REVIEW Topical nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis Zahi Touma, Lan Chen Osteoarthritis is the most common degenerative joint disease and is particularly common in & Thurayya Arayssi† the elderly. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may represent a rational †Author for correspondence treatment in this situation because of their favorable side-effect profile. The majority of American University of topical NSAIDs decrease pain and relieve functional disability caused by osteoarthritis over Beirut Medical Center, the short term, however, there are insufficient data for their long-term efficacy. Department of Internal Medicine, Division of Rheumatology, 3 Dag Osteoarthritis (OA) is the most common disease patients with OA of the knees [9]. Other interven- Hammarskjöld Plaza, of synovial joints, associated with locomotor tions include the use of assistive devices (cane or 8th floor, New York, pain, chronic disability and morbidity [1]. It is crutch), application of braces and patellar taping NY, 10017, USA estimated by the WHO to be the fourth most and/or orthotics, especially in patients with insta- Tel.: +1 961 135 0000 Ext: 5383; important cause of disability among women and bility of the knee and varus malalignment [8,10,11]. Fax: +1 961 136 5189; the eighth amongst men [2]. Its prevalence and Participation in patient self-management pro- [email protected] incidence are projected to rise as the elderly pro- grams and personalized social support through portion of the population increases, which will telephone contact have also been shown to help have a significant impact on society [3]. The in decreasing pain and improving function in onset of the disease most commonly occurs patients with OA [10]. between the age of 50 and 60 years and fre- Acupuncture has been evaluated in rando- quently affects the hands, spine, knees and hips mized controlled trials and been shown to [4]. Involvement of the wrists, elbows, ankles and provide added benefit in patients with knee OA shoulders is uncommon [5]. The majority of per- with a favorable safety profile [12,13]. sons show radiographic evidence of OA by Topical traditional Chinese medicine 65 years of age, although most are asymptomatic (TTCMs) and other alternative remedies are still [6]. In the Framingham study, for example, 30% widely used, especially in Chinese and other eth- of patients aged over 60 years had radiological nic communities. When all the ‘modern’ prepa- evidence of OA of the knee, which was not rations have been exhausted, some ‘old remedies’ always symptomatic [4]. have been explored by patients [14]. Litt has OA was previously thought to be a normal offered a list of 73 alternative topical measures consequence of aging, thereby linked to the term that are often beneficial, mostly for dermatologic degenerative joint disease. It is now recognized disorders [15]. TTCMs have many varieties. A that OA results from a complex interplay of common misconception is that TTCM is a com- multiple factors, including joint integrity, genet- plicated, exotic art. Difficulties in understanding ics, metabolic, local inflammation, mechanical these measures are due first to more than one forces, previous injury of a joint, and cellular and ingredient in one formulation, second to the biochemical processes [7,8]. myriad of preparations available and third due to To date, there are no means to prevent the labeling, with brands such as Tiger Balm, occurrence of OA. Thus, treatment is directed 3-Snake Oil and Dragon Balm. First and fore- towards pain relief, improving function and most, it must be understood that brand names health-related quality of life [8]. A combination are just brand names. The names are symbolic of nonpharmacologic (Box 1), pharmacologic [14]. Tiger Balm and 3-Snake Oil do not contain (Table 1) and surgical (Box 2) treatment is usually any material from either of these animals. Keywords: diclofenac, needed and should be individualized according Indeed, TTCMs are mixtures containing many ibuprofen, ketoprofen, meta-analysis, osteoarthritis, to patient needs, presence of comorbidities and herbs, ranging from three to 20 different types. piroxicam, randomized drug–drug interactions. Mixtures are based on the concept of traditional controlled trials, topical Chinese medicine. The formulations use differ- nonsteroidal anti- inflammatory drugs Nonpharmacologic treatment ent ingredients to balance the body and to bal- Current treatment guidelines recommend the ance the opposite properties of different herbals. part of combination of weight loss and exercise pro- However, all these myriads of preparations can grams to reduce pain and improve function in be grouped into three classes, according to usage. 10.2217/17460816.2.2.163 © 2007 Future Medicine Ltd ISSN 1746-0816 Future Rheumatol. (2007) 2(2), 163–175 163 REVIEW – Touma, Chen & Arayssi Box 1. Nonpharmacologic therapy for be soothing. They usually are not irritating to patients with osteoarthritis. the skin unless the patients are allergic to these ingredients. Other paste preparations are mix- • Patient education tures of various herbals with a petrolatum base. • Self-management programs Zingiber officinale rhizoma, Polygonum multiflo- • Telephone contact rum radix, Peonia lactiflora radix, rhizoma et • Weight loss (if overweight) radix notopterygii, myrrha and other herbals • Physical therapy and aerobic exercise are commonly used for rheumatic pain, a • Patellar taping • Corrective footwear, bracing, joint protection, bi-syndrome in TTCM. None of these have lateral-wedged insoles (for genu varum) been assessed in controlled trials available in • Assistive devices for activities of daily living english [14,17]. • Laser • Pulsed electromagnetic field, ultrasound, Pharmacologic treatment transcutaneous electrical nerve stimulation Paracetamol, up to 4 g/day, remains the most • Acupuncture commonly prescribed drug in patients with mild- • Nutrients, herbal remedies, vitamins/minerals to-moderate pain. A meta-analysis published in •Spa 2004 confirmed the efficacy of acetaminophen in relieving pain due to OA, which should be the In each class, the ingredients revolve around a first-line treatment, reserving nonsteroidal common theme, with only minor differences. anti-inflammatory drugs (NSAIDs) for patients The three classes are: who do not respond [18]. • Oils, ointments, pastes for aches and pains; Both classical NSAIDs and cyclo-oxygenase (Cox)-2 inhibitors are used commonly and are • Oils, ointments, pastes for orthopedic injuries; more effective than placebo and acetaminophen • Lotions and ointments for skin diseases. in reducing pain and functional disabilities in Here, only the first class will be briefly patients with OA of knees and hips [19,20]. This summarized [14,16]. superiority of NSAIDS over acetaminophen, The classic example of class 1 TTCMs used however, is modest and because of the high inter- for rheumatic pain is Tiger Balm [17]. It is an individual variability in patient response to both oil-based balm containing camphor, menthol of these drug classes, it is impossible to predict and one or more essential oils, such as cinna- the patient’s response to them [8,21]. mon oil, oil of clove, cassia oil, citronella oil, oil Opiate analgesic agents, including tramadol, of lavender or cajuput oil. These are compound can also be used and may be of benefit in together in a base oil or petrolatum. It can thus patients with severe pain resistant to NSAIDs or be appreciated that the formulation is meant to in those who have contraindication to treatment with other drugs [11]. Glucosamine and chondroitin are natural Table 1. Pharmacologic therapy of osteoarthritis. substances derived from animal products that Route Pharmacologic agent have acquired substantial popularity in the Oral therapy Acetaminophen treatment of OA [22]. The most important merit NSAIDs is their safety, although their mechanisms of Cyclooxygenase-2 action are unclear [11]. In a 2003 meta-analysis that included 15 randomized, double-blind, Nonacetylated salicylate placebo-controlled trials that assessed either glu- Tramadol cosamine or chondroitin on structure modifica- Opioids tion of knee or hip OA, glucosamine was found Glucosamine sulfate to have a positive effect in reducing joint space Chondroitin sulfate narrowing [23]. In a recently published rand- Intra-articular therapy Glucocorticoids omized controlled trial of glucosamine and Hyaluronan chondroitin, the drugs were not helpful in effec- Tidal irrigation tively reducing pain in patients with OA of the knees. Exploratory analyses, however, suggest Topical therapy NSAIDs that the combination may be effective in the Capsaicin subgroup of patients with moderate-to-severe NSAID: Nonsteroidal anti-inflammatory drug. knee pain [24]. 164 Future Rheumatol. (2007) 2(2) futurefuture sciencescience groupgroup Topical nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis – REVIEW Box 2. Surgical treatment for patients with osteoarthritis. hospital with GI problems for regular users of oral NSAIDs is 1.3–1.6% annually [30]. In the • Arthroscopic management USA, GI tract bleeding secondary to NSAIDs – Lavage accounts for 41,000 hospitalization and 3300 – Debridement deaths each year [31]. Additionally, approxi- – Abrasion arthroplasty mately 40% of hospital admissions with upper – Subchondral penetration procedures (drilling and microfracture) GI bleeding, and 40% of associated deaths in – Laser/thermal chondroplasty older