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).
Finally, I list the Bottom Line, which is my interpretation of the evidence.
Glucosamine for Dogs with Arthritis
- 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.
- 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
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