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.

A humeral intracondylar repair system for the management of humeral intracondylar fissure and humeral condylar fracture.

OBJECTIVES: To report complications, clinical outcomes and CT-imaging outcomes of a surgical system designed for the management of humeral intracondylar fissures and humeral condylar fractures. MATERIALS AND METHODS: Retrospective review of fracture healing from medical records, direct owner contact and an online data-submission service. Follow-up included CT scans and a calculated "bone-opacity continuity index" to quantify bone healing. RESULTS: There was one major surgical complication and one major medical complication out of 34 fissure cases, and two major surgical and one major medical complication out of 14 fractures. Follow-up times ranged from 29 to 1268 days. All cases with CT follow-up had some continuity of bone opacity across the condyle. CLINICAL SIGNIFICANCE: In the cases included in this study, this repair system was associated with low complication rates and favourable healing rates, particularly for humeral intracondylar fissure.

Canine mesenchymal stem cells are neurotrophic and angiogenic: An in vitro assessment of their paracrine activity.

Mesenchymal stem cells (MSCs) have been used in cell replacement therapies for connective tissue damage, but also can stimulate wound healing through paracrine activity. In order to further understand the potential use of MSCs to treat dogs with neurological disorders, this study examined the paracrine action of adipose-derived canine MSCs on neuronal and endothelial cell models. The culture-expanded MSCs exhibited a MSC phenotype according to plastic adherence, cell morphology, CD profiling and differentiation potential along mesenchymal lineages. Treating the SH-SY5Y neuronal cell line with serum-free MSC culture-conditioned medium (MSC CM) significantly increased SH-SY5Y cell proliferation (P <0.01), neurite outgrowth (P = 0.0055) and immunopositivity for the neuronal marker ßIII-tubulin (P = 0.0002). Treatment of the EA.hy926 endothelial cell line with MSC CM significantly increased the rate of wound closure in endothelial cell scratch wound assays (P = 0.0409), which was associated with significantly increased endothelial cell proliferation (P <0.05) and migration (P = 0.0001). Furthermore, canine MSC CM induced endothelial tubule formation in EA.hy926 cells in a soluble basement membrane matrix. Hence, this study has demonstrated that adipose-derived canine MSC CM stimulated neuronal and endothelial cells probably through the paracrine activity of MSC-secreted factors. This supports the use of canine MSC transplants or their secreted products in the clinical treatment of dogs with neurological disorders and provides some insight into possible mechanisms of action.

Mechanical performance in axial compression of a titanium polyaxial locking plate system in a fracture gap model.

OBJECTIVE: To evaluate the bending strength of the VetLOX® polyaxial locking plate system. MATERIALS AND METHODS: Thirty-five 3.5 mm 12-hole titanium VetLOX® plates were used to stabilize seven different construct designs in a 1 cm fracture gap simulation model. Each construct was subjected to axial compression. Mean bending stiffness (BS) and yield load (YL) of each construct design were analysed using a one-way ANOVA and Tukey post-hoc analysis. Screw angulation was measured on reconstructed computed tomography (CT) images. RESULTS: Reducing plate working length for fixed-angle constructs significantly increased BS (p <0.01) and YL (p <0.01). For a constant plate working length, increasing screw number did not significantly affect BS (p = 1.0) or YL (p = 0.86). Screw angulation measurement technique was validated by intra-class correlation coefficients (ICC) (ICC >0.9 for inter- and intra-observer measurements). An average screw angle of 13.2° did not significantly affect mechanical performance although incomplete screw head-plate engagement was noted on some reconstructed CT images when angulation exceeded 10°. Prefabricated screw-head inserts did not significantly increase mechanical performance. A 4 mm bone-plate stand-off distance significantly reduced BS and YL by 63% and 69% respectively. CLINICAL RELEVANCE: The VetLOX® system allows the benefits of polyaxial screw insertion whilst maintaining comparable bending properties to fixed angle insertion. The authors recommend accurate plate contouring to reduce the risk of plate bending.

Ex vivo kinematic studies of a canine unlinked semi-constrained hybrid total elbow arthroplasty system.

OBJECTIVES: Introduction of the Sirius® canine total elbow arthroplasty system, and presentation of the results of a passive range-of-motion analysis based on ex vivo kinematic studies pre-and post-implantation. MATERIALS AND METHODS: Thoracic limbs (n = 4) of medium sized dogs were harvested by forequarter amputation. Plain orthogonal radiographs of each limb were obtained pre- and post-implantation. Limbs were prepared by placement of external fixator pins and Kirschner wires into the humerus and radius. Each limb was secured into a custom-made box frame and retro-reflective markers were placed on the exposed ends of the pins and wires. Each elbow was manually moved through five ranges-of-motion manoeuvres. Data collected included six trials of i) full extension to full flexion and ii) pronation and supination in 90° flexion; a three-dimensional motion capture system was used to collect and analyse the data. The Sirius elbow prosthesis was subsequently implanted and the same measurements were repeated. Data sets were tested for normality. Paired t-tests were used for comparison of pre- and post-implantation motion parameters. RESULTS: Kinematic analysis showed that the range-of-motion (mean and SD) for flexion and extension pre-implantation was 115° ± 6 (range: 25° to 140°). The range-of-motion in the sagittal plane post-implantation was 90° ± 4 (range: 36° to 130°) and this reduction was significant (p = 0.0001). The ranges-of-motion (mean and SD) for supination and pronation at 90° were 50° ± 5, whereas the corresponding mean ranges-of-motion post-implantation were 38° ± 6 (p = 0.0188). CONCLUSION: Compared to a normal elbow, the range-of-motion was reduced. Post-implantation, supination and pronation range-of-motion was significantly reduced at 90° over pre-implantation values. CLINICAL RELEVANCE: These results provide valuable information regarding the effect of the Sirius system on ex vivo kinematics of the normal canine elbow joint. Further, this particular ex vivo model allowed for satisfactory and repeatable kinematic analysis.

Genome-wide association study identifies genomic regions of association for cruciate ligament rupture in Newfoundland dogs.

Cranial cruciate ligament rupture (CCLR) is the most common cause of pelvic limb lameness in dogs. To investigate the genetic basis of canine CCLR, we conducted a genome-wide association study using a canine SNP array in Newfoundland pedigree dogs with and without CCLR (n = 96). We identified three main chromosomal regions of CCLR association (on chromosomes 1, 3 and 33). Each of these regions was confirmed by Sequenom genotyping in a further cohort of Newfoundlands (n = 271). The results, particularly SNPs identified in the SORCS2 and SEMA5B genes, suggest that there may be neurological pathways involved in susceptibility to canine CCLR.

Mavacoxib and meloxicam for canine osteoarthritis: a randomised clinical comparator trial.

NSAIDs are the cornerstone of medical management of canine osteoarthritis (OA). Meloxicam is a daily-administered NSAID widely available in a liquid formulation and manufacturer's summary of product characteristics (SPC) advise that it is given at the lowest effective dose. Mavacoxib is a long-acting NSAID given as a monthly tablet. This study compares these drugs in the management of canine OA. In all, 111 dogs with OA of the elbow, hip or stifle were randomly assigned to receive one of these NSAIDs for a 12-week period, and to administer them as per the manufacturer's SPC. Outcomes, including ground reaction forces and three validated clinical metrology instruments, were measured at baseline, 6 and 12 weeks. Improvements were seen in all outcome measures for both groups to a similar degree, and adverse events occurred at a similar rate. There were significant improvements in outcome measures from week 6 to week 12, as well as from baseline. Long-term meloxicam dose was more important than recent dose. Clinical efficacy and adverse event rates are similar for meloxicam and mavacoxib when administered as per their UK SPC. This is relevant information for veterinary surgeons when prescribing NSAID treatment for canine OA.

Intra-articular botulinum toxin A for the treatment of osteoarthritic joint pain in dogs: a randomized, double-blinded, placebo-controlled clinical trial.

The aim of this study was to investigate the efficacy of intra-articular (IA) botulinum toxin A (IA BoNT A) for the treatment of osteoarthritic joint pain in dogs. The study was a placebo-controlled, randomized, double-blinded clinical trial with parallel group design and 12-week follow-up. Thirty-six dogs with chronic lameness due to stifle, hip or elbow osteoarthritis were randomized to receive an IA injection of 30IU of BoNT A or placebo. The main outcome variables were vertical impulse (VI) and peak vertical force (PVF) measured with a force platform, and Helsinki chronic pain index (HCPI). Subjective pain score and the need for rescue analgesics were secondary variables. The response to treatment was assessed as the change from baseline to each examination week. The variables were analyzed by ANOVA with repeated measurements and results were considered statistically significant if P ⩽ 0.05. The improvement from baseline to 12 weeks after baseline was statistically significant in VI, PVF and HCPI in the treatment group (P=0.001, P=0.054 and P=0.053, respectively). Additionally, there were statistically significant improvements in VI in the treatment group at 2, 4 and 8 weeks after baseline (P=0.037, P=0.016 and P=0.016, respectively). The difference between groups in improvement in VI was statistically significant at 12weeks after baseline (P=0.005). There was no significant change in the subjective pain score or in the requirement for rescue analgesics in either group. No major adverse events thought to be related to trial protocol were detected. These results suggest that IA BoNT A has some efficacy in reducing osteoarthritic pain in dogs.

Elastin content is high in the canine cruciate ligament and is associated with degeneration.

Cruciate ligaments (CLs) are primary stabilisers of the knee joint and canine cranial cruciate ligament disease (CCLD) and rupture is a common injury. Elastin fibres, composed of an elastin core and fibrillin containing microfibrils, are traditionally considered minor components of the ligament extracellular matrix (ECM). However, their content and distribution in CLs is unknown. The purposes of this study were to determine the elastin content of canine CLs and to ascertain its relationship to other biochemical components and histological architecture. Macroscopically normal CLs were harvested from Greyhounds (n=11), a breed with a low risk of CCLD. Elastin, collagen and sulfated glycosaminoglycan content were measured and histological scoring systems were developed to quantify ECM changes using a modified Vasseur score (mVS) and oxytalan fibre (bundles of microfibrils) staining. Elastin contents were 9.86 ± 3.97% dry weight in the cranial CL and 10.79 ± 4.37% in the caudal CL, respectively, and did not alter with advancing histological degeneration. All CLs demonstrated mild degenerative changes, with an average mVS score of 11.9 ± 3.3 (maximum 24). Increasing degeneration of the ligament ECM showed a positive correlation (r=0.690, P<0.001) with increased oxytalan fibre staining within the ECM. Elastin is an abundant protein in CLs forming a greater proportion of the ligament ECM than previously reported. The appearance of oxytalan fibres in degenerative CL ECM may reflect an adaptive or reparative response to normal or increased loads. This finding is important for future therapeutic or ligament replacement strategies associated with cranial CL injury.

Evaluation of cartilage, synovium and adipose tissue as cellular sources for osteochondral repair.

Osteochondral lesions are a major cause of pain and disability in several species including dogs, horses and human beings. The objective of this study was to assess three potential sources of canine cells for their osteochondral regenerative potential. Cartilage, synovium and adipose tissue cells were grown in pellet culture in chondrogenic or osteogenic media. Cartilage-derived pellets displayed the best chondrogenic differentiation as indicated by significantly higher COL2A1 and SOX9 mRNA expression, greater glycosaminoglycan content, and higher retention of Safranin-O stain compared to the synovium and adipose-derived cells. Following application of the osteogenic media, all three cell sources exhibited small areas of positive alizarin red staining. Poor intracellular alkaline phosphatase activity was found in all three cell types when stimulated although osteocalcin and RUNX2 expression were significantly increased. Cells isolated and cultured from canine articular cartilage retained their specific chondrocytic phenotype. Furthermore, canine adipocytes and synovial cells did not undergo chondrogenic differentiation and did not exhibit evidence of multipotency. Although osteogenic differentiation was initiated at a genomic level, phenotypic osteoblastic differentiation was not observed. The findings of this study suggest that cells isolated from canine adipose tissue and synovium are sub-optimal substitutes for chondrocytes when engineering articular cartilage in vitro.

Ethical and evidential considerations on the use of novel therapies in veterinary practice.

Novel therapies may be necessary both in the interests of the individual animal and in the advancement of veterinary science. However, special consideration is necessary to safeguard the welfare of the animals, ensure fully informed consent from the owner, determine the procedure's value in other cases and appropriately disseminate results. This article reviews ethical and evidential considerations raised when novel therapies are undertaken in veterinary practice, based on a series of committee meetings and intervening discussions held between members of the British Small Animal Veterinary Association Scientific Committee and Officers (2010-2011). The aim of this article is to encourage the advancement of novel veterinary therapies while safeguarding the welfare of animals.

Variations in cell morphology in the canine cruciate ligament complex.

Cell morphology may reflect the mechanical environment of tissues and influence tissue physiology and response to injury. Normal cruciate ligaments (CLs) from disease-free stifle joints were harvested from dog breeds with a high (Labrador retriever) and low (Greyhound) risk of cranial cruciate ligament (CCL) rupture. Antibodies against the cytoskeletal components vimentin and alpha tubulin were used to analyse cell morphology; nuclei were stained with 4',6-diamidino-2-phenylindole, and images were collected using conventional and confocal microscopy. Both cranial and caudal CLs contained cells of heterogenous morphologies. Cells were arranged between collagen bundles and frequently had cytoplasmic processes. Some of these processes were long (type A cells), others were shorter, thicker and more branched (type B cells), and some had no processes (type C cells). Processes were frequently shown to contact other cells, extending longitudinally and transversely through the CLs. Cells with longer processes had fusiform nuclei, and those with no processes had rounded nuclei and were more frequent in the mid-substance of both CLs. Cells with long processes were more commonly noted in the CLs of the Greyhound. As contact between cells may facilitate direct communication, variances in cell morphology between breeds at a differing risk of CCL rupture may reflect differences in CL physiology.

Observer variation in the evaluation and classification of severe central tarsal bone fractures in racing Greyhounds.

OBJECTIVES: To determine observer agreement on radiographic evaluation of central tarsal bone (CTB) fractures and compare this with evaluation of the same fractures using computed tomography (CT). METHODS: Radiographs and CT scans were obtained of the right tarsi from limbs of Greyhounds euthanatized after sustaining severe CTB fracture during racing. Four observers described and classified each fracture. Inter- and intra-observer agreements were calculated. RESULTS: Inter-observer agreement was higher for assessment of fractures using CT. Several fractures assessed by radiography were misclassified as a less severe type. Intra-observer agreement for assessment and classification of CTB fractures via radiography versus CT was variable. Overall agreement among all four observers was higher for CT than radiography. Additionally, when identifying fractures of the adjacent tarsal bones, observer agreement was higher for CT than radiography. CLINICAL SIGNIFICANCE: Computed tomography improved observer ability to correctly evaluate CTB fracture and detect the degree of displacement and extent of any comminution. Identification of fractures of adjacent tarsal bones was also improved when tarsi were assessed using CT. These data suggest that treatment decisions based solely on radiographic assessment of CTB fractures may not produce the expected outcome.

Demineralised bone matrix in veterinary orthopaedics: a review.

Demineralised bone matrix (DBM) is commonly used in human orthopaedics as an allograft prepared from cortical bone. As such, there is a background of literature on the basic science, experimental animal studies and clinical human use of DBM. Because canine DBM is now increasingly available and used in veterinary orthopaedics, this review aims to update the veterinary orthopaedic specialist with the properties and activities of this bone allograft product.

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.

Effect of surgical technique on radiographic fusion of the anconeus in the treatment of ununited anconeal process.

OBJECTIVES: The aim of this study was to determine if internal fixation of the anconeus combined with a proximal ulnar osteotomy was more likely to result in fusion of the anconeus to the ulna compared with a proximal ulnar osteotomy alone. METHODS: A total of 12 orthopaedic referral clinics reviewed their clinical databases for cases of ununited anconeal process. Demographic and clinical parameters were collected along with radiographic follow-up at a minimum of four weeks. Cases treated with proximal ulnar osteotomy alone were compared with those treated with proximal ulnar osteotomy + internal fixation. Both groups were compared for background and disease variables. We tested for an association between treatment method and whether radiographic anconeal union had occurred. RESULTS: A total of 47 elbows (44 dogs) were identified. Of these, 28 cases (average age 7.6 months) were treated with proximal ulnar osteotomy (of which eight were stabilised with an intramedullary pin) alone. Nineteen cases (average age 7.1 months) were treated with proximal ulnar osteotomy + internal fixation. The two groups were not significantly different in age (P=0.638, Mann-Whitney U test). Fourteen of 28 cases with proximal ulnar osteotomy alone displayed anconeal union at follow-up compared with 16 of 19 cases of proximal ulnar osteotomy + internal fixation, and this difference was statistically significant (P=0.029, Fisher's exact test). CLINICAL SIGNIFICANCE: These data suggest that use of a lag screw to stabilise and compress the ununited anconeal process in addition to proximal ulnar osteotomy produces a better radiographic outcome. It is argued that radiographic union of the anconeus is likely to be associated with better long-term clinical outcome but further studies are required to confirm this.

Validation of a client-based clinical metrology instrument for the evaluation of canine elbow osteoarthritis.

OBJECTIVE: To validate a disease-specific client-based clinical metrology instrument (questionnaire) for dogs with chronic osteoarthritis of the elbow joint. MATERIALS AND METHODS: This was a prospective cohort study involving 26 dogs with chronic osteoarthritis of the elbow with 24 associated clients. Validity (face and criterion), reliability and responsiveness of the metrology instrument (named "Liverpool Osteoarthritis in Dogs [elbow]") were tested in a sequence of studies. Face validity involved use of international peer review. Reliability was assessed using a test-retest scenario with a two week interval; peak vertical force as measured by a force platform was used as an external standard measure. Responsiveness was tested with a two week, single-blinded placebo-controlled intervention using a licensed non-steroidal anti-inflammatory drug. RESULTS: The reliability of Liverpool Osteoarthritis in Dogs (elbow) in the test-retest scenario was good; intraclass correlation coefficient is 0.89, 95 per cent confidence interval 0.75 to 0.95, compared with intraclass correlation coefficient 0.92, 95 per cent confidence interval 0.74 to 0.98, for peak vertical force. Responsiveness testing indicated that the "net" effect size (allowing for placebo effect) for Liverpool Osteoarthritis in Dogs (elbow) was 0.13 compared with (-)0.18 for the force platform. Criterion validity for Liverpool Osteoarthritis in Dogs (elbow) against peak vertical force was poor; Spearman's rank correlation is -0.24 (P=0.30). CLINICAL SIGNIFICANCE: Liverpool Osteoarthritis in Dogs (elbow) was considered reliable with satisfactory responsiveness. The poor criterion validity suggests a mismatch between force platform peak vertical force and client perceptions of lameness. This instrument requires further validation in larger studies with alternative client groups and alternative therapeutic interventions, but this initial validation suggests that Liverpool Osteoarthritis in Dogs (elbow) is worthy of continued investigation.

Systematic review of the management of canine osteoarthritis.

This review assesses the evidence for the efficacy of therapies used in the management of osteoarthritis in dogs on the basis of papers published in peer-reviewed journals in English between 1985 and July 2007. Sixty-eight papers were identified and evaluated. They considered four alternative therapies, one use of functional food, two intra-articular agents, six nutraceutical agents, 21 pharmacological agents, two physical therapies, three surgical techniques and two combinations of weight control. There was a high level of comfort (strong evidence) for the efficacy of carprofen, firocoxib and meloxicam, and a moderate level of comfort for the efficacy of etodolac in modifying the signs of osteoarthritis. There was a moderate level of comfort for the efficacy of glycosaminoglycan polysulphate, licofelone, elk velvet antler and a functional food containing green-lipped mussel for the modification of the structures involved in the disease. There was weak or no evidence in support of the use of doxycycline, electrostimulated acupuncture, extracorporeal shockwave therapy, gold wire acupuncture, hyaluronan, pentosan polysulphate, P54FP (extract of turmeric), tiaprofenic acid or tibial plateau levelling osteotomy.