N. I. Dolvik

Epiphyseal cartilage canal blood supply to the tarsus of foals and relationship to osteochondrosis.

REASON FOR PERFORMING STUDY Pathological changes in the blood supply to growth cartilage have been implicated in the pathogenesis of osteochondrosis (OC) in horses, but have not been reported using vascular perfusion techniques. OBJECTIVE To describe the developmental pattern of cartilage canal vessels in the distal tibial epiphysis and talar growth cartilage of foals. METHODS Nine foals bred from parents with OC were sacrificed between the ages of 0 and 7 weeks to undergo a barium perfusion procedure. The distal end of the tibia and the entire talus were cleared in methyl salicylate and perfused vessels studied in the intact bones. Slabs with a thickness of 4-5 mm from 3 predilection sites for OC were examined in the stereomicroscope and with light microscopy. RESULTS Cartilage canals were present for a limited period of growth. Perfused vessels initially entered canals from the perichondrium. Vessels in the proximal portion of canals retained their perichondrial arterial source throughout. With time, the ossification front advanced to incorporate the mid-portion of canals; and anastomoses formed between canal vessels and subchondral vessels. A shift occurred and vessels in the distal terminus of canals came to use subchondral vessels as their arterial source. Twelve histological lesions were found in 7 foals. All contained necrotic vessels surrounded by necrotic growth cartilage and 3 caused macroscopically visible delay in endochondral ossification. Lesions were located where vessels traversed the ossification front to enter the distal terminus of canals. CONCLUSION Cartilage canal vessels are particularly susceptible to failure at the point where they cross the ossification front, with consequences for the viability of those chondrocytes that depend on them. POTENTIAL RELEVANCE A better understanding of how lesions of OC arise may improve the ability to identify, monitor, prevent and treat this disorder. Involvement of cartilage canals in the pathogenesis of equine tarsal OC plausibly explains several clinical features of this disease.

Articular osteochondrosis: a comparison of naturally-occurring human and animal disease.

BACKGROUND Osteochondrosis (OC) is a common developmental orthopedic disease affecting both humans and animals. Despite increasing recognition of this disease among children and adolescents, its pathogenesis is incompletely understood because clinical signs are often not apparent until lesions have progressed to end-stage, and examination of cadaveric early lesions is not feasible. In contrast, both naturally-occurring and surgically-induced animal models of disease have been extensively studied, most notably in horses and swine, species in which OC is recognized to have profound health and economic implications. The potential for a translational model of human OC has not been recognized in the existing human literature. OBJECTIVE The purpose of this review is to highlight the similarities in signalment, predilection sites and clinical presentation of naturally-occurring OC in humans and animals and to propose a common pathogenesis for this condition across species. STUDY DESIGN Review. METHODS The published human and veterinary literature for the various manifestations of OC was reviewed. Peer-reviewed original scientific articles and species-specific review articles accessible in PubMed (US National Library of Medicine) were eligible for inclusion. RESULTS A broad range of similarities exists between OC affecting humans and animals, including predilection sites, clinical presentation, radiographic/MRI changes, and histological appearance of the end-stage lesion, suggesting a shared pathogenesis across species. CONCLUSION This proposed shared pathogenesis for OC between species implies that naturally-occurring and surgically-induced models of OC in animals may be useful in determining risk factors and for testing new diagnostic and therapeutic interventions that can be used in humans.

Early lesions of articular osteochondrosis in the distal femur of foals.

Failure of the cartilage canal blood supply to epiphyseal growth cartilage has been implicated in the pathogenesis of articular osteochondrosis in horses and other animal species. In a previous study of the developmental pattern of the blood supply in the tarsus of foals, early lesions of osteochondrosis were consistently found in regions where the cartilage canal vessels traversed the chondro-osseous junction. The developmental pattern of blood vessels has also been described in the distal femoral epiphysis; however, the group of foals examined in that study did not have lesions of osteochondrosis in this location. Therefore, the relationship between the occurrence of early lesions of osteochondrosis and the developmental pattern of the blood supply to epiphyseal growth cartilage in this site in foals has not been examined. Distal femora were collected from 30 fetuses and foals (up to 11 months old) submitted for postmortem examination. Sections from the lateral trochlear ridge and medial femoral condyle of both hind limbs were examined histologically. Sixteen cartilage lesions were found in 7 of the 30 fetuses and foals. All lesions contained evidence of cartilage canal necrosis and ischemic chondronecrosis. The lesions were located in regions where cartilage canal vessels traversed the chondro-osseous junction, as previously observed in the tarsus. The location and morphology of lesions indicated that a subclinical stage of ischemic chondronecrosis existed that preceded and predisposed to the development of osteochondrosis dissecans and subchondral bone cysts.

Transection of vessels in epiphyseal cartilage canals leads to osteochondrosis and osteochondrosis dissecans in the femoro-patellar joint of foals; a potential model of juvenile osteochondritis dissecans

OBJECTIVE To transect blood vessels within epiphyseal cartilage canals and observe whether this resulted in ischaemic chondronecrosis, an associated focal delay in enchondral ossification [osteochondrosis (OC)] and pathological cartilage fracture [osteochondrosis dissecans (OCD)] in the distal femur of foals, with potential translational value to the pathogenesis of juvenile osteochondritis dissecans (JOCD) in children. METHOD Ten Norwegian Fjord Pony foals were operated at the age of 13-15 days. Two vessels supplying the epiphyseal growth cartilage of the lateral trochlear ridge of the left distal femur were transected in each foal. Follow-up examination was carried out from 1 to 49 days post-operatively and included plain radiography, macroscopic and histological examination. RESULTS Transection of blood vessels within epiphyseal cartilage canals resulted in necrosis of vessels and chondrocytes, i.e., ischaemic chondronecrosis, in foals. Areas of ischaemic chondronecrosis were associated with a focal delay in enchondral ossification (OC) in foals examined 21 days or more after transection, and pathological cartilage fracture (OCD) in one foal examined 42 days after transection. CONCLUSION The ischaemic hypothesis for the pathogenesis of OC has been reproduced experimentally in foals. There are several similarities between OCD in animals and JOCD in children. It should be investigated whether JOCD also occurs due to a focal failure in the cartilage canal blood supply, followed by ischaemic chondronecrosis.

Micro-computed tomography of early lesions of osteochondrosis in the tarsus of foals

INTRODUCTION Osteochondrosis (OC) is an important developmental orthopedic disease of human and equine patients. The disease is defined as a focal disturbance in enchondral ossification. In horses, the disturbance can occur secondary to failure of the blood supply to growth cartilage. Diagnosis of the early, subclinical stages that can clarify the etiology is currently confined to cross-sectional histological examination. The potential for micro-computed tomography (micro-CT) with angiography to detect early lesions of OC has not yet been investigated. MATERIALS AND METHODS Nine Standardbred foals bred from parents with OC of the tarso-crural joint were sacrificed at weekly intervals from birth to 7 weeks of age. Permanent barium angiograms were created within one hind limb post mortem, and samples collected from two predilection sites for OC within the tarso-crural joint of the perfused hind limb. The resulting 18 sample blocks were scanned with a custom-built micro-CT equipment set-up, and analyzed as 2D slices and 3D volume rendered models before sectioning for conventional histological examination. RESULTS Histological examination identified eight early lesions in seven locations within six joints from the nine foals. Micro-CT with angiography was able to detect seven lesions in the same sites as histological examination. Lesions consisted of non-perfused foci within growth cartilage. No perfused vessels exited from subchondral bone deep to any lesion. Six of the seven lesions were associated with focal defects in the subchondral bone plate. Evidence of ongoing ossification was seen in three out of the seven lesions and included one separate center of ossification. CONCLUSION Micro-CT was a useful technique for examination of early lesions of OC. The results of micro-CT were compatible with failure of cartilage canal vessels at the point where they cross the ossification front. Resultant areas of ischemic chondronecrosis were associated with focal delay in enchondral ossification as visualized in 3D volume rendered models. Micro-CT combined with histology clarified the role of different forms of ossification in the secondary repair responses to lesions.

Epiphyseal cartilage canal blood supply to the distal femur of foals.

REASONS FOR PERFORMING STUDY The developmental pattern of the cartilage canal blood supply to epiphyseal growth cartilage has been linked to osteochondrosis (OC) in the tarsus of foals. This pattern has not yet been described in the distal femur, another site frequently affected by OC. OBJECTIVE To describe the developmental pattern of the blood supply to the distal femoral epiphyseal growth cartilage in 8 Standardbred foals age 0-7 weeks. METHODS One foal was sacrificed weekly from birth to age 7 weeks (n=8) to undergo a barium perfusion procedure to demonstrate vessels within cartilage canals of one hindlimb. The distal end of the femur was cleared in methyl salicylate and perfused vessels were studied in the intact bones. Each distal femur was then sawed into 5 mm thick slabs in the transverse plane, and the slabs decalcified and radiographed. Finally, the lateral trochlear ridge was separated from each slab and examined histologically. RESULTS The cartilage canal blood supply regressed with increasing age, but several regions remained vascularised in the oldest foal at age 7 weeks. Vessels arose from perichondrial and subchondral arterial sources, and coursed perpendicular or parallel to the ossification front. The midsection of parallel vessels became incorporated into the ossification front during growth. Anastomoses formed and vessels within the distal portion of canals with an original perichondrial source shifted to use subchondral vessels as their arterial source. Both parallel and perpendicular vessels therefore traversed the ossification front to enter cartilage canals. No histological lesions were observed in sections from any of the foals. CONCLUSION The same anatomical feature (traversing the ossification front to enter cartilage canals) reported to render vessels vulnerable to failure in the tarsus was also present in the distal femur of foals. POTENTIAL RELEVANCE OC may occur by the same pathogenetic mechanism in the distal femur as in the tarsus of foals.

Osteochondrosis and osteochondral fragments in Standardbred trotters: Prevalence and relationships

REASONS FOR PERFORMING STUDY Developmental orthopaedic diseases (DOD) such as osteochondrosis (OC)/osteochondrosis dissecans (OCD), palmar/plantar osteochondral fragments (POF), ununited palmar/plantar eminences (UPE) and dorsoproximal first phalanx fragments are well recognised in the horse. Aetiopathogeneses are controversial and molecular genetic screening of DNA has recently been employed for their elucidation. Precise phenotypic definition and knowledge of breed-specific prevalence and interrelations are essential for the interpretation of following genomic studies in Standardbred trotters. OBJECTIVES To assess the prevalence, trend of development and interrelation of DOD in tarsocrural, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints in Standardbred trotters. METHODS The tarsocrural and MCP/MTP joints of 464 Norwegian Standardbred yearlings were radiographed and the prevalence and interrelation of osteochondral lesions calculated. RESULTS Osteochondral lesions were diagnosed in 50.7% of the horses. The prevalence of tarsocrural OC/OCD at the distal intermediate ridge of the tibia (DIT) and the lateral trochlear ridge of the talus (LTT) was 19.3%. The prevalence of OC/OCD in MCP joints was 3.6%, whereas those of POF and UPE in MCP/MTP joints were 23.1 and 3.9%, respectively. Interrelation was evident for 1) most equivalent lesions in joint homologues, 2) OCD DIT and OCD LTT and 3) POF and UPE. Lesions in hock and fetlock joints were generally not significantly associated. CONCLUSIONS The prevalence of tarsocrural OC/OCD in Norwegian Standardbreds is apparently increasing, whereas that of other articular DOD appears stable. Association analyses verify bilateralism for most equivalent lesions and suggest aetiological resemblance also between other lesions. The absence of a significant association between tarsocrural OCD and POF implies that the lesions must be considered statistically different disorders. POTENTIAL RELEVANCE The prevalence results emphasise that DOD should be considered in Standardbred breeding regimens (e.g. by sire selection subsequent to progeny testing). Also, improved phenotypic definitions will help elucidate the true causal genes in following genomic studies.

Epiphyseal cartilage canal blood supply to the metatarsophalangeal joint of foals

REASONS FOR PERFORMING STUDY It is presently unknown whether cartilage ischaemia plays any part in the pathogenesis of osteochondral fragmentation within the equine metatarsophalangeal joint, as no detailed studies on microcirculation in the area have been reported. OBJECTIVE To describe the developmental pattern of the blood supply to the epiphyseal growth cartilage in the metatarsophalangeal joint of foals. METHODS Eight Standardbred foals were sacrificed between birth and age 7 weeks to undergo a barium perfusion procedure to demonstrate vessels within growth cartilage canals of one hindlimb. The metatarso-phalangeal joint was cleared in methyl salicylate and perfused vessels studied in the intact bones. The bones were sawed into 5 mm thick slabs, decalcified and radiographed. Selected slabs were cleared in methyl salicylate for a second time and examined at low magnification. The dorsal half of the sagittal ridge of the distal third metatarsal bone and the plantar half of the proximal phalanx were examined histologically. RESULTS Regions of the epiphysis with thick cartilage contained a greater number of perfused vessels than regions with thin cartilage. The cartilage canal vessels were oriented either parallel or perpendicular to the underlying ossification front. Cartilage canal vessels were incorporated into the ossification front during growth and became reliant on a subchondral arterial source. Macroscopically visible lesions were not detected in the current group of foals. On histological examination, pathological changes consisting of an area of chondronecrosis surrounded by fibrovascular granulation tissue were found in sections from the lateral proximo-plantar eminence of the proximal phalanx in the 7-week-old foal. CONCLUSION The same anatomical feature (traversing the ossification front to enter cartilage canals) reported to render vessels vulnerable to failure in the tarsus was also present in the metatarso-phalangeal joint of foals. POTENTIAL RELEVANCE Osteochondrosis may occur by the same pathogenetic mechanism in the metatarso-phalangeal joint as in the tarsus of foals.

Heritability estimates of tarsocrural osteochondrosis and palmar/plantar first phalanx osteochondral fragments in Standardbred trotters

REASONS FOR PERFORMING STUDY The pathogenesis of osteochondrosis (OC) and palmar/plantar first phalanx osteochondral fragments (POFs) is multifactorial, but specific knowledge of heritability is limited. OBJECTIVES To improve the precision of heritability estimates and to estimate the genetic correlation between tarsocrural OC and POFs in Standardbred trotters. Further aims were to examine whether the prevalence of OC/POFs was different in the American and French lineages that have contributed to the Norwegian population, and if the prevalence was affected by heterozygosity. STUDY DESIGN Retrospective cohort study. METHODS Categorical data on tarsocrural OC and POFs from 2 radiographic studies performed in 1989 and 2007/2008 (n = 1217) were analysed with sire threshold models that included 230 sires. RESULTS Heritability of OC at the distal intermediate ridge of the tibia and/or the lateral trochlear ridge of the talus was estimated at 0.29 ± 0.15. For OC at the distal intermediate ridge of the tibia only, the estimate was 0.40 ± 0.17. Heritability of POFs in all 4 limbs was estimated at 0.23 ± 0.13; for metatarsophalangeal POFs this was 0.26 ± 0.13 and for medial metatarsophalangeal POFs 0.32 ± 0.14. Estimates of genetic correlation between OC and POFs ranged from 0.68 ± 0.27 to 0.73 ± 0.28 but were not significantly different from a zero-genetic correlation. Effects of lineages or heterozygosity were not observed. CONCLUSIONS AND POTENTIAL RELEVANCE This study confirmed a moderate to high heritability of tarsocrural OC and POF, providing further evidence of the heritable nature of these diseases. Examination of specific lesions yielded the highest heritability; therefore, breeding programmes and future genome-analysis studies should focus on predilection sites rather than the entire disease complex.

Ossification defects detected in CT scans represent early osteochondrosis in the distal femur of piglets

The purpose of the current study was to validate the use of CT for selection against osteochondrosis in pigs by calculating positive predictive value and comparing it to the positive predictive value of macroscopic evaluation, using histological examination as the reference standard. Eighteen male, hereditarily osteochondrosis‐predisposed piglets underwent terminal examination at biweekly intervals from the ages of 82–180 days old, including CT scanning, macroscopic, and histological evaluation of the left distal femur. Areas of ischemic chondronecrosis (osteochondrosis) were confirmed in histological sections from 44/56 macroscopically suspected lesions, resulting in a positive predictive value of 79% (95% CI: 67–84%). Suspected lesions, that is; focal, radiolucent defects in the ossification front in CT scans corresponded to areas of ischemic chondronecrosis in 36/36 histologically examined lesions, resulting in a positive predictive value of 100% (95% CI: 90–100%). CT was superior to macroscopic evaluation for diagnosis of early stages of osteochondrosis in the distal femur of piglets. The current histologically validated observations can potentially be extrapolated to diagnostic monitoring of juvenile osteochondritis dissecans in children, or to animal models of human juvenile articular cartilage injury and repair.