Clinical Perspectives on Canine Joint Disease Clinical Perspectives

Transcription

Skeletal Health
Clinical Perspectives
on Canine Joint Disease
®
Presented at
The North American
Veterinary Conference
Orlando, Florida, USA
January 17, 2001
Contents
Summary of Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Author Profiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Articular Cartilage in Health and Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Allan J. Lepine, PhD; Michael G. Hayek, PhD
The Benefit of Weight Management in Dogs with Joint Problems . . . . . . . . . . . . 18
Mark A. Tetrick, DVM, PhD; Joseph A. Impellizeri, DVM; Peter Muir, BVSc,
MVetClinStud, PhD, MACVSc, DACVS, DECVS
Physical Therapy for Dogs with Joint Disease . . . . . . . . . . . . . . . . . . . . . . . . . 22
Darryl L. Millis, MS, DVM, Diplomate ACVS
Pathophysiology and Diagnosis of Intervertebral Disk Degeneration . . . . . . . . . 28
Takayoshi Miyabayashi, BVS, MS, PhD, Diplomate ACVR
Balanced Management of Osteoarthritis in Companion Animals . . . . . . . . . . . . 32
Steven A. Martinez, DVM, MS, Diplomate ACVS
Cover illustration: Jeff D. Fulwiler, Pavone Fite Fulwiler
Copyright © 2001
The Iams Company, Dayton, OH 45414, USA
All rights reserved.
Internet address: www.iams.com
Printed in the United States of America.
Item #RD 0024
1
Clinical Perspectives on Canine Joint Disease (TNAVC 2001)
Summary of Contents
CHAPTER 1: ARTICULAR CARTILAGE IN HEALTH AND DISEASE
Allan J. Lepine, Michael G. Hayek
Pages 8–17
Summary.
Nutritional management of articular cartilage health requires an understanding of the changes that
normally occur during life, as well as the alterations caused by disease or injury.
Findings.
• Components of articular cartilage extracellular matrix
– Proteoglycans – comprised of various glycosaminoglycans
– Hyaluronan
– Chondroitin sulfate and dermatan sulfate
– Heparan sulfate
– Keratan sulfate
– Collagen
• The ability of articular cartilage to respond to compressive stress depends on the characteristics
and interrelationships between proteoglycans and collagen
• Significant structural changes occur during the maturation of articular cartilage
– Amounts and proportions of collagen types change
– Proteoglycans become smaller and enriched with keratan sulfate
– Result of aging changes is a reduced ability to withstand normal joint functioning forces
• Three types of articular cartilage damage
– Microdamage or blunt trauma
– Chondral fractures
– Osteochondral fractures
• Osteoarthritis – noninflammatory degenerative joint disease
– Changes in proteoglycan amounts and ratios
– Matrix degradation often exceeding synthesis
– Cytokine release stimulates production of degradation enzymes and suppresses protein
biosynthesis in chrondrocytes
• Nutritional management of articular cartilage health
– Eicosanoid production can be manipulated by dietary fatty acids and thereby assist
in inflammation management
– Dietary glucosamine and chondroitin sulfate may help increase cartilage biosynthesis
and decrease degradation
Application. Dietary fatty acids and chondroprotective nutrients such as chondroitin sulfate and glucosamine
may be useful in maintaining joint health and managing joint injury or disease.
CHAPTER 2: THE BENEFIT OF WEIGHT MANAGEMENT IN DOGS WITH JOINT PROBLEMS
Mark A. Tetrick, Joseph A. Impellizeri, Peter Muir
Pages 18–21
Summary.
An observable improvement in lameness can be achieved when overweight dogs lose body weight.
Findings.
• Lameness severity was significantly influenced by weight loss in overweight dogs with hip
osteoarthritis and lameness
2
Findings.
(continued)
• Rapid or prolonged increases in blood glucose and, therefore, insulin secretion may promote
greater weight gain and fat deposition. Specially formulated foods containing a blend of barley
and grain sorghum may help improve glucose tolerance and stabilize blood glucose levels in
overweight dogs
• Dietary carnitine addition resulted in lower fat mass and greater lean body tissue in dogs during
weight loss
• Diets containing chromium tripicolinate may lead to an improvement in glucose tolerance and
blood glucose stability in overweight pets
Application. Weight loss can influence lameness severity. Achieving weight loss in dogs can be facilitated by
the use of specially formulated diets containing carnitine, chromium tripicolinate, and a blend of
barley and grain sorghum.
CHAPTER 3: PHYSICAL THERAPY FOR DOGS WITH JOINT DISEASE
Darryl L. Millis
Pages 22–27
Summary.
Joint disease is a common problem in dogs. Patients with osteoarthritis (OA) can have restricted
activity, limited ability to perform, pain and discomfort, and decreased quality of life. Physical
therapy can enhance or supplement other treatments for OA.
Findings.
• Although mechanical stress can cause biochemical, histological and biomechanical changes in
articular cartilage, a lifetime of regular low-impact exercise in dogs with normal joints did not
cause significant alterations
• Older dogs may be more vulnerable to articular cartilage changes from mechanical stress than
younger dogs
• The goals of therapeutic exercise should be to reduce body weight, increase joint mobility, and
reduce joint pain through the use of low-impact weight-bearing exercises designed to strengthen
supporting muscles
• Exercise should be performed only after correction of major OA risk factors, such as joint
instability or obesity
• The ideal exercise program is one that provides sufficient benefits without causing discomfort
• Initially, antiinflammatory drugs should not be administered prior to exercise so that the proper
level of exercise can be determined
• Suggested exercise methods include swimming, controlled exercise on a leash, and treadmill walking
• Physical agents that can be useful aids in physical therapy include:
– Superficial heat modalities
– Cryotherapy
– Massage
– Ultrasound
– Neuromuscular Electrical Simulation
• Progress should be documented to assist in further treatment decisions and help maintain the dog
owner’s enthusiasm for the program
Application. Physical rehabilitation is a valuable, but underused part of the management of dogs with OA. It
can be used in combination with nutritional, medical, and surgical management to reduce pain and
lameness and improve quality of life.
3
CHAPTER 4:
PATHOPHYSIOLOGY AND DIAGNOSIS OF INTERVERTEBRAL DISK DEGENERATION
Takayoshi Miyabayashi
Pages 28–31
Summary.
Intervertebral (IV) disk disease is a common neurological condition in dogs that causes pain and
motor dysfunction. The age-related degeneration of IV disks in dogs cannot be avoided but it may
be possible to delay the process. Research in chondrocyte metabolism and its relationship in
degeneration should help in finding ways to maintain canine IV disk health for as long as possible.
Findings.
• Intervertebral disks have two distinct components, which work together to act as a shock absorber
• Anulus fibrosus – stretches evenly to distribute force
• Nucleus pulposus – contains proteglycans that can hold high water content
• Degenerative changes of canine IV disks with age are unavoidable
– Loss of proteoglycans is initial step
– Eventually fissures form within the anulus fibrosus
– Nucleus pulposus protrudes through fissures
– IV disk space narrows
– Spondylosis deformans develops around vertebral end-plates
– End-plate sclerosis and malalignment may develop
– All IV disk tissues herniate from the IV disk space
– Further bony remodeling at end-plates
– Finally, protruded nucleus pulposus undergoes endochondral ossification.
• As dogs live longer, more severe degenerative changes may be observed that may be confused with
discospondylitis or neoplasia, even though the associated motor dysfunction is minor
• MRI is the diagnostic method of choice in human radiology but plain radiography and
myelography are still the most commonly used imaging methods in diagnosis of IV disk disease in
veterinary medicine
4
CHAPTER 5: BALANCED MANAGEMENT OF OSTEOARTHRITIS IN COMPANION ANIMALS
Steven A. Martinez
Pages 32–37
Summary.
No single treatment will adequately manage osteoarthritis (OA) in all dogs. A combination of three
treatment components should be considered when medically managing a dog with OA: 1) weight
control, 2) exercise/activity, 3) pharmacological/disease-modifying osteoarthritic drugs. Exclusion of
one or more of these components from a treatment protocol will usually result in an overall poorer
clinical response.
Findings.
• Weight Control
– Obesity is a major risk factor for the development of OA
– Achieving weight control can be challenging
– Dogs with OA that inhibits movement cannot utilize consumed or stored fat efficiently
– Dogs with underlying endocrine disorders have a tendency to maintain body fat even
on a reducing diet
– Estimations of dog’s ideal weight and energy requirements are often inaccurate
– Owners may not be willing to be proactive in helping dogs reduce weight
– All weight-control programs should include an exercise program
• Exercise
– Controlled exercise is an important aspect in the management of OA in dogs
– High-impact activities may over-stress damaged joints and increase inflammation
– Low-impact activities are thought to reduce loads on an OA joint and result in less
discomfort for patient while maintaining good muscle strength/mass and joint function
• Pharmocologics
– The primary goal of the pharmacological management of OA is to relieve the patient
of discomfort associated with joint movement
– Toxicity concerns are present with long-term, chronic therapy with NSAIDs; therefore,
they probably should be administered only on a PRN basis, especially for the dog that
has only intermittent discomfort due to OA.
– Glucosamine and chondroitin sulfate reportedly have a positive effect on cartilage
matrix; they enhance proteoglycan production and inhibit catabolic enzyme production
or activity in arthritic joints
Application. Osteoarthritis can be a debilitating diseases for dogs; however, new concepts in a balanced
management of OA can result in an acceptable quality of life for the OA patient. Medical
management must be considered beyond pharmacological treatment to include a balance with
exercise/activity and weight control management. Failure to consider this treatment “triad”
concept will usually result in a poorer clinical response to therapy and quality of life as perceived
by the owner of the arthritic dog.
5
Author Profiles
Steven A. Martinez, DVM, MS, Diplomate ACVS
Washington State University
Dr. Martinez received his MS degree in Comparative Pathology in 1984 and his DVM degree in
1985 from the University of California at Davis. After completing a small animal internship at
California Animal Hospital from 1985-1986 and a small animal surgical residency at Michigan
State University from 1986-1989, Dr. Martinez accepted an academic appointment as Assistant
Professor of Small Animal Surgery at the Atlantic Veterinary College at the University of Prince
Edward Island, Canada from 1989-1990. Dr. Martinez returned to Michigan State University and
served as Assistant Professor of Small Animal Surgery from 1990-1997. Dr. Martinez has been
serving as an Assistant Professor of Small Animal Orthopedic Surgery at Washington State
University since 1997. His current research interests include bone grafting, cytokine delivery
systems in bone, and gait analysis in dogs.
University of Tennessee
Dr. Millis received his BS degree in Animal Science from Cornell University in 1981, and his MS
degree in Animal Nutrition from the University of Florida in 1983. After receiving his DVM
degree from Cornell University in 1987, he completed a small animal internship in 1988 and a
surgical residency in 1991, both at Michigan State University. Dr. Millis served as an Assistant
Professor of Small Animal Surgery at Mississippi State University from 1991–1993, at which time
he joined the faculty at the University of Tennessee where he currently serves as Associate
Professor of Orthopedic Surgery and Section Head of Small Animal Surgery. His research
interests include physical therapy in small animals, osteoarthritis, and bone healing.
Takayoshi Miyabayashi, BVS, MS, PhD, Diplomate ACVR
University of Florida
Dr. Miyabayashi received his BVS degree in 1977 from the University of Osaka Prefecture in
Japan. After spending two years in private practice, he came to the University of California,
Davis to study for MS (1982) and PhD (1994) degrees in comparative pathology. He was a
radiology resident at the University of Wisconsin-Madison from 1987 to 1990 when he was hired
as an assistant professor of veterinary radiology at The Ohio State University. Dr. Miyabayashi
was board certified by the American College of Veterinary Radiology in 1991 and moved to the
University of Illinois in 1995. Since 1997, he has served an associate professor in veterinary
radiology at the University of Florida. Dr. Miyabayashi’s teaching and research interests include
aging changes in intervertebral disks, musculoskeletal disorders, and imaging diagnosis using MRI
and other advanced diagnostic techniques.
6
Allan J. Lepine, PhD
The Iams Company
Dr. Lepine received his PhD in nonruminant nutrition from Cornell University in 1987, after
which he joined the faculty at The Ohio State University as an Assistant Professor in the
Department of Animal Science. In 1993, he accepted a position in Research and Development at
The Iams Company where he is currently Principal Research Nutritionist. His research interests
include neonatal nutrition, growth and development as well as the effects of nutrition on
reproduction in companion animals. Dr. Lepine has published more than 60 scientific papers and
abstracts in peer-reviewed journals.
Mark A. Tetrick, DVM, PhD
The Iams Company
Dr. Mark Tetrick received his BS degree in Meat and Animal Science in 1984 and Doctor of
Veterinary Medicine degree in 1988 from the University of Wisconsin-Madison. After a year in
large/companion animal practice, he returned to the University of Wisconsin-Madison and
received his PhD in Nutritional Sciences in 1996. His thesis research dealt with utilizing medium
chain triglycerides as an energy supplement for newborn animals. In July, 1996, Dr. Tetrick joined
the Strategic Research group in the Research and Development division of The Iams Company.
His research interests include the clinical impact of nutrition, with emphasis on the influence of
nutrition on urinary tract health.
7
STRUCTURE AND FUNCTION
OF ARTICULAR CARTILAGE
Synovial Joints
Synovial joints (diarthroses) are composite structures
consisting of articular cartilage, a joint capsule filled with
synovial fluid, and underlying osseous structures (Figure 1).
A physiologically normal synovial joint provides a virtually
wear-resistant and friction-free articulating surface that can
withstand considerable compressive, tensile, and shear
forces. Cells that line the synovial membrane of the joint
capsule produce synovial fluid, a clear and viscous
substance. Synovial fluid serves as a protective barrier by
providing lubrication to the opposing articular surfaces and
preventing contact between surfaces. It also supplies
nutrients to the cells of the articular cartilage and removes
waste products. Without an adequate protective barrier,
rapid joint degeneration can occur when forces, especially
weight bearing forces, are applied.
Articular
Cartilage in
Health and
Disease
Allan J. Lepine, PhD
Michael G. Hayek, PhD
Bone
Joint Capsule
Research and Development Division
The Iams Company, Lewisburg, Ohio, USA
Synovial
Fluid
Articular
Cartilage
INTRODUCTION
Understanding the changes in the physiologic and
morphologic relationships of articular cartilage during
normal life stages, as well as during more dramatic events
such as joint trauma or disease, can allow for the
application of nutritional management to minimize
negative outcomes. Nutritional interventions can include
managing growth in those breeds prone to joint problems,
decreasing incidence and symptoms of obesity, and
providing nutrients such as omega-3 fatty acids and
chondroprotective agents that aid the inflamed or
damaged joint. A review of the structure and function of
articular cartilage is important in order to better
understand the control and management of companion
animal joint health.
Bone
Figure 1. Basic structure of the synovial joint. (Used with permission.
Lepine AJ. Structure and function of articular cartilage. In: Reinhart GA,
Carey DP, eds. Recent Advances in Canine and Feline Nutrition,
Vol. III: 2000 Iams Nutrition Symposium Proceedings. Wilmington,
OH: Orange Frazer Press, 2000; 481-494.)
Components of the Articular Cartilage
Extracellular Matrix
Proteoglycans. Proteoglycans, a primary component
of the articular cartilage extracellular matrix, are comprised
8
of numerous glycosaminoglycan chains that are covalently
linked to a central core protein (Figure 2). Glycosaminoglycans are repeating disaccharide units in which one
of the saccharides in each disaccharide is generally a
sulfated amino sugar.
Four primary glycosaminoglycans associated with
proteoglycans are: (1) hyaluronan, (2) chondroitin sulfate
and dermatan sulfate, (3) heparan sulfate, and (4) keratan
sulfate. These glycosaminoglycans are distinguished by the
specific sugar residues included, the type of linkage
between these residues, and the number and location of
sulfate groups.1 Hyaluronan is a repeating disaccharide of
glucuronate and N-acetyl glucosamine and is the only
glycosaminoglycan that is nonsulfated. Chondroitin sulfate
is a repeating disaccharide of glucuronate and N-acetyl
galactosamine; dermatan sulfate is derived from
chondroitin sulfate by the epimerization of glucuronate to
iduronate. Keratan sulfate is a disaccharide of galactose
and N-acetyl glucosamine; heparan sulfate contains
iduronate and N-acetyl glucosamine. While the majority of
these glycosaminoglycans are covalently bound to a core
protein to form proteoglycans, hyaluronan does not bind to
a core protein.
Aggrecan, the most common and well-defined
proteoglycan in articular cartilage, is comprised of a core
protein to which as many as 100 glycosaminoglycan chains
are attached. The attachment to the core protein is at a
serine residue and is stabilized by a link tetrasaccharide.
While the majority of the glycosaminoglycans in aggrecan
are chondroitin sulfate and keratan sulfate, they are not
randomly attached to the core protein but are located
within specific binding regions. This generally results in
aggrecan having a greater chondroitin sulfate content than
keratan sulfate since the keratan sulfate-rich binding
region is located closer to the NH2 terminal end of the
core protein while a larger, chondroitin sulfate-rich
binding region is more distal.2
Aggrecan is generally found as a large aggregate with
as many as 200 aggrecan molecules covalently bound to a
single hyaluronan molecule.3 This linkage to hyaluronan is
Keratan Sulfate
Chains
Chondroitin Sulfate
Chains
Keratan Sulfate
Rich Region
Condroitin Sulfate
Rich Region
GLYCOSAMINOGLYCAN (GAG) CHAINS
Core
Protein
Linked To
CH2OH
CH2OH
O
O
H
HO
O
H
O
O
H
H
H
OH
H
H
H
H
H
NHCOCH3
Keratan Sulfate
COO
_
O
H
AGGRECAN
_
CH2OSO 3
O
H
HO
O
O
O
OH
H
H
OH
H
H
H
H
H
NHCOCH3
Core Protein
Link Protein
To
Form
Chondroitin 6-Sulfate
AGGRECAN AGGREGATE
Hyaluronan
Figure 2. Proteoglycan, one of the 2 main classes of the articular cartilage extracellular matrix, is a complex structure formed by glycosaminoglycan
(GAG) chains covalently linked to core proteins, which are then bound to form the proteoglycan, aggrecan. (Used with permission. Lepine AJ.
Structure and function of articular cartilage. In: Reinhart GA, Carey DP, eds. Recent Advances in Canine and Feline Nutrition, Vol. III:
2000 Iams Nutrition Symposium Proceedings. Wilmington, OH: Orange Frazer Press, 2000; 481-494.)
9
Molecules
stabilized by a small glycoprotein
self-assemble
referred to as link protein.4 The
to form
link protein is homologous with
Collagen
the NH2 terminal region of
Fibril
aggrecan, thus allowing hyalurCollagen Molecules
(triple helix of polypeptide α-chains)
onan to covalently bind to both
Collagen Fibril
link protein and aggrecan. These
bonds serve to stabilize the
aggrecan aggregate.1 To provide
further stabilization, cross-links
between the link proteins and the
core protein are also present.
Collagen. Collagen, a
second primary component of the
Fibrils
extracellular matrix, is composed
aggregate
of a triple helix of polypeptide
to form
Collagen Fiber
α-chains (Figure 3). These
Collagen
polypeptide chains of collagen are
Fiber
unique, relative to other proteins
of animal origin, due to high
Figure 3. Collagen, the second main class of the articular cartilage extracellular matrix, is formed by
proportions of hydroxylysine and
a triple helix of polypetide a-chains which self-assemble into collagen fibrils which then aggregate to form
hydroxyproline residues. The
a collagen fiber. (Used with permission. Lepine AJ. Structure and function of articular cartilage. In:
collagen molecules self assemble
Reinhart GA, Carey DP, eds. Recent Advances in Canine and Feline Nutrition, Vol. III: 2000
into collagen fibrils. Within those
Iams Nutrition Symposium Proceedings. Wilmington, OH: Orange Frazer Press, 2000; 481-494.)
fibrils, interchain hydrogen bonds
The proteoglycans are hydrophilic in nature and
and covalent intramolecular cross-links form between
thus provide an extremely high hydration capacity.
modified lysine residues of adjacent triple helices. These
Proteoglycans swell as water is attracted to the matrix,
bonds and cross-links help to stabilize not only the triple
however, the degree of swelling is limited to about 20% of
helix, but ultimately the collagen structure. Collagen
the maximum potential since the proteoglycans are
fibrils then aggregate into a single collagen fiber.
imbedded in a matrix of collagen fibers.3 Inherent in the
Several collagen variations are distinguished by the
fibrillar structure of collagen and enhanced by the crosscomposition of the α-chains that form the triple helix. In
links between collagen molecules,3 collagen fibers exhibit
articular cartilage, approximately 90–95% of the collagen
maximal tensile strength. The tensile stress imposed upon
is type II3,5 with the remaining collagen types reported to
the collagen network by the swelling pressure of the
be types V, VI, IX, and XI.5 The incorporation of these
proteoglycans demonstrates the importance of the tensile
minor amounts of collagen types into the collagen matrix
strength of collagen. One important outcome of this
may be important to the physical organization of the
functional relationship is that the collagen network holds
matrix. For example, type IX collagen is located at the
the proteoglycan molecules within the extracellular matrix
surface of the type II collagen fibril linked by a lysineand prevents their escape (Figure 4). This is particularly
derived hydroxypyridinium cross-link.6,7 Two regions of the
important since there are no covalent links between
type IX collagen, the COL3 arm and the NC4 domain,
collagen and the proteoglycans8 and it is solely the size of
project out from the surface and are suspected to serve as
the hydrated proteoglycans that maintains them within
binding sites for other matrix components. It is also
the articular cartilage.
speculated that fibril thickness is controlled by Type XI
The ability of the articular cartilage matrix to
collagen which is present within the type II fibrils.3
respond to compressive loads is dependent upon the
characteristics and interrelationships between proteoFunction of Extracellular Matrix Components
glycans and collagen. The compressive force placed on
The unique physiologic relationship between the
articular cartilage upon loading forces the fluid phase to
proteoglycans and collagen makes articular cartilage a
flow through the permeable solid phase. As the compresbiphasic material with a porous-permeable fiber-reinforced
sive force increases, the hydraulic pressure increases.8 This
solid phase and a freely flowing fluid phase.3 It is precisely
is due to decreased pore size as the solid matrix is
because of this biphasic nature that articular cartilage has
compressed causing increased resistance to fluid flow until
the biomechanical properties necessary to withstand the
an equilibrium is reached with the compressive force
stresses associated with normal joint functioning.
10
EXTRACELLULAR MATRIX
Collagen
Proteoglycan
Maximum Tensile Strength
High Hydration Capacity
Figure 4. The components of articular cartilage function together to produce a biphasic matrix that can withstand the stress of normal joint function.
(Used with permission. Lepine AJ. Structure and function of articular cartilage. In: Reinhart GA, Carey DP, eds. Recent Advances in Canine
and Feline Nutrition, Vol. III: 2000 Iams Nutrition Symposium Proceedings. Wilmington, OH: Orange Frazer Press, 2000; 481-494.)
Zone 1 — Superficial or tangential zone. Contains
flattened, elongated chondrocytes and collagen
fibrils that are parallel to the articular surface.
resulting in a ceasing of cartilage deformation. Further
contributing to this equilibrium is the increasing negative
charge density within the matrix as water is extruded from
the matrix following increased compression.3 After
compression ceases, water and nutrients reenter the
cartilage matrix, thereby allowing the proteoglycans to
swell and the cartilage to recover to its nondeformed
conformation.
As cartilage deformation occurs in response to
compressive forces, considerable tensile forces are placed
upon the collagen network. Without adequate resistance
to tension by the collagen fibers the cartilage would
rupture as the compressions increase. The experimental
removal of glycosaminoglycans from bovine articular
cartilage9 clearly demonstrated the importance of the
proteoglycan–collagen relationship in articular cartilage.
In this study, the compressive strength of the cartilage was
largely eliminated but the rupture strength of the cartilage
was only slightly reduced.
Zone 2 — Transitional or intermediate zone.
Chondrocytes are oval or round, are distributed
randomly, and contain greater numbers of
mitochondria, rough endoplasmic reticulum, and
golgi apparatus. Collagen fibrils are more oblique
and appear less organized.
Zone 3 — Radiate or deep zone. Chondrocytes are
large and rounded, arranged in columns
perpendicular to the articular surface.
Zone 4 — Calcified zone. Farthest removed from the
articular surface. The “tidemark” delineates zones 3
and 4. The few chondrocytes observed are necrotic
due to the calcified matrix.
Within the transitional and deep zones,
chondrocytes are the most metabolically active and have
the capacity to synthesize and degrade all components of
the extracellular matrix, including the precursors for
collagen and the proteoglycans.10,11 Aggrecan, link protein,
and hyaluronan are extruded into the extracellular matrix
where they spontaneously aggregate.8 The collagen fibrils
in zone 3 are arranged perpendicular to the articular
DEVELOPMENT OF MATURE
ARTICULAR CARTILAGE
“Zones” are descriptive reference points for the
organizational layers that encompass the thickness of
mature articular cartilage5,8,10 (Figure 5).
11
ARTICULAR SURFACE
ZONE I
ZONE II
ZONE III
ZONE IV
TIDE
MARK
SUBCHONDRAL
BONE
Figure 5. Structural demarcations in mature articular cartilage. (Used
with permission. Lepine AJ. Structure and function of articular cartilage.
In: Reinhart GA, Carey DP, eds. Recent Advances in Canine and
Feline Nutrition, Vol. III: 2000 Iams Nutrition Symposium
Proceedings. Wilmington, OH: Orange Frazer Press, 2000; 481-494.)
surface. The deep zone forms an interlocking network that
anchors the cartilage to the bony substrate.12 The
concentration and composition of collagen and proteoglycans varies depending on the specific articular cartilage
zone. For example, the concentration of collagen is highest
in the superficial zone and decreases by approximately 15%
within the deep zone.2 In contrast, proteoglycan concentration is lowest in the superficial zone and highest in the
deep zone. Furthermore, the proteoglycan composition
varies across these zones with less keratan sulfate apparent
in the superficial zone as compared to the deeper zones.2
Significant structural modifications occur during the
maturation process of articular cartilage. It is interesting to
note that developing cartilage does not exhibit the zone
distinctions observed in mature articular cartilage. The
zones seen in adult articular cartilage are not entirely
distinguishable, as shown in research in the young rabbit
(6–8 weeks of age).13 At 6–7 weeks of age, a surface zone
(likely encompassing both the surface and transitional
zones) and the deep zone layers are present. By 8 weeks of
age a distinction is apparent between the surface and
transitional zones but tidemark is not seen until 12–14
weeks of age.14
The composition of the extracellular matrix
continues to change during growth and development.
Proteoglycans become smaller as the body matures, most
likely due to a decreased chain length of the chondroitin
12
sulfate and possibly also decreased core protein length.15,16
This reduced proteoglycan size is likely due to the action of
extracellular matrix proteases. The proteoglycans become
proportionately enriched with keratan sulfate as a result of
the decreased chain lengths of chondroitin sulfate and core
protein. The specific chondroitin sulfate chains that are
present within the articular cartilage also are altered with
maturity. Immature cartilage has a ratio of chondroitin-4sulfate to chondroitin-6-sulfate of 1:1 with this ratio
decreasing as age increases.15 These maturational changes
are likely of functional significance since the stiffness of
the cartilage and the resultant resistance to deformation
are dependent upon the fixed charge density and
glycosaminoglycan content. In this respect, keratan sulfate
influences stiffness to a greater degree than chondroitin
sulfate, thereby providing a potential advantage to keratan
sulfate-rich proteoglycans in articular cartilage subjected to
high load such as is the case in the adult.15
The amounts and proportions of collagen types
changes throughout development. A study of fetal and
neonatal rabbits14 revealed that the cartilage of a 17-dayold rabbit fetus contained collagen types I, III, and V but
no type II collagen. By day 25, the fetal articular cartilage
still contained type I collagen but no type II. It was only by
6 weeks postnatally that type II collagen was present and
type I collagen disappeared. Furthermore, the concentration of hydroxyproline increased 2-fold in the chicken
through 22 days of age indicative of an increased
concentration of collagen in the articular cartilage of the
young animal.17 These collagen changes are likely due to
structural modifications that are necessary as the stresses
on the articular cartilage are increased.
An important aspect of appropriate maturation in
response to increasing joint-related forces is the ability of
articular cartilage to develop differentially from growth
plate cartilage, structures that are similar during early life.
A primary difference is in the maturation of the
chondrocytes of these two cartilage types. In contrast to
articular cartilage chondrocytes, growth plate chondrocytes
undergo hypertrophy and maturation as the extracellular
matrix matures.18 Although the mechanism by which this
distinction occurs remains equivocal, evidence exists that
tenascin-C, a large glycoprotein found in the extracellular
matrix of some embryonic and adult tissues18 (also called
cytotacin or hexabrachion), may have a role in assembly
and restructuring of the cartilage matrix.19 It is suggested
that tenascin-C may promote a stable phenotype (round)
of the articular cartilage chondrocyte while the absence of
tenascin-C in the growth plate may allow flattening,
proliferation, and maturation of the chondrocytes and
thereby the replacement of the cartilage with bone. The
presence of tenascin-C throughout life in the articular
cartilage, albeit at decreasing concentrations with increasing age, allows functional chondrocytes to be maintained
throughout life in contrast to epiphyseal bone growth.
PHYSIOLOGIC CHANGES
ASSOCIATED WITH AGING
underlying bone, resulting in chondrocyte damage
and marrow cell involvement. Since vascular
structures are now involved, inflammation occurs.
This is in contrast to the lack of inflammatory
response to less traumatic articular cartilage injuries
resulting from the inherent avascular nature of this
tissue. Following a full thickness injury, fibroblasts
differentiate into chondrocytes and repair of the
tissue is attempted, but the fibrocartilaginous repair
tissue produced is not “normal” articular cartilage.23,24
After several phases of remodeling, the repair tissue
has a lower proteoglycan content and a substantial
component of type I collagen rather than type II.24
Therefore, the resulting repair is often of suboptimal
quality resulting in compromised joint function.
It is normal for articular cartilage to undergo
physiological changes throughout the aging process. Swine
studies have shown age-related decreases in hydration,
collagen (dry matter basis), glycosaminoglycan
concentration (especially chondroitin sulfate), and
proteoglycan size.20,21 Although the total glycosaminoglycan concentration may not vary much with increased
age, the ratio of keratan sulfate to chondroitin sulfate does
increase.21 With respect to chondroitin sulfate it was also
noted that the 4-sulfated compound decreased while the 6sulfated compound increased. The alteration of
proteoglycan composition and size is most likely the result
of proteolytic cleavages that are not limited to the period
of growth and maturation but appear to occur throughout
the aging process in all species.22 The link proteins are also
subject to proteolytic cleavage as aging progresses.22 This is
likely a normal component of aging and could contribute
to the destabilization of the proteoglycan component of
the extracellular matrix. The inherent result of these
normal age-related changes of the articular cartilage will
be a matrix of reduced capability to withstand the forces
associated with normal joint functioning.
EFFECTS OF OSTEOARTHRITIS
Osteoarthritis is defined as a noninflammatory
degenerative joint disease characterized by degeneration of
the articular cartilage, hypertrophy of the bone at the
margins, and changes in the synovial membrane.
Chondrocytes are normally able to synthesize the
proteoglycans, collagen, fibronectin, and other
components needed to maintain joint homeostasis and
integrity due to the relatively low turnover of the
extracellular matrix. When chronic trauma or disease
disrupts this homeostasis, however, the articular cartilage
may progressively degenerate, ultimately resulting in the
development of osteoarthritis.
During the initial stage of osteoarthritis, responses
similar to those seen in subchondral injury of the articular
cartilage occur. Chondrocyte proliferation is observed with
subsequent increased synthesis of extracellular matrix. In
early osteoarthritic cartilage the concentration of keratan
sulfate is decreased, the length of the chondroitin sulfate
side chain is reduced25 and the ratio of chondroitin-4sulfate to chondroitin-6-sulfate is increased.26 The newly
synthesized proteoglycan subunits do not demonstrate
normal aggregation with hyaluronic acid.26
Concurrent with the increased synthetic response by
the chondrocyte is matrix degradation, often proceeding at
a rate exceeding that of synthesis. Proteoglycan and
collagen breakdown is mediated by an increase in matrix
metalloproteinases, serine proteases, lysosomal enzymes
and other proteases at the articular surface early in the
degenerative process and are responsible for the extensive
matrix degradation associated with osteoarthritis.27 In
healthy articular cartilage the activity of the
metalloproteinases is low. Enzyme activity is regulated by
the presence of tissue inhibitors of metalloproteinases
(TIMPs) resulting in a low turnover of extracellular matrix
proteins. During the osteoarthritic disease process the
production of metalloproteinases greatly exceeds the
ability of heightened release of TIMPs to maintain
EFFECTS OF JOINT DISEASE/INJURY
Articular cartilage injuries are characterized by the
degree of involvement of the extracellular matrix
composition and resultant damage to the chondrocytes and
generally fall into three categories.23,24
Microdamage or blunt trauma — Microdamage
may be caused by a single impact or repetitive blunt
trauma and is characterized by a loss of matrix
components, most notably proteoglycans, without
chondrocyte damage. If the traumatic event is short
in duration, the chondrocytes may be able to repair
the cartilage by restoring the lost proteoglycans and
matrix components. Damage resulting from
sustained blunt trauma, however, may eventually
become irreversible.24
Chondral fractures — Chondral fractures result
from a penetrating traumatic event disrupting the
articular surface not effecting the subchondral plate.
The pathophysiological response of articular
cartilage surrounding the injury results in
chondrocyte proliferation and synthesis of
extracellular matrix protein. Unfortunately, since
chondrocytes cannot migrate to the lesion, these
efforts do not result in complete repair.23
Osteochondral fractures — This injury is
considered a full thickness defect and is characterized
by an insult crossing the tidemark into the
13
and lipoxygenase or arachidonic acid (an omega-6 fatty
homeostasis.28 Cytokines such as IL-1 and TNF-α
acid) and eicosapentaenoic acid (an omega-3 fatty acid).33
stimulate chondrocytes to synthesize metalloproteinases
Eicosanoids mediate inflammation, pain and fever, blood
and serine proteases that subsequently further degrade the
pressure, blood clotting, several reproductive functions,
extracellular matrix components.25,26 The cytokines also
and the sleep/ wake cycle.33
serve to suppress protein biosynthesis by the chondrocytes,
NSAIDs and Corticosteroids. Administration of
further depleting the extracellular matrix.29 Both IL-1 as
NSAIDs or corticosteroids is often included in treatment
well as TNF-α can cause substantial loss of matrix molecules,
regimens for patients with traumatic and degenerative joint
presumably by inducing proteolytic degradation.30 The
problems. Both drug therapies are aimed at reducing the
presence of fibronectin fragments and possibly other
production of arachidonic acid metabolites, which are
peptides further enhance catabolic activity and levels of
released as a result of cell membrane damage and cause
cytokines.29 IL-1 also stimulates chondrocytes and synovial
inflammation and pain.34 These drugs act directly to
cells to release arachidonic acid metabolites such as PGE2,
inhibit the enzymes that help produce these eicosanoids
leukotriene B4 and thromboxane. Inflammation of the
(Figure 6).
synovium is present in established osteoarthritis although
the inflammatory response is
Membrane Phospholipids
considerably less than would be
Corticosteroids
NSAIDS
expected in other joint diseases.27
One of the earliest changes
Phospholipase A2
Corticosteroids
seen in an experimental model of
Arachidonic Acid
osteoarthritis was an increase in
hydration (2–3%) in the entire
cartilage of the joint.31 This
Cyclooxygenase
12-Lipoxygenase
5-Lipoxygenase
15-Lipoxygenase
hydration appears to be the result of
the cleavage of type II collagen by
PGG2
15-HPETE
15-HPETE
5-Lipoxygenase
collagenase. The functional collagen
network is disrupted thereby
PGH2
permitting the proteoglycans, the
12-HETE
hydration capacity of which are no
15-HETE
12-HETE
Leukotriene A4
longer restricted by the collagen
TXA2
PGE2
network, to bind increased amounts
Leukotriene C4 Leukotriene B4
of water resulting in the cartilage
PGI2
swelling described in early
osteoarthritis.26-28,32
Figure 6. Effect of corticosteroids and non-steroidal antiinflammatory drugs on the arachidonic acid
Chondrocyte necrosis is
cascade. (Used with permission. Hayek MG, Lepine AJ, Sunvold GD, Reinhart GA. Nutritional
evident as osteoarthritis progresses.
management of joint problems in dogs, in Proceedings. Articular Cartilage and Joint Health. 27th
The synthesis of extracellular matrix
Annual VOS Conference, 2000; 18-23.
ceases while degradative activity
Dietary Fat. Dietary fatty acids can also effectively
remains elevated. The collagen network becomes
manipulate eicosanoid production. A total dietary
increasingly disorganized and disintegrated. The content of
approach alters the substrates presented to the enzymes
several extracellular components including collagen and
which dictate the types of eicosanoids produced. For
proteoglycans are progressively reduced.26 The removal of
instance, feeding omega-3 fatty acids results in the
functional proteoglycans from the extracellular matrix
replacement of arachidonic acid (omega-6) in the cell
results in decreased water content of the cartilage and a
membrane with eicosapentanoic acid.35 The eicosanoids
subsequent loss of biomechanical properties, such as
derived from arachidonic acid (prostaglandin E2,
resilience and elasticity. As a result the chondrocytes are
leukotriene B4, leukotriene C4, and thromboxane A2) are
subjected to increasing mechanical stress and trauma
proinflammatory,36,37 whereas eicosanoids synthesized from
thereby accelerating the osteoarthritic process.26
eicosapentaenoic acid (prostaglandin E3 and leukotriene
B5) are less inflammatory.
NUTRITIONALLY MANAGING THE EFFECTS
It has been reported that feeding dogs a diet that
contains an omega-6 to omega-3 fatty acid ratio between
OF JOINT DISEASE AND INJURY
Eicosanoids. Eicosanoids are local chemical 5:1 and 10:1 results in decreased leukotriene B4 and
increased leukotriene B5 secretion in skin and neutrophils
mediators (leukotrienes, thromboxanes, prostaglandins, and
compared to dogs fed higher fatty acid ratios (25:1, 50:1,
prostacyclins) produced by the actions of cyclooxygenase
14
Glucosamine and chondroitin sulfate have not
produced reports of safety concerns. One study found that
glucosamine and chondroitin sulfate (2 capsules, PO, q 12;
daily dose of 800 mg sodium chondroitin sulfate; 1,000 mg
glucosamine hydrochloride; and 152 mg manganese
ascorbate) administered to 13 clinically normal Beagles for
30 days produced statistically significant but clinically
unimportant changes in hematocrit, hemoglobin, WBC,
segmented neutrophils, and RBC; however, no changes
were seen in the prothrombin time, activated partial
thromboplastin time, or mucosal bleeding time.48
In considering oral supplementation of glucosamine
and chondroitin sulfate for management of joint problems
one must be cognizant of the route of supplementation. If
capsules or pills are utilized owner compliance may be an
issue of concern. Inclusion of these compounds in a total
diet will eliminate any concerns for compliance.
and 100:1).38 Caution should be raised in feeding diets
with very low omega-6 to omega-3 fatty acid ratios since
high consumption of omega-3 fatty acids may result in
problems such as increased bleeding times, delayed wound
healing, and depressed immune responses.39,40
Chondroprotective Agents
Oral chondroprotective agents, including
glucosamine and chondroitin sulfate, may modulate joint
structure and physiology.41
Glucosamine. Glucosamine is a ubiquitous
amino sugar used in the synthesis of the disaccharide units
of GAGs.42 In humans, an oral dose of glucosamine sulfate
is 90% absorbed and 26% bioavailable.43 A recent study
found the bioavailability, pharmacokinetics, and excretion
pattern in the human to be consistent with those of the
dog.44 Chondrocyte studies in vitro found that
glucosamine has a stimulatory effect causing increased
production of normal collagen and proteoglycans.41 Using
rat models of subacute inflammation and subacute
mechanical arthritis, oral glucosamine was found to be
50–300 times less potent than indomethacin but its
chronic toxicity is 1,000–4,000 times less than
indomethacin which suggests a therapeutic margin 10–30
times more favorable for using glucosamine in prolonged
oral treatments.45
Chondroitin sulfate. Chondroitin sulfate is a
GAG which can be sulfated on the fourth or sixth
carbon.41 Chondroitin-4-sulfate is the predominant GAG
in growing mammalian hyaline cartilage but, with age,
production of chondroitin-4-sulfate decreases and the
production of other types of GAGs is increased by
chondrocytes.41 Two chondroprotective activities
produced by chondroitin sulfate but not by glucosamine
are prevention of thrombi formation in microvasculature
and inhibition of metalloproteases via the modulation of
interleukin-3.41 A recent study in humans with mono- or
bilateral-knee osteoarthritis found that both chondroitin
sulfate-dosing regimen (40 people received a single daily
dose of 1,200 mg of chondroitin sulfate in an oral gel and
43 received 400 mg capsules TID) produced improvement
of the subjective symptoms and improved mobility.46
Chondroitin sulfate and glucosamine. In a
recent study,47 13 Beagles (age < 1 year, weight 4.2–5.1 kg)
received 2 capsules of glucosamine, chondroitin sulfate,
and ascorbate orally twice daily for 30 days (daily dose of
800 mg sodium chondroitin sulfate, 1,000 mg glucosamine
hydrochloride, and 152 mg manganese ascorbate). Serum
GAGs (12 dogs) were elevated by 37% with no change in
circulating hexosamine (3 dogs). Calf cartilage segments
were incubated in serum collected (9 dogs) before and
after treatment. Biosynthetic activity increased 50% and
proteolytic degradation decreased 59%.
CONCLUSION
The structure/function relationship of articular
cartilage is clearly demonstrated in the structural
modifications observed during growth and development of
the joint in response to the increasing forces naturally
applied during this period. It is also clear that traumatic
injury or disease can substantially disrupt the normal
architecture of the joint by altering the concentrations of
glycosaminoglycans, proteoglycans, collagens, and
associated structures within the cartilage. Failure to correct
such damage can allow for the progression to advanced joint
disease from which complete reversal may not be possible.
An overall regimen for treatment of primary and
secondary joint diseases should include weight
management (discussed elswhere in these proceedings),
exercise modification, and administration of nonsteroidal
antiinflammatory drugs (NSAIDs), glucocorticoids, or
polysulfated glycosaminoglycans (GAGs).49 Several of
these treatments either directly require or may be
influenced by nutritional management. The provision of
nutritional compounds that decrease cartilage degradation,
increase matrix synthesis, provide matrix precursors, or
assist in the control of the inflammatory response must be a
primary directive in the control and management of joint
health of the companion animal.
15
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19. Savarese JJ, Erickson H, Scully SP. Articular chondrocyte TenascinC production and assembly into de novo extracellular matrix. J
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16
45. Setnikar I, Pacini MA, Revel L. Antiarthritic effects of glucosamine
sulfate studied in animal models. Drug Res 1991; 41:542-545.
46. Bourgeois P, Chales G, Dehais J, Delcambre B, Kuntz J-L, Rozenberg
S. Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs
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biochemical effects in dogs receiving an oral chondroprotective
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27:46-48.
17
important cause of lameness in dogs of all ages,7 we
selected naturally-occurring cases of obese dogs with hip
osteoarthritis to evaluate the hypothesis that lameness
severity would be significantly influenced by weight loss.
A RECENT STUDY: INFLUENCE OF WEIGHT
MANAGEMENT ON JOINT HEALTH 8
The Benefit
of Weight
Management
in Dogs with
Joint Problems
The influence of weight reduction on pelvic limb
function was prospectively examined in 9 overweight
client-owned dogs with hip osteoarthritis and lameness.
Dogs studied were at least 10% over their ideal body
weight. Dogs were screened using a serum chemistry panel
with thyroid screen and complete blood count to rule out
concurrent systemic disease. A numerical rating scale
(NRS; Figure 1) and a visual analog scale (VAS; Figure
2) were used to subjectively assess lameness (by JI) prior to
the dogs beginning a weight loss program. The weight loss
program included Eukanuba Veterinary Diets® Nutritional
Weight Loss Formula™ Restricted-Calorie™/Canine fed at
60% of maintenance calories for initial body weight.
Lameness assessment was repeated at the mid-point
and end of the 10- to 19-week weight loss period. The
effect of time on lameness and body condition were
evaluated using repeated-measures analysis-of-variance and
the Friedman test. Differences were considered significant
at P<.05. Over the weight loss period, dogs lost between 11
and 18% of their initial body weight. Body weight decreased
linearly over time (P<.001) and body condition score
improved (P<.05). Numerical rating lameness scores
improved significantly with time (P<.05) and there was
also a linear improvement in VAS scores with time
(P<.005). Visual analog scale assessment scores for
lameness improved 76% over the study period. No dog was
withdrawn from the study because of worsening lameness.
Mark A. Tetrick, DVM, PhD
Research and Development Division
The Iams Company, Lewisburg, Ohio
Joseph A. Impellizeri, DVM
University of Illinois Cancer Care Center
University of Illinois School of Veterinary Medicine,
Urbana, Illinois
Peter Muir, BVSc, MVetClinStud, PhD,
MACVSc, DACVS, DECVS
School of Veterinary Medicine,
Department of Surgical Sciences
University of Wisconsin-Madison, Madison, Wisconsin
Hind Limb Lameness Score
Score
0
1
2
3
4
5
INTRODUCTION
Obesity is recognized as an important factor
influencing the clinical expression of osteoarthritis in
humans.1-3 The incidence of obesity in the canine
population has been estimated to be on the order of 25%
and likely affects at least this proportion of dogs with
osteoarthrtis.4-6 While veterinarians have used nutritional
therapy to achieve weight reduction in overweight
osteoarthritic dogs, no data describing the effect of weight
loss on lameness severity or the effect of weight loss on the
prevalence or progression of osteoarthritis in dogs has been
described. Because osteoarthritis of the hip joint is an
Criteria
Clinically sound
Barely detectable lameness
Mild lameness
Moderate lameness
Severe lameness (carries limb when trotting)
Could not be more lame
Figure 1. Numerical rating scale (NRS).
Clinically
sound
Could not be
more lame
Figure 2. Visual analog scale (VAS) score using a 100 mm
horizontal line. This method is considered to be a more sensitive
assessment method.
18
Data from this study support the hypothesis that
lameness severity can be significantly influenced by weight
loss (Figure 3). Weight loss alone can result in a
significant decrease in lameness. Increased emphasis
should be placed on normalizing body weight in dogs with
hip osteoarthritis. Although not examined in this study,
normalization of the body weight of the osteoarthritic
patient also has the potential to slow disease progression.
120
a
b
100
80
such as diabetes, hyperthyroidism or hypothyroidism,
hyperadrenocorticism, and heart disease.
Weight Assessment. Next evaluate the patient’s
weight. Comparing the dog’s weight to breed standards
where appropriate can be a first step to evaluating the
degree of obesity. Given the wide ranges within breeds and
the popularity of mixed breed dogs, assigning a Body
Condition Score (BCS) may be a more practical approach
to determining level of obesity. Determining a BCS requires
a visual and tactile evaluation of the ribs, spine, pelvis,
waist, and abdomen (Figure 4). If you don’t put your hands
on the dog you have not completed an accurate BCS!
c
a
Body Weight (lb)
60
40
b
Thin Dog
Ribs, lumbar vertebrae, and
pelvic bones easily visible
No palpable fat
Obvious waist and abdominal tuck
Prominent pelvic bones
VAS Score (Trotting)
20
c
0
Baseline
Midpoint
Final
Values between time points with different superscripts
are significantly different P<.05
Underweight Dog
Ribs easily palpable
Minimal fat covering
Waist easily noted when viewed
from above
Abdominal tuck evident
Figure 3. Body weight and visual analog scale ratings of lameness
during weight loss for lame, overweight dogs.
Current medical treatments for the management of
dogs with osteoarthritis are primarily symptomatic. Longer
treatment courses using nonsteroidal antiinflammatory
drugs should not be given without using a concurrent
nutritional program to normalize the dog’s body weight.
Many overweight dogs with lameness due to hip osteoarthritis may not require drug treatment after excess weight
has been lost.
Ideal Dog
Ribs palpable, but not visible
Waist observed behind ribs when
viewed from above
Abdomen tucked up when viewed
from the side
Overweight Dog
Ribs palpable, with slight excess
of fat covering
Waist discernable when viewed
from above, but not prominent
Abdominal tuck apparent
ACHIEVING WEIGHT LOSS
Weight loss in dogs can some-times be difficult to
achieve. As in this study it is advisable to thoroughly
evaluate the patient before beginning an obesity
management program.
Diet History. Start with a dietary history to
determine the types and quantities of food fed. Include
feeding patterns such as the times fed per day and who
feeds the pet. Also evaluate the activity level and overall
lifestyle of the pet. You may need to continue to probe to
get a complete picture of the situation — does anyone else
(a neighbor?) feed or treat the dog? A physical exam,
including a serum chemistry panel with thyroid screen and
urine tests, is important to rule out medical conditions
Obese Dog
Ribs not easily palpable
under a heavy fat covering
Fat deposits over lumbar area
and tail base
Waist barely visible to absent
No abdominal tuck; may exhibit
obvious abdominal distention.
Figure 4.
19
Owner Involvement. One of the most important
factors in achieving successful weight loss (including the
weight loss in this study) is to involve the owner. The
owner must want the pet to lose weight. Recognition of
the dog’s obesity is a big step in enlisting the owner’s
commitment to weight loss. Demonstrate to the owner
using visual cues or palpation that the dog is overweight.
Ensure that the client understands the health risks
associated with obesity.
For the purposes of this study specific weight loss
goals, timelines, and periodic weigh-ins were established
and agreed to from the beginning. The same holds for any
successful weight loss program. Setting short- and longterm weight-loss goals with target dates for the owner
allows for interim goals with positive reinforcement. These
weigh-ins can be every 1–2 weeks at first to ensure the
program gets off to a good start and can be less frequent as
the program progresses.
Diet. Determine the daily caloric allotment that
will achieve the targeted degree of weight loss and ultimate
BCS. Be sure the client understands that this allotment
may change during the program, depending on the amount
of exercise and/or metabolic adaptations that occur. Make
the client responsible for restricting the food appropriately.
Encourage them to measure and record all food given.
Involve everyone in the household who provides treats or
food for the dog.
Exercise. Although an exercise regime was not
included as part of this study, exercise can play an
important role in weight loss. Varying degrees of exercise
can be prescribed, depending on the health of the client
and the patient. Goals can be set for increasing duration
and intensity of exercise, but keep it reasonable. Exercise is
just one additional facet of the entire weight loss program.
Client Support. Provide support and positive
reinforcement. Celebrate success. For the purposes of this
study, rewards (such as a leash) for reaching certain study
weight loss milestones were provided. Rewards need not be
expensive. Inexpensive but meaningful rewards such as a
certificate documenting the target weight loss and progress
toward that goal serves both as a reminder and a reward.
nutrition. Carbohydrate contains less than half the calories
of fat, which allows clients to feed an amount of food they
perceive as adequate while reducing calories consumed by
the pet. Reduced quantities of fat necessitate attention to
the type and quality of the dietary fat. Ensuring that the
ratio of omega-6:omega-3 fatty acids is between 5:1 and 10:1
will help promote healthy skin and coat during weight loss.
Likewise, it is important to carefully select the starch
sources used to replace fat in the diet. The carbohydrate
component of pet foods provides the primary source of the
increase in blood glucose after a meal. Starch sources
behave very differently in the way that they influence
blood glucose and insulin responses. Grain sorghum and
barley are utilized as starch sources in the Restricted
Calorie diet. This
results in lower
Specially formulated foods
postprandial blood
glucose levels and
containing a blend of barley
lower blood insulin
and grain sorghum may help
levels than if other
improve glucose intolerance
starch sources such
and stabilize blood glucose
as wheat or rice are
used as the source
levels in overweight pets.
of starch. 9 By
minimizing post
prandial increases in blood glucose and insulin, specially
formulated foods containing a blend of barley and grain
sorghum may help improve glucose intolerance and
stabilize blood glucose levels in overweight pets.
Caloric density of the diet may also be reduced by
the addition of fiber to the diet. The Restricted-Calorie
diet contains normal levels of moderately fermentable fiber
instead of high levels of nonfermentable fiber such as
cellulose. Increased nonfermentable fiber levels can result
in increased stool volume, poor skin and coat quality, and
ultimately result in poor client compliance.
ENHANCING WEIGHT LOSS
Other dietary approaches, beyond feeding a low-fat,
low-calorie diet to assist with canine weight management
is to affect the way nutrients are metabolized to help
promote weight loss and improve body composition.
Chromium can help optimize body composition during
weight loss. Dogs fed diets containing supplemental
chromium (as chromium tripicolinate) had greater loss of
fat mass compared with that from feeding a diet
supplemented with carnitine only (data on file; The Iams
Company). In addition to its role in improving body
composition during weight loss, dogs fed diets
supplemented with chromium tripicolinate had improved
glucose tolerance and an increased rate of glucose removal
from the bloodstream after intravenous glucose infusion.10
By enhancing tissue use of glucose, diets containing
DIETARY CONSIDERATIONS
The major contributing factor to obesity is excess
caloric intake in relation to the dog’s caloric requirements.6
In this study Eukanuba Veterinary Diets ® Nutritional
Weight Loss Formula™ Restricted-Calorie™/ Canine
(Restricted-Calorie) was fed at 60% of maintenance
calories for initial body weight. Several features of this diet
help to acceptably reduce caloric intake.
By replacing some dietary fat with carbohydrate
instead of fiber, the caloric density of the RestrictedCalorie diet is reduced while maintaining a high level of
20
chromium tripicolinate may lead to an overall
improvement in glucose tolerance and blood glucose
stability in overweight pets.
Another dietary component that can affect nutrient
metabolism is carnitine. Carnitine is a water-soluble,
vitamin-like compound made in the body from the amino
acids lysine and methionine. It is naturally present in
animal-based protein ingredients. By forming acylcarnitines, carnitine “escorts” fatty acids into the cells’
mitochondria for oxidation and energy production. In this
way, carnitine helps reduce body fat storage and blood lipid
levels. When added to a canine weight-loss diet, carnitine
resulted in a tendency for lower fat mass and greater lean
body mass, even with greater energy intake11 (Figure 5).
7%
Diet Without Carnitine
6%
Diet With Carnitine
REFERENCES
1. Felson DT, Chaisson CE. Understanding the relationship between
body weight and osteoarthritis. Ballieres Clin Rheumatol 1997;
11:671-681.
2. Cooper C, Inskip H, Croft P, Campbell L, Smith G, McLaren M,
Coggon D. Individual risk factors for hip osteoarthritis: obesity, hip
injury and physical activity. Am J Epidemiol 1998; 147:516-522.
3. Oliveria SA, Felson DT, Cirillo PA, Reed JI, Walker AM. Body
weight, body mass index and incident symptomatic osteoarthritis of
the hand, hip and knee. Epidemiology 1999; 10:161-166.
4. Mason E. Obesity in pet dogs. Vet Rec 1970; 86:612-616.
5. Edney AT, Smith PM. Study of obesity in dogs visiting veterinary
practices in the United Kingdom. Vet Rec 1986; 118:391-396.
6. Sloth C. Practical management of obesity in dogs and cats. J Small
Anim Prac 1992; 33:178-182.
7. Kealy RD, Lawler DF, Ballam JM, Lust G, Smith GK, Biery DN,
Olsson SE. Five-year longitudinal study on limited food consumption
and development of osteoarthritis in coxofemoral joints of dogs. J Am
Vet Med Assoc 1997; 210:222-225.
8. Impellizeri JA, Tetrick MA, Muir P. Effect of weight reduction on
clinical signs of lameness in dogs with hip osteoarthritis. JAVMA
2000; 216:1089-1091.
9. Sunvold GD, Bouchard GF. The glycemic response to dietary starch.
In: Reinhart GA, Carey DP, eds. Recent Advances in Canine and Feline
Nutrition, Vol II: 1998 Iams Nutrition Symposium Proceedings.
Wilmington, OH: Orange Frazer Press, 1998; 123-131.
10. Spears JW, Brown TT Jr, Sunvold GD, Hayek MG. Influence of
chromium on glucose metabolism and insulin sensitivity. In:
Reinhart GA, Carey DP, eds. Recent Advances in Canine and Feline
Nutrition, Vol II: 1998 Iams Nutrition Symposium Proceedings.
Wilmington, OH: Orange Frazer Press, 1998; 103-112.
11. Sunvold GD, Vickers RJ, Kelley R, Tetrick MA, Davenport GM,
Bouchard GF. Effect of dietary carnitine during energy restriction in
the canine. FASEB J 1999; 13:A268.
12. Sunvold GD, Tetrick MA, Davenport GM, Bouchard GF. Carnitine
supplementation promotes weight loss and decreased adiposity in the
canine, in Proceedings. World Small Anim Vet Assoc 1998; 746.
5%
4%
3%
2%
1%
0%
% Weight Loss
After 7 Weeks
% Body Fat Loss
After 7 Weeks
Figure 5. Greater weight and body fat loss in dogs with carnitine,
even with ad libitum feeding.12
CONCLUSION
Achieving weight loss in overweight dogs can be
challenging. However, successful weight loss can be
achieved by engaging the owner, agreeing to achievable
weight loss milestones with positive feedback, and by using
diets with dietary features that can help achieve the desired
weight loss. Additional motivation for successful weight
loss can also be derived from the observable improvement
in lameness as lame overweight dogs lose weight.
Eukanuba Veterinary Diets is a registered trademark of The Iams Company.
Nutritional Weight Loss Formula and Restricted-Calorie are trademarks of
The Iams Company.
21
EXERCISE AND OSTEOARTHRITIS
Although the exact relationship between exercise
and OA is uncertain, several factors have been identified
in people, and most of these likely apply to animals.6,7 It is
generally believed that mild to moderate exercise and
training in normal humans and dogs do not cause OA by
themselves, but biochemical, histologic, and biomechanical changes do occur in articular cartilage. Cartilage of
dogs regularly subjected to high levels of stress shows a
higher proteoglycan (PG) content and is stiffer than
cartilage exposed to low stress levels. Most studies of
running exercise have indicated that this activity produces
no injury to articular cartilage, assuming that there are no
abnormal biomechanical stresses acting on the joints.
Running exercise of 4 km/day for 15 weeks in young Beagle
dogs caused a 6% increase in stiffness of cartilage of the
stifle joint.8 Thickness of the cartilage also increased so it
is likely that moderate exercise has an anabolic effect on
the physiological properties of cartilage, and may diminish
the chance of developing OA. Using the same model,
running exercise of 20 km/day for 15 weeks did not further
improve the mechanical properties of articular cartilage.
Another study evaluated whether an increased level
of low-impact lifelong weight-bearing exercise causes
degeneration of articular cartilage by exercising dogs on a
treadmill at 3 kilometers per hour for 75 minutes,
5 days/week for 527 weeks while wearing jackets weighing
130% of their body weight.9 Ten control dogs were allowed
unrestricted activity in cages for 550 weeks. No joints had
ligament or meniscal injuries, cartilage erosions, or
osteophytes. Furthermore, tibial articular cartilage thickness and mechanical properties did not differ between the
two groups. These results suggest that a lifetime of regular
low-impact exercise in dogs with normal joints does not
cause alterations in articular cartilage.
Heavy training programs may result in changes
which predispose to the development of OA. In one study,
dogs underwent a gradually increasing treadmill exercise
regimen of up to 40 km/day, while control dogs lived
normally in their cages.10 The articular cartilage response
to training was site dependent. After the year-long exercise
period, stiffness of the cartilage decreased by 12-14 percent
in the lateral, but not in the medial condyles of the femur
and tibia. Similar changes were seen in glycosaminoglycan
content of the superficial zone of cartilage, confirming the
role that PGs have in modulated cartilage stiffness.
Although there was no overt cartilage damage, the
softening of the cartilage may jeopardize the ability of the
cartilage to maintain its normal structural and functional
properties over time. In another study, strenuous running
of old dogs at 6-8 mph with 20 degrees uphill inclination
for 1 hour per day, 6 days/week for 8 months, led to
accelerated matrix degradation in the femoral head.
Proteoglycan content decreased and there was irreversible
Physical Therapy
for Dogs with
Joint Disease
Department of Small Animal Clinical Sciences
College of Veterinary Medicine
University of Tennessee, Knoxville, Tennessee
INTRODUCTION
Joint disease is a common problem in dogs. Patients
with osteoarthritis (OA) have restricted activity, limited
ability to perform, pain and discomfort, and decreased
quality of life.1-3 As animals reduce their activity level, a
vicious cycle of decreased flexibility, joint stiffness, and loss
of strength occurs. Traditional management of dogs with
OA has included weight loss, antiinflammatory and
analgesic drugs, changes in lifestyle and exercise habits
(usually restricted), and surgical management.
Advances in the management of human OA by
physical modalities have reduced the severity of symptoms
and reliance on medications to control pain and
discomfort.4,5 Some of the benefits include increasing
muscle strength and endurance, increasing joint range of
motion (ROM), decreasing edema, decreasing muscle
spasm and pain, and improving performance, speed, quality
of movement, and function.
22
destruction of collagen fibrils. Older dogs may be more
vulnerable to mechanical stress changes than younger
animals. Therefore, although mild to moderate training
protocols have an anabolic effect on cartilage, rather
severe training protocols may result in detrimental
alterations in cartilage.
Certain activities are associated with OA of
particular joints, presumably because of the chronic
impacts on joints which may not be biomechanically
sound or are placed under abnormal loads. For example,
Huskies tend to have more OA of the hips and shoulders
associated with pulling sleds. Young dogs with coxofemoral
joint laxity develop OA over time if corrective surgery,
such as triple pelvic osteotomy, is not performed to
improve joint biomechanics. Pathologic motion in a joint,
such as cranial drawer as a result of a ruptured cranial
cruciate ligament, results in progressive OA changes.
Human runners with abnormal joint conformation appear
to be predisposed to OA, while humans with normal joint
conformation do not.11,12
Although initiating an improper exercise program in
a patient with abnormal joints may hasten the progression
of OA, a well-designed training program increases muscle
strength and tone, which may help stabilize joints, and
possibly decrease abnormal stresses on joints. Human
patients with knee OA in a supervised walking program
walk farther in a period of time, have decreased pain, and
use medication less frequently to control pain.13 Patients
that exercise have improved strength, ROM, function, and
decreased need for medication.14
possible. Antiinflammatory medications are also prescribed
as needed for comfort. Body composition is documented to
establish the percent body fat. That, combined with the
weight of the animal, gives the veterinarian and the owner
a target to reduce a specific amount of body fat. In general,
our goal is to reduce fat composition to 20–25% of body
weight. In many cases, the owners feel that the dog is
doing well enough clinically after weight loss and the
initiation of an exercise program that they no longer wish
to pursue surgery.
THERAPEUTIC EXERCISE
The goals of therapeutic exercise should be to
reduce body weight, increase joint mobility, and reduce
joint pain through the use of low-impact weight-bearing
exercises designed to strengthen supporting muscles.19
Muscle disuse results in atrophy and weakness. Muscles
also act as shock absorbers and strengthening of periarticular muscles may help protect joints. Mild weight-bearing
exercise also helps stimulate cartilage metabolism and
increases nutrient diffusion. Exercise may also increase
endogenous opiate production and relieve OA pain.
Exercise should only be performed after correction of
major risk factors, such as joint instability or obesity.
Exercising a dog with an unstable cranial cruciate ligament
speeds the development of OA. An initial exercise
program should consist of several short periods interspersed
with rest periods throughout the day. The exercise periods
should be evenly spaced throughout the day. Regular
intermittent cartilage loading may increase cartilage
metabolism and glycosaminoglycan synthesis as compared
to constant loading or very slow loading. It is best to have
regular exercise periods throughout the week, rather than
compacting all of the weekly activity into a weekend.
Increased levels of exercise should occur gradually and
progressively.
The ideal exercise program is one which provides
sufficient benefits without causing discomfort. If joint pain
is greater after exercise than prior to exercise, the length of
activity should be decreased by half. It is important to
differentiate joint pain from muscle soreness. Some
muscular discomfort may be expected early in exercise
programs. The level of exercise must be prescribed for each
individual based on the severity of OA, response to concurrent therapy, the patient’s pain tolerance, and the owner.
Ideally, antiinflammatory drugs should not initially
be administered prior to exercise because it is important to
determine if the level of exercise is too great and causes
joint pain following a training period. After titrating the
appropriate level of exercise so that pain is not worsened
with exercise, oral antiinflammatory drugs should be
administered about 1 hour prior to exercise. Treatment
with an antiinflammatory drug allows a small increase in
THE ROLE OF OBESITY IN OSTEOARTHRITIS
Obesity is strongly associated with the development
of OA in people and its management is important in the
treatment of OA.15 Heavy people are 3.5 times more likely
to develop OA than light people, and loss of 5 kg decreases
the odds of developing OA by over 50%.16 This may have
implications on the initiation of exercise programs for
obese animals with OA. Overloading joints should be
minimized by performing activities such as walking and
swimming until weight loss occurs. In man, weight loss
results in less joint pain and a decreased need for
medication to treat OA. After weight loss, 90% of people
in one study had complete relief of pain in one or more
joints.17 A similar report exists in veterinary medicine, in
which overweight dogs with hip dysplasia underwent
weight reduction.18 Losses of 11–18% of body weight
resulted in significant improvements in body condition
scores and the severity of hind limb lameness. Currently, I
do not perform total hip replacements in obese patients
with hip dysplasia. Rather, these patients are placed on a
weight loss program combined with a low-impact exercise
program of walking, jogging (if tolerated), and swimming if
23
stopping. In prescribing the activity, owner compliance
must be considered, and an exercise prescription should
accommodate the owner’s schedule and benefit the animal.
Light jogging on grass may be added as the dog tolerates
increased activity. For additional muscle strengthening,
1–2 pound strap-on weights may be fastened to the lower
limbs (Figure 2). A backpack with weights may also
be used. Walking up and
down inclines or stairs are
good low-impact activities
that are easily incorporated
into a walking program and
improve muscle strength
and cardiovascular fitness. If
strengthening the pelvic
limb muscles is desired in
dogs with hip dysplasia,
repeated rising from a sitting
position may be beneficial.
Some assistance may initially be required in the
Figure 2. Strap-on weights can
form of sling support. Highbe fastened to the limbs to aid in
impact exercises should be
muscle strengthening.
avoided.
If facilities and climate allow, swimming is one of
the best activities for dogs. The buoyancy of water is
significant and limits impact on joint surfaces, while
promoting muscle strength and tone, joint motion, and
cardiovascular fitness. Clean lakes or pools may be used.
Self-contained tubs with whirlpool action are also
available. Careful patient monitoring and assistance are
important to prevent excessive thrashing. Fear of water
must be addressed to avoid injury. Initially, dogs may swim
for 1–3 minutes once daily, for 3 to 7 days per week. As
strength and stamina improve, dogs may swim 5–10
minutes per session. When done carefully, swimming is an
effective, functional exercise.
We have been using an underwater treadmill for
dogs with OA and have been impressed with the results
(Figure 3). In general, a 2-week training period in the
activity and stress to the tissues to gradually increase
function. As training events are stepped up over time,
antiinflammatory agents are withheld to allow a true
evaluation of the patient without the aid of medication.
The goal is to reach the desired level of function and
maintain that level without the aid of long-term
antiinflammatory drugs. Early in the training program,
however, antiinflammatory drugs may help address minor
muscle and joint soreness as tissues adapt to the new
stresses placed upon them.
Type of Exercise
Exercise programs must be tailored to account for
the typical course of exacerbations and remissions of OA.
The animal should not be forced to exercise during times
of aggravation. Vigorous exercise may increase
inflammation. During pain-free times, low-impact
exercises are beneficial to maintain muscle strength, joint
mobility and function. Stretching of affected muscle groups
and joints during a warmup period is recommended.20,21
Application of superficial heat may relax tissues and the
dog and allow more effective stretching of muscles,
tendons, ligaments, and joint capsules.
Common activities include controlled activity on
leash, treadmill walking (Figure 1), swimming, going up
and down stairs or ramped inclines, and holding either the
front or rear half of the dog up and encouraging the other
half to exercise.3,22 Long leash walks provide good low
impact, aerobic forms of exercise. The length of walks
should be titrated so there is no increased pain after
activity. Also, it is better in the early phases of training to
provide three 20-minute walks than one 60-minute walk.
The walks should be brisk and purposeful, minimizing
Figure 1. A variable speed ground treadmill is useful to provide
a consistent pace and footing for exercising dogs.
Figure 3. An underwater treadmill is useful to exercise dogs
with joint osteoarthritis.
24
underwater treadmill may increase peak weight-bearing
forces by 5–15%, which is similar to that typically achieved
with medication. We have performed force plate analysis of
gait and documented a 10% increase in weight-bearing
immediately following exercise, which carries over for a
period of time. The length of the workout, speed of the
treadmill, and the height of the water may be adjusted as
training progresses (Figure 4). Even dogs which fear water
generally perform well in this unit because the water rises
around the dog, rather than lowering the dog into the water.
Following exercise, a 10-minute warmdown period is
necessary to allow muscles to cool down. The first 5
minutes may be spent walking at a slower pace after a brisk
walk or swimming. Range of motion exercises may be
repeated for the next 5 minutes. Finally, ice may be applied
to painful areas for 15–20 minutes to control post-exercise
inflammation. Massage is commonly used to decrease pain,
swelling, and muscle spasm.
Figure 5. Commercially available cold packs can be kept
cold until needed and then inserted into a cloth covering
which is then strapped on to the affected area.
including less stiffness and pain, and improved joint ROM,
although some discomfort is initially associated with
application of cold.
Massage
PHYSICAL AGENTS
Massage is the systematic and scientific manipulation
of soft tissues.25 The different types of massage include
effleurage, vigorous cross-fiber friction over muscles or
ligaments to break up adhesions, Swedish massage, deep
tissue massage, neuromuscular massage, accupressure,
myofascial release, and reflexology.
The beneficial effects of massage include relaxation
of soft tissues, decreased muscle spasm and trigger points,
increased muscle flexibility, improved venous and
lymphatic flow with reduction of edema, and increased
local blood flow to an area. Massage has been used to
increase blood flow to muscles to “warm up” the area
before activity, and to decrease stiffness after activity.
Superficial heat modalities
Ultrasound
Superficial heating agents typically heat the skin
and subcutaneous tissues to a depth of 1–2 cm.23,24 The
tissue is usually heated to 40–45˚ C for 15 to 20 minutes.
Superficial heating agents include hot packs (moist and
dry), circulating warm water heating blankets, and warm
baths. Heat increases blood flow to the area, promotes
tissue extensibility, decreases pain, muscle spasm and joint
stiffness, and causes general relaxation. Heat is contraindicated if swelling or edema are present.
Ultrasound (US) has been used to treat OA,
rheumatoid arthritis, and bursitis (Figure 6).1,2 The most
38%
85%
91%
Figure 4. The buoyancy effect of water depends on the water level.
Raising the water level decreases the weight that distal joints experience.
Cryotherapy
The application of cold decreases blood flow,
inflammation, hemorrhage, and metabolic rate.23,24
Commercially available cold packs or ice wrapped in a
towel may be applied to an area for 15 to 20 minutes, 3 to
6 times daily (Figure 5). An entire limb or limbs may be
immersed in a cold water or water and ice bath to decrease
inflammation. Most studies of cryotherapy treatment for
OA indicate that patients experience positive benefits,
Figure 6. Therapeutic ultrasound is applied to the affected area.
25
THE ROLE OF THE ENVIRONMENT IN
THE MANAGEMENT OF OSTEOARTHRITIS
common frequencies are 1 and 3 MHz. Most US units have
continuous and pulsed modes. Ultrasound has thermal and
non-thermal effects. These effects are related to the
treatment time, intensity, frequency, and the area being
treated. Thermal effects include decreased pain, and
increased blood flow, metabolic rate, and tissue
extensibility. Non-thermal effects include increased cell
membrane permeability, calcium transport across cell
membranes, nutrient exchange, and phagocytic activity of
macrophages.
Ultrasound is capable of heating tissues deeper than
superficial heating agents, heating tissues 5 cm deep to
40–45˚ C, without overheating the superficial tissues.
Generally, 10 minutes of US application to a small area
adequately increases tissue temperature. Because the tissue
temperature increase is short-lived, stretching of joints and
tissues should be performed during the latter half of
treatment or immediately after. The indications,
contraindications, and physiological effects must be
thoroughly understood.
Animals with severe OA require modifications in
their habitat. The principles of environmental modification
for dogs are similar to those of people. Whenever possible,
animals should be moved from a cold, damp outdoor
environment to a warm, dry inside environment. A soft,
well-padded bed or waterbed should be provided. A
circulating warm-water blanket under the blankets provides
heat which may reduce morning stiffness.
The playful activities of other pets may be a source
of irritation to dogs with moderate to severe OA. Affected
animals may attempt to keep up, and in the process,
become more lame and painful. In some instances,
however, play with other animals stimulates activity and
provides a welcome break in the exercise routine.
Severely affected patients may no longer be able to
negotiate stairs. Changes may be necessary to minimize
stair climbing. Steps are negotiated easier if they are wider
and spaced farther apart. A ramp may be used instead of
steps. In climates with ice and snow, walks should be
shoveled and ice cleared to minimize the risk of falling.
Neuromuscular Electrical Stimulation
A wide variety of neuromuscular electrical stimulators (NMES) are available (Figure 7). Neuromuscular
electrical stimulators provide benefits, including increasing
muscle strength and joint ROM, decreasing edema and
pain, and helping to improve
function.26-28 Pulsed AC
units are the most useful for
increasing muscle strength
and joint ROM, and
decreasing edema and pain.
The commonly used TENS
(transcutaneous electrical
nerve stimulation) refers
only to a particular type of
electrical stimulator that is
applied for pain control, but
is not used for muscle
strengthening or other
Figure 7. A neuromuscular
applications.
electrical stimulation unit is used
In general, neuromusto elicit muscle contractions.
cular electrical stimulation
appears to relieve pain in
human patients with OA as long as the treatment is
continued. Its role in pain relief of OA in animals is
unknown, but it appears to attenuate muscle atrophy
following some surgical procedures.
SUMMARY
Physical rehabilitation is a valuable, but underused
part of the management of dogs with OA. The
veterinarian, physical therapist, veterinary technician, and
owner are vital to determine and carry out an appropriate
therapeutic regimen. A variety of physical rehabilitation
techniques are available to supplement and enhance other
treatments for OA. To maintain enthusiasm for the
program and to help with decision-making for further
treatment, progress should be documented.
26
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Energizing Methods. East Norwalk, CT: Appleton and Lange, 1988.
26. Johnson JM, Johnson AL, Pijanowski GJ, Kneller SK, Schaeffer DJ,
Smith CW, Swan KS. Rehabilitation of dogs with surgically treated
cranial cruciate ligament-deficient stifles by use of electrical
stimulation of muscles. Am J Vet Res 1997; 58:1473-1478.
27. Caggiano E, Emrey T, Shirley S. Effects of electrical stimulation or
voluntary contraction for strengthening the quadriceps femoris
muscles in an aged male population. J Orthop Sports Phys Ther 1994;
20:22-28.
28. Morrissey MC, Brewster CE, Shields-CL J. The effects of electrical
stimulation on the quadriceps during postoperative knee
immobilization. Am J Sports Med. 1985; 13:40-45.
27
disk protrusion or extrusion is the most common cause.1 In
this presentation, pathophysiological changes of IV disk
degeneration are reviewed along with radiographic
abnormalities. In this discussion, an aging model is used.
Furthermore, a type III IV disk degeneration pattern is
introduced and fully discussed with differential diagnoses
in aged dogs.
Pathophysiology
and Diagnosis
of Intervertebral
Disk
Degeneration
ANATOMY AND PHYSIOLOGY
Intervertebral disks have two distinctive
components: anulus fibrosus and nucleus pulposus. The
anulus fibrosus is in the outer layer, encasing the gelatinous
nucleus pulposus (Figure 1). Although anulus fibrosus
implies a circular structure, it is not a concentric ring-like
structure. The dorsal aspect is thin and incomplete. Thus,
nucleus pulposus is located in a dorsal location. The anulus
fibrosus and nucleus pulposus work together to act as a
shock absorber. The anulus fibrosus can stretch to evenly
distribute a force due to their alignment of collagen fibers
or fibrous tissues.8 The nucleus pulposus contains
proteoglycans that can hold high water contents. The
results of biochemical analysis of the anulus fibrosus and
nucleus pulposus show their similarity to articular cartilage.
As seen in the articular cartilage, IV disks lose their
proteoglycans with aging or degeneration.9-12 This is most
likely caused by altered metabolic function of
chondrocytes. However, compared to articular cartilage,
information regarding metabolic function of chondrocytes
is limited in canine IV disk research.
Takayoshi Miyabayashi, BVS, MS,
PhD, Diplomate ACVR
Department of Small Animal Clinical Sciences
University of Florida, Gainesville, Florida, USA
INTRODUCTION
Intervertebral (IV) disk disease is a common neurological disease that causes pain and motor dysfunction.
Results of complete clinical history and thorough physical
examination facilitate neuroanatomical localization of a
lesion. In addition, results of neurological examinations
further localize the lesion.1 Then, imaging examinations
are in order to confirm the neuroanatomical location of
the lesion, not only longitudinal (for example, at C6-7)
but also transverse (for example, extradural, intradural and
extramedullary, intramedullary) location. Plain radiography,
myelography, computed tomography, and magnetic
resonance imaging have been used to accomplish this.2-6
Additional examination such as cerebraspinal fluid analysis
assists ruling in and out of certain differential diseases such
as neoplasia and infection (for example, meningitis).7
Among many different causes of spinal cord
dysfunction, extradural spinal cord compression due to IV
Figure 1. Normal lumbar intervertebral disk. Transverse and
sagittal views. Concentric rings of anulus fibrosus are evident.
The inner nucleus pulposus is located in a slightly dorsal location.
SIGNIFICANCE OF PROTEOGLYCANS
A significance of proteoglycans can be readily
demonstrated in a chemonucleolysis study of IV disks.13
Normal IV disk widths are maintained by healthy anulus
fibrosus and nucleus pulposus. When proteolytic enzymes
such as collagenase, chymopapain, and chondroitinase
ABC are injected directly into the nucleus pulposus, the
proteoglycans are lost. Consequently, the IV disk spaces
collapse. This chemical change can be readily noted on
28
magnetic resonance imaging (MRI) (Figure 2). It is
reasonable to assume that these chemical changes are
developing in a more subtle fashion in clinical situations
most likely modulated by altered metabolic function of
chondrocytes. Yet, again the information is limited in the
literature.
Figure 2. Sagittal T2-weighted magnetic resonance image. Note
decreased signal in an intervertebral disk that was treated by chymopapain
(chemonucleolysis). Due to a loss of water-rich proteoglycans, the signal
intensity is not as bright as the rest of normal intervertebral disks.
DEGENERATION OF IV DISKS AND
SIGNIFICANCE OF BREEDS
Unfortunately, degenerative changes of IV disks are
unavoidable. With aging, the composition of proteoglycans
changes, causing a loss of water contents. A wear-and-tear
occurs in IV disks, and eventually fissures form within the
anulus fibrosus. This may be called a progressive aging
pattern.
In a study using a colony of Beagle dogs, the
following aging pattern was noted (Figure 3).14,15 Gross
pathological change developed around 5 years of age.
Orientation and order of the anulus fibrosus was altered
6 years
8 years
10 years
Figure 3. Sagittal histology slides of lumbar intervertebral
disks of Beagle dogs. Disruption of anulus fibrosus and dorsal
herniation of nucleus pulposus are expected aging changes.
29
and mild dorsal protrusion of the anulus fibrosus occured
around 7 years of age. A narrowed IV disk space was also
noted with this change. A sagittal section of the vertebrae
showed disorientation of the anulus fibrosus and fissure
tracts through which the nucleus pulposus protruded
dorsally. Color of the nucleus pulposus was whitish and
opaque. Around 9 years of age, further dorsal bulging of the
anulus fibrosus was noted. The anulus fibrosus lost its
layered appearance, and it was blended with protruded
nucleus pulposus. Further degenerative changes were noted
in the spine of a 10-year-old dog. The dorsal bulging of IV
disks was seen with disorientation of the anulus fibrosus
with separation of layers in the ventral side and fissure in
the dorsal area. The nucleus pulposus appeared as blended
with the anulus fibrosus. There was collapse of the IV disk
space with dorsal and ventral protrusions of both anulus
fibrosus and nucleus pulposus. The protruded nucleus had
yellowish discoloration. Cartilaginous end-plates were not
present, leaving smooth ground surfaces of the bony or
vertebral end-plates. This change was seen most
prominently in the ventral half of the vertebral end-plates
which had thickened, whitish plate of bones. Along the
ventral surfaces of vertebrae, new bone was formed
adjacent to the cortex as spondylosis deformans.
Malalignment of the adjacent vertebrae was also noted.
These changes were noted in both cervical and
lumbar vertebrae. The most common and severe changes
were centered around C5-6 and C6-7 in the cervical spine
and T13-L1 through L2-3 in the lumbar spine.
The pattern described above can be called as
Hansen type II degeneration and develops commonly in
non-chondrodystrophic breeds.16 Since IV disks lose their
proteoglycans gradually, the onset of IV disk disease is
usually gradual and at middle ages. Good examples of these
that become clinically significant are seen in the cervical
spine of Dobermans and as a cauda equina syndrome at a
lumbosacral junction in large breed dogs.
Hansen also noted much earlier degeneration of IV
disks in chondrodystrophic dogs such as Dachshunds,
Miniature Poodles, etc.16 Histologically, these breeds of
dogs showed degenerative changes as early as 4 months of
age. In addition, “chondroid” degeneration occurred with
early calcification of the nucleus pulposus. Calcification of
IV disks or nucleus pulposus does not allow IV disks to
work as a shock absorber. Thus, unusual force can cause
extrusion of the nucleus pulposus. This process is acute and
causes severe spinal cord damage leading to paralysis of legs
(Figure 4). Here, it is imperative to remember that
chondrodystrophic dogs have a narrow spinal canal that
tightly accommodates the spinal cord. Thus, even a minor
extrusion can cause severe clinical signs.
Plain radiography and myelography are still the most
commonly used imaging modality in diagnosis of IV disk
disease in veterinary medicine.6 Although the degree of
degeneration cannot be directly assessed with these studies,
it is often possible to suspect the site based on abnormal
radiographic findings in light of clinical signs. For example,
a 4-year-old Dachshund is presented with acute hind leg
paralysis. Plain lateral and dorsoventral radiographs
showed a narrowed IV disk space at L1-2 with an increased
opacity in the intervertebral foramen and narrowed facet
joint at the same level. Since this is a relatively young dog
with acute history of paraparalysis, this is most likely due
to IV disk disease. If the surgery is desired, myeolography
can confirm the site and lateralize the lesion. Decompressive surgery such as hemilaminectomy can certainly
facilitate the recovery of motor function. However, if this
is a 10-year-old Dachshund, the imaging diagnosis can be
confusing at best with narrowed or collapsed IV disk spaces
in many levels with moderate spondylosis deformans.
Figure 4. Lateral lumbar myelogram of a 7-year-old Dachshund
with acute paraparalysis. The ventral contrast column is deviated
dorsally. Severe spinal cord compression is noted. In addition, a
mineralized disk material is noted in the ventral spinal canal. This
is a classic appearance of Type I intervertebral disk extrusion.
IMAGING DIAGNOSIS OF IV DISK
DEGENERATION
We need to assume that IV disks are degenerated in
aged animals. Currently, MRI is the diagnostic modality of
choice in human radiology.17 Degenerated IV disks do not
contain water-rich proteoglycans, and thus they appear
hypointense on T2-weighted images compared to normal
IV disks. In addition, sagittal and transverse images can
delineate the dorsal border of the protruding disks and
spinal cord compression. This modality is also exclusively
used for detection of spinal diseases in some veterinary
institutions, but its availability is limited. Most veterinary
specialists agree to use this modality in a cauda equina
syndrome, ruling in and out IV disk protrusion at the
lumbosacral junction (Figure 5).2
TYPE III IV DISK DEGENERATION PATTERN
The aging or degenerative pattern described above is
progressive. With the life expectancy of dogs prolonged,
we are now facing a drastic degenerative change in IV
disks. This change can be referred to as the type III
degenerative change.15
Radiographically, the IV disk degenerative changes
develop as a narrowed IV disk space, sclerosis of vertebral
end-plates, and spondylosis deformans. With time, this
further progresses to a collapsed IV disk space with severe
spondylosis. At the same time, remodeling of vertebral
bodies may result in malalignment or kyphosis. At older
ages, around 15 years or so, the IV disk spaces are totally
collapsed and a mineralized mass appears in the spinal
canal. This mass is a protruded or extruded IV disk tissue
(mainly nucleus pulposus) that is subsequently calcified
and ossified (Figure 6). The ossification is the result of
endochondral ossification of the protruded nucleus that
Figure 5. Sagittal T2-weighted magnetic resonance image of a 3-yearold German Shepherd Dog with clinical signs of cauda equina syndrome.
The signal intensity of the lumbosacral intervertebral disk is significantly
lost compared to the L6-7 intervertebral disk. In addition, severe dorsal
protrusion of disk material is noted with marked narrowing of the spinal
canal. High signal intensity areas dorsal and dorsocranial to the
protruded disk is most likely due to fluid accumulation in the facet joint.
30
Figure 6. High-detail radiograph of a thin section of lumbar spine.
This is an example of Type III intervertebral disk degeneration. The
dorsally-protruded disk is calcified. A mottled mineral opacity suggests
ossification within the mass. The intervertebral disk is completely gone
with severe remodeling changes of the vertebral end-plates. Ventral
spondylosis deformans are also evident.
REFERENCES
contains chondrocytes and neovascularization. At the
same time, severe vertebral end-plate changes are
recognized (Figure 6). Protrusion of the IV disk tissue
through the vertebral end-plates can occur (Schmorl’s
node). In one Beagle dog that had extrusion of calcified
disks at 2 years of age, the dog eventually developed a large
bony bridge on the dorsal aspect of the vertebral body
within the spinal canal. Again, endochondral ossification
was the apparent cause of this change.
Clinical significance of type III IV disk degneration
is the recognition of the condition. The type III disk
degeneration appears so severe that this can be confused
with discospondylitis or even neoplasia. The condition can
also make remodeling changes of the pedicles due to longstanding presence of a mass at the spinal canal. The spinal
cord is certainly misshapen due to the presence of the
mass. Yet, a gradual onset appears to allow the spinal cord
to adapt to the condition, causing only mild motor
dysfunction. Decompressive surgery may not be indicated
in these cases.
1. Hoerlein BF. Canine Neurology. Diagnosis and Treatment. 3rd ed.
Philadelphia: W. B. Saunders Company, 1978.
2. de Haan JJ, Shelton SB, Ackerman N. Magnetic resonance imaging
in the diagnosis of degenerative lumbosacral stenosis in four dogs.
Vet Surg 1993; 22:1-4.
3. Kärkkäinen M, Mero M, Nummi P, Punto L. Low field magnetic
resonance imaging of the canine central nervous system. Vet Radiol
1991; 32:717-4.
4. Kärkkäinen M, Punto LU, Tulamo R-M. Magnetic resonance
imaging of canine degenerative lumbar spine disease. Vet Radiol
Ultrasound 1993; 34:399-404.
5. Thomson CE, Kornegay JN, Burn RA, Drayer BP, Hadley DM,
Levesque DC, Gainsburg LA, Lane SB, Sharp NJH, Wheeler SJ.
Magnetic resonance imaging: a general overview of principles and
examples in veterinary neurodiagnosis. Vet Radiol Ultrasound 1993;
34:2-17.
6. Widmer WR. Intervertebral disc disease and myelography. In: Thrall
DE, ed. Textbook of Veterinary Diagnostic Radiology. Philadelphia:
W. B. Saunders Company, 1998; 89-104.
7. Thomson CE, Kornegay JN, Stevens JB. Analysis of cerebrospinal
fluid from the cerebellomedullary and lumbar cisterns of dogs with
focal neurologic disease: 145 cases (1985-1987). JAVMA 1990;
196:1841-1844.
8. Johnson EF, Caldwell RW, Berryman HE, Miller A, Chetty K. Elastic
fibers in the anulus fibrosus of the dog intervertebral disc. Acta Anat
1984; 118:238-42.
9. Ghosh P, Taylor TKF, Braund KG, Larsen LH. A comparative
chemical and histochemical study of the chondrodystrophoid and
non-chondrodystrophoid canine intervertebral disc. Vet Pathol 1976;
13:414-427.
10. Ghosh P, Taylor TKF, Braund KG, Larsen LH. The collagenous and
non-collagenous protein of the canine intervertebral disc and their
variation with age, spinal level and breed. Gerontol 1976; 22:124-134.
11. Ghosh P, Taylor TKF, Braund KG. The variation of the
glycosaminoglycans of the canine intervertebral disc with aging.
I. Chondrodystrophoid breed. Gerontol 1977; 23:87-98.
12. Ghosh P, Taylor TKF, Braund KG. Variation of the
glycosaminoglycans of the intervertebral disc with aging.
II. Non-chondrodystrophoid breed. Gerontol 1977; 23:99-109.
13. Miyabayashi T, Takiguchi M. Chemonucleolysis with chymopapain
followed by magnetic resonance imaging: A pilot study, in Proceedings.
1993 American College of Veterinary Radiology Annual Scientific
Meeting, 1993.
14. Morgan JP, Miyabayashi T. Degenerative changes in the vertebral
column of the dog: A review of radiographic findings. Vet Radiol
1988; 29:72-77.
15. Miyabayashi T. Aging changes in the spine of Beagle dogs, in
Division of Comparative Pathology. 1994, University of California,
Davis: Davis; 117.
16. Hansen H-J. A pathologic-anotomical study on disc degeneration in
dog, with special reference to the so-called enchondrosis
intervertebralis. Acta Orthop Acand 1952; Suppl. XI.
17. Chafetz N, Genant HK, Gillespy T, et al. Magnetic resonance
imaging. In: Kricun ME, eds. Imaging Modalities in Spinal Disorders.
Philadelphia: W. B. Saunders Company, 1988; 478-502.
CONCLUSION
Pathophysiology of IV disk degeneration involves
biochemical changes developing in IV disks. A loss of
proteoglycans appears to be the initial step to
degeneration. A predictable course follows with disruption
of anulus fibrosus and protrusion of nucleus pulposus
through these fissures. As a result, the IV disk space
narrows, and this can be readily detected by radiography.
With persistent instability, spondylosis deformans develops
around the end-plates. The end-plates sclerosis and
malalignment may develop. With advanced aging, all IV
disk tissues escape from
the IV disk space.
The degenerative process
Spondylosis deformans
of IV disks cannot be
continues to develop.
Further remodeling
avoided. Yet, it is possible
occurs at the end-plates.
to delay the process.
Dorsally
protruded
nucleus pulposus undergoes endochondral ossification. The spinal cord adapts to
this gradual process of spinal cord compression. The
mineralized mass can be readily detectable on radiographs.
This should not be confused with discospondylitis or
neoplasia.
It is important to understand that the degenerative
process of IV disks cannot be avoided. Yet, it is possible to
delay the process. Research in chondrocyte metabolism
and its relationship with degeneration should broaden
understanding of maintaining healthy IV disks.
31
the diarthrodial joint better than the older term
“degenerative joint disease”. Typically, OA is an insidiously
progressive, degenerative condition that targets high
motion synovial joints. Etiologies may include infectious
(eg, septic arthritis) or noninfectious (eg, immune
mediated, trauma, developmental/congenital) environment development within the joint. This discussion will be
limited to medical management of secondary lowinflammatory-based OA or what has been classically
labeled “secondary degenerative joint disease” or noninfectious, nonimmune-mediated osteoarthritis.
Micro and macroscopic changes within the synovial
joint may result in the clinical signs of lameness due to
joint pain (synovitis,
microfractures
of
Typically, osteoarthritis is
subchondral bone,
osteophytes, and joint
an insidiously progressive,
effusion/distention).
degenerative condition
The clinical signs
that targets high motion
associated with OA
synovial joints.
vary from patient to
patient and may range
from subclincal to a
severe functional disability. Fundamentally, no one
treatment will be all encompassing for all patients with OA.
A balance of a “triad” of treatment components must be
considered when medically managing a patient with OA:
1) weight control, 2) exercise/activity, 3) pharmacologic/
disease modifying osteoarthritic drugs (Figure 1).
Exclusion of one or more of these components from a
treatment protocol will result in an overall poorer clinical
response from the patient.
Balanced
Management
of Osteoarthritis
in Companion
Animals
Steven A. Martinez, DVM, MS,
Diplomate ACVS
Department of Veterinary Clinical Sciences
Washington State University, Pullman, Washington, USA
WEIGHT CONTROL
Obesity is a major risk factor for the development of
OA1,2 while weight loss can reduce the symptomatic effects
INTRODUCTION
Osteoarthritis (OA, syn. ostoarthrosis, degenerative
joint disease, DJD) is a syndrome that affects synovial or
diarthrodial joints and may manifest its presence by
causing pain in association with degeneration of articular
cartilage (loss of extracellular cell matrix and
chondrocytes, inflammatory response of synovium, and
critical changes in proteoglycan ratios within matrix and
synovial fluid) and changes in periarticular soft tissues.
Since typically a low-grade inflammatory process is
associated with the development and maintenance of the
degenerative process of articular cartilage, the underlying
subchondral bone response (eg, sclerosis), intra and
periarticular response (eg, synovial hypertrophy, fibrosis),
the term “osteoarthritis” describes the disease process of
PHARMACOLOGIC
TREATMENT
EXERCISE/
ACTIVITY
MANAGEMENT
WEIGHT
CONTROL
Figure 1. “Triad” of osteoarthritis treatment.
32
of OA in humans.3,4 Until recently, it was assumed that
the same held true in other animals. A recent clinical
study investigating the effects of obesity on dogs with hip
dysplasia concluded that
overweight dogs that achieved
Obesity is a major
an 11–18% body weight
risk factor for the
reduction were significantly
less lame compared to their
development of
pre-weight reduction lameness
osteoarthritis.
scores.5 Currently, Washington
State University is performing
a study to examine the effects of obesity on the clinical
expression of OA in dogs with canine hip dysplasia.
Weight control can be one of the most challenging
aspects of the medical management of OA in dogs for
several reasons. Any one or a combination of the following
factors will maintain a patient in an obese condition
indefinitely.
additional calories in the form of table scraps or “dog
treats”. Also important is the frequency of feeding. Dogs
on weight-reducing plans appear to be less hungry if fed a
divided volume of the reducing diet over the course of the
day. In addition, feeding in-between “snacks” of low
calorie and high fiber quality (raw carrot sticks, raw celery
sticks, non-flavored rice cakes) or ice cubes will satisfy
most dogs. Appropriate caloric restriction should result in
the loss of 1–2% of body weight per week.6
All weight reduction/control programs must include
an exercise program to ensure constant weight loss and
eventual body weight
maintenance.
To
All weight reduction/
encourage activity in
control programs must
the debilitated OA
include an exercise
patient, regular pharmacologic treatment
program to ensure
may be required for a
constant weight loss
short period until the
and eventual body
patient becomes more
ambulatory.
weight maintenance.
1. A patient that is clinically inhibited by moving an
OA joint(s) will not be able to utilize consumed
or stored body energy efficiently and will instead
increase body stores of energy (fat) when given a
constant caloric intake.
MODIFICATION OF EXERCISE AND ACTIVITY
2. Dogs with underlying endocrine disease (eg,
hyperadrenocorticism, hypothyroidism) will have
the metabolic propensity to maintain body fat
stores even in the face of a reducing diet.
It is known from the human literature that exercise
is very important in maintaining strength, stamina, joint
range of motion, and reducing dependency on medication
when OA patients are allowed to exercise.7–11 It is assumed
that the same is true in other animals as well and
supported by a recent study in hamsters.12 Therefore, an
important aspect in the management of OA in animals
should be a controlled exercise. Depending on the animal’s
activity history, it may be necessary to modify a patient’s
regular level and type of activity that is part of that
animal’s daily exercise regime.
It may be intuitive that an OA animal should not be
allowed to have hard-impact, prolonged exercise activity,
but controlled clinical studies have not been performed to
evaluate this recommendation; however, from clinical
experience, practitioners are used to hearing the usual
owner’s report of greater clinical signs in OA patients after
hard, prolonged activity. It is known from kinetic and
kinematic gait analysis that dogs with OA will modify
their gait to reduce the load of weight-bearing and motion
of the affected joint.13–15 It is therefore safe to assume that
prolonged “over activity” should result in greater
modification of gait due to exacerbation of the discomfort
associated with an OA joint. Some recommendations for
the duration of certain activities in dogs have been made,16
but recommendations for activity duration can also be
based on “common sense” and the observations made by
the owner of their pet’s apparent gait response/comfort
level to an activity period.
3. Dogs that are in a multi-pet household (eg, other
dogs and cats) are more prone to consume greater
volumes of food than dogs in single-pet households.
4. Inaccurate estimation of animal’s ideal body weight.
5. Inaccurate estimation of animal’s energy
requirements.
6. Most critical is the owner’s lack of willingness to be
proactive in trying to reduce their pet’s body weight.
Prior to starting a weight-reducing program, a
complete physical exam should be performed. If the
clinical history (attempted weight reduction in the past
with poor results, lethargy, “heat seeking”, PU/PD, etc.)
and physical exam findings (pendulous abdomen,
symmetrical alopecia, recurrent dematopathy, etc.)
indicate, a complete minimum data base (CBC, serum
chemistry profile, UA) should also be obtained.
Weight reduction can be obtained in healthy
patients by simply reducing current caloric intakes; using
reductions by 1 ⁄3 to 1 ⁄2 of the “normal” volume of the
regular diet, calculating caloric content of regular diet and
caloric needs based on basal metabolic rates, or using
specially formulated commercial diets with recommended
intake volumes per the manufacturer, and avoiding
33
Just as important as duration of activity is the type of
activity involved with the animal’s daily life style. Lowimpact activities (eg, walking, cycling) have positive
effects on human OA patients.7,8,17 In veterinary medicine,
low-impact activities (walking, swimming) have been
traditionally favored over hard-impact aerobic activities
(jumping, hard starting/running, vigorous climbing/
running on irregular terrain), which can over-stress
degenerative joints. High-impact activities may over-stress
degenerative joints and increase the inflammatory
condition of OA. Low-impact activities are thought to
reduce loads on an OA joint and result in less discomfort
for patient in maintaining good muscle strength/mass and
joint function. Walking under controlled conditions (leash
restraint) and/or swimming can be recommended to the
owner with further instructions to eventually attempt to
have the patient increase the duration of these activities
gradually so long as the animal appears to remain
comfortable in doing so.
NSAIDs have a toxicity potential especially if a patient
has underlying hepatic or renal disease, or a
thrombocytopathy. Several in vivo studies using
chondrocyte cell cultures or cartilage explants have
reported a decrease in proteoglycan synthesis in those
tissues incubated with selected NSAIDs.25–28 It would
appear to be a wiser clinical practice to administer
NSAIDs on a PRN basis especially for the patient that has
only intermittent discomfort due to osteoarthritis.
Disease-modifying osteoarthritis agents (DMOA)
have recently been developed for the treatment of human
and veterinary OA patients. These agents have become
common-place in the treatment of OA despite the lack of
definitive scientific studies confirming their efficacy. Most
of these products contain mixtures of glucosamine and
chondroitin sulfate, which supposedly enhance cartilage
health by providing the necessary precursors to maintain
and repair cartilage. Glucosamine and chondroitin sulfate
reportedly have a positive effect on cartilage matrix,
enhance proteoglycan production, and inhibit catabolic
enzyme production or activity in OA joints. These
properties have contributed to the labeling of these agents
as “condroprotective”.29 With the exception of one
product which is a true pharmaceutical by definition
(Adequan®, Luitpold Pharmaceuticals, FDA approved in
PHARMACOLOGIC/DISEASE-MODIFYING
OA AGENTS TREATMENT
The primary goal with the pharmacologic
management of OA is to relieve the patient of discomfort
associated with joint movement.
Ideally, this would involve oral or
Table 1. Selected nonsteroidal antiinflammatory drug doses for the dog
injectable agents with analgesic,
antiinflammatory, and potential
Drug
Dose
Route
Strength
Side Effects
condromodulating
properties
(disease-modifying OA agents,
carprofen
2.2 mg/kg q
PO
25, 50, 75, 100 Vomiting, diarrhea, changes in appetite,
(Rimadyl)
12hr
(inj. soon)
mg tablets
lethargy, behavioral changes, constipation
aka “DMOA”). Such agents
would ideally biochemically block
etodolac
10-15
PO
150, 300
Vomiting, lethargy, diarrhea/loose stool,
(Etogesic)
mg/kg q
mg tablets
hypoproteinemia, behavior change,
the inducible cyclooxegenase-2
24hr
uticaria, anorexia, regurgitation
(COX-2) and lipoxygenase
*ketoprofen 1-2 mg/kg
PO
12.5 mg
Vomiting, diarrhea, serum increase of
pathways. Nonsteroidal anti(Orudis)
loading
tablets
creatinine
inflammatory drugs (NSAID)
(once)
have been developed for this
1 mg/kg q
purpose (Table 1) but generally,
24 hr
do not all selectively block mainly
(maint.)
the COX-2 pathway18–20 or
1 mg/kg q
SC
Injectable
24 hr
leukotrienes production from the
lipoxygenase pathway.21–23
*meloxicam .1-.2
PO, SC Suspension
Vomiting
(Metacam;
mg/kg q
Injectable
Two NSAIDs (carprofen,
approved
24 hr
etodolac) have been recently
only in
approved for use in dogs. These
Europe)
NSAIDs are considered to have a
*piroxicam 0.3 mg/kg q
PO
10, 20 mg
Vomiting
low COX-2:COX-1 ratio, but
24 hr or
capsules
once, e.o.d
have toxicity potential as with
any NSAID. Concerns are present
*rofecoxib
5 mg/kg
PO
12.5, 25, 50
Vomiting
mg tablets
(Vioxx™)
with long-term, chronic therapy
Suspension
with NSAIDs. Hepatic toxicosis
*aspirin
10-20 mg/kg q PO
325 mg
Vomiting, lethargy,
due to NSAID administration has
24
(Ascriptin)
8-12
hr
(w/
Malox)
gastroduodenal ulceration
been reported ; however, all
*currently not labeled for small animal use
34
horses and dogs), these agents are marketed as oral
nutritional supplements and not “drugs” and as such, the
Federal Drug Administration does not require the
manufacturer to provide efficacy data of their product.
Bioavailability reported of orally-ingested forms of
glucosamine and chondroitin sulfate are 87%30,31 and
70%32 in humans and experimental animals, respectively.
Limited investigations have been preformed on the in vitro
and in vivo activity of glucosamine and chondroitin sulfate
separately, but products containing both agents have
become popular for treating OA symptoms in humans and
other animals.
Two commonly used combination glucosamine and
chondroitin sulfate oral products in dogs are Cosequin
(Nutramax) and Glycoflex (Vetri-Science Laboratories).
Although clinically noted not to have predicable efficacy
in all dogs, this combination of glycosaminoglycans appears
to have a prophylactic effect on the development of OA in
dogs. Dogs undergoing a Pond-Nuki model for the
development of OA with or without stifle stabilization that
were administered Cosequin for 5 months following surgery,
subjectively had less OA and less periarticular fibrosis than
dogs not receiving Cosequin.33 Chymopapain-induced
acute carpal synovitis was significantly attenuated based on
nuclear scintigraphy and lameness evaluation when dogs
were pre-treated with glucosamine and chondroitin sulfate
(Cosequin).34 Current research suggests that glucosamine
and chondroitin sulfate products may be prophylactically
beneficial in patients that are prone to develop OA (eg,
CHD, elbow dysplasia, OCD, cranial cruciate ligament
injury, etc.) or patients that may aggravate preexisting OA
with activity. Further controlled clinical studies are still
truly warranted to support these statements.
that were not treated with Adequan.35 Coxofemoral joint
assessment made post euthanasia was not significantly
different from untreated dogs.35 A clinical study
investigating the use of PSGAG on hip dysplasia patients
found no significant difference in orthopedic scores
(lameness, range of motion, pain on manipulation of hip
joints) compared to PSGAG non-treated dogs.36 In a
menisectomy model in dogs, PSGAG provided partial
protection to articular cartilage damage associated with the
menesectomy.37 Polysulfated glycosaminoglycan has been
reported to have chondroprotective properties in joints
with a chemically-induced articular cartilage damage
model versus no effect on a physical articular cartilage
damage model in horses.38 Recently, there have been
anecdotal reports indicating that there may be a positive
synergism between injectable PSGAG and oral
glucosamine and chondroitin sulfate when administered
concurrently to a patient.
Hyaluronic acid (sodium hyaluronate, HA) is a
major component of synovial fluid. Hyaluronic acid is
postulated to enhance joint health by increasing the
viscosity of the joint fluid and by reducing inflammation
and scavenging free radicals. A study using a Pond-Nuki
model for OA in dogs followed by intraarticular injections
of HA did not modify OA and reduced overall
proteoglycan concentrations in treated stifles.39
Other products reported that have disease-modifying,
anti-OA potential include pentosan polysulfate,
tetracyclines (doxycycline, minocycline, and modifications
of these molecules), S-adenosyl-L-methionine (SAMe),
methylsulfonylmethane (MSM), capsaicin, and fatty acid
ratio manipulation (omega-6:omega-3). To date, the
limited number of studies conducted suggest that some of
these products may eventually have a place as adjuncts to
the treatment of OA in animals.40–48
Adjuncts to pharmacologic, exercise/activity, and
weight control treatment are the application of heat, cold,
massage, hydrotherapy, ultrasound/diathermy, and electrotherapy.16 Although based on antidotal observations only,
these adjuncts appear to help some patients. Wellcontrolled clinical trials are needed to test the supposition
that these modalities are as positively effective in
veterinary OA patients as they are in human OA patients.
Current research suggests that glucosamine
and chondroitin sulfate products may be
prophylactically beneficial in patients that
are prone to develop osteoarthritis or
patients that may aggravate preexisting
osteoarthritis with activity.
Injectable forms of DMOA available are Adequan,
which is a polysulfated glycosaminoglycans (PSGAG)
product, and hyaluronic acid (HA), a non-sulfated GAG.
The U.S. and European product (Arteparon) has been
used in horses and dogs. Though conflicting evidence
exists that PSGAG have a positive anabolic effect on
hyaline cartilage, studies have shown that PSGAG may
decrease hyaline cartilage catabolism. In one study,
immature dogs prone to hip dysplasia administered
Adequan developed better hip conformation than dogs
SUMMARY
Osteoarthritis can be a debilitating disease for dogs;
however, new concepts in a balanced management of OA
can result in an acceptable quality of life for the OA
patient. Medical management must be considered beyond
conventional and nonconventional pharmacologic
treatment to include a balance created with
exercise/activity and weight control management. Failure
to consider this treatment “triad” concept will usually
35
12. Otterness IG, Eskra JD, Bliven ML, Shay AK, Pelletier JP, Milici AJ.
Exercise protects against articular cartilage degeneration in the
hamster. Arthritis Rheum 1998; 41:2068-2076.
13. Jevens DJ, DeCamp CE, Hauptman J, Braden TD, Richter M,
Robinson R. Use of force-plate analysis of gait to compare two
surgical techniques for treatment of cranial cruciate ligament rupture
in dogs. Am J Vet Res 1996; 57:389-393.
14. Bennett RL, DeCamp CE, Flo GL, Hauptman JG, Stajich M.
Kinematic gait analysis in dogs with hip dysplasia. Am J Vet Res 1996;
57:966-971.
15. DeCamp CE. Kinetic and kinematic gait analysis and the assessment
of lameness in the dog. Vet Clin North Am Small Anim Pract 1997;
27:825-840.
16. Millis DL, Levine D. The role of exercise and physical modalities in
the treatment of osteoarthritis. Vet Clin North Am Small Anim Pract
1997; 27:913-930.
17. Mangione KK, McCully K, Gloviak A, Lefebvre I, Hofmann M,
Craik R. The effects of high-intensity and low-intensity cycle
ergometry in older adults with knee osteoarthritis. J Gerontol A Biol
Sci Med Sci 1999; 54:184-190.
18. Lanza FL: Gastrointestinal toxicity of newer NSAIDs. Am J
Gastroenterol 1993; 88:1318-1323.
19. Vasseur PB, Johnson AL, Budsberg SC, Lincoln JD, Toombs JP,
Whitehair JG, Lentz EL. Randomized, controlled trial of the efficacy
of carprofen, a nonsteroidal anti-inflammatory drug, in the treatment
of osteoarthritis in dogs. J Am Vet Med Assoc 1995; 206:807-811.
20. Budsberg SC, Johnston SA, Schwarz PD, DeCamp CE, Claxton R.
Efficacy of etodolac for the treatment of osteoarthritis of the hip
joints in dogs. J Am Vet Med Assoc 1999; 214:206-210.
21. Brooks PM, Day RO. Nonsteroidal antiinfllammatory drugsdifferences and similarities. N Engl J Med 1991; 324:1716-1725.
22. Dawson W, Boot JR, Harvey J, Walker JR. The pharmacology of
benoxaprofen with particular to effects on lipoxygenase product
formation. Eur J Rheumatol Inflamm 1982; 5:61-68.
23. Vane JR, Botting RM. The mode of action of anti-inflammatory
drugs. Postgrad Med J 1990; 66 (suppl):S2-17.
24. Bjorkman D. Nonsteroidal anti-inflammatory drug-associated
toxicity of the liver, lower gastrointestinal tract, and esophagus. Am J
Med 1998; 105:17S-21S.
25. Manicourt DH, Druetz-Van Egeren A, Haazen L, Nagant de
Deuxchaisnes C. Effects of tenoxicam and aspirin on the metabolism
of proteoglycans and hyaluronan in normal and osteoarthritic human
articular cartilage. Br J Pharmacol 1994; 113:1113-1120.
26. Srinivas GR, Chichester CO, Barrach HJ, Matoney AL. Effects of
certain antiarthritic agents on the synthesis of type II collagen and
glycosaminoglycans in rat chondrosarcoma cultures. Agents Actions
1994; 41:193-199.
27. Bassleer C, Magotteaux J, Geenen V, Malaise M. Effects of
meloxicam compared to acetylsalicylic acid in human articular
chondrocytes. Pharmacology 1997; 54:49-56.
28. Wang B, Chen MZ. Effects of indomethacin on secretory function of
synoviocytes from adjuvant arthritis rats. Int J Tissue React 1998;
20:91-94.
29. Gosh P, Smith M, Wells C. Second line agents in osteoarthritis. In:
Dixon JS and Furst DE, Eds. Second Line Agents in the Treatment of
Rheumatic Diseases. Marcel Dekker, New York, 1992; 363.
30. Setnikar I, Giachetti C, Zanolo G. Absorption, distribution and
excretion of radioactivity after a single intravenous or oral
administration of [14C] glucosamine to the rat. Pharmatherapeutica
1984; 3:538-550.
31. Setnikar I, Giacchetti C, Zanolo G. Pharmacokinetics of
glucosamine in the dog and in man. Arzneimittelforschung 1986;
36:729-735.
result in a poorer clinical response to therapy and quality
of life as perceived by the owner of the OA patient.
Excellent progress continues in the development of new
pharmacologics and other agents to combat or even
reverse the degenerative processes of OA. In contrast,
research and development into exercise/activity
management for the
OA companion animal
New concepts in a
lags significantly behind
that of human medicine,
balanced management
but since the mid-1990’s,
of osteoarthritis can
is beginning to grow in
result in an acceptable
interest in veterinary
quality of life for the
medicine. Nonetheless,
large controlled clinical
osteoarthritis patient.
trials are needed for
developing balanced
treatment protocols that will allow us to treat our OA
patients beyond the “clinical experience”.
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37
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Clinical Perspectives on Canine Joint Disease Clinical Perspectives

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