J. F. Innes

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.

Proposed Definitions and Criteria for Reporting Time Frame, Outcome, and Complications For Clinical Orthopedic Studies in Veterinary Medicine

Outcome, and Complications For Clinical Orthopedic Studies in Veterinary Medicine James L. Cook, DVM, PhD, Diplomate ACVS, Richard Evans, PhD, Michael G. Conzemius, DVM, PhD, Diplomate ACVS, B. Duncan X. Lascelles, BVSc, PhD, Diplomate ECVS, Diplomate ACVS, C. Wayne McIlwraith, BVSc, PhD, Diplomate ACVS, Antonio Pozzi, DMV, MS, Diplomate ACVS, Peter Clegg, MA, VetMB, PhD, Diplomate ECVS, MRCVS, John Innes, BVSc, PhD, DSAS (Orth), MRCVS, Kurt Schulz, DVM, Diplomate ACVS, John Houlton, MA, VetMB, DVR, DSAO, MRCVS, Diplomate ECVS, Lisa Fortier, DVM, PhD, Diplomate ACVS, Alan R. Cross, DVM, Diplomate ACVS, Kei Hayashi, DVM, PhD, Diplomate ACVS, Amy Kapatkin, DVM, MS, Diplomate ACVS, Dorothy Cimino Brown, DVM, MSCE, Diplomate ACVS, and Allison Stewart, DVM, MS, Diplomate ACVS Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO, College of Veterinary Medicine, University of Illinois, Urbana, IL, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, Comparative Pain Research Laboratory, North Carolina State University,

Dog MHC alleles containing the human RA shared epitope confer susceptibility to canine rheumatoid arthritis.

Abstract. To determine whether canine rheumatoid arthritis (CRA) is associated with dog MHC (DLA-DRB1) alleles which contain the QRRAA/RKRAA conserved third hypervariable region (3HVR) sequence, DNA samples were extracted from 61 dogs with clinically diagnosed small-joint polyarthritis and from 425 controls. Breed-matched controls were available for 41 cases. DLA-DRB1 genotypes were identified using molecular typing methods. Phenotype frequencies were compared between cases and controls and odds ratios with 95% confidence intervals calculated. Several DLA-DRB1 alleles were associated with increased risk for CRA: DLA-DRB1*002, DRB1*009, and DRB1*018. This was also observed for the presence of any shared epitope (SE)-bearing allele. The associations with DLA-DRB1*002 and the SE were maintained when only breed-matched cases and controls were compared. This study suggests that a conserved amino acid motif in the 3HVR present in some DRB1 alleles of both dogs and humans is associated with rheumatoid arthritis in both species.

Review of the safety and efficacy of long-term NSAID use in the treatment of canine osteoarthritis

The published, peer-reviewed literature was systematically searched for information on the safety and efficacy of long-term (defined as 28 days or more of continuous therapy) NSAID use in the treatment of canine osteoarthritis. Online databases were reviewed in June 2008 and papers were selected based on their relevance. Fifteen papers were identified and evaluated. Six of seven papers indicated a benefit of long-term treatment over short-term treatment in terms of the reduction of clinical signs or lameness; one study showed no benefit. Fourteen papers evaluated safety with calculated experimental (adverse) event rates (EER) between 0 and 0.31, but there was no correlation between study length and EER (rs=-0.109, P=0.793). The balance of evidence for the efficacy of NSAIDs supports longer-term use of these agents for increased clinical effect. There is no indication in the literature that such an approach is associated with a reduction in safety, although robust data on the safety of long-term NSAID use are lacking in large numbers of dogs.

Nutraceutical Therapies for Degenerative Joint Diseases: A Critical Review

There is growing recognition of the importance of nutritional factors in the maintenance of bone and joint health, and that nutritional imbalance combined with endocrine abnormalities may be involved in the pathogenesis of osteoarthritis (OA) and osteochondritis dissecans (OCD). Despite this, dietary programs have played a secondary role in the management of these connective tissue disorders. Articular cartilage is critically dependent upon the regular provision of nutrients (glucose and amino acids), vitamins (particularly vitamin C), and essential trace elements (zinc, magnesium, and copper). Therefore, dietary supplementation programs and nutraceuticals used in conjunction with non-steroidal, anti-inflammatory drugs (NSAIDs) may offer significant benefits to patients with joint disorders, such as OA and OCD. This article examines the available clinical evidence for the efficacy of nutraceuticals, antioxidant vitamin C, polyphenols, essential fatty acids, and mineral cofactors in the treatment of OA and related joint disorders in humans and veterinary species. This article also attempts to clarify the current state of knowledge. It also highlights the need for additional targeted research to elucidate the changes in nutritional status and potential alterations to the expression of plasma membrane transport systems in synovial structures in pathophysiological states, so that current therapy and future treatments may be better focused.

Analysis of normal and osteoarthritic canine cartilage mRNA expression by quantitative polymerase chain reaction

The molecular basis to mammalian osteoarthritis (OA) is unknown. We hypothesised that the expression of selected proteases, matrix molecules, and collagens believed to have a role in the pathogenesis of OA would be changed in naturally occurring canine OA cartilage when compared to normal articular cartilage. Quantitative (real-time) reverse transcriptase-polymerase chain reaction assays were designed measuring the expression of selected matrix molecules (collagens and small leucine-rich proteoglycans), key mediators of the proteolytic degradation of articular cartilage (metalloproteinases, cathepsins), and their inhibitors (tissue inhibitors of matrix metalloproteinases). All data were normalised using a geometric mean of three housekeeping genes, and the results subjected to power calculations and corrections for multiple hypothesis testing. We detected increases in the expression of BGN, COL1A2, COL2A1, COL3A1, COL5A1, CSPG2, CTSB, CTSD, LUM, MMP13, TIMP1, and TNC in naturally occurring canine OA. The expression of TIMP2 and TIMP4 was significantly reduced in canine OA cartilage. The patterns of gene expression change observed in naturally occurring canine OA were similar to those reported in naturally occurring human OA and experimental canine OA. We conclude that the expression profiles of matrix-associated molecules in end-stage mammalian OA may be comparable but that the precise aetiologies of OA affecting specific joints in different species are presently unknown.

Biomarkers of cartilage turnover. Part 1: Markers of collagen degradation and synthesis

Type II collagen is a major component of articular cartilage and its breakdown is a key feature of osteoarthritis. Products of cartilage collagen metabolism can be detected in the blood, synovial fluid and urine. Several biomarker assays have been developed which can be used to measure the synthesis and degradation of collagen, and therefore provide information regarding cartilage turnover. This is the first part of a two-part review and describes the need for accurate, reliable information regarding collagen turnover, the processes by which the biomarker epitopes are generated, their application to the study of both healthy and diseased cartilage and the results of currently published studies, with particular reference to the veterinary species. The second part of the review considers the non-collagenous biomarkers of cartilage matrix turnover.

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

BackgroundThere 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.ResultsCBPI 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).ConclusionsThese 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.