Treatment with Cosequin of Bilateral Coxofemoral Osteoarthritis in a Great Dane
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The Nutramax/Cosequin®
CASE byCASE
Student Competition
winning entry
Treatment with Cosequin®
of Bilateral Coxofemoral
Osteoarthritis in a Great Dane
Oklahoma State University
Allison R. Hoffman, DVM
This article represents the second of two winning entries in the Nutramax/Cosequin®
Case by Case Student Competition. Dr. Hoffman was a senior student at Oklahoma
State University when she wrote this case study. She is currently affiliated with Cali-
fornia Eye Clinic for Animals, Tustin, California.
Osteoarthritis (OA), the most modifying agents; or a combina- the progression of OA while pro-
common cause of degenerative tion of both. The most commonly viding some symptomatic relief.
joint disease (DJD) in dogs, is a used antiinflammatory agents for The first substance that over-
chronic, progressive, noninfectious treating OA are NSAIDs. Al- came these shortcomings was Ade-
joint disorder that leads to degen- though NSAIDs are effective in quan® Canine (Luitpold Pharma-
eration of articular cartilage and reducing pain, these agents can re- ceuticals, Shirley, NY). Adequan®,
proliferative changes. Damage to sult in unwanted side effects such an injectable polysulfated gly-
articular cartilage may result from as gastrointestinal upset, hepato- cosaminoglycan (PSGAG), 10 has
abnormal stresses that disrupt the cellular toxicosis, renal disease, been shown to positively affect the
normal articular surface, in turn and occasionally death.2–4 In addi- cartilage degradation associated
leading to joint instability. Conse- tion, the newer cyclooxygenase-2 with OA. 10,11 Early research has
quently, the normal wear pattern inhibitors have been associated shown that very young, growing
as well as the turnover of articular with side effects.3 Dose-depend- dogs predisposed to hip dysplasia
matrix are accelerated.1 This process ent, nonsteroidal therapy can also treated with this PSGAG had bet-
is also accelerated by cytokines and result in a decrease in the gly- ter hip conformation than did
prostaglandins released by synovial cosaminoglycan content in the control dogs.12 The drawback to
cells into the joint. As a result, the cartilage, causing OA to worsen Adequan® use is that it must be
joint capsule thickens and periar- over time.5–8 The current rationale given by injection. Because many
ticular osteophytes form in an ef- is not to use NSAIDs continually owners are unable to comply with
fort to improve joint stability. unless they are needed to control this route of administration, re-
inflammation associated with per- search has focused on the use of
OSTEOARTHRITIS TREATMENT sistent pain.9 The shortcomings of oral products.
Current therapy for sympto- NSAIDs have encouraged research The oral product most com-
matic treatment of OA in dogs in- efforts toward safe, disease-modi- monly used to treat cartilage-relat-
cludes the use of antiinflammatory fying substances that can be used ed problems in veterinary medi-
medications; slow-acting, disease- long term and can possibly alter cine is Cosequin ® (NutramaxCompendium October 2001 Small Animal/Exotics 889
Laboratories, Edgewood, MD). which is found in the structural cartilage breakdown. Low-molecu-
Cosequin® is a patented nutraceuti- matrix of joints. Glucosamine is not lar-weight chondroitin sulfate has
cal combination of glucosamine a glycosaminoglycan but an amino been shown to be efficacious in
hydrochloride, low-molecular- sugar that has shown bioavailability treating OA in humans.25 Human
weight chondroitin sulfate, and in dogs.21 Its primary biologic role trials using low-molecular-weight
manganese ascorbate. Some practi- seems to be its ability to stimulate chondroitin sulfate show a carry-
tioners recommend combining chondrocytes to produce gly- over effect of up to 3 months after
modalities by starting with PSGAG cosaminoglycans. 14 Glucosamine cessation of therapy.26 This is im-
injections then switching to Cose- does not have any effect on inhibi- portant because it may take up to
quin® for long-term therapy.10 tion of proteases or their degradato- 3 months for signs to return when
In my opinion, the use of oral ry components to the cartilage ma- therapy is stopped or medication
nutraceuticals is gaining in popu- trix. Glucosamine has two main changed. In two human trials,26,27
larity. Much of the early research salts, which are available in hy- chondroitin sulfate was shown to
associated with their use has been drochloride and sulfate forms. The slow the progression of OA.
subjective (e.g., positive feedback hydrochloride form seems to deliver Chondroitin sulfate also has an
from owners). However, controlled more bioavailable glucosamine than antiinflammatory action similar to
experimental data as well as clini- does the sulfate form.22 To date, vet- that of NSAIDs, possibly because
cal data on mechanism of action, erinary research has evaluated only of its mechanism of action.27
efficacy, and safety in animals have the hydrochloride salt in combina- Glucosamine and chondroitin
been reported recently.1,13–20 tion with low-molecular-weight sulfate have different mechanisms
chondroitin sulfate. of action, which are evident when
NUTRACEUTICAL Chondroitin sulfate (whether comparative studies are evaluat-
COMPONENTS absorbed intact or broken into ed. 28,29 The combination of glu-
It is important to remember that constituents) may also provide for cosamine and chondroitin sulfate
the first major biochemical change the formation of a healthy joint used in the study presented here
that occurs in cartilage disease and matrix. Chondroitin sulfate is the was thought to protect the carti-
DJD is the loss of proteoglycans.10 most common glycosaminoglycan lage matrix as well as slow the pro-
Therefore, based on their compo- found in cartilage and has also gression of arthritic changes, as
nents (e.g., glucosamine–chon- shown bioavailability in dogs when shown in an animal instability
droitin sulfate–manganese combi- given in a pure form.23 The molec- model of DJD. 14 Because of its
nations), nutraceuticals may ular weight of the chondroitin sul- glucosamine, chondroitin sulfate,
theoretically have some beneficial fate has an effect on its bioavail- and manganese ascorbate compo-
effects in small animals. These sub- ability. 24 The primary role of nents, Cosequin ® is believed to
strates are the backbone needed for chondroitin sulfate is to inhibit provide the raw materials essential
the formation of proteoglycan, degradatory enzymes that lead to for synovial fluid synthesis and the
Chondrocytes and other
connective tissue cells
Hyaluronic acid
(50% Glucosamine)
se the backbone of
+Mangane proteoglycans
Glucose Glucosamine +Mang
anese Core protein
+Sulfa GAGs
te Link protein Proteoglycan
Chondroitin
sulfate Zinc, manganese, Stimulates Hyaluronic
vitamin C otein acid
d link pr
+Core an
}
}
Amino acids Procollagen
}
Keratin
sulfates
Chondroitin Other
sulfates saccharides
Copper, iron, vitamin C, silicon
Glycosaminoglycans (GAGs) Core
protein
COLLAGEN
Link
protein
FIGURE 1—Mechanism of action of Cosequin®.890 Small Animal/Exotics Compendium October 2001
complete cartilage matrix, includ- exercises, and measurements of
ing collagen, hyaluronic acid, and thigh circumference. Quantitative
glycosaminoglycans (Figure 1). evaluations included state-of-the-
art force-plate technology (piezo-
CASE PRESENTATION electric quartz-crystal type) to de-
A 1-year-old, 51-kg, spayed Great termine if there was improved
Dane was presented to the Boren joint function and analyze how
Veterinary Medical Teaching Hos- these data correlated with the
pital at Oklahoma State University qualitative data.
on October 20, 1998, with a During the 6-month evalua-
shortened limb stride bilaterally, tion period, there was a decrease
quadriceps fibrosis, an intermittent in the dog’s lameness scores
“bunny-hop” gait, and hyperexten- (Table 1). Initial lameness scores
sion of the tarsi. The patient were established using the fol-
demonstrated severe loss of hip lowing criteria:
range of motion and became ag-
gressive on palpation of the cox-
FIGURE 2—Ventrodorsal radiograph of
• Grade I—Subtle and inconsis-
ofemoral joints. No other abnor- the pelvis obtained during the initial patient tent lameness not apparent at a
malities were observed on history, evaluation revealed good congruity of walk and not consistently iden-
physical examination, complete both coxofemoral joints, a mild degree of tified at a trot
blood count, or biochemical analy- periarticular osteophytosis along the cranial
sis. Radiography revealed good
borders of both acetabula, and underlying • Grade II—Consistent and
subchondral sclerosis. The femoral heads
joint congruity, bilateral periarticu- have no such osteophytosis or subchondral
mild lameness at a trot
lar osteophytosis, and a mild de- sclerosis.
• Grade III—Consistent mod-
gree of bilateral subchondral scle- erate lameness at a walk
rosis (Figure 2). during treatment with the nu-
traceutical. This approach could • Grade IV—Severe, non–
TREATMENT AND then be used as a standard by which weight-bearing lameness
CLINICAL COURSE other patients with DJD
A twofold hypothesis was made. could be evaluated, TABLE 1. Lameness Scores
First, it was thought that the com- whether untreated or
During the Treatment Period
bination of glucosamine, chon- treated with a nutraceu-
droitin sulfate, and manganese tical or pharmaceutical. Time Period Grade
ascorbate would slow the progres- Qualitative evaluations
sion of DJD. Secondly, it was hy- at 3 weeks, 4 months, Initial evaluation III
pothesized that treatment with a and 6 months after the 3-week follow-up III
nutraceutical would show objective initial examination in- 4-month follow-up II
evidence of weight transfer from cluded lameness scores,
the forelimbs to the hindlimbs, in- hindlimb goniometry 6-month follow-up I/II
dicating improved coxofemoral using range-of-motion
joint function as demonstrated by
force-plate analysis. TABLE 2. Thigh Circumference Measurements
The patient was started on Cose- During the Treatment Period
quin® DS at a dose of two capsules
in the morning and one in the Time Period Right (inches) Left (inches)
evening. Each tablet contains glu-
cosamine (500 mg), sodium chon- Initial evaluation 15.75 16
droitin sulfate (400 mg), ascorbate 3-week follow-up 15.75 16
(66 mg), and manganese (10 mg). 4-month follow-up 16.75 17.25
The dog required several reevalua- 6-month follow-up 17 17.5
tions over time; therefore, a quanti- Total increase 1.25 1.5
tative and qualitative method was
designed to evaluate the patientCompendium October 2001 Small Animal/Exotics 891
TABLE 3. Hindlimb Goniometry Evaluation
Time Period Right Extension Right Abduction Left Extension Left Abduction
Initial evaluation 90˚ 40˚ 70˚ 60˚
3-week follow-up 90˚ 40˚ 80˚ 60˚
4-month follow-up 120˚ 50˚ 90˚ 70˚
6-month follow-up 130˚ 90˚ 110˚ 75˚
Net increase 40˚ 50˚ 40˚ 15˚
The patient initially presented with Radiographs obtained 6 months the 6-month follow-up, the dog
grade III lameness. On the final after the initial evaluation revealed showed pronounced clinical im-
evaluation, the dog tested at lame- that the OA was still present, as provement with Cosequin® treat-
ness grade I/II. were periarticular osteophytes and ment over the 6-month period
Thigh circumference was also as- subchondral sclerosis (Figure 5). with no side effects. This improve-
sessed. With the dog in a standing ment was assessed qualitatively by
position, thigh circumference was DISCUSSION a decrease in lameness score, a bi-
measured high in the flank region at This is the first known published lateral increase in thigh circumfer-
the level of the ischiatic tuberosity. clinical evaluation regarding the use ence, and a bilateral goniometric
The measuring tape was kept paral- of an oral nutraceutical in a young increase. Final analysis of the
lel to the ground. There was a 1.25- animal with radiographically evi- force-plate graphs revealed an in-
inch increase in right thigh circum- dent hip dysplasia and using the de- crease in the vertical force applied
ference and a 1.5-inch increase in fined parameters for
left thigh circumference during the qualitative-quantitative 500
treatment period (Table 2). analysis. Traditionally, Force in a plane perpendicular
to direction of movement
Hindlimb goniometry using these compounds have Parallel force
range-of-motion exercises was per- been used in older ani- 400
Vertical force
formed during the testing period. mals with established
During the final evaluation, go- disease or as a preventive
niometry revealed a 40˚ increase for measure in predisposed
both the right and left hindlimb ex- dogs.10 In a retrospective 300
tensions. Increases for right and left survey, 3000 veterinari-
hindlimb abduction were 50˚ and ans who evaluated thou-
Force (N)
15˚, respectively (Table 3). sands of dogs (96% of
200
Evaluation of Cosequin® efficacy which were older than 5
also involved trotting the patient years of age) concluded
across a force plate. Four trials for that Cosequin® alleviat-
the right and left forelimbs and ed the pain and discom- 100
hindlimbs were conducted during fort of OA with less than
the four evaluations, generating 64 2% of the animals show-
graphs (Figure 3). Data generated ing side effects.30
0
by the graphs indicated an upward The study presented
slope, demonstrating an overall in- here evaluated a young
crease in hindlimb loading by a Great Dane with radi-
44-N average or an 11-lb differ- ographic and clinical -100
ence for the treatment period (Fig- signs of hip dysplasia 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0
ure 4). A significant increase was with secondary OA Time (seconds)
detected using the r 2 analysis (co- changes. Although the
efficient of determination) with a patient still had radi- FIGURE 3—Standard force-plate graph. The
hindlimb vertical force detected by the force plate
P value of less than .001. ographic OA changes at is shown as the second spike on the graph.892 Small Animal/Exotics Compendium October 2001
325 –
Hindlimb vertical force (N)
300 –
275 –
250 –
225 – r 2 = .42
P < .001
200 –
175 –
–
–
–
–
–
–
–
0 10 20 30 40 50 60
Days between 4- and 6-month evaluations
FIGURE 4—Analysis of force plate measurements yields
a 44-N average increase in hindlimb loading during the
treatment period.
to the hindlimbs that was in fact promote topical or
transferred from the forelimbs, sug- liquid products as
gesting improved joint function. having improved FIGURE 5—Ventrodorsal radiograph of the pelvis
Veterinarians often prescribe oral bioavailability, but obtained at the 6-month follow-up evaluation.
Periarticular osteophytosis and subchondral sclerosis
nutraceuticals alone or in combina- there is no research were still evident with significant remodeling.
tion with NSAIDs. When given to document this
this combined therapy, patients re- claim. A recent study24
ceive the benefits of quick pain re- showed that some products contain Dane treated in this case study re-
lief and minimal side effects from none of the label ingredients. In re- sponded quickly to treatment and
the NSAID as well as the safe, long- sponse to these findings, the Arthri- maintained improvement. Other
term, disease-modifying potential tis Foundation recommends using dysplastic dogs treated for a 40-day
provided by the nutraceutical. Hu- caution when choosing products for period with injectable low-molecu-
man trials using the equivalent of the treatment of OA.36 lar-weight chondroitin sulfate have
the test agent showed a decreased Because this report evaluated also shown clinical improvement.12
dependence on NSAIDs. 31 This only a single dog, it is impossible to However, a large percentage of
case study reported the efficacy of assess whether the treatment slowed young dogs with secondary OA
an agent that has been used with the progression of the OA disease will improve over an 18-month
good clinical results in both veteri- process. There currently does not period without clinical treatment.38
nary and human medicine.13,19,20,31,32 exist a validated method to radi- Therefore, further controlled stud-
The same agent has also recently ographically assess OA progression ies should be completed in young
been shown to palliate joint inflam- in animals. It is also unknown dogs to confirm or dismiss the re-
mation and protect cartilage when whether 6 months is enough time sults found in this study.
given prior to cartilage insult.13,33 to show significant change. Human The knowledge base regarding
This may result in the further use of trials have used validating tech- the use of oral nutraceuticals con-
oral disease-modifying agents as niques to show that the low-molec- tinues to grow; however, much re-
preventive agents. ular-weight chondroitin sulfate mains unknown about their rele-
Because oral nutraceuticals are found in Cosequin® has slowed the vance in veterinary medicine.
not drug compounds, their purity, progression of OA in knees and Also, when evaluating slow-acting,
molecular size, and efficacy can vary hands.26,37 Experimental placebo- disease-modifying agents, the out-
greatly. Some compounds promoted controlled trials in animal models come measurements used to study
as disease-modifying agents (e.g., of arthritis have also shown a carti- faster-acting antiinflammatory
Perna mussel supplements) cannot lage protective effect of the same agents may be inappropriate.
be substantiated.34,35 Products that studied combination.1,13,14,33 However, the combined qualita-
make such claims (e.g., cures arthri- tive and quantitative evaluations
tis, regenerates and rebuilds carti- CONCLUSION used in this study may be an ac-
lage) should be considered as ques- Osteoarthritis in young dogs is a ceptable protocol in which to
tionable. Some manufacturers variable disease process. The Great monitor patients with joint insta-Compendium October 2001 Small Animal/Exotics 893
bility, regardless of the treatment Compend Contin Educ Pract Vet 16(4): 23. Conte A, Volpi N, Palmieri L: Bio-
501–506, 1994. chemical and pharmacokinetic aspects
selected.
12. Lust G, Williams A, Burton-Wurster of oral treatment with chondroitin sul-
At the 28-month follow-up eval- N, et al: Effects of intramuscular ad- phate. Arzniemittelforschung 45(8):
uation, the patient was reported to ministration of glycosaminoglycan 918–925, 1995.
be showing little or no clinical polysulfates on signs of incipient hip 24. Adebowale A, Cox D, Eddington N:
signs of joint discomfort while con- dysplasia in growing pups. Am J Vet Analysis of glucosamine and chon-
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13. Canapp SO, McLaughlin RM, products and the Caco-2 permeability
Hoskinson JJ, et al: Scintigraphic eval- of chondroitin sulfate raw materials.
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