ArticlePDF Available

What Is the Evidence?

Authors:
  • 1) Loyal 2) Adobe Animal Hospital
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.
Article
Full-text available
Osteoarthritis is a slowly progressive and debilitating disease that affects canines of all breeds. Pain and decreased mobility resulting from osteoarthritis often have a negative impact on the affected canine's quality of life, level of comfort, daily functioning, activity, behaviour, and client-pet companionship. Despite limited and conflicting evidence, the natural products glucosamine hydrochloride (HCl) and chondroitin sulfate are commonly recommended by veterinarians for treating osteoarthritis in dogs. There is a paucity of well-designed clinical veterinary studies investigating the true treatment effect of glucosamine and chondroitin. The purposes of this review article are to provide a brief background on glucosamine and chondroitin use in canine osteoarthritis and to critically review the available literature on the role of these products for improving clinical outcomes. Based on critical review, recommendations for practice are suggested and a future study design is proposed.
Article
Full-text available
Persistent right aortic arch (PRAA) in cats is an uncommon vascular anomaly with clinical signs referable to oesophageal obstruction. To our knowledge no reports of axial skeletal malformations concomitant to PRAA have been reported in cats. The aim of this case series is to depict a new clinical feature in cats affected by PRAA. In the study six cats with a diagnosis of vascular ring anomaly were enrolled. A complete physical examination, a neurological examination and a total body radiograph were performed on each animal. Four of the six cats showed contemporary PRAA and skeletal malformations. Additionally, for the first time, a genetic test was performed on one subject to detect DNA alterations in the homologous DiGeorge region of cat. The percentage of skeletal malformations reported in the normal population was compared with animals with PRAA and showed a higher frequency. Genetic testing failed to demonstrate a correlation between PRAA and DiGeorge genomic deletion. A review of veterinary and human diseases that presented both conditions was assessed. The few animals enrolled do not allow definitive conclusions. Further studies are required to corroborate the correlation between PRAA and axial skeletal malformations in cats.
Article
Related articles: https://www.researchgate.net/publication/348819760_Chondroprotectives_used_for_the_treatment_of_knee_osteoarthritis_A_comment https://www.researchgate.net/publication/327136697_Glycosaminoglycans_and_their_precursors_in_osteoarthritis IN RUSSIAN: https://www.researchgate.net/publication/273145413_K_voprosu_o_roli_hondroprotektorov_v_lecenii_artroza_na_puti_k_dokazatelnoj_medicine
Article
Full-text available
This review assesses the evidence for the efficacy of therapies used in the management of osteoarthritis in dogs on the basis of papers published in peer-reviewed journals in English between 1985 and July 2007. Sixty-eight papers were identified and evaluated. They considered four alternative therapies, one use of functional food, two intra-articular agents, six nutraceutical agents, 21 pharmacological agents, two physical therapies, three surgical techniques and two combinations of weight control. There was a high level of comfort (strong evidence) for the efficacy of carprofen, firocoxib and meloxicam, and a moderate level of comfort for the efficacy of etodolac in modifying the signs of osteoarthritis. There was a moderate level of comfort for the efficacy of glycosaminoglycan polysulphate, licofelone, elk velvet antler and a functional food containing green-lipped mussel for the modification of the structures involved in the disease. There was weak or no evidence in support of the use of doxycycline, electrostimulated acupuncture, extracorporeal shockwave therapy, gold wire acupuncture, hyaluronan, pentosan polysulphate, P54FP (extract of turmeric), tiaprofenic acid or tibial plateau levelling osteotomy.
Article
THE final article of this three-part series discusses a key skill required for the practice of evidence-based veterinary medicine (EBVM) - the ability to appraise the evidence presented in scientific papers. Having identified information needs and searched for evidence - processes discussed in Parts 1 and 2 - the clinician needs to evaluate the usefulness of the evidence by asking questions such as, 'Is it true?' and 'Is it relevant to my patient?'. Clearly, an understanding of study design and methods of analysing the results is required in order to determine the validity and relevance of clinical studies.
Article
The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.
Article
Thirty-five dogs were included in a randomised, double-blind, positive controlled, multi-centre trial to assess the efficacy of an orally-administered glucosamine hydrochloride and chondroitin sulfate (Glu/CS) combination for the treatment of confirmed osteoarthritis of hips or elbows. Carprofen was used as a positive control. Dogs were re-examined on days 14, 42 and 70 after initiation of treatment. Medication was then withdrawn and dogs were re-assessed on day 98. Response to treatment was based on subjective evaluation by participating veterinarians who recorded their findings at each visit. Dogs treated with Glu/CS showed statistically significant improvements in scores for pain, weight-bearing and severity of the condition by day 70 (P<0.001). Onset of significant response was slower for Glu/CS than for carprofen-treated dogs. The results show that Glu/CS has a positive clinical effect in dogs with osteoarthritis.
Article
To identify and critically evaluate the quality of evidence of the most commonly used pharmacologic, nutraceutical, and purported slow-acting drugs of osteoarthritis for the management of osteoarthritis in dogs by use of the FDA's evidence-based medicine scoring system. Systematic review. 16 clinical trials. A broad bibliographic search was performed prior to May 2006. Inclusion criteria focused on prospective trials evaluating commonly used medical treatment interventions for the management of osteoarthritis in dogs and published in peer-reviewed journals. The analysis consisted of the following: study design rating, quality factor rating, quantity rating, consistency rating, relevance to disease risk reduction rating, and cumulative strength of evidence ranking. 4 trials evaluating meloxicam were rated as type I. Three trials evaluating carprofen were rated as type I, and 2 trials were rated as type III. One trial evaluating each of the following agents was rated as type 1: etodolac; P54FP; polysulfated glycosaminoglycan; and a combination of chondroitin sulfate, glucosamine hydrochloride, and manganese ascorbate. Two trials evaluating pentosan polysulphate and 2 trails evaluating green-lipped mussels were rated as type I. One trial evaluating hyaluronan was rated as type III. A high level of comfort exists for meloxicam that the claimed relationship is scientifically valid and that its use is clinically efficacious for the treatment of osteoarthritis in dogs. A moderate level of comfort exists for carprofen; etodolac; pentosan polysulphate; green-lipped mussels; P54FP; polysulfated glycosaminoglycans; and a combination of chondroitin sulfate, glucosamine hydrochloride, and manganese ascorbate. An extremely low level of comfort exists for hyaluronan.
Handbook of evidence-based veteri-nary medicine
  • Cockcroft Pd Holmes
  • Ma
Cockcroft PD, Holmes MA. Handbook of evidence-based veteri-nary medicine. Oxford, England: Blackwell Publishing, 2003.