Introduction: The study aimed to clarify the changes in the concentration of inflammatory mediators, proteases, and cartilage degradation biomarkers in the synovial fluid of joints in an equine osteoarthritis model. Material and Methods: Osteoarthritis was induced in eight Mongolian horses by a sterile intra-articular injection of amphotericin B, which was injected into the left carpal joint in a dose of 2 mL (25 mg/mL). The control group comprised five horses which were injected with an equal dose of sterile physiological saline into the left carpal joint. Synovial fluid was obtained at baseline and every week after injection. Test methods were based on ELISA. Results: In the course of the osteoarthritis, the concentration of biomarkers in joint synovial fluid showed an increasing trend. IL-1, IL-6, MMP-9, MMP-13, ADAMTS-5, CS846, GAG, HA, CTX-II, and COMP concentrations sharply increased before the onset of significant symptoms of lameness, whereas TNF-α, MMP-2, and MMP-3 concentrations rose sharply after the occurrence of such symptoms. Conclusion: The results obtained confirm that the concentrations of IL-1, IL-6, MMP-9, MMP-13, ADAMTS-5, CS846, GAG, HA, CTX-II and COMP increase substantially in equine osteoarthritis, which provides a theoretical basis for the rapid diagnosis of the disease.

OBJECTIVE To develop methods to identify and characterize activity monitor (AM) data signatures for jumps performed by cats. ANIMALS 13 healthy, client-owned cats without evidence of osteoarthritis or degenerative joint disease. PROCEDURES Each cat was fitted with the same AM, individually placed in an observation room, then simultaneously recorded by 3 video cameras during the observation period (5 to 8 hours). Each cat was encouraged to jump up (JU), jump down (JD), and jump across (JA) during the observation period. Output from the AM was manually annotated for jumping events, each of which was characterized by functional data analysis yielding relevant coefficients. The coefficients were then used in linear discriminant analysis to differentiate recorded jumps as JUs, JDs, or JAs. To assess the model's ability to distinguish among the 3 jump types, a leave-one-out cross-validation method was used, and the misclassification error rate of the overall categorization of the model was calculated. RESULTS Of 731 jumping events, 29 were misclassified. Overall, the mean misclassification error rate per cat was 5.4% (range, 0% to 12.5%), conversely indicating a correct classification rate per cat of 94.6%. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the model was successful in correctly identifying JUs, JDs, and JAs in healthy cats. With advancements in AM technology and data processing, there is potential for the model to be applied in clinical settings as a means to obtain objective outcome measures.

The objective of this study was to assess veterinarians' understanding of nutraceutical use in humans and companion animals and their motivation and circumstances for recommending nutraceuticals to clients. We administered a cross-sectional survey to veterinarians attending continuing education sessions at the University of Georgia (USA) College of Veterinary Medicine from 2012 to 2015 (N = 126). Information regarding veterinarians' age, year of graduation, practice focus, and typical approaches to nutraceutical use was compiled from the returned surveys. The results indicated that veterinarians are more familiar with nutraceutical use in animals than in humans and primarily recommend nutraceuticals to their clients for preventative purposes and/or due to client interest. Veterinarians believed that nutraceuticals were most useful for osteoarthritis and therefore use omega-3 fatty acid and glucosamine/chondroitin products more often than other products for both their patients and their own pets. Safety and efficacy were the most important considerations when deciding which nutraceuticals to recommend to clients. The survey results show that veterinarians are familiar with nutraceuticals and open to their use in patients when they perceive these products to be safe and efficacious.

OBJECTIVE To characterize delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) features of healthy hyaline cartilage of the distal interphalangeal joint (DIPJ) of horses, to determine whether dGEMRIC can be used to differentiate various stages of naturally occurring osteoarthritis of the DIPJ, and to correlate relaxation times determined by dGEMRIC with the glycosaminoglycan concentration, water content, and macroscopic and histologic findings of hyaline cartilage of DIPJs with and without osteoarthritis. SAMPLE 1 cadaveric forelimb DIPJ from each of 12 adult warmblood horses. PROCEDURES T1-weighted cartilage relaxation times were obtained for predetermined sites of the DIPJ before (T1preGd) and after (T1postGd) intra-articular gadolinium administration. Corresponding cartilage sites underwent macroscopic, histologic, and immunohistochemical evaluation, and cartilage glycosaminoglycan concentration and water content were determined. Median T1preGd and T1postGd were correlated with macroscopic, histologic, and biochemical data. Mixed generalized linear models were created to evaluate the effects of cartilage site, articular surface, and macroscopic and histologic scores on relaxation times. RESULTS 122 cartilage specimens were analyzed. Median T1postGd was lower than the median T1preGd for normal and diseased cartilage. Both T1preGd and T1postGd were correlated with macroscopic and histologic scores, whereby T1preGd increased and T1postGd decreased as osteoarthritis progressed. There was topographic variation of T1preGd and T1postGd within the DIPJ. Cartilage glycosaminoglycan concentration and water content were significantly correlated with T1preGd and macroscopic and histologic scores but were not correlated with T1postGd. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dGEMRIC relaxation times varied for DIPJs with various degrees of osteoarthritis. These findings may help facilitate early detection of osteoarthritis.

OBJECTIVE To evaluate the 3-D geometry of canine pelves and to characterize the long-term effects of juvenile pubic symphysiodesis (JPS) on pelvic geometry by comparing the pelvic configuration between littermates that did and did not undergo the procedure. ANIMALS 24 Labrador Retriever, Golden Retriever, or Labrador Retriever–Golden Retriever crossbred service dogs from 13 litters. PROCEDURES At 16 weeks old, puppies with a hip joint distraction index ≥ 0.5 were randomly assigned to undergo thermal JPS (n = 9), mechanical JPS (7), or a sham (control) surgical procedure (8). Ten years later, each dog underwent a CT scan of the pelvic region. Modeling software was used to create 3-D reconstructions from the CT scans, and various pelvic measurements were made and compared among the 3 treatments. RESULTS Compared with the control treatment, thermal and mechanical JPS increased the hemipelvis acetabular angle by 4°, the acetabular angle of lateral opening by 5°, and the orientation of the medial acetabular wall in a transverse plane by 6°, which indicated that JPS increased dorsal femoral head coverage by the acetabulum. Both JPS procedures decreased the pelvic canal area by approximately 20% and acetabular inclination by 6° but did not alter acetabular retroversion. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that thermal and mechanical JPS were equally effective in altering the 3-D pelvic geometry of dogs. These findings may help guide future studies of alternatives for optimizing canine pelvic anatomy to minimize the risk of hip dysplasia and associated osteoarthritis.

OBJECTIVE To evaluate the biomechanical properties of 4 methods for fusion of the centrodistal and tarsometatarsal joints in horses and compare them among each other and with control tarsi. SAMPLE 24 sets of paired tarsi without substantial signs of osteoarthritis harvested from equine cadavers. PROCEDURES Test constructs (n = 6/type) were prepared from 1 tarsus from each pair to represent surgical drilling; 2 medially to laterally placed kerf-cut cylinders (MLKCs); a single large, dorsally applied kerf-cut cylinder (DKC); and a dorsomedially applied locking compression plate (DMLCP). Constructs and their contralateral control tarsi were evaluated in 4-point bending in the dorsoplantar, lateromedial, and mediolateral directions; internal and external rotation; and axial compression. Bending, torsional, and axial stiffness values were calculated. RESULTS Mean stiffness values were consistently lower for surgical drilling constructs than for contralateral control tarsi. Over all biomechanical testing, surgical drilling significantly reduced joint stability. The MLKC constructs had superior biomechanical properties to those of control tarsi for 4-point bending but inferior properties for external and internal rotation. The DMLCP and DKC constructs were superior to control tarsi in dorsoplantar, rotational, and axial compression directions only; DMLCP constructs had no superior stiffness in lateromedial or mediolateral directions. Only the DKC constructs had greater stiffness in the mediolateral direction than did control tarsi. Over all biomechanical testing, DMLCP and DKC constructs were superior to the other constructs. CONCLUSIONS AND CLINICAL RELEVANCE These biomechanical results suggested that a surgical drilling approach to joint fusion may reduce tarsal stability in horses without clinical osteoarthritis, compared with stability with no intervention, whereas the DMLCP and DKC approaches may significantly enhance stability.

OBJECTIVE To evaluate safety and toxicokinetic profiles associated with daily oral administration of grapiprant, a new analgesic that selectively blocks the prostaglandin E2 EP4 receptor, to cats. ANIMALS 24 healthy domestic shorthair cats (12 males and 12 females). PROCEDURES Cats were randomly assigned (3 of each sex/group) to receive a placebo capsule or grapiprant at 3, 9, or 15 mg/kg, administered PO once daily for 28 days, beginning on day 0. Food consumption and behavior were observed daily, body weight was measured weekly, and clinicopathologic tests were performed on blood and urine samples collected on days −7, 14, and 25. Blood samples for toxicokinetic analyses were collected after treatment on days 0 and 27. Cats were euthanized on day 28, and full necropsies and histologic evaluations were performed. RESULTS Grapiprant rapidly reached peak serum concentrations and maintained substantial concentrations throughout the 28-day period. By day 27, maximum serum concentrations ranged from 683 ng/mL to 4,950 ng/mL, which were attained by 1 to 4 hours after administration. Serum half-lives on day 27 ranged from approximately 2 to 14 hours (median, approx 5 to 6 hours). Grapiprant was well tolerated, and no adverse effects were detected at doses ≤ 15 mg/kg. No significant effects of grapiprant were identified on body weight, food consumption, clinicopathologic variables, or gross or histologic necropsy findings. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested the safety of daily oral administration of grapiprant to cats. Additional studies are needed to evaluate the efficacy of grapiprant for treatment of cats with osteoarthritis.

OBJECTIVE To investigate the safety of daily oral administration of grapiprant to dogs. ANIMALS Thirty-six 9-month-old Beagles of both sexes. PROCEDURES Dogs were randomly assigned to groups that received grapiprant via oral gavage at 0, 1, 6, or 50 mg/kg (total volume, 5 mL/kg), q 24 h for 9 months. Each group contained 4 dogs of each sex (ie, 8 dogs/group), except for the 50 mg/kg group, which included 4 additional dogs that were monitored for an additional 30 days after treatment concluded (recovery period). All dogs received ophthalmologic, ECG, and laboratory evaluations before treatment began (baseline) and periodically afterward. All dogs were observed daily. Dogs were euthanized at the end of the study for necropsy and histologic evaluation. RESULTS All dogs remained clinically normal during treatment, with no apparent changes in appetite or demeanor. Emesis and soft or mucoid feces that occasionally contained blood were observed in all groups, although these findings were more common in dogs that received grapiprant. In general, clinicopathologic findings remained within baseline ranges. Drug-related changes in serum total protein and albumin concentrations were detected, but differences were small and resolved during recovery. No drug-related gross or microscopic pathological changes were detected in tissue samples except mild mucosal regeneration in the ileum of 1 dog in the 50 mg/kg group. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested the safety of long-term oral administration of grapiprant to dogs. Efficacy of grapiprant in the treatment of dogs with osteoarthritis needs to be evaluated in other studies.

Objective—To assess effects of zoledronic acid on biomarkers, radiographic scores, and gross articular cartilage changes in dogs with induced osteoarthritis. Animals—21 purpose-bred hound-type dogs. Procedures—The left stifle joint of each dog was examined arthroscopically to determine initial articular cartilage status, which was followed by cranial cruciate ligament (CrCL) transection to induce osteoarthritis. Dogs were assigned to 3 groups (control group, low dose [10 μg of zoledronic acid/kg], or high dose [25 μg of zoledronic acid/kg). Treatments were administered SC every 3 months for 1 year beginning the day after CrCL transection. Serum and synovial fluid samples and radiographs were obtained 0, 1, 3, 6, 9, and 12 months after transection. At 12 months, each joint was scored for cartilage defects. Serum and synovial fluid biomarkers of bone and cartilage turnover (bone-specific alkaline phosphatase, type I and II collagen, carboxy-propeptide of type II collagen, and chondroitin sulfate 846) were analyzed with ELISAs. Results—The high-dose group had fewer total articular defects and lower severity scores in CrCL-transected stifle joints than did the control group. In addition, the high-dose group had significantly less change in collagenase cleavage of type I or II collagen in the synovial fluid at 1 and 3 months after CrCL transection than did the control group and also had greater changes in bone-specific alkaline phosphatase in synovial fluid at 3 months after CrCL transection than did the control group. Conclusions and Clinical Relevance—Zoledronic acid had a chondroprotective effect in dogs with a transected CrCL.

Objective-To ultrasonographically quantify experimentally induced effusion of the distal interphalangeal (DIP) joint of horses and compare results with those obtained with palpation. Sample-8 forelimbs from equine cadavers and forelimbs of 5 mares. Procedures-Preliminary ex vivo experiments were performed to validate the methods. Then, the DIP joints of the forelimbs of standing horses were serially distended with saline (0.9% NaCl) solution (1, 4, and 10 mL) by injection through an intra-articular catheter. Two ultrasonographers measured distension of the dorsal recess of the DIP joint, and 2 surgeons, who were not aware of the volume injected, graded joint effusion by palpation. Results-Intraobserver and interobserver repeatability was excellent for ultrasonographic measurements. Interobserver agreement for use of palpation to detect joint distension was moderate (κ = 0.45). There was an overall increase in the palpation distension grade with an increase in injected volume. Sensitivity for detection with palpation of larger volumes (4 and 10 mL) was high (92% and 100%, respectively). However, sensitivity was lower (57%) for detection with palpation of minimal distension (1 mL). Conclusions and Clinical Relevance-Although palpation provided a reliable clinical assessment of DIP joint effusion for volumes of 4 to 10 mL, ultrasonographic measurements were easy to obtain, more accurate, and able to detect smaller amounts of distension. This may be clinically relevant for the assessment of effusion of the DIP joint that can arise in horses with early osteoarthritis or infectious arthritis with concomitant soft tissue swelling that precludes accurate assessment with palpation.