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  • Author or Editor: Alma J. Williams x
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Abstract

Objective—To determine whether abnormal laxity of hip joints of canine pups with genetic predisposition to hip dysplasia (HD+) is related to ingestion of milk-borne hormones.

Animals—7 female Labrador Retrievers with HD+ and 8 with low predisposition to hip dysplasia (HD–) and their offspring.

Procedures—Immunoactive relaxin, estrogen, and estrogen precursor concentrations in milk of HD+ lactating bitches and in serum of their pups were compared with those of HD– bitches and pups. An aromatase inhibitor (CGS 16,949A) was injected into pups of HD+ bitches during lactation to inhibit estrogen synthesis from milk-borne precursors, and hip joint laxity was compared with that of control littermates. Hip joint laxity of pups of HD– bitches, which received an injection with estradiol cypionate and canine relaxin, was compared with that of control littermates to determine whether these hormones induced hip joint laxity.

Results—High concentrations of estrogens and relaxin were found in milk of HD+ and HD– bitches throughout lactation. Serum concentrations of milk-derived relaxin and total estrogens were similar in all pups, but estradiol-17B was detected only in pups of HD+ bitches. Hip joint laxity was reduced in pups that received CGS 16,949A. Hip joint laxity was increased in pups of HD– bitches that received estradiol cypionate and relaxin.

Conclusions and Clinical Relevance—Milk-borne maternal hormones and precursors were absorbed into the circulation of canine neonates and may play a role in hip joint laxity in HD+ pups. Phenotypic expression of hip dysplasia may therefore be preventable by antihormone treatment.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare the bone mineral density (BMD) of the proximal portion of the femur in dogs with and without early osteoarthritis secondary to hip dysplasia.

Animals—24 dogs (3 Greyhounds, 6 Labrador-Greyhound crossbreeds, and 15 Labrador Retrievers).

Procedure—Computed tomography (CT) of the pelvis, including a bone-density phantom, was performed for each dog. Centrally located transverse CT slices and a computer workstation were used to identify 16 regions of interest (ROIs) in the proximal portion of the femur. For each ROI, the mean Hounsfield unit value was recorded; by use of the bone-density phantom and linear regression analysis, those values were converted to equivalent BMD (eBMD). Mean eBMD values for the subchondral and nonsubchondral ROIs in dogs with and without osteoarthritis (determined at necropsy) were compared. A mixed-model ANOVA and post hoc linear contrasts were used to evaluate the effects of osteoarthritis, breed, and sex on the BMD value.

Results—At necropsy, osteoarthritis was detected in 14 hip joints in 9 dogs; all lesions included early cartilage fibrillation. After adjusting for breed and sex, eBMD in subchondral ROIs 8 and 12 (adjacent to the fovea) were 8% and 6% higher, respectively, in osteoarthritis-affected dogs, compared with unaffected dogs; in the nonsubchondral ROIs, eBMD was 10% higher in osteoarthritis-affected dogs.

Conclusions and Clinical Relevance—Compared with findings in unaffected dogs, increased eBMD in hip joints of dogs with early osteoarthritis supports a strong relationship between the subchondral and epiphyseal regions and articular cartilage in the pathogenesis and progression of osteoarthritis.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare the accuracy of the extended- hip radiographic (EHR) score, the distraction index (DI), and the dorsolateral subluxation (DLS) score for identifying hip dysplasia in dogs at 8 months of age.

Design—Cohort study

Animals—129 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbreds.

Procedure—Radiography was performed when dogs were 8 months of age. Dogs were euthanatized at 8 to 36 months of age; hip dysplasia was diagnosed at the time of necropsy on the basis of results of a gross examination of the articular cartilage of the hip joints for signs of osteoarthritis.

Results—The EHR score, DI, and DLS score at 8 months of age were all significantly correlated with degree of cartilage degeneration at necropsy. Sensitivity and specificity of using EHR score at 8 months of age to diagnose hip dysplasia (scores > 3 were considered abnormal) were 38 and 96%, respectively; sensitivity and specificity of using DI (values > 0.7 were considered abnormal) were 50 and 89%; and sensitivity and specificity of using DLS score (scores ≤ 55% were considered abnormal) were 83 and 84%.

Conclusions and Clinical Relevance—Results suggested that specificities of the 3 methods for diagnosing hip dysplasia in dogs at 8 months of age were similar. However, the DLS score had higher sensitivity, indicating that there were fewer false-negative results. (J Am Vet Med Assoc 2001;219:1242–1246)

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine whether dorsolateral subluxation (DLS) scores in young dogs could be used to reliably predict which dogs would develop evidence of hip osteoarthritis and whether DLS scores measured at various ages correlated with each other.

Animals—129 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbreds.

Procedures—DLS scores were measured on radiographs taken at 4, 8, and 12 months of age and at necropsy (8 to 36 months of age). At necropsy, the hip joints were examined macroscopically and a score assigned for degree of cartilage degeneration.

Results—DLS scores at 4 (n = 35, r s = –0.62), 8 (n = 106, r s = –0.54), and 12 (n = 15, r s = –0.87) months of age were significantly correlated with cartilage degeneration scores, and DLS scores at 8 months of age were significantly correlated with scores obtained at the time of necropsy (n = 39, r s = 0.87). The DLS scores at 4 months of age were significantly different from scores at 8 months of age, but scores did not differ significantly thereafter. Likelihood ratios for cartilage lesions for low (< 45%), intermediate (≥ 45 but ≤ 55%), and high (> 55%) DLS scores at 8 months of age were 8.0, 2.6, and 0.2, respectively.

Conclusions and Clinical Relevance—Results suggest that DLS score at 8 months of age was a reasonable, albeit imperfect, predictor of the condition of the hip joint cartilage at necropsy. Thus, the DLS method might be useful for early identification of dogs with hip dysplasia. (Am J Vet Res 2001;62:1711–1715)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To estimate heritabilities and genetic correlations among 4 traits of hip joints (distraction index [DI], dorsolateral subluxation [DLS] score, Norberg angle [NA], and extended–hip joint radiograph [EHR] score) and to derive the breeding values for these traits in dogs.

Animals—2,716 dogs of 17 breeds (1,551 dogs in which at least 1 hip joint trait was measured).

Procedures—The NA was measured, and an EHR score was assigned. Hip joint radiographs were obtained from some dogs to allow calculation of the DI and DLS score. Heritabilities, genetic correlations, and breeding values among the DI, DLS score, NA, and EHR score were calculated by use of a set of multiple-trait, derivative-free, restricted maximum likelihood computer programs.

Results—Among 2,716 dogs, 1,411 (52%) had an estimated inbreeding coefficient of 0%; the remaining dogs had a mean inbreeding coefficient of 6.21%. Estimated heritabilities were 0.61, 0.54, 0.73, and 0.76 for the DI, DLS score, NA, and EHR score, respectively. The EHR score was highly genetically correlated with the NA (r = −0.89) and was moderately genetically correlated with the DI (r = 0.69) and DLS score (r = −0.70). The NA was moderately genetically correlated with the DI (r = −0.69) and DLS score (r = 0.58). Genetic correlation between the DI and DLS score was high (r = −0.91).

Conclusions and Clinical Relevance—Establishment of a selection index that makes use of breeding values jointly estimated from the DI, DLS score, NA, and EHR score should enhance breeding programs to reduce the incidence of hip dysplasia in dogs.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To identify the quantitative trait loci (QTL) that contribute to hip dysplasia in dogs.

Animals—192 Labrador Retrievers.

Procedures—Hip dysplasia was measured by use of the Norberg angle (NA), dorsolateral subluxation (DLS) score, and distraction index (DI). Genome-wide screening was conducted by use of 276 unique microsatellites. Linkage analysis was performed with a variance-based linear model. Logarithm of the odds (LOD) scores were reported when values were > 2.0.

ResultsCanis familiaris autosomes (CFAs) 01, 02, 10, 20, 22, and 32 harbored significant QTL at LOD scores > 2.0. Among the 6 QTL, the QTL on CFA02 had not been reported to harbor QTL for hip dysplasia. The highest LOD score of 3.32 on CFA20 contributed to the second principal component of the DLS score and NA of the right hip joint. The QTL that was mapped on CFA01 (LOD score of 3.13 at 55 centimorgans) was located on the same chromosome reported to harbor a QTL for hip dysplasia in Portuguese Water Dogs and German Shepherd Dogs. In this study, CFAs 10, 20, 22, and 32 harbored QTL for hip dysplasia that have been identified in a Labrador Retriever–Greyhound pedigree and in German Shepherd Dogs.

Conclusions and Clinical Relevance—Multiple QTL were clearly involved with hip dysplasia. Identification of these QTL will enable fine-resolution mapping and subsequent assessment of candidate genes within the refined intervals to enable researchers to develop genetic screening tests and preventative and novel therapeutic regimens.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the radiographic methods that best predict the development of osteoarthritis in the hip joints of a cohort of dogs with hip dysplasia and unaffected dogs.

Animals—205 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbred dogs.

Procedure—Pelvic radiography was performed when the dogs were 8 months old. Ventrodorsal extendedhip, distraction, and dorsolateral subluxation (DLS) radiographs were obtained. An Orthopedic Foundation for Animals-like hip score, distraction index, dorsolateral subluxation score, and Norberg angle were derived from examination of radiographs. Osteoarthritis was diagnosed at the time of necropsy in dogs ≥ 8 months of age on the basis of detection of articular cartilage lesions. Multiple logistic regression was used to determine the radiographic technique or techniques that best predicted development of osteoarthritis.

Results—A combination of 2 radiographic methods was better than any single method in predicting a cartilage lesion or a normal joint, but adding a third radiographic method did not improve that prediction. A combination of the DLS score and Norberg angle best predicted osteoarthritis of the hip joint or an unaffected hip joint. All models that excluded the DLS score were inferior to those that included it.

Conclusions and Clinical Relevance—A combination of the DLS score and Norberg angle was the best predictor of radiographic measures in 8-month-old dogs to determine whether a dog would have normal or osteoarthritic hip joints. (Am J Vet Res 2003;64:1472–1478)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree.

Animals—147 Labrador Retrievers, Greyhounds, and their crossbreed offspring.

Procedure—Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined.

Results—For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7.

Conclusions and Clinical Significance—Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs. (Am J Vet Res 2003;222:418–424)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the genetic influence on expression of traits associated with canine hip dysplasia.

Animals—193 dogs from an experimental canine pedigree.

Procedure—An experimental canine pedigree was developed for linkage analysis of hip dysplasia by mating dysplastic Labrador Retrievers with nondysplastic Greyhounds. A statistical model was designed to test the effects of Labrador Retriever and Greyhound alleles on age at detection of femoral capital epiphyseal ossification, 8-month distraction index, and 8-month dorsolateral subluxation score.

Results—The additive effect was significant for age at detection of femoral capital epiphyseal ossification. Restricted maximum likelihood estimates (± SD) for this trait were 6.4 ± 1.95, 10.2 ± 2.0, 10.8 ± 3.1, 11.4 ± 2.1, and 13.6 ± 4.6 days of age for Greyhounds, Greyhound backcross dogs, F1 dogs, Labrador Retriever backcross dogs, and Labrador Retrievers, respectively. The additive effect was also significant for the distraction index. Estimates for this trait were 0.21 ± 0.07, 0.29 ± 0.15, 0.44 ± 0.12, 0.52 ± 0.18, and 0.6 ± 0.17 for the same groups, respectively. For the dorsolateral subluxation score, additive and dominance effects were significant. Estimates for this trait were 73.5 ± 4.1, 71.3 ± 6.5, 69.1 ± 6.0, 50.6 ± 12.9, and 48.4 ± 7.7%, respectively, for the same groups.

Conclusions—In this canine pedigree, traits associated with canine hip dysplasia are heritable. Phenotypic differences exist among founder dogs of each breed and their crosses. This pedigree should be useful for identification of quantitative trait loci underlying the dysplastic phenotype. (Am J Vet Res 2002;63: 1029–1035)

Full access
in American Journal of Veterinary Research