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  • Author or Editor: Alma J. Williams x
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SUMMARY

We tested the hypothesis that treatment of growing, susceptible (to hip dysplasia) pups by im administration of glycosaminoglycan polysulfates would mitigate the signs of incipient hip dysplasia. In 1 experiment, 7 pups, selected at random from 2 litters, were administered glycosaminoglycan polysulfates (2.5 mg/kg of body weight, im) twice weekly, and 7 control pups from the same litters were given sterile buffered 0.9% saline solution from the age of 6 weeks to 8 months. Hip joints were examined by radiography, with pups in the standard, limbs-extended position. At 8 months of age, all pups in this experiment did not manifest femoral head subluxation radiographically. The Norberg angle, a measure of coxofemoral congruity, improved from a mean ± sem value of 102° ± 1° in controls to 106° ± 1° in treated pups (P = 0.008). Pups were not subjected to necropsy.

In the second experiment, 8 pups were selected at random from 2 litters and were administered 5 mg of glycosaminoglycan polysulfates/kg, im, twice weekly from 6 weeks to 8 months of age. Similarly, 8 control pups were administered saline solution. At 8 months of age, hip joints were examined by radiography with pups in the standard position; at necropsy, intra-articular tissues were evaluated macroscopically and biochemically. Of 8 treated pups, none had subluxation radiographically, whereas 4 of 8 control dogs had femoral head subluxation. Mean Norberg angle on the radiographs was 109.7° ± 1.6° for the treated group and was 101.5° ± 1.6° for controls, representing a mean improvement in coxofemoral congruity of 8.2° in the treated pups. The radiographic diagnosis (normal vs dysplastic) and the Norberg angle measurements were significantly (P = 0.04 and 0.002, respectively) different for treated and control pups.

At necropsy, 1 of 8 treated pups had cartilage degeneration, whereas 4 of 8 control pups had cartilage degeneration. The mean pathologic score determined for the hip joints of treated pups was 1.6 ± 0.8, whereas for those of controls, the score was 3.3 ± 1.2 (P = 0.09). Normal (disease-free) pups had hip pathologic scores of zero. The mean fibronectin content of femoral head articular cartilage was reduced from 2.19 ± 0.61 μg/mg in nontreated pups to 0.59 ± 0.56 μg/mg for treated pups (P = 0.04).

Fibronectin content was used as a measure of the extent of cartilage degeneration, and the cartilage of disease-free hip joints contained 0.32 ± 0.03 μg/mg. The mean proteoglycan content of the cartilage was unaffected by drug treatment. A trend was evident for lower synovial fluid volume and lower ligament volume (more normal volumes) in treated pups, but the differences were not statistically significant.

Hip joint laxity was assessed by use of a distraction method during radiogaphy of pups in experiments 1 and 2. The differences in laxity determinations between the treated and control pups were not statistically significant.

Taken together, the data indicated that im administration of gycosaminoglycan polysulfates from 6 weeks to 8 months of age in growing pups that were susceptible to hip dysplasia resulted in less subluxation, as determined from the standard radiographic projection. Treated pups had closer coxofemoral congruity when they were 8 months old (P < 0.05); at necropsy, the joint pathologic scores of treated pups indicated a trend toward improvement (P < 0.09), but the differences were not statistically significant. The mechanism of action for this drug effect is unknown.

Free 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 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 determine whether dorsolateral subluxation (DLS) of the femoral head reflects osseous conformation of the coxofemoral (hip) joint and represents a property distinct from maximum passive laxity of the hip joint in dogs.

Animals

14 Labrador Retrievers, 16 Greyhounds, 58 Greyhound-Labrador Retriever mixed-breed dogs, and 1 Rottweiler.

Procedures

DLS of the femoral head (DLS score) and passive laxity of the hip joint (distraction index) were determined radiographically in 3 groups of dogs: not treated (167 joints of 84 dogs); before and after injecting 2 ml of hyaluronan into 25 hip joints of 13 dogs; and before and after unilateral triple pelvic osteotomy in 5 dogs. Results of the 2 methods were compared for each group.

Results

In untreated dogs, the correlation coefficient (r) of DLS score versus distraction index was −0.73 and −0.69 for 84 left and 83 right hip joints, respectively. Mean coefficient of determination (r 2) for both hips was 0.5. Mean DLS score did not differ before and after intra-articular injection of hyaluronan into either hip joint, whereas mean distraction index increased significantly after intra-articular injection. Unilateral triple pelvic osteotomy resulted in a significant increase in DLS score, compared with values obtained before surgery. However, distraction index before and after surgery did not differ significantly.

Conclusions and Clinical Relevance

The DLS test assesses the congruity of the acetabulum and the femoral head in a canine hip joint and thus represents a characteristic distinct from maximum passive laxity. The DLS score and the distraction index evaluate different components of hip joint stability. (Am J Vet Res 1999;60:1571–1576)

Free access
in American Journal of Veterinary Research

Summary

A study was done to determine whether radiographic-distraction measurement of coxofemoral joint (hip) laxity at 4 and 8 months of age can serve as a predictor of hip dysplasia in older Labrador Retrievers. The method of Smith, Biery, and Gregor was used for radiologic examination of hips and for evaluation of radiographs. Mean (± sem) distraction laxity (ie, distraction index) for 10 adult disease-free dogs was 0.29 ± 0.05, whereas a group of 8 dogs with dysplastic hips had mean distraction index of 0.60 ± 0.10 (P < 0.05). Mean distraction index at 4 months of age for 11 pups of 4 litters from matings between dogs with normal hips was 0.39 ± 0.07, and was 0.54 ± 0.04 for 31 pups of 7 litters from matings between dogs with hip dysplasia. The distraction index and, thus, joint laxity at that age was significantly (P = 0.0351) different for the 2 groups. The distraction index at 4 months correlated positively with the distraction index at a later age at necropsy (r = 0.43; P = 0.0289). Distraction index < 0.4 at 4 months of age predicted normal hips in 88% of cases and distraction index ≥ 0.4 predicted hip dysplasia in 57% of the dogs. Logistic regression modeling indicated that the odds of a hip being normal decreased with increasing distraction index, and thus, with increasing joint laxity. The logistic regression models provided a reasonable mathematical description of the data. Based on the logistic model of the data, distraction indexes between 0.4 and 0.7 at either 4 or 8 months of age were not associated strongly enough with evidence of disease to be clinically reliable in predicting, on an individual basis, the outcome for dysplastic hip conformation when dogs were older. Index > 0.7 was associated with high probability for developing dysplastic joints and distraction index < 0.4 predicted normal hips with high probability.

Free access
in American Journal of Veterinary Research

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 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)

Full access
in Journal of the American Veterinary Medical Association

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 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 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