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GUEST EDITORIAL

Food for Thought on Canine Developmental Orthopedic Disease


Although its genesis is presumed to be multifactorial, by
its very nature, developmental orthopedic disease in the
dog intimately links the disciplines of orthopedics, nutri-
tion, and genetics, as illustrated in the report by Lopez et
al (214218). Growth occurs within a genetically deter-
mined time frame, but is inuenced by a variety of en-
vironmental factors, including nutrition. The relationship
between nutrition and developmental orthopedic disease
has been the subject of scientific investigation for dec-
ades. No one specific cause has been identied as being
ultimately responsible for the clinical manifestations of
developmental orthopedic disease, but research indicates
that 2 of the more important nutritional factors are cal-
cium and energy. Whereas simple deciencies of both of
these variables can induce growth and developmental
problems, it is their excess (in the case of both calcium
and energy) or alterations in calcium homeostasis that are
likely to be of more practical significance.
Numerous, eloquent studies have elucidated the role of
calcium in developmental orthopedic disease. Large breed
puppies raised on diets containing high calcium or high
calcium and phosphorus concentrations manifest several
developmental bone abnormalities, including retained
cartilaginous cores in the radius and ulna, abnormal
endochondral ossication, and delayed skeletal matura-
tion.
13
Proposed mechanisms of excessive calcium inu-
ence on skeletal development include direct competition
with other minerals, alteration of acidbase balance, or
indirect stimulation of hormones such as parathyroid
hormone or calcitonin.
46
More recent work has exam-
ined the role of vitamin D
3
metabolism in calcium home-
ostasis and skeletal development in growing dogs. The
ndings of Tryfonidou et al
7
support that the increased
susceptibility to developing skeletal disorders of large
versus small breed dogs nds part of its etiopathogenesis
in the interrelationship between the growth hormone
(GH)insulin like growth factor 1 (IGF-1) axis and vi-
tamin D
3
metabolism. High concentrations of GH and
IGF-1 result in a relative excess of plasma 1,25(OH)
2
D
3
and a relative deciency of 24,25(OH)
2
D
3
in rapidly
growing large breed dogs.
7,8
Tryfonidou et al
9
proposed
that the increased calcitonin levels and/or a relative de-
ciency in 24,25(OH)
2
D
3
at the growth-plate level may
both be responsible for the retarded maturation of chon-
drocytes, thereby causing retained cartilage cones and
osteochondrosis. The authors suggest that this may be a
pathophysiological factor for the increased susceptibility
of large breed dogs to developing skeletal disorders.
9
Multiple studies on the effects of energy intake on
bone growth and development have given rise to the hy-
pothesis that excess energy, or overnutrition, resulting in
accelerated growth rates and/or obesity plays a key role
in the etiopathogenesis of developmental orthopedic dis-
ease. Excess energy alters growth rate and bone develop-
ment directly through nutrient supply and indirectly
through changes in multiple hormones such as GH, in-
sulin, IGF-1, triiodothyronine (T
3
), and thyroxine (T
4
).
1
IGF-1, T
3
, and T
4
were determined to be significantly
higher in growing dogs fed free choice compared with
dogs on food restriction.
1,10
Chondrocyte proliferation
and differentiation are stimulated by GH and IGF-1. In
addition to stimulating general metabolism, thyroid hor-
mones increase the rate of bone formation and resorpt-
ion.
1
Partly through the inuence of these hormones, free
choice feeding, and accelerated growth appear to create a
scenario where there is a mismatch between bone devel-
opment and body mass; thereby requiring immature
bones to carry more weight than they were designed to
carry during any given developmental stage. This coupled
with excessive weight gained through free choice feeding
can lead to biomechanical stress and developmental or-
thopedic disease.
Perhaps nowhere are the effects of limited food con-
sumption during growth and adulthood on orthopedic
disease better described than in a series of reports by
Kealy et al. Results from an 14-year study indicated
that limiting food consumption starting at 8 weeks of age
in a matched group of Labrador Retrievers to 75% of
that fed to control dogs resulted in a 67% reduction in
the prevalence of hip dysplasia at 2 years.
11
Continued
restriction substantially reduced the prevalence and se-
verity of hip joint osteoarthritis at 5 years of age.
12,13
The
prevalence and severity of osteoarthritis in several joints
was still less in the dogs with long-term reduced food
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Veterinary Surgery
35:211213, 2006
intake (10%) compared with control dogs (77%) by 8
years of age.
13
The study continued until all dogs had
died, for about 14 years, and found that restricted dogs
also had a lower hazard of death from all musculoskeletal
causes.
14
In addition to the benets of a lower prevalence
and severity of orthopedic disease, 25% restriction in
food intake increased median life span and delayed the
onset of signs of other chronic diseases.
15
Recent research in humans and rodents opens yet an-
other avenue to consider when evaluating the relationship
between nutrition and developmental orthopedic disease.
In addition to the alterations in hormonal metabolism
and biomechanical stress induced by accelerated growth
and obesity, adipose tissue, historically thought to be
only a medium for storage and release of fatty acids, is
now recognized as a major endocrine organ.
16
Adipocytes
release a wide range of protein signals and factors, many
of which are linked to immunity and inammation, called
adipokines.
1618
Obesity increases the expression, pro-
duction, and release of a number of inammation-related
adipokines, including tumor necrosis factor, interleukin
6, plasminogen activator inhibitor 1, haptoglobin and
leptin, from adipose tissue.
17,18
Alternatively the expres-
sion of adiponectin, an anti-inammatory adipokine, de-
clines in obesity.
18,19
It is hypothesized that as white
adipose tissue expands with obesity, hypoxia develops
(white adipose tissue is not highly vascularized), and low
oxygen levels stimulate the production and release of in-
ammatory cytokines, chemokines, and angiogenic fac-
tors with the ultimate goal of increasing blood ow and
vascular growth.
17,18
The rst steps to explore this hy-
pothesis in companion animals have begun with the
characterization of adipokine gene expression in adipose
tissue stores of dogs.
20
If it is determined that ad-
ipose tissue in dogs produces and releases adipokines
similar to rodents and humans, such ndings may
provide a connection to a previous postulate regarding
the role of overnutrition and/or obesity in osteoarthritis
advanced by Kealy et al.
13
Upon nding a lower
prevalence and severity of osteoarthritis in dogs that
were limit-fed and therefore frequently weighed less
(with presumptively less fat mass) compared with con-
trols, the authors hypothesized that osteoarthritis may in
fact have a systemic cause, with variable expression in
different joints.
13
Although not necessarily directly connected, there are
threads between the causes discussed above; however, I
believe that a collaborative effort from individuals with
expertise in different disciplines is required to complete
the picture. The current report by Lopez et al underscores
the need and opportunities for interdisciplinary work in
this eld. Many questions remain to be answered; how we
choose to approach them will ultimately determine our
success.
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212 EDITORIAL
16. Trayhurn P, Beattie JH: Physiological role of adipose tissue:
white adipose tissue as an endocrine and secretory organ.
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Andrea J. Fascetti, VMD, PhD,
Diplomate ACVIM & ACVN
Department of Molecular Biosciences
School of Veterinary Medicine,
University of California, Davis, CA 95616.
E-mail: ajfascetti@ucdavis.edu.
213 EDITORIAL