Portal de Periódicos da CAPES

Medical management of osteoarthritis

2001; Elsevier BV; Volume: 76; Issue: 5 Linguagem: Inglês

10.4065/76.5.533

1942-5546

Nisha J. Manek,

Medicinal plant effects and applications

Osteoarthritis (OA) is the most common articular disease, and it continues to be a major public health problem related to pain, disability, loss of time from work, and economics. Most patients with OA seek medical attention because of pain. In the past few years, changes in the treatment of OA have been substantial. More effective nonnarcotic analgesics, cyclooxygenase-2-specific inhibitors, nutraceuticals, and intra-articular hyaluronates are some of the new medications and agents that are now available. The understanding and use of nonpharmacological interventions, including patient education, exercise programs, and weight reduction when appropriate, have also improved. Relief of pain and restoration of function can be accomplished in many patients, particularly with an integrated approach. This article focuses on medical treatment approaches for OA, both pharmacological and nonpharmacological. Osteoarthritis (OA) is the most common articular disease, and it continues to be a major public health problem related to pain, disability, loss of time from work, and economics. Most patients with OA seek medical attention because of pain. In the past few years, changes in the treatment of OA have been substantial. More effective nonnarcotic analgesics, cyclooxygenase-2-specific inhibitors, nutraceuticals, and intra-articular hyaluronates are some of the new medications and agents that are now available. The understanding and use of nonpharmacological interventions, including patient education, exercise programs, and weight reduction when appropriate, have also improved. Relief of pain and restoration of function can be accomplished in many patients, particularly with an integrated approach. This article focuses on medical treatment approaches for OA, both pharmacological and nonpharmacological. Osteoarthritis (OA) is the most common form of arthritis to affect synovial joints. Radiographic and/or pathologic changes of OA are present in most people older than 65 years. For many years OA was viewed as normal wear and tear of the joint, an inevitable consequence of aging, for which few treatment options were available. This simplistic view is changing rapidly. Osteoarthritis is much more complex than previously thought. Available treatment modalities range from simple analgesics to intra-articular injections and nutraceuticals to patient education interventions.1Felson DT Lawrence RC Hochberg MC et al.Osteoarthritis: new insights, part 2: treatment approaches.Ann Intern Med. 2000; 133: 726-737Crossref PubMed Scopus (411) Google Scholar The principal clinical features reported by patients are joint pain and decreased joint function. Typically, the pain worsens with weight bearing and activity and improves with rest. Patients may also report symptoms of joint instability, periarticular muscle weakness, and fatigue. The onset of these symptoms is almost invariably insidious, with episodes of pain that increase in frequency and duration until eventually the patient is in constant pain. The goals of management of OA as outlined in the 1995 American College of Rheumatology (ACR) guidelines are to control pain, maintain or improve joint mobility, minimize disability, and educate patients and their families about the disease and its treatment.2Hochberg MC Altman RD Brandt KD American College of Rheumatology et al.Guidelines for the medical management of osteoarthritis, part II: osteoarthritis of the knee.Arthritis Rheum. 1995; 38: 1541-1546Crossref PubMed Scopus (799) Google Scholar, 3Hochberg MC Altman RD Brandt KD American College of Rheumatology et al.Guidelines for the medical management of osteoarthritis, part I: osteoarthritis of the hip.Arthritis Rheum. 1995; 38: 1535-1540Crossref PubMed Scopus (477) Google Scholar These guidelines were revised in 2000.4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Although glucosamine and chondroitin sulfate have not been evaluated by the ACR, they are discussed in this review. Persons with OA are a heterogeneous population, ranging widely in age, disease impairment, functional goals, and interests. Therefore, management of the patient with OA should be comprehensive and individualized, taking into account the anatomical distribution, the phase, and the progression rate of the disease. Comorbid conditions such as cardiac disease, hypertension, peptic ulcer disease, or renal disease must be considered, as well as the patient's needs and expectations. The management of OA is broadly divided into nonmedicinal or nonpharmacological therapy and drug or pharmacological treatments. Surgical treatments, including joint lavage, osteotomy, and total joint arthroplasty, are not discussed in this review, but indications for surgery generally are failed medical management and functional disability affecting a patient's quality of life. Nonpharmacological modalities are the cornerstone of management of OA of the hip and of the knee (Figure 1). Indeed, analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) should not be used as sole therapy but as adjuncts to the nonpharmacological program. Exercise may be the most effective and inexpensive physical intervention available for reducing joint pain and impairment in patients with OA.5Puett DW Griffin MR Published trials of nonmedicinal and noninvasive therapies for hip and knee osteoarthritis.Ann Intern Med. 1994; 121: 133-140Crossref PubMed Scopus (210) Google Scholar The 3 categories of therapeutic exercise are range of motion and flexibility, muscle conditioning, and aerobic cardiovascular exercise.4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Because OA of the hip and OA of the knee are the major disabling diagnoses and have been the focus of OA exercise research, most current evidence covers these 2 conditions. Traditionally, a therapeutic exercise program is provided by a physical or occupational therapist and is based on an individualized assessment of range-of-motion factors, muscle strength, endurance, pain, aerobic capacity function, and need of orthotics. Of importance, the program should not cause long-standing pain or deterioration of function. The patient performs the exercises in a clinical setting with supervision (individual or group) or in an unsupervised home program. The intended outcomes of interventions and clinical goals should be clearly documented, with periodic review of the patient's status and revision of the exercise program as needed. Exercise management includes muscle conditioning for increased strength and endurance; range-of-motion and flexibility exercises; instructions in joint positioning, joint protection, and posture; and use of external devices (canes, orthotics). Whichever activity or exercise program is adopted, novice exercisers must be encouraged regarding their ability to exercise successfully and safely. Improvement in function and general health requires more than a single-joint approach. Osteoarthritis in 1 joint is a multiple-joint problem; range-of-motion and strength deficits are generally found in adjacent joints and bilaterally. Quadriceps weakness is common among patients with knee OA, and isometric exercises to strengthen the quadriceps muscle, especially the vastus medialis, are beneficial. The exercises are easy to teach, can be performed with no equipment, are usually well tolerated, and do not cause flare of the OA process. The Fitness Arthritis and Seniors Trial (FAST) confirmed the beneficial effects of both quadriceps-strengthening and aerobic exercise.6Ettinger Jr, WH Burns R Messier SP et al.A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis: the Fitness Arthritis and Seniors Trial (FAST).JAMA. 1997; 277: 25-31Crossref PubMed Google Scholar All patients with OA of the knee should be taught quadriceps-strengthening exercises and should be encouraged to perform such exercises every day. The association between obesity and OA is most pronounced in overweight postmenopausal women. The association is not so apparent in men or in patients with hip disease. The 1995 ACR guidelines recommended that overweight patients with hip or knee OA lose weight.2Hochberg MC Altman RD Brandt KD American College of Rheumatology et al.Guidelines for the medical management of osteoarthritis, part II: osteoarthritis of the knee.Arthritis Rheum. 1995; 38: 1541-1546Crossref PubMed Scopus (799) Google Scholar, 3Hochberg MC Altman RD Brandt KD American College of Rheumatology et al.Guidelines for the medical management of osteoarthritis, part I: osteoarthritis of the hip.Arthritis Rheum. 1995; 38: 1535-1540Crossref PubMed Scopus (477) Google Scholar A relationship between loss of body fat and improvement in symptoms of knee OA has been shown.4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Weight loss may also substantially decrease a patient's pain medication regimen; thus, a weight reduction program should be recommended to all overweight patients. Ergonomic and assistive devices can decrease joint load. For example, using an appropriately selected cane can substantially reduce hip loading. The cane is held on the unaffected or contralateral aspect of the body. Patients with OA who walk for occupation or recreation may need special shoes with shock absorption, extra depth or width, or metatarsal bars to improve toe alignment. Many devices are available to assist in activities of daily living, and occupational therapy has an important role in the evaluation of the personal and microenvironmental support required by individual patients. Similar to other chronic diseases, OA can also alter the psychological state of patients. Patient education in OA consists of informational leaflets, verbal information during the physician consultation, and telephone contacts. Regular telephone contact has been shown to reduce psychosocial disability and thereby reduce joint pain without increasing cost.4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar The recognition that pain in OA is not necessarily due to inflammation has led to an increased awareness of the role of simple analgesics in the treatment of this disease. For some patients with OA, relief of mild to moderate pain with use of acetaminophen is comparable to that achieved with an NSAID.1Felson DT Lawrence RC Hochberg MC et al.Osteoarthritis: new insights, part 2: treatment approaches.Ann Intern Med. 2000; 133: 726-737Crossref PubMed Scopus (411) Google Scholar, 2Hochberg MC Altman RD Brandt KD American College of Rheumatology et al.Guidelines for the medical management of osteoarthritis, part II: osteoarthritis of the knee.Arthritis Rheum. 1995; 38: 1541-1546Crossref PubMed Scopus (799) Google Scholar, 3Hochberg MC Altman RD Brandt KD American College of Rheumatology et al.Guidelines for the medical management of osteoarthritis, part I: osteoarthritis of the hip.Arthritis Rheum. 1995; 38: 1535-1540Crossref PubMed Scopus (477) Google Scholar, 4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Acetaminophen should be the initial therapy based on its overall cost, efficacy, and toxicity profile.1Felson DT Lawrence RC Hochberg MC et al.Osteoarthritis: new insights, part 2: treatment approaches.Ann Intern Med. 2000; 133: 726-737Crossref PubMed Scopus (411) Google Scholar, 2Hochberg MC Altman RD Brandt KD American College of Rheumatology et al.Guidelines for the medical management of osteoarthritis, part II: osteoarthritis of the knee.Arthritis Rheum. 1995; 38: 1541-1546Crossref PubMed Scopus (799) Google Scholar, 3Hochberg MC Altman RD Brandt KD American College of Rheumatology et al.Guidelines for the medical management of osteoarthritis, part I: osteoarthritis of the hip.Arthritis Rheum. 1995; 38: 1535-1540Crossref PubMed Scopus (477) Google Scholar, 4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Acetaminophen is the ACR's drug of choice for OA of the hip and the knee. Treatment is usually initiated at 500 to 1000 mg twice daily and increased up to 1000 mg 3 or 4 times daily to control pain. The daily dose of acetaminophen should not exceed 4 g. Analgesics should be prescribed as a constant regimen to ensure success. Patients should be taught to take the drugs at regular dosage intervals and not depend on an as-needed regimen. Regular intervals are more effective for breaking the pain cycle. Although rare at therapeutic doses, acetaminophen has been associated with hepatotoxicity at massive overdose levels. If a patient normally consumes 3 or more alcohol-containing drinks per day, clinicians should encourage the patient to reduce alcohol consumption before recommending long-term use of any analgesic, including acetaminophen. Acetaminophen may be associated with important drug interactions, such as prolongation of the half-life of warfarin.1Felson DT Lawrence RC Hochberg MC et al.Osteoarthritis: new insights, part 2: treatment approaches.Ann Intern Med. 2000; 133: 726-737Crossref PubMed Scopus (411) Google Scholar, 4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar For patients taking warfarin who require concurrent use of acetaminophen, the international normalized ratio should be monitored closely and the warfarin dose adjusted to maintain the target international normalized ratio. Because acetaminophen does not affect prostaglandin synthesis, its effect on renal function is minimal. Acetaminophen is the National Kidney Foundation's drug of choice for patients with renal disease.1Felson DT Lawrence RC Hochberg MC et al.Osteoarthritis: new insights, part 2: treatment approaches.Ann Intern Med. 2000; 133: 726-737Crossref PubMed Scopus (411) Google Scholar, 4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar For patients whose pain is not adequately controlled with acetaminophen, NSAIDs should be considered. The initial choice of NSAIDs is the nonacetylated salicylates or the traditional NSAIDs used at low doses to decrease the risk of NSAID-induced toxic events. The use of non-acetylated salicylates and low-dose NSAID therapy may provide some patients the benefit of anti-inflammatory activity with a minimal risk for a poor gastrointestinal or renal outcome. Nonacetylated salicylates (such as choline magnesium trisalicylate and salsalate) do not produce the antiplatelet effects or renal toxicity associated with nonselective NSAIDs and can be considered in the management of high-risk patients; however, ototoxicity and central nervous system toxicity at clinically efficacious doses may limit their use.4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Although NSAIDs are analgesic at low doses and anti-inflammatory at high doses, there is minimal evidence to date that they modify the course of OA. These agents vary in half-life, and little evidence suggests that they vary substantially in efficacy. However, for unknown reasons, 1 type of NSAID can be beneficial when others have failed. In elderly patients with comorbid conditions, the best approach is to begin with an NSAID that has a short half-life, such as ibuprofen, and the lowest available dose should be used initially and increased slowly. An important adverse effect of NSAIDs is potentiation of renal insufficiency (Table 1). NSAIDs also inhibit platelet aggregation and can prolong bleeding time. For this reason, concurrent use of NSAIDs and warfarin is relatively contraindicated. Hypersensitivity reactions and hepatic toxicity are other recognized adverse effects. However, the major adverse effect and probably the most common cause of pronounced morbidity due to NSAIDs is gastrointestinal toxicity.7Lichtenstein DR Syngal S Wolfe MM Nonsteroidal antiinflammatory drugs and the gastrointestinal tract: the double-edged sword.Arthritis Rheum. 1995; 38: 5-18Crossref PubMed Scopus (243) Google Scholar Among people 65 years of age or older, an estimated 20% to 30% of all hospitalizations and deaths due to peptic ulcer disease are attributable to NSAIDs.1Felson DT Lawrence RC Hochberg MC et al.Osteoarthritis: new insights, part 2: treatment approaches.Ann Intern Med. 2000; 133: 726-737Crossref PubMed Scopus (411) Google Scholar, 4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar A history of gastric or duodenal ulcers or a history of an abnormal Helicobacter pylori titer or biopsy specimen will help physicians decide whether NSAIDs are appropriate to use in individual patients. If a patient is found to have H pylori, treatment to eradicate the bacterium from the gastric or duodenal mucosa is recommended before initiation of NSAID treatment.8Lanza FL Members of the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology A guideline for the treatment and prevention of NSAID-induced ulcers.Am J Gastroenterol. 1998; 93: 2037-2046Crossref PubMed Scopus (301) Google Scholar Physicians should advise their patients to not take NSAIDs on an empty stomach. Factors that increase the risk of NSAID-induced gastropathy are summarized in Table 2.Table 1Risk Factors for Renal Failure With Use of Nonsteroidal Anti-inflammatory Drugs*Data from American College of Rheumatology Subcommittee on Osteoarthritis Guidelines.4 Age >65 yPresence of hypertensionCongestive heart failureConcomitant use of diureticsConcomitant use of angiotensin-converting enzyme inhibitorsExisting renal insufficiency* Data from American College of Rheumatology Subcommittee on Osteoarthritis Guidelines.4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Open table in a new tab Table 2Risk Factors for Gastropathy Induced by Nonsteroidal Anti-inflammatory Drugs*NSAIDs = nonsteroidal anti-inflammatory drugs (adapted with permission from Lichtenstein et al7). Definite risk factors Age >65 yPrevious ulcer disease or upper gastrointestinal tract bleedingUse of multiple NSAIDs or use of a high dosage of 1 of these drugsConcomitant oral corticosteroid therapyConcomitant anticoagulant therapyDuration of therapy (risk is higher in the first 3 mo of treatment)Possible risk factors SmokingAlcohol consumptionHelicobacter pylori infection* NSAIDs = nonsteroidal anti-inflammatory drugs (adapted with permission from Lichtenstein et al7Lichtenstein DR Syngal S Wolfe MM Nonsteroidal antiinflammatory drugs and the gastrointestinal tract: the double-edged sword.Arthritis Rheum. 1995; 38: 5-18Crossref PubMed Scopus (243) Google Scholar). Open table in a new tab Medical management options for a patient with OA who has a high risk of a serious adverse upper gastrointestinal event include use of a nonselective NSAID with gastroprotective therapy or a cyclooxygenase (COX)-2-specific inhibitor. The approach endorsed by the American College of Gastroenterology is to use a nonselective NSAID with a gastroprotective agent for prevention of NSAID-induced gastric complications.8Lanza FL Members of the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology A guideline for the treatment and prevention of NSAID-induced ulcers.Am J Gastroenterol. 1998; 93: 2037-2046Crossref PubMed Scopus (301) Google Scholar Misoprostol is a synthetic prostaglandin E1 analogue. When used as cotherapy with a nonselective NSAID at a dosage of 200 µg 3 to 4 times daily, misoprostol has been shown to reduce the incidence of gastric and duodenal ulcers. Adverse effects include diarrhea and flatulence. Proton pump inhibitors (omeprazole or lansoprazole) are an acceptable alternative. Histamine2 receptor antagonists in usual doses have been shown to prevent duodenal ulcers. In the treatment of NSAID-induced ulcers, the preferred approach is to discontinue NSAID therapy. A proton pump inhibitor is the agent of choice when NSAIDs must be continued in the presence of ulcer disease.8Lanza FL Members of the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology A guideline for the treatment and prevention of NSAID-induced ulcers.Am J Gastroenterol. 1998; 93: 2037-2046Crossref PubMed Scopus (301) Google Scholar Efforts to create safe and efficacious NSAIDs have centered on selectively targeting the isoforms of the prostaglandin-producing enzyme, COX. Specific inhibition of COX-2 enzyme is anti-inflammatory without affecting the cytoprotective gastric prostaglandin (COX-1). Celecoxib and rofecoxib are 2 COX-2-specific inhibitors that have been approved by the US Food and Drug Administration (FDA) for use in patients with OA.4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar In patients with hip or knee OA, these analgesic drugs are comparable in efficacy to the standard nonselective NSAID.9Hawkey CJ COX-2 inhibitors.Lancet. 1999; 353: 307-314Abstract Full Text Full Text PDF PubMed Scopus (1058) Google Scholar Endoscopic studies have shown that COX-2 inhibitors are associated with an incidence of ulcers similar to that with placebo and lower than that with comparative NSAIDs.9Hawkey CJ COX-2 inhibitors.Lancet. 1999; 353: 307-314Abstract Full Text Full Text PDF PubMed Scopus (1058) Google Scholar COX-2 inhibitors do not cause pronounced inhibition of bleeding time or platelet aggregation, both of which are added advantages. As with nonselective NSAIDs, however, COX-2-specific inhibitors can impair renal function and should be used with caution in patients with mild to moderate renal insufficiency, and they should be avoided in patients with severe renal insufficiency.1Felson DT Lawrence RC Hochberg MC et al.Osteoarthritis: new insights, part 2: treatment approaches.Ann Intern Med. 2000; 133: 726-737Crossref PubMed Scopus (411) Google Scholar, 4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Of note, celecoxib is contraindicated in patients with a history of allergic reaction to a sulfonamide. Tramadol hydrochloride, a synthetic opioid, is a centrally acting oral analgesic that has been approved by the FDA for the treatment of moderate to severe OA pain. It is equivalent to many moderate-strength narcotics such as codeine. Tramadol has at least 2 mechanisms of action: low affinity binding to the µ-opioid receptor site and inhibition of norepinephrine and serotonin reuptake by nerve cells. Tramadol may be particularly useful as an alternative in patients, such as the elderly, who are at risk for NSAID-associated adverse effects. It may also be useful as adjunctive therapy during OA flares when additional pain relief is needed because of inadequate control with NSAIDs.4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Daily doses of tramadol are usually 200 to 300 mg given in 4 divided doses. Common adverse effects include drowsiness, nausea, and constipation. Seizures have been reported as a rare adverse effect, either at doses higher than recommended or in patients with a history of epilepsy. The potential for addiction and tolerance appears to be low, and tramadol is an unscheduled drug. In patients whose chronic pain cannot be controlled with acetaminophen, NSAIDs, or tramadol, opiates may be a last option. Opiates, either alone or in combination with acetaminophen or aspirin, have been shown to be helpful for acute painful flares of OA. However, opiates may cause excessive sedation, respiratory depression, nausea, vomiting, and constipation, as well as physical dependence and addiction. These agents are best used in occasional brief time frames (2-4 weeks) for severe pain not responding to other medication. Capsaicin, a pepper plant derivative, has been shown to be more effective than placebo in relieving the pain of OA.2Hochberg MC Altman RD Brandt KD American College of Rheumatology et al.Guidelines for the medical management of osteoarthritis, part II: osteoarthritis of the knee.Arthritis Rheum. 1995; 38: 1541-1546Crossref PubMed Scopus (799) Google Scholar Although of limited use for patients with OA pain in multiple joints, capsaicin is a good alternative to systemic therapy for those with localized disease, such as OA of the knee or hand. Capsaicin is available over the counter as a cream in concentrations of 0.025%, 0.075%, and 0.25%. A local burning sensation is common but decreases in frequency with continued use. Patients should be advised to apply capsaicin cream with a glove to prevent inadvertent spread to the eyes or mucous membranes. Methylsalicylate and topical NSAIDs are also available. Glucosamine and chondroitin sulfate, agents marketed as nutritional supplements in the United States, have been purported to be effective in the treatment of OA in several short-term trials in Europe and Asia during the past 3 to 4 decades. These nutraceuticals have received much publicity in recent years in popular books and the media, and subsequently the use of these agents has increased considerably. Glucosamine is an aminomonosaccharide and a component of cartilage. Experimental evidence in vitro suggests that glucosamine may have a beneficial role in cartilage metabolic responses, such as an increase in the synthesis of cartilage-specific type II collagen in human fetal chondrocytes.10Deal CL Moskowitz RW Nutraceuticals as therapeutic agents in osteoarthritis: the role of glucosamine, chondroitin sulfate, and collagen hydrolysate.Rheum Dis Clin North Am. 1999; 25: 379-395Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar When glucosamine is added to cultures of chondrocytes from OA cartilage, proteoglycan synthesis increases. Chondroitin sulfate appears to have similar effects of increasing proteoglycan concentration in the collagen matrix and of decreasing collagenolytic activity.10Deal CL Moskowitz RW Nutraceuticals as therapeutic agents in osteoarthritis: the role of glucosamine, chondroitin sulfate, and collagen hydrolysate.Rheum Dis Clin North Am. 1999; 25: 379-395Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar A chondroprotective effect has not been demonstrated in vivo. A meta-analysis reviewing trials of glucosamine and chondroitin sulfate concluded that these supplements are likely to be effective for the symptomatic management of OA, but deficiencies in study designs and conduct did not allow a definitive evaluation.11McAlindon TE Lavalley MP Gulin JP Felson DT Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis.JAMA. 2000; 283: 1469-1475Crossref PubMed Scopus (735) Google Scholar Studies in the United States have revealed that several nutritional supplements have questionable doses of glucosamine and chondroitin sulfate. Furthermore, glucosamine is available in health food stores as the sulfate, hydrochloride, N-acetyl, or chlorhydrate salt. Most clinical studies have been done with glucosamine sulfate, and less information is available on the clinical effects of other forms of glucosamine.10Deal CL Moskowitz RW Nutraceuticals as therapeutic agents in osteoarthritis: the role of glucosamine, chondroitin sulfate, and collagen hydrolysate.Rheum Dis Clin North Am. 1999; 25: 379-395Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar The various forms of glucosamine differ in their purity, bioactivity, and equivalent dosages. Pending definitive studies from the National Institutes of Health, which is supporting a multicenter randomized, double-blind, placebo-controlled study of patients taking glucosamine and chondroitin sulfate, these agents cannot at present be recommended for OA treatment. Intra-articular injection of a long-acting corticosteroid is indicated for acute exacerbation of knee pain, especially if accompanied by an effusion. In patients with knee OA with moderate to severe pain and in whom signs of joint inflammation and effusion are present, joint aspiration accompanied by intra-articular injection of glucocorticoids merits consideration as the initial therapeutic approach.4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Pain relief from such injections is generally good but short term. Few studies have assessed predictors of response. When injecting an acutely inflamed OA joint, it is important to aspirate as much of the synovial fluid as possible and send it for cell count, examination for crystals, Gram stain, and culture. These tests rule out crystal-induced arthropathy or joint infection. Patients with painful OA of the hip may benefit from an intra-articular corticosteroid injection, which can be performed under fluoroscopic control. Oral corticosteroids should be avoided because no evidence supports their use in OA. The 3 principal concerns with intra-articular injections of corticosteroids are postinjection flare, long-term joint damage, and infection. An increase in pain, stiffness, or swelling during the first 24 hours after intra-articular glucocorticoid injection has been noted and can generally be treated with cold compresses and analgesics. Long-term joint damage is difficult to evaluate because intra-articular injections may be used more frequently in patients with more severe disease and because of the many different factors that contribute to the progression of OA over long periods. However, most rheumatologists do not recommend more than 4 glucocorticoid injections in any 1 joint per year. The risk of introducing infection into an OA joint is small if an aseptic injection technique is used.4American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.Arthritis Rheum. 2000; 43: 1905-1915Crossref PubMed Scopus (1981) Google Scholar Hyaluronic acid is a major nonstructural component of the synovial and cartilage extracellular matrix. It confers viscoelastic and lubricating properties to the joint. In patients with OA, the concentration and molecular weight of hyaluronic acid are decreased. Thus, viscosupplementation with hyaluronic acidlike compounds has been developed as intra-articular treatment of knee OA. The FDA has approved sodium hyaluronate and hylan G-F 20 injections for treatment of pain secondary to OA of the knee. With both agents, weekly injections must be administered for 3 or 5 weeks, and this regimen can be used only twice per year. Although pain relief with viscosupplementation is achieved more slowly than with intra-articular glucocorticoid injections, the effect may last for several weeks or months. This approach may be considered in patients in whom a combined nonpharmacological and simple analgesic program has failed or in those in whom nonselective NSAIDs and COX-2-specific inhibitors are contraindicated. Intra-articular hyaluronan therapy is not approved for hip OA. The approach to the treatment of OA of the knee joint is summarized in Figure 1. The treatment of hip OA is similar; however, topical analgesics are not used because of the depth of the joint, and intra-articular glucocorticoid injections, if used, must be administered under fluoroscopic control. Most investigational therapies are targeted toward the inhibition of breakdown of cartilage by collagenolytic enzymes or matrix metalloproteinases or at stimulating repair activity by chondrocytes. Other important advances include autologous chondrocyte transplantation, cartilage repair using mesenchymal stem cells, and autologous osteochondral plugs for repair of focal chondral defects. The clinical applications of these approaches are currently limited to research settings. All patients with OA should be provided with self-help materials, which can be obtained from local branches of the Arthritis Foundation. Patients can also contact the foundation directly by telephone (1-800-283-7800 or 1-404-872-7100) or via the internet (www.arthritis.org). The Web site is a useful starting point for obtaining access to the activities and information about exercise opportunities in local communities across the United States.