Electronic letters to:

Research:
Arthur A.M. Bookman, Kate S.A. Williams, and J. Zev Shainhouse
Effect of a topical diclofenac solution for relieving symptoms of primary osteoarthritis of the knee: a randomized controlled trial
CMAJ 2004; 171: 333-338 [Abstract] [Full text] [PDF]
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Electronic letters published:

[Read eLetter] Topical Diclofenac in Renal Disease
Raman Joshi   (7 September 2004)
[Read eLetter] Is topical treatment of osteoarthritis site specific?
Vivian C McAlister   (23 August 2004)

Topical Diclofenac in Renal Disease 7 September 2004
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Raman Joshi
Rheumatologist, Brampton Campus, William Osler Health Centre

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Re: Topical Diclofenac in Renal Disease

rjoshi{at}canada.com Raman Joshi

Co-submitters: Hitesh Mehta, Nephrologist, Brampton Campus, William Osler Health Centre, Brampton ON; Jasdip Sachdeva, Nephrologist, Brampton Campus, William Osler Health Centre, Brampton ON.

To the Editor:

We read with interest the study of Bookman et al. (1) on the use of topical diclofenac in patients with osteoarthritis of the knee.

We note that that patients with renal dysfunction were excluded from this study. There is scant data on the use of topical NSAIDs in patients with chronic renal failure or receiving chronic dialysis.

In our practices, we have started and monitored at least five patients with renal dysfunction on topical diclofenac. Two of the patients were receiving chronic hemodialysis and three had chronic renal failure (Creatinine clearance 25-37 mL/minute). Both inflammatory and non -inflammatory conditions (including osteoarthritis) were treated with variable success. The topical diclofenac was well tolerated by all patients with no significant deterioration in renal function secondary the topical diclofenac.

A direct head-to-head comparison of topical diclofenac with acetominophen or intra-articular corticosteroids (in the case of knee osteoarthritis) in patients with renal dysfunction would be valuable. It could it help clafity the safety and efficacy of this agent patients with renal dysfunction, and in so doing, allow us to better treat the pain and limitation these patients suffer.

1. Bookman AAM, Williams KSA, Shainhouse JZ. Effect of a topical diclofenac solution for relieving symptoms of primary osteoarthritis of the knee: a randomized controlled trial. CMAJ;171(4)333-8.

Conflict of Interest:

None declared
Is topical treatment of osteoarthritis site specific? 23 August 2004
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Vivian C McAlister
Surgeon

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Re: Is topical treatment of osteoarthritis site specific?

mcalistv{at}lhsc.on.ca Vivian C McAlister

The topical treatment of osteoarthritis has until now been left to the questionable domain of patent medicines and television advertising. The authors of a recent placebo controlled study of topical diclofenac and the editors of the journal, by virtue of giving the article the prominence of a cover illustration, are to be congratulated on bringing some science to the area.1 Like all good trials, it raises other questions.

The study does not present data that topical treatment is site specific. The appropriate control for this assertion would be the application of topical diclofenac to an unaffected site. It is unlikely that a lipid soluble agent dissolved in ethanol would travel from the skin to the joint without first being absorbed by veins or lymphatics into the systemic circulation. The authors themselves have shown that topical diclofenac is absorbed and metabolized.2 Poor bioavailability may be enhanced by peri-articular inflammation but this also has not been shown.

However the pharmacokinetic profile of topically applied diclofenac, by avoiding the peaks and valleys associated with toxicity, may be superior to oral administration. If efficacy of topically applied diclofenac is related to its systemic level, it may also be that Bookman and colleagues have discovered a new ultra-low therapeutic range for non-steroidal agents, much like low dose aspirin in other areas. In this respect it would be interesting to know if use of concomitant low dose aspirin affected outcome.

The cover illustration employs the same eye-catching technique as patent medicine advertising. In Bookman’s study both placebo groups enjoyed a benefit that was both clinically and statistically significant. Again it is not known if the placebo effect is site dependent but it would seem that inclusion of placebo creams should be continued in experimental design and considered in clinical practice.

1. Bookman AA, Williams KS, Shainhouse JZ. Effect of a topical diclofenac solution for relieving symptoms of primary osteoarthritis of the knee: a randomized controlled trial. CMAJ 2004;171(4):333-8.

2. Hui X, Hewitt PG, Poblete N, Maibach HI, Shainhouse JZ, Wester RC. In vivo bioavailability and metabolism of topical diclofenac lotion in human volunteers. Pharm Res 1998;15(10):1589-95.

Vivian C. McAlister Department of Surgery University of Western Ontario, London, Ont.

Conflict of Interest:

None declared