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Canine Osteoarthritis and Treatments: A Review
Stephanie D. Bland
Ph.D Student at Southern Illinois University
Acknowledgements
The author would like to acknowledge Ramesh Gupta, DVM, Ph.D. for serving as a mentor and
providing general support and David Lightfoot, Ph.D. for critical revisions.
Southern Illinois University, 1205 Lincoln Drive, Carbondale, IL, 62901,
Tel: 618-550-9490
Email: sbland@siu.edu
Key words: canine, osteoarthritis, NSAID, nutraceutical
Author’s Contributions
SB was responsible for the extensive literature review in general osteoarthritis and osteoarthritis
in canine and equine, specifically. SB was responsible for writing and formatting this
manuscript.
Competing Interests
The author declares that she does not have any competing interest.
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Abstract
Arthritis is a commonly occurring chronic illness in human and animals alike. Among all
domestic and pet animal species, dogs suffer from arthritis more often because of excessive
running or exercise, injury, and/or genetic predisposition. Presently, one in four of 77.2 million
pet dogs in the United States are diagnosed with some form of arthritis. In dogs, osteoarthritis is
more common than rheumatoid arthritis and pain is the number one observation. Osteoarthritis,
also known as degenerative joint disease, is a slowly progressive inflammatory disease, which is
characterized by degeneration of the cartilage, hypertrophy of bone at the margins, and changes
in the synovial membrane, and that eventually results in pain and stiffness of joints. Alterations
in joint structures, decreased flexibility, and severe pain ensues, due to lack of hydration and
inflammation. Cells within the damaged joints release pro-inflammatory cytokines, which further
the inflammatory process. This causes more breakdown of the cartilage collagen type II and
proteoglycans, which results in a perpetual destructive cycle. This perpetuating cycle ultimately
results in cartilage destruction, subchondral bone thickening, and synovial membrane
inflammation. This review focuses on osteoarthritis, the disease, causes, treatments, and presents
a glimpse of some new therapies under study.
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Introduction
Osteoarthritis, also known as degenerative joint disease (DJD), is a chronic inflammatory
joint disease, which causes pain/soreness, stiffness, swelling, and lameness due to the diminished
cushion and changes in the synovial fluid.1,2,3 Osteoarthritis affects the entire synovial joint
including the cartilage, synovial fluid, and bone. This disease is characterized by degeneration of
the cartilage and soft tissues, hypertrophy of bone at the margins, and changes in the synovial
membrane.1,2,3 Mechanical stress is thought to induce changes in biochemical factors within
affected joints, leading to articular cartilage degradation.4 The disease process limits the amount
of protein, released from the cartilage’s cells, to repair cartilage in the joints; this is referred to as
pitting and fraying of cartilage.5 This pitting and fraying results in the cartilage losing its
elasticity and protective surface due to enzymatic cleavage of proteoglycans.6 As the cartilage
continues to break down and deteriorate completely, it causes friction between the bones, which
leads to inflammation, thickening of soft tissues, and loss of mobility of the joint.7 Trying to
maintain its normal balance of injury and repair, as the cartilage wears away the joints begin to
lose its normal shape and the space between the joints narrow. Osteophytes (spurs) formation
begins where the ligaments and joint capsule attach to the bone. In addition, fluid filled cysts
form and fragments of bone and cartilage can be found floating in the joint space.5 All of the
changes in the joints and bones can cause pain, swelling, and the joint may even appear enlarged.
Disease Overview
Osteoarthritis is a disease that has been described for over a hundred years.8 Currently
there are about 27 million Americans diagnosed, but is expected to reach 67 million by 2030.9
Osteoarthritis is the most common form of arthritis in humans and in dogs. In almost every form
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of arthritis there is a loss of bone or cartilage that results in changes in the shape of joints.10
There are three different types of joints; fibrous, cartilaginous, and synovial. Fibrous and
cartilaginous joints consist of fibrous tissues or hyaline cartilages, which allow little or no
movement. Synovial joints are made up of synovial fluid and dense irregular connective tissue,
which creates a synovial joint capsule allowing the joints to freely move.3 The main focus will be
on the synovial joint, especially the ball and socket (hip and shoulder) and hinge joints (elbow),
because these joints are most commonly affiliated with osteoarthritis, especially in canines.3 The
synovial fluid in the synovial joint capsule provides nutrients, lubrication, and a cushion for
articular cartilage.1,2,3 Articular cartilage, which is composed of hyaline cartilage, is avascular
tissue consisting of chondrocytes embedded within an extracellular matrix of collagens,
proteoglycans, and non-collagenous proteins. Articular cartilage reduces friction and makes
movement of the synovial joints painless.11 The hyaline cartilage, which has a high content of
collagen type II, serves as a shock absorber by distributing pressure from the load over the
subchondral bone. In healthy joints, there is a fine balance between injury and repair amongst
chondroblasts and chondroclasts.5 However, in osteoarthritis this balance is disrupted by an
overproduction of osteoblasts that can cause pain and swelling. Osteoarthritis has multiple causes
and risk factors; however, once the cartilage is lost, the joint fails.12
Osteoarthritis is a progressive disease that consists of four stages. In stage one of
osteoarthritis, minor bone spurs begin to develop. The cartilage matrix begins to break down due
to chondrocyte’s metabolism being affected and increasing the production of matrix destroying
enzymes, metalloproteinases (MMPs). The severity of cartilage lesions can be correlated with the
levels of collagenase present (MMP-1).13 Cartilage lesions disrupt the function of cartilage,
increasing friction and inflammation in the joints, resulting in pain. Stage two of osteoarthritis is
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considered the “mild” stage. This stage involves erosion of the bone due to the cartilage lesions.
This can cause new bone growth, osteophyte, also called bone spurs, which affect normal joint
movement. In this stage, proteoglycan and collagen fragments are released into the synovial
fluid.10 In the adult dog, protecoglycan turnover is quicker (300 days) than estimated collagen
turnover (120 years). Marked protecoglycan loss of articular cartilage is irreversible and results
in joint degeneration.4 Stage three is considered “moderate” osteoarthritis. The cartilage, in-
between the bones, thins out and loses cushion. The space between the bones is also narrowing,
causing grinding between the adjacent subchondral bones.10 During stage three, symptoms are
more severe and inflammation begins to occur. Production of synovial macrophages occurs,
including MMP, cytokines (interleukin 1), and tumor necrosis factor-alpha.4,6 Once the synovial
macrophages are produced they can destroy tissues by diffusing back into the cartilage and can
also stimulate chondrocytes. The fourth and final stage of osteoarthritis is considered “severe”
osteoarthritis. In this stage the joint space is dramatically reduced, the cartilage is almost gone,
and joint mobility is reduced greatly.4,10 Early diagnosis of osteoarthritis is key to prevent further
damage to the joint and alleviate symptoms.
Diagnosis of Canine Osteoarthritis
Osteoarthritis is the most common type of arthritis in dogs and is the most common
source of chronic pain in older dogs.7 This is due to the constant wearing away of the cartilage
from dogs running, jumping, and other strenuous exercise. Arthritis commonly affects large
breed dogs, i.e. German Shepherds, Labradors Retrievers, Siberian Huskies, and Rottweilers,
more than small breed dogs. Prevalence of osteoarthritis can be as high as 20% in dogs more
than a year old, with middle-aged and older dogs being at higher risk. Dogs that are diagnosed
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with arthritis tend to be lethargic, have difficulty moving from a sitting or lying position,
cracking joints, stiffness, muscle wastage, and visible pain.7 Diagnosing osteoarthritis in dogs
begin with owners observing the pain and stiffness while the animal is running, walking,
jumping, or rising from a lying or sitting position. Radiographic evidence, patient symptoms, and
osteoarthritis risk factors such as age, gender, and body mass index, can all aid in predicting the
risk of rapid, highly predictable joint degradation. During physical exams, the patient may show
signs of pain, including whining, biting, or trying to move away. Radiographic evidence can
show the breaking down of cartilage between bones and inflammation in the joints. By properly
diagnosing patients with osteoarthritis, this will help establish a future plan to help ease pain,
prevent further damage, and overall increase the quality of life.
Canine Hip Dysplasia
Along with osteoarthritis, dogs may also suffer from hip dysplasia, a form of
osteoarthritis present in the ball and socket joints. Hip dysplasia can be a genetically inherited
condition from improperly formed hip joints typically seen in large breed dogs.14 Dogs that
suffer from inherited hip dysplasia, show signs within the first year and should be spayed or
neutered to avoid passing this genetic tendency to malformation to offspring. Bulldogs, St.
Bernard’s, Blood Hounds, and Boykin Spaniels are a few examples of breeds that are at a higher
risk factor for developing hip dysplasia. Dogs can also be at risk for hip dysplasia if there is
excessive weight gain during the early stages of growth, typically 3-8 months of age, and from
putting excessive pressure on the hip joint from strenuous exercise. Hip dysplasia is caused from
an abnormal development of the hip joint, leading to excess laxity in the hip joint. Laxity in the
hip joint can cause stretching of the supporting ligaments, joint capsules, and surrounding
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muscles, leading to permanent damage to the anatomy of the hip joint.15 The permanent damage
to the anatomy causes the poorly developed head of the femur to loosely fit into a shallow
acetabulum.16 Orthopedic Foundation for Animals (OFA) radiographs can also be done to
diagnose hip dysplasia. According to the Orthopedic Foundation for Animals, OFA radiographs
must be performed with the animal in dorsal recumbancy with rear limbs extended parallel. The
stifles are rotated inward and the pelvis is symmetric. This type of radiograph allows
veterinarians to assess how the femoral head fits into the acetabulum, which aids in the diagnosis
of hip dysplasia.16
Measuring Joint Mobility
Osteoarthritis patients struggle with limited range of motion (ROM), a reduction in the
ability to move one’s joints. Pain, stiffness, and swelling, all symptoms of osteoarthritis, can
hinder mobility. Measuring the range of motion can help identify what condition the articular
surface, joint capsule, ligaments, and muscles, are in.17 Assessing the range of motion is widely
used in human medicine and is becoming more popular in canine veterinary medicine, as more
patients are being diagnosed with arthritis (Table 2). Universal Goniometry is a commonly
preferred way to measure range of motion in humans and other species.18 A goniometer is an
affordable, reliable, commonly used, non-invasive tool used to measure flexion and extension
degrees of joint mobility in the forelimbs and hind limbs in canine, as well as humans during
physical therapy sessions. When using a goniometer, place the tool over the fulcrum of the joint,
aligning the stationary arm with the stationary line of the body. Move the desired joint, either
flexed or extend, and follow the moving line of the body with the moving arm of the goniometer;
look at the readings on the goniometer for the degree of range of motion.
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Table 1. Maximum joint range of motion in canine
Joint
Extension
Flexion
Shoulder
142 degrees-ground
125 degrees-ground
Elbow
124 degrees-ground
98 degrees-ground
Carpus
124 degrees-ground
97 degrees-ground
Hip
141 degrees-ground
115 degrees-ground
Stifle
141 degrees-ground
109 degrees-ground
Hock
135 degrees-ground
115 degrees-ground
Erythrocyte Sedimentation Rate
In addition, a multitude of blood tests can be used to determine the degree of
inflammation in the joints from arthritis, aiding in the diagnosis. One test used to assess
inflammation is the erythrocyte sedimentation rate test along with complete blood counts and
chemistry panels. The erythrocyte sedimentation rate (ESR) test, also known as the sed rate,
sedimentation rate, and Westergren sedimentation rate, is a quick and simple test that has been
used for many years to detect inflammation associated with infections, autoimmune diseases, and
arthritis. A Polish pathologist, Edmund Biernacki, invented the ESR test in 1897. In 1918, two
Swedish pathologists, Robert Sanno Fahraeus and Alf Vilhelm Albertsson Westergren used
sodium citrate-anticoagulant specimens. This method of the test is widely used today and known
at the Westergren method.19
Due to the ESR test not being specific, it is used in addition to other blood tests
including c-reactive protein, antinuclear antibody (ANA), and rheumatoid factor. Typically, ESR
tests are ordered when a condition or disease is suspected to cause some form of inflammation in
the body. For example, people who suffer from arthritis may have an ESR test run to detect the
amount of inflammation in the joints. ESR is the rate at which red blood cells sediment in a
period of one hour. The test is performed by anticoagulated blood, typically in an
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ethylenediaminetetraacetic acid (EDTA) tube that is placed in an upright 150mm tube, also
known as a Westergren tube. After an hour, the rate at which the red blood cells have fallen is
reported in millimeters of plasma per hour (mm/hr) .20 Normal ranges for canine and feline ESR
are listed below in Table 2. The ESR test works by a precise balance of pro-sedimentation
factors, specifically fibrinogen, and resisting sedimentation factors, such as the negative charge
of erythrocytes. During a state of inflammation, the fibrinogen increased causing the red blood
cells to stick together in a stacked pattern known as rouleaux. The stacked erythrocytes are
denser and cause the cells to settle faster than normal.21
Table 2. Erythrocyte sedimentation rate normal ranges
Species
Normal Range (mm/hr)
Feline
0-12
Canine
0-5
Drugs and Disease Management
Animals with osteoarthritis are treated with various approaches, involving invasive and
non-invasive measures. The objectives in managing osteoarthritis include minimizing joint pain
by reducing the inflammation and slowing the progression of the cartilage damage, resulting in
increased joint flexibility and ultimately improving quality of life. To achieve these goals, a
variety of conventional pharmaceuticals, experimental treatments, nutracetuicals and
supplements, and life change, such as stem cell therapy, physical therapy with acupuncture, and
weight loss and exercise programs.
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Conventional Treatments
Non-Steroidal Anti-Inflammatory Agents (NSAIDs)
Pharmacological management of osteoarthritis includes steroidal or non-steroidal anti-
inflammatory (NSAID) agents. These drugs do not address the underlying issue; they just control
pain and inflammation. NSAIDs work against prostaglandins, which are a family of chemicals
that are produced by cells and promote inflammation. Their inflammation properties also result
in pain, fever, and increased platelet clumping.1,7 The cells that produce prostaglandins are called
cyclooxygenase (COX). There are two forms of COX enzymes, COX-I produces prostaglandins
that support platelet clumping and protect the stomach, and COX-II enzymes produce
prostaglandins that are responsible for pain and inflammation. Since NSAIDs inhibit both forms
of COX enzymes, NSAIDs can result in gastrointestinal side effects, including ulceration,
vomiting, anorexia, melena, and abdominal pain.1,17
Aspirin (acetylsalicylic acid) was the first NSAID to be used in modern medicine and still
is widely used. Aspirin, despite its side effects, is commonly recommended in veterinary
medicine for dogs that suffer from osteoarthritis due to it being relatively inexpensive. However,
studies have shown that aspirin can decrease chondrocyte production of collagen and
proteoglycans and can enhance cartilage degradation over time.1 Aspirin is also a unique NSAID
in the fact that it prolongs blood clotting for 4-7 days. This makes in an ideal drug for preventing
blood clots that cause heart attacks and strokes, rather than an osteoarthritis event.1,7 Since there
are many problems associated with aspirin for osteoarthritis treatment, other NSAIDS are
becoming more popular. The six types of NSAIDs that are commonly prescribed by
veterinarians, other than aspirin, for osteoarthritis patients include, RimadylTM, DeramaxxTM,
EtogesicTM, MetacamTM, ZubrinTM, and PrevicoxTM.7
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Corticosteroids
Corticosteroids and gluccorticosteroids, often referred to as steroids, may be lifesaving
and certainly increase the quality of life of dogs and humans.22 Cortisone is a hormone that
naturally occurs in the cortex of the adrenal gland. This is where the “cortico” prefix comes
from. Corticosteroids are produced from the same chemical base that produces the sex
hormones.24 Cortisol is naturally produced when an animal gets stressed; however, man-made
cortisol is 5-6 times stronger than naturally produced cortisol. Any production, natural or drug
induced, of cortisol has a negative feedback and slows or stops natural production. Suppression
of naturally produced cortisol typically occurs within 12-48 hours and takes a few days to start
the process back up.25 Stopping the use of steroids quickly can result in a withdrawal syndrome,
which includes fatigue, joint pain, stiffness, tenderness, and fever.26
Corticosteroids are the most used, and misused, pharmaceuticals in veterinary medicine.22
Steroids, generally in an oral tablet, are used for stress response, immune system issues,
inflammation, nutrient metabolism, and maintaining electrolyte levels in the blood.22
Corticosteroids are a popular treatment plan for patients suffering from arthritis because they are
extremely effective in relieving pain and inflammation.23 Steroids inhibit the production of
arachidonic acid, which can stop the inflammation and stop the production of prostaglandins,
similar to NSAIDs.26 However, when using steroids the body cannot separate the anti-
inflammatory properties from the immunosuppressant properties.26 Therefore, low doses of
steroids are used to suppress inflammation and high doses of steroids are used as
immunosuppressants.22 Since steroids affect nearly all cells of the body, their benefits are
widespread, however, their side effects can be long lasting and devastating.26 The side effects,
which vary depending on the dose and duration of steroid use, include sore mouth, weight gain,
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osteoporosis, high blood sugar levels (diabetes), cataracts, insomnia, gastrointestinal bleeding
and ulcers, suppressed immune systems, fluid retention, atherosclerosis resulting in increased
risk of heart disease, and aseptic necrosis. To reduce the probability of side effects from steroid
use, one must avoid using steroids on a daily basis and no longer than 3-4 months without re-
evaluating organ functions. Due to the devastating side effects of steroid use, alternative
medicine such as acupuncture, nutraceuticals, and therapy can be used to treat osteoarthritis
patients.
Experimental Treatments
Insulin Growth Factor-I (IGF-I)
Insulin growth factor-I (IGF-I) is peptide produced by the liver that promotes growth by
reaching the articular cartilage through the synovial fluid. IGF-I can also be synthesized by
chondrocytes.27 This peptide is vital for childhood growth, but continues to have anabolic affects
in adults. IGF-I is stimulated by growth hormones and helps cartilage maintain structural and
functional integrity by inhibiting interleukin-1’s ability to stimulate proteoglycan degredation.27
However, under malnutrition conditions, hormone and receptor insensitivity, and failure to
downstream signaling, can affect growth and stimulate damage to cartilage health. Past studies
have shown that IGF-I can be important to the development of osteoarthritis and osteoporosis
due to IGF-I being abundant in the cartilage and bone; therefore, it is suggested that it can
prevent cartilage damage and the progression of osteoarthritis.27 This is because IGF-I plays a
role in the regulation and homeostasis of normal cell growth and cartilage. In adults, if damage
occurs, i.e. tumors, this can lead to overgrowth of bony tissue, which can cause osteoarthritis.28
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However, due to many inconclusive studies, more work needs to be done to understand the
mechanism and to what extent IGF-I has on osteoarthritis.
Oral Doxycycline
Doxycycline, broad spectrum, bacteriostatic antibiotic, is commonly used for bacterial
infections and to treat malaria. However, preliminary studies on animals have been conducted to
study the effects of doxycycline on osteoarthritis. It is speculated that low dosages of tetracycline
analogue, specifically doxycycline, can inhibit the MMPs, which play an essential role in
cartilage degradation. Due to doxycycline being more lipid soluble it is able to penetrate areas
such as the synovial joint, which in the main site of damage in dogs with osteoarthritis. In one
study conducted by the Johns Hopkins’ Arthritis Center (1995), oral administration of
doxycycline showed to prevent narrowing of the knee joint in subjects. Studies have also shown
that oral administration of doxycycline can reduce the severity of articular cartilage, which plays
a vital role in the process of osteoarthritis.29 In Nganvonpanit et al., (2009), the therapeutic effect
of oral doxycycline on canine hip osteoarthritis, by reducing the rate of joint pathology in
osteoarthritis, was studied. Overall, after a six-month period, dogs showed significant signs of
improvement in joint mobility, pain upon limb manipulation, lameness, and were able to bear
more weight on their hips. Signs of improvement were shown as early as two months.30
However, the results were not consistent and further studies should be conducted at the
therapeutic effects of oral doxycycline and canine osteoarthritis and lameness. In addition, the
overuse of doxycycline can result in microbial resistance; therefore, long-term side effects and
dosage recommendations need to be further studied.
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Sodium Pentosan Polysulfate
Originally made for humans who suffer from interstitial cystitis, sodium pentosan
polysulfate is a semi-synthetic, poysulphated polysaccharide that has anti-inflammatory and anti-
arthritis properties and is classified as a disease modifying osteoarthritis drug (DMAOD).
Sodium pentosan polysulfate is structurally similar to glycosaminoglycans. Sodium pentosan
polysulfate is also similarly structured to the anti-coagulant, heparin; however, does not have the
same strength. Sodium pentosan polysulfate has been studied in Europe for over 40 years, but
only recently has been combined with calcium to increase its anti-arthritic properties.31 These
properties are due to it being able to stimulate chondrocytes to synthesis cartilage, stimulate
synoviocyte biosynthesis, and inhibit degradation of cartilage matrix and acrachidonic acid,
which promotes an inflammatory cascade.32 Sodium pentosan polysulfate is recommended to be
injected into the joint in 5-7 day intervals with provided three months of relief.32 Currently, it is
leading experimental treatment for osteoarthritis in canines and other animals by inhibiting
MMPs and maintaining the cartilage structure and biochemistry.32 Other than mild
gastrointestinal upset, not other side effects have been noted. Therefore being relatively safe,
even at three times the recommended dose and having minimal side effects, sodium pentosan
polysulfate is becoming a more popular alternative treatment for canine osteoarthritis.31
However, more in vivo studies need to be performed to evaluate the bioavailability of oral route
versus intramuscular.
Glycoaminoglycans: Glucosamine and Chondroitin Sulfate
As the body ages the production of glucosamine slows down; therefore, it is important to
supplement glucosamine to avoid joint issues.37 Glucosamine (2-amino-2-deoxy-D glucose), the
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most abundant monosaccharide, is a naturally occurring compound composed of sugar and
amino acids. Glucosamine has been used for nearly 40 years in human medicine.25 It is strictly
used as a dietary supplement in the United States, but is a regulated pharmaceutical throughout
Europe.16 There are three different types of glucosamine; glucosamine sulfate, glucosamine
hydrochloride, and N-acetyl-glucosamine. However, glucosamine sulfate may be more effective
for arthritis treatment because sulfate is needed to produce cartilage and the other two forms of
glucosamine do not contain sulfates.25 Glucosamine supplements are extracted from crustacean
exoskeletons or from fermentation of grains such as corn or wheat.21 Glucosamine is one of the
most commonly used nutraceuticals, especially for arthritic patients, due to it being involved in
the body’s production of joint lubrication and shock absorption and maintaining healthy cartilage
and joint function.25 Glucosamine is the precursor in the biochemical synthesis of glycosylated
proteins and lipids, glycosaminoglycans. Glycosaminoglycans are a major component of joint
cartilage and the extracellular matrix of articular cartilage.25 Glucosamine also aids in the
rebuilding of damaged cartilage and is a building block for articular cartilage.25 Glucosamine has
anti-inflammatory properties by inhibiting synthesis of degradation enzymes, increasing
synthesis of extracellular matrix, and reduces apoptosis of articular chondrocytes.25 Glucosamine
is also good for nail growth, tendons, skin, eyes, synovial fluid, ligaments, heart valves, and
mucous secretions of the digestive, respiratory, and urinary tract.21 Glucosamine supplements
have little to no side effects when used at the recommended dose; however, if taken above the
recommended dose, it can cause damage to pancreatic cells and increase the risk of diabetes.
Short-term side effects include stomach upset, constipation, diarrhea, headaches, and rashes.16 In
recent years, in a series of preliminary experiments, researchers have evaluated several
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nutraceuticals individually and in combination with several other supplements, and found that
they are significantly effective in ameliorating arthritic pain.
Glucosamine supplements are often combined with chondroitin sulfate. Chondroitin
sulfate, a type of gylcoaminogycan, addresses the disease process of arthritis by aiding in the
repair of damaged connective tissue. Chondroitin sulfate is one of the most abundant
glycoaminoglycans in joint cartilage, bones, tendons, cornea, and heart valves.21 It is also
beneficial to stress injuries, by keeping joints hydrating and protecting existing cartilage
breakdown.21 Studies has theorized that supplementation of chondroitin sulfate will maximize
blood circulation to subchondral bone and synovial joints. Chondroitin sulfate is vital for
articular cartilage and joint structure because it can bind collagen fibrils and is used as a
chondroprotective agent by inhibiting the degradations of cartilage matrix and synovial fluid.21
Supplementation of chondroitin sulfate is important because as the body ages, less chondroitin
sulfate is produced and other glycoaminoglycans, such as keratin sulfate, are produced which
predisposes the joint to osteoarthritis. In addition to the joint benefits, chondroitin sulfate
supplements are noted to have up to 70% bioavailability when taken orally, this is significantly
more than the bioavailability of other supplements and nutraceuticals. Overall, glucosamine
chondroitin sulfate and other joint related glycosaminoglycans, seem to be relatively safe and do
not display any long term side effects. Therefore, making glycoaminoglycans a popular
alternative treatment for osteoarthritis in canines.21,25
Stem Cell Therapy
Stem cell therapy, acupuncture, and massage therapy are all becoming popular aliments
used to treat dogs that suffer from osteoarthritis symptoms. While most osteoarthritic treatments
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are the same for humans and dogs, stem cell therapy is only available for dogs. When anti-
inflammatory agents are no longer improving the quality of life for arthritic dogs, stem cell
therapy can be the next option. First discovered in 2005, by Dr. Brian Voynick of the American
Animal Hospital, this therapy is an option for dogs with osteoarthritis or hip dysplasia. Stem
cells are platelet rich plasma that can help inhibit the inflammatory process and repair damaged
tissue.33 Currently, several therapeutic regenerative strategies have investigated whether
autologous mesenchymal stem cells (MSCs) have significant effects on regeneration and
maintenance of articular cartilage.33 Stem cell therapy is based on the isolation of these cells
from fat or bone marrow tissues and then after culture expansion, they are injected back to the
patient’s damaged joints.33 Veterinarians claim that harvesting stem cells from fat is less invasive
than a spay. A positive aspect to this therapy is that it is the dog’s cells and therefore the risk of
rejection is lower. Mesenchymal stem cells are responsible for releasing anti-inflammatory
chemicals, which are speculated to repair damage in the joint.33 However, little is known about
the mode of action when injected into the damaged joint. While stem cell therapy is still
relatively new and seems to have promising effects for treating and preventing osteoarthritis in
canines, it is a relatively expensive treatment, averageng around $3,000, and results may vary
from individual and severity of osteoarthritis.
Nutraceuticals and Natural Products
Pharmaceuticals have a high risk of toxicity and adverse side effects, because of this;
there is push for alternative treatments in the form of food supplements. A nutraceutical is
defined as a food, typically plant based, which provides medical or health benefits including the
prevention and treatment of a disease.13 Stephen DeFelice, MD, the founder and chairman of the
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Foundation for Innovation in Medicine, coined the word “nutraceutical” in 1989 from the words
“nutrition” and “pharmaceutical”.34 However, the use of food supplements to treat diseases dates
back to Hippocrates, the father of medicine, (460-377 BC) when he predicted the health benefits
of foods.35 Since certain foods play an important role in maintaining normal functions in the
human body, nutraceuticals are gaining popularity with health professionals and the public.
Currently, there are over 470 nutraceuticals with documented health benefits.13,15 Nutraceuticals
are classified into two types; traditional foods and non-traditional foods. Traditional food is
defined as natural, whole food with new information about potential health qualities. For
example, omega-3 fatty acids in salmon and other seafood help reduce undesirable cholesterols.
Non-traditional foods result from agriculture, crop and animal breeding or adding nutrients and
ingredients to boost traditional food’s nutritional value. Examples include orange juice that is
fortified with calcium; milk fortified with vitamins; crops fortified with vitamins, minerals, and
omega 3s. However, to date few focus directly on osteoarthritis.
Unlike pharmaceuticals, there are no FDA regulations for the health claims of
nutraceuticals or non-traditional foods.13 Even though there are few regulations on the health
claims of nutraceuticals, safety must be assured in advance. Therefore, extensive, independent,
testing must be reported on a nutraceutical before health professionals recommend it to their
patients. During the research process, nutraceuticals can be classified as potential or established
nutraceuticals. Nutraceuticals provide a promising approach towards a particular health or
medical benefits, while established nutraceuticals have multiple, independent, peer-reviewed,
research reports backing up their claimed benefits.31,36
Herbal medicine is increasing its popularity in veterinary medicine.7 Popularity may be
due to low cost and a belief it has minimal to no side effects. Herbal medicine is becoming a
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common treatment for mastitis occurrences, foot-and-mouth disease outbreaks, skin allergies,
food poisonings, tympany, and expulsion of placentae. In the past, nutraceuticals were a common
therapy for livestock in treating a variety of diseases including hepatitis, chronic heart disease,
skin disorders, wounds, and arthritis.24 Some nutraceuticals affect the progression of arthritis by
preventing degradation and enhancing the repair of joint cartilage.36
Weight Control, Exercise, and Physical Rehabilitation
When treating osteoarthritis the main goals are to reduce pain and inflammation, improve
joint function, eliminate or control the cause of arthritis, and even halt the process. Treatment can
either occur through therapy or through medication. Osteoarthritis is more common in
overweight dogs, so by putting the dogs on a strict diet to promote weight loss it can decrease
mechanical stress that is placed on the joints. Obesity, and inactivity, which leads to obesity, can
cause the joint to wear away faster due to extra pressure that is exerted on a joint.1,38 According
to the Arthritis Foundation, for every pound gained, three pounds of pressure are added to the
knees and six pounds of pressure are added to the hips.1,38 By incorporating a weight loss
program into the treatment plan this can lower the amount of medication the dog will need to
take. Females, older dogs, and specific breeds, such as Beagles, Dachshunds, Collies, and
Labrador Retrievers, are more prone to obesity. Therefore, a diet plan should be enforced to
prevent and control body weight. Diets should be high protein and low fat, with a negative
energy balance. Along with strict dieting, a modified exercise plan should also be established for
the dog. An exercise program can help in reducing weight while maintaining range of motion
and muscle mass. Modified exercises, low-impact like walking or swimming, can also strengthen
joint supporting structures, muscles, ligaments, tendons, and joint capsules.1,7 Animal hospitals
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and rehabilitation facilities are starting to promote underwater treadmill therapy. This provides
exercise with the lowest possibly impact due to the dog being in water. Overall, to create a
successful treatment program the pet owner must be committed and willing to learn, the diet and
exercise must be monitored, and post-diet weight monitoring by a veterinary should be done on a
monthly basis.
Future Perspectives
Currently, osteoarthritis is treated or managed by invasive as well as noninvasive
means.24 In the recent past, the treatment options for arthritis were typically non-steroidal anti-
inflammatory drugs (NSAIDs) given alone or in combination with other disease-modifying
agents. NSAIDS (COX enzymes inhibitors) eliminate pain, but do not eliminate the signs and
symptoms of active disease nor do they repair cartilage. In recent years, chronic use of NSAIDs
has been linked to numerous side effects, including gastrointestinal (GI) bleeding, and renal and
hepatic dysfunction. Anti-inflammatory drugs such as aspirin and ibuprofen are non-specific
inhibitors of COX enzymes (COX-I and COX-II).37 They inhibit the production of inflammatory
prostaglandins, resulting in their therapeutic effect, but also inhibit the production of constitutive
prostaglandins, resulting in side effects, such as GI bleeding.37 Therefore, under these
circumstances, a safe therapy is warranted for arthritic dogs. Nutraceuticals are also gaining
popularity due to being readily available, inexpensive, and having minimal to no side
effects.34,37,39,40,41 Nutraceuticals, such as type-II cartilage, shilajit, 5-loxin, avocado/soybean
unsaponifiables, and curcumin have gained immense popularity for their anti-arthritic and anti-
inflammatory uses in humans and animals. However, with alternative medicine, there is no
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guarantee that the condition will improve; therefore, further safety and efficiency tests need to be
performed to ensure the quality of these new treatments.
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References
1. Vaughn-Scott T, Taylor JH. The pathophysiology and medical management of canine
osteoarthritis. J S Africa Assoc. 1997;68:21-25.
2. Lennon E, Marcellin-Little D. 2005. Canine osteoarthritis. Arthritis M.D. Accessed 13 Jan
2014.
3. Pasquini C, Spurgeon T, Pasquini S. Anatomy of domestic animals stemic and regional
approach. 11th ed. Pilot Point: Sudz; 2007.
4. Renberg WC. Pathophysiology and management of arthritis. Vet Clin Sm Anim. 2005;
35:559-564.
5. Scherer E. 2014. What happens in osteoarthritis? http://health.howstuffworks.com/diseases-
conditions/arthritis/osteoarthritis/what-happens-in-osteoarthritis.html. Accessed 21 Jan 2014.
6. Reid DM, Miller GC. Clin Trails Rheum Arthr Osteoarthr. Aberdeen, UK: Springer-Verlag
London Limited; 2008.
7. Baurys. Osteoarthritis in Dogs. http://www.osteoarthritisindogs.com/. Accessed 13 Jan 2014.
8. Nelson AE, DeVellis R F, Renner JB. Quantification of the whole-body burden of
radiographic osteoarthritis using factor analysis. Arthr Res Ther. 2011;13:R176.
9. Iliades C. 2014. The stages of osteoarthritis progression.
http://www.everydayhealth.com/osteoarthritis/stages-of-progression.aspx. Accessed 21 Jan 2014.
10. Holland K. Stages of osteoarthritis of the knee.
http://www.healthline.com/health/osteoarthritis-stages-of-oa-of-the-knee?toptoctest=expand.
Accessed 21 Jan 2014.
11. Bos PK, Van Melle LM, Van Osch, GJVM. Articular cartilage repair and the evolving role of
regenerative medicine. Open Access Surg. 2010;3:109-122.
12. Eyre DR, Weis M, Wu J. Articular cartilage collagen: An irreplaceable framework? Eur Cells
and Mater. 2006;12:57-63.
13. Rajat S, Manisha S, Robin S. Nutraceuticals: A review. Inter Res J Pharmacol. 2012;3:95-99.
14. ASPCA. Hip Dysplasia. http://www.aspca.org/pet-care/dog-care/hip-dysplasia. Accessed 1
Apirl 2014.
15. Tomiosso TC, Gomes L, De Campos Vidal B. Extracellular matrix of ostrich articular
cartilage. Biocell. 2005;29:47-54.
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23
16. WebMD. Hip Dysplasia in Dogs: Causes, Symptoms, and Tests.
http://pets.webmd.com/dogs/hip-dysplasia-dogs-causes-symptoms-tests. Accessed 1 April 2014.
17. Lin H, Shin F, Hou S. Digital imaging measuring of hip joint range of motion in dogs.
Taiwan Vet J. 2013;39:110-118.
18. Ates S, Hallaceli C, Hallaceli H. Goniometric measurements of the angular values of the
joints in the fore- and hindlimbs of kangal dogs. Israel J Vet Med. 2011;66:166-170.
19. MedlinePlus. ESR. http://www.nlm.nih.gov/medlineplus/ency/article/003638.htmMenon.
Accessed 25 Aug 2014.
20. AACC. ESR. American Association for Clinical Chemistry.
http://labtestsonline.org/understanding/analytes/esr/tab/test/. Accessed 25 Aug 2014.
21. Narcy SJ, Vangsness CT. Critical appraisal of the role of glucosamine and chondroitin in the
management of osteoarthritis of the knee. Nutr Diet Suppl. 2010;2:13-25.
22. Ward E. Steroid treatment- Long-term effects in dogs. VCA Animal Hopsital.
http://www.vcahospitals.com/main/pet-health-information/article/animal-health/steroid-
treatment-long-term-effects-in-dogs/951. Accessed 5 Feb 2014.
23. Kidd R. Use corticosteroids on your canine with caution. The Whole Dog Journal.
http://www.whole-dog-journal.com/issues/7_7/features/Corticosteroids-For-Canine_5647-
1.html. Accessed 5 Feb 2014.
24. Mahima, Verma AK, Tiwari R. Nutraceuticals from fruits and vegetables at a glance: A
review. J Bio Sci. 2013;13:38-47.
25. Simoens S, Laekeman G. Pharmacotherapeutic aspects of treating knee osteoarthritis with
glucosamine sulfate. Health. 2010; 2:705-707.
26. Fields T. 2009. Steroid side effects: How to reduce corticosteroid side effects. Hopsital for
Special Surgery Journal. http://www.hss.edu/conditions_steroid-side-effects-how-to-reduce-
corticosteroid-side-effects.asp. Accessed 5 Feb 2014.
31. Ghosh P. The pathobiology of osteoarthritis and the rationale for the use of petnosan
polysulfate for its treatment. Seminars Arthr Rheum. 1999;28(4).
27. Lloyd ME, Hart DJ, Nandra D, McALindon TE, Wheeler M, Doyle DV, et al. Relation
between insulin-like growth factor-I concentrations, osteoarthritis, bone density, and fractures in
general population: The Chingford study. Amm Rheum Dis. 1996;55:870-874.
28. Velloso CP. Regulation of muscle mass by growth hormone and IGF-I. British J Pharm.
2008;154:557-568
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29. Brandt KD. Modification by oral doxycycline administration of articular cartilage breakdown
in osteoarthritis. J Rheum Suppl. 1995;43:149-151.
30. Nganvongpanit K, Pothacharoen P, Suwankong N, Ong-Chai S, Kongtawelert P. The effect
of doxycycline on canine hip osteoarthritis: Design of a 6-month clinical trial. J. Vet. Sci.
2009;10:239-247.
32. Drugs.com. Cartophen vet (Canada) for animal use. Drugs.com.
http://www.drugs.com/vet/cartrophen-vet-can.html. Accessed 15 April 2015.
33. Franklin SP. Surgery STAT: Stem cell therapy in canine medicine. DVM360.
http://veterinarynews.dvm360.com/surgery-stat-stem-cell-therapy-canine-medicine?pageID=3.
Accessed 15 April 2015.
34. D’Altilio MD, Peal A, Alvey M. Therapeutic efficacy and safety of undenatured type-II
collagen singly or in combination with glucosamine and chondroitin in arthritic dogs. Tox Mech
Meth. 2001;17:189-196.
35. Singh P, Rani B, Chauhan AK. Healthy living with nurtaceuticals. Intern Res J Pharmcol.
2012;2:12-14.
36. Sanghi D, Avasthi S, Srivastava RN. Nutritional factors and osteoarthritis: A review article.
Inter J Med Up. 2008;4:42-53.
37. PetMD. Remedies for arthritis in dogs: Glucosamine, chondroitin sulfate, steroids, and
NSAIDs. http://www.petmd.com/dog/general health/evr_dg_remedies_for_arthritis_in
_dogs?page=2. Accessed 17 Feb 2014.
38. Suszynski M. 2014. Understanding primary and secondary osteoarthritis.
http://www.everydayhealth.com/osteoarthritis/primary-and-secondary-osteoarthritis.aspx.
Accessed 19 Jan 2014.
39. Deparle LA, Gupta RC, Canerdy TD. Efficacy and safety of glycosylated undenatured type-
II collagen (UC-II) in therapy of arthritic dogs. J Vet Pharmacol Thera. 2005;28:385-390.
40. Gupta RC, Canerdy TD, Lindley J. Comparitive therapeutic efficacy and safety of type-II
collagen (uc-II), glucosamine and chondroitin in arthritic dogs: Pain evaluation by ground force
plate. J Anim Physio Anim Nutr. 2011;96:770-777.
41. Gupta RC, Canerdy TD, Skaggs P. Therapeutic efficacy of undenatured type-II collagen (uc-
II) in comparison to glucosamine and chondroitin in arthritic horses. J Vet Pharmacol Therap.
2009;32: 577-584.
42. Millis DL. Canine rehabilitation & physical therapy. St. Louis, Mo.: Saunders. 2004;536.
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43. Provet. Hematology. http://www.provet.co.uk/geriatrics/5a65c32.htm. Accessed 25 Aug
2014.
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