Outcomes and complications reported from a multiuser canine hip replacement registry over a 10-year period.

OBJECTIVE: To report outcomes and complications associated with total hip replacements (THR) using a multiuser canine hip registry (CHR) and owner-administered questionnaire. STUDY DESIGN: Prospective longitudinal clinical study. ANIMALS: Dogs (n = 1852). METHODS: Total hip replacement cases submitted to a CHR were reviewed. An online questionnaire including an adapted "Liverpool Osteoarthritis in Dogs" (LOAD) score was e-mailed to owners. Data were analyzed to determine associations between clinical variables and the agreement by veterinary surgeons and owners for complications. RESULTS: A group of 1329 (72%) dogs had unilateral THRs and another group of 523 (28%) dogs had bilateral THRs, resulting in 2375 THRs. Indications included hip dysplasia and osteoarthritis (n = 2028/2375, 85%). Implants were manufactured by Kyon (n = 1087, 46%), BioMedtrix CFX (n = 514, 22%), BioMedtrix hybrid (n = 264, 11%), BioMedtrix BFX (n = 221, 9%), and Helica (n = 107, 4.5%). Median veterinary surgeon and owner follow up were 1328 and 900 days respectively. Postoperative LOAD scores (21 ± 9) reported by 461 owners improved compared to preoperative scores (11 ± 9) (P < .001). Veterinary surgeons reported complications in 201/2375 (8.5%) THRs and owners in 107/461 (23%) THRs, with moderate agreement (weighted kappa = 0.44). No associations were identified between complications and weight, age, sex, or breed. BioMedtrix BFX and Helica implants were associated with increased complications (P = .031) when used for revisions of femoral head and neck excisions. CONCLUSION: Excellent outcomes, including improved canine mobility, were reported after THRs. Complications were underreported by veterinary surgeons compared to owners in this first multiuser CHR. CLINICAL SIGNIFICANCE: Canine THRs are safe, effective procedures but THR implants should be carefully selected when revising femoral head and neck excisions.

The effect of intra-articular botulinum toxin A on substance P, prostaglandin E2, and tumor necrosis factor alpha in the canine osteoarthritic joint.

BACKGROUND: Recently, intra-articular botulinum toxin A (IA BoNT A) has been shown to reduce joint pain in osteoarthritic dogs. Similar results have been reported in human patients with arthritis. However, the mechanism of the antinociceptive action of IA BoNT A is currently not known. The aim of this study was to explore this mechanism of action by investigating the effect of IA BoNT A on synovial fluid (SF) and serum substance P (SP), prostaglandin E2 (PGE2), and tumor necrosis factor alpha (TNF-α) in osteoarthritic dogs. Additionally, the aim was to compare SF SP and PGE2 between osteoarthritic and non-osteoarthritic joints, and investigate associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs. Thirty-five dogs with chronic naturally occurring osteoarthritis and 13 non-osteoarthritic control dogs were included in the study. Osteoarthritic dogs received either IA BoNT A (n = 19) or IA placebo (n = 16). Serum and SF samples were collected and osteoarthritic pain was evaluated before (baseline) and 2 and 8 weeks after treatment. Osteoarthritic pain was assessed with force platform, Helsinki Chronic Pain Index, and joint palpation. Synovial fluid samples were obtained from control dogs after euthanasia. The change from baseline in SP and PGE2 concentration was compared between the IA BoNT A and placebo groups. The synovial fluid SP and PGE2 concentration was compared between osteoarthritic and control joints. Associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs were evaluated. RESULTS: There was no significant change from baseline in SP or PGE2 after IA BoNT A. Synovial fluid PGE2 was significantly higher in osteoarthritic compared to control joints. Synovial fluid PGE2 correlated with osteoarthritic pain. No associations were found between SP or PGE2 and the signalment of dogs. The concentration of TNF-α remained under the detection limit of the assay in all samples. CONCLUSIONS: The results suggest that the antinociceptive effect of IA BoNT A in the joint might not be related to the inhibition of SP nor PGE2. Synovial fluid PGE2, but not SP, could be a marker for chronic osteoarthritis and pain in dogs.

Peak Vertical Force and Vertical Impulse in Dogs With Cranial Cruciate Ligament Rupture and Meniscal Injury.

OBJECTIVE: To compare the peak vertical force (PVF) and vertical impulse (VI) in dogs with naturally occurring cranial cruciate ligament (CCL) disease with or without concurrent meniscal injury. STUDY DESIGN: Prospective case series. STUDY POPULATION: Client-owned dogs with naturally occurring CCL disease. METHODS: Dogs with hind limb lameness because of CCL disease that required surgery underwent force plate gait analysis. Force plate analysis was performed at a walking gait (speed 1-1.3 m/s; acceleration ± 0.5 m/s(2)) and data were analyzed using commercial proprietary software. Meniscal injury was diagnosed either by mini-arthrotomy or arthroscopy. The primary outcome was PVF and the secondary outcome was VI. Comparisons were made between dogs with or without meniscal injury, and dogs with partial or complete CCL rupture. RESULTS: Forty dogs were included. Meniscal injury was present in 18/40 dogs (45%). PVF (P = .003) and VI (P = .01) were significantly lower in dogs with meniscal injury than in dogs without meniscal injury. CONCLUSION: Dogs with CCL disease and medial meniscal injury had significantly reduced PVF and VI.

A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain.

BACKGROUND: There is a critical need for proven drugs other than non-steroidal anti-inflammatory drugs for treatment of degenerative joint disease (DJD) pain in dogs. Antibodies against nerve growth factor (NGF) are analgesic in rodent models and in humans with DJD. This pilot study aimed to evaluate the efficacy of a novel caninised anti-NGF antibody (NV-01) for the treatment of DJD pain in dogs. In a randomized, parallel group, stratified, double masked, placebo controlled, proof of principle clinical pilot study design, 26 dogs with DJD received NV-01 (200 mcg/kg IV) or placebo on day 0 (D0). In addition to objective accelerometry measures, owners completed clinical metrology instruments (Client-Specific Outcome Measures [CSOM], Canine Brief Pain Inventory [CBPI] and Liverpool Osteoarthritis in Dogs Index [LOAD]) on D0, D14 and D28. CBPI subscales (pain severity [PS] and pain interference [PI]), CSOM and LOAD scores were evaluated within and between groups for change over time. Recognized success/failure criteria were applied and success compared between groups. RESULTS: CBPI PS and PI scores significantly improved in the NV-01 group (PS: D0-14, P = 0.012 and D0-28, P = 0.019; PI: D0-14, P = 0.012 and D0-28, P = 0.032) but not in the placebo group. CSOM scores showed similar patterns with a significant difference between within-group changes at D14 and D28 (P = 0.038 and P = 0.009, respectively), and significantly more successes at D28 (P = 0.047). LOAD scores significantly improved in the NV-01 group (D0-14, P = 0.004 and D0-28, P = 0.002) but not in the placebo group. There were significant differences between the groups for change in LOAD score at D14 (P = 0.014) and D28 (P = 0.033). No side effects were noted. Activity in the NV-01 group increased over the study period compared to placebo (P = 0.063) and the difference between the groups for change in activity over the time period 9am-5pm (8 hours) was significant (P = 0.006). CONCLUSIONS: These pilot data demonstrate a positive analgesic effect of anti-NGF antibody in dogs suffering from chronic pain. The magnitude of the effect appeared identical to that expected with an NSAID.

Mechanical Testing of a Synthetic Canine Gastrocnemius Tendon Implant.

OBJECTIVE: To test a polyethylene terephthalate prosthesis (STIF, Chenove, France) for gastrocnemius tendon repair in dogs (cadaver model). STUDY DESIGN: In vitro mechanical study. ANIMALS: Pelvic limbs (n = 8) from 4 recently euthanatized adult dogs (weighing 30-45 kg). METHODS: Proximally the implant was sutured at the myotendinous junction of the gastrocnemius and distally secured in a 4.5 mm blind ending tunnel in the medullary cavity of the calcaneus using an interference screw (STIF, Chenove, France). Proximal and distal fixation were tested independently using an electrodynamic testing machine (Electropuls 3000, Instron, UK). RESULTS: Mean ± SD failure loads for the proximal fixation (266.13 ± 43.88 N) was significantly less than for the distal fixation (649.25 ± 210.36 N; P = .042, paired t-test). Mean stiffness of the proximal and distal constructs were 19.08 ± 8.16 N/mm and 139.76 ± 24.51 N/mm, respectively. CONCLUSIONS: Failure loads exceeded the values reported after experimental repair of chronic gastrocnemius tendon injuries using other methods involving suturing tendon to bone. Failure of this repair method clinically is predicted to occur proximally at the level of the myotendinous junction.

Genetic basis of cranial cruciate ligament rupture (CCLR) in dogs.

Cranial Cruciate Ligament rupture (CCLR) is one of the most common forms of lameness in dogs and is analogous to rupture of the anterior cruciate ligament in humans, for which it can serve as a model. As there is a strong breed-related predisposition to CCLR in dogs, a study was undertaken to consider putative genetic components in susceptible dog breeds. A candidate gene, single nucleotide polymorphism (SNP) genotyping approach using MALDI-TOF mass spectrometry (Sequenom Ltd) was designed to investigate several CCLR-susceptible dog breeds and identify CCLR-associated genes/gene regions that may confer susceptibility or resistance. A meta-analysis was performed using the breed case/control candidate gene data to identify SNP associations that were common to the whole cohort of susceptible dogs. We identified SNPs in key genes involved in ligament strength, stability and extracellular matrix formation (COL5A1, COL5A2, COL1A1, COL3A1, COL11A1, COL24A1, FBN1, LOX, LTBP2) which were significantly associated with CCLR susceptibility across the dog breeds used in this study. These SNPs could have an involvement in CCLR due to a detrimental effect on ligament structure and strength. This is the first published candidate gene study that has revealed significant genetic associations with canine CCLR.

Minimal clinically-important differences for the "Liverpool Osteoarthritis in Dogs" (LOAD) and the "Canine Orthopedic Index" (COI) in dogs with osteoarthritis.

OBJECTIVE: Osteoarthritis is the most common joint disease in companion animals. Several client-report outcome measures (CROMs) have been developed and validated to monitor patients and their response to treatment. However, estimates for minimal clinically-important differences for these CROMs in the context of osteoarthritis have not been published. PATIENTS AND METHODS: Data from the Clínica Veterinária de Cães (Portuguese Gendarmerie Canine Clinic) clinical records were extracted. Baseline and 30-day post-treatment follow-up data from 296 dogs treated for hip osteoarthritis were categorized based on an anchor question, and estimates of minimal clinically-important differences (MCIDs) using distribution-based and anchor-based methods were performed. RESULTS: For the LOAD, the anchor-based methods provided a MCID estimate range of -2.5 to -9.1 and the distribution-based methods from 1.6 to 4.2. For the COI, the anchor-based methods provided a MCID estimate range of -4.5 to -16.6 and the distribution-based methods from 2.3 to 2.4. For the dimensions of COI, values varied from -0.5 to -4.9 with the anchor-based methods and from 0.6 to 2.7 with the distribution-based methods. Receiver operator characteristic curves provided areas under the curve >0.7 for the COI, indicating an acceptable cut-off point, and >0.8 for the LOAD, indicating an excellent cut-off point. CONCLUSION: Our estimates of MCIDs for dogs with OA were consistent with previously proposed values of -4 for the LOAD and -14 for the COI in a post-surgical intervention context. ROC curve data suggest that LOAD may more reliably differentiate between anchor groups. We also presented estimates from COI of -4 for Stiffness, Function, and Gait and -3 for quality of life. These estimates can be used for research and patient monitoring.

Long term outcomes of the Humeral Intracondylar Repair System for management of canine humeral intracondylar fissures and humeral condylar fractures.

Objective: To document long-term client-reported clinical outcomes and complications for the Humeral Intracondylar Repair System (HIRS) for treatment of humeral intracondylar fissures (HIF) and humeral condylar fractures (HCF) in dogs. Method: Data collection involved the review of clinical records and analysis of an owner questionnaire regarding complication occurrence and client-reported outcome. The "Liverpool Osteoarthritis in Dogs" (LOAD) instrument was incorporated into the questionnaire. Results: Twenty-six cases of HIF and 14 cases of HCF were included in the study, with follow-up times of over 12 months (range 13-97 months). Thirty-seven out of 40 cases reached long-term follow up: 25 out of 26 HIF cases, 11 out of 11 lateral condylar fracture cases and one out of three dicondylar fracture cases. Two cases of HIF suffered a gradual return of lameness in the long term; both dogs had concomitant medial coronoid disease. No other complications were reported in the long term. Excluding cases with concurrent issues affecting exercise, the median LOAD score at follow-up was 4 and 5 (out of 52) for HIF and HCF cases, respectively. At long-term follow-up, 36 out of 37 cases were reported to have regained "full function of the limb." Clinical significance: The results of this study, together with previously reported short and medium-term outcomes, support the use of HIRS for management of humeral intracondylar fissures and humeral condylar fractures.

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.

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.

Complications and owner assessment of canine total hip replacement: a multicenter internet based survey.

OBJECTIVE: To assess the variables associated with the complications of total hip replacement (THR) and report owner-assessed outcomes, through surgeon-based registration of cases via an online database, informed owner consent, and prospective outcomes assessment using a client-administered clinical metrology instrument. STUDY DESIGN: Prospective case series ANIMALS: Dogs (n = 170) METHODS: Entries into the British Veterinary Orthopaedic Association-Canine Hip Registry (BVOA-CHR) between January 2010 and August 2011 were reviewed. Variables evaluated included dog age, body weight, breed, and indication for THR and prosthesis. Associations between each variable and the incidence of complications were assessed using logistic regression. Additionally, an on-line, owner-administered outcomes assessment questionnaire (modified from the Liverpool Osteoarthritis in Dogs (LOAD) questionnaire) was used to collect data from owners. RESULTS: One hundred and seventy cases met the inclusion criteria. Surgical indications included hip dysplasia and coxofemoral osteoarthritis (n = 150), Legg-Calves-Perthes disease (7), coxofemoral luxation (6), fracture (4), slipped capital physis (2), and femoral head and neck ostectomy revision (1). Surgical implants were from 4 systems. The incidence of surgeon-reported complication was 9.4%. No significant association was identified between weight, age, sex, breed, indication for THR, surgical technique and prosthesis, and the incidence of complications. In 82% of the cases, owners described their satisfaction with the outcome of THR as "very good" and a total of 20% complication rate was reported. There was a statistically significant improvement in owner-assessed questionnaire score before and after THR (P < .001). CONCLUSIONS: The BVOA-CHR offers a novel framework for the prospective studies on THR and on a national/international scale. Initial complication rates from the BVOA-CHR are similar to previous studies.

The organisation of elastin and fibrillins 1 and 2 in the cruciate ligament complex.

Although elastin fibres and oxytalan fibres (bundles of microfibrils) have important mechanical, biochemical and cell regulatory functions, neither their distribution nor their function in cruciate ligaments has been investigated. Twelve pairs of cruciate ligaments (CLs) were obtained from 10 adult dogs with no evidence of knee osteoarthritis. Elastic fibres were identified using Verhoeff's and Miller's staining. Fibrillins 1 and 2 were immunolocalised and imaged using confocal laser scanning microscopy. Hydrated, unfixed tissue was analysed using Nomarski differential interference microscopy (NDIC), allowing structural and mechanical analysis. Microfibrils and elastin fibres were widespread in both CLs, predominantly within ligament fascicles, parallel to collagen bundles. Although elastin fibres were sparse, microfibrils were abundant. We described abundant fibres composed of both fibrillin 1 and fibrillin 2, which had a similar pattern of distribution to oxytalan fibres. NDIC demonstrated complex interfascicular and interbundle anatomy in the CL complex. The distribution of elastin fibres is suggestive of a mechanical role in bundle reorganisation following ligament deformation. The presence and location of fibrillin 2 in oxytalan fibres in ligament differs from the solely fibrillin 1-containing oxytalan fibres previously described in tendon and may demonstrate a fundamental difference between ligament and tendon.

Comparative rheumatology: what can be learnt from naturally occurring musculoskeletal disorders in domestic animals?

Examples of naturally occurring musculoskeletal disorders are extremely common in veterinary species and provide a valuable comparative research resource, which can provide compelling comparative data on the aetiopathogenesis and treatment of many common human musculoskeletal diseases. In particular, orthopaedic diseases are a common morbidity in both dogs and horses. In this review, we give an overview of the common musculoskeletal diseases encountered in these species: for instance, tendon and ligament injuries, arthropathies and stress fractures, as well as an insight into the basic biology of these conditions. In doing so, we aim to demonstrate the similarities and differences between these disorders and similar conditions in man.

A candidate gene study of canine joint diseases.

Canine osteoarthritis (OA) commonly occurs in association with articular diseases, such as hip dysplasia (HD), elbow dysplasia (ED), or cranial cruciate ligament rupture (CCLR). We hypothesized that a common genomic risk for the development of canine joint disease and canine OA would be identified by evaluating the allele frequencies of candidate gene single nucleotide polymorphisms (SNPs) in dogs with OA associated with different articular diseases when compared with a general population of breed-matched dogs. DNA was extracted from blood samples obtained from Labrador Retrievers and Golden Retrievers surgically treated for ED, HD, and CCLR and confirmed to have radiographic evidence of OA. One hundred and thirteen SNPs in 20 candidate genes were genotyped. No significant associations were identified for SNPs or haplotypes in the candidate genes for the diseases evaluated. The candidate gene approach for the study of genetic association is unlikely to be successful for complex canine diseases such as OA without prior trait mapping evaluation.

Elbow Arthrodesis Using a Medially Positioned Plate in 6 Dogs.

OBJECTIVE: The aim of this study was to report the surgical technique, associated complications and clinical outcome of elbow arthrodesis using a medially positioned plate. STUDY DESIGN: This was a retrospective case series. RESULTS: Six cases met the inclusion criteria. In all cases, the elbow was approached medially without the requirement for ulnar osteotomy. A non-locking 2.7/3.5- mm pre-contoured elbow arthrodesis plate was applied in 5/6 cases and a 2.0-mm String of Pearls plate applied in one case. The mean angle of arthrodesis was 118° (range: 113-130°). One major intraoperative complication occurred. Three minor and 3 major postoperative complications occurred. Postoperative imaging was available for 5/6 cases. Complete arthrodesis was confirmed by imaging in 4/5 cases, partial progression of arthrodesis was documented in 1/5 cases and no further images were deemed necessary. Postoperative Liverpool Osteoarthritis in Dogs score was available for two cases with scores of 20/52 and 10/52, respectively. Subjective outcomes in the remaining three cases were rated as acceptable more than 1 year postoperatively. CONCLUSION: Positioning the plate medially for elbow arthrodesis simplified the surgical approach, could be performed with a pre-contoured plate and allowed successful revision of an arthrodesis previously stabilized with a caudally positioned plate. The cases in this series had acceptable outcomes despite a high risk of complications.

An In Vitro Comparison of the Neurotrophic and Angiogenic Activity of Human and Canine Adipose-Derived Mesenchymal Stem Cells (MSCs): Translating MSC-Based Therapies for Spinal Cord Injury.

The majority of research into the effects of mesenchymal stem cell (MSC) transplants on spinal cord injury (SCI) is performed in rodent models, which may help inform on mechanisms of action, but does not represent the scale and wound heterogeneity seen in human SCI. In contrast, SCI in dogs occurs naturally, is more akin to human SCI, and can be used to help address important aspects of the development of human MSC-based therapies. To enable translation to the clinic and comparison across species, we have examined the paracrine, regenerative capacity of human and canine adipose-derived MSCs in vitro. MSCs were initially phenotyped according to tissue culture plastic adherence, cluster of differentiation (CD) immunoprofiling and tri-lineage differentiation potential. Conditioned medium (CM) from MSC cultures was then assessed for its neurotrophic and angiogenic activity using established cell-based assays. MSC CM significantly increased neuronal cell proliferation, neurite outgrowth, and ßIII tubulin immunopositivity. In addition, MSC CM significantly increased endothelial cell migration, cell proliferation and the formation of tubule-like structures in Matrigel assays. There were no marked or significant differences in the capacity of human or canine MSC CM to stimulate neuronal cell or endothelial cell activity. Hence, this study supports the use of MSC transplants for canine SCI; furthermore, it increases understanding of how this may subsequently provide useful information and translate to MSC transplants for human SCI.

An exploration of the ability of tepoxalin to ameliorate the degradation of articular cartilage in a canine in vitro model.

BACKGROUND: To study the ability of tepoxalin, a dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX) and its active metabolite to reduce the catabolic response of cartilage to cytokine stimulation in an in vitro model of canine osteoarthritis (OA).Grossly normal cartilage was collected post-mortem from seven dogs that had no evidence of joint disease. Cartilage explants were cultured in media containing the recombinant canine interleukin-1beta (IL-1beta) at 100 ng/ml and recombinant human oncostatin-M (OSM) at 50 ng/ml. The effects of tepoxalin and its metabolite were studied at three concentrations (1 x 10(-5), 1 x 10(-6) and 1 x 10(-7) M). Total glycosaminoglycan (GAG) and collagen (hydroxyproline) release from cartilage explants were used as outcome measures of proteoglycan and collagen depletion respectively. PGE2 and LTB4 assays were performed to study the effects of the drug on COX and LOX activity. RESULTS: Treatment with IL-1beta and OSM significantly upregulated both collagen (p = 0.004) and proteoglycan (p = 0.001) release from the explants. Tepoxalin at 10(-5) M and 10(-6) M caused a decrease in collagen release from the explants (p = 0.047 and p = 0.075). Drug treatment showed no effect on GAG release. PGE2 concentration in culture media at day 7 was significantly increased by IL-1beta and OSM and treatment with both tepoxalin and its metabolite showed a trend towards dose-dependent reduction of PGE2 production. LTB4 concentrations were too low to be quantified. Cytotoxicity assays suggested that neither tepoxalin nor its metabolite had a toxic effect on the cartilage chondrocytes at the concentrations and used in this study. CONCLUSION: This study provides evidence that tepoxalin exerts inhibition of COX and can reduce in vitro collagen loss from canine cartilage explants at a concentration of 10(-5) M. We can conclude that, in this model, tepoxalin can partially inhibit the development of cartilage degeneration when it is available locally to the tissue.

Anti-nerve growth factor monoclonal antibodies for the control of pain in dogs and cats.

Nerve growth factor (NGF) is essential for the survival of sensory and sympathetic neurons during development. However, in the adult, NGF and its interaction with tropomyosin receptor kinase A receptor (TrkA) has been found to play a critical role in nociception and nervous system plasticity in pain conditions. Thus, various monoclonal antibody (mAb) therapies targeting this pathway have been investigated in the development of new pharmacotherapies for chronic pain. Although none of the mAbs against NGF are yet approved for use in humans, they look very promising for the effective control of pain. Recently, species-specific anti-NGF mAbs for the management of osteoarthritis (OA)-associated pain in dogs and cats has been developed, and early clinical trials have been conducted. Anti-NGF therapy looks to be both very effective and very promising as a novel therapy against chronic pain in dogs and cats. This review outlines the mechanism of action of NGF, the role of NGF in osteoarthritis, research in rodent OA models and the current status of the development of anti-NGF mAbs in humans. Furthermore, we describe and discuss the recent development of species-specific anti-NGF mAbs for the treatment of OA-associated pain in veterinary medicine.

Relationship between objective and subjective assessment of limb function in normal dogs with an experimentally induced lameness.

OBJECTIVE: To evaluate the relationship between previously used subjective and objective measures of limb function in normal dogs that had an induced lameness. STUDY DESIGN: Prospective, blinded, and induced animal model trial. ANIMALS: Normal, adult, and mixed-breed dogs (n=24) weighing 25-35 kg. METHODS: Force platform gait analysis was collected in all dogs before and after induction of lameness. All gait trials were videotaped; 60 video trials were evaluated by 3 surgeons with practice limited to small animal orthopedics and 3 first year veterinary students in an effort to establish the relationship between subjective and objective measures of lameness. Evaluators were unaware of the force platform data. RESULTS: Concordance coefficients were low for all observers and were similar between students and surgeons. These values were further decreased when normal and non-weight bearing trials were removed. Agreement with the force platform data was low even when observers only had to be within +/-10% of the ground reaction forces. When repeat trials were evaluated surgeons had a much higher repeatability compared with students. CONCLUSIONS: Subjective evaluation of the lameness in this study varied greatly between observers and agreed poorly with objective measures of limb function. CLINICAL RELEVANCE: Subjective evaluation of gait should be interpreted cautiously as an outcome measure whether performed from a single or from multiple observers.

Interaction with macrophages attenuates equine fibroblast-like synoviocyte ADAMTS5 (aggrecanase-2) gene expression following inflammatory stimulation.

The joint synovium consists of a heterogeneous cell population, chiefly comprised of macrophages, and fibroblast-like synoviocytes (FLS). An inter-species co-culture model was developed to examine interactions between these cells. Equine FLS and the canine macrophage line DH82 were differentially labeled using fluorescent markers and results from direct co-culture compared with those from both indirect co-culture, and conditioned media experiments. The transcript expression of IL-1ß, IL-6, ADAMTS4, and ADAMTS5 in each cell type were determined using species-specific qPCR assays. Lipopolysaccharide stimulation of EFLS rapidly increased IL-1ß, IL-6, ADAMTS4, and ADAMTS5 mRNAs. The induction of ADAMTS5 was significantly reduced when equine FLS were cultured with DH82 cells directly or indirectly. Exposure of equine FLS to denatured conditioned media also significantly reduced ADAMTS5 induction. DH82 cells increased interleukin-1ß expression substantially following LPS stimulation. However, knockdown of interleukin-1ß in DH82 cells, or inhibition of NF-κB in equine FLS prior to co-culture did not change the inhibitory effect on equine FLS ADAMTS5 gene expression. This work indicates that macrophages can influence FLS gene expression through a soluble mediator, and modulate the expression of an enzyme critical in osteoarthritis pathology during inflammatory stimulation. © 2018 The Authors. Journal of Orthopaedic Research® Published by WileyPeriodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 9999:1-8, 2018.