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.

Three-dimensional assessment of the influence of juvenile pubic symphysiodesis on the pelvic geometry of dogs.

OBJECTIVE To evaluate the 3-D geometry of canine pelves and to characterize the long-term effects of juvenile pubic symphysiodesis (JPS) on pelvic geometry by comparing the pelvic configuration between littermates that did and did not undergo the procedure. ANIMALS 24 Labrador Retriever, Golden Retriever, or Labrador Retriever-Golden Retriever crossbred service dogs from 13 litters. PROCEDURES At 16 weeks old, puppies with a hip joint distraction index ≥ 0.5 were randomly assigned to undergo thermal JPS (n = 9), mechanical JPS (7), or a sham (control) surgical procedure (8). Ten years later, each dog underwent a CT scan of the pelvic region. Modeling software was used to create 3-D reconstructions from the CT scans, and various pelvic measurements were made and compared among the 3 treatments. RESULTS Compared with the control treatment, thermal and mechanical JPS increased the hemipelvis acetabular angle by 4°, the acetabular angle of lateral opening by 5°, and the orientation of the medial acetabular wall in a transverse plane by 6°, which indicated that JPS increased dorsal femoral head coverage by the acetabulum. Both JPS procedures decreased the pelvic canal area by approximately 20% and acetabular inclination by 6° but did not alter acetabular retroversion. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that thermal and mechanical JPS were equally effective in altering the 3-D pelvic geometry of dogs. These findings may help guide future studies of alternatives for optimizing canine pelvic anatomy to minimize the risk of hip dysplasia and associated osteoarthritis.

Asymmetrical lumbosacral transitional vertebrae in dogs may promote asymmetrical hip joint development.

OBJECTIVES: This study examines the relationship between the morphology of the lumbosacral transitional vertebra (LTV) and asymmetrical development of the hip joints in dogs. METHODS: A total of 4000 dogs which had been consecutively scored for canine hip dysplasia were checked for the presence of a LTV. A LTV was noted in 138 dogs and classified depending on the morphology of the transverse processes and the degree of contact with the ilium. RESULTS: In dogs with an asymmetrical LTV, the hip joint was significantly more predisposed to subluxation and malformation on the side of the intermediate or sacral-like transverse process (p <0.01), on the side of the elevated pelvis (p <0.01), or when an asymmetrical LTV resulted in pelvic rotation on its long axis (p <0.01), whereas hip joint conformation was less affected on the side featuring a free transverse process (p <0.01). CLINICAL SIGNIFICANCE: The results support our hypothesis that an asymmetrical LTV favours pelvic rotation over its long axis, resulting in inadequate femoral head coverage by the acetabulum on one side. Inadequate coverage of the femoral head favours subluxation, malformation of the hip joint, and secondary osteoarthritis. Asymmetrical hip conformation may therefore be the sequela of a LTV and mask or aggravate genetically induced 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.

Vertical forces assessment according to radiographic hip grade in German shepherd dogs.

OBJECTIVE: To investigate the correlation between radiographic hip grade and kinetic parameters in German shepherd dogs. METHODS: Dogs were distributed into five groups of eight dogs each according to hip grade (A, B, C, D or E). Dogs were submitted to clinical evaluation and kinetic analysis. Five valid passages were analysed using data collected from a pressure walkway. Peak vertical force, vertical impulse and stance phase duration were evaluated at velocity (1 · 2 to 1 · 4 m/s) ±0 · 1 m/s(2) acceleration. Kinetic data between groups were compared. RESULTS: In pelvic limbs, mean peak vertical force decreased progressively from grade C (mild) to grade E (severe) hip dysplasia. The vertical impulse was decreased in groups C and E compared to groups A, B and D; stance phase duration did not differ significantly between groups. CLINICAL SIGNIFICANCE: Mean peak vertical force was lower in dogs with severe hip dysplasia compared with mildly dysplastic dogs. These results suggest that hip dysplasia degree can affect lameness severity.

The effects of positioning, reason for screening and the referring veterinarian on prevalence estimates of canine hip dysplasia.

Although the prevalence of canine hip dysplasia (HD) has been the subject of a number of published studies, estimates vary widely. This study evaluated several possible causes for these differences. Sixty Belgian, Dutch and German veterinarians were asked to submit all hip radiographs obtained for screening purposes (irrespective of HD status) over a 2-year period, resulting in a database of 583 dogs. Each set of radiographs was accompanied by information on the reason for screening (breeding soundness examination, clinical complaint, assistance dogs, or other reasons), and dog breed, date of birth and age. Dog positioning exerted an effect at multiple levels. The agreement among different observers regarding correct or incorrect positioning was limited and incorrect positioning itself reduced the inter-observer agreement for radiographic hip conformation. Dysplastic dogs were more commonly positioned incorrectly than non-dysplastic dogs. The clinical complaint population had a high prevalence of dysplastic dogs (>70%) compared with the breeding population (11%) and the assistance dogs (6%). There was a significantly lower prevalence of HD among cases referred by veterinarians who frequently submitted hip-extended radiographs for evaluation (P = 0.002) compared to those who refer less frequently. However, this was likely to be selection bias, as radiographs that were from dogs suspected to be dysplastic were not submitted by frequent senders. The prevalence of dysplastic dogs varied widely between breeds (16.7-71.4%). Dogs diagnosed with dysplasia were significantly older than dogs considered healthy (P = 0.001) and dogs classified as borderline dysplastic (P = 0.035). Inter-observer agreement for hip conformation was moderately low, resulting in >7% variation in prevalence estimates for dysplasia.

Neutering dogs: effects on joint disorders and cancers in golden retrievers.

In contrast to European countries, the overwhelming majority of dogs in the U.S. are neutered (including spaying), usually done before one year of age. Given the importance of gonadal hormones in growth and development, this cultural contrast invites an analysis of the multiple organ systems that may be adversely affected by neutering. Using a single breed-specific dataset, the objective was to examine the variables of gender and age at the time of neutering versus leaving dogs gonadally intact, on all diseases occurring with sufficient frequency for statistical analyses. Given its popularity and vulnerability to various cancers and joint disorders, the Golden Retriever was chosen for this study. Veterinary hospital records of 759 client-owned, intact and neutered female and male dogs, 1-8 years old, were examined for diagnoses of hip dysplasia (HD), cranial cruciate ligament tear (CCL), lymphosarcoma (LSA), hemangiosarcoma (HSA), and mast cell tumor (MCT). Patients were classified as intact, or neutered early (<12 mo) or late (≥12 mo). Statistical analyses involved survival analyses and incidence rate comparisons. Outcomes at the 5 percent level of significance are reported. Of early-neutered males, 10 percent were diagnosed with HD, double the occurrence in intact males. There were no cases of CCL diagnosed in intact males or females, but in early-neutered males and females the occurrences were 5 percent and 8 percent, respectively. Almost 10 percent of early-neutered males were diagnosed with LSA, 3 times more than intact males. The percentage of HSA cases in late-neutered females (about 8 percent) was 4 times more than intact and early-neutered females. There were no cases of MCT in intact females, but the occurrence was nearly 6 percent in late-neutered females. The results have health implications for Golden Retriever companion and service dogs, and for oncologists using dogs as models of cancers that occur in humans.

Retrospective evaluation of the long-term outcome of non-surgical management of 74 dogs with clinical hip dysplasia.

The long-term outcome for dogs treated non-surgically for clinical signs of canine hip dysplasia were evaluated retrospectively; 74 dogs were evaluated by a postal questionnaire sent to their owners, and 24 of these were also evaluated by a veterinary clinical examination. A total of 11 outcome variables were evaluated. Depending on the variable assessed, between 31 (41.9 per cent) and 49 (66.2 per cent) of the dogs remained clinically affected according to their owner's assessment, and between 17 (70.8 per cent) and 23 (95.8 per cent) of the 24 dogs had abnormalities attributed to hip osteoarthritis according to the veterinary assessment. Orthopaedic abnormalities other than hip dysplasia affected 17 of the 24 dogs. Long-term medications had been prescribed for the treatment of clinical signs associated with hip dysplasia in 41 of the 74 dogs.

Comparison of three distraction methods and conventional radiography for early diagnosis of canine hip dysplasia.

Two radiographic distraction techniques (one employing a wooden lath and, the other, a PennHip distractor), an ultrasonographic distraction method and conventional radiographic Fédération Cynologique Internationale (FCI) hip score were evaluated in eight-month-old Labrador retrievers to determine the most reliable method for predicting radiographic FCI hip score at the age of one year. With reference to the FCI hip score, sensitivity and specificity of the PennHip method were 100 per cent and 54 per cent; sensitivity and specificity of the lath technique were 85 per cent and 71 per cent; whereas they were 62 per cent and 67 per cent for the ultrasonographic method. For all distraction methods, the positive predictive value (PPV) was moderate and the negative predictive value (NPV) was high. Sensitivity, specificity, PPV and NPV were 100 per cent for the FCI hip score. It is concluded that, at the age of eight months, FCI hip score is the most reliable method for predicting FCI hip score at the age of one year in the colony of dogs investigated. Both the PennHip and lath method were also clinically reliable techniques in predicting true negatives. The ultrasonographic distraction method was moderately reliable.

Prevalence of canine hip dysplasia in a veterinary teaching hospital population.

The purpose of this study was to determine the prevalence of canine HD in a population in which there was minimal or no prior screening of radiographs for the disorder. Patient information was obtained from the radiographic database at the University of Missouri-Columbia Veterinary Teaching Hospital during the five-year period of 1991-1995. The coxofemoral joints on ventrodorsal radiographs of the pelvis were independently evaluated by three veterinary radiologists. A consensus evaluation of normal, borderline, or dysplastic was compiled. There were 2885 dogs identified representing 116 breeds and the mixbreds. There were 2236 purebred dogs (1071 males and 1165 females) and the prevalence of HD was 19.7%. There were 649 mixbred dogs (340 males and 309 females) and the prevalence of HD was 17.7%. There was no significant difference in the prevalence of HD between sexes or between purebred and mixbred dogs (P = 0.16; P = 0.29). Degenerative joint disease (DJD) was the most common radiographic manifestation of HD and there appeared to be a threshold at 12 months of age after which the presence of DJD was the primary diagnostic criteria.

Evaluation of risk factors for degenerative joint disease associated with hip dysplasia in German Shepherd Dogs, Golden Retrievers, Labrador Retrievers, and Rottweilers.

OBJECTIVE: To determine whether age, breed, sex, weight, or distraction index (DI) was associated with the risk that dogs of 4 common breeds (German Shepherd Dog, Golden Retriever, Labrador Retriever, Rottweiler) would have radiographic evidence of degenerative joint disease (DJD) associated with hip dysplasia. DESIGN: Cross-sectional prevalence study. ANIMALS: 15,742 dogs. PROCEDURE: Hips of dogs were evaluated radiographically by use of the ventrodorsal hip-extended view, the compression v ew, and the distraction view. The ventrodorsal hip-extended view was examined to determine whether dogs had DJD. For each breed, a multiple logistic regression model incorporating age, sex, weight, and DI was created. For each breed, disease-susceptibility curves were produced, using all dogs, regardless of age, and dogs grouped on the basis of age. RESULTS: Weight and DI were significant risk factors for DJD in all breeds. For German Shepherd Dogs, the risk of having DJD was 4.95 times the risk for dogs of the other 3 breeds combined. In all breeds, the probability of having DJD increased with age. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the probability of having hip DJD increased with hip joint laxity as measured by use of DI. This association was breed-specific, indicating that breed-specific information on disease susceptibility should be incorporated when making breeding decisions and when deciding on possible surgical treatment of hip dysplasia.

Recent information about hip dysplasia.

Dogs suffering from HD have a genetic background, but the releasing factors are many. Two of the most important are overnutrition and overexercising, especially in the young puppy. Radiography can give an estimate of the degree of secondary OA, and by evaluating the laxity in the hip joints at an early age, it seems to be possible to predict the chances for later development of OA. The eradication program has to be instituted in such a way that only the best dogs are accepted into breeding programs. It seems to be more efficient to eradicate the genetic part of the etiology by creating a breeding index by means of evaluating the offspring of the male dogs.

Correlation between hip joint laxity and subsequent coxarthrosis in dogs.

In a prospective study the degree of hip joint laxity was compared with subsequent hip joint development. A total of 70 non-selected adult dogs from 34 breeds presented for hip dysplasia screening was examined. The degree of hip laxity was quantitated using a newly developed radiographic stress technique. The dogs were re-examined according to the standard radiographic technique after 1 year or more. There was a positive correlation (r = 0.58) between the degree of subluxation (SI) and the subsequent Canine hip dysplasia (CHD) grade. All dogs with an SI value of up to 0.35 developed hip joints ranging between normal and mildly dysplastic at worst. Of the dogs with an SI value higher than 0.35, 76% developed hip dysplasia. Of those 40 dogs grading normal or borderline normal on standard radiographs, 15% demonstrated lax hip joints with an SI of more than 0.35. Breed-specific differences in the correlation of degree of hip joint laxity to the development of coxarthrosis were noted. If both excessive hip joint laxity and development of arthrosis are considered exclusion criteria for breeding dogs, then the current mode of selection does not adequately restrict potential breeding stock. Only dogs demonstrating an SI of 0.35 or less on stress radiographs and graded normal or borderline normal on standard radiographs should be used for breeding, equivalent to 49% of all dogs examined in this study. A further 36% of the dogs examined, most of them currently still accepted as breeding dogs, would not pass. Breed-specific acceptable degree of hip joint laxity in breeding dogs should be determined. Selecting breeding dogs based on the results of hip joint laxity assessment may further decrease the incidence of CHD in the offspring.

Dynamic ultrasonographic measurement of passive coxofemoral joint laxity in puppies.

A new method of dynamic ultrasonographic evaluation of passive coxofemoral joint laxity was used to examine a total of 30 greyhound (n = 13) and nongreyhound (n = 17) puppies. Puppies were evaluated sonographically at four, six, eight, 12, 16, and 26 weeks of age. The coxofemoral joints were distracted manually, and the femoral head displacements were measured during distraction. The greyhounds had significantly smaller (p less than 0.01) maximum distraction distance (mean +/- standard deviation [SD], 0.11 +/- 0.04 cm) than nongreyhound puppies (mean +/- SD, 0.26 +/- 0.10 cm). In six- to eight-week-old puppies, the maximum distraction distance was correlated significantly (p of 0.0001, adjusted correlation coefficient [r2] of 0.27) with stress radiographic indices. Coxofemoral joints interpreted as being abnormal on hip-extended radiographs taken at one year of age were associated significantly (p of 0.0001) with higher maximum distraction distances in six- to eight-week-old puppies.

An overview of the pathogenesis of canine hip dysplasia.

Canine hip dysplasia (CHD) is an inherited, developmental condition that involves a lack of conformity between the femoral head and acetabulum and invariably leads to osteoarthritis. In this paper, the author briefly reviews what is known about the genetics of CHD, how joint laxity and growth rate are related to development of CHD, and the possibility that CHD is a systemic disease involving multiple joints, not just the hip joint.

Advances in diagnosing canine hip dysplasia.

The DI method was developed, at least in part, because of perceived variations among radiologists in regard to subjective hip scores assigned to radiographs. It also was recognized that the prevalence of CHD among many dog breeds was disturbingly high, despite efforts to lower the prevalence using subjective score as a selection criterion. The DI method was developed on the basis of results of mechanical testing of cadaver hip joints, which accomplished 3 principal objectives. First, it showed that when the hip joint is in the standard, hip-extended, internally rotated position, passive laxity is minimized. Second, it showed that passive laxity was maximized when the hip joint is in the neutral position. Third, it demonstrated the sigmoidal nature of the load/displacement curve for the hip joint in the neutral position, which suggested that high repeatability from examiner to examiner in regard to DI could be expected without the need to standardize applied force. The mean and range of DI were shown to vary from 1 breed to the next, but within an individual dog, DI appears to remain constant (within limits of scientific acceptability and clinical applicability) from 16 weeks of age. Passive hip laxity measured on the distraction view is, on average, 2.5 to 11 times greater than that measured on the standard, hip-extended radiographic view. Performance Borzois and Greyhounds, which have an extremely low prevalence of CHD, uniformly have tight hip joints (DI < 0.3), and mean DI for dog breeds that have a high prevalence of CHD is significantly greater than mean DI for Borzois and Greyhounds. However, individual dogs that have DI < 0.3, even though members of breeds prone to CHD, have a low risk of developing DJD. Some, but not all, dogs with DI > 0.3 will develop DJD by 3 years of age, and DI has been shown to be the principal risk factor for development of DJD. Susceptibility to development of DJD appears to be breed-specific. For example, given equivalent DI, German Shepherd Dogs are more at risk for developing DJD than are Rottweilers. Heritability of DI is higher than that of the subjective hip score; thus, selection pressure based on DI should result in faster genetic change than selection pressure based on subjective hip scores. Finally, the DI method has been performed on approximately 14,000 dogs, some of which were evaluated multiple times. It is apparent that this method is no more harmful than the standard, hip-extended radiographic method or palpation performed as part of a routine orthopedic examination.

The joint capsule and joint laxity in dogs with hip dysplasia.

Present knowledge of the complexity of joint diseases makes it difficult to investigate the causes and early pathogenesis of canine hip dysplasia. Clinical signs of canine hip dysplasia including joint laxity may be a result of primary or secondary alterations of the joint. We already know that joint laxity is related to effusive synovitis (ie, accumulation of synovial fluid) and to other primary collagenous diseases. Canine hip dysplasia may be a third collagenous disease associated with joint laxity. This paper summarizes some of the studies that investigated the relationship between joint laxity and a defect in collagen metabolism and the influence that alterations in transsynovial flow have on joint laxity.

Association between pelvic muscle mass and canine hip dysplasia.

OBJECTIVE: To investigate the relationship between pelvic muscle mass and development and expression of canine hip dysplasia (CHD). DESIGN: Prospective study. ANIMALS: 5 Greyhounds with anatomically normal hip joints, 59 German Shepherd Dogs (23 with CHD, 24 with near-normal hip joints, and 12 with normal hip joints), and 18 German Shepherd Dog-Greyhound crossbreeds (7 with CHD, 6 with near-normal hip joints, and 5 with normal hip joints) between 12 and 47 months old in which pelvic muscle mass was evaluated. Pectineal muscle and hip joint development were evaluated in 25 German Shepherd Dogs at 8 and 16 or 24 weeks of age. PROCEDURES: For evaluation of pelvic muscle mass, individual pelvic muscles were weighed and hip joints were assigned a score on the basis of severity of degenerative changes. For evaluation of pectineal muscle development, muscle sections were stained and examined. RESULTS: Pelvic muscle mass was greatest in Greyhounds, intermediate in crossbred dogs, and smallest in German Shepherd Dogs. Differences in pelvic muscle mass among breeds were attributable to differences in weights of individual muscles. Hip score was negatively correlated with pelvic muscle mass and weights of selected pelvic muscles. Dogs with pectineal hypotrophy at 8 weeks of age had type-2 muscle fiber paucity or muscle fiber-type grouping at 16 or 24 weeks of age. At 8 weeks of age, hip joints were composed of multiple centers of ossification, and the acetabulum was largely cartilaginous. By 24 weeks of age, the pelvic bones were largely, although incompletely, fused. CLINICAL IMPLICATIONS: Diminished pelvic muscle mass in dogs with CHD and altered muscle fiber size and composition in 8-week-old dogs that subsequently develop CHD strongly suggest that abnormalities of pelvic musculature are associated with development of CHD. The complex development of the hip joint from multiple centers of ossification may make the joint susceptible to abnormal modeling forces that would result from abnormalities in pelvic muscle mass.

The pathogenesis and diagnosis of canine hip dysplasia: a review.

Hip dysplasia is a common developmental problem affecting the canine population. Despite extensive research into the condition, many questions remain unanswered and numerous misconceptions are present among the general public. The purpose of this paper is to review the current knowledge on the development of hip dysplasia, factors modifying its development, and current diagnostic techniques.A computerized literature search was conducted for the period of January 1983 to April 1985 using the MEDLINE and CAB databases, and the keywords hip dysplasia, hip, dog, and canine. Other articles,wherever possible original research articles, published before 1983 were also reviewed. Animals affected by hip dysplasia are born with normal hips, but quickly develop subluxation of the femoral head. Degenerative joint disease follows. Hip dysplasia is a complex, inherited, polygenic trait. Selective breeding of only normal dogs with normal littermates, parents, and grandparents is there commended method of reducing the incidence in the general population.Gene expression in affected individuals may be modified by a number of environmental factors. These factors do not cause hip dysplasia, but they alter manifestations of the trait and its severity. Nutrition is a major environmental factor. Excess energy consumption increases the frequency and severity of hip dysplasia in genetically predisposed dogs. Food intake should be regulated to maintain a slender figure with the ribs and dorsal vertebral spines easily palpable, but not visible. Excess dietary calcium and vitamin D contribute to hip dysplasia in genetically predisposed individuals and should be avoided. High dose vitamin C supplementation ingrowing puppies does not prevent hip dysplasia, and this practice should be discontinued. Animals must be 2 years old before they can be certified as normal, but the disease may be diagnosed earlier. Earlier diagnosis of the condition would be very useful for the selection of breeding stock, but palpation techniques and the standard extended view radiographs have unacceptably high rates of error in young puppies. Stress radiography techniques may improve the accuracy of early diagnosis in the future.