Gut Microbiome and Osteoarthritis: Insights From the Naturally Occurring Canine Model of Osteoarthritis.

OBJECTIVE: The purpose of this study was to enhance the current knowledge of the relationship between the gut microbiome and osteoarthritis (OA) and associated pain using pet dogs as a clinically relevant translational model. METHODS: Fecal samples were collected from 93 owned pet dogs. Dogs were designated as either clinically healthy or OA pain using validated methods. Metagenomic profiling was performed through shotgun sequencing using the Illumina NovaSeq platform. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance. Comparisons between healthy and OA-pain groups were performed individually for each taxa using nonparametric tests following Benjamini and Hochberg adjustment for multiple comparisons. Permutation analysis of variance was performed using Bray-Curtis distance matrices. All downstream analyses were completed in R. RESULTS: No significant differences between healthy and OA-pain dogs were observed for alpha and beta diversity. We found 13 taxa with nominally significant (P < 0.05) associations with OA case status, but none of the associations remained significant after adjustment for multiple comparisons. No differences in alpha or beta diversities or the Firmicutes to Bacteroidetes ratio were found regarding pain severity, mobility or activity level, age, or body composition score. CONCLUSION: Similar to recent studies in humans, the present study did not demonstrate a significant difference in the fecal microbial communities between dogs with OA pain and healthy control dogs. Future research in this naturally occurring model should expand on these data and relate the gut microbiome to gut permeability and circulating proinflammatory and anti-inflammatory molecules to better understand the influence of the gut microbiome on OA and OA pain.

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.

Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.

Bone injuries such as fractures are one major cause of morbidities worldwide. A considerable number of fractures suffer from delayed healing, and the unresolved acute pain may transition to chronic and maladaptive pain. Current management of pain involves treatment with NSAIDs and opioids with substantial adverse effects. Herein, we tested the hypothesis that the purine molecule, adenosine, can simultaneously alleviate pain and promote healing in a mouse model of tibial fracture by targeting distinctive adenosine receptor subtypes in different cell populations. To achieve this, a biomaterial-assisted delivery of adenosine is utilized to localize and prolong its therapeutic effect at the injury site. The results demonstrate that local delivery of adenosine inhibited the nociceptive activity of peripheral neurons through activation of adenosine A1 receptor (ADORA1) and mitigated pain as demonstrated by weight bearing and open field movement tests. Concurrently, local delivery of adenosine at the fracture site promoted osteogenic differentiation of mesenchymal stromal cells through adenosine A2B receptor (ADORA2B) resulting in improved bone healing as shown by histological analyses and microCT imaging. This study demonstrates the dual role of adenosine and its material-assisted local delivery as a feasible therapeutic approach to treat bone trauma and associated pain.

Veterinary education and experience shape beliefs about dog breeds Part 1: Pain sensitivity.

Over 95% of veterinarians report believing that dog breeds differ in pain sensitivity. Ratings made by veterinarians differ from those of the general public, suggesting these beliefs may be learned during veterinary training or clinical experiences. Therefore, the current study's primary objective was to evaluate dog breed pain sensitivity ratings during veterinary training and compare these ratings to those of the general public and undergraduates in animal-health related fields. Using an online survey, members of the general public, undergraduates, veterinary students across all four years, and veterinary faculty and staff rated pain sensitivity of 10 different dog breeds, identified only by their pictures. Compared to the general public and undergraduates, veterinary students rated pain sensitivity across breeds of dog more similarly to veterinary faculty and staff. Further, when undergraduates had clinical experience, they also rated certain dog breeds in a similar way to the veterinary students and professionals. Our findings suggest that veterinary education and clinical experiences influence pain sensitivity ratings across dog breeds. Future research should identify how these pain sensitivity beliefs are communicated and whether these beliefs affect recognition and treatment of pain by veterinarians.

Veterinary education and experience shape beliefs about dog breeds. Part 2: Trust.

Dog breed stereotypes are frequently used to inform people's expectations about canine behavior, despite evidence that breed is largely uninformative in predicting individual dog behavior. Further, these beliefs differ among populations. However, it remains unknown how ratings of warmth toward a breed are associated with ratings of other social behavioral domains, and whether differences exist between populations with varying experience with dogs. The purpose of this study was to evaluate ratings of trust and warmth among survey respondents including veterinary students, veterinary faculty and staff, undergraduates in animal-health related majors and members of the general public. Using an online survey, respondents rated their likelihood to trust a dog in varying scenarios for 10 different dog breeds. Additionally, respondents used a feelings thermometer to rate how warm or cool they felt towards each breed. Findings revealed differences in feelings thermometer and trust ratings across populations. All ratings were lower among the veterinary academic respondents compared to the general public and undergraduates. Veterinary students further along in their training, as well as undergraduates with clinical experience, reflected perceptions similar to those of the veterinary faculty and staff providing support for cultural transmission of beliefs during veterinary education and training.

Corrigendum: Study of the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the treatment of dogs with hip osteoarthritis: a prospective, block-randomized, double-blinded, placebo-controlled clinical trial.

[This corrects the article DOI: 10.3389/fvets.2023.1033188.].

COAST Development Group's international consensus guidelines for the treatment of canine osteoarthritis.

This report describes consensus guidelines and recommendations for the treatment of canine osteoarthritis (OA) according to the "Canine OsteoArthritis Staging Tool excluding radiography" (COASTeR) stage of OA, by the COAST Development Group. The recommendations are based on evidence-based medicine and clinical experience and are proposed with international relevance in mind. The aim is to provide veterinarians with a practical reference to consolidated information and to support the development of patient-specific OA management protocols and informed treatment choices based on the stage of OA.

Pain sensitivity differs between dog breeds but not in the way veterinarians believe.

Background: Veterinarians hold distinct breed-specific pain sensitivity beliefs that differ from the general public but are highly consistent with one another. This is remarkable as there is no current scientific evidence for biological differences in pain sensitivity across dog breeds. Therefore, the present study evaluated whether pain sensitivity thresholds differ across a set of dog breeds and, if so, whether veterinarians' pain sensitivity ratings explain these differences or whether these ratings are attributed to behavioral characteristics. Methods: Pain sensitivity thresholds [using quantitative sensory testing (QST) methods] and canine behaviors (using owner questionnaires and emotional reactivity tests) were prospectively measured across selected dog breeds. Adult, healthy dogs from 10 dog breeds/breed types were recruited, representing breeds subjectively rated by veterinarians as high (chihuahua, German shepherd, Maltese, Siberian husky), average (border collie, Boston terrier, Jack Russell terrier), or low (golden retriever, pitbull, Labrador retriever) pain sensitivity. A final sample of 149 dogs was included in statistical analyses. Results: Veterinarians' pain sensitivity ratings provided a minimal explanation for pain sensitivity thresholds measured using QST in dogs; however, dog breeds did differ in their pain sensitivity thresholds across the QST methods evaluated. Breed differences were observed for some aspects of emotional reactivity tests; however, these behavioral differences did not explain the differences in pain sensitivity thresholds found. Veterinarians' pain sensitivity ratings were positively associated with dog approach scores for the disgruntled stranger test suggesting that the way dogs greet strangers may be a factor influencing veterinarians' ratings of pain sensitivity across dog breeds. Conclusions and clinical relevance: Overall, these findings highlight a need to investigate biological mechanisms that may explain breed differences in pain sensitivity because this may inform pain management recommendations. Further, future research should focus on when and how these breed-specific pain sensitivity beliefs developed in veterinarians, as veterinarians' beliefs could impact the recognition and treatment of pain for canine patients.

Acute radiotherapy-associated oral pain may promote tumor growth at distant sites.

Introduction: Patients developing acute radiotherapy induced dermatitis or oral mucositis commonly experience pain. When severe, this radiotherapy-associated pain (RAP) can necessitate treatment breaks; unfortunately, in a variety of cancers, prolongation of the radiotherapy course has been associated with early cancer relapse and/or death. This is often attributed to accelerated repopulation, but it is unknown whether pain or pain signaling constituents might alter tumor behavior and hasten metastatic disease progression. We studied this by testing the hypothesis that severe acute RAP at one site can hasten tumor growth at a distant site. Methods: Mice underwent single fraction tongue irradiation (27 Gy, or 0 Gy "sham" control) to induce severe glossitis. At the time of maximal oral RAP, one of three luciferase-transfected tumor cell lines were injected via tail vein (4T1, B16F10, MOC2; each paired to their syngeneic host: BALB/c or C57BL/6); tumor burden was assessed via in vivo transthoracic bioluminescence imaging and ex vivo pulmonary nodule quantification. Survival was compared using Kaplan-Meier statistics. Results: Tongue irradiation and resultant RAP promoted lung tumor growth of 4T1-Luc2 cells in BALB/c mice. This effect was not a result of off-target radiation, nor an artefact of environmental stress caused by standard (subthermoneutral) housing temperatures. RAP did not affect the growth of B16F10-Luc2 cells, however, C57BL/6 mice undergoing tail vein injection of MOC2-Luc2 cells at the time of maximal RAP experienced early lung tumor-attributable death. Lung tumor growth was normalized when RAP was reduced by treatment with resiniferatoxin (300 µg/kg, subcutaneously, once). Discussion: This research points towards radiation-induced activation of capsaicin-responsive (TRPV1) neurons as the cause for accelerated growth of tumors at distant (unirradiated) sites.

Activity patterns are associated with fractional lifespan, memory, and gait speed in aged dogs.

Maintaining an active lifestyle is considered a hallmark of successful aging. Physical activity significantly reduces the risk of cognitive decline and Alzheimer's disease in humans. However, pain and lack of motivation are important barriers to exercise. Dogs are a remarkable model for translational studies in aging and cognition as they are prone to Canine Cognitive Dysfunction syndrome, which has many similarities with Alzheimer's disease. According to owner reports, changes in activity levels are characteristic of this syndrome, with decreased daytime activity, but also excessive pacing, especially at sleep time. We used physical activity monitors to record the activity of 27 senior dogs and evaluated the association between activity level and age, fractional lifespan, cognitive status measured by an owner questionnaire and cognitive tests. We also assessed the relationship between activity and joint/spinal pain, and the off/on leash gait speed ratio (a potential marker of gait speed reserve and motivation). We found that activity patterns in dogs are associated with fractional lifespan and working memory. Additionally, dogs with higher on/off leash gait speed are more active in the afternoon of weekdays. These results encourage future studies evaluating how physical activity can improve or delay cognitive impairment in senior dogs.

Study of the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the treatment of dogs with hip osteoarthritis: A prospective, block-randomized, double-blinded, placebo-controlled clinical trial.

Introduction: Glucosamine hydrochloride and chondroitin sulfate are commonly used in dogs with OA, but evidence around efficacy is mixed. This study evaluated the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the alleviation of canine hip OA pain. This was a prospective, block-randomized, double-blinded, placebo-controlled clinical trial. Methods: Seventy-five owned pet dogs with hip OA were assigned randomly into five treatment groups: PCSO-524, Glucosamine and chondroitin sulfate, EAB-277, carprofen, and Placebo (sunflower oil). Peak vertical force (PVF) and subjective orthopedic assessment scores (OAS) were evaluated before treatment (week 0), and at weeks 2, 4, and 6 during treatment. Results: At week 2, the carprofen group showed a significant increase in PVF (3.14 ± 5.33; mean ± SD). After 4 weeks, the increases in PVF of the PCSO-524 (3.90 ± 3.52), EAB-277 (4.17 ± 4.94), and carprofen (3.08 ± 5.87) groups were significant, and significantly greater than placebo (0.08 ± 1.90) and glucosamine (-0.05 ± 6.34) groups. After 6 weeks, the change of PVF in the PCSO-524 (4.14 ± 4.65), EAB-277 (4.45 ± 4.23), and carprofen (4.21 ± 6.52) groups were significant and significantly higher than the placebo group (-0.33 ± 3.65). The change in PVF in the glucosamine group (1.08 ± 5.49) lay between the placebo group and the other treatment groups. The OAS did not show any significant change in any group. Discussion: PCSO-524 and EAB-277, but not glucosamine/chondroitin, resulted in significant improvements in PVF from baseline after 4 weeks, and 6 weeks, and to a similar degree to that seen with carprofen.

Minimal clinically-important differences for the 'Liverpool Osteoarthritis in Dogs' (LOAD) and the 'Canine Orthopedic Index' (COI) client-reported outcomes measures.

Client-reported outcomes measures (CROMs) have been previously validated for the evaluation of canine osteoarthritis. A published systematic review indicated that the 'Liverpool Osteoarthritis in Dogs' (LOAD) and the 'Canine Orthopedic Index' (COI) can be recommended for use in dogs with osteoarthritis; these CROMs have also been used in the context of measuring surgical outcomes of dogs with orthopaedic conditions. However, the minimal clinically-important differences (MCIDs) for these CROMs have not been investigated. Such estimates would be useful for investigators and regulators so that these CROMs can be used in clinical trials. Data from the RCVS Knowledge Canine Cruciate Registry were extracted, and baseline and 6 week follow-up data on dogs that had received surgery for cranial cruciate ligament rupture were used to make estimates of MCIDs using distribution-based and anchor-based methods. Data from 125 dogs were categorised based on the anchor question and LOAD and COI scores analysed accordingly. The four anchor-based methods provided a range of MCIDs for each CROM (1 to 8.8 for LOAD and 3.5 to 17.6 for COI). In the two different distribution-based methods, the MCIDs for LOAD ranged from 1.5 (effect size) to 2.4 (standard error of measurement) and the effect size method yielded a result of 2.2 for COI. The results showed that the value of the MCIDs depended on the method that was applied. Receiver operator characteristic curves provided areas under the curve (AUCs) greater than 0.7, which indicated that the cut-off point was acceptable; LOAD had the greater AUC at 0.867. In summary, the authors currently recommend a MCID of '4' for LOAD and '14' for COI although further work in other clinical contexts (such as osteoarthritis associated with chronic pain) is required to add confidence to these estimates. For the first time, we have provided estimates for MCIDs for these two CROMs which will facilitate sample size estimates in future clinical studies that use these CROMs as outcomes measures.

Nine-axis inertial measurement unit output discriminates activities of varying intensity in the dog.

OBJECTIVE: To explore relationships between 9-axis inertial measurement unit (IMU) output and activities of varying intensity in dogs of various sizes. ANIMALS: 20 healthy, agility course-trained dogs of various ages and sizes. PROCEDURES: Height, weight, body condition score, age, length from IMU to the ischium, and height of IMU to the floor were recorded. Dogs performed a series of activities (rest, walk, trot, and agility course) while wearing the IMU device. IMU and video output were reviewed by independent investigators. Correlations and multiple regression models were used to explore relationships between independent variables and IMU output. RESULTS: Calibration demonstrated excellent correlation and concordance between IMUs (intraclass correlation > 0.9) and that the IMUs reliably measured a known acceleration (gravity at rest). Resultant vector magnitude {sqrt[(x^2) + (y^2) + (z^2)]} normalized to body size was calculated from the data. IMU output clearly discriminates between activities of varying intensity in the dog. CLINICAL RELEVANCE: The inability to accurately measure chronic pain is a barrier to the development of new, or critical evaluation of, therapeutics. Activity monitors (AM) may be the ideal diagnostic target since they are small and provide objective data that can be collected while the pet remains in its natural environment. These results demonstrate the concurrent and predictive validity of the IMU tested. Our long-range goal is to validate an open-source algorithm for the IMU so activity in a pet's natural environment can be used as an outcome measure in future studies.

Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).

Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague-Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes.

Initial exploration of the discriminatory ability of the PetPace collar to detect differences in activity and physiological variables between healthy and osteoarthritic dogs.

Background: Accelerometry has been used to evaluate activity in dogs with osteoarthritis (OA) pain, especially in relation to effect of treatment; however no studies have compared accelerometry-measured activity in dogs with OA-pain and healthy dogs. The aims of this study were to (1) compare activity output from the PetPace collar with the validated Actical monitor and (2) determine if PetPace collar outputs (overall activity, activity levels, body position, and vital signs) differed between healthy dogs and dogs with OA-pain. Methods: This was an observational, non-interventional study in healthy dogs and dogs with OA-pain. All dogs were outfitted with the PetPace collar and the Actical monitor simultaneously for 14 days. Output from these devices was compared (correlations), and output from the PetPace device was used to explore differences between groups across the activity and vital sign outputs (including calculated heart rate variability indices). Results: There was moderate correlation between the PetPace collar and Actical monitor output (R 2 = 0.56, p < 0.001). Using data generated by the PetPace collar, OA-pain dogs had lower overall activity counts and spent less time standing than healthy dogs. Healthy dogs spent more time at higher activity levels than OA-pain dogs. Certain heart rate variability indices in OA-pain dogs were lower than in healthy dogs. Conclusions and clinical relevance: The results of this study suggest that the PetPace collar can detect differences between healthy dogs and those with OA-pain, and that OA-pain negatively impacts overall activity levels in dogs, and especially higher intensity activity.

The beneficial role of companion animals in translational pain research.

The use of spontaneous painful disease in companion pet animals has been highlighted as one of the changes that could be made to help improve translation of basic science to new therapeutics, acting as a bridge between preclinical and clinical studies, with the goal of accelerating the approval of new therapeutics. This review focuses on the utility of companion pet dogs for translational research by reviewing what outcome measures can be measured, and importantly, the relevance of these outcome measures to human translational research. It also details the practical considerations involved in incorporating companion dogs into human therapeutic development.

Static posturography as a novel measure of the effects of aging on postural control in dogs.

Aging is associated with impairment in postural control in humans. While dogs are a powerful model for the study of aging, the associations between age and postural control in this species have not yet been elucidated. The aims of this work were to establish a reliable protocol to measure center of pressure excursions in standing dogs and to determine age-related changes in postural sway. Data were obtained from 40 healthy adult dogs (Group A) and 28 senior dogs (Group B) during seven trials (within one session of data collection) of quiet standing on a pressure sensitive walkway system. Velocity, acceleration, root mean square, 95% ellipse area, range and frequency revolve were recorded as measures of postural sway. In Group A, reliability was assessed with intraclass correlation, and the effect of morphometric variables was evaluated using linear regression. By means of stepwise linear regression we determined that root mean square overall and acceleration in the craniocaudal direction were the best variables able to discriminate between Group A and Group B. The relationship between these two center-of-pressure (COP) measures and the dogs' fractional lifespan was examined in both groups and the role of pain and proprioceptive deficits was evaluated in Group B. All measures except for frequency revolve showed good to excellent reliability. Weight, height and length were correlated with most of the measures. Fractional lifespan impacted postural control in Group B but not Group A. Joint pain and its interaction with proprioceptive deficits influence postural sway especially in the acceleration in the craniocaudal direction, while fractional lifespan was most important in the overall COP displacement. In conclusion, our study found that pressure sensitive walkway systems are a reliable tool to evaluate postural sway in dogs; and that postural sway is affected by morphometric parameters and increases with age and joint pain.

Long-term follow up of 44 cats undergoing total hip replacement: Cases from a feline hip registry (2010-2020).

OBJECTIVE: To report indications, complications, and long-term outcomes following feline total hip replacement (THR) using a client-based clinical metrology questionnaire, the Feline Musculoskeletal Pain Index (FMPI), and owner satisfaction. STUDY DESIGN: Multi-institutional retrospective cohort study. ANIMALS: Cats (n = 44) that underwent THR (n = 56). METHODS: Feline THRs submitted to a registry over a 10-year period were reviewed. The FMPI and owner satisfaction surveys were used to assess outcome. RESULTS: Forty-four cats met the inclusion criteria. Median age was 2 years (range: 0.9-11), and median bodyweight 5 kg (range: 3.3-7.6). British Shorthair and Domestic Shorthair were the most frequent breeds. Most cats were neutered males (33/44) and slipped capital femoral epiphysis (SCFE) was the most common surgical indication (34/56). All implants were cemented micro and nano hip implants. Overall complications (11/56) included 9 major complications. The median duration of follow up was 752 days (range: 102-3089). No association was found between clinical variables and complications. The FMPI score improved from 0.111 (range: 0-1.222) to 2.111 (range: 0.888-3.666) postoperatively (P < .001). Owner satisfaction was reported as "very good" in 30/33 cases (90.9%). CONCLUSION: A validated client metrology questionnaire showed clinical improvement in cats following THR. The most common indication for THR in cats was SCFE occurring in young male neutered cats. Complication rates were comparable to previous reports. CLINICAL SIGNIFICANCE: Total hip replacement appears to be a successful surgical treatment for feline hip disease with very good owner satisfaction and acceptable complication rates.

A Pilot, Open-Label Study to Evaluate the Efficacy of Intra-Articular Administration of a Caninized TNF Receptor Fc Fusion Protein as a Treatment for Osteoarthritis-Associated Joint Pain.

Tumor necrosis factor-α (TNF-α) is a potential target for osteoarthritis (OA) treatment. In several recent clinical studies in human OA, anti-TNF-α therapy showed promising results; however, these were open-label and based on patient-reported outcome measures. In this study, we developed a caninized TNF-α receptor-Fc (caTNFR-Fc) fusion protein and conducted a non-randomized, open-label, pilot study in dogs with OA using objectively measured ground reaction forces and activity. The aims of the study were to assess the efficacy of the intra-articular (IA) injection of the caTNFR-Fc fusion protein as a treatment for OA pain, and additionally to evaluate TNF concentrations in synovial fluid (SF) between joints with/without OA in dogs. Dogs (n = 12) with single-limb lameness due to single joint appendicular OA were recruited. All dogs received caTNFR-Fc fusion protein injection into the affected joint under sedation. Objective kinetic gait analysis using force plate was performed prior to (baseline), and at 14- and 28-days following treatment. Additionally, SF samples were collected from OA joints (n = 69) and non-OA joints (n = 79) in a different cohort of dogs and TNF-α were measured using enzyme-linked immunosorbent assay. No significant treatment effects on the limb use, activity, and the questionnaire were found. The concentration of TNF-α was significantly higher in OA joints than in healthy joints (p = 0.0019), but TNF-α was detected in only 10/69 OA samples. The IA injection of caTNFR-Fc fusion protein provided no benefit in terms of objective limb use and activity data in dogs with OA in this pilot study. Although the SF concentration of TNF-α was significantly higher in OA joints, few OA joints had measurable TNF-α. Collectively, the data indicate TNF-α may not be a good therapeutic target in canine OA.

Determination of the center of mass in a heterogeneous population of dogs.

The center of mass (CoM) is the location in a body where mass distribution is balanced. It has a fundamental role in balance and motion which has been poorly described in the dog. The objective of this study was to estimate the variance of the center of mass (CoM) in a heterogeneous population of client-owned dogs and to describe the relationship between CoM, subject morphometrics and an inertial measurement unit (IMU) box positioned ventrally on a neck collar. A single force platform and a reaction board were used to determine CoM in the transverse, sagittal and dorsal planes in thirty-one healthy adult dogs. A series of morphometric measurements were acquired with each dog standing, including distances relative to an IMU box positioned ventrally on a neck collar. Mean transverse plane CoM was 48% the distance from ischium to the IMU box, near the xiphoid process. Mean sagittal place CoM was 59% the width of the chest on the left side. Mean dorsal plane CoM was 41% the distance from the most dorsal to the most ventral aspect of the body. Dog length was the primary variable required to maximize the relationship between three-dimensional CoM and identifiable variables measured. A CoM based normalization procedure should be considered to normalize mass or motion based outcome measure output (e.g., ground reaction forces, vector acceleration) in a heterogeneous population of dogs. Future research will be needed to determine if CoM-based normalization procedures reduce variance in outcome measures affected by subject morphometrics.