Roth introduced a tremendous cost burden due to the widespread chronic use of systemic NSAIDs in the elderly.55 In addition to gastrointestinal adverse events, oral nonselective NSAID therapy and treatment with COX-2 selective agents also increase the risk of cardiovascular events in a dose-dependent manner.12 Therefore, clinicians need strategies to reduce the risk of NSAID-related systemic adverse events as part of an overall approach to the management of osteoarthritis. One important possible risk-reduction strategy is the use of topical NSAIDs, which have been shown to be effective in osteoarthritis, but with a generally reduced risk of systemic adverse events compared with oral NSAIDs.48 All of the topical NSAIDs available in the US contain diclofenac and vary in formulation, use of penetration enhancers, and evidence base to support their use. Only topical diclofenac solution has been studied in direct comparison with oral diclofenac. In these studies, topical diclofenac solution exhibited comparable efficacy and a reduced incidence of systemic adverse events versus oral diclofenac.40,41 Several reviews and meta-analyses have shown topical NSAIDs to have significant safety advantages to minimize gastrointes- tinal risk while improving tolerability in high-risk patients. Rates of gastrointestinal adverse events and ulcers, perfora- tion, or bleeding have been much higher with oral nonse- lective NSAIDs and celecoxib than with topical diclofenac formulations.52,56,57 In addition, there have been two studies in patients with osteoarthritis of the knee showing simi- lar efficacy between topical diclofenac solution and oral diclofenac. Additional head-to-head studies in patients with osteoarthritis are needed to determine whether diclofenac gel performs similarly relative to oral diclofenac. Because of the differences in evidence base and in potential, as yet unknown, differences in actual efficacy and systemic adverse events among the topical diclofenac for- mulations, generalizations about the relative risk of topical versus oral NSAIDs should be minimized in favor of specific discussion of the relevant risks of each topical diclofenac formulation. Due to their demonstrated efficacy, safety, and potential to reduce systemic adverse events when compared with oral NSAIDs, topical NSAIDs can be considered important additions to the armamentarium for the treatment of osteoarthritis.43 Future long-term studies on chronic use will likely reveal that topical NSAIDs are a safer alternative to oral systemic NSAIDs, and may relieve high-risk elderly patients from common gastrointestinal and cardiorenal NSAID-related adverse events, as well as diminish systemic NSAID levels in the elderly. 130 submit your manuscript | www.dovepress.com Dovepress Dovepress Disclosure Dr Roth is a current stakeholder withinTransdel Pharmaceuticals, and serves as a consultant and speaker for Covidien. References 1. Centers for Disease Control and Prevention. Arthritis-related statistics, August 2010. Available from: http://www.cdc.gov/arthritis/data_ statistics/arthritis_related_stats.htm. Accessed October 19, 2010. 2. 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