What You Know That Ain’t Necessarily So: Glucosamine & Arthritis in Dogs

I recently gave a lecture at the Western Veterinary Conference called “What You Know that Ain’t Necessarily So.” The purpose of this was to take some common or controversial beliefs and practices in veterinary medicine and discuss the scientific evidence pertaining to these. This was not intended as a definitive, “final word” on these subjects, but as an illustration of how weak and problematic the evidence often is even behind widely held beliefs. In some cases, these practices or ideas may actually be valid, but without good quality scientific evidence, we should always be cautious and skeptical about them.

Eventually, I will post recordings of the presentations themselves, but for now I am posting a summary of each topic.

Each starts with a focused clinical question using the PICO format.

P– Patient, Problem Define clearly the patient in terms of signalment, health status, and other factors relevant to the treatment, diagnostic test, or other intervention you are considering. Also clearly and narrowly define the problem and any relevant comorbidities. This is a routine part of good clinical practice and so does not represent “extra work” when employed as part of the EBVM process.

I– Intervention Be specific about what you are considering doing, what test, drug, procedure, or other intervention you need information about.

C– Comparator What might you do instead of the intervention you are considering? Nothing is done in isolation, and the value of most of our interventions can only be measured relative to the alternatives. Always remember that educating the client, rather than selling a product or procedure, should often be considered as an alternative to any intervention you are contemplating.

O– Outcome What is the goal of doing something? What, in particular, does the client wish to accomplish. Being clear and explicit, with yourself and the client, about what you are trying to achieve (cure, extended life, improved performance, decreased discomfort, etc.) is essentially in evidence-based practice.

This is then followed by a summary of the evidence available at each of the levels in the following pyramid (which is a pragmatic reinterpretation of the classical pyramid of evidence that is a bit more useful for general practice veterinarians).

evidence pyramid

 

Finally, I list the Bottom Line, which is my interpretation of the evidence.

Glucosamine for Dogs with Arthritis

  1. Clinical question

P– Dogs with naturally occurring arthritis

I– oral glucosamine

C– NSAID, nothing

O– Reduced pain, lameness

2. Synthetic Veterinary Literature

a. Three systematic reviews:

the global strength of evidence of efficacy was low…In addition, results were contradictory in the 2 studies conducted in dogs.  (Vandeweerd et al., 2012)

Low quality & quantity of evidence, no overall recommendation. (Sanderson et al., 2009)

One study included, good quality, no benefit (Aragon, Hofmeister, & Budsberg, 2007)

b. Three critically appraised topics (include same 2 studies as systematic reviews)

Best Bets for Vets Nutraceuticals versus carprofen in dogs with osteoarthritis

Carprofen is superior to glucosamine/chondroitin supplements in reducing the clinical signs of osteoarthritis (McCarthy et al. 2007). Glucosamine and chondroitin supplement efficacy cannot be commented on, as there was no placebo group or there was no comparison made with the placebo group in the studies.

Banfield Evaluation of glucosamine hydrochloride/ chondroitin sulfate nutraceuticals as a treatment to improve symptoms associated with canine and feline joint disease

Despite some evidence that a combination of glucosamine hydrochloride and chondroitin sulfate nutraceuticals improves symptoms associated with joint disease in dogs and cats, strong clinical evidence of efficacy is lacking, and these compounds are understudied.

What’s the Evidence? Glucosamine for osteoarthritis in dogs 2 studies, mixed results, better quality study found no benefit, carprofen better (McKenzie, 2010)

2. Primary Veterinary Literature

Already reviewed in synthetic literature

3. Human Literature

a. Systematic Reviews (dozens, these are just a few representative ones)

[Glucosamine] is ineffective for pain reduction in patients with knee OA. GS may have function-modifying effects in patients with knee OA when administered for more than 6 months. However, it showed no pain-reduction benefits after 6 months of therapy. (Wu, 2013)

Significant improvement in pain and functional indices and a decrease in the loss of joint space width were demonstrated in some but not all studies…The safety of these nutraceuticals has been demonstrated across all of the reviewed trials, and there were no significant issues with tolerance…An overall recommendation to use nutraceuticals in the treatment of all patients with OA is not strongly supported by the available data. (Ragle, 2012)

Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged. (Wandel, 2010)

Pooled results from studies using a non-Rotta preparation or adequate allocation concealment failed to show benefit in pain and WOMAC function while those studies evaluating the Rotta preparation showed that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA. (Towheed, 2005)

Most of the observed heterogeneity in glucosamine trials is explained by brand…Large inconsistency was found though. Low risk of bias trials, using the Rottapharm|Madaus product, revealed a small effect size. (Eriksen, 2014)

b. Clinical Practice Guidelines

We cannot recommend using glucosamine and chondroitin for patients with symptomatic osteoarthritis of the knee…. At this time, both glucosamine and chondroitin sulfate have been extensively studied. Despite the availability of the literature, there is essentially no evidence that minimum clinically important outcomes have been achieved compared to placebo, whether evaluated alone or in combination. American Academy of Orthopedic Surgeons

We conditionally recommend that patients with OA should not use the following:

Chondroitin sulfate Glucosamine

American College of Rheumatology

Glucosamine and chondroitin were both found to be “not appropriate” for all patients when used for disease modification and “uncertain” for all patients when used for symptom relief.  Osteoarthritis Research Society International

c. Primary Human Literature

Glucosamine/Arthritis Intervention Trial (GAIT)

Over 2 years, no treatment achieved a clinically important difference in WOMAC pain or function as compared with placebo…. Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain.

At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo.

Bottom Line-

  • Almost certainly safe
  • Basic science supports potential benefits
  • Very limited research in dogs
    • Weak and conflicting evidence
    • Little reason to believe significant benefits
  • Extensive human research
    • Conflicting evidence
    • Most likely little to no benefit

 

References

Aragon, C. L., Hofmeister, E. H., & Budsberg, S. C. (2007). Topics in Drug Therapy of treatments for osteoarthritis in dogs. Journal of the American Veterinary Medical Association, 230(4).

McKenzie, B. A. (2010). What Is the Evidence?? Glucosamine for osteoarthritis in dogs. Journal of the American Veterinary Medical Association, 237(12), 1382–1383.

Ragle, RL. et al. Nutraceuticals in the management of osteoarthritis : a critical review. Drugs Aging. 2012 Sep;29(9):717-31.

Sanderson, R. O., Beata, C., Flipo, R.-M., Genevois, J.-P., Macias, C., Tacke, S., … Innes, J. F. (2009). Systematic review of the management of canine osteoarthritis. The Veterinary Record, 164, 418–424. doi:10.1136/vr.164.14.418

Vandeweerd, J.-M., Vandeweerd, S., Gustin, C., Keesemaecker, G., Cambier, C., Clegg, P., … Gustin, P. (2012). Understanding Veterinary Practitioners’ Decision-Making Process: Implications for Veterinary Medical Education. Journal of Veterinary Medical Education, 39, 142–151. doi:10.3138/jvme.0911.098R1

Wu, D. et al.  Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomised, double-blind, placebo-controlled trials. Int J Clin Pract. 2013

 

 

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4 Responses to What You Know That Ain’t Necessarily So: Glucosamine & Arthritis in Dogs

  1. Lindsey says:

    Hello,

    Thank you for sharing your research.

    I have an older dog with arthritis and we actually just started her on a higher quality GC and have actually noticed some improvements. I am a dietitian so research is very, very important to me and have been doing some investigating on the benefits of curcumin, boswellin, and bioperine for her arthritis but was wondering if you had any feedback on that combination supplement for dogs. I only seem to find isolated curcumin supplements or boswellin for dogs but not this combo and I want to ensure it’s safe for her. We currently give her boswellin but it doesn’t seem to be doing a whole lot. Any thoughts, please? Our current vet is very mainstream and isn’t able to help us much in this area.

  2. skeptvet says:

    I’m not aware of any controlled research on the combination. I have written about curcumin, and so far there isn’t much direct research evidence to show benefits. Some promising preliminary evidence exists, but nothing solid. There is far less evidence for Boswellia, so in general I’m not yet convinced that has much value.

  3. Chris says:

    Brennen ,

    What do you think of this new study:https://www.ncbi.nlm.nih.gov/pubmed/28533290

    ?

  4. skeptvet says:

    This seems to show a pattern quite similar to other similar studies of nutraceutical for OA. All patients improve by a significant amount in the study, and the differences between the extent of improvement among treatment groups are much smaller than the effect of being in the study. This raises significant questions about how much real, meaningful impact the treatment had. For example, on a 100-point pain scale, the three groups showed the following improvement:

    Placebo- 33.4 points
    Chondroitin- 42.6 points
    Celecoxib- 39.5 points

    So the pain decreased an average of 40.5 points on a 100-point scale, but the differences between the groups were 6.1-9.2 points. That means the differences were pretty small compared to the overall improvement, suggesting just being in the trial contributed to most of the change. At most, the true underlying effect of the chondroitin would have been 9% better than nothing, which may be statistically significant but of questionable real-world significance.

    Looked at another way, the minimum difference thought to have any clinical significance is 5 points, so technically a 9-point difference might be detectable by a patient. However, doing nothing except enrolling in the trial yielded 33-point difference, which is a LOT bigger! Perhaps just giving out placebos should be our first therapy for OA. 🙂

    I also noticed that more people in the chondroitin group (39) and the placebo group (33) dropped out of the study than in the celecoxib group (27), which raises the question of whether subjects in those groups were more likley to drop out because they weren’t getting as much relief. And the number dropping out due to side effects from the drug was the same for chondroitin and celecoxib (8), which undermines the argument that chondroitin is better tolerated than NSAIDs.

    It is possible that the chondroitin really did have as much effect and the celecoxib and that both were only barely more effective than placebo. If so, this seems more an indictment of the celecoxib than a validation of the use of chondroitin since NSAIDs usually perform better than this against placebo. In a meta-analysis, for example, celecoxib was on average 17% better than placebo (0.86 on a 5-point scale), which is almost three times the difference in this study (6.1% or 6.1 points on a 100-point scale). It makes one wonder about the accuracy of assessment or the effectiveness of the positive comparator inthis study.

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