Is topical treatment of osteoarthritis site-specific?
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* Vivian C. McAlister

*   © 2005 CMA Media Inc. or its licensors

The topical treatment of osteoarthritis has until now been left to the questionable domain of patent medicines and television advertising. Arthur Bookman and associates1 are to be congratulated for bringing some science to the area through their placebo-controlled study of topical diclofenac. However, like all good trials, this study raises other questions.

The authors state that topical treatment is site-specific but do not present data in support of this assertion. The appropriate control to determine site specificity would be topical application of 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 the lymphatic vessels and then entering the systemic circulation. A previous study, in which one of the authors participated, showed that topical diclofenac is in fact absorbed and metabolized.2 Poor bioavailability may be enhanced by periarticular inflammation, but this has not been demonstrated either.

Nonetheless, because of the pharmacokinetic profile of topically applied diclofenac, which avoids the peaks and valleys associated with toxicity, this route may be superior to oral administration. If the efficacy of topically applied diclofenac is related to the systemic level of the drug, Bookman and associates1 may have discovered a new ultra-low therapeutic range for non-steroidal agents, much like low-dose acetylsalicylic acid (ASA) in other situations. In this respect it would be interesting to know if concomitant use of low-dose ASA affected outcome.

The 2 placebo groups in this study 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 use of placebo creams should be continued in experimental design and considered in clinical practice.

## Footnotes

*   *Competing interests:* None declared.

## References

1.  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 2004; 171 (4):333-8. 
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo5OiIxNzEvNC8zMzMiO3M6NDoiYXRvbSI7czoyMDoiL2NtYWovMTcyLzUvNjE3LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

2.  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.
    
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