Etiology of Elbow Dysplasias
H.A.W. Hazewinkel, DVM, PhD, DECVS, DECVCN
Dept. Clinical Sciences for Companion Animals, Utrecht University
The Netherlands

Introduction to seminar of International Elbow Working Group

Dear colleagues,

The board of the International Elbow Working Group (IEWG) is grateful to the organisers of the 30th World Congress of the Worlds Small Animal Veterinary Association (WSAVA)--FIAVA--AMMVEPE for the hospitality offered, to organise a seminar dedicated to elbow dysplasias. The IEWG has been founded in 1989 by a group of veterinarians and dog breeders with a concern about ED. The purpose of this non-profit working group is to gather and exchange knowledge and experiences about hereditary elbow diseases regarding aetiology, diagnosis, treatment, and prevention as well as screening on its presence. The latter includes a standardised method of radiological film reading, a standardised method of scoring of the presence of the primary lesion or secondary osteoarthrosis as well as a standardized scoring form. Later this year (2nd September 2005) the screening and scoring of radiographs of elbow joints will be discussed among screeners working for or with the Federation Cynologique Internationale (FCI) in Munich (Germany) during an event of the European Society for Veterinary Orthopedics and Traumatology (ESVOT). An ED-certificate will be introduced; it gives insight not only into the identification of dog, owner and screeners, but especially also into the amount and direction of radiological views used for screening and the findings the final score was based upon. All the aspects of concern of the IEWG are directed to diminish the incidence of the developmental disturbances of the elbow joint in growing dogs of numerous breeds, with a great impact on the quality of life for both the patient and its owner. Therefore the WSAVA recognised the IEWG as an affiliated group.

The IEWG can only accomplish this goal with the help of several experts who accepted the invitation to give an update in their field of expertise, by the organisers of the congress of the WSAVA~FIAVACÃMMVEPE providing space in the congress programme and a lecture room to have the meeting, by the moral support of the WSAVA, and by the financial support of its sponsors Iams Pet Food and Pfizer.

We are looking forward to an interesting, scientific meeting together with colleagues of the hemisphere were till so far IEWG members has not met before. Since the IEWG meeting is open to all veterinarians, members and non-members, both present at the WSAVA~VPAT congress as those visiting us at the web page (www.iewg-vet.org) are assured of a large group of interested veterinarians to exchange knowledge.

Dr. H.A.W. Hazewinkel, president
H.A.W.Hazewinkel@vet.uu.nl

Dr. B. Tellhelm, treasurer
Bernd.Tellhelm@vetmed.uni-giessen.de

Dr. K.L. How, secretary
how@wxs.nl

Elbow dysplasias (ED) occur frequently in 4-6 months old dogs of medium and large body size, during the period of high growth velocity. Since developmental skeletal diseases, either due to genetic disease or due to nutritional influences or trauma, are frequently seen in this category of companion animals all three can be hold responsible for the occurrence of ED. It is known that each form of ED will lead to osteoarthritis with possibly severe consequences for the well-being of the animal and its owner, and therefore great effort has been undertaken by different research groups to elucidate the etiology of ED to come to guidelines how to prevent their occurrence.

Genetic influences

Purebred dog populations represent genetically closed populations, in which high selection intensities and subsequent high levels of consanguinity are common. When only few of the members of the breed (e.g., mainly the champions) are used for reproduction, than a genetic bottle neck is created unintentionally but surely, reducing the genetic heterogeneity. It is to be expected that this selection procedure, which is common place in many breeds, may lead to increasing incidence of genetic diseases when the selected breeding stock by chance carried the genetic risk factor for ED or any other genetic disease. When the genetic risk factor has a dominant inheritance pattern leading to clinical signs before breeding age, than the dog and its parent(s) can be discarded from reproduction, like in chondrodysplasia (Carrig et al, 1988). But in case the genetic risk factor has a recessive or polygenetic inheritance pattern, has a variable penetrance pattern, or is based on a genetic diseases with a high influence of environmental aspects than, especially when manifest at older age, the entity has all chances to spread around in the population before being recognised. This is especially so, when there is a lack of adequate disease registration. In such diseases, the spread of the disease allele can be considerable before these diseases are recognised as genetic diseases within certain breeds (Ubbink 1998, Patterson et al, 1989).

Although ED occurs in well described breeds, not each form of ED is seen in all of them:

 Incongruity of the elbow joint (INC) due to a radial overgrowth is seen in Bernese Mountain Dogs in 80% of the dogs with osteoarthrosis in the elbow joint. In a survey of a large group of Bernese Mountain dogs this type of incongruity was seen in all cases with elbow lameness in conjunction with a fragmented coronoid process (Ubbink et al, 1999). Population analyses revealed that the disease was introduced right after WW II by a limited number of founding fathers and from there introduced in the breed.

 Fragmented coronoid process of the medial aspect of the ulna (FCP) is seen in many breeds and in large percentages, up till 50% of the screened population (Svenson et al, 1997, Ubbink et al, 1999). The heritability estimates are between 0.24-0.43 for Bernese Mountain Dogs, 0.77 for Labradors and 0.45 for Golden Retrievers (Guthrie and Pidduck, 1990). For Retrievers, these figures are for osteochondritis dissecans of the medial humeral condyle (OCD) plus FCP, and thus found to be polygenetic in addition to multifactorial (Padgett et al, 1995). For FCP and OCD alone, these figures are not calculated yet.

 The ununited anconeal process (UAP) was called elbow dysplasia long before the above entities were covered by this term as well (Corley et al, 1965). It is seen in chondrodystrophic breeds (like Bassets) and as part of elbow incongruity in certain breeds (German Shepherd, St Bernard) as well as due to nutrition induced or traumatic radius curvus syndrome (Hazewinkel, 1998).

Cluster analysis, using computerized programmes containing all pedigree of the investigated population, reveals histograms representing a group of related dogs with 1/8 th of the genome in common. We evaluated Labrador Retrievers, Bernese Mountain dogs and Golden Retrievers in groups, as electively chosen from the Dutch population and representative for that population. All dogs were screened radiologically for FCP on 4 radiographs according to the technique described by the IEWG on their web page. Certain related groups revealed members positive for FCP in 27-50% of the investigated dogs. These groups of dogs are spread over the country so the environment (i.e., housing, rural vs town area) are different in many cases. In Labradors the affected groups were quit related and less related with non- affected groups, whereas in Bernese Mountain dogs all groups of 1/8th-related dogs were affected with ED and all groups were connected which each other at the 8th generation (just after 1945); in Golden Retrievers ED was seen frequently in related groups and these groups were related with each other although to a lesser grade as was seen in Labradors (Dijkshoorn et al, 2005). Although this method does not show the inheritance pattern, it is proven to be an effective method for persuading kennel clubs to take measurements like obligation of screening before breeding.

Environmental influences

From the heritability estimates it can be concluded that other factors may play a significant role in the manifestation of ED. From different studies it became clear that breeding with ED-negative dogs (based on radiological screening) will decrease the incidence of ED considerably when compared with breeding of positive x positive, or positive x negative, or negative x unknown (Svenson et al 1997). ED in Labradors and Golden Retrievers is seen more frequent in male than in female dogs, although it can be expected that environmental factors do not differ to such a degree between genders. We calculated that, in case ED follows the hereditary pattern of a variability in expression of a major gene, the penetration of FCP in male dogs is 70% and in female dogs is only 28%. In other words, in a Labrador with the disease allele for FCP, this disease comes to expression in 70% of the males and only in 28% of the females, thus a phenotypical negative female has a larger chance to pass the genes to the next generation than a negative male Labrador, even when screened carefully. For breeders this is important information, since it warrants not only the screening of the breeding stock, but also of related animals (i.e., littermates) and offspring, which might tell more about the genetic make-up of a particular dog than the radiograph of its own elbow joints.

Nutritional influences

From a variety of studies it became clear that nutrition has a major impact on skeletal development. Food with a high calcium content has proven in field studies (Slater et al, 1992, Kallfelz & Dzanis, 1989) as well as in standardised laboratory circumstances (Hazewinkel et al, 1985, Schoenmakers et al 2000) that high mineral intake will cause disturbances in endochondral ossification. This makes the skeleton more vulnerable to mechanical influences like over weight as well as to OCD lesions. More recently, it became clear that vitamin D intake increased to a level that it will not lead to hypervitaminosis D (with calcification of soft tissues), will also disturb endochondral ossification by direct influence and not by increasing intestinal calcium absorption (Tryfonidou et al, 2002). High food intake and thereby excessive calcium and vitamin D intake does also lead to osteochondrosis (Lavelle 1989, Hedhammar et al, 1974). High calcium or high vitamin D intake will cause retained cartilage in growth plates and thus a disturbance of growth in length of the fast growing growth plates, in particular of the distal ulna and distal radius. Disturbance of growth in length may lead to radius curvus syndrome or short radius syndrome, respectively. Elbow incongruity in case of radius curvus syndrome may coincide with UAP, whereas incongruity with a shortened radius may coincide with FCP.

These findings are of great value for owners of a single dog, who want to prevent ED to develop in their pet by providing an optimal environment to mature. A high quality dog food prepared particularly for puppies of large breeds should be provided, characterized by a lowered (~1.0% calcium of dry matter base) calcium content and a controlled vitamin D content (~500 IU/ kg food). It has been shown that an increased protein level of high quality, typical for the better puppy diets, does not have a negative influence on skeletal development whereas it is of importance for soft tissue growth and immunological defence systems (Nap et al, 1993).

Mechanical influences

Traumatic injury of growth plates, especially Salter Harris type V fractures, may disturb growth in length of either the radius of the ulna and as such may be responsible for the overloading of ulna or radius, respectively. In case the coronoid is mainly cartilaginous or the anconeal process is still separated from the olecranon by a cartilaginous layer (< 5 months of age), this can result in a FCP or UAP, respectively. Only seldom, there can be an indication of a traumatic fracturing of the anconeal process or of a coronoid process in adult dogs, while both age and history will differ from that of ED in young, fast growing dogs.

Not too much is known yet about the influence of loading on skeletal development in dogs. It is known that unloading will cause both disuse osteoporosis as cartilage degradation, especially in young fast growing individuals. Some of most compelling evidence that supports a causal relationship between cartilage function and form comes from animal experiments in which the joint loading is either increased or decreased above normal levels. Increasing the functional loading of joints though moderate exercise causes an increase in articular cartilage thickness, proteoglycan content, and mechanical stiffness of the tissue, though strenuous exercise can lead to the formation of cartilage lesions (Wong & Carter, 2003). In a large, well controlled study in fowls it became clear that a functional adaptation of joint cartilage to weight bearing occurs during the first months of life and is important for the development of resistance to injury during later life (Brama 1999). Immobilization or other means of joint unloading has lead to a thinning and softening of the uncalcified part of articular cartilage, an increase in subchondral vascular eruptions, and a decrease in proteoglycan content. The structural and biochemical changes associated with joint unloading can only partially be reversed when the joint is remobilised. Physiologic joint loading results in functional adaptations that increase the resistance of the cartilage and are beneficial to the overall health of the tissue. The areas of enriched proteoglycan content are logically the areas most resistant to the degenerative changes that beset a joint during osteoarthritis (Wong & Carter, 2003).

Further research is needed to learn more about the optimal weight bearing or training activities of young, fast growing animals to develop optimal functional adaptation. Joint incongruity as seen in Bernese Mountain dogs, with constant overloading of the remaining weight bearing surface, i.e, the contact area of the humeroulnar joint, can hold responsible for the fragmentation of the apex of the medial coronoid process, although Bernese Mountain dogs with a FCP without INC can be seen in approximately 20% of the Bernese with ED. The FCP in Labradors, Golden Retrievers and Rottweilers, characterized by a fragmentation of the coronoid process at the radio-ulnar joint is still unknown, however the anatomical study of Wolschrijn & Weijs (2004) in coronoid processes of Golden Retrievers pups may give an indication. An anisotropic structure of the trabeculae with an orientation in the direction of the proximodistal axis of the ulna is already present at 6 weeks after birth. This primary alignment is perpendicular to the humeroulnar articular surface, matching the direction of the compressive forces applied to the medial coronoid process by the humeral condyle. The secondary alignment appears at 13 weeks after birth and is directed along the craniocaudal axis of the medial coronoid process, toward the attachment of the annular ligament. Excessive pulling force of this ligament might be responsible for the fragmentation of the coronoid process in Retrievers. In any case, it is very unlikely that normal weight bearing even during playing can be hold responsible for the FCP frequently seen in particular breeds.

Conclusion

In summary, elbow dysplasias (including UAP, FCP, OCD and INC) could spread among certain dog breed, due to the use of a limited amount of breeding dogs affected with a disease allele which comes not to expression in all cases. Based on the heritability estimates as published in veterinary literature, environment will play a significant role in cases the genotype comes to expression. Since dietary intake of calcium and vitamin D may cause disturbances in endochondral ossification and thus play a role in the occurrence of UAP, FCP, OCD and INC, unbalanced diets or excessive food (and thereby mineral) intake should be avoided. Although trauma may play a role in the occurrence of UAP or FCP in only a limited amount of cases, the preventive or causative influence of physical activity or over-use on elbow joint development in dogs is still largely unknown.

References

1.  Brama PAJ, TeKoppele JM, Bank RA, Barneveld A, van Weeren PR. Influence of different exercise levels and age on the biochemical characteristics of immature equine articular cartilage. Equine Vet J Suppl. 1999 Nov;(31):55-61.

2.  Carrig CB, Sponenberg DP, Schmidt GM, Tvedten HW. Inheritance of associated ocular and skeletal dysplasia in Labrador retrievers JAVMA 193, 1269-1272, 1988

3.  Dijkshoorn NA, Ubbink G, Nap RC, Meij BP, Hazewinkel HAW, Incidence of elbow dysplasia in Golden Retrievers in The Netherlands, submitted, 2005

4.  Everts RE Molecular genetic studies in the dog: application to FCP in the Labrador Thesis Utrecht University, 2000

5.  Hedhammar A, Wu FM, Krook L Schryver HF et al Overnutrition and skeletal disease, an experimental study in growing Great Dane dogs. Cornell Vet 64; suppli 1-160, 1974

6.  Lafond E, Breur GJ, Austin CC. Breed predilections for developmental orthopedic diseases in dogs Vet Surg. 27, 526-527, 1998

7.  Lavelle RB. The effects of overfeeding of a balanced complete commercial diet to a group of Great Danes in: Nutrition of the dog and cat (IH Burger & JPW Rivers, eds) Cambridge University Press, UK, 1989, pp. 303-315

8.  Nap RC, Mol JA, Hazewinkel HAW Age-related plasma concentrations of growth hormone (GH) and insulin-like growth factor I(IGF-I) in Great Dane pups fed different dietary levels of protein. Domest Anim Endocrinol. 10:237-47, 1993

9.  Schoenmakers I, Hazewinkel HAW, Voorhout G, Carlson CS, Richardson D. Effect of diets with different calcium and phosphorous contents on the skeletal development and blood chemistry of growing Great Danes Vet Rec 147; 652-660, 2000

10. Svenson L, Audell L, Hedhammar A. Prevalence and heritance of and selection for ED in Bernese mountain dogs in Sweden and benefit:cost analysis of a screening and control program JAVMA 210, 215-221, 1997

11. Ubbink GJ, Hazewinkel HAW, van den Broek J, Rothuizen J. Familial clustering and risk analysis for FCP and elbow joint incongruity in Bernese Mountain Dogs in The Netherlands AJVR 60, 1082-1087, 1999

12. Ubbink GJ, van den Broek J, Hazewinkel HAW, Wolvekamp WTC, Rothuizen J. Prediction of the genetic risk for fragmented coronoid process in Labrador retrievers. Vet Rec. 147, 149-152, 2000

13. Wong M, Carter DR Articular cartilage functional histomorphology and me chanobiology: a research perspective Bone 33, 1-13, 2003

14. Wolschrijn CF, Weijs WA. Development of the trabecular structure within the ulnar medial coronoid process of young dogs. Anat Rec A Discov Mol Cell Evol Biol.;278:514-519, 2004

15. Guthrie A, Pidduck HG. Heritability of elbow osteochondrosis within a closed population of dogs JSAP 32, 460-464, 1990

16. Padgett GA, Mostosky UV, Probst CW, Thomas MW, Krecke CF. The inheritance of osteochondritis dissecans and fcp of the elbow joint in Labrador Retrievers JAAHA 31,327-330, 1995

17. Patterson DF, Aguirre GA, Giger U, Green PL. Is this a genetic disease. J. Small Anim Pract 30, 127-139, 1989.

18. Corley WD, Carlson WB. Radiographic, genetic and pathologic aspects of elbow dysplasia JAVMA 147, 1651-1653, 1965

19. Hazewinkel HAW, Meij BP, Theyse LFH. Asynchronous growth of the radius and ulna in the dog in: Iams Company Proceedings 1998 Canine skeletal development & soundness, pp. 5-14.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

H.A.W. Hazewinkel, DVM, PhD, DECVS, DECVCN
The Netherlands


SAID=27