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Osteoarthritis: How to Make Optimal Use of Medications


ABSTRACT: Topical agents can provide temporary relief from osteoarthritis symptoms with little or no risk. Acetaminophen is first-line oral therapy. Be alert for risk factors for NSAID-induced GI toxicity, such as concurrent use of prescription and OTC agents. Tramadol, narcotic analgesics, muscle relaxants, and antidepressants are options when NSAIDs are ineffective or contraindicated. Intra-articular injections of corticosteroids or hyaluronan are appropriate for patients who have a single joint exacerbation. Total knee and total hip arthroplasty are considered the most effective surgical interventions.


Here we continue our discussion of treatment strategies for osteoarthritis (OA). On page 53 of this issue, we described how education and physical modalities can control pain and other symptoms, improve function, and minimize disability. In this article, we review the numerous topical, oral, and intra-articular agents available for the treatment of OA; we also discuss the pros and cons of various surgical procedures (see Algorithms I and II on pages 57 and 58, in our first article). In a future issue, we will address the numerous complementary therapies currently available for OA.


Topical agents. These can provide temporary relief from symptoms with little or no risk. Menthol-containing products can safely and temporarily soothe minor joint pain by producing a cooling sensation. Many such products are available over the counter.

Application of topical salicylates can result in intra-articular salicylate levels as high as 60% of those measured after oral administration of aspirin. Products that contain methyl salicylate appear to be better absorbed than other salicylate preparations.

Capsaicin cream can reduce pain by as much as 40% in patients with OA of the hands or knees. Capsaicin's proposed mechanism of action is depletion of the neurotransmitter substance P in sensory neurons involved in pain signaling. Adverse effects and the inconvenience of frequent application may result in discontinuation.

Capsaicin is available over the counter in 3 different concentrations. Advise patients to start therapy with one of the lower concentrations (0.025% or 0.075%) and to apply the cream 4 times daily. Warn them that a burning sensation in the area of application is common in the early days of treatment, but point out that this typically subsides after 7 to 10 days. The same amount of time is usually required for benefit to become apparent. If improvement is insufficient with a lower-concentration cream, try increasing the concentration to 0.25% (with twice-daily application).

Topical corticosteroids may also offer relief-but only when delivered by means of phonophoresis or iontophoresis by an occupational therapist. Simple topical application of corticosteroids in which neither of these methods of delivery is used is ineffective.

Oral agents. A large number of oral pharmacotherapeutic options are available. To choose wisely from this wide array of agents:

Keep in mind that the degree of inflammation in OA is usually relatively minor.

Consider the frequency of comorbidities (eg, peptic ulcer disease, renal insufficiency, hypertension, and conditions that require anticoagulation) in the population with OA.

Review NSAID side-effect profiles (Table 1).

Acetaminophen is the first-line choice among oral agents. The drug has a favorable side-effect profile, and at a dosage of 1 g 4 times daily it is as effective as NSAIDs in relievingOA pain in many patients. Often, lower doses will suffice. However, use acetaminophen with caution in patients who drink heavily or who have liver dysfunction.

NSAIDs are the next choice for patients whose symptoms do not respond to acetaminophen (Table 2).1 The efficacy of different NSAIDs appears equivalent in large groups of patients2; however, individual responses to specific agents vary widely, which makes a trial-and-error approach necessary.

Be alert to the presence of risk factors for serious NSAID-induced GI toxicity (Table 3).3 One of these is the use of more than 1 NSAID, so be sure to ask patients about their use of over-the-counter medications. The GI safety of nonselective NSAIDs is improved by the addition of misoprostol or a proton pump inhibitor.4-9 Histamine2 blockers may alleviate NSAID-induced dyspepsia and reduce the risk of NSAID-associated duodenal ulcer; however, they do not lower the risk of gastric ulcers.10,11 Table 4 lists guidelines for the safe use of NSAIDs in patients with OA. A complete risk-benefit analysis requires the results of a recent complete blood cell count, urinalysis, and comprehensive metabolic or chemistry panel.

Nonacetylated salicylates and selective cyclooxygenase (COX)-2 inhibitors offer safety advantages over nonselective or nonspecific COX inhibitors. Nonacetylated salicylates are very weak COX inhibitors and, therefore, have minimal effects on platelet function, GI mucosa, glomerular filtration rate (GFR), and renal excretion of sodium and water. Selective COX-2 inhibitors preserve COX-1 function; thus, they also eliminate antiplatelet effects and markedly reduce the risk of serious GI toxicity.12-15However, selective COX-2 inhibitors arenot problem-free. They can cause fluid retention, reduce GFR, and blunt the effectiveness of antihypertensive therapy.

For patients in whom NSAIDs are ineffective or contraindicated, other options include tramadol, opioids, antidepressants, and muscle relaxants.

Tramadol is a more potent alternative to NSAIDs than acetaminophen and is generally well tolerated.16 Tramadol relieves pain by inhibiting the opioid and serotonergic pathways. It has limited abuse potential.

Narcotic analgesics are potent but pose a greater risk of adverse effects.17,18

Antidepressants in low doses offer direct pain relief and also may effectively treat an established sleep disorder or one that develops as a result of the pain of OA. Amitriptyline and doxepin pose the greatest risk of anticholinergic effects. Accordingly, begin therapy at very low dosages (eg, 10 mg qhs) or consider potentially less problematic agents, such as nortriptyline or trazodone. Begin with a dosage of 25 to 50 mg qhs; titrate upward in increments of 25 mg per week if needed and tolerated. Selective serotonin reuptake inhibitors may help alleviate a coexisting mood disorder; however, these agents do not provide proven pain relief in OA.

Muscle relaxants can help ameliorate symptoms of soft tissue origin. These agents can also potentiate the analgesic effects of NSAIDs.

Systemic corticosteroids have no role in the management of OA.

Intra-articular therapies. These are particularly appropriate for patients with a single joint exacerbation and for those who have contraindications to or who have not benefited from topical and oral agents.

Intra-articular corticosteroid injections have long been a mainstay of OA management.19 Benefit presumably results from reduction of the inflammatory component of the disease.

Years ago, animal studies raised concerns about the safety of intra-articular corticosteroids. However, those studies involved extremely high doses of corticosteroids. There is no convincing evidence that these injections cause cartilage damage in humans when treatment guidelines are followed. No more than 3 or 4 injections per year should be administered in a single joint. In addition, prudence dictates that patients avoid repetitive stress or heavy impact to the joint for at least several days following an injection.

Intra-articular hyaluronan is a relatively recent addition to the therapeutic armamentarium for OA of the knee.20,21 The purported method of action of the 2 products currently available in the United States is that of viscosupplementation: exogenous hyaluronic acid restores some of the lubrication lost as a result of OA. However, the supplemental hyaluronan is cleared from the joint within days, despite reports of pain relief lasting months. Thus, the mechanism of any therapeutic effect of these agents has not yet been established.

The dosing regimen for hyaluronan is 3 to 5 injections per week, depending on the product selected. Results of randomized, double-blind, placebo-controlled trials are inconsistent. Of the 7 published studies that used currently approved dosing regimens, 2 demonstrated no benefit.22,23 The largest trial, which included 495 patients, reported efficacy equal to the active comparator, naproxen (500 mg bid).24 Four other trials found superior pain relief and joint function in participants treated with hyaluronan.25-28 Reported adverse effects are rare and consist primarily of exacerbations of joint pain and swelling; some of these have required intra-articular corticosteroid injection for resolution.29 Comparisons with intra-articular corticosteroids are too limited to permit meaningful interpretation.


Consider referral to a surgeon when nonsurgical therapies no longer control pain or permit a satisfactory level of function.30 Surgical options for patients with OA include cartilage-sparing and cartilage-sacrificing procedures. The selection of a specific procedure depends on severalfactors, including:

Patient age.

Functional expectations.

Activity demands.

Which joint is affected.

How much cartilage has been lost.

Osteotomy. The purpose of hip and knee osteotomy is to cut and realign bone in order to shift the major weight-bearing forces away from the arthritic compartments of the joint to healthier ones. The procedure is generally indicated for younger patients (age less than 50 years) who are not obese and who have early or localized cartilage degeneration. These generally healthy persons may then achieve successful load distribution with healthier cartilage. However, because only 25% of patients remain pain-free after 10 years, osteotomy is usually of limited benefit. Nonetheless, the procedure can "buy time" fora patient before he or she must undergo total joint arthroplasty that involves a prosthesis of finite durability.

First metacarpal osteotomy is an option for patients with OA of the first carpometacarpal (CMC) joint, particularly those with relatively early or mild disease.

Arthroscopic surgery. This is another cartilage-sparing procedure for OA of the knee; it usually consists of joint debridement and lavage. However, results have been discouraging. Half of patients who undergo arthroscopic surgery with joint debridement and lavage report failure after 2 years. Nevertheless, patients with specific mechanical symptoms-such as knee locking with minimal radiographic evidence of cartilage loss-may benefit from arthroscopic debridement.

Arthrodesis. Because of resultant function loss, arthrodesis (surgical fusion of the joint) is not an attractive option for OA of the hip or knee. However, patients with OA of the first CMC joint that is refractory to medical management may benefit from arthrodesis. Although joint immobility results, the local anatomy and the mobility of other hand and wrist joints usually preserves adequate hand function.

Arthroplasty. Patients with advanced OA of the first CMC joint may benefit from trapezial excision with interposition arthroplasty.31 Trapezial excision with abductor pollicis longus (APL) tendon arthroplasty involves excising the trapezium bone in the wrist and replacing it with the APL tendon, which is then secured at the first metacarpal base.

Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are the most effective surgical procedures available for restoring function.32,33 Patients who undergo total joint replacement surgery for hip or knee OA report significant improvements in quality of life and pain control. Three fourths of patients who undergo THA and over half of those who undergo TKA report symptom relief similar to age-related population norms for both functioning and incidence of pain.32-34

Contraindications to total joint arthroplasty include limited life expectancy, severe medical comorbidities, infection of the arthritic joint, and bedridden status. Complications associated with THA include postoperative deep venous thrombosis, pulmonary embolism, infection, dislocation, and periprosthetic fractures. In addition, patients who undergo TKA are at risk for knee stiffness with subsequent decreased range of motion, peroneal nerve palsies, and fat emboli. Other potential complications include patellar fractures, dislocation, and/or osteonecrosis.


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