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1382 Vet Med Today: What Is the Evidence? JAVMA, Vol 237, No. 12, December 15, 2010
Problem
A 13-year-old castrated male mixed-breed dog
weighing 33.6 kg (73.9 lb) was evaluated for a history
of bilateral, gradually progressive hind limb weakness,
reluctance to climb stairs or jump, and intermittent
mild left hind limb lameness. The dog had a previous
history of severe left-sided hip joint osteoarthritis and
dysplasia diagnosed via radiography at 7 years of age;
an acute rupture of the right cranial cruciate ligament
at 8 years of age, which was treated successfully with
a tibial plateau leveling osteotomy (TPLO); and atopy
with intermittent mild to moderate pruritus and super-
ficial pyoderma that was well controlled with a short
course of antihistamines, prednisone, and antimicrobi-
als. The dog was receiving no medication at the time it
was brought to the hospital, and no other clinical prob-
lems were reported by the owner.
Physical examination revealed mild paresis and
moderate muscle atrophy in both hind limbs. The dog
showed signs of pain on extension of the left hip joint,
and the TPLO plate was palpable on the proximal aspect
of the right tibia. Posture, placing responses, neurologic
reflexes, and sensation were unremarkable in all limbs.
The hind limb gait was stiff, and a mild left hind limb
lameness was evident when the dog walked. The dog was
in good body condition (3 on a 5-point scale). The rest
of the physical examination revealed no abnormalities.
Results of a CBC, serum biochemical analysis, and
urinalysis were all within reference limits except for a
mildly high increase in alkaline phosphatase activity
(342 U/L; reference limits, 10 to 150 U/L). Radiography
of both hind limbs revealed severe sclerosis, periarticu-
lar osteophytes, and subluxation of the left hip joint;
mild periarticular osteophytes and a healed TPLO sur-
gical site in the right stifle joint; and mild sclerosis and
spondylosis deformans at the lumbosacral joint.
The owner was interested in medical treatment
for osteoarthritis but was concerned about potential
adverse effects of NSAIDs and inquired about the use
of glucosamine and chondroitin-containing nutritional
supplements, either alone or as an adjunct, to reduce
the dose or frequency of NSAID needed to control the
dog’s lameness and pain.
Formulation of the Clinical Question
The problem was identified as severe osteoarthri-
tis of the left hip joint and mild osteoarthritis of the
right stifle joint. The efficacy of NSAID administration
This report was submitted by Brennen A. McKenzie, MA, VMD; from
Adobe Animal Hospital, 4470 El Camino Real, Los Altos, CA 94022.
Address correspondence to Dr. McKenzie (mckenzievmd@gmail.
com).
What Is the Evidence?
In cooperation with
for control of osteoarthritis pain in dogs has been well
documented, but NSAIDs also have potential adverse
effects, some of which can be serious, and these drugs
should not be used concurrently with prednisone.1
Oral administration of glucosamine and chondroitin
is often used for prevention and treatment of osteo-
arthritis in dogs, and there is widespread belief in
the safety and efficacy of this practice. However, it is
important to base recommendations to clients on the
best possible research evidence and not solely on the
popularity of a practice or anecdotal reports of posi-
tive outcomes.
Clinical Question
Would treatment with a supplement containing
glucosamine and chondroitin be likely to yield a clini-
cally meaningful improvement in the signs of chronic
osteoarthritis in a dog without unacceptable adverse
effects, either as an alternative or adjunct to NSAID
treatment?
Evidentiary Search Strategy
Ideally, evaluation of the potential usefulness of a
drug or procedure would include thorough assessment
of basic biologic plausibility, hypothesized mechanisms
of actions, relevant in vitro and laboratory animal
model research, and the results of clinical trials grad-
ed in terms of quality and relevance.2 However, such a
strategy is time-consuming and requires some degree
of expertise in evaluation of published research; thus,
it may not always be practical in the general practice
setting. More limited, focused review of the scientific
literature has the potential to improve clinical decision
making, although there is a necessary trade-off between
efficiency and the risk of basing clinical judgments on
incomplete information.
With this in mind, a search of the PubMed database
was conducted by use of the following 4 terms: glu-
cosamine, chondroitin, dog, and arthritis. The search
yielded 16 reports, of which 33–5 appeared directly rel-
evant to the clinical question. Full-text copies of these
articles were obtained from a variety of sources, includ-
ing a member-accessible online archive at the AVMA
website, an alumni copy service at the University of
Pennsylvania Veterinary School Library, and the com-
mercial ScienceDirect copy service.
One of the identified reports was a systematic re-
view3 of clinical trials for osteoarthritis treatments in
dogs. This review included a single study of the use
of glucosamine and chondroitin in osteoarthritis treat-
ment, and that study revealed no significant improve-
ment in clinical signs for dogs treated PO with glu-
cosamine and chondroitin, compared with the effects
JAVMA, Vol 237, No. 12, December 15, 2010 Vet Med Today: What Is the Evidence? 1383
of placebo treatment. On the basis of an analysis of
the quality of the study and the totality of the clinical
trial evidence, the authors of the review article con-
cluded, “A moderate level of comfort exists that the
claimed relationship is scientifically valid. The lack of
response and the limited number of controlled trials
make it difficult to formulate any recommendations
at this time.” According to the authors, “A moderate
level of comfort describes a relationship as promising
but not definitive.”
The clinical trial4 cited in the systematic review was
also obtained. This was a prospective, randomized, dou-
ble-blinded, placebo-controlled trial in which changes
were assessed in subjective and objective measures of
clinical signs associated with confirmed osteoarthritis
in dogs. Subjects were assigned to groups treated with
carprofen, meloxicam, a glucosamine-chondroitin com-
bination product, or an inert placebo. Seventy-one sub-
jects were recruited, and 3 failed to complete the study
(1 from each of the placebo, carprofen, and meloxicam
groups). The subjects were evaluated after 30 and 60
days of treatment. Results indicated that objectively mea-
sured variables improved significantly with carprofen
and meloxicam treatment but not with the glucosamine-
chondroitin product nor with the placebo. Subjective
findings of veterinary surgeons agreed with the results of
the objective evaluation, whereas subjective assessment
by owners identified improvement only with meloxicam.
There were no changes in serum biochemical or hemato-
logic values for any dog, and 1 dog had a serious adverse
reaction to carprofen.
The third study5 was a prospective, double-blinded
trial in which effects were compared between oral ad-
ministration of a glucosamine-chondroitin combination
product and carprofen. Dogs with osteoarthritis of hip or
elbow joints were assigned to groups by alternate alloca-
tion, and no placebo was used as a control treatment.
Forty-two subjects were enrolled, and 6 failed to com-
plete the study (5 in the glucosamine-chondroitin group
and 1 in the carprofen group). Changes in 5 subjective
measures of clinical signs assessed by participating vet-
erinarians were compared between groups at 3 points
during the 70-day treatment period and at 1 point after
cessation of treatment. Results indicated that carprofen-
treated dogs had improvement in all measures, often
at multiple assessment times for each measure. On the
other hand, dogs treated with glucosamine-chondroitin
had significant improvement in 3 of 5 measures but only
at the final assessment point during the treatment pe-
riod. The only adverse events associated with treatment
pertained to 2 dogs in the glucosamine-chondroitin
group, which were withdrawn from the trial because of
unspecified adverse drug reactions.
Given the aforementioned evidence, what decision
would you make?
Decision and Outcome
Given the information contained in the 3 reports,
there was insufficient evidence to support a recommen-
dation of glucosamine and chondroitin as an alternative
to NSAID medication for treatment of clinical signs at-
tributed to osteoarthritis in dogs. The clinical trial evi-
dence was severely limited, and results were mixed; how-
ever, the larger size, superior design, and objective as-
sessment criteria of the study4 that failed to find an effect
of oral glucosamine-chondroitin administration would
support giving greater weight to those results than to the
limited positive results of the other trial.5 Both clinical
trials revealed significant benefit from NSAID treatment,
and both involved uncommon but potentially impor-
tant adverse effects from glucosamine-chondroitin and
NSAID treatment. No literature addressing the possible
use of a glucosamine-chondroitin product as an adjunct
to NSAID treatment was identified.
The evidence was discussed with the owner, who
elected to begin meloxicam treatment without concur-
rent glucosamine or chondroitin supplementation. Po-
tential adverse effects were discussed, and the owner
was informed that meloxicam should not be given con-
currently with prednisone. Meloxicam at a dosage of
0.1 mg/kg (0.045 mg/lb), PO, every 24 hours was dis-
pensed, and a follow-up evaluation was scheduled for 2
to 4 weeks afterward.
At follow-up, no change in serum biochemical or
hematologic results and no signs of adverse reaction to
the medication were evident. Subjective observations
by the owner and clinician suggested moderate im-
provement in the dog’s clinical signs of osteoarthritis.
Discussion
One objection to an evidence-based approach to
veterinary medicine in general practice is the percep-
tion that research using the scientific literature is dif-
ficult and time-consuming. The evidence gathered in
the case reported here was obtained easily and quickly
with minimal cost. It is also a common complaint that
the limited quantity and quality of veterinary clinical
research are barriers to evidence-based practice. How-
ever, there is often relevant and accessible research evi-
dence to answer common and important clinical ques-
tions, and when such evidence is available, it is a more
reliable basis for decision making than anecdote or per-
sonal experience.
Glucosamine and chondroitin are perhaps the most
widely used nutraceuticals for treatment of osteoarthri-
tis in human and veterinary patients. It is worth con-
sidering, however, that there is only very weak clinical
trial evidence to support this practice and that it is ap-
propriate for veterinarians to temper their recommen-
dations to their clients accordingly.
References
1. Sanderson RO, Beata C, Flipo RM, et al. Systematic review of
the management of canine osteoarthritis. Vet Rec 2009;164:418–
424.
2. Cockcroft PD, Holmes MA. Handbook of evidence-based veteri-
nary medicine. Oxford, England: Blackwell Publishing, 2003.
3. Aragon CL, Hofmeister EH, Budsberg SC. Systematic review of
clinical trials of treatments for osteoarthritis in dogs. J Am Vet
Med Assoc 2007;230:514–521.
4. Moreau M, Dupuis J, Bonneau NH, et al. Clinical evaluation of
a nutraceutical, carprofen and meloxicam for the treatment of
dogs with osteoarthritis. Vet Rec 2003;152:323–329.
5. McCarthy G, O’Donovan J, Jones B, et al. Randomized double-
blind, positive-controlled trial to assess the efficacy of glucos-
amine/chondroitin sulfate for the treatment of dogs with osteo-
arthritis. Vet J 2007;174:54–61.
