PART VI
Developmental Orthopedic
Disease and Lameness
54 
Chapter mineralized in the zone of provisional calcification. The
Pathogenesis of
Osteochondrosis
Janet Douglas
OSTEOCHONDROSIS: DEFINITIONS
AND TERMINOLOGY
Equine osteochondrosis (OC) is characterized by focal
failures of endochondral ossification that typically occur
in well-defined predilection sites. Lesions that result from
external trauma or infection are not generally regarded
References as OC.1,2 The thickened, retained growth cartilage that
on page
1295 characterizes typical lesions (Figure 54-1) in the articular-
epiphyseal cartilage complex (AECC) may be complicated
by development of fissures that extend from the deepest
layers of the lesion to the articular surface. Cartilaginous
or osteochondral fragments may then detach from the
parent bone, forming intraarticular fragments.3 Once
lesions extend to the articular surface, thereby causing
inflammation of the joint, the condition may be referred
to as osteochondritis.4,5 The term osteochondritis dissecans
(OCD) is usually reserved for lesions in which a dissecting
flap of tissue is present (Figure 54-2).3 Although it has been
proposed that the term dyschondroplasia should be used in
place of OC,3,6 the term OC remains in widespread use and
is used in this chapter to refer to the primary lesion. Dys-
chondroplasia is used only when referring to work by authors
who prefer this term. A condition similar to equine OC
occurs in a number of other animal species, as well as in
people.1
ENDOCHONDRAL OSSIFICATION
Endochondral ossification is the process by which growing
cartilage is systematically replaced by bone to form the
growing skeleton.7 This process occurs at three main sites:
the physis, the epiphysis, and the cuboidal bones of the
carpus and tarsus. Chondrocytes in the physis can be
divided into a series of layers or zones (Figure 54-3). The
zone farthest from the metaphysis is the resting or reserve
zone. Adjacent to this is the proliferative zone, in which
chondrocytes divide. These cells progress to the hyper­
trophic zone, in which they enlarge and form ordered
columns. During this stage the chondrocytes become
surrounded by extracellular matrix that gradually becomes
chondrocyte columns are then invaded by metaphyseal
blood vessels, and bone forms on the residual columns of
calcified cartilage. This mixture of calcified cartilage and
immature bone (primary spongiosa) is then gradually
remodeled to produce the mature bone of the metaphysis.7
Endochondral ossification, which continues throughout
the period of growth, also occurs in the AECC at the ends
of long bones (Figure 54-4).8 The chondrocytes of the
AECC that are closest to the articular surface produce
articular cartilage, whereas those cells closer to the epiphy-
sis participate in endochondral ossification in the same
manner as occurs in the physis. It is generally accepted that
the growth cartilages of both the physis and the AECC are
susceptible to OC.1,3,8-11
CHARACTERISTICS OF OSTEOCHONDROSIS
Equine OC characteristically manifests as one or two lesions
that occur in known predilection sites. In this so-called
“typical pattern” of the disease, lesions are often bilaterally
symmetrical, although only one lesion may cause clinical
signs.12 The femoropatellar (lateral and medial femoral
trochlear ridges, lateral facet of patella), tarsocrural (cranial
aspect of the intermediate ridge and medial malleolus of
the distal aspect of the tibia, lateral and medial trochlear
ridges of the talus), scapulohumeral (glenoid fossa and
humeral head), and metacarpophalangeal and metatarso-
phalangeal joints (midsagittal ridge and condyles of the
third metacarpal or metatarsal bone) are affected most com-
monly. OC of the elbow, hip, and cervical vertebral joints
has also been described,12,13 but lesions in these sites are less
common and the etiology is more controversial.12 This
typical pattern of OC contrasts with that of the atypical
pattern in which animals show numerous articular (and
sometimes physeal) lesions.12,14 Predilection and nonpredi-
lection sites may be affected in these horses, and bilaterally
symmetrical lesions are absent or infrequent. A third pattern
of lesion distribution, the mixed pattern, describes horses
in which both typical and atypical lesions are present.14
OC may manifest very early in life. For example, lesions
of the cranial aspect of the intermediate ridge of the tibia
have been identified in foals that are less than 1 month
old.15-17 Lesions of the lateral trochlear ridge of the femur
may appear later (3 to 4 months of age),17 but lesions at
this site, on the medial femoral condyle, and in the tarso-
crural and fetlock joints all develop before approximately
7 or 8 months of age.18,19 The studies from which these
conclusions were drawn were conducted in a range of
breeds. In contrast, recent radiological data suggest that the
617
618 PART VI  Developmental Orthopedic Disease and Lameness
Fig. 54-1  •  Section through the articular-epiphyseal cartilage complex
and epiphysis showing thickened retained cartilage (arrows). (Courtesy
Gustavo Hernández-Vidal, Faculty of Veterinary Medicine, Universidad
Autónoma de Nuevo León, Monterrey, Mexico.)
Fig. 54-2  •  Dissecting flap of articular cartilage (osteochondritis dissecans
lesion) on the lateral trochlear ridge of the femur. (Courtesy Gustavo
Hernández-Vidal, Faculty of Veterinary Medicine, Universidad Autónoma
de Nuevo León, Monterrey, Mexico.)
Resting
zone
Early
proliferative
zone
Late
proliferative
zone
Hypertrophic
zone
Calcified
zone
Fig. 54-3  •  Sagittal section of the epiphysis, metaphysis, and diaphysis of
growing bone, with sequential histological sections showing the different
zones of the physis (metaphyseal growth cartilage). 1, Articular-epiphyseal
growth cartilage complex; 2, secondary ossification center in the epiphysis;
3, metaphyseal growth cartilage; 4, primary ossification center in the
diaphysis. Toluidine blue stain. (Courtesy Gustavo Hernández-Vidal, Faculty
of Veterinary Medicine, Universidad Autónoma de Nuevo León, Monterrey,
Mexico.)
prevalence of OC may increase substantially after approxi-
mately 1 year of age in South German Coldbloods.20 Further
work is necessary to establish whether there are breed dif-
ferences in the timing of lesion development.
It is important to realize that most osteochondral
lesions identified radiologically in young horses heal
without intervention17,21-23 and that lesions that lead to
clinical signs represent only a small fraction of the total.
Thus many of the lesions identified in postmortem studies
would never have become clinically relevant and may not
even be evident radiologically. The age at which lesions
are capable of repair appears to depend on the joint
involved. A longitudinal study involving Dutch Warm-
bloods determined that OC lesions of the hock (the cranial
aspect of the intermediate ridge of the tibia and the lateral
trochlear ridge of the talus) that were still present at 5
months of age never regressed.17 Five months was thus
designated as the “age of no return” for tarsocrural lesions.
In contrast, lesions of the lateral trochlear ridge of the
femur did not become permanent until the animal was 8
months of age.17
 Chapter 54  Pathogenesis of Osteochondrosis 619
Superficial
zone
Resting
zone
Early
proliferative
zone
Late
proliferative
zone
Hypertrophic
zone
Calcified
zone
Fig. 54-4  •  Sagittal section of the epiphysis with sequential histological
sections showing the different zones of the articular-epiphyseal cartilage
complex. Toluidine blue stain. (Courtesy Gustavo Hernández-Vidal, Faculty
of Veterinary Medicine, Universidad Autónoma de Nuevo León, Monterrey,
Mexico.)
The features of equine OC lesions were reported as early
as 1947.9 Since then the gross and histological characteris-
tics of the condition have been described and defined by
numerous authors. Early descriptions characterized OC as
a lack of chondrocyte differentiation that prevented provi-
sional calcification of the matrix and invasion of the car-
tilage by blood vessels.3 Necrosis was described as a
secondary change.3 A more recent histological study that
examined AECC samples from the lateral trochlear ridge of
the femur of horses ranging in age from 270 days’ gestation
to 4 years defined OC (“dyschondroplasia”) as the presence
of cartilage cores (i.e., cartilage extending into subchondral
bone).24 This study identified two types of lesion that could
be differentiated on the basis of type VI collagen immuno-
reactivity. However, both types showed evidence of chon-
drocyte clusters and chondronecrosis. Lesions of one type
(group A) showed disruption of the normal sequential tran-
sition of chondrocytes through the stages of proliferation
and maturation and were characterized by accumulation
of large numbers of small, rounded chondrocytes, appar-
ently arrested at the prehypertrophic stage. In contrast,
Fig. 54-5  •  Chondrocyte clusters (arrows) surrounding an area of necrotic
cartilage. Toluidine blue stain. (Courtesy Frances Henson, Department 
of Veterinary Medicine, University of Cambridge, Cambridge, United
Kingdom.)
group B lesions showed alteration in the staining pattern
of mineralized cartilage and adjacent subchondral bone
and complete absence of invading capillaries into newly
formed bone.24,25 Differentiation of lesions into subcatego-
ries was not reported in a recent histological study in
which necrosis of growth cartilage was described as a
common feature of OC lesions.15 This study was carried out
using material from the distal tibiae of foals that were all
5 months old or younger (the age range during which the
disease is initiated at this site).17 The results suggested that
chondrocyte necrosis precedes matrix change (identified
histologically as relative eosinophilia and pallor in hema-
toxylin-eosin–stained sections and as pallor in toluidine
blue–stained sections), delayed ossification, and fissure for-
mation. Moreover, these authors considered chondrocyte
clusters to be a sign of attempted repair rather than a
primary change.15
It is obvious from this short summary that histological
definitions and descriptions of OC vary, making accurate
identification of lesions difficult.24 Even chondrocyte clus-
ters (Figure 54-5), considered by many to be one of the
most consistent findings in OC lesions,24,26 are not pathog-
nomonic for the disease,15,24 and, unless used to define
the condition, necrosis is not a universal finding.25,27 It
is thus not surprising that the relevance to OC of some of
the lesions studied has been questioned.28 The matter is
complicated further by the limited repertoire of responses
that bone and cartilage can mount to injury and develop-
mental abnormalities12 and by the fact that many lesions
are not identified until they have reached the chronic
stage. The features of such chronic lesions may represent
the results of secondary change and attempted repair,
rather than primary osteochondrotic change. The results
of studies based on such lesions may thus be misleading.
This situation has resulted in a wide-ranging, heteroge-
neous, and somewhat confusing body of literature, in
which equine OC has been ascribed to genetic, dietary,
endocrine, biomechanical, traumatic, ischemic, and toxic
causes.12,18,26,29-33
620 PART VI  Developmental Orthopedic Disease and Lameness
RELATIONSHIP AMONG PHYSEAL DYSPLASIA
(PHYSITIS), SUBCHONDRAL BONE CYSTS,
AND OSTEOCHONDROSIS
The relationship between OC and physeal dysplasia (phy-
sitis or epiphysitis) is poorly defined. Retained cartilage has
long been regarded as a possible cause of physeal dyspla-
sia,16,34 and OC lesions of the physis have been described in
clinically affected horses (thickened and irregular metaphy-
seal growth cartilage)5,10 and in foals with experimentally
induced dyschondroplasia (retained cartilage cores).26,35 If
OC truly is a generalized or multifocal disturbance of endo-
chondral ossification, it would seem logical that metaphy-
seal growth cartilage has the potential for involvement.
However, some have questioned whether articular and
physeal lesions have the same cause and have proposed that
physitis be regarded as a manifestation of developmental
orthopedic disease but not of OC.12 Moreover, the results
of a recent study suggest that many enlargements of the
distal aspect of the third metacarpal and metatarsal bones,
including those with evidence of increased metaphyseal
cartilage thickness, represent physiological remodeling
rather than a pathological process.36 The role of OC in the
pathogenesis of equine physeal dysplasia thus remains
unclear. However, it should be noted that a similar patho-
genic mechanism (failure of blood supply to growth carti-
lage) has been proposed for both articular OC and physeal
lesions in pigs.1 Physitis is covered in more detail in Chapter
57 and is not discussed further here.
The relationship among OC, subchondral bone cysts,
and osseous cystlike lesions is also controversial. In con-
trast to OCD lesions, which are most commonly found on
the nonloaded margins of high-motion joints, bone cysts
typically occur in the central, loaded areas of joints.2 Origi-
nally interpreted as a manifestation of retained cartilage of
the AECC,10,37-39 many cysts are now thought to be trau-
matic in origin.40,41 This proposed cause was demonstrated
experimentally by the successful induction of cysts in the
medial femoral condyle (a predilection site) after creation
of a linear slit in the articular cartilage followed by normal
weight bearing.42 OC may thus be only one of several pos-
sible causative mechanisms,12,40,43 and cysts may result
from a number of nonspecific articular injuries sustained
at a load-bearing site.12
PROPOSED CAUSATIVE FACTORS
Numerous studies aimed at determining the cause and
pathogenesis of equine OC have been performed, and
many of the factors investigated have been shown to influ-
ence the incidence of osteochondral lesions. However,
because OC cannot yet be diagnosed on anything other
than morphological grounds, it is unclear whether the
lesions induced by some of these potential causative factors
are the same as those that occur under “natural” condi-
tions. A pertinent example is low copper intake, which has
been shown to induce osteochondral lesions44 but which
is not believed to be a causative factor in most horses with
naturally occurring OC.1,45
It is generally accepted that equine OC has a multifacto-
rial cause.1,25,45 This renders more difficult the task of unrav-
eling the pathogenesis of the disease. Further complications
are introduced by the presence of interrelationships among
a number of proposed causative factors. For example, a
horse’s growth rate may be affected by its genetic back-
ground,46 its plane of nutrition,47 and possibly also by its
hormonal response to carbohydrate intake,48 all factors that
have been implicated in the pathogenesis of OC.
Another topic that requires clarification is the balance
between generalized or systemic and local factors. OC has
historically been described as a generalized failure of endo-
chondral ossification.16 However, the propensity for lesions
to occur in a small number of bilaterally symmetrical pre-
dilection sites argues strongly that local factors are impor-
tant in the cause. It remains to be determined whether
lesions can be induced solely by these local factors or
whether the presence of an underlying generalized disorder
(e.g., biomechanically or biochemically inferior tissue) is a
prerequisite for lesion development. The following discus-
sion summarizes major findings relating to the pathogen-
esis of equine OC.
Involvement of Cartilage Canals
There has been much interest recently in the role of carti-
lage canals in the pathogenesis of equine OC. Cartilage
canals are channels that invade the epiphyseal growth car-
tilage from the surrounding perichondrial plexus.49 The
arterioles, venules, and capillaries that they contain assist
in the nutrition of epiphyseal cartilage, much of which is
too far from synovial fluid to obtain nutrients by diffu-
sion.1 Under normal circumstances the cartilage canals
become obliterated in a regionally staggered sequence29,49
as endochondral ossification (and therefore growth) ceases.
Studies performed to date have found no evidence of car-
tilage canals in foals after approximately 6 or 7 months of
age.18,27,50 There is an apparent anatomical association
between prolonged dependence of cartilage on a vascular
supply and predisposition to OC.29
A number of investigations have highlighted an
association between the presence of cartilage canals and
development of OC. However, the proposed pathogenic
mechanism differs among studies. A report published in
1995 that involved examination of tissue from 35 horses
younger than 18 months of age found that cartilage canals
containing patent blood vessels were present in all samples
taken from OC predilection and nonpredilection sites in
foals younger than 3 weeks of age.18 Overall, 34% of the
horses had lesions of OC in the medial femoral condyle,
lateral femoral trochlear ridge, and/or distal aspect of
the tibia, and the prevalence rose to 56% in horses 3
weeks to 5 months of age. All the lesions seen in this age
group (3 weeks to 5 months) were associated with necrotic
cartilage canal blood vessels. Lesions found in horses
7 months of age and older had extensive involvement
of subchondral bone and bone marrow and were con­
sidered to be chronic. The authors concluded that OC
lesions develop before 7 months of age and that ischemic
necrosis of cartilage is involved in the pathogenesis of the
condition.18
This conclusion is supported by the results of more
recent work conducted using tissue from the distal tibiae
and tarsi of foals 5 months of age or younger.15,29,51 From
the results of a histopathological study, it was concluded
that early OC lesions manifest as areas of cartilage canal
and chondrocyte necrosis within the proliferative zone.15
 Chapter 54  Pathogenesis of Osteochondrosis 621
1 mm
Fig. 54-6  •  Histological section from the intermediate ridge of the tibia of
a 3-week-old foal showing an area of chondrocyte necrosis within the
proliferative zone (stippled outline) and a band of chondronecrosis within
the ossification front (between arrows). Both are associated with necrotic
cartilage canals (arrowheads). Toluidine blue stain. (Courtesy Osteochon-
drosis Research Group at the Equine Clinic, Norwegian School of Veterinary
Science, Oslo, Norway.)
As the ossification front advances, these lesions become
incorporated in the chondro-osseous junction where the
necrotic chondrocytes and altered matrix are believed to
represent conditions unfavorable for vascular invasion and
replacement by bone (Figure 54-6). Vascular perfusion
techniques were used to show that as foals grow the mid-
portion of each cartilage canal becomes incorporated into
the ossification front.29 Anastomoses then form between
canal vessels and subchondral vessels at this point.29 As a
result, tissue that is nourished by the vessels in the end of
the cartilage canal farthest from the perichondrium comes
to be nourished by subchondral vessels. The histological
lesions identified were consistently characterized by the
presence of necrotic growth cartilage in association with
necrotic cartilage canal vessels located at the point where
the vessels cross the ossification front, suggesting that the
vessels are prone to failure at this point.29 These results are
supported by the results of micro–computed tomography
analysis.51
An earlier study proposed a different mechanism for
involvement of cartilage canals in the pathogenesis of OC.
In this investigation, which involved horses that were in
some cases considerably older than those in the previous
study (≤15 months), nonnecrotic dyschondroplastic lesions
were associated with cartilage canals containing patent
vessels.27 This finding led the investigators to propose that
in some circumstances the presence of cartilage canals may
be associated with failure of chondrocytes to hypertrophy
and that this may be the initiating lesion. It was suggested
that blood vessels within cartilage canals may expose local
growth cartilage to any imbalance of systemic hormones
(such as that induced by a high-energy diet) and that
chronicity of lesions accounted for the difference between
these findings27 and those of studies in which necrosis is a
dominant feature. It should be noted that proximity of
osteochondral lesions to the remnants of cartilage canals
has been reported in many studies, but is not a universal
finding.52
Body Size and Growth Rate
The widespread anecdotal belief that OC is more prevalent
in large horses and those with a rapid growth rate gained
support from the results of a Swedish survey involving 77
Standardbred (STB) foals.53 This study reported a positive
relationship between radiologically evident OC of the tar-
socrural joint and body weight at birth, body weight during
the growth period, average daily weight gain, and skeletal
frame size. Seven of the eight foals that developed tarso-
crural OC were sired by the same stallion, but the relation-
ship among OC, body measurements, and growth rate was
still present when affected and unaffected foals by this sire
were considered in isolation.
In postmortem studies, positive associations were
reported between various measures of body size and
number and severity of OC or OC-like lesions in the limbs
and cervical vertebrae of 12-month-old animals of various
breeds47 and between recent average daily weight gain
and tarsocrural osteochondral lesions in 5-month-old
Thoroughbred (TB) foals.54 However, this latter study found
no significant association between body weight and the
frequency or severity of lesions, a finding that was echoed
in a recent study involving Hanoverian foals.55
Further evidence for a relationship among OC, body
size, and growth rate comes from a study performed in
Warmbloods.56 Weight and height were measured from
birth to 5 or 11 months of age in 43 foals with a presumed
genetic predisposition to OC of the femoropatellar or tar-
socrural joints. The foals’ stifle and hock joints were evalu-
ated radiologically, macroscopically, and histologically.
Development of femoropatellar OC was associated with a
higher overall rate of weight gain and greater final body
weight and height. Moreover, the period during which
weight gain of the OC-positive foals was significantly
higher than that of the OC-negative foals coincided with
the period during which femoropatellar joint lesions
become visible radiologically.17 In contrast to the previ-
ously described findings in STBs,53 no relationship existed
between tarsocrural OC and body size or growth rate in
this population of Dutch Warmbloods.56 A similar lack of
correlation between surgical OC lesions and body weight
has been reported in TBs.57
Nutrition
A number of dietary factors have been implicated in the
pathogenesis of OC. These include digestible energy, phos-
phorus, and copper.
Digestible Energy and Protein
The results of a French study have suggested that a high
plane of nutrition does not in itself predispose to develop-
ment of OC, as long as the ration is balanced.47 However,
a high nutrient intake was implicated in the pathogenesis
of OC for many years10 and the topic has been explored in
a number of studies. One landmark trial investigated the
effects on skeletal development of feeding 129% of National
Research Council (NRC, 1989)58 recommendations for
digestible energy or 126% of NRC recommendations for
crude protein to foals approximately 5 months of age.26 A
control group received 100% of NRC recommendations for
energy and protein. After 12 to 16 weeks on the experi-
mental diets, all foals were euthanized, growth plates and
the growth cartilage of the AECC were examined, and a
622 PART VI  Developmental Orthopedic Disease and Lameness
definitive diagnosis of dyschondroplasia was made only
when a retained core of cartilage was identified histologi-
cally. Dyschondroplasia occurred in two of 12 control foals
(17%), four of six foals on the high-protein diet (67%), and
all 12 foals on the high-energy diet. The lesions in the foals
in the high-protein group were minor and were mainly
single lesions of the growth plates, with no AECC involve-
ment. No significant difference in incidence occurred
between the control and high-protein groups. In contrast,
many of the foals in the high-energy group had lesions of
the AECC and the growth plates, and the difference in
incidence between the control and high-energy groups was
significant.
The effects of overfeeding on endochondral ossification
within the growth plate have been described. Twelve TB
weanlings aged 6 to 8 months were randomly assigned
to receive diets containing 70%, 100%, or 130% of the
National Research Council recommendations (1978)59 for
digestible energy and protein.60 All diets contained 100%
of the recommended levels of calcium and phosphorus.
Biopsies of the distal radial physis obtained after 8 months
showed that physeal thickness was directly proportional to
digestible energy level. Moreover, the physes of the overfed
horses showed many features similar to those of OC: the
reserve and hypertrophic zones were enlarged, the hyper-
trophic cartilage had lost its normal columnar organization,
and metaphyseal capillaries appeared unable to penetrate
this abnormal hypertrophic cartilage. It was concluded that
the lesions associated with overfeeding were similar to those
caused by hypothyroidism and that the link between
dietary excess and OC is mediated by endocrine factors.60
Subsequent work showed that ingestion of a high-
energy meal is associated with accelerated insulin secre-
tion, decreased thyroxine (T4) secretion, and accelerated
conversion of T4 to triiodothyronine (T3).61 Insulin, T3, and
T4 play a role in controlling the terminal differentiation of
chondrocytes,62,63 and it is possible that the transient post-
prandial hypothyroxemia induced by diets high in energy
could adversely affect osteochondral development. More-
over, studies conducted on equine tissue suggest that
insulin may promote the survival or depress the differentia-
tion of chondrocytes in growth cartilage, potentially reduc-
ing the rate at which cells enter the terminal phases of
hypertrophy and leading to accumulation of prehypertro-
phic chondrocytes.64
The possibility of a relationship between abnormal
insulin levels and osteochondral lesions is supported by the
finding that postprandial plasma glucose and insulin levels
are significantly higher in young horses with OC than in
unaffected animals,57,65 an association that may be medi-
ated, at least in part, by the glycemic index of the feed.57
An association between feeds with a high glycemic index
and increased plasma levels of insulin-like growth factor I
(IGF-I) has been observed during periods of rapid growth.66
IGF-I, which is structurally similar to insulin, is primarily
involved in the control of growth and differentiation,67
including regulation of chondrocyte growth and endo-
chondral ossification.64,68 However, recent data show that
there is cross-talk between the insulin and IGF-I pathways,
and that IGF-I participates in metabolic activities such as
promotion of glucose uptake.67 The suggestion that a high
glycemic index feeding regimen and osteochondrotic risk
may be linked via increased IGF-I levels is contradicted by
a study in which OC-positive foals were found to have
significantly lower IGF-I activity than those without the
disease.69 The significance of the IGF-I pathway in the
pathogenesis of OC thus remains unclear.
Calcium and Phosphorus
The effects of overfeeding phosphorus (388% of NRC
[1989] recommendations), calcium (342%), and both
calcium and digestible energy (342% and 129%, respec-
tively) for 16 to 18 weeks was assessed in foals aged 2 1 2 to
6 1 2 months at the start of the study.35 The diets containing
excessive phosphorus and calcium provided 100% of NRC
recommendations for digestible energy. Histologically con-
firmed dyschondroplastic lesions were found in numerous
joints and growth plates in two control foals (17%), five
foals fed excess phosphorus (83%), two foals fed excess
calcium (33%), and six foals fed excess digestible energy
and calcium (100%). The lesions were more numerous and
severe in the foals fed high-phosphorus or high–digestible
energy and high-calcium diets than in the control foals or
those fed high-calcium diets only. Dyschondroplasia is
thus not induced by diets high in calcium and is not allevi-
ated by excessive calcium in foals fed excessive energy. The
apparent association between excessive dietary phosphorus
and abnormal endochondral ossification may be mediated
by acidosis35 or by osteoporosis-induced weakening of the
subchondral bone plate.45
Copper
Copper is a necessary cofactor of lysyl oxidase, the enzyme
that catalyzes the oxidative deamination of lysine and
hydroxylysine residues to their corresponding aldehydes.
This is a necessary step in the formation of pyridinoline
cross-links in collagen and elastin. Low-copper diets have
been associated with an increase in the soluble fraction of
articular collagen, reduced collagen cross-linking of carti-
lage and bone, and an increased incidence of osteochon-
dral lesions in growing foals.44,70 A plausible mechanistic
link thus exists between low copper levels and the develop-
ment of OC, via the formation of biomechanically weak
cartilage and bone. However, the clinical significance of
this proposed pathogenic mechanism in the cause of natu-
rally occurring OC remains unclear.
Several early studies showed an association between
primary or secondary copper deficiency and equine osteo-
chondral lesions.70-72 However, the lesions reported—which
included intrachondral splitting through the hypertrophic
zone and denudation of subchondral bone—were generally
much more widespread and severe than typically occur
under field conditions.70-72 Moreover, retention of cartilage
was not a major pathological feature.70 This link between
copper deficiency and development of osteochondral
lesions prompted investigations into the effects on equine
skeletal development of copper supplementation during
late gestation and the early growing period. In one such
study, 21 pregnant mares were assigned to a control group
(13 ppm dietary copper) or a supplemented group (32 ppm)
during the last 3 to 6 months of pregnancy and the first 3
months of lactation.32 The foals were subsequently fed diets
containing 15 ppm (control) or 55 ppm (supplemented)
copper for up to 6 months. The copper content of the
control foals’ diet was close to NRC recommendations. OC
was defined as thickening of cartilage within the physis or
 Chapter 54  Pathogenesis of Osteochondrosis 623

AECC. Compared with the supplemented foals, 6-month- in incidence attributed to genetic factors is expressed as the
old control foals had nearly twice as many lesions in the heritability coefficient, and values of up to 0.52 have been
physes and more than five times as many in the AECC. The reported for OC of the hock (Table 54-1).33,74-77 Although
most notable lesions in the control group were cartilage the standard errors are in some studies substantial and the
thickening and separation of the cranial aspect of the inter- range of heritability coefficients reported is quite wide (a
mediate ridge of the tibia.32 factor that may be attributed, in part, to variation in the
A separate study investigated the effects of feeding diets mathematical approaches used),75,77 these findings suggest
containing 8 and 25 ppm copper to 3-month-old foals for that at least some manifestations of OC have a genetic
6 months.44 Cartilage and bone lesions were rare in the component.
foals fed 25 ppm copper. In contrast, the majority of the Recent genome-wide searches for markers associated
foals fed 8 ppm copper were severely affected with numer- with OC have identified significant quantitative trait loci
ous lesions. Cartilaginous flaps and cartilage thinning, on a number of equine chromosomes in Hanoverians and
erosion, and eburnation comprised the majority of the South German Coldbloods.78,79 Further study has revealed
lesions, many of which were associated with microfractures a significant association between a single nucleotide poly-
within the physes and primary spongiosa of the long bones morphism in the AOAH gene and fetlock OC in South
and cervical vertebrae. Biochemical analysis of tissues from German Coldbloods,80 but a role in osteochondral develop-
four low-copper–diet foals with OCD-like lesions revealed ment or repair for the protein encoded by this gene (acyl-
significantly fewer pyridinoline cross-links in articular car- oxyacyl hydrolase) has not been identified.
tilage, physeal cartilage, and bone than in tissues from a In spite of the success of these early genomic studies,
group of six foals (four supplemented, two on low-copper it remains likely that OC is a polygenic disorder81 that
diets) with no lesions. This study thus demonstrated a link develops from the superimposition of environmental
among low dietary copper, inferior collagen quality, and factors on a susceptible genetic background. Moreover,
OCD-like lesions.44 genetic factors may influence the development of disease
The pathological condition induced in these two studies either directly or via influences on other factors that appear
by dietary copper levels of 8 and 15 ppm appeared similar to be associated with OC such as conformation, growth
to naturally occurring OC grossly, radiologically, and in rate, and the hormonal response to ingestion of food.53,56,57,65
many cases histologically.32,44 However, the relevance to Analysis of large numbers of genotypes will therefore be
the field situation of the lesions recorded remains unknown. required for successful identification of the genes involved,82
Foals fed the lower amount of dietary copper in these and identification of a simple set of genetic markers is a
studies typically had numerous lesions, many of which goal that may well prove elusive.
were present in the cervical vertebrae.32,44 This lesion dis- An alternative strategy for reducing the incidence of
tribution would thus be described as atypical.12,14 More- OC is to exclude affected mares and stallions from breeding
over, it is evident that relatively high levels of dietary programs. The results of genomic and heritability studies
copper (25 and 55 ppm) do not completely prevent osteo- suggest that OC lesions at different anatomical sites may
chondral lesions,32,44 and that relatively low levels (4 to be genetically related,75,78 and this raises the possibility that
11 ppm) do not always result in foals with numerous osteo- it may be possible to reduce the overall incidence of the
chondral abnormalities.26,52,73 Supplementation of foals’ disease by such a strategy of selective breeding. The results
diets with copper is thus not a panacea, nor is it always of mathematical modeling suggest that the incidence of
effective.73 Provision of copper supplements to pregnant OC in Maremmano horses could be reduced from 16%
mares has also generally been unsuccessful in reducing the to 2% over five generations by active selection of both
incidence of osteochondral lesions at 5 to 6 months of stallions and mares free of the disease.77 Researchers who
age,52,54 although one study did show a positive effect.73 simulated the effects of various selection strategies in
Dutch Warmbloods came to a similar conclusion,83 esti-
Heredity mating that the incidence of OC would decrease from 25%
Heritability studies of equine OC have been completed in to 13% over 50 years (2.4% reduction per generation) as a
a number of breeds. The proportion of the total variation result of two alternative strategies: (1) active selection for

TABLE 54-1 
Incidence and Heritability of Osteochondrosis Lesions
RANGE OF INCIDENCE HERITABILITY
AMONG PROGENY COEFFICIENT*
SITE OF LESION BREED GROUPS (%) (MEAN ± SE) REFERENCE
Hock Standardbred 3.4 to 30 0.26 ± 0.14 Schougaard et al, 199074
Hock Standardbred 0 to 24 0.24 ± 0.19 to 0.27 ± 0.08 Philipsson et al, 199333
Hock South German Coldblood — 0.04 ± 0.07 Wittwer et al, 200775
Hock Standardbred 0 to 69 0.52 Grøndahl and Dolvik, 199376
Fetlock South German Coldblood — 0.16 ± 0.16 Wittwer et al, 200775
Stifle, hock, and fetlock Maremmano — 0.09 ± 0.24 to 0.14 ± 0.22 Pieramati et al, 200377
SE, Standard error.
*The heritability coefficient may overestimate the true heritability if there is a high incidence of lesions in one progeny group (as occurred in the study of Grøndahl and Dolvik, 199376).
624 PART VI  Developmental Orthopedic Disease and Lameness
OC-negative mares and stallions, and (2) progeny testing
of stallions. The model output concluded that these strate-
gies were more effective than selection of OC-negative stal-
lions only (17% incidence at 50 years) and no active
selection (21%).
Gender
Early reports suggested that the incidence of equine OC
was substantially higher in males than females.9,10 Nonsig-
nificant relationships between male gender and OC were
reported in epidemiological studies in which male/female
incidence ratios of 1.6 : 1 and 1.4 : 1 were found.84,85 However,
a controlled study involving Warmbloods reported no
gender predisposition for OC of the tarsocrural or femoro-
patellar joints,56 and similar findings were reported in TBs.54
In contrast, a study involving South German Coldbloods
found a twofold higher risk for OC of the hock and fetlock
joints in female horses,20 and a study involving feral horses
found typical OC lesions only in fillies.86
Exercise
The role of exercise in the pathogenesis of OC has been
investigated experimentally, with conflicting results. In one
study the incidence of OC was compared in foals subjected
to low- and high-exercise regimens from ages 3 to 24
months.87 All foals were housed in groups or kept in boxes
and allowed paddock exercise for 2 to 4 hours per day. In
addition, the low-exercise group received 15 to 45 minutes
of walking exercise per day. The high-exercise group
received 15 to 45 minutes of walking and trotting, plus
eight to 20 gallop sprints of short duration (10 to 15
seconds). At the end of the study, hock and stifle joints were
examined clinically and radiologically. OC was detected
in only three (6%) of the 50 foals in the high-exercise
group, but in 13 (20%) of the 66 foals in the low-exercise
group, demonstrating a significant protective effect of high-
intensity, short-duration exercise on the incidence of OC.
These findings were not supported by the results of a
subsequent extensive investigation into the effects of exer-
cise on musculoskeletal development. Forty-three foals
with a presumed genetic predisposition to OC of the femo-
ropatellar or tarsocrural joints were subjected to one of
three exercise regimens: pasture exercise only, confine-
ment to a box stall, and confinement to a box stall with
an increasing number of gallop sprints.23 These exercise
regimens were imposed from 1 week of age to 5 months,
and the incidence of OC, including subchondral bone
cysts, was determined at postmortem examination in a
subset of the foals at 5 months of age (eight per group).
The remaining foals were subjected to the same light exer-
cise regimen for an additional 6 months before euthanasia
at 11 months of age. Lesions were found in all 5-month-old
foals.23 Frequency was highest in the tarsocrural joints (1.9
lesions per foal), with a lower incidence in the femoropatel-
lar or femorotibial (1.0), cervical intervertebral (1.0), and
metatarsophalangeal joints (0.6). Exercise did not influ-
ence the number of lesions, although there was a tendency
for lesions to be more severe in the box-rested foals. Exer-
cise also appeared to influence the type and distribution of
lesions within the stifle joint: the foals subjected to box
rest were more likely to develop subchondral bone cysts
(femoral condyles), whereas the trained foals tended to
develop OC or OCD lesions (lateral trochlear ridge of the
femur). This difference suggests an effect of mechanical
loading on lesion development because the lateral troch-
lear ridge is loaded by the patella during exercise,12 and
subchondral bone cysts tend to develop at the point of
maximum load bearing during the support phase of the
stride.23,40,43 It was concluded that exercise has no role in
the pathogenesis of OC, although it may alter the appear-
ance and distribution of lesions.23 It should be noted that
other studies conducted on tissues from these foals sug-
gested that a regimen of box rest supplemented with short
bouts of high-intensity exercise (gallop sprints) had delete-
rious long-term effects on chondrocyte metabolism and
viability88,89 and cannot be recommended for optimal mus-
culoskeletal development.
Trauma and Biomechanical Force
The roles of trauma and biomechanical force in the patho-
genesis of osteochondral lesions are not well established.
It is generally agreed that biomechanical forces are respon-
sible for converting an OC lesion into a dissecting OCD
lesion,5,10,16 although little solid evidence exists to support
this assertion. More pertinent is establishment of the roles
of trauma and biomechanical force as primary causative
factors. The consistent location of typical OC lesions
within joints does suggest involvement of physical factors
in the pathogenesis.90 It has been proposed that physeal
dysplasia could result from excessive force on normal
tissues or from the superimposition of normal force on
structurally deficient tissues,34 and a similar hypothesis has
been suggested for the development of articular OC.14,28
Many of the factors discussed previously could lead to
generation of abnormal skeletal tissues, and abnormally
high forces could result from excessive or inappropriate
exercise, excessive body weight, or poor conformation.34 A
possible relationship between severe outward rotation of
the hindlimb and tarsocrural OC was noted in a study of
growing STB foals,53 but proof of a causative effect requires
further research.
The Role of Enzymes and Signaling Peptides
There is evidence that disturbances in the expression or
function of a number of enzymes and/or signaling peptides
may be involved in the pathogenesis of OC. Cathepsins
and matrix metalloproteinases (MMPs) are proteases that
are involved in the degradation of collagen and other
extracellular matrix components. Cathepsin B is present in
the AECC of normal growing horses, particularly in the
hypertrophic zone,52,91,92 and is abundant in the chondro-
cyte clusters that are commonly found in OC lesions.52,91,93
Increased MMP activity was identified in OC lesions, par-
ticularly in the deep zone adjacent to subchondral bone,
around chondrocyte clusters, and in lines that radiate from
the deep zone toward the articular surface.94 Other altera-
tions in collagen metabolism that have been identified in
association with the presence or severity of OC include
changes in serum levels of biomarkers of collagen degrada-
tion and synthesis, reduced hydroxylysyl pyridinoline
cross-linking (unassociated with copper deficiency), and
reduced total collagen content of cartilage.95-97
The potential roles of parathyroid hormone–related
protein (PTHrP) and Indian hedgehog (Ihh) in the patho-
genesis of OC have been evaluated. These signaling mol-
ecules, which regulate chondrocyte differentiation and
 Chapter 55  The Role of Nutrition in Developmental Orthopedic Disease 625
hypertrophy in growth cartilage via a negative feedback
loop,98 are expressed at significantly higher levels in osteo-
chondrotic cartilage than in control tissue, and it has been
proposed that this may result in retention of prehypertro-
phic cartilage and delayed endochondral ossification.99,100
However, identification of reduced levels of Gli1 (the
primary transcription factor for Ihh) in diseased cartilage
suggests that further work in this area is necessary.100
Another peptide that may be involved in the patho­
genesis of OC is transforming growth factor–β1 (TGF-β1),
a signaling peptide that is particularly important in con­
trolling mammalian endochondral ossification101,102 and
that has been shown to stimulate PTHrP expression.103,104
Reduced TGF-β1 expression has been identified in the
AECC of the lateral trochlear ridge of the femur in horses
with dyschondroplasia at this site, and it was suggested that
this may result in cessation of chondrocyte hypertrophy
and an accumulation of prehypertrophic chondrocytes.105
However, the clinical significance of these findings has not
been established. In this work, as in all other investigations
into the pathogenesis of OC, it is important that distinc-
tions be made between primary and secondary change
whenever possible.
Toxic Causes of Osteochondral Lesions
Foals exposed to excessive amounts of zinc and zinc and
cadmium in combination have been found to develop
generalized, severe osteochondral lesions.31,106-108 The gross
lesions described in these reports were characterized by
separation of articular cartilage from subchondral bone.
The role of cadmium in the pathogenesis of these lesions
is unclear.31,106,108 However, the effect of excessive dietary
zinc is likely to be mediated by secondary copper defi-
ciency.109 These environmental contaminants are clearly
toxic causes of osteochondral lesions and are not con­
sidered to be factors in the pathogenesis of naturally occur-
ring OC.
SUMMARY
A range of conditions results in failure of endochondral
ossification and retention of cartilage cores at the cartilage-
bone interface. However, opinions regarding pathogenesis
of OC still differ widely on the major factors involved in
the cause of the naturally occurring condition. The situa-
tion is complicated by the apparently multifactorial nature
of the condition,1,5,8,25,45 by the fact that environmental
influences and genetic susceptibility apparently combine
to determine the final outcome,53 and by the superimposi-
tion of secondary changes on primary lesions. However, it
is hoped that a renewed focus on the examination of early
lesions may allow development of a unified theory on the
pathogenesis of the disease.