Breed Susceptibility for Developmental Orthopedic Diseases in Dogs

Introduction

Developmental orthopedic diseases (DODs) are a group of diseases that cause skeletal abnormalities in young, growing dogs.^1–12 The etiology of most of the DODs is considered to be multifactorial, attributable to both genetic and environmental factors.

The advantages of knowing which breeds of dogs are at increased risk for DODs are evident. The information can help practitioners during their evaluation of young dogs with skeletal disorders by providing differential diagnoses. It can heighten awareness among breed club members, helping them make decisions about how to spend their foundation dollars, and it can lead to more emphasis being placed on methods to diagnose and genetically screen for the disease in that breed before animals are bred and genes are recycled to the gene pool.

The purpose of the study reported here was to test the hypothesis that some breeds are at significantly higher risk for DODs. Therefore, the authors determined the breed-associated odds ratios (ORs) and confidence intervals (CIs) for 12 DODs in a large referral population during a 10-year period.

Materials and Methods

Results

The 10 veterinary teaching hospitals submitted a total of 300,122 new canine case records to the VMDB between 1986 and 1995. Approximately 27% (81,831) of the cases were diagnosed with a musculoskeletal disorder, and approximately 8% (24,373) of the cases were diagnosed with any of the 12 studied DODs. Frequency of diagnosis of DODs during the 10-year period ranged from 35 cases (CMO) to 10,637 cases (CHD) [Table 1]. The number of breeds at increased risk compared to mixed-breed dogs ranged from one (CMO) to 35 (CHD). All breeds at significantly increased risk for any of the 12 studied DODs along with ORs and 95% CI are listed in Table 1.

Discussion

In this study, a large referral patient population was used to identify canine breeds at increased risk for any of the 12 DODs. To the authors’ knowledge, this is the first study in which breeds at risk for panosteitis, FCP, or UAP have been determined. Several breeds identified as being at increased risk for any one or more of the other nine DODs have been identified in previous studies.^91114–23 The significance of identifying breeds at increased risk for a disease is that it may suggest a genetic predisposition of the breed for the disease.²⁴²⁵ Therefore, breeds determined in this study to be at increased risk for a studied DOD may have a genetic predisposition and thus may be more susceptible to effects that the environment may have on skeletal development.

Puppies from breeds at increased risk for a DOD with a demonstrated nutritional etiology may benefit from environmental manipulation (such as dietary modification) to minimize disease-associated morbidity. Developmental orthopedic diseases with a demonstrated nutritional etiology include CHD and OCD.^26–30 Specific nutritional risk factors for these diseases include excess energy intake,²⁶²⁸ excess calcium intake,³¹³² and electrolyte imbalance.²⁷ Excess protein intake per se has not been shown to have an adverse effect on skeletal development.³³ For other DODs (i.e., FCP,³⁴ HOD,¹⁰³⁵ and panosteitis³⁶), a nutritional background has also been suggested. Breeds that are identified to be at increased risk for a DOD with a confirmed or suspected nutritional etiology may benefit from nutritional modification.

Recognition of the environmental influences of DODs can facilitate control for individual dogs. For example, it has been shown that the development of degenerative joint disease associated with CHD can be manipulated to some extent by limited food consumption.²⁶²⁸ Manipulation of the phenotype in such cases, however, does not affect the animal’s underlying genetic makeup. Therefore, regardless of phenotypic manipulation of the disease process, the propensity for the disease to be transmitted to subsequent generations remains intact.

An alternative approach to environmental management for disease control is manipulation of the genetic makeup of future generations of dogs by using controlled breeding. The recognition that some of the DODs have a substantial genetic component has resulted in the establishment of genetic screening programs such as the Orthopedic Foundation for Animals^e (OFA), the University of Pennsylvania Hip Improvement Program^f (PennHIP), and the Institute for Genetic Disease Control in Animals^g (GDC). These programs utilize phenotypic screening to identify low-risk animals within breeds for inclusion in breeding programs. There is evidence that application of selective breeding using these types of screening programs can facilitate improvement in the evaluated phenotype,^2337–39 although the degree of genetic involvement in the etiology of the diseases evaluated by these organizations is not always known.

The ultimate method to characterize genetic etiology for a disease is the determination of its heritability and mode of inheritance. Although multiple heritability studies have been published on the heritability of CHD, primarily for the German shepherd dog,^1619–2123 heritability studies of other DODs are few^3740–42 and are limited to one or a few breeds. It has been suggested that a higher prevalence of a disease within a group of related animals (such as a breed or a family within a breed) is the first evidence that a disease may have a genetic etiology.²⁴²⁵ Accordingly, knowledge of specific dogs or breeds of dogs at risk for DODs may provide a better understanding of the etiology of the disease and facilitate genetic or environmental intervention. Some investigators have identified breeds at increased risk for specific DODs using epidemiological techniques.^911151821 Additional references^1124344 suggest that various breeds may be over-represented for some DODs, based on subjective observation of breeds seen more often in the clinical setting. However, these claims have not previously been substantiated by epidemiological studies.

The present study was performed in a larger population and included more DODs than previous studies. The comprehensive scope of the study is evidenced by the fact that the overwhelming majority of breeds already reported in the literature to be at increased risk for specific DODs^91114–23 were also identified in this analysis [Table 2]. Furthermore, many of the breeds identified as potentially predisposed to DODs were not previously recognized, suggesting that this study has expanded the current knowledge base on this subject. For example, although Great Danes have previously been identified to be at increased risk for OCD of the stifle,¹¹ this study suggests that eight additional breeds may also be predisposed.

Because this study was performed on such a large scale, some breeds that are infrequently encountered⁴⁵ within the studied population, and therefore potentially omitted in previous smaller studies, could be identified as being at increased risk in this study. Previous smaller studies of individual diseases were able to draw conclusions about breed susceptibility for only the more prevalent breeds within their study population. Even with the large number of cases used in this study, the authors acknowledge that there may be additional breeds that are at increased risk for some of the 12 studied diseases. That is, this study may not have identified some breeds at increased risk, owing to the small number of diagnosed cases within that breed (i.e., <5 cases).

This epidemiological survey, like the smaller epidemiological studies previously reported,^91114–23 is an initial step in identifying the genetic role in a DOD’s etiology. Subsequent steps for characterization of breed risk for a specific disease may include verification of breed susceptibilities from breed health club surveys; comparison of the present data with data from other databases such as OFA, PennHIP, and GDC; and investigation of the mode of inheritance within a breed. The ultimate goal may be the development of genetic control programs for breeds at risk.

The VMDB is a source of information consisting of more than six million cases. However, the information recorded for each case is limited to signalment, diagnosis, and procedure information as encoded in the database. Therefore, the ORs recorded in this study must be interpreted in light of the limitations of the VMDB. First, it is possible that some of the diagnoses encoded in the VMDB were initial diagnoses that were not verified with further workup. Second, there is undoubtedly some variability in how a disease is diagnosed among institutions and over time within the same institution because of changes in diagnostic ability and diagnostic or specialists’ emphasis. Finally, the coding used for the VMDB may vary to some degree among institutions and over time. Some of the effects of these sources of variation were minimized by including only institutions that participated for 10 consecutive years and by choosing controls from the same institution during the same year that the diagnosis of the DOD was made.

Conclusion

The authors identified breeds of dogs that were at increased risk for 12 DODs. This information may assist veterinarians in developing differential diagnoses for orthopedic diseases of young dogs and help breed clubs establish their priorities for research funding and in educational efforts targeted at breeders. Acknowledgment of breed specificity and the possibility of a genetic etiology for these diseases may ultimately lead to the development of breeding programs aimed at population control of the disease. The recognition by practicing veterinarians of individual patients that are members of breeds identified to be at increased risk for DODs can also facilitate environmental (e.g., nutritional) intervention at an early age.