Osteochondrosis - genetic causes and early diagnosis

 Osteochondrosis: genetic causes and early diagnosis     By Celia M. Marr     Osteochondrosis (OC) is a common lesion in young horses affecting the growing cartilage of the articular/epiphyseal complex of predisposed joints at specific predilection sites. In the young Thoroughbred, it commonly affects the stifles, hocks and fetlocks. As this condition has such important impact on soundness across many horse breeds, it is commonly discussed in  Equine Veterinary Journal . Four recent articles covered causes of the disease, its genetic aspects, and a new and very practical approach to early diagnosis through ultrasound screening programs on stud farms.     << EVJ logo near here>>     OC is a disease of joint cartilage. Cartilage covers the ends of bones in joints, and healthy cartilage is central to unrestricted joint movement. With OC, abnormal cartilage can be thickened, collapsed, or progress to cartilage flaps or osteochondral fragments separated from the subchondral bone leading to osteochondrosis dissecans (OCD). OC and OCD can be regarded as a spectrum rather than two discrete conditions.  Certain joints are prone to OC and OCD, and there is some variation between breeds on which joints have the highest prevalence. In Australian Thoroughbreds, 10% of yearlings had stifle OC, 8% had fetlock OC, and 6% had hock OC. The prevalence data may seem very high, but Thoroughbred breeders may take some comfort in learning that similar, and indeed slightly higher prevalences, are reported in the warmblood breeds, Standardbreds, and Scandinavian and French trotters. Heavy horse breeds have the highest prevalences.  In an article discussing progress in OC/OCD research, Professor Rene Van Weeren concludes that the clinical relevance of OC is man made. In feral horses, where there is no human influence on mating pairings, OC does occur but at much lower prevalence than in horse breeds selected for sports or racing. Similarly, in pony breeds where factors other than speed and size are desirable characteristics, OC is also rare. These facts suggest that sports and racehorse breeders have inadvertently introduced a trait for OC along with other desired traits. There is a strong link between height and OC, suggesting that one of the desired traits with unintended consequences is height. This is of particular relevance in sports horses: the Dutch warmblood has become taller at a rate of approximately 1 mm per year over the past decades, which might not seem much but it is still an inch in 25 years. Van Weeren points out that if the two-hands tall Eohippus or Hyracotherium and the browsing forest-dweller with which equine evolution started some 65 millions of years ago had evolved at this speed, the average horse would now have stood a staggering 40 miles at the withers.  Drs. Naccache, Metzger and Distal, based at the Institute for Animal Breeding and Genetics in Hannover, Germany, have worked extensively on heritability and the genetic aspects of OC in horses. Their work has shown that there is not one single gene involved. In fact, genes located on not less than 20 of the 33 chromosomes of the horse are relevant to OC.  These researchers use whole genome scanning—otherwise known as genome-wide association studies, or GWAS. This approach has only been possible since the equine genome was mapped. GWAS look at the entire genetic map to detect differences between subjects with and without a particular trait or disease. Millions of genetic variants can be read at the same time to identify genetic variants that are associated with the disease of interest. Based on the number of genetic markers already found in warmblood OC, it is unlikely that a simple single-gene test will prove to be useful for screening young Thoroughbreds for OC.  Understanding which genetic variants are associated with a particular disease can give important clues on the biological processes that contribute to that condition. This, in turn, can reveal novel drug targets and improve therapy. Gene expression studies can also explain exactly how some undesirable traits, like OC, are closely linked to desirable traits. Equine genetic studies of this type are still relatively rare. Dr. Naccache’s group in Hannover are applying these cutting edge technologies to study OC in the hanoverian breed, where OC is highly heritable. But this research area is relatively unexplored in racing breeds, and more work is urgently needed for the Thoroughbred.  What we do know about genetics and OC in Thoroughbreds is that OC actually has lower heritability compared to warmbloods. Drs. John and Tom Russell of Victoria Equine Group in Australia recently reported some of their work, which involved collaboration with researchers Richard Reardon and Oswald Matika from the University of Edinburgh to look at this issue. Sales X-rays from almost 2,000 Thoroughbred yearlings were reviewed, and horses were classified as being OC-affected or not. Pedigree information was analyzed to granddam and grandsire level. An important outcome was that it showed that non-genetic factors such as nutrition also are very important in Thoroughbred OC. Heritability of OC is lower in Thoroughbreds than in other breeds, but among the various forms of OC seen in this group of yearlings, stifle OC and in particular OC lesions of the lateral trochlear ridge of the distal femur (LRTF) were more heritable than OC of the hock and fetlock.  LRTF lesions are one of the forms of OC most likely to adversely affect a horse’s racing career. On the other hand, these lesions can heal in foals up to about eight months of age with appropriate management. Therefore, there is considerable benefit in identifying these lesions early—ideally before joint distension is easily apparent on visual inspection. To meet this clinical need, a group of Canadian veterinarians led by Professor Sheila Laverty has developed an ultrasound technique for screening the stifle of young foals. Dr. Gabrielle Martel reported on work performed on 46 Thoroughbreds on a single farm. The foals were examined with an ultrasound unit similar to the equipment used for tendon scanning. X-rays—the current standard technique for diagnosing OC—were obtained for comparison.  Very young foals have thick cartilage that gradually remodels to bone as the foal grows. The interface between the cartilage and bone (i.e., the chondro-osseus interface) is highly indented in young foals and gradually becomes smoother and thinner with age. There is also change in the pattern of small blood vessels within the cartilage as the joint develops. Looking for changes in these three features can identify OC.  In early OC lesions, characteristic semi-circular indentations are easily distinguished with ultrasound. Ultrasound imaging effectively monitored healing, and subtle changes not obvious with radiography could be picked up with ultrasonography. Ultrasound is widely available and, with training, easy to perform. Repeated ultrasound exams are more practical than multiple X-rays. In this work, Dr. Martel has provided stud vets with very useful information that will allow them to more effectively identify and manage OC of the stifle in young Thoroughbreds.     Legends     Fig. 1. Each row of X-rays on the left and standard and magnified ultrasound images on the right are from the same young foal. In the top foal’s ultrasound images (b) distinct V-shape indentations and in the next row, small circular areas of cartilage retention in US image (d) are normal. In the bottom set (f) early osteochondrosis creates the semicircular wider indentation.     Fig. 2. The top row shows subclinical osteochondrosis lesions in a 67-day-old foal. The OC lesion is obvious in the lateromedial X-ray (arrow, a) but not on the oblique projection (b). Ultrasonography showed defects in two areas, visualized here in long axis (c) and transverse planes (d). The lower row shows a 118-day-old foal with a healing lesion. Changes are minimal on X-rays (arrows e & f), but the ultrasonographic examination revealed a multifocal semicircular defect (red circle, g & h). This illustrates that ultrasonography is a more effective tool for monitoring healing that radiography.

By Celia M. Marr

Osteochondrosis (OC) is a common lesion in young horses affecting the growing cartilage of the articular/epiphyseal complex of predisposed joints at specific predilection sites. In the young Thoroughbred, it commonly affects the stifles, hocks and fetlocks. As this condition has such important impact on soundness across many horse breeds, it is commonly discussed in Equine Veterinary Journal. Four recent articles covered causes of the disease, its genetic aspects, and a new and very practical approach to early diagnosis through ultrasound screening programs on stud farms.

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OC is a disease of joint cartilage. Cartilage covers the ends of bones in joints, and healthy cartilage is central to unrestricted joint movement. With OC, abnormal cartilage can be thickened, collapsed, or progress to cartilage flaps or osteochondral fragments separated from the subchondral bone leading to osteochondrosis dissecans (OCD). OC and OCD can be regarded as a spectrum rather than two discrete conditions.

Certain joints are prone to OC and OCD, and there is some variation between breeds on which joints have the highest prevalence. In Australian Thoroughbreds, 10% of yearlings had stifle OC, 8% had fetlock OC, and 6% had hock OC. The prevalence data may seem very high, but Thoroughbred breeders may take some comfort in learning that similar, and indeed slightly higher prevalences, are reported in the warmblood breeds, Standardbreds, and Scandinavian and French trotters. Heavy horse breeds have the highest prevalences.

In an article discussing progress in OC/OCD research, Professor Rene Van Weeren concludes that the clinical relevance of OC is man made.  In feral horses, where there is no human influence on mating pairings, OC does occur but at much lower prevalence than in horse breeds selected for sports or racing. Similarly, in pony breeds where factors other than speed and size are desirable characteristics, OC is also rare. These facts suggest that sports and racehorse breeders have inadvertently introduced a trait for OC along with other desired traits. There is a strong link between height and OC, suggesting that one of the desired traits with unintended consequences is height. This is of particular relevance in sports horses: the Dutch warmblood has become taller at a rate of approximately 1 mm per year over the past decades, which might not seem much but it is still an inch in 25 years. Van Weeren points out that if the two-hands tall Eohippus or Hyracotherium and the browsing forest-dweller with which equine evolution started some 65 millions of years ago had evolved at this speed, the average horse would now have stood a staggering 40 miles at the withers.

Drs. Naccache, Metzger and Distal, based at the Institute for Animal Breeding and Genetics in Hannover, Germany, have worked extensively on heritability and the genetic aspects of OC in horses. Their work has shown that there is not one single gene involved. In fact, genes located on not less than 20 of the 33 chromosomes of the horse are relevant to OC.

These researchers use whole genome scanning—otherwise known as genome-wide association studies, or GWAS. This approach has only been possible since the equine genome was mapped. GWAS look at the entire genetic map to detect differences between subjects with and without a particular trait or disease. Millions of genetic variants can be read at the same time to identify genetic variants that are associated with the disease of interest. Based on the number of genetic markers already found in warmblood OC, it is unlikely that a simple single-gene test will prove to be useful for screening young Thoroughbreds for OC.

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