Population genetic analysis and genome-wide association study of patellar luxation in a Thai population of Pomeranian dogs.

The genetics of patellar luxation (PL) were investigated in Pomeranian dogs presented at the Small Animal Hospital, Faculty of Veterinary Science, Chulalongkorn University. A cohort of 339 Pomeranian dogs, part of a four-generation pedigree of 842 Pomeranians, was screened for PL from 2006 to 2013. PL was present in 77% of the screened dogs, with 84% having bilateral and 16% unilateral luxation. Medial PL was more common (95%) than lateral PL (2%) or bidirectional PL (3%). The risk of PL was similar in male and female dogs (female:male relative risk 1.11, 95% CI 0.98-1.25). The heritability of PL in the screened population was 0.44±0.04 using a threshold model. A genome-wide association study of PL (48 cases and 48 controls) using a high-density SNP array indicated the possible involvement of 15 chromosomal regions, of which CFA05 and CFA32 remained associated in a larger study involving an additional 128 cases and 7 controls. Candidate genes in these regions may be involved in the pathogenesis of PL in Pomeranian dogs.

The oldest case yet reported of osteoarthritis in a dog: an archaeological and radiological evaluation.

A century ago the remains of a dog skeleton were found in an archaeological double human burial, near Bonn-Oberkassel (Germany). Recent re-examination of the dog remains revealed that they were about 14,500 years old. Based on the growth plates, the animal was considered to be approximately 7·5 months old at the time of death. Based on the minimal humeral diameter, it was calculated that it was approximately 0·47 m tall at the shoulder and weighed approximately 15·7 kg. The right proximal ulna of this skeleton showed osteoarthritis, manifested by an osteophyte of 5×3×1·5 mm3 at its cranial edge, with no identified primary developmental causes for osteoarthritis. Osteochondritis dissecans, joint incongruity and trauma are possible aetiologies. The left ulna did not reveal any abnormalities.

Breeding implications resulting from classification of patellae luxation in dogs.

Patellar luxation (PL) is one of the major hereditary orthopaedic abnormalities observed in a variety of dog breeds. When the patellae move sideways out of the trochlear groove, this is called PL. The PL score varies between dogs from normal to very severe. Reducing the prevalence of PL by breeding could prevent surgery, thereby improve welfare. Orthopaedic specialists differentiate between normal and loose patellae, where the patellae can be moved to the edge of the trochlear groove, considering scoring loose patellae as normal in the future. Loose patellae are considered acceptable for breeding so far by the breeding organization. The aim of this study was to analyse the genetic background of PL to decide on the importance of loose patellae when breeding for healthy dogs. Data are available from two dog breeds, that is Flat-coated Retrievers (n = 3808) and Kooiker dogs (n = 794), with a total of 4602 dogs. Results show that loose patellae indicate that dogs are genetically more susceptible to develop PL because family members of the dogs with loose patellae showed more severe PL. In addition, the estimated breeding values for dogs with loose patellae indicate that breeding values of dogs with loose patellae were worse than breeding values obtained for dogs with a normal score. Given these results, it is advised to orthopaedic specialists to continue to score loose patellae as a separate class and to dog breeders to minimize the use of dogs in breeding with a genetically higher susceptibility for PL.

Proximo-distal patellar position in three small dog breeds with medial patellar luxation.

INTRODUCTION: Medial patellar luxation is thought to be associated with a high proximal position of the patella in the trochlear groove. OBJECTIVE: To determine whether the ratio of patellar ligament length and patellar length (L:P) is influenced by the stifle angle (75°, 96°, 113°, 130°, and 148°) in small dog breeds and to compare the L:P ratio in dogs of three small dog breeds with and without medial patellar luxation. METHODS: A mediolateral radiograph of the stifle joint was used to measure the L:P ratio in the stifle joints of dogs of three small breeds with and without medial patellar luxation. The L:P ratio was evaluated at five stifle angles (75°, 96°, 113°, 130°, and 148°) in 14 cadavers (26 stifle joints) of small dog breeds in order to identify the best stifle angle to measure the L:P ratio. Then the mean ± SD L:P ratio was calculated for normal stifles and stifles with medial patellar luxation grades 1, 2, and 3 in 194 Pomeranians, 74 Chihuahuas, and 41 Toy or Standard Poodles. RESULTS: The L:P ratio was the same for all five stifle angles in the cadavers (p = 0.195). It was also not significantly different in the three breeds (p = 0.135), in normal and medial patellar luxation-affected stifles overall (p = 0.354), and in normal and medial patellar luxation-affected joints within each breed (p = 0.19). CLINICAL SIGNIFICANCE: We conclude that a proximo-distal patellar position is not associated with medial patellar luxation in Pomeranians, Chihuahuas, and Toy or Standard Poodles. Thus a longer patellar ligament length does not play a role in the pathophysiology of medial patellar luxation in these small dog breeds.

Radiographic and computed tomographic assessment of the development of the antebrachia and elbow joints in Labrador Retrievers with and without medial coronoid disease.

OBJECTIVES: To compare the development, monitored by radiography and computed tomography, of the antebrachia and elbow joints in seven Labrador Retrievers with healthy elbow joints and in seven Labrador Retrievers that developed medial coronoid disease (MCD), in order to determine whether disturbances in the development of the antebrachia and elbow joints, between the age of six and 17 weeks may lead to medial coronoid disease. METHODS: A prospective study of 14 Labrador Retrievers in their active growth stage was performed. The development of the antebrachia and elbow joints was assessed between six and 17 weeks of age using radiography and computed tomography determining the development of secondary ossification centres, radioulnar length ratio, radial angulation, and inter-relationship between the humerus, ulna and radius. RESULTS: For the parameters of ossification of secondary ossification centres, radioulnar length ratio, radial angulation, and joint congruence evaluation, there was no significant difference in the development of the antebrachia and elbow joints of seven Labrador Retrievers positive and seven Labrador Retrievers negative for MCD at the age of six to 17 weeks. CLINICAL SIGNIFICANCE: These findings demonstrate that the development of MCD in the Labrador Retrievers in our study was not related to any disturbance in the development of the antebrachia and elbow joints during the rapid growth phase.

Extended proximal trochleoplasty for the correction of bidirectional patellar luxation in seven Pomeranian dogs.

Seven Pomeranians with bidirectional patellar luxation (BPL) were prospectively studied regarding aetiology and results of a new surgical technique. Radiographic evaluation of the ratio between patellar ligament length and patellar bone length revealed no differences between Pomeranians with bidirectional patellar luxation and healthy stifle joints. Functional rather than anatomic patella alta might be associated with bidirectional patellar luxation in Pomeranians. The surgical outcome of extended proximal trochleoplasty was good-to-excellent in 87·5% of the stifles and all dogs achieved functional recovery. There was only minimal radiographic progression of osteophyte formation at 48 weeks after surgery. To the authors' knowledge, this is the first report on bidirectional patellar luxation in small breed dogs and its successful surgical treatment.

Skeletal and hepatic changes induced by chronic vitamin A supplementation in cats.

The first aim of this study was to determine whether vitamin D supplementation influenced the effects of high vitamin A intake on new bone formation in adult cats. The second aim was to determine whether high vitamin A intake in cats caused liver pathology and, if so, whether the current upper limit for the dietary intake of vitamin A for healthy adult cats would be safe. Twenty-four healthy adult cats were divided into four groups that received a control diet supplemented with peanut oil (control), or peanut oil containing a 100-fold increase in vitamin A (HA), or a 100-fold increase in vitamin A and a fivefold increase in vitamin D (HAMD), or a 100-fold increase in vitamin A and a 65-fold increase in vitamin D (HAHD) over a period of 18 months. Cats did not show abnormal locomotion or clinical signs of liver failure after 18 months of supplementation but did show subtle skeletal changes and liver pathology, suggesting that the current National Research Council (2006) safe upper limit for vitamin A for cats is too high. The addition of vitamin D did not seem to influence bone pathology. While moderately elevated dietary vitamin D levels (HAMD) seemed to protect cats against the liver pathology caused by the consumption of large amounts of vitamin A, higher dietary levels of vitamin D (HAHD) did not seem to be protective.

Forelimb and hindlimb ground reaction forces of walking cats: assessment and comparison with walking dogs.

The primary aim of this study was to assess the potential of force plate analysis for describing the stride cycle of the cat. The secondary aim was to define differences in feline and canine locomotion based on force plate characteristics. Ground reaction forces of 24 healthy cats were measured and compared with ground reaction forces of 24 healthy dogs. Force-time waveforms in cats generated by force plate analysis were consistent, as reflected by intra-class correlation coefficients for peak vertical force, peak propulsive force and peak braking force (0.94-0.95, 0.85-0.89 and 0.89-0.90, respectively). Compared with dogs, cats had a higher peak vertical force during the propulsion phase (cat, 3.89 ± 0.19 N/kg; dog, 3.03 ± 0.16 N/kg), and a higher hindlimb propulsive force (cat, -1.08 ± 0.13 N/kg; dog, (-0.87 ± 0.13 N/kg) and hindlimb impulse (cat, -0.18 ± 0.03 N/kg; dog, -0.14 ± 0.02 N/kg). Force plate analysis is a valuable tool for the assessment of locomotion in cats, because it can be applied in the clinical setting and provides a non-invasive and objective measurement of locomotion characteristics with high repeatability in cats, as well as information about kinetic characteristics. Differences in force-time waveforms between cats and dogs can be explained by the more crouched position of cats during stance and their more compliant gait compared with dogs. Feline waveforms of the medio-lateral ground reaction forces also differ between cats and dogs and this can be explained by differences in paw supination-pronation.

Prevalence and genetics of patellar luxation in Kooiker dogs.

The prevalence of patellar luxation (PL) and genetic factors potentially involved in the disorder were investigated in Dutch Kooiker dogs. A cohort of 842 Kooiker dogs, the offspring of 195 sires and 318 dams, was screened for PL from 1994 to 2011. The cohort was included in a pedigree of 1737 Kooiker dogs comprising nine generations. PL was present in 24% of screened dogs, with unilateral and bilateral luxation being observed equally frequently. Medial PL was more common (61%) than lateral PL (32%) or bidirectional PL (7%). The frequency of PL was similar in male and female dogs, with a female:male relative risk of 1.15 (95% confidence interval, CI, 0.90-1.48). The heritability of PL in the screened population was 0.27 ± 0.07. Since the start of the screening programme, the prevalence of PL decreased from 28% to 19%. A genome-wide association study of PL with 48 cases and 42 controls suggested the possible involvement of a region on chromosome 3 (Praw = 1.32 × 10(-)(5), Pgenome = 0.142), but the involvement of this region could not be confirmed in a validation group. Breeding programmes for complex diseases, such as PL, would benefit from combining pedigrees, phenotypes and genotypes, i.e. from genomic selection, as is currently the method of choice for breeding of production animals.

Prevalence and co-occurrence of hip dysplasia and elbow dysplasia in Dutch pure-bred dogs.

Hip as well as elbow dysplasia (HD, ED) are developmental disorders leading to malformation of their respective joints. For a long time both disorders have been scored and targeted for improvement using selective breeding in several Dutch dog populations. In this paper all scores for both HD and ED, given to pure bred dogs in the Netherlands from 2002 to 2010, were analyzed. Heritabilities and correlations between HD and ED were calculated for the 4 most frequently scored breeds. Heritabilities ranged from 0.0 to 0.37 for HD related traits (FCI-score, osteoarthritis, congruity, shape and laxity (Norberg angle); FCI: Fédération Cynologique Internationale) and from 0.0 to 0.39 for ED related traits (IEWG score, osteoarthritis, sclerosis and indentation; IEWG: International Elbow Working Group). HD related traits showed high genetic and residual correlations among each other but were only to a minor extent correlated with ED related traits, which also showed high correlations among each other. Genetic correlations were higher than residual correlations. Phenotypic and genetic trends since 2001 for the four most scored breeds were slightly positive but decreasing over time, indicating that selection over the past decade has not been effective.

Phenotypic and genetic trends of patellar luxation in Dutch Flat-Coated Retrievers.

Canine patellar luxation has been described in various dog breeds, with high prevalence especially in smaller dogs. Most dogs suffer from medial displacement of the patella, although in larger dogs lateral displacement is also seen. A sex predisposition has been described for females. Patellar luxation is considered a polygenic, multifactorial disorder. From 1990 to 2007, in total 3834 Flat-Coated Retrievers were screened; 23.6% of those animals were affected with patellar luxation. Lateral displacement of the patella was most common in this breed (61% of cases), whereas medial (31% of cases) and lateral and medial (8% of cases) were less common. Unilateral involvement (51% of cases) was just as often observed as was bilateral involvement (49% of cases). Females were more often affected with patellar luxation (30% of all tested females) than were males (17% of all tested males). The heritability of patellar luxation was 0.17 ± 0.03 in this population, and breeding with one affected parent increased the prevalence of patellar luxation in offspring by 45% compared to that with two unaffected parents. Since the start of the screening program, there was an initial decrease from 28% to 18% in incidence, but this stagnated thereafter. The annual average estimated breeding values followed the same pattern. With approximately one quarter of the Dutch Flat-Coated Retrievers being affected with patellar luxation, this population shows unusually high prevalence compared with reports in other large-breed dogs. The heritability for patellar luxation in this population was moderate (0.17), indicating that environmental factors play a large role in the manifestation of the disorder. A screening program reduced the prevalence of patellar luxation in this breed, but improvement has recently stagnated. Inclusion of breeding values in the screening program could improve its effectiveness.

Assessment of articular cartilage and subchondral bone using EPIC-microCT in Labrador retrievers with incipient medial coronoid disease.

The aetiopathogenesis of medial coronoid disease (MCD) remains obscure, despite its high prevalence. The role of changes to subchondral bone or articular cartilage is much debated. Although there is evidence of micro-damage to subchondral bone, it is not known whether this is a cause or a consequence of MCD, nor is it known whether articular cartilage is modified in the early stages of the disease. The aim of the present study was to use equilibrium partitioning of an ionic contrast agent with micro-computed tomography (microCT) to investigate changes to both the articular cartilage and the subchondral bone of the medial coronoid processes (MCP) of growing Labrador retrievers at an early stage of the disease and at different bodyweights. Of 14 purpose-bred Labrador retrievers (15-27 weeks), six were diagnosed with bilateral MCD and one was diagnosed with unilateral MCD on the basis of microCT studies. The mean X-ray attenuation of articular cartilage was significantly higher in dogs with MCD than in dogs without MCD (P<0.01). In all dogs, the mean X-ray attenuation of articular cartilage was significantly higher at the lateral (P<0.001) than at the proximal aspect of the MCP, indicating decreased glycosaminoglycan content. Changes in parameters of subchondral bone micro-architecture, namely the ratio of bone volume to tissue volume (BV/TV), bone surface density (BS/TV), bone surface to volume ratio (BS/BV), trabecular thickness (Tb.Th; mm), size of marrow cavities described by trabecular spacing (Tb.Sp; mm), and structural model index (SMI), differed significantly by litter (P<0.05) due to the difference in age and weight, but not by the presence/absence of MCD (P>0.05), indicating that subchondral bone density is not affected in early MCD. This study demonstrated that cartilage matrix and not subchondral bone density is affected in the early stages of MCD.

Delayed endochondral ossification in early medial coronoid disease (MCD): a morphological and immunohistochemical evaluation in growing Labrador retrievers.

Medial coronoid disease (MCD) is a common joint disease of dogs. It has a multifactorial aetiology, but the relationship between known causal factors and the disease has yet to be elucidated. As most of the published literature is clinical and it reports changes associated with advanced disease, it is not known whether the changes reflect the cause or consequences of the condition. The aim of this study was to investigate early micromorphological changes occurring in articular cartilage and to describe the postnatal development of the medial coronoid process (MCP) before MCD develops. Three litters of MCD-prone young Labrador retrievers were purpose-bred from a dam and two sires with MCD. Comparisons of the micromorphological appearance of the MCP in MCD-negative and MCD-positive joints demonstrated that MCD was initially associated with a disturbance of endochondral ossification, namely a delay in the calcification of the calcifying zone, without concurrent abnormalities in the superficial layers of the joint cartilage. Cartilage canals containing patent blood vessels were only detected in dogs <12 weeks old, but the role of these channels in impaired ossification requires further investigation. Retained hyaline cartilage might ossify as the disease progresses, but weak areas can develop into cracks between the retained cartilage and the subchondral bone, leading to cleft formation and fragmentation of the MCP.

Evaluation of surgical treatment of medial patellar luxation in Pomeranian dogs.

In a prospective study, the outcome of surgical correction of medial patellar luxation of 70 stifle joints in 55 Pomeranian dogs was evaluated. Trochlear block recession alone was performed in 46 stifle joints, or in combination with tibial tuberosity transposition in 24 stifle joints in cases with grade II, III or IV medial patellar luxation. Additional procedures were performed to restore lateral and medial retinacular function. The recurrence of patellar luxation and the degree of lameness were evaluated up to at least 16 weeks after surgery. The overall recurrence rate was 10%. The outcome of surgery was considered good for grade II luxation with a 100% success rate. Recurrent medial patellar luxation was diagnosed in approximately 11% of dogs with grade III and in 36% of dogs with grade IV luxation. The postoperative lameness score decreased significantly in comparison with the preoperative score at four weeks and thereafter until the end of the study.

The early development of medial coronoid disease in growing Labrador retrievers: radiographic, computed tomographic, necropsy and micro-computed tomographic findings.

Medial coronoid disease (MCD) encompasses lesions of the entire medial coronoid process (MCP), both of the articular cartilage and the subchondral bone. To detect the earliest signs of MCD, radiography and computed tomography were used to monitor the development of MCD in 14 Labrador retrievers, from 6 to 7 weeks of age until euthanasia. The definitive diagnosis of MCD was based on necropsy and micro-computed tomography findings. The frequency of MCD in the dogs studied was 50%. Radiographic findings did not provide evidence of MCD, ulnar subtrochlear sclerosis or blunting of the cranial edge of the MCP. Computed tomography was more sensitive (30.8%) than radiography (0%) in detecting early MCD, with the earliest signs detectable at 14 weeks of age. A combination of the necropsy and micro-computed tomography findings of the MCP showed that MCD was manifested as a lesion of only the subchondral bone in dogs <18 weeks of age. In all dogs (affected and unaffected), there was close contact between the base of the MCP and the proximal radial head in the congruent joints. Computed tomography and micro-computed tomography findings indicated that the lesions of MCD probably originated at the base of the MCP.

Spinal hyperostosis in humans and companion animals.

Both spondylosis and diffuse idiopathic skeletal hyperostosis (DISH) are prevalent in humans and are considered distinct entities. Nowadays, the term spondylosis is in the biomedical literature mostly used when also degenerative disc disease is present. In companion animals, many reports on spondylosis, often without intervertebral disc degeneration, are described. The nomenclature and the definitions of both spondylosis and DISH in the biomedical and veterinary literature should be more in line to facilitate comparison. DISH occurs in dogs but has not been described in cats yet. DISH and spondylosis can co-occur in dogs in one animal. Boxers may serve as translational disease models for the elucidation of the gene(s) involved in the (etio)pathogenesis of DISH or serve as a test population for newly developed treatment options.

Incidence and genetic aspects of patellar luxation in Pomeranian dogs in Thailand.

There is a high incidence of patellar luxation (PL) in Pomeranian dogs from Thailand. DNA samples were collected from 59 dogs originating from 15 families. PL was present in 75% of the dogs with a male:female ratio of 1:1.95. Polymorphic microsatellites situated close to the COL6A1, COL6A3, COL9A1, COL9A2, and COL9A3 genes were analyzed for linkage to the phenotype. Sibling-pair analysis revealed that none of the collagen markers analyzed had a high non-parametric linkage score with the highest score, 1.56, for COL9A2 (P=0.07). The low LOD scores for these collagen genes indicated a non-involvement in the pathogenesis of PL in Pomeranians. An association study with a low density single nucleotide polymorphism (SNP) set indicated the possible involvement of a region on chromosome 7. The association of this region remained indicative when larger groups of 43 cases and 40 controls were compared (Chi square test P=0.01).

Intervertebral disc disease in dogs - part 1: a new histological grading scheme for classification of intervertebral disc degeneration in dogs.

Intervertebral disc (IVD) degeneration is common in dogs and can lead to serious disorders. Current treatments can relieve clinical signs of disease, but do not restore IVD function. The development of regenerative strategies for IVD dysfunction requires detailed knowledge of the pathogenesis of IVD degeneration and its underlying mechanisms. Histological examination of IVDs at different stages of degeneration might provide this knowledge, but as there is currently no histological grading scheme for canine IVD degeneration, the aim of this study, which is the first of a two-part series, was to design and validate an appropriate scheme. Three independent observers evaluated 35 IVDs at different stages of degeneration using the scheme. Glycosaminoglycan contents of the nucleus pulposus and macroscopic grading according to Thompson, which are considered 'gold standards' for IVD degeneration, were used to validate the scheme. Reproducibility was assessed by analysing the inter-observer reliability of all individual variables of the grading scheme, using a weighted κ analysis. Significant correlations were found between Thompson grading and total histological score (r=0.94; P<0.01) and between glycosaminoglycan content and total histological score (r=-0.72; P<0.01). Most individual histological variables showed 'moderate' to 'almost perfect' inter-observer reliability. The high correlation with the gold standards in combination with the high reproducibility indicates that the proposed histological grading scheme is reliable and objective for classification of IVD degeneration in both chondrodystrophic and non-chondrodystrophic dog breeds.

The effect of dietary long-chain omega-3 fatty acid supplementation on owner's perception of behaviour and locomotion in cats with naturally occurring osteoarthritis.

The aim of this randomized, double-blinded, placebo-controlled, cross-over designed study was to demonstrate the clinical effect, registered by a survey, of a 10-week period of omega-3 fatty acid supplementation of the diet (1.53 g eicosapentaenoic acid (EPA) and 0.31 g DHA, both per 1000 kcal ME, equivalent to the complete diet) of 16 cats with radiologically documented, naturally occurring osteoarthritis (OA), in comparison with a 10-week period of supplementation with corn oil (0.00 g EPA and 0.00 g DHA, both per 1000 kcal ME). Cats on the fish oil revealed higher activity level (p = 0.07), more walking up and down the stairs (p = 0.07), less stiffness during gait (p = 0.03), more interaction with the owner (p = 0.07) and higher jumps (p = 0.03) compared to those on corn oil supplementation. In conclusion, supplementation of long-chain omega-3 polyunsaturated fatty acids changes the owner's perception of some aspects of behaviour and locomotion in cats with naturally occurring OA.

Treatment of spinal fractures using Lubra plates. A retrospective clinical and radiological evaluation of 15 cases.

The purpose of this retrospective study was to review the clinical use along with the short- and long-term outcome in patients treated with Lubra plates to stabilize spinal fracture and dislocations that were considered unstable at time of surgery according to the 'three compartment theory'. The data that were collected included breed, age, gender, body weight of the patients, cause of injury, neurological grade (pre- and postoperative), radiographic findings, surgical treatment, and clinical and radiological outcome. Thirteen dogs and two cats were included with thoracic (1 case), thoracolumbar (3 cases), midlumbar (5 cases) and caudal lumbar (6 cases) vertebral fractures. For stabilization, the small-sized (3 cases), medium-sized (6 cases), and large-sized (6 cases) Lubra plates were used. The clinical outcome was excellent in 10/15 patients, functional in 2/15 and poor in 3/15 with a median follow-up period of nine years (range 2 months to 12 years). The fractures eventually stabilized by ventral spondylosis. No implant failure was seen, however demineralization of the spinous processes necessitated implant removal in one case. Our results suggest that Lubra plating is an appropriate technique for thoracolumbar and lumbar vertebral fractures as well as luxations in dogs and cats. The prognosis for neurological recovery was excellent when the animal had a neurological grade of 3 and was not paralyzed.