mean (± standard deviation) bedinvetmab half-life was 19.1 (8.3) days. Adverse events were similar between groups and not considered treatment-related. There was a significant effect of bedinvetmab versus placebo on all CBPI components (PIS, PSS, QoL). CONCLUSIONS AND CLINICAL RELEVANCE: These results corroborated those previously reported and provide further support of safety and effectiveness of bedinvetmab (0.5-1.0 mg kg-1) administered subcutaneously at monthly intervals to dogs for control of osteoarthritis-related pain.

Equine Bone Marrow Aspirate Concentrate.

Bone marrow concentrate is generated by centrifugation of bone marrow aspirate. It contains mesenchymal stromal cells, anabolic chemokines/cytokines, and supraphysiological concentrations of interleukin-1 receptor antagonist protein (IL-1RA). It is an effective treatment for osteoarthritis or desmitis, or as an adjunct in surgery to enhance bone or cartilage repair.

An update on mobility assessment of dogs with musculoskeletal disease.

Mobility impairments associated with musculoskeletal diseases, such as osteoarthritis and degenerative joint disease, affect approximately 200,000 dogs annually and pose a notable challenge to canine health and welfare. Osteoarthritis causes the remodelling of synovial joints, alongside inflammation and impaired mechanical function which can be extremely debilitating. Secondary osteoarthritis commonly affects dogs and can be exacerbated by previous joint abnormalities, such as patellar luxation or cranial cruciate ligament rupture. Although musculoskeletal diseases can affect dogs of any age, the early subtle signs of gait abnormalities are perhaps missed by owners, thus, dogs may be in the latter stages of osteoarthritis progression when they are presented to veterinarians. Dogs showing subtle signs of gait abnormalities must be presented to veterinary practices for acute diagnosis to prevent long-term deterioration. Musculoskeletal diseases, such as osteoarthritis and degenerative joint disease, are commonly diagnosed via visible radiographic changes. However, veterinarians can use a combination of subjective and objective clinical scoring systems, such as clinical metrology instruments and gait assessment in conjunction with radiography to aid their diagnosis and longitudinal monitoring of musculoskeletal diseases. These scoring systems may be more sensitive to earlier signs of mobility impairments in dogs, ultimately, promoting increased canine health and welfare by enabling pain reduction, improvement of muscle strength and preservation of joint function. Current canine mobility scoring systems available to veterinarians will be discussed in turn throughout this review for implementation into clinical practice.