The Pathogenesis of Hip Dysplasia

Canine hip dysplasia (CHD) is one of the most common orthopedic complaints in dogs. The severity of clinical signs can vary from occasional lameness to severe dysfunction. It is a complex, polygenic or multifactorial disease which results in osteoarthritis (OA) of the hip joint. This developmental trait is inherited quantitatively and is expressed clinically and morphologically in response to heritable and environmental influences [1-3].

Dogs affected with hip dysplasia seem to have normal hip joints at birth, but joint laxity accompanied by incongruity develops as early as the first few weeks of life [2,4-6]. It is postulated that initial joint laxity leads to subsequent subluxation of the hip joint during weight-bearing, causing tension on the joint capsule. This trauma is followed by joint capsule thickening, osteophytosis, and enthesophyte formation [7]. The underlying etiology of joint laxity is unknown.

In this chapter we provide an overview of the etiology and pathogenesis of canine hip dysplasia, discuss the proposed genetic and environmental causes of the disease, and discuss hip screening by means of radiography.

Etiology

Historically, CHD has been characterized by the following factors: joint laxity [8-11], abnormalities of pelvic musculature [12], chondrosseous factors such as delayed onset of capital femoral ossification [13-15], altered composition of the chondroepiphysis,16 and incongruity between the acetabulum and femoral head resulting in dorsolateral subluxation [17,18]. Which of these is the initiating factor is still unknown. Today, two broad etiologies are proposed: hip laxity and abnormal progression of endochondral ossification in multiple joints. These are not mutually exclusive as both could result in an abnormal mechanical environment in the hip that results in OA.

Both the hip joint capsule and the chondrosseous conformation of the hip are major contributors toward the stability of the hip joint during loading and, therefore, must be taken into account when considering an underlying etiology of joint laxity. The round ligament of the femoral head may be the main supporting structure of the hip joint in dogs up to 1 month of age [7], after which the joint capsule assumes this function. The joint capsule originates in the lateral acetabular rim and inserts into the femoral neck. The strength of the capsule is predominantly due to its fibrillar collagen content and organization, whereas its compliance is due to the extracellular matrix composite of collagen, proteoglycan, water, and elastin [19-23]. As age increases, collagen cross-linking and content increase [24], contributing to the strength and stiffness of the joint capsule. When load is applied to a normal hip joint capsule, it returns to its original configuration when the load is removed. In the lax capsule, the stress-strain curve is shifted to the right compared with the tight capsule, resulting in further deformation for an equivalent stress than in a tight hip capsule [25]. As a result, the femoral head can undergo lateral translation relative to the acetabulum, a movement that jeopardizes the structural integrity of articular cartilage. This lateral and dorsal translation can be observed in the passive state in the dorsolateral subluxation position. Joint effusion can also cause hip laxity [17,26].

The joint capsules of dysplastic hips contain a higher ratio of type III to type I collagen in comparison with those of normal greyhounds [27,28]. Whether this is because of tissue immaturity, injury [29,30], endocrine imbalance [31] or a genetic abnormality is unknown. These results could be explained by capsular injury [32]; type III collagen is expressed after tissue injury and the dogs in this report were mature and some had been referred for total hip replacement, indicating that OA was advanced [28]. Transmission electron microscopy was used to compare the joint capsules of a dog with hip instability (distraction index 0.8) to one without instability (distraction index 0.4). A heterogeneous group of collagen fibrils was found in the dog with hip laxity and homogeneous collagen fibrils in the capsule of the dog without hip laxity. These same structural differences in collagen fibrils of the ligament of the femoral head were observed in the same loose-hipped and tight-hipped Labrador retrievers. It was not ascertained whether the capsular laxity preceded or was coincident with synovitis, but it is considered a precursor and risk factor for the development for OA. [6,20,33]. Dorsolateral hip luxation cannot develop without passive hip laxity [17]. Dysplastic dogs have abnormal round ligaments of the femoral head. It was shown initially that, in young pups with moderate to severe OA, the volume of this ligament increases [34]. A more recent study comparing the volume of the round ligament of the femoral head and the degree of radiographic OA in adult German shepherds demonstrated that no difference exists between the volume of the ligament of the femoral head in normal joints and those with only "mild" OA (shallow acetabulum/marked dorsal rim attenuation, moderately osteophytic acetabular margin, rounded femoral head, and minimal osteophytes on the femoral neck) [35]. An inverse correlation exists between the severity of radiographic OA and the volume of the round ligament of the femoral head [35].

The second broad etiologic category of CHD is an abnormality in endochondral ossification. The developing hip is composed of two articulating surfaces: the proximal femoral capital chondroepiphysis (including the articular epiphyseal complex, the region where the secondary center of ossification appears and the growth plate) and the acetabulum (Fig. 104-1).

Figure 104-1. A. Ultrasound image of the secondary center of ossification in the femoral head of a neonatal pup. B. Computed tomographic image of the pelvis of a 2-week-old pup. C. A magnetic resonance image of the pelvis and femur of a 2-week-old pup in the dorsolateral subluxation. D. A ventrodorsal radiograph of the pelvis of a pup at 2 weeks of age. Arrows show the secondary center of ossification in the femoral heads. (Compliments of WS Vanden Berg-Foels, Bioengineering, Cornell University).

In the developing acetabulum are four anlagen that give rise to the ilium, ischium, pubis, and acetabular bone, all contributing to the mature acetabulum. Each anlage has a primary center of ossification and a growth plate that results in growth of each anlage away from the center of the acetabulum. The ilium, ischium, and pubis all have a common epiphysis within which the primary center of ossification of the acetabulum appears. As mineralization proceeds, the growth centers localize in the acetabular cup. This creates the inverted Y shape on a lateral view termed the triradiate growth plate. The acetabular anlage ossifies between the two ventral arms of this growth plate and a secondary center of ossification develops in the common epiphysis prior to closure of the triradiate growth plate. This growth plate closes radiographically at 4 to 5 months of age in medium- to large-breed dogs, whereas the capital physeal growth plate closes between 9 to 11 months of age. This closure is delayed in dysplastic hips [15]. For normal hip joint formation and conformation to occur, proper contact, load, and congruence between the femoral head and the acetabulum are required. This is demonstrated by the success of pelvic harnesses for the treatment of dysplastic human hips. In CHD, this contact is interrupted.

Dogs with the genetic predisposition to CHD have grossly normal hips at birth, but this changes within the first few weeks of life. Whether laxity precedes osseous disconformity or vice versa is unknown. As the hip joint matures, the secondary centers of ossification and the femoral head and acetabular growth plates become histologically apparent and can be seen by diagnostic ultrasound, with radiographs, with computed tomography, and with magnetic resonance imaging (Fig. 104-1). Any femoral head dislocation affects the direction, magnitude, and distribution of the resultant femoral head force [36], leading to a lag in development of the craniodorsal acetabular rim [37]. Additionally, femoral capital chondroepiphyseal ossification is detected later in dysplastic hips than in normal hips [13,15]. It is likely that this early neonatal stage of development is the critical time in hip development when even small perturbations in the mechanical environment and gene expression sequence result in long-term detrimental effects [38]. Serial imaging in this early stage of development may hold the key to early diagnosis of CHD.

Epidemiology and Pathogenesis

The prevalence of canine hip dysplasia in one teaching hospital in the United States was 19.7% in purebreds and 17.7% in mixed breed dogs. There was no significant difference in the prevalence of CHD between sexes or between purebreds and mixed breed dogs [39]. The top four breeds presented to teaching hospitals that have been reported to be at increased risk for CHD in comparison with mixed breeds are the Bernese mountain dog, German wirehaired pointer, the Kuvasz, and Newfoundland [40]. Hip dysplasia affects dogs of all breeds but is clinically more common in large-breed dogs [41-46]. The prevalence of CHD within breeds is 1% to 75%, as estimated by the OFA (www.ofa.org/diseases/breed-statistics). The estimate may be low because radiographs of normal dogs are more likely to be submitted for certification than are those of dysplastic dogs, thus biasing the database.

The age of the dog at clinical detection of CHD varies depending on the severity of the disease and owner acuity. Dysplastic dogs often develop gait abnormalities and/or lameness during growth (between 3 and 8 months of age). Examination by palpation and radiographs may reveal subluxation of the hip joint(s). Synovitis, joint capsule thickening, and articular cartilage injury are uniformly present if subluxation is detected. The cartilage and soft-tissue changes characteristic of OA in dysplastic hips have been defined [47,48]. The initial cartilaginous lesion occurs parafoveally, suggesting that abnormal direction or magnitude of load results in increased focal stress in this area [47,49]. The result is joint pain, articular cartilage degeneration, and bony remodeling characteristic of OA (Fig. 104-2). As abnormal weight-bearing continues to cause excess articular cartilage wear, the underlying bone is also damaged, possibly causing painful microfractures and sclerosis. In young dogs, perifoveal articular cartilage lesions are accompanied by increased subchondral and femoral head bone density [50]. As the animal ages, the hip laxity decreases as the capsule undergoes fibrosis and the synovial effusion resolves.

Figure 104-2. A. Dorsal surface of a normal femoral head of a dog. B. Lateral aspect of a normal acetabulum of a dog. C. Medial surface of the femoral head of an 18-month-old dog with full-thickness erosion of the articular cartilage and loss of the round ligament of the femoral head. D. Lateral aspect of the acetabulum of the same dog as in C, with secondary OA from hip dysplasia.

Osteoarthritis remains and is a debilitating chronic condition characterized by loss of articular cartilage, fibrosis, bony remodeling, and eventual loss of function. Radiographic evidence of OA can be clinically apparent as early as 5 to 9 months of age in some dogs, whereas in other dogs it is not evident until 2 years of age or later [51]. Early OA changes such as synovitis, partial or complete tears of the ligament of the femoral head, and partial- to full-thickness articular cartilage abnormalities cannot be radiographically detected (Fig. 104-2) [5,52,53]. Using arthroscopy to directly evaluate the hip joint grossly in dogs undergoing a triple pelvic osteotomy, only 50% of dogs with Grade 2 to 3 arthroscopic lesions (articular cartilage surface fibrillation and deep fissuring, respectively) had radiographic evidence of OA in the extended hip view [52].

Genetics

Two main factors are associated with development of CHD: genetics and environment. A dog’s phenotype is the result of a complex interaction of its genotype and the environment to which it is exposed [18,37,54-56].

Canine hip dysplasia is considered a quantitatively inherited, complex, polygenic, or multifactorial disease that results in OA of the hip. Quantitatively inherited genetic traits vary along a continuum from one individual to the next and are influenced by two or more genes in addition to environmental factors [18]. The phenotypic and population genetic correlation is moderate and positive (0.24) [57] and the signs of subluxation reveal the highest heritability estimates [58]. Larger breeds share a heritable tendency to CHD and hip OA, yet many dogs with the genetic susceptibility do not show the clinical phenotype [46]. The heritability estimates (h2) of CHD vary among authors and study population. Based on radiographic screening studies, the heritability estimates for CHD range from 0.1-0.68 [41,45,46,55,57-62]. The maternal effect is additive (hm2 (additive genetic maternal effect) = 0.1 +/- 0.02) [60], dam and sire hip scores have a significant effect on progeny conformation scores [63]. No significant difference exists in progeny hip conformation scores between the sexes [63],. nor between mixed and purebred dogs [39]. The higher the heritability estimate, the more likely we are to make phenotypic improvements using selective breeding programs.

Using genetic selection to improve the phenotype has been achieved in controlled populations such as the Seeing Eye Inc., Morristown, NJ, by combining individual phenotypic information with parental and offspring information to obtain estimated breeding values [55]. One of the best genetic improvements reported is that of one standard deviation during 10-year period in Finland [57]. Screening programs through open registries such as those conducted in Sweden have resulted in improvement in hip quality [62], but in other countries [44,64-66] the improvement in phenotypes has been minimal. As CHD has a polygenic mode of inheritance, future attempts to control the disease using tests based on a single genetic marker would not be immediate [67], unless there was a major contributing locus and it was shown that mutations at that loci had to be present to express CHD. At our present knowledge level of its molecular genetics, this seems unlikely.

The pattern of inheritance indicates that CHD is controlled by several genes located at quantitative trait loci (QTLs) and the expression of which is influenced by environmental factors. Inductive or protective QTLs that control expression of hip OA may exist independent of those controlling the dysplastic phenotype [68,69]. Some dog breeds appear to display different susceptibilities to CHD based on their distraction indices and may tolerate more passive hip laxity than do other breeds [70,71]. Other breeds may develop radiographically detectable hip OA as a result of antecedent CHD faster than others [70]. A major locus contributing to CHD has been implicated in German shepherds, golden retrievers, Labrador retrievers, Rottweilers, and greyhound-dysplastic Labrador retriever crosses based on statistical models [55,72,73]. Using Portuguese water dogs to identify the QTL that regulates CHD, two separate QTLs were found, both on chromosome 1 separated by about 95 Mb, one associated with the Norberg angle of each hip and contributing up to 16% of the phenotypic variance. A major locus is thought to contribute 20% of the phenotypic variance so that molecular genetic results and population genetics are currently at odds [74]. It is interesting to note that any asymmetry in subluxation during extended hip radiographs was not heritable [74]. Alleles contributing to a complex trait such as CHD may be dominant or additive. The magnitude of their effect is independent of its mode of inheritance [75].

Environment

Many nongenetic and/or environmental factors influence the development and severity of hip dysplasia in genetically predisposed dogs. Not one of these has been shown to cause CHD in dogs that do not have the genetic predisposition. Factors such as body size, growth rate, the season of birth, nutrition, dietary anion gap, in utero endocrine influences, and muscle mass are considered to influence the development and clinical signs of CHD [18,33]. High caloric intake, excess protein intake, excess calcium intake, rapid growth rate, lack of or excessive exercise all result in increased severity of CHD [18,37,54,55].

Maternal/Litter Effects

Hormones and growth-promoting peptides such as insulin, cortisol, epidermal growth factor, insulin-like growth factors (IGFs), parathyroid-hormone-related peptide, relaxin, estrogen, and estrogen precursors are present in canine colostrum and milk [76,77]. These peptides, absorbed through the gastrointestinal tract particularly in the early postnatal period [78], have the ability to influence the connective tissue metabolism, especially that of genetically susceptible tissues. Relaxin, estrogen, and estrogen precursors are abundant in the milk of Labrador retrievers [31]. Relaxin persists in the serum of dysplastic Labrador retriever bitches throughout lactation but is detectable for only the first 1 to 2 weeks of lactation in nondysplastic bitches. Relaxin is a potent inducer of neutral matrix metalloproteinase 1 (collagenase 1) and 3 (stromelysin 1) and plasminogen-activator expression. These activated enzymes degrade the extracellular matrix and, therefore, affect the structure and metabolism of joint capsule and ligaments. Local relaxin activity on estrogen-primed tissues may contribute to the capsular and ligamentous laxity associated with CHD. The total serum estrogen is similar in pups born of dysplastic and normal matings, but testosterone was detected only in the milk of dysplastic Labrador retriever bitches, and estradiol-17β appeared only in the serum of pups born to dysplastic matings. Injection of an aromatase inhibitor (preventing the conversion of testosterone to 17β-estradiol) into pups from birth throughout lactation significantly reduced hip joint laxity at maturity in dysplastic-bred Labrador retrievers [79]. Dosing estrogen repetitively during the growing period can induce CHD [2,80].

The litter effect has been reported to contribute 4% of phenotypic variation; this percentage includes all environmental and genetic effects common to members of the same litter, but also contains the breed effect [57]. Therefore, it appears that the maternal effect is almost negligible (1.5%) [57,61].

Abundant food consumption shortens the time to first appearance and increases the severity of CHD [34]. Whereas overfeeding itself does not cause CHD, it does maximize trait expression in genetically susceptible individuals. The frequency and severity of CHD and concomitant OA in affected hips were greatly reduced in Labrador retrievers by limiting food consumption to 25% of ad libitum-fed control litter mates [81-83]. Reduction of food resulted in a 67% reduction of CHD at 2 years of age [83] and substantially reduced the prevalence and severity of hip joint OA at 5 years of age [82]. The dogs on the restricted diet had significantly less OA in their hips, shoulders, and lumbar vertebrae when maintained on this diet [81]. One study showed that a dog’s body mass at birth is an important factor in determining the age of onset of femoral head ossification as well as the laxity of the immature joint, with dogs of greater body mass having reduced femoral head coverage [38]. The mechanism of operation of these nutritional effects remains unknown, but may be explained by mechanics (maximizing growth allows maximum load to be placed on genetically susceptible hips), or by the effect of nutritional components on local gene expression. Lower body weight (i.e., restricted feeding) delays onset and limits severity of radiographic signs of OA [81-83]. Perinatal nutrition can have long-term effects on metabolism. Bottle-feeding, compared with breastfeeding, of puppies predisposed to CHD after caesarean section resulted in reduced growth rate and a low incidence of the trait. Ad libitum feeding of Great Danes induced the expression of several unwanted orthopedic traits including CHD when compared with dogs on restricted feeding [43]. It has also been suggested that excessive exercise in dogs with much joint laxity is likely to cause or worsen CHD, but there is no scientific evidence to support this impression.[84].

Besides reduced food intake, systemic polysulfated glycosaminoglycan (Adequan) is the only treatment that has been shown to significantly reduce the expression of hip OA in CHD when administered to dysplasia-prone Labrador retrievers from 6 weeks to 8 months of age [85]. Polysulfated glycosaminoglycans are inhibitors of neutral matrix metalloproteinase activity and also significantly reduce pubic symphyseal relaxation in estrogen-primed guinea pigs [86].

Many large-scale studies have attempted to evaluate the environmental factors that affect the incidence of CHD expression. In one study of Rottweilers in Finland (n=2764), the environmental effects influencing CHD were age (the older the dogs, the worse the condition), birth year (1998 best, 1995 worst), birth year x season interaction (season by itself was not a factor as in other studies [45,59,61], and the experience of veterinarian radiographing the dog (but with no clear trend and small differences between classes) [57]. In a more recent study of British Labrador retrievers and Gordon setters, the mean hip scores of dogs born between June and October were lower than those of dogs born during the rest of the year. These results are similar to those of Hanssen 1991 and Olerth et al. 2001 [87]. One hypothesis for this effect is that dogs born during the warmer season can exercise on soft ground, creating a supportive musculature and preventing HD [88]. Many other factors probably influence the results regarding season of birth. Body mass at birth was a significant predictor of age at onset of proximal capital ossification (the greater the mass, the earlier the onset) and of 4-month-old femoral head subluxation (the greater the birth weight, the more reduced coverage in the dorsolateral subluxation position) [38].

Results of studies conflict when trying to determine whether gender influences the expression of CHD. Increased frequency in females [1,62], males [59], and equal sex distribution [71,89] have all been reported. Therefore, it is unknown if the influence of sex is a direct expression of genes on the sex chromosomes or a result of the secondary effects of sex (hormones, weight) [62]. The estrus cycle of a dog had no significant effect on hip laxity as measured by the distraction index [90].

Diagnostics

Dogs with CHD present most commonly at two different ages: as pups at 5 to 9 months of age and as mature adults. Dogs as young as 16 weeks of age with hip joint laxity as measured by the distraction index are at risk for OA [71]. The most common findings on physical examination in young dogs with CHD are discomfort on extension or abduction of the hip and/or a positive Ortolani sign. In 6-month-old dogs, the angle of reduction is repeatable, suggesting that it may be used by multiple examiners with comparable and consistent results [91]. A positive Ortolani sign is thought to be a risk factor for development of OA later in life, but the significance of its presence or absence has not been evaluated long-term [49]. As dogs age, those with subclinical lameness secondary to hip OA will compensate by shifting their weight between trotting pairs rather than within them [92]. As the pain of chronic OA increases, the effects are best judged by an owner or a person familiar with the dog after receiving training regarding the clinical signs of this disease [93].

Prevention and Radiographs

Radiography is the most common tool used in the diagnosis of CHD, but it also has great utility in determining the likelihood of the development of CHD in pups. Several radiographic techniques have been researched extensively to determine their sensitivity and specificity in determining which dog will develop radiographic, clinical, or histopathologic evidence of CHD. The problem with all radiographic techniques is that a dog’s phenotype is no guarantee of its genotype. Much of the information published is conflicting or not comparable owing to different study scenarios and end-points. We will give an overview of the different radiographic techniques and the indications for them.

Several radiographic signs have been reported to occur first in CHD. Femoral head subluxation and a lag in the development of the acetabular rim seen as early as 2 to 9 months of age was reported in 1973 [37], and delayed ossification of the femoral head was reported to be the earliest radiographic predictor of CHD on a population basis [13,15]. Later OA changes secondary to CHD include subchondral sclerosis, osteophytosis, joint deformity, proliferative and lytic changes at attachments of joint capsule and supporting ligaments, and intra-articular bodies [94-96]. Radiographic OA can be apparent at 5 to 9 months of age, but some are not evident until at least 24 months of age or later [51].

All of the available radiographic tests are considered to be inaccurate at 4 months of age or earlier, most likely owing to ongoing endochondral ossification and the inherent difficulty of imaging cartilage with standard radiographic techniques [9,11,15,97]. Diagnostic methods are more accurate at 8 months of age or later [9,11,15,97,98]; once the hip joints are fully mature after the period of rapid growth is complete [99]. When evaluating any dog radiographically for CHD, one must keep in mind that not all dogs with radiographic subluxation develop radiographic evidence of OA by 2 years of age [97].

Extended-Hip Radiograph

The extended-hip radiograph (EHR) is frequently used for CHD screening purposes (Fig. 104-3). It is performed with the dog in dorsal recumbency, usually heavily sedated. The femurs are pulled parallel to the table top and each other, and the knees extended and rotated such that the patellae are centered in the trochlear grooves. The Orthopedic Foundation for Animals (OFA, www.ofa.org) uses this view to grade CHD. (The radiographic view allows determination of the presence of OA, its severity, and of certain degrees of subluxation. Using the EHR, evaluations earlier than 2 years of age are considered preliminary because younger widely affected dogs may not have evidence of subluxation when radiographed in the extended position [11,33]. Findings suggest that the strength of the EHR at 8 months of age is its specificity [98]. It is commonly accepted that the OFA-type hip scoring method is the most specific (96%) [53], but it underestimates the susceptibility to CHD [100]. Smith et al. (1995) found that the Norberg angle, obtained from EHR, is not a significant risk factor for subsequent radiographic hip OA [71].

Figure 104-3. A. Ventrodorsal radiograph of the pelvis of a dog with good hip conformation. B. Ventrodorsal radiograph of the pelvis of a dog with severe hip dysplasia. C. Extracted hips of an old dog with severe hip remodeling characteristic of the OA that progresses in a dysplastic hip. D. Ventrodorsal radiograph of the pelvis of a dog with hip OA secondary to hip dysplasia.

One finding on the EHR that has shown predictive value in later OA development is the caudolateral curvilinear osteophyte (CCO). First identified in 1961, it appears at the insertion of the joint capsule into the femoral neck [101]. The importance of its appearance has been questioned [7,96,102-104], as it is often present without any other evidence of OA, and has prompted questioning of its use as an early sign indicating that OA will develop later [84]. It must be differentiated from what has been termed the "puppy line", which resembles the CCO but is thought to be nonpathologic [84]. The puppy line is found in dogs up to about 18 months of age and either disappears or transforms into a CCO [105]. No statistical relationship exists between the puppy line and later development of OA. The original hypothesis was that the CCO develops secondary to increases in stress on the joint capsule insertion in dogs with excessive laxity [96]. Other studies have shown that, in Labrador retrievers, a relationship exists between the CCO and subsequent OA development. Dogs with a CCO are 3.7 times more likely to develop radiographically evident OA than are those without a CCO [105]. The CCO was the first radiographic sign in 76% of dogs that later developed radiographic OA and 95% of dogs with histopathologic OA had a CCO [105]. Another study showed that dogs with a CCO are 7.9 times more likely to have radiographic OA than are those without a CCO. The animal’s distraction index, weight, and age are significant risk factors for the CCO [84], but this contemporaneous relationship does not predict ultimate OA development. When evaluating the CCO in relation to feeding groups (ad libitum control group or restricted-fed group), it was found that 100% of control dogs with a CCO and 55% of restricted-fed dogs with a CCO developed later radiographic OA [105]. Regardless of the feeding group, dogs with a puppy line were not more likely to develop OA or a CCO compared with dogs without a puppy line. Diet did not influence the frequency of the CCO, only the time of onset of CCO. This may suggest that the CCO is a more sensitive radiographic marker for susceptibility for OA that is not confounded by environmental factors such as restricted feeding [105].

Distraction Index (PennHip) and Dorsolateral Subluxation Score

The distraction index (DI) (Fig. 104-4A) and the dorsolateral subluxation score (DLS) (Fig. 104-4B) assess the laxity of the hip joint. The DI is also measured in dorsal recumbency. For the DI radiograph, the hips are flexed so that the patellae point to the ceiling. A custom-made levering device is placed over the coxofemoral joints between the femurs and an inward force is applied to the stifles to determine the amount of laxity present in the hip joint. The DI is calculated between these views and is used to predict the likelihood of the development of CHD. Individual logistic regression curves can be established for each breed to relate DI to the presence of hip OA secondary to CHD. The operator must have received special training to perform this technique and submit the radiographs for evaluation. However, this ensures a complete unbiased registry. Additionally, the DI can be artificially increased by increasing intra-articular volume, as well as cavitation, without affecting DLS score [17,106]. The DLS view is also performed under heavy sedation or general anesthesia. The animal is placed in sternal recumbency on a pad with a cutout for the rear legs, such that the knees are flexed and weight-bearing. The radiograph is centered over the hip joints and shows the conformation of the hip joints as the animal bears weight. The advantages of the DLS are that it is easy to perform, requires only one radiograph, can be done with the animal anesthetized or sedated, and does not require the operator to hold the dog during radiography. The method and measurements are reproducible [49]. External factors such as dorsal hip loading and whether the test is performed under general anesthesia or heavy sedation do not have marked clinical effects on the DLS score, although loading the hips does increase the DLS score in some cross-breeds [107]. The 6% change between loaded and unloaded DLS scores overall is statistically significant but is unlikely to be clinically significant [107]. The DLS score is an objective measurement of coxofemoral subluxation, whereas the OFA score is subjective.

Figure 104-4. A. Ventrodorsal radiograph of the pelvis of a dog in the distraction (PennHip) position. B. Dorsoventral radiograph of the pelvis of a dog in the dorsolateral subluxation position. Both of these dogs have hip laxity, and the dog in 4B has hip dysplasia and subluxation.

The DI and DLS scores are associated, but likely represent distinct features of hip joint structure and evaluate different components of joint stability [17]. Several studies have suggested that both the DI and DLS scores remain constant after 8 months of age [9,18,98]. In a mature hip, the laxity (DI) can change independently of the DLS score [17]. The use of either the DI or the DLS score improves the detection of subtle cases of CHD compared to the EHR. The specificity of the DLS score for prediction of hip OA at 8 months of age is similar (84%, DLS score < 55%) to the DI (89%, DI > 0.7) in dysplastic Labrador retrievers, greyhounds, and their cross-bred offspring [73]. The sensitivity appears to be better for the DLS score than the DI: depending on the cut-off used for the DI (> 0.7) and the DLS score (< 55%), the former had a sensitivity of 50% and the latter a sensitivity of 83%. At 8 months of age, dogs with DLS scores less than 42% suffered from hip OA at early maturity, whereas those with DLS scores over 55% were highly likely to have normal hips. We have argued that the DLS score represents a component of hip joint conformation independent of passive laxity, yet both are important to subsequent OA development [49,108].

Several studies have compared a multitude of radiographic techniques with different endpoints – radiographic evidence of OA, gross necropsy findings, and histopathologic OA. One such study compared the EHR, DI, and DLS in 8-month-old dogs and used gross necropsy findings as the endpoint. All radiographic findings were significantly correlated with the gross findings. Specificities were similar for all 3 methods, but the DLS score had higher sensitivity and, therefore, fewer false negatives [96]. Another more recent study also compared the radiographic findings in 8-month-old dogs with gross necropsy findings. Specifically evaluated were the EHR, DI, DLS score, and the Norberg angle (NA). The DLS score and the NA together were best at determining normal joints versus joints with OA, and all models excluding the DLS score were worse than those that included it. The conclusion of this study suggested that two tests were better than one, especially if one was the DLS score, with no improvement if a third test was added for detection of CHD [109].

Treatment and Prognosis

Two different treatment options are commonly recommended for CHD: medical management and surgical management. Surgical management consists of juvenile pubic symphysiodesis, triple pelvic osteotomy, excision arthroplasty, and total hip replacement. These are discussed elsewhere. Medical management is multifaceted and consists of preventative measures early in the animal’s life and treatment to ameliorate the progression and clinical signs of OA later in life.

The two main preventative measures that can be taken in a dog genetically predisposed to CHD are the administration of systemic polysulfated glycosaminoglycans (PSGAG) and limiting the food intake. Administration of systemic PSGAG at 5 mg/kg during growth can significantly ameliorate progression of CHD and secondary OA in susceptible dogs [85]. In dogs with severe OA secondary to CHD, there was no statistically significant difference between the treatment groups with PSGAG at 3 increasing doses or the placebo. The authors attributed this either to a lack of response or a response too small to be detected by the physical examination used to determine effectiveness [110]. PSGAG have chondroprotective effects when used prophylactically or therapeutically [111-118]. Polysulfated glycosaminoglycan (Adequan®) is derived from bovine lung and tracheal tissue, which is structurally similar to the glycosaminoglycans found in hyaline cartilage [119,120]. In vitro, PSGAG can inhibit the rate of collagen and glycosaminoglycan degradation [121-123]. Other in vitro studies suggest that PSGAG treatment may modify the progression of OA in articular cartilage by maintaining chondrocyte viability as well as protecting against extracellular matrix degradation [124]. Similar serum and joint concentrations of PSGAG are achieved after intramuscular and intra-articular administration [125].

Another method of decreasing the severity of CHD is by limiting food consumption starting at 8 weeks of age. Reduction of food intake by 25% compared with ad libitum-fed controls resulted in a 67% reduction of CHD at 2 years of age 83 and substantially reduced the prevalence and severity of hip-joint OA at 5 years of age [82]. Osteoarthritis also affected multiple joints significantly less commonly in limit-fed dogs [81]. Once a dog is suffering from CHD-induced OA, several recommendations to the owner are suggested: weight reduction to the breed’s ideal body weight if the animal is overweight; moderate exercise, which increases the supporting muscle mass of the hip joints; and the addition of nonsteroidal anti-inflammatory medications if they can be tolerated by the animal. The addition of a supplement containing glucosamine and chondroitin sulfate or injection of PSGAG is also recommended, especially in younger dogs.

Rigorous application of any detection method for CHD combined with progeny testing seems to be as important as the method of hip evaluation itself in reduction of trait incidence. Simply breeding animals with better hips than the average for the breed will not eliminate the trait [65]. Until genetic screening is available, the best indication of a dog’s genetic makeup is the phenotype of its parents and grandparents, its offspring, and its siblings and half siblings. Prospective purchasers of puppies should request from breeders phenotypic information on the puppies’ relatives. In the end, the best solution to eliminating the trait from a breed is to know the linked genetic markers and ultimately the mutations at the major contributing loci in that breed. That could lead to genetic screening of pups before purchase and breeding and informed decisions regarding breeding programs.