Nonoperative management of osteoarthritis of the knee

K. Wayne Marshall, MD, PhD; David D. Waddell, MD

From A Special Report: Osteoarthritis of the Knee

Keeping Aging Adults Active

Preview: The goals in treating osteoarthritis of the knee are to alleviate pain and improve functional ability. Available treatments range from reduced activity, weight loss, and physical therapy to nonsteroidal anti-inflammatory drugs, nonnarcotic and narcotic analgesics, chondroitin and glucosamine, and viscosupplementation. However, use of these therapies is largely empiric because of the poor correlation between osteoarthritic disease and symptom severity, the highly idiosyncratic responses to various therapies, and the lack of evidence-based studies to assess and validate these therapies. When answers to these questions are available, it should be possible to design algorithms for optimal treatment of this costly and crippling disease.

Osteoarthritis places a tremendous physical and economic burden on society because it is the most prevalent musculoskeletal disorder. The knee is the joint most frequently involved in osteoarthritis.1,2 As baby boomers enter the osteoarthritis years and life expectancies are steadily prolonged, the number of patients with disabling osteoarthritis of the knee will dramatically increase.3 Because the expectations of this group of arthritis patients will be greater than that of previous generations, the providers of musculoskeletal care will be under increased pressure to provide therapies that are safe, effective, economical, and as minimally invasive as possible.

It is important to understand that few, if any, of the therapeutic options that are available have been extensively investigated by well-validated, evidence-based studies. In addition, the correlation between disease severity and symptom severity is often poor.4 As many as 40% of men and 20% of women with radiographic evidence of advanced (grades III and IV) osteoarthritis of the knee have few or no symptoms. Furthermore, the mechanisms that underlie joint pain are not fully understood, although there is mounting evidence that inflammation plays an important role.

It should also be understood that the therapies currently used for osteoarthritis of the knee treat symptoms only. They do not modify or cure the disease process. With the application of autologous chondrocyte transplantation for isolated cartilage defects,5 there has been expanding interest in developing disease-modifying therapies for diffuse osteoarthritis of the knee. Possibilities currently under investigation include chondrocyte transplantation, gene therapy, and small-molecule therapy.6-8

In addition to the poor correlation between disease and symptom severity, the response to symptom-modifying therapies is highly idiosyncratic. Unfortunately, reliable predictors for identifying subgroups that are likely to respond to a specific therapy have not been forthcoming. Standardized treatment algorithms built on evidence-based methods are yet to be developed.

This article will offer an overview of the nonoperative therapies that are available for treating osteoarthritis of the knee (table 1). Because standardized treatment regimens are lacking, therapy must be individualized to fit the circumstances and needs of each individual patient.

Table 1. Nonoperative treatment options for osteoarthritis of the knee
Nonpharmacologic therapy
Reduced activity
Weight loss
Supports and braces
Topical therapy
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Systemic therapy
Nonnarcotic analgesics
Narcotic analgesics
Chondroitin and glucosamine
Intra-articular therapy

Therapeutic goals

Detailed consideration of the symptoms, signs, and diagnostic tests for osteoarthritis of the knee is beyond the scope of this review. Symptoms include pain, swelling, weakness, stiffness, clicking, catching, and decreased functional ability. Physical findings may include pain, effusion, increased temperature, crepitus, diminished range of motion (ROM), muscle atrophy, ligamentous laxity, and angular deformity. Plain radiographs, including standing anteroposterior view of both knees, are the primary diagnostic modality. However, magnetic resonance imaging and ultrasound are being examined as potential methods that allow for earlier diagnosis and monitoring of response to putative disease-modifying therapies.

The fundamental goals in treating osteoarthritis of the knee are to alleviate pain and improve functional ability. Pain, inflammation, and effusion result in potent inhibitory feedback from joint receptors onto quadriceps alpha-motoneurons. Thus, patients with significant symptoms frequently have chronic quadriceps inhibition resulting in decreased muscle bulk and tone.9-11 Thus, the goal of symptom-modifying therapy is to decrease pain, inflammation, and effusion in order to strengthen the quadriceps and optimize functional ability.

Nonpharmacologic therapies

Nonpharmacologic therapies, including reduced activity, weight loss, supports and braces, and physiotherapy are important initial steps in managing patients with osteo-arthritis of the knee. If these approaches fail, more aggressive treatment is warranted.

REDUCED ACTIVITY—Decreased physical activity can diminish symptoms or reduce the incidence of osteoarthritic flares in some patients. However, these advantages must be balanced against the negative aspects of decreased activity, including weight gain, diminished general fitness, and increased quadriceps weakness. It is preferable, and for many patients nonnegotiable, that they maintain or increase their level of physical activity. A pragmatic approach is to eliminate or decrease involvement in activities that are more likely to ignite an osteoarthritic flare, such as high-impact and pivoting sports. Safe exercise programs should be designed to improve function and conditioning levels.

WEIGHT LOSS—Weight loss can ameliorate the severity of symptoms,12 but it is less certain whether weight loss can slow the rate of disease progression. Unfortunately, weight loss can be difficult to achieve and maintain. Many patients have pain and functional disability that limit or preclude exercise. For these patients weight loss is exceptionally difficult to achieve. They may require intervention to improve their knee pain before they can exercise at adequate levels to achieve weight loss. Low-impact alternatives, such as cycling or water-based exercises, should be encouraged.

SUPPORTS AND BRACES—Some patients experience subjective improvement with the use of an elastic support around the knee. This approach must be used cautiously, if at all, in patients with a history of deep venous thrombosis or lower limb edema. Although the efficacy of this approach is not well established, it may enhance stabilizing inputs from articular and periarticular sensory receptors onto the motoneurons of muscles acting across the knee.

Bracing can be effective in patients who have relatively focused unicompartmental medial or lateral osteoarthritis. Thus, valgus bracing is often used for varus knees in which osteoarthritis primarily involves the medial compartment. Less frequently, varus bracing may be indicated for lateral-compartment osteoarthritis associated with a valgus deformity. Unfortunately, even when a brace is prescribed and found to be efficacious, many patients stop using it after a short time.

PHYSIOTHERAPY—Physiotherapy for osteoarthritis of the knee is used to decrease inflammation, maintain or improve ROM, and strengthen muscles, especially the quadriceps. Methods used to treat pain, inflammation, and weakness include cold and heat therapy, ultrasound, shortwave diathermy, interferential, laser, transcutaneous electrical neuromuscular stimulation, and faradic muscle stimulation.13 These methods have not, for the most part, undergone appropriate evidence-based studies to validate their efficacy for osteoarthritis of the knee, so their use is largely empiric.

A critical concept in the application of physiotherapy for osteoarthritis of the knee, especially during flares or postoperatively, is that inflammation must be brought under control before ROM and strengthening are aggressively pursued. ROM is initially a higher priority than strengthening, because failure to expeditiously reestablish a functional ROM can result in the development of intra-articular and periarticular adhesions and permanent loss of range of motion. However, these cautionary notes do not diminish the critical importance of quadriceps strengthening if the patient is to achieve optimal functional recovery. Quadriceps isometric exercises are safe and well tolerated in patients with osteoarthritis of the knee, even during times of inflammation.

Topical therapies

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)—Topical NSAID therapy has been advocated as a potentially safer alternative to oral NSAIDs. Indeed there is some evidence that topical NSAIDs work and can have efficacies similar to those of oral NSAIDs.14 However, because of poor understanding of the pharmacokinetics and mode of action of topical NSAIDs, combined with few well-designed studies attesting to their clinical safety and efficacy, skepticism continues to limit their widespread acceptance.

CAPSAICIN—In the past few years, topical capsaicin cream has been introduced as a symptomatic therapy for osteoarthritis. The neuropeptide substance P is present in A delta- and C-fiber sensory nerves. It has been implicated as a transmitter in articular pain pathways and is a putative contributor to joint inflammation.15 Application of capsaicin to A delta- and C-fibers depletes them of substance P, blocking subsequent intraneuronal axonal transport and synthesis of substance P.16 Thus, capsaicin can potentially ameliorate symptoms of osteoarthritis through 2 mechanisms: by attenuating transmission in articular pain pathways and by diminishing joint inflammation. Studies support the safety and efficacy of capsaicin for treating osteoarthritis of the knee.17,18

Unfortunately, people in warm climates may have difficulty using capsaicin. They may experience an extreme burning sensation when using capsaicin and exercising strenuously in a hot environment.

Systemic therapies

NONNARCOTIC ANALGESICS—Acetaminophen is a nonnarcotic analgesic that has an excellent safety profile and provides good pain control for many osteoarthritis patients. Acetaminophen can be an efficacious alternative to NSAIDs, and it is safer and less expensive.19,20 Thus, acetaminophen should be strongly considered as first-line drug therapy in patients who have symptomatic osteoarthritis of the knee. Acetaminophen should be used cautiously in patients with hepatic and renal dysfunction.

NARCOTIC ANALGESICS—Narcotic analgesics can be very effective for relieving pain in osteoarthritis of the knee. However, the side effects associated with these drugs, most notably dependence, should limit their use to short-term treatment of severe pain associated with an acute osteoarthritic flare. Prolonged use of these drugs for pain management in this chronic disease process is inappropriate.

ANTIDEPRESSANTS—The role, if any, of antidepressants such as amitriptyline in managing symptomatic osteoarthritis of the knee is unclear. Some patients with osteoarthritis of the knee exhibit chronic pain behavior.

NSAIDS—These agents have long been aggressively used to treat osteoarthritis of the knee, although conclusive evidence-based support for their widespread use is lacking.21,22 The clinical response to NSAIDs can be highly idiosyncratic between different osteoarthritis patients as well as between different NSAID preparations. Traditional NSAIDs provide anti-inflammatory activity by blocking the enzyme cyclooxygenase-2 (COX-2). Unfortunately, they also inhibit COX-1, a constitutive enzyme that plays an important role in maintaining normal function in the gastrointestinal (GI) mucosa, liver, kidneys, and platelets. Thus, complications of traditional NSAID treatment include GI bleeding as well as hepatic, renal, and platelet dysfunction. Indeed, information from the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) Post-Marketing Surveillance Program suggests that at least 16,500 deaths per year in the United States are caused by NSAID-induced GI bleeding in arthritis patients.23 This is cause for great concern considering that arthritis, and especially osteoarthritis, is not generally considered a life-threatening disease.

More recently, NSAIDs that are selective COX-2 inhibitors have been developed.24 They do not block COX-1 and are expected to have a greatly reduced incidence of side effects, resulting in much improved tolerance and safety compared with traditional, nonselective NSAIDs. Selective COX-2 inhibitors hold great promise for the treatment of osteoarthritis of the knee. However, our understanding of their relative therapeutic efficacy is still evolving, and the effect of their long-term use on chondrocytes and cartilage matrix is largely unknown.25,26 Early results show some promise and effectivness. Certainly more basic science and clinical research are needed.

CHONDROITIN AND GLUCOSAMINE—Chondroitin and glucosamine have become popular as putative symptomatic and disease-modifying therapies for osteoarthritis of the knee. It is hypothesized that these important constituent components of cartilage matrix can be ingested, enter plasma, cross the blood-synovial fluid barrier, and enter synovial fluid in sufficient concentrations to provide analgesia and promote cartilage healing. The mechanisms, if any, underlying these alleged therapeutic effects remain undiscovered. Some clinical trials data are starting to become available.27,28 Given their widespread use by patients, it is fortunate that these products appear to be safe, and they can be a useful adjunct, especially in patients who cannot tolerate NSAIDs.

Intra-articular therapies

CORTICOSTEROIDS—Intra-articular corticosteroids are frequently used to treat symptomatic osteoarthritis of the knee. Surprisingly few studies support their efficacy.29 The response to this therapy is highly idiosyncratic and tends to be short-lived. However, some patients experience a prolonged duration of improvement. Corticosteroid injections can be particularly effective for managing acute, inflammatory flares. Advantages of intra-articular corticosteroids include safety and cost. A cautionary note is that repeated injections may promote cartilage degradation. Injections should be limited to no more than 3 per year in any given joint. Patients should be warned of a possible corticosteroid-related flare in the injected joint 24 to 48 hours after injection. The application of ice can help prevent this type of reaction.

VISCOSUPPLEMENTATION—Hyaluronan (HA) in both articular tissues and synovial fluid plays an important role in contributing to joint homeostasis and maintaining normal joint function.30 In osteoarthritis, the molecular weight and concentration of HA is diminished.31 This has led to the concept of viscosupplementation, in which pathologic synovial fluid is aspirated and HA-based products are injected into the articular space in order to restore HA concentration and molecular weight to relatively normal levels.32 Therapeutic benefit is believed to occur by restoring the viscoelastic, antinociceptive, anti-inflammatory, and autoregulatory functions of HA in synovial fluid.33

Clinical studies of HA-based products have demonstrated clinical benefit for about 70% of patients in a heterogenous osteoarthritis population.34 Duration of improvement ranges from months to years. Two types of HA products are available for treating osteoarthritis of the knee: low-molecular weight HAs and high-molecular weight hylan (cross-linked HA). Hylan closely replicates the molecular weight of the HA found in normal synovial fluid.

HA-based products are safe. Local inflammatory reactions typically occur after 3% of injections.34,35 These are usually mild and self-limited. Marked reactions usually respond well to aspiration and corticosteroid injection. Severe reactions mimicking a septic joint occur at a rate of about 1 in 500 injections. After obtaining a Gram stain and cultures to rule out infection, response to aspiration and corticosteroid injection is usually dramatic. Systemic reactions are rare.

Injection technique is critical. It is essential to ensure that the HA is injected intra-articularly. There is evidence that 30% of putative knee joint injections miss the intra-articular space.36 In the case of corticosteroid injections, this may not greatly affect efficacy. However, with viscosupplementation, if the HA product is not injected into the joint space, efficacy diminishes and the incidence of local flare reactions increases. Before injection it is also critical to aspirate as much of the pathologic osteoarthritic synovial fluid as possible so the injected HA-based replacement is not diluted.

Experience with viscosupplementation has been encouraging. However, many unresolved issues surround the use of HA products. These include developing optimal dosing regimens, determining the most appropriate positioning in treatment algorithms, assessing their role in osteoarthritic joints other than the knee, exploring efficacy in inflammatory arthritides, and determining the importance of molecular weight in selecting HA products.

It has been argued that HA products have enhanced efficacy as their molecular weight increases. Both in vitro and in vivo animal evidence supports this view.33 A recent clinical study35 found that the high-molecular weight HA product hylan G-F 20 was more effective than a low-molecular weight HA product in relieving the pain of osteoarthritis of the knee. Although these data are suggestive, a definitive answer to this question awaits further clinical trials that directly compare these 2 classes of HA products.


Nonoperative therapies can be very effective at relieving pain and improving functional ability in osteoarthritis of the knee. However, there is a need for well-designed, evidence-based studies that thoroughly assess the safety, efficacy, and economy of all currently available operative and nonoperative therapies for osteoarthritis of the knee. Armed with these data, it should be possible to design algorithms for optimally treating this costly and crippling disease.

K. Wayne Marshall, MD, PhD is on staff in the division of orthopedic surgery and Arthritis Center of Excellence at the Toronto Western Hospital and University of Toronto. He has been a consultant for Biomatrix and Wyeth-Ayerst Laboratories.

Address correspondence to K. Wayne Marshall, MD, PhD, Toronto Western Hospital, 399 Bathurst St, ECW 1-024, Toronto, Ontario M5T 2S8. E-mail address: [email protected]

David D. Waddell, MD is affiliated with Orthopedic Specialists of Louisiana Inc, Shreveport, Louisiana. Dr Waddell declares that he has no relationships with companies that manufacture products used to treat the patients under discussion.


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