Clinical Interventions in Aging Open Access Full Text Article open access to scientific and medical research Dovepress R e v I e w Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety Sanford H Roth Arizona Research and education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USA Correspondence: Sanford H Roth Arizona Research and education, 6831 North 58th Place, Paradise valley, AZ 85253, USA Tel +1 480 948 0504 Fax +1 480 948 0504 email sroth16@cox.net Abstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropa- thy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limit- ing systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis. Keywords: NSAIDs, osteoarthritis, topical administration, synovial fluid, peptic ulcer, Helicobacter pylori Introduction Osteoarthritis is a chronic, degenerative joint disorder characterized by destruction of articular cartilage, synovial inflammation, and subchondral bone alterations.1 It is the most common type of arthritis, affecting approximately 27 million people in the US.1 Optimal management of osteoarthritis requires both pharmacologic and nonpharma- cologic approaches, with nonsteroidal anti-inflammatory drugs (NSAIDs) frequently selected as the mainstay of pharmacologic treatment.2 Although NSAIDs may be the most effective analgesic for many patients with osteoarthritis, when administered orally they confer significant gastrointestinal, cardiovascular, and renal risks.2,3 Elderly patients, who constitute the greatest population of patients with osteoarthritis, are at high risk for developing gastrointestinal adverse events, that range from mild dys- pepsia or abdominal discomfort to potentially life-threatening complications, such as perforation and hemorrhage.4–6 This range of events, known as “NSAID gastropathy”, has been recognized for more than two decades as an important complication of long- term NSAID treatment. Despite concomitant administration of medications such as proton pump inhibitors and prostaglandins (misoprostol), this condition persists today in many patients who require NSAID therapy. Optimizing safety in these individuals, who often must take NSAID therapy for extended periods of time, is critical.5,7 submit your manuscript | www.dovepress.com Dovepress DOI: 10.2147/CIA.S21107 Clinical Interventions in Aging 2011:6 125–131 © 2011 Roth, publisher and licensee Dove Medical Press Ltd.This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. 125