Common Orthopedic Traits and Screening for Breeding Programs.

Orthopedic diseases are complex traits, meaning genetics and environmental factors affect risk, making identification of genetic associations difficult. In the United States, hip and elbow scores, patellar luxation scores, Legg-Calvé-Perthes disease, and shoulder osteochondrosis affectedness are available in the Orthopedic Foundation for Animals registry. Distraction indices and extended, ventrodorsal hip conformation scores are recorded by PennHIP. Application of estimated breeding values for hip and elbow dysplasia in breeder selection reduces the severity and prevalence of these traits. Genomic prediction and whole-genome sequence technologies and methods should improve knowledge of genetics underlying orthopedic diseases, leading to improved canine orthopedic genetic quality.

Complex Feline Disease Mapping Using a Dense Genotyping Array.

The current feline genotyping array of 63 k single nucleotide polymorphisms has proven its utility for mapping within breeds, and its use has led to the identification of variants associated with Mendelian traits in purebred cats. However, compared to single gene disorders, association studies of complex diseases, especially with the inclusion of random bred cats with relatively low linkage disequilibrium, require a denser genotyping array and an increased sample size to provide statistically significant associations. Here, we undertook a multi-breed study of 1,122 cats, most of which were admitted and phenotyped for nine common complex feline diseases at the Cornell University Hospital for Animals. Using a proprietary 340 k single nucleotide polymorphism mapping array, we identified significant genome-wide associations with hyperthyroidism, diabetes mellitus, and eosinophilic keratoconjunctivitis. These results provide genomic locations for variant discovery and candidate gene screening for these important complex feline diseases, which are relevant not only to feline health, but also to the development of disease models for comparative studies.

Genomic Prediction of Two Complex Orthopedic Traits Across Multiple Pure and Mixed Breed Dogs.

Canine hip dysplasia (CHD) and rupture of the cranial cruciate ligament (RCCL) are two complex inherited orthopedic traits of dogs. These two traits may occur concurrently in the same dog. Genomic prediction of these two diseases would benefit veterinary medicine, the dog's owner, and dog breeders because of their high prevalence, and because both traits result in painful debilitating osteoarthritis in affected joints. In this study, 842 unique dogs from 6 breeds with hip and stifle phenotypes were genotyped on a customized Illumina high density 183 k single nucleotide polymorphism (SNP) array and also analyzed using an imputed dataset of 20,487,155 SNPs. To implement genomic prediction, two different statistical methods were employed: Genomic Best Linear Unbiased Prediction (GBLUP) and a Bayesian method called BayesC. The cross-validation results showed that the two methods gave similar prediction accuracy (r = 0.3-0.4) for CHD (measured as Norberg angle) and RCCL in the multi-breed population. For CHD, the average correlation of the AUC was 0.71 (BayesC) and 0.70 (GBLUP), which is a medium level of prediction accuracy and consistent with Pearson correlation results. For RCCL, the correlation of the AUC was slightly higher. The prediction accuracy of GBLUP from the imputed genotype data was similar to the accuracy from DNA array data. We demonstrated that the genomic prediction of CHD and RCCL with DNA array genotype data is feasible in a multiple breed population if there is a genetic connection, such as breed, between the reference population and the validation population. Albeit these traits have heritability of about one-third, higher accuracy is needed to implement in a natural population and predicting a complex phenotype will require much larger number of dogs within a breed and across breeds. It is possible that with higher accuracy, genomic prediction of these orthopedic traits could be implemented in a clinical setting for early diagnosis and treatment, and the selection of dogs for breeding. These results need continuous improvement in model prediction through ongoing genotyping and data sharing. When genomic prediction indicates that a dog is susceptible to one of these orthopedic traits, it should be accompanied by clinical and radiographic screening at an acceptable age with appropriate follow-up.

Synovial fluid lubricin increases in spontaneous canine cruciate ligament rupture.

Lubricin is an important boundary lubricant and chondroprotective glycoprotein in synovial fluid. Both increased and decreased synovial fluid lubricin concentrations have been reported in experimental post-traumatic osteoarthritis (PTOA) animal models and in naturally occurring joint injuries in humans and animals, with no consensus about how lubricin is altered in different species or injury types. Increased synovial fluid lubricin has been observed following intra-articular fracture in humans and horses and in human late-stage osteoarthritis; however, it is unknown how synovial lubricin is affected by knee-destabilizing injuries in large animals. Spontaneous rupture of cranial cruciate ligament (RCCL), the anterior cruciate ligament equivalent in quadrupeds, is a common injury in dogs often accompanied by OA. Here, clinical records, radiographs, and synovial fluid samples from 30 dogs that sustained RCCL and 9 clinically healthy dogs were analyzed. Synovial fluid lubricin concentrations were nearly 16-fold greater in RCCL joints as compared to control joints, while IL-2, IL-6, IL-8, and TNF-α concentrations did not differ between groups. Synovial fluid lubricin concentrations were correlated with the presence of radiographic OA and were elevated in three animals sustaining RCCL injury prior to the radiographic manifestation of OA, indicating that lubricin may be a potential biomarker for early joint injury.

Bayesian and Machine Learning Models for Genomic Prediction of Anterior Cruciate Ligament Rupture in the Canine Model.

Anterior cruciate ligament (ACL) rupture is a common, debilitating condition that leads to early-onset osteoarthritis and reduced quality of human life. ACL rupture is a complex disease with both genetic and environmental risk factors. Characterizing the genetic basis of ACL rupture would provide the ability to identify individuals that have high genetic risk and allow the opportunity for preventative management. Spontaneous ACL rupture is also common in dogs and shows a similar clinical presentation and progression. Thus, the dog has emerged as an excellent genomic model for human ACL rupture. Genome-wide association studies (GWAS) in the dog have identified a number of candidate genetic variants, but research in genomic prediction has been limited. In this analysis, we explore several Bayesian and machine learning models for genomic prediction of ACL rupture in the Labrador Retriever dog. Our work demonstrates the feasibility of predicting ACL rupture from SNPs in the Labrador Retriever model with and without consideration of non-genetic risk factors. Genomic prediction including non-genetic risk factors approached clinical relevance using multiple linear Bayesian and non-linear models. This analysis represents the first steps toward development of a predictive algorithm for ACL rupture in the Labrador Retriever model. Future work may extend this algorithm to other high-risk breeds of dog. The ability to accurately predict individual dogs at high risk for ACL rupture would identify candidates for clinical trials that would benefit both veterinary and human medicine.

Decreased incidence of perioperative inadvertent hypothermia and faster anesthesia recovery with increased environmental temperature: A nonrandomized controlled study.

OBJECTIVE: To determine perioperative inadvertent hypothermia (PIH) incidence, risk factors, prevention methods, and effect of PIH prevention on anesthesia recovery times. STUDY DESIGN: Nonrandomized controlled before-and-after trial. ANIMALS: Dogs (n = 277) and cats (n = 20) undergoing open surgery. METHODS: Incidence and risk factors for PIH (core temperature <96.8°F), existing thermal care practices, and recovery times were documented at baseline. For group 1, a thermal care bundle consisting of protocol-driven active warming combined with raised environmental temperatures (75°F) in induction rooms (IR) and operating rooms (OR) was implemented. Perioperative inadvertent hypothermia incidence and recovery times were recorded. For group 2, baseline active warming practices were resumed while environmental temperatures remained elevated. RESULTS: Perioperative inadvertent hypothermia was associated with preoperative imaging (P = .039) and percentage clip area (P = .037). Perioperative inadvertent hypothermia decreased in group 1 (13.5%, n = 96, P < .001) and group 2 (13.0%, n = 100, P < .001) compared with baseline (35.6%, n = 101). Median time from anesthesia withdrawal to extubation decreased in group 1 (5 minutes, P = .028) and group 2 (5 minutes, P = .018) compared with baseline (7 minutes). Median time from anesthesia recovery to spontaneous food intake decreased in group 1 (6 hours, n = 92, P = .016) but not in group 2 (6.0 hours, n = 88, P = .060) compared with baseline (n = 94, 6.7 hours). No group differences in PIH risk factors were identified. CONCLUSION: Perioperative inadvertent hypothermia incidence was high but reducible by raising environmental temperatures alone or in combination with increased focus on active warming. Reductions in PIH shortened recovery times. CLINICAL SIGNIFICANCE: Maintaining IR and OR temperatures at the standard-of-care for human pediatric surgery reduces PIH and may improve outcomes.

Genetic mapping of distal femoral, stifle, and tibial radiographic morphology in dogs with cranial cruciate ligament disease.

Cranial cruciate ligament disease (CCLD) is a complex trait. Ten measurements were made on orthogonal distal pelvic limb radiographs of 161 pure and mixed breed dogs with, and 55 without, cranial cruciate partial or complete ligament rupture. Dogs with CCLD had significantly smaller infrapatellar fat pad width, higher average tibial plateau angle, and were heavier than control dogs. The first PC weightings captured the overall size of the dog's stifle and PC2 weightings reflected an increasing tibial plateau angle coupled with a smaller fat pad width. Of these dogs, 175 were genotyped, and 144,509 polymorphisms were used in a genome-wide association study with both a mixed linear and a multi-locus model. For both models, significant (pgenome <3.46×10-7 for the mixed and< 6.9x10-8 for the multilocus model) associations were found for PC1, tibial diaphyseal length and width, fat pad base length, and femoral and tibial condyle width at LCORL, a known body size-regulating locus. Other body size loci with significant associations were growth hormone 1 (GH1), which was associated with the length of the fat pad base and the width of the tibial diaphysis, and a region on CFAX near IRS4 and ACSL4 in the multilocus model. The tibial plateau angle was associated significantly with a locus on CFA10 in the linear mixed model with nearest candidate genes BET1 and MYH9 and on CFA08 near candidate genes WDHD1 and GCH1. MYH9 has a major role in osteoclastogenesis. Our study indicated that tibial plateau slope is associated with CCLD and a compressed infrapatellar fat pad, a surrogate for stifle osteoarthritis. Because of the association between tibial plateau slope and CCLD, and pending independent validation, these candidate genes for tibial plateau slope may be tested in breeds susceptible to CCLD before they develop disease or are bred.

Imputation of canine genotype array data using 365 whole-genome sequences improves power of genome-wide association studies.

Genomic resources for the domestic dog have improved with the widespread adoption of a 173k SNP array platform and updated reference genome. SNP arrays of this density are sufficient for detecting genetic associations within breeds but are underpowered for finding associations across multiple breeds or in mixed-breed dogs, where linkage disequilibrium rapidly decays between markers, even though such studies would hold particular promise for mapping complex diseases and traits. Here we introduce an imputation reference panel, consisting of 365 diverse, whole-genome sequenced dogs and wolves, which increases the number of markers that can be queried in genome-wide association studies approximately 130-fold. Using previously genotyped dogs, we show the utility of this reference panel in identifying potentially novel associations, including a locus on CFA20 significantly associated with cranial cruciate ligament disease, and fine-mapping for canine body size and blood phenotypes, even when causal loci are not in strong linkage disequilibrium with any single array marker. This reference panel resource will improve future genome-wide association studies for canine complex diseases and other phenotypes.

Spontaneous dog osteoarthritis - a One Medicine vision.

Osteoarthritis (OA) is a global disease that, despite extensive research, has limited treatment options. Pet dogs share both an environment and lifestyle attributes with their owners, and a growing awareness is developing in the public and among researchers that One Medicine, the mutual co-study of animals and humans, could be beneficial for both humans and dogs. To that end, this Review highlights research opportunities afforded by studying dogs with spontaneous OA, with a view to sharing this active area of veterinary research with new audiences. Similarities and differences between dog and human OA are examined, and the proposition is made that suitably aligned studies of spontaneous OA in dogs and humans, in particular hip and knee OA, could highlight new avenues of discovery. Developing cross-species collaborations will provide a wealth of research material and knowledge that is relevant to human OA and that cannot currently be obtained from rodent models or experimentally induced dog models of OA. Ultimately, this Review aims to raise awareness of spontaneous dog OA and to stimulate discussion regarding its exploration under the One Medicine initiative to improve the health and well-being of both species.

Gene expression in hip soft tissues in incipient canine hip dysplasia and osteoarthritis.

Canine hip dysplasia and developmental dysplasia of the human hip share demographic, phenotypic, and clinical features including the predisposition to develop osteoarthritis in affected joints. To support the results of genetic mapping studies for CHD and its concomitant osteoarthritis with functional information, we performed RNA-seq on hip capsule and teres ligament of affected and unaffected dogs. RNA seq showed that expressed genes segregated according age, capsule or ligament, and hip phenotype. Expression of HHIP, DACT2, and WIF1 was significantly higher in capsule from control hips than dysplastic hips indicating a disruption of the hedgehog signaling pathway. Expression of SPON 1, a key component of the WNT pathway, was increased significantly in both dysplastic capsule and ligament while FBN2 and EMILIN3 were significantly increased in dysplastic capsule. Of genes associated with human hip osteoarthritis, expression of ACAN, IGF1, CILP2, COL11A1, COL8A1, and HAPLN was increased significantly in dysplastic capsule. The significant increase in expression of PLA2F, TNFRSF, TMEM, and IGFBP in dysplastic capsule indicated an injury response. Gene set enrichment analysis revealed that genes involved in extracellular matrix structure, epithelial to mesenchymal transition, myogenesis, growth factor signaling, cancer and immune pathways were enriched in dysplastic capsule. For teres ligament from dysplastic joints, genes in retinoic signaling pathways and those encoding extracellular matrix molecules, but not proteoglycans, were enriched. Hip tissues respond to abnormal mechanics early in dysplastic hip development and these pathways present targets for intervention in the early synovitis and capsulitis secondary to canine and human hip dysplasia. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:313-324, 2019.

Retrospective study of factors associated with surgical site infection in dogs following tibial plateau leveling osteotomy.

OBJECTIVE To identify risk factors associated with surgical site infection (SSI) in dogs following tibial plateau leveling osteotomy (TPLO). DESIGN Retrospective cohort study. ANIMALS 320 dogs that underwent unilateral or bilateral TPLO (n = 405 procedures) between 2007 and 2015 and were reexamined by a veterinarian at least once ≥ 8 weeks after the procedure. PROCEDURES Data were extracted from medical records regarding signalment, TPLO procedure details, medical history of dermatitis, and SSI status. Logistic regression was performed to identify factors associated with SSI development. RESULTS An SSI developed following 34 (8.4%; 95% confidence interval [CI], 6.1% to 11.5%) procedures. Prophylactic antimicrobial administration was provided following 36.8% (n = 149) of procedures. For 71 (17.5%) procedures, the dog had dermatitis at the time of surgery; 12 of these procedures involved dermatitis at the surgical site. The incidence of SSI following the 12 procedures for dogs with dermatitis at the surgical site was 16.7% (2/12 [95% CI, 3.3% to 54.3%]) and was 10.2% (6/59 [95% CI, 4.5% to 21.3%]) for dogs with dermatitis elsewhere; however, these differences in incidence were not significant. On multivariable analysis, German Shepherd Dogs (vs other breeds), meniscectomy (vs no meniscectomy), and attending surgeon having performed ≤ 20 (vs > 20) procedures during the study period were associated with increased odds of SSI. CONCLUSIONS AND CLINICAL RELEVANCE SSI following TPLO was associated with the German Shepherd breed, meniscectomy, and surgeon. Prospective studies are needed to investigate the mechanisms underlying these associations.

Joint Genomic Prediction of Canine Hip Dysplasia in UK and US Labrador Retrievers.

Canine hip dysplasia, a debilitating orthopedic disorder that leads to osteoarthritis and cartilage degeneration, is common in several large-sized dog breeds and shows moderate heritability suggesting that selection can reduce prevalence. Estimating genomic breeding values require large reference populations, which are expensive to genotype for development of genomic prediction tools. Combining datasets from different countries could be an option to help build larger reference datasets without incurring extra genotyping costs. Our objective was to evaluate genomic prediction based on a combination of UK and US datasets of genotyped dogs with records of Norberg angle scores, related to canine hip dysplasia. Prediction accuracies using a single population were 0.179 and 0.290 for 1,179 and 242 UK and US Labrador Retrievers, respectively. Prediction accuracies changed to 0.189 and 0.260, with an increased bias of genomic breeding values when using a joint training set (biased upwards for the US population and downwards for the UK population). Our results show that in this study of canine hip dysplasia, little or no benefit was gained from using a joint training set as compared to using a single population as training set. We attribute this to differences in the genetic background of the two populations as well as the small sample size of the US dataset.

Canine hip dysplasia: A natural animal model for human developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) in humans is a common condition that is associated with hip pain, functional limitations, and secondary osteoarthritis (OA). Surgical treatment of DDH has improved in the last decade, allowing excellent outcomes at short- and mid-term follow-up. Still, the etiology, mechanobiology, and pathology underlying this disease are not well understood. A pre-clinical animal model of DDH could help advance the field with a deeper understanding of specific pathways that initiate hip joint degeneration secondary to abnormal biomechanics. An animal model would also facilitate different interventional treatments that could be tested in a rigorous and controlled environment. The dog model exhibits several important characteristics that make it valuable as a pre-clinical animal model for human DDH. Dogs are naturally prone to develop canine hip dysplasia (CHD), which is treated in a similar manner as in humans. Comparable to human DDH, CHD is considered a pre-OA disease; if left untreated it will progress to OA. However, progression to OA is significantly faster in dogs than humans, with progression to OA within 1-2 years of age, associated with their shorter life span compared to humans. Animal studies could potentially reveal the underlying biochemical pathway(s), which can inform refined treatment modalities and provide opportunities for new treatment and prevention targets. Herein, we review the similarities and differences between the two species and outline the argument supporting CHD as an appropriate pre-clinical model of human DDH. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1807-1817, 2018.

Demographics of hip dysplasia in the Maine Coon cat.

Objectives The aim of this study was to report the demographics of feline hip dysplasia (FHD) in the Maine Coon cat. Methods The complete hip dysplasia registry (public and private) collected by the Orthopedic Foundation for Animals through April 2015 was accessed. There were 2732 unique cats; 2708 (99.1%) were Maine Coons, and only these were studied. Variables analyzed were sex, month/season of birth and hip dysplasia score. Two groups were created: those with and without FHD. P <0.05 was considered statistically significant. Results The youngest cat with FHD was 4 months of age. The majority of the radiographs (2604/2708 [96.2%]) were performed between 4 and 60 months of age. Non-borderline scores for these 2604 cats were available in 2548, and were the data used for this study. The overall prevalence of FHD was 24.9% (635/2548), and was slightly higher in males (279/1023 [27.3%]) than females (356/1525 [23.3%]) ( P = 0.025). Those with more severe dysplasia were older. The percentage of bilateral FHD was 56%, and bilateral cases had more severe dysplasia than unilateral cases but with no age difference. Month/season of birth or geographic region of origin did not influence the prevalence of FHD. Conclusions and relevance This is the largest demographic study of FHD in the Maine Coon cat. The overall prevalence in the Orthopedic Foundation for Animals registry was 24.9%, and slightly higher in males (27.3%) than females (23.3%). Dysplasia was more severe in bilateral than unilateral cases and with increasing age. Caution should be used when extrapolating these findings to other feline breeds or other groups of Maine Coon cats. Further studies need to be performed among other breeds and geographic locations to better understand the demographics of feline hip dysplasia.

A novel iterative mixed model to remap three complex orthopedic traits in dogs.

Hip dysplasia (HD), elbow dysplasia (ED), and rupture of the cranial (anterior) cruciate ligament (RCCL) are the most common complex orthopedic traits of dogs and all result in debilitating osteoarthritis. We reanalyzed previously reported data: the Norberg angle (a quantitative measure of HD) in 921 dogs, ED in 113 cases and 633 controls, and RCCL in 271 cases and 399 controls and their genotypes at ~185,000 single nucleotide polymorphisms. A novel fixed and random model with a circulating probability unification (FarmCPU) function, with marker-based principal components and a kinship matrix to correct for population stratification, was used. A Bonferroni correction at p<0.01 resulted in a P< 6.96 ×10-8. Six loci were identified; three for HD and three for RCCL. An associated locus at CFA28:34,369,342 for HD was described previously in the same dogs using a conventional mixed model. No loci were identified for RCCL in the previous report but the two loci for ED in the previous report did not reach genome-wide significance using the FarmCPU model. These results were supported by simulation which demonstrated that the FarmCPU held no power advantage over the linear mixed model for the ED sample but provided additional power for the HD and RCCL samples. Candidate genes for HD and RCCL are discussed. When using FarmCPU software, we recommend a resampling test, that a positive control be used to determine the optimum pseudo quantitative trait nucleotide-based covariate structure of the model, and a negative control be used consisting of permutation testing and the identical resampling test as for the non-permuted phenotypes.

The Demographics of Canine Hip Dysplasia in the United States and Canada.

Canine hip dysplasia (CHD) is a common problem in veterinary medicine. We report the demographics of CHD using the entire hip dysplasia registry from the Orthopedic Foundation for Animals, analyzing differences by breed, sex, laterality, seasonal variation in birth, and latitude. There were 921,046 unique records. Each dog was classified using the American Kennel Club (AKC) and Fédération Cynologique Internationale (FCI) systems. Statistical analysis was performed with bivariate and logistic regression procedures. The overall CHD prevalence was 15.56%. The OR for CHD was higher in females (1.05), those born in spring (1.14) and winter (1.13), and those in more southern latitudes (OR 2.12). Within AKC groups, working dogs had the highest risk of CHD (OR 1.882) with hounds being the reference group. Within FCI groups, the pinscher/molossoid group had the highest risk of CHD (OR 4.168) with sighthounds being the reference group. The similarities between CHD and DDH are striking. Within DDH there are two different types, the typical infantile DDH and the late onset adolescent/adult acetabular dysplasia, with different demographics; the demographics of CHD are more similar to the later onset DDH group. Comparative studies of both disorders should lead to a better understanding of both CHD and DDH.

Genetic mapping of principal components of canine pelvic morphology.

BACKGROUND: Concentrated breeding effort to produce various body structures and behaviors of dogs to suit human demand has inadvertently produced unwanted traits and diseases that accompany the morphological and behavioral phenotypes. We explored the relationship between pelvic conformation and canine hip dysplasia (HD) because purebred dogs which are predisposed, or not, to HD share common morphologic features, respectively. Thirteen unique bilateral anatomical features of the pelvis were measured on 392 dogs of 51 breeds and 95 mixed breed dogs. Principal components (PCs) were derived to describe pelvic morphology. Dogs were genotyped at ~183,000 single nucleotide polymorphisms and their hip conformation was measured by the Norberg angle and angle of inclination between the femoral neck and diaphysis. RESULTS: No associations reached genome wide significance for the Norberg angle when averaged over both hips. PC1 was negatively correlated with the Norberg angle (r = -0.31; P < 0.05) but not the angle of inclination (r = -0.08; P > 0.05). PC1, 2, 4, and 5 differed significantly between male and female dogs confirming pelvic sexual dimorphism. With sex as a covariate, the eigenvector contribution to PC1 reflected the overall size of the pelvis and was significantly associated with the IGF-1 locus, a known contributor to canine body size. PC3, which represented a tradeoff between ilial length and ischial length in which a longer ischium is associated with a shorter ilium, was significantly associated with a marker on canine chromosome 16:5181388 bp. The closest candidate gene is TPK1, a thiamine-dependent enzyme and part of the PKA complex. Associations with the remaining PCs did not reach genome wide significance. CONCLUSION: IGF-1 was associated with the overall size of the pelvis and sex is related to pelvic size. Ilial/ischial proportion is genetically controlled and the closest candidate gene is thiamine-dependent and affects birth weight and development of the nervous system. Dogs with larger pelves tend to have smaller NAs consistent with increased tendency toward HD in large breed dogs. Based on the current study, pelvic shape alone was not strongly associated with canine hip dysplasia.

The Norberg angle is not an accurate predictor of canine hip conformation based on the distraction index and the dorsolateral subluxation score.

Canine hip dysplasia (CHD) is a common complex trait characterized by abnormal hip joint development. Hip joint laxity, an early characteristic of CHD, results in degeneration of the joint due to mechanical trauma, which is a clinical problem mostly in medium to large breed dogs. Clinical signs include pain, decreased activity and lameness. A retrospective, multi-center, cross sectional study of 437 dogs was performed to determine if a Norberg angle (NA) ≥105° accurately predicts a non-dysplastic hip based on a distraction index (DI) cut-off of ≤0.3 or a dorsolateral subluxation (DLS) score cut-off of ≥55%. The predictive capacity of the NA against a DI ≤0.3 or a DLS score ≥55% was assessed using area under the receiver operator characteristic (ROC) curve analysis. The ROC curve of NA for the prediction of a DI ≤0.3 was 0.59 (95% CI=0.50-0.69) and for the prediction of DLS score ≥55% was 0.69 (95% CI=0.63-0.75). Optimizing the specificity of the NA to ≥80% for prediction of a DI ≤0.3 and a DLS score ≥55% gave a cut-point for the NA of ≥112° and 108.7°, respectively. In conclusion, at the cut-point of 105°, the NA is not an accurate measurement to score normal or abnormal hips, based on the DI or DLS score. Application of screening methods for CHD based on hip laxity, such as the DI or the DLS score, would help to remove additional dysplastic dogs from the breeding pool or the NA criterion should be higher when selecting unaffected dogs for breeding.

Long Term Functional Outcome of Tibial Tuberosity Advancement vs. Tibial Plateau Leveling Osteotomy and Extracapsular Repair in a Heterogeneous Population of Dogs.

OBJECTIVE: To determine a long term function of tibial tuberosity advancement (TTA) for treatment of ruptured cranial cruciate ligament (CCL) in dogs, and to compare this to the long term function of previously reported tibial plateau leveling osteotomy (TPLO), extracapsular reconstruction (ECR), and a population of normal dogs. STUDY DESIGN: Prospective clinical trial. ANIMALS: Dogs with unilateral ruptured CCL treated with TTA (n = 14), TPLO (n = 15), and ECR (n = 23), and normal adult dogs (control, n = 80). MATERIALS AND METHODS: Force plate gait analysis was performed at 1 time point for the normal control group and preoperatively, and at 2 and 8 weeks and 6 and 12 months postoperatively for the treatment groups. Using serial force plates, symmetry indices (SI) were calculated between the operated and unoperated pelvic limbs for peak vertical force (PVF), contact time (CT), and vertical impulse (VI). Ground reaction forces (GRF) of the treatment and control group were compared using a general linear model. RESULTS: Walk SI for dogs with TTA were not significantly different from the control group at 12 months postoperatively. At the trot, neither TTA nor ECR achieved normal GRF. SI of the TPLO group were not different from the normal control group by 6-12 months postoperatively. CONCLUSION: At the walk, TTA achieves normal function by 12 months; however, at the trot TTA is indistinguishable from ECR. TPLO resulted in operated limb function that was similar to the control population by 6-12 months postoperatively at the walk and the trot.