Osteoarthritis

Author: Carlos J Lozada, MD; Chief Editor: Herbert S Diamond,

Background
Osteoarthritis is the most common type of joint disease, affecting more than 20 million individuals in the United States alone (see Epidemiology). It represents a heterogeneous group of conditions resulting in common histopathologic and radiologic changes. It can be thought of as a degenerative disorder arising from biochemical breakdown of articular (hyaline) cartilage in the synovial joints. However, the current view holds that osteoarthritis involves not only the articular cartilage but also the entire joint organ, including the subchondral bone and synovium. Osteoarthritis predominantly involves the weight-bearing joints, including the knees, hips, cervical and lumbosacral spine, and feet. Other commonly affected joints include the distal interphalangeal (DIP), proximal interphalangeal (PIP), and carpometacarpal (CMC) joints. This article primarily focuses on osteoarthritis of the hand, knee, and hip joints (see Pathophysiology). For more information on arthritis in other joints, see Glenohumeral Arthritis and Wrist Arthritis. Although osteoarthritis was previously thought to be caused largely by excessive wear and tear, increasing evidence points to the contributions of abnormal mechanics and inflammation. Therefore, the term degenerative joint disease is no longer appropriate in referring to osteoarthritis. (See Pathophysiology.) Historically, osteoarthritis has been divided into primary and secondary forms, though this division is somewhat artificial. Secondary osteoarthritis is conceptually easier to understand: It refers to disease of the synovial joints that results from some predisposing condition that has adversely altered the joint tissues (eg, trauma to articular cartilage or subchondral bone). Secondary osteoarthritis can occur in relatively young individuals (see Etiology).[1, 2, 3, 4, 5, 6, 7,
8, 9, 10, 11]

The definition of primary osteoarthritis is more nebulous. Although this form of osteoarthritis is related to the aging process and typically occurs in older individuals, it is, in the broadest sense of the term, an idiopathic phenomenon, occurring in previously intact joints and having no apparent initiating factor. Some clinicians limit the term primary osteoarthritis to the joints of the hands (specifically, the DIP and PIP joints and the joints at the base of the thumb). Others include the knees, hips, and spine (apophyseal articulations) as well. As underlying causes of osteoarthritis are discovered, the term primary, or idiopathic, osteoarthritis may become obsolete. For instance, many investigators believe that most cases of primary osteoarthritis of the hip may, in fact, be due to subtle or even unrecognizable congenital or developmental defects.

No specific laboratory abnormalities are associated with osteoarthritis. Rather, it is typically diagnosed on the basis of clinical findings, with or without radiographic studies (see Workup). The goals of osteoarthritis treatment include pain alleviation and improvement of functional status. Nonpharmacologic interventions are the cornerstones of osteoarthritis therapy and include the following:

Patient education Application of heat and cold Weight loss Exercise Physical therapy Occupational therapy Joint unloading, in certain joints (eg, knee and hip)

Intra-articular pharmacologic therapy includes corticosteroid injection and viscosupplementation, which may provide pain relief and have an anti-inflammatory effect on the affected joint. (See Treatment.) Oral pharmacologic therapy begins with acetaminophen for mild or moderate pain without apparent inflammation. If the clinical response to acetaminophen is not satisfactory or the clinical presentation is inflammatory, consider nonsteroidal anti-inflammatory drugs (NSAIDs). (See Medication.) If all other modalities are ineffective and osteotomy is not viable, or if a patient cannot perform his or her daily activities despite maximal therapy, arthroplasty is indicated. The high prevalence of osteoarthritis entails significant costs to society. Direct costs include clinician visits, medications, and surgical intervention. Indirect costs include such items as time lost from work. Costs associated with osteoarthritis can be particularly significant for elderly persons, who face potential loss of independence and who may need help with daily living activities. As the populations of developed nations age over the coming decades, the need for better understanding of osteoarthritis and for improved therapeutic alternatives will continue to grow. (See Epidemiology.)

Anatomy
Joints can be classified in either functional or structural terms. A functional classification, based on movement, would categorize joints as follows:

Synarthroses (immovable) Amphiarthroses (slightly moveable) Diarthroses (freely moveable)

A structural classification would categorize joints as follows:

Synovial Fibrous
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Cartilaginous

Normal synovial joints allow a significant amount of motion along their extremely smooth articular surface. These joints are composed of the following:

Articular cartilage Subchondral bone Synovial membrane Synovial fluid Joint capsule

The normal articular surface of synovial joints consists of articular cartilage (composed of chondrocytes) surrounded by an extracellular matrix that includes various macromolecules, most importantly proteoglycans and collagen. The cartilage facilitates joint function and protects the underlying subchondral bone by distributing large loads, maintaining low contact stresses, and reducing friction at the joint. Synovial fluid is formed through a serum ultrafiltration process by cells that form the synovial membrane (synoviocytes). Synovial cells also manufacture hyaluronic acid (HA, also known as hyaluronate), a glycosaminoglycan that is the major noncellular component of synovial fluid. Synovial fluid supplies nutrients to the avascular articular cartilage; it also provides the viscosity needed to absorb shock from slow movements, as well as the elasticity required to absorb shock from rapid movements.

Pathophysiology
Primary and secondary osteoarthritis are not separable on a pathologic basis, though bilateral symmetry is often seen in cases of primary osteoarthritis, particularly when the hands are affected.[12, 13] Traditionally, osteoarthritis was thought to affect primarily the articular cartilage of synovial joints; however, pathophysiologic changes are also known to occur in the synovial fluid, as well as in the underlying (subchondral) bone, the overlying joint capsule, and other joint tissues (see Workup).[14, 15, 16, 17] Although osteoarthritis has been classified as a noninflammatory arthritis, increasing evidence has shown that inflammation occurs as cytokines and metalloproteinases are released into the joint. These agents are involved in the excessive matrix degradation that characterizes cartilage degeneration in osteoarthritis.[18] Therefore, it is no longer appropriate to use the term degenerative joint disease when referring to osteoarthritis. In early osteoarthritis, swelling of the cartilage usually occurs, because of the increased synthesis of proteoglycans; this reflects an effort by the chondrocytes to repair cartilage damage. This stage may last for years or decades and is characterized by hypertrophic repair of the articular cartilage. As osteoarthritis progresses, however, the level of proteoglycans eventually drops very low, causing the cartilage to soften and lose elasticity and thereby further compromising joint surface integrity. Microscopically, flaking and fibrillations (vertical clefts) develop along the normally smooth articular cartilage on the surface of an osteoarthritic joint. Over time, the loss of cartilage results in loss of joint space.
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In major weight-bearing joints of persons with osteoarthritis, a greater loss of joint space occurs at those areas experiencing the highest loads. This effect contrasts with that of inflammatory arthritides, in which uniform joint-space narrowing is the rule. In the osteoarthritic knee, for example, the greatest loss of joint space is commonly seen in the medial femorotibial compartment, though the lateral femorotibial compartment and patellofemoral compartment may also be affected. Collapse of the medial or lateral compartments may result in varus or valgus deformities, respectively. Erosion of the damaged cartilage in an osteoarthritic joint progresses until the underlying bone is exposed. Bone denuded of its protective cartilage continues to articulate with the opposing surface. Eventually, the increasing stresses exceed the biomechanical yield strength of the bone. The subchondral bone responds with vascular invasion and increased cellularity, becoming thickened and dense (a process known as eburnation) at areas of pressure.[19] The traumatized subchondral bone may also undergo cystic degeneration, which is attributable either to osseous necrosis secondary to chronic impaction or to the intrusion of synovial fluid. Osteoarthritic cysts are also referred to as subchondral cysts, pseudocysts, or geodes (the preferred European term) and may range from 2 to 20 mm in diameter. Osteoarthritic cysts in the acetabulum (see the image below) are termed Egger cysts.

This radiograph demonstrates osteoarthritis of the right hip, including the finding of sclerosis at the superior aspect of the acetabulum. Frequently, osteoarthritis at the hip is a bilateral finding, but it may occur unilaterally in an individual who has a previous history of hip trauma that was confined to that one side. At areas along the articular margin, vascularization of subchondral marrow, osseous metaplasia of synovial connective tissue, and ossifying cartilaginous protrusions lead to irregular outgrowth of new bone (osteophytes). Fragmentation of these osteophytes or of the articular cartilage itself results in the presence of intra-articular loose bodies (joint mice). Along with joint damage, osteoarthritis may also lead to pathophysiologic changes in associated ligaments and the neuromuscular apparatus. For example, lateral collateral ligament complex abnormalities are common in knee osteoarthritis.

Pain mechanisms in osteoarthritis

Pain, the main presenting symptom of osteoarthritis, is presumed to arise from a combination of mechanisms, including the following:

Osteophytic periosteal elevation Vascular congestion of subchondral bone, leading to increased intraosseous pressure
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Synovitis with activation of synovial membrane nociceptors Fatigue in muscles that cross the joint Overall joint contracture Joint effusion and stretching of the joint capsule Torn menisci Inflammation of periarticular bursae Periarticular muscle spasm Psychological factors Crepitus (a rough or crunchy sensation) Central pain sensitization

When the spine is involved in osteoarthritis, especially the lumbar spine, the associated changes are very commonly seen from L3 through L5. Symptoms include pain, stiffness, and occasional radicular pain from spinal stenosis. Foraminal narrowing is caused by facet arthritic changes that result in compression of the nerve roots. Acquired spondylolisthesis is a common complication of arthritis of the lumbar spine.

Etiology
The daily stresses applied to the joints, especially the weight-bearing joints (eg, ankle, knee, and hip), play an important role in the development of osteoarthritis. Most investigators believe that degenerative alterations in osteoarthritis primarily begin in the articular cartilage, as a result of either excessive loading of a healthy joint or relatively normal loading of a previously disturbed joint. External forces accelerate the catabolic effects of the chondrocytes and further disrupt the cartilaginous matrix.[20, 21, 22, 23] Risk factors for osteoarthritis include the following[24, 25, 26, 27] :

Age Obesity[28, 29, 30] Trauma Genetics (significant family history) Reduced levels of sex hormones Muscle weakness[31] Repetitive use (ie, jobs requiring heavy labor and bending)[32] Infection Crystal deposition Acromegaly Previous inflammatory arthritis (eg, burnt-out rheumatoid arthritis) Heritable metabolic causes (eg, alkaptonuria, hemochromatosis, and Wilson disease) Hemoglobinopathies (eg, sickle cell disease and thalassemia) Neuropathic disorders leading to a Charcot joint (eg, syringomyelia, tabes dorsalis, and diabetes) Underlying morphologic risk factors (eg, congenital hip dislocation and slipped femoral capital epiphysis) Disorders of bone (eg, Paget disease and avascular necrosis) Previous surgical procedures (eg, meniscectomy)

Advancing age
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With advancing age come reductions in cartilage volume, proteoglycan content, cartilage vascularization, and cartilage perfusion. These changes may result in certain characteristic radiologic features, including a narrowed joint space and marginal osteophytes. However, biochemical and pathophysiologic findings support the notion that age alone is an insufficient cause of osteoarthritis.

Obesity
Obesity increases the mechanical stress in a weight-bearing joint. It has been strongly linked to osteoarthritis of the knees and, to a lesser extent, of the hips. A study that evaluated the associations between body mass index (BMI) over 14 years and knee pain at year 15 in 594 women found that a higher BMI at year 1 and a significant increase in BMI over 15 years were predictors of bilateral knee pain at year 15.[30] The association between BMI increase and knee pain was independent of radiographic changes. In addition to its mechanical effects, obesity may be an inflammatory risk factor for osteoarthritis. Obesity is associated with increased levels (both systemic and intra-articular) of adipokines (cytokines derived from adipose tissue), which may promote chronic, lowgrade inflammation in joints.[33]

Other causes
Trauma or surgery (including surgical repair of traumatic injury) involving the articular cartilage, ligaments, or menisci can lead to abnormal biomechanics in the joints and accelerate osteoarthritis. Although repairs of ligament and meniscal injuries usually restore joint function, osteoarthritis has been observed 5-15 years afterward in 50-60% of patients.[34] Insults to the joints may occur even in the absence of obvious trauma. Microtrauma may also cause damage, especially in individuals whose occupation or lifestyle involves frequent squatting, stair-climbing, or kneeling. Muscle dysfunction compromises the bodys neuromuscular protective mechanisms, leading to increased joint motion and ultimately resulting in osteoarthritis. This effect underscores the need for continued muscle toning exercises as a means of preventing muscle dysfunction. Valgus malalignment at the knee has been shown to increase the incidence and risk of radiographic progression of knee osteoarthritis involving the lateral compartment.[35]

Genetics
A hereditary component, particularly in osteoarthritis presentations involving multiple joints, has long been recognized.[36, 37, 38] Several genes have been directly associated with osteoarthritis,[39] and many more have been determined to be associated with contributing factors, such as excessive inflammation and obesity. Genes in the BMP (bone morphogenetic protein) and WNT (wingless-type) signaling cascades have been implicated in osteoarthritis. Two genes in particular, GDF5 (growth and differentiation factor 5) and FRZB (frizzled related protein) have been identified in the articular cartilage in animal studies and share a strong correlation with osteoarthritis.[40, 41, 42,
43]

Genome-wide association studies (GWAS) have identified an association between osteoarthritis of large joints and the MCF2L gene. This gene is key in neurotrophin-mediated regulation of peripheral nervous system cell motility.[44] Genetic factors are also important in certain heritable developmental defects and skeletal anomalies that can cause congenital misalignment of joints. These may result in damage to cartilage and the structure of the joint. Currently, clinical genetic testing is not offered to patients who have osteoarthritis unless they also have other anomalies that could be associated with a genetic condition. In the future, testing may allow individualization of therapeutics.

Epidemiology
United States and international statistics
Osteoarthritis affects more than 20 million individuals in the United States, though statistical figures are influenced by how the condition is definedthat is, by self-report, by radiographic or symptomatic criteria, or by a combination of these.[45] On the basis of the radiographic criteria for osteoarthritis, more 50% of adults older than 65 years are affected by the disease. Internationally, osteoarthritis is the most common articular disease. Estimates of its frequency vary across different populations.

Age-related demographics
Primary osteoarthritis is a common disorder of the elderly, and patients are often asymptomatic. Approximately 80-90% of individuals older than 65 years have evidence of radiographic primary osteoarthritis.[46] Symptoms typically do not become noticeable until after the age of 50 years. The prevalence of the disease increases dramatically among persons older than 50 years, likely because of age-related alterations in collagen and proteoglycans that decrease the tensile strength of the joint cartilage and because of a diminished nutrient supply to the cartilage.[46]

Sex-related demographics
In individuals older than 55 years, the prevalence of osteoarthritis is higher among women than among men.[46] Women are especially susceptible to osteoarthritis in the DIP joints of the fingers. Women also have osteoarthritis of the knee joints more frequently than men do, with a female-to-male incidence ratio of 1.7:1. Women are also more prone to erosive osteoarthritis, with a female-to-male ratio of about 12:1.

Race-related demographics
Interethnic differences in the prevalence of osteoarthritis have been noted.[47] The disorder is more prevalent in Native Americans than in the general population. Disease of the hip is seen

less frequently in Chinese patients from Hong Kong than in age-matched white populations. Symptomatic knee osteoarthritis is extremely common in China.[48] In persons older than 65 years, osteoarthritis is more common in whites than in blacks. Knee osteoarthritis appears to be more common in black women than in other groups. Jordan et al found that in comparison with whites, African American men and women had a slightly higher prevalence of radiographic and symptomatic knee osteoarthritis but a significantly higher prevalence of severe radiographic knee osteoarthritis.[49]

Prognosis
The prognosis in patients with osteoarthritis depends on the joints involved and on the severity of the condition. No proven disease- or structure-modifying drugs for osteoarthritis are currently known; consequently, pharmacologic treatment is directed at symptom relief. A systematic review found the following clinical features to be associated with more rapid progression of knee osteoarthritis[50] :

Older age Higher BMI Varus deformity Multiple involved joints

Patients with osteoarthritis who have undergone joint replacement have a good prognosis, with success rates for hip and knee arthroplasty generally exceeding 90%. However, a joint prosthesis may have to be revised 10-15 years after its placement, depending on the patients activity level. Younger and more active patients are more likely to require revisions, whereas the majority of older patients will not. (See Treatment.)

Patient Education
Educate patients on the natural history of and management options for osteoarthritis, emphasizing the benefits of exercise and weight loss. Explain the differences between osteoarthritis and more rapidly progressive arthritides, such as rheumatoid arthritis. Several Arthritis Foundation studies have demonstrated that education in osteoarthritis benefits the patient. Through education, patients can learn and implement strategies for reducing pain and improving joint function. Emphasize the need for physician follow-up visits. For patient education information, see the Arthritis Center, as well as Osteoarthritis.

History
The progression of osteoarthritis is characteristically slow, occurring over several years or decades. Over this period, the patient can become less and less active and thus more susceptible to morbidities related to decreasing physical activity (including potential weight gain).
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Early in the disease process, the joints may appear normal. However, the patients gait may be antalgic if weight-bearing joints are involved. Pain is usually the initial source of morbidity in osteoarthritis, with the diseases primary symptom being deep, achy joint pain exacerbated by extensive use. Also, reduced range of motion and crepitus are frequently present. Stiffness during rest (gelling) may develop, with morning joint stiffness usually lasting for less than 30 minutes. Initially, pain can be relieved by rest and may respond to simple analgesics. However, joints may become unstable as the osteoarthritis progresses; therefore, the pain may become more prominent (even during rest) and may not respond to medications.

Physical Examination
Physical examination findings in patients with osteoarthritis are mostly limited to the affected joints.[51, 52, 53] Reduced range of motion and crepitus are frequently present. Malalignment with a bony enlargement may occur. Most cases of osteoarthritis do not involve erythema or warmth over the affected joint(s); however, a bland effusion may be present. Limitation of joint motion or muscle atrophy around a more severely affected joint may occur. Osteoarthritis of the hand most often affects the distal interphalangeal (DIP) joints but also typically involves the proximal interphalangeal (PIP) joints and the joints at the base of the thumb. Heberden nodes, which represent palpable osteophytes in the DIP joints, are more characteristic in women than in men. Inflammatory changes are typically absent or at least not pronounced.

Progression of Osteoarthritis
The etiopathogenesis of osteoarthritis has been divided into 3 stages as follows:

Stage 1 Proteolytic breakdown of the cartilage matrix occurs Stage 2 Fibrillation and erosion of the cartilage surface develop, with subsequent release of proteoglycan and collagen fragments into the synovial fluid Stage 3 Breakdown products of cartilage induce a chronic inflammatory response in the synovium, which in turn contributes to further cartilage breakdown

Several systems have been advocated for use in the grading of focal cartilage change; however, a simple description of the extent of disease (ie, surface, partial-thickness, or fullthickness irregularity with or without underlying subchondral bone change) is generally sufficient and prevents the confusion that may occur with numeric grading systems. Such systems are in any case intended more for research purposes than for clinical use. Certain diseases are often categorized as subsets of primary osteoarthritis. These include primary generalized osteoarthritis (PGOA), erosive osteoarthritis, and chondromalacia patellae.

Diagnostic Considerations
The initial diagnostic goal is to differentiate osteoarthritis from other arthritides, such as rheumatoid arthritis. The history and physical examination findings are usually sufficient to diagnose osteoarthritis. Radiographic findings confirm the initial impression (see Workup), and laboratory values are typically within the reference range. Rheumatoid arthritis Rheumatoid arthritis predominantly affects the wrists, as well as the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. It rarely, if ever, involves the distal interphalangeal (DIP) joints or the lumbosacral spine. Rheumatoid arthritis is associated with prominent, prolonged (> 1 hour) morning stiffness and overtly swollen, warm joints. Radiographic findings include bone erosion (eg, periarticular osteopenia or marginal erosions of bone) rather than formation. Laboratory findings that further differentiate rheumatoid arthritis from osteoarthritis include the following:

Systemic inflammation (elevated erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP] level) Positive serologies (rheumatoid factor [RF] or anticyclic citrullinated peptide [antiCCP] antibodies) Inflammatory joint fluid with a predominance of polymorphonuclear leukocytes (PMNs) Elevated white blood cell (WBC) count

Additional arthritides Back pain may result from spondyloarthropathy or from osteoarthritis with sacroiliac and lumbosacral spine involvement. Clinical history and characteristic radiographic findings can be used to differentiate these disorders. Secondary osteoarthritis must be considered in individuals with any of the following:

Chondrocalcinosis History of joint trauma Metabolic bone disorders Hypermobility syndromes Neuropathic diseases

The following disorders should also be considered in the differential diagnosis:

Crystalline arthropathies (ie, gout and pseudogout) Inflammatory arthritis (eg, rheumatoid arthritis) Seronegative spondyloarthropathies (eg, psoriatic arthritis and reactive arthritis) Septic arthritis or postinfectious arthropathy Fibromyalgia Tendonitis
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In patients with knee pain, other disorders to consider in the differential diagnosis are patellofemoral syndrome and prepatellar bursitis.

Differential Diagnoses

Ankylosing Spondylitis Avascular Necrosis Fibromyalgia Gout and Pseudogout Imaging in Neuropathic Arthropathy (Charcot Joint) Lyme Disease Patellofemoral Arthritis Psoriatic Arthritis Rheumatoid Arthritis

Approach Considerations
Osteoarthritis is typically diagnosed on the basis of clinical and radiographic evidence.[12, 54, 55, 56, 57] No specific laboratory abnormalities are associated with osteoarthritis. Researchers have investigated the use of monoclonal antibodies, synovial fluid markers, and urinary pyridinium cross-links (ie, breakdown products of cartilage) as osteoarthritic indicators.[58] No single biomarker has proved reliable for diagnosis and monitoring, but combinations of cartilage-derived and bone-derived biomarkers have been used to identify osteoarthritis subtypes, with possible impact on treatment.[59] levels of acute-phase reactants are typically within the reference range in patients with osteoarthritis. The erythrocyte sedimentation rate (ESR) is not usually elevated, though it may be slightly so in cases of erosive inflammatory arthritis. The synovial fluid analysis usually shows a white blood cell (WBC) count below 2000/L, with a mononuclear predominance.

Plain Radiography
Plain radiography is the imaging method of choice because it is more cost-effective than other modalities and because radiographs can be obtained more readily and quickly.[55, 60] One important characteristic of primary osteoarthritis is that the abnormalities found in the loadbearing (ie, highly stressed) areas of the affected joint differ from those found in the non load-bearing areas. In the load-bearing areas, radiographs can depict joint-space loss, as well as subchondral bony sclerosis and cyst formation (see the image below).

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This radiograph demonstrates osteoarthritis of the right hip, including the finding of sclerosis at the superior aspect of the acetabulum. Frequently, osteoarthritis at the hip is a bilateral finding, but it may occur unilaterally in an individual who has a previous history of hip trauma that was confined to that one side. The elbow is not commonly affected in osteoarthritis. However, elbow arthritis (see the images below) can occur as a result of trauma.

Osteoarthritis of the elbow is not commonly seen; however, it

can occur with a history of previous trauma. Osteoarthritis of the elbow is not commonly seen; however, it can occur with a history of previous trauma.

Osteoarthritis of the elbow is not commonly seen; however, it can occur with a history of previous trauma.

MRI, CT, and Ultrasonography

Magnetic resonance imaging (MRI) can depict many of the same characteristics of osteoarthritis that plain radiography can, but it is not necessary in most patients with osteoarthritis, unless additional pathology amenable to surgical repair is suspected. Pathology that can be seen on MRI includes joint narrowing, subchondral osseous changes, and
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osteophytes. Unlike radiography, MRI can directly visualize articular cartilage and other joint tissues (eg, meniscus, tendon, muscle, or effusion). Computed tomography (CT) is rarely used in the diagnosis of primary osteoarthritis. However, it may be used in the diagnosis of malalignment of the patellofemoral joint or of the foot and ankle joints. Currently, ultrasonography has no role in the routine clinical assessment of the patient with osteoarthritis. However, it is being investigated as a tool for monitoring cartilage degeneration, and it can be used for guided injections of joints not easily accessed without imaging. For more information, see Imaging in Osteoarthritis.

Bone Scanning
Bone scans may be helpful in the early diagnosis of osteoarthritis of the hand.[61] Bone scans in osteoarthritis typically yield a symmetrically patterned, very mild increased uptake. In contrast, bone scans are often negative in the early stages of multiple myeloma, a cause of bone pain in older adults that can be confused with osteoarthritis. Bone scans also can help to differentiate osteoarthritis from osteomyelitis and bone metastases.

Arthrocentesis
A diagnostic joint aspiration for synovial fluid analysis can help exclude inflammatory arthritis, infection, or crystal arthropathy. The presence of noninflammatory joint fluid helps distinguish osteoarthritis from other causes of joint pain. Other synovial fluid findings that aid in the differentiation of osteoarthritis from other conditions are negative Gram stains and cultures, as well as the absence of crystals when fluid is viewed under a polarized microscope. For more information, see the following:

Knee Arthrocentesis Metacarpophalangeal Arthrocentesis Shoulder Arthrocentesis

Approach Considerations
The goals of osteoarthritis treatment include alleviation of pain and improvement of functional status.[62] Optimally, patients should receive a combination of nonpharmacologic and pharmacologic treatment.[63] Nonpharmacologic interventions, which are the cornerstones of osteoarthritis therapy, include the following:

Patient education Heat and cold

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Weight loss[64] Exercise Physical therapy Occupational therapy Unloading in certain joints (eg, knee, hip)

A physiatrist may help in formulating a nonpharmacologic management plan for the patient with osteoarthritis, and a nutritionist may help the patient to lose weight. A referral to an orthopedic surgeon may be necessary if the osteoarthritis fails to respond to a medical management plan. Surgical procedures for osteoarthritis include arthroscopy, osteotomy, and (particularly with knee or hip osteoarthritis) arthroplasty.

Pharmacologic Treatment
American College of Rheumatology guidelines
The American College of Rheumatology (ACR) has issued guidelines for pharmacologic treatment of osteoarthritis of the hand, hip, and knee.([49] For hand osteoarthritis, the ACR conditionally recommends using 1 or more of the following:

Topical capsaicin Topical nonsteroidal anti-inflammatory drugs (NSAIDs), including trolamine salicylate Oral NSAIDs Tramadol

The ACR conditionally recommends against using intra-articular therapies or opioid analgesics for hand osteoarthritis. For patients 75 years and older, the ACR conditionally recommends the use of topical rather than oral NSAIDs. For knee osteoarthritis, the ACR conditionally recommends using 1 of the following:

Acetaminophen Oral NSAIDs Topical NSAIDs Tramadol Intra-articular corticosteroid injections

The ACR conditionally recommends against using chondroitin sulfate, glucosamine, or topical capsaicin for knee osteoarthritis. The ACR has no recommendations regarding the use of intra-articular hyaluronates, duloxetine, and opioid analgesics. For hip osteoarthritis, the ACR conditionally recommends using 1 or more of the following for initial management:

Acetaminophen Oral NSAIDs Tramadol Intra-articular corticosteroid injections

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The ACR conditionally recommends against using chondroitin sulfate or glucosamine for hip osteoarthritis. The ACR has no recommendation regarding the use of topical NSAIDs, intraarticular hyaluronate injections, duloxetine, or opioid analgesics.

Agency for Healthcare Research and Quality findings

A comparison of analgesics for osteoarthritis carried out by the Agency for Healthcare Research and Quality (AHRQ) found that no currently available analgesic reviewed in this report offers a clear overall advantage compared with the others.[65] The choice of analgesic for an individual patient should take into account the trade-off between benefits and adverse effects, which differs across analgesics. Patient age, comorbid conditions, and concomitant medication are key considerations. The AHRQ comparison found that acetaminophen was modestly inferior to NSAIDs in reducing osteoarthritic pain but was associated with a lower risk of GI adverse effects.[65] On the other hand, acetaminophen poses a higher risk of liver injury. AHRQ findings on adverse effects included the following:

Selective NSAIDs as a class were associated with a lower risk of ulcer complications than were the nonselective NSAIDs naproxen, ibuprofen, and diclofenac The partially selective NSAIDs meloxicam and etodolac were associated with a lower risk of ulcer-related complications and symptomatic ulcers than were various nonselective NSAIDs The risk of serious GI adverse effects was found to be higher with naproxen than with ibuprofen Celecoxib and the nonselective NSAIDs ibuprofen and diclofenac were associated with an increased risk of cardiovascular adverse effects when compared with placebo The nonselective NSAIDs ibuprofen and diclofenac, but not naproxen, were associated with an increased risk of heart attack when compared with placebo

The AHRQ noted that topical diclofenac was found to have efficacy similar to that of oral NSAIDs in patients with localized osteoarthritis. No head-to-head trials compared topical salicylates or capsaicin with oral NSAIDs for osteoarthritis.[65] All NSAIDs had deleterious effects on blood pressure, edema, and kidney function. However, the AHRQ found no consistent clinically relevant differences between celecoxib, partially selective NSAIDs, and nonselective NSAIDs with regard to the risk of hypertension, heart failure, or impaired kidney function.[65]

Analgesics, NSAIDs, and COX-2 inhibitors

Begin treatment with acetaminophen for mild or moderate osteoarthritic pain without apparent inflammation. If the clinical response to acetaminophen is not satisfactory or if the clinical presentation of osteoarthritis is inflammatory, consider using an NSAID. Use the lowest effective dose or intermittent dosing if symptoms are intermittent, then try full doses if the patients response is insufficient.

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Topical NSAID preparations, particularly diclofenac, are available. These preparations can be particularly useful in patients with symptomatic disease that is limited to a few sites or in patients who are at increased risk for adverse events with systemic NSAIDs. In patients with highly resistant pain, consider the analgesic tramadol. Options in patients at an elevated risk for GI toxicity from NSAIDs include the addition of a proton-pump inhibitor or misoprostol to the treatment regimen and the use of the selective cyclooxygenase (COX)-2 inhibitor celecoxib instead of a nonselective NSAID.

Duloxetine
The selective serotonin-norepinephrine reuptake inhibitor duloxetine has been found to be effective in treating osteoarthritis pain.[66] For example, in patients with knee osteoarthritis who had persistent moderate pain despite optimized NSAID therapy, a randomized, doubleblind trial found significant additional pain reduction and functional improvement with duloxetine as compared with placebo.[67] However, duloxetine was also associated with significantly more nausea, dry mouth, constipation, fatigue, and decreased appetite than placebo was.[67] To date, trials of duloxetine in osteoarthritis have been short in duration (10-13 weeks), and studies comparing duloxetine directly with other therapies have not been performed.

Intra-articular injections
Intra-articular pharmacologic therapy includes injection of a corticosteroid or sodium hyaluronate (ie, hyaluronic acid [HA] or hyaluronan), which may provide pain relief and have an anti-inflammatory effect on the affected joint.[68, 69] Ultrasound guidance can facilitate arthrocentesis and injection and is increasingly being adopted by physicians such as rheumatologists and physiatrists for this purpose. Corticosteroid After the introduction of the needle into the joint and before steroid administration, aspiration of as much synovial fluid as possible should be attempted. Aspiration often provides symptomatic relief for the patient and allows laboratory evaluation of the fluid, if necessary. Infected joint fluid and bacteremia are contraindications to steroid injection. In patients with osteoarthritic knee pain, steroid injections generally result in clinically and statistically significant pain reduction as soon as 1 week after injection. The effect may last, on average, anywhere from 4 to 6 weeks per injection, but the benefit is unlikely to continue beyond that time frame.[70] For hip osteoarthritis, a randomized, placebo-controlled study confirmed the effectiveness of corticosteroid injection, with benefits often lasting as long as 3 months.[71] Some controversial evidence exists regarding frequent steroid injections and subsequent damage to cartilage (chondrodegeneration). Accordingly, it is usually recommended that no more than 3 injections per year be delivered to any individual osteoarthritic joint. Systemic glucocorticoids have no role in the management of osteoarthritis. For more information, see Corticosteroid Injections of Joints and Soft Tissues.
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Sodium hyaluronate Intra-articular injection of sodium hyaluronate, also referred to as viscosupplementation, has been shown to be safe and possibly effective for symptomatic relief of knee osteoarthritis.[72, 73] In the United States, intra-articular HAs are classified as medical devices rather than as drugs.[74] Intra-articular HAs approved by the FDA for the treatment of osteoarthritic knee pain include the naturally extracted, noncross-linked sodium hyaluronate products Hyalgan,[75] Supartz, Orthovisc, and Euflexxa, as well as the cross-linked sodium hyaluronate product known as hylan G-F 20 (Synvisc). Euflexxa is derived from a fermentation process (Streptococcus), whereas the source material for the other products listed is chicken combs. At present, no distinct advantage or disadvantage has been associated with any particular source of HA. Some differences between the viscosupplements do exist in the FDA-approved prescribing information. For example, whereas Hyalgan and Synvisc have been established as safe for repeat treatment, the safety and efficacy of other products for repeat treatment have not been established. The exact mechanisms of action through which HAs provide symptomatic relief are unknown. Possible mechanisms include direct binding to receptors (CD44 in particular) in the synovium and cartilage that can lead to several biologic activation pathways.[76, 77] The HA class in general has demonstrated a very favorable safety profile for chronic pain management in knee osteoarthritis, with the most common adverse event being injection-site pain. Although any intra-articular injection (whether of HAs or of steroids) may elicit an inflammatory response and possible effusion, only the cross-linked hylan G-F 20 product has been associated with a clinically distinct acute inflammatory side effect (ie, severe acute inflammatory reaction [SAIR] or HA-associated intra-articular pseudosepsis).

Additional pharmacologic agents

Muscle relaxants may benefit patients with evidence of muscle spasm. Judicious use of narcotics (eg, oxycodone and acetaminophen with codeine) is reserved for patients with severe osteoarthritis. Glucosamine and chondroitin sulfate have been used in Europe for many years and continue to be popular with patients worldwide. In the United States, however, the glucosamine/chondroitin arthritis intervention trial (GAIT) reported, at best, limited benefit from glucosamine (500 mg 3 times daily), chondroitin sulfate (400 mg 3 times daily), or the combination of the 2 in patients with knee osteoarthritis.[78, 79] In GAIT patients overall, glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively at 24 weeks, but in patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2% vs. 54.3%).[79] At 2 years, no treatment achieved a clinically important difference in loss of joint-space width, though treatment effects on Kellgren-Lawrence grade 2 knees showed a trend toward improvement relative to the placebo group.[78]
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The AHRQ comparison found no clear difference between glucosamine or chondroitin and oral NSAIDs for relieving pain or improving function.[65] However, the AHRQ observed that most trials showing therapeutic benefits from glucosamine used pharmaceutical-grade glucosamine that is not available in the United States, noting that the trial findings may therefore be inapplicable to currently available over-the-counter preparations. Another agent, S-adenosylmethionine (SAM-e), is a European supplement receiving significant attention in the United States. A systematic review of SAM-e found that the evidence was inconclusive, with a number of small trials of questionable quality; the authors concluded that the effects of SAM-e on pain and function may be potentially clinically relevant but are expected to be small.[80] Chondroprotective drugs (ie, matrix metalloproteinase [MMP] inhibitors and growth factors) are being tested as disease-modifying drugs in the management of osteoarthritis. For example, MMP-13 is specifically expressed in the cartilage of individuals with osteoarthritis but not in the cartilage of normal adults.[81] German researchers reported on the synthesis and biologic evaluation of an MMP-13 selective inhibitor that has demonstrated efficacy as a disease-modifying intra-articular injection for osteoarthritis.[82] Other investigational agents include monoclonal antibodies that inhibit nerve growth factor (NGF), such as tanezumab. Anti-NGF agents have been shown to reduce chronic pain in patients with osteoarthritis.

Lifestyle Modification, Physical/Occupational Therapy, and Other Nonpharmacologic Measures

Lifestyle modification, particularly exercise and weight reduction, is a core component in the management of osteoarthritis.[83, 84] Guidelines from Osteoarthritis Research Society International (OARSI) advise that nonpharmacologic treatment of hip and knee osteoarthritis should initially focus on self-help and patient-driven modalities rather than on modalities delivered by health professionals.[63] The ACR strongly recommends the following nonpharmacologic measures for patients with knee or hip osteoarthritis[85] :

Cardiovascular or resistance land-based exercise Aquatic exercise Weight loss, for overweight patients

The ACR conditionally recommends the following measures for patients with knee or hip osteoarthritis:

Self-management programs Manual therapy in combination with supervised exercise Psychosocial interventions Thermal agents Walking aids, as needed

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For patients with knee osteoarthritis, the ACR also conditionally recommends the following measures:

Medially directed patellar taping Medially wedged insoles for lateral-compartment osteoarthritis Laterally wedged subtalar strapped insoles for medial-compartment osteoarthritis Tai chi

For knee osteoarthritis, an American Academy of Orthopaedic Surgeons (AAOS) guideline suggests encouraging patients to participate in self-management educational programs such as those conducted by the Arthritis Foundation and to incorporate activity modifications into their lifestyle (eg, walking instead of running or engaging in alternative activities). Instruct the patient to avoid aggravating stress to the affected joint. Implement corrective procedures if the patient has poor posture. Weight reduction relieves stress on the affected knees or hips. The benefits of weight loss, whether obtained through regular exercise and diet or through surgical intervention, may extend not only to symptom relief but also to a slowing in cartilage loss in weight-bearing joints (eg, knees).[86] In addition, weight loss lowers levels of the inflammatory cytokines and adipokines that may play a role in cartilage degradation.[87] Some patients with osteoarthritis benefit from heat placed locally over the affected joint. A minority of patients report relief with ice.[88]

Physical activity
Although people with osteoarthritis tend to avoid activity, exercise is an effective treatment for this condition, producing improvements in pain, physical function, and walking distance. Long-term walking and resistance-training programs have been shown to slow the functional decline seen in many patients with osteoarthritis, including older patients.[87] Osteoarthritis of the knee may result in disuse atrophy of the quadriceps. Because these muscles help protect the articular cartilage from further stress, quadriceps strengthening is likely to benefit patients with knee osteoarthritis. Stretching exercises are also important in the treatment of osteoarthritis because they increase range of motion. In a study of patients with knee osteoarthritis, Jan et al found that in most respects, non weight-bearing exercise was as therapeutically effective as weight-bearing exercise.[89] After an 8-week exercise program, the 2 types of exercise resulted in equally significant improvements in function, walking speed, and muscle torque. However, patients in the weight-bearing group demonstrated greater improvement in position sense, which may help patients with complex walking tasks, such as walking on a spongy surface. Chaipinyo and Karoonsupcharoen found no significant difference between home-based strength training and home-based balance training for knee pain caused by osteoarthritis. However, greater improvement in knee-related quality of life was noted in the strengthtraining group.[90]

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The importance of aerobic conditioning, particularly low-impact exercises (if osteoarthritis is affecting weight-bearing joints), should be stressed as well. Swimming, especially the aerobic aquatic programs developed by the Arthritis Foundation, can be helpful. The benefits of exercise have been found to decline over time, possibly because of poor adherence. Factors that determine adherence to exercise have not been carefully studied in patients with osteoarthritis. In a review of this topic, Marks and Allegrante concluded that interventions to enhance self-efficacy, social support, and skills in the long-term monitoring of progress are necessary to foster exercise adherence in people with osteoarthritis.[91]

Tai chi
A prospective, single-blind, randomized, controlled study by Wang et al suggested that tai chi is a potentially effective treatment for pain associated with osteoarthritis of the knee.[92] In this trial, 40 patients with symptomatic tibiofemoral osteoarthritis who performed 60 minutes of tai chi twice weekly for 12 weeks experienced significantly greater pain reduction than did control subjects who underwent 12 weeks of wellness education and stretching. The mean difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores was 118.80 mm.[92] The tai chi cohort also had significantly better WOMAC physical function scores, patient and physician global visual analog scale scores, chair stand times, Center for Epidemiologic Studies Depression Scale scores, self-efficacy scores, and Short Form 36 physical component summaries. Similarly, a systematic review and meta-analysis concluded that research results are encouraging and suggest that tai chi may be effective in controlling pain and improving physical function in patients with knee osteoarthritis.[93] The researchers noted, however, that the strength of the evidence is limited by the small number of randomized, controlled trials with a low risk of bias.

Assistive devices
The use of assistive devices for ambulation and for activities of daily living (ADLs) may be indicated for patients with osteoarthritis. Braces and appropriate footwear may also be of some use. A cane can be used in the contralateral hand for hip or knee osteoarthritis. The patient can be taught joint-protection and energy-conservation techniques. For patients with hand osteoarthritis, the ACR conditionally recommends evaluating the patients ability to perform ADLs and providing assistive devices as needed. The ACR conditionally recommends splints for patients with trapeziometacarpal joint involvement.[85]

Occupational therapy and physical therapy

Occupational adjustments may be necessary for some patients with osteoarthritis. An occupational therapist can assist with evaluating how well the patient performs ADLs, as well as with retraining of the patient as necessary. Joint-protection techniques should be emphasized. Physical therapy modalities, especially those aimed at deconditioned patients, can be helpful, particularly in patients with hip or knee involvement.

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Electromagnetic field stimulation and TENS

A pulsed electromagnetic field stimulation device (Bionicare) has been approved by the US Food and Drug Administration (FDA) for use in patients with knee osteoarthritis. Pulsed electromagnetic field stimulation is believed to act at the level of articular cartilage by maintaining the proteoglycan composition of chondrocytes through downregulation of its turnover.[94] A multicenter, double-blind, randomized, placebo-controlled 4-week trial in 78 patients with knee osteoarthritis found improved pain and function in those who were treated with the device.[95] A double-blind, placebo-controlled 3-month trial in 58 patients with moderate-tosevere knee osteoarthritis showed that the use of a highly optimized, capacitively coupled, pulsed electrical stimulus device yielded significant symptomatic and functional improvement.[96] Another randomized clinical trial demonstrated that pulsed short-wave treatment was effective in relieving pain and improving function and quality of life in women with knee osteoarthritis on a short-term basis; additional studies are needed to validate the 12-month follow-up.[97] Transcutaneous electrical nerve stimulation (TENS) may be another treatment option for pain relief. To date, however, there is only limited evidence that TENS is beneficial in this setting. A systematic review could not confirm that TENS is effective for pain relief in knee osteoarthritis.[98] A randomized controlled trial found that TENS applied in conjunction with therapeutic exercise and daily activities increased quadriceps activation and function in patients with tibiofemoral osteoarthritis.[99]

Acupuncture
Acupuncture is becoming a more frequently used option for treatment of the pain and physical dysfunction associated with osteoarthritis. Some evidence supports its use. For example, a review article of randomized, controlled trials reported that the level of pain persisting after acupuncture was significantly lower than the level of pain persisting after control treatments.[100] Several groups have issued guidelines regarding acupuncture for knee osteoarthritis. The AAOS neither recommends nor opposes the use of acupuncture for pain relief in knee osteoarthritis, citing inconclusive evidence.[101] OARSI suggests that acupuncture may yield symptomatic benefit in these patients.[63] The ACR recommends traditional Chinese acupuncture for patients with chronic moderate-to-severe pain who would be candidates for total knee arthroplasty but who either do not want it or have contraindications to it.[85]

Arthroscopy
A procedure of low invasiveness and morbidity, arthroscopy will not interfere with future surgery. However, a randomized, controlled trial in patients with moderate-to-severe osteoarthritis found that arthroscopic surgery for osteoarthritis of the knee provided no additional benefit beyond that afforded by optimized physical and medical therapy.[1]

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Arthroscopy is indicated for removal of meniscal tears and loose bodies; less predictable arthroscopic procedures include debridement of loose articular cartilage with a microfracture technique and cartilaginous implants in areas of eburnated subchondral bone (see the images below). These treatments have varying success rates and should be performed only by surgeons experienced in arthroscopic surgical techniques.[1, 102, 103] Overall, arthroscopy is not recommended for nonspecific cleaning of the knee in osteoarthritis.

Arthroscopic view of a torn meniscus before (top) and after (bottom)

removal of loose meniscal fragments.

Arthroscopic view of an

arthritic knee.

Arthroscopic view of a knee after the removal

of loose fragments of articular and meniscal cartilage. Arthroscopic view of the removal of cartilaginous loose body. Patients who undergo arthroscopy usually require a period of crutch use or exercise therapy. This period typically lasts days but sometimes extends for weeks.

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Osteotomy
Osteotomy is used in active patients younger than 60 years who have a malaligned hip or knee joint and want to continue with reasonable physical activity.[104] The principle underlying this procedure is to shift weight from the damaged cartilage on the medial aspect of the knee to the healthy lateral aspect of the knee. Osteotomy is most beneficial for significant genu varum, or bowleg deformity. (The effectiveness of osteotomy for genu valgum is not highly predictable.) Osteotomy often can help individuals avoid requiring a total knee replacement until they are older. It can lessen pain, but it can also lead to more challenging surgery if the patient later requires arthroplasty. Contraindications for osteotomy are as follows:

Knee flexion of less than 90 A flexion-extension contracture of more than 15 Varus over 15-20 Instability from previous trauma or surgery Severe arterial insufficiency Bicompartmental involvement

Patients undergoing osteotomy require partial weight-bearing until bony healing occurs. Afterward, exercise is indicated.

Arthroplasty
Arthroplasty consists of the surgical removal of joint surface and the insertion of a metal and plastic prosthesis (see the images below). The prosthesis is held in place by cement or by bone ingrowth into a porous coating on the prosthesis. The use of cement results in faster pain relief, but bone ingrowth may provide a more durable bond; accordingly, prostheses with a porous coating are used in younger patients.

Anteroposterior radiograph shows knee replacement in 1 knee and arthritis in the other, with medial joint-space narrowing and subchondral sclerosis.

Anteroposterior radiograph of the pelvis and hips shows an

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arthritic hip not treated surgically and a total hip replacement.

Anteroposterior radiograph obtained after knee replacement. radiograph obtained after knee replacement (same patient as in the above image).

Lateral

Arthroplasty is performed if all other modalities are ineffective and osteotomy is not appropriate or if a patient cannot perform ADLs despite maximal therapy.[105, 106] This procedure alleviates pain and may improve function. At a minimum, 10-15 years of viability are expected from joint replacement in the absence of complications. Infection is a particular postoperative concern in cases of total joint replacement. This complication is now rare, however, especially with the use of perioperative antibiotics. Prevention of thrombophlebitis and resultant pulmonary embolism is important in patients who undergo lower-extremity arthroplasty procedures for osteoarthritis. The surgeon must use all means available to prevent these complications. Early motion and ambulation, when possible, are of particular importance. The use of low-molecular-weight heparin or warfarin is also indicated. After joint replacement, patients require partial weight-bearing, which progresses to full weight-bearing in 1-3 months; range-of-motion and strengthening exercises are started within a few days after joint-replacement surgery and continued until the patient has good range of motion and strength. After resection arthroplasty of the hip, patients require instruction in the use of crutches or a walker, which are usually needed permanently. For more information, see the following articles:

Total Knee Arthroplasty Unicompartmental Knee Arthroplasty Surgical Treatment of Interphalangeal Joint Arthritis Minimally Invasive Total Hip Arthroplasty
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Fusion and Joint Lavage

Fusion consists of the union of bones on either side of the joint. This procedure relieves pain but prevents motion and puts more stress on surrounding joints. Fusion is sometimes used after knee replacements fail or as a primary procedure for ankle or foot arthritis. Observational studies suggested a benefit for joint lavage. However, sham-controlled trials yielded conflicting results, and a meta-analysis concluded that joint lavage does not result in pain relief or improvement of function in patients with knee osteoarthritis.[107]

Prevention
Overweight patients who have early signs of osteoarthritis or who are at high risk should be encouraged to lose weight. Recommend quadriceps-strengthening exercises in patients with osteoarthritis of the knees, except in those with pronounced valgus or varus deformity at the knees. (See Lifestyle Modification, Physical/Occupational Therapy, and Other Nonpharmacologic Measures.) It has been proposed that low vitamin D levels may play a role in the development and progression of osteoarthritis; however, studies of vitamin D status and osteoarthritis have produced conflicting results.[108, 109] A systematic review found no convincing evidence that selenium, vitamin A, or vitamin C is effective for the treatment of osteoarthritis.[110] A prospective cohort study also found no evidence that vitamin C supplementation slowed the progression of knee osteoarthritis; however, it did find that patients who reported taking vitamin C were 11% less likely to develop knee osteoarthritis.

Medication Summary
The goals of pharmacotherapy in osteoarthritis are to reduce morbidity and to prevent complications. To date, no disease-modifying or structure-modifying intervention has been proved effective in osteoarthritis. Pay careful attention to a particular pharmacologic regimens adverse-event profile. Pharmacologic agents used in the treatment of osteoarthritis include the following:

Acetaminophen Nonsteroidal anti-inflammatory drugs (NSAIDs), oral and topical Intra-articular corticosteroids Intra-articular sodium hyaluronate Opioids Duloxetine Muscle relaxants Nutriceuticals (eg, glucosamine/chondroitin sulfate)

Analgesics, Other
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Class Summary
Pain control is essential to the management of osteoarthritis. The goals of treatment include pain alleviation and improvement of functional status. View full drug information

Acetaminophen (Tylenol, Panadol, Aspirin-Free Anacin)

An initial trial with acetaminophen is warranted in patients with mild-to-moderate osteoarthritis symptoms who do not derive sufficient relief from nonpharmacologic measures. Acetaminophen is the drug of choice for patients who have a documented hypersensitivity to aspirin or NSAIDs, who have a history of upper gastrointestinal (GI) tract disease, or who are on anticoagulants.

NSAIDs
Class Summary
NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. They are used to relieve osteoarthritis pain when the clinical response to acetaminophen is unsatisfactory. The mechanism of action is nonselective inhibition of cyclooxygenase (COX)-1 and COX-2, resulting in reduced synthesis of prostaglandins and thromboxanes. Other mechanisms may also exist, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions. In more inflammatory presentations of osteoarthritis, such as knee involvement with effusion, these agents may be used as first-line pharmacologic therapy. Use the lowest effective dose or intermittent therapy if symptoms are intermittent. All of these medications increase the risk for GI ulcers and have been associated with increased risk of cardiovascular disease. Patients at high risk for GI toxicity may consider adding misoprostol or a proton-pump inhibitor to the regimen or substituting a COX-2specific inhibitor for the NSAID. View full drug information

Ketoprofen (Orudis, Oruvail)

Ketoprofen is indicated for relief of mild-to-moderate pain and inflammation. Small dosages are initially indicated in small and elderly patients and in those with renal or liver disease. Doses higher than 75 mg do not increase therapeutic effects. Administer high doses with caution, and closely observe the patient for response. View full drug information

Piroxicam (Feldene)
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Piroxicam decreases the activity of cyclooxygenase, which in turn inhibits prostaglandin synthesis. These effects decrease formation of inflammatory mediators. View full drug information

Ibuprofen (Ibuprin, Advil, Motrin)

Ibuprofen relieves pain and inflammation. It is widely available and is relatively inexpensive as a generic drug. After the very early stages of osteoarthritis, inflammation begins to play a role in the disease. Thus, medications with a combination of analgesic and anti-inflammatory properties become more desirable, at least in theory. View full drug information

Meloxicam (Mobic)

To some extent, meloxicam is more selective for COX-2 receptors than traditional NSAIDs are. It decreases the activity of cyclooxygenase, thereby, in turn, inhibiting prostaglandin synthesis. These effects decrease the formation of inflammatory mediators. View full drug information

Diclofenac (Voltaren, Arthrotec, Cataflam)

Diclofenac is one of a series of phenylacetic acids that have demonstrated anti-inflammatory and analgesic properties in pharmacologic studies. It is believed to inhibit cyclooxygenase, which is essential in the biosynthesis of prostaglandins. Diclofenac can cause hepatotoxicity; hence, liver enzymes should be monitored in the first 8 weeks of treatment. Diclofenac is rapidly absorbed; metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation. The delayed-release, enteric-coated form is diclofenac sodium, and the immediate-release form is diclofenac potassium. It poses a relatively low risk for bleeding GI ulcers. View full drug information

Celecoxib (Celebrex)

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Celecoxib is a COX-2specific inhibitor. At therapeutic concentrations, COX-2 (inducible by cytokines at sites of inflammation, such as the joints) is inhibited, and COX-1 isoenzyme (present in platelets and the GI tract) is spared; therefore, in nonaspirin users, the incidence of GI toxicity (eg, endoscopic peptic ulcers, bleeding ulcers, perforations, and obstructions) is decreased in comparison with that seen in patients taking nonselective NSAIDs. COX-2 is expressed in the kidney; however, the renal safety profile of celecoxib is not significantly superior to that of nonselective NSAIDs. Selective COX-2 inhibitors may increase the risk of cardiac disease; 1 drug in this class, rofecoxib, has already been removed from the market for this reason. Celecoxib is currently under investigation for a possible associated risk of accelerated cardiac disease. View full drug information

Naproxen (Aleve, Anaprox, Anaprox DS, Naprelan, Naprosyn)

Naproxen is used for relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which is responsible for prostaglandin synthesis. NSAIDs decrease intraglomerular pressure and decrease proteinuria.

Antidepressants, SNRIs
Class Summary
The selective serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine may be effective for reducing osteoarthritis pain. View full drug information

Duloxetine (Cymbalta)

Potent inhibitor of neuronal serotonin and norepinephrine reuptake. Indicated for chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain.

Analgesic, Topical
Class Summary
Topical analgesics are used for osteoarthritis involving relatively superficial joints, such as the knee joint and the joints of the hands. They are much less effective for deeper joints, such as the hip joint. View full drug information

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Capsaicin (Dolorac, Capsin, Zostrix, Civamide)

Capsaicin is a topical analgesic of choice in osteoarthritis. Derived from plants of the Solanaceae family, it may render skin and joints insensitive to pain by depleting substance P in peripheral sensory neurons. Capsaicin must be used for at least 2 weeks for the full effects to be appreciated.

Opioid Analgesics
Class Summary
Opioid analgesics are used in patients whose pain has not been controlled with weaker analgesic medications. They are a particularly reasonable choice in patients who do not want joint-replacement surgery, are too medically ill for joint replacement, are not candidates for joint replacement for other reasons, or are trying to buy time for subsequent joint-replacement surgery. Elderly patients (aged 65 years and older) with arthritis are more likely to incur a fracture when initiating opioid therapy as opposed to NSAID therapy. A higher opioid dose is associated with a greater risk of fracture; this risk is due to an increased risk of falls. During the first 2 weeks after initiation of opioid treatment, short-acting opioids are associated with a greater fracture risk than long-acting opioids are.[112] View full drug information

Tramadol (Ultram, Ultram ER)

Tramadol inhibits ascending pain pathways, altering perception of and response to pain. This agent also inhibits the reuptake of norepinephrine and serotonin.

Oxycodone (OxyContin, Roxicodone)

Pure narcotic analgesics, such as oxycodone, might be the initial drug of choice. Eventually, this short-acting narcotic can be replaced with a long-acting transdermal preparation, such as fentanyl (Duragesic patch).

Corticosteroids
Class Summary
Intra-articular pharmacologic therapy includes corticosteroid injection and viscosupplementation. Steroid injections generally result in a clinically and statistically significant reduction in osteoarthritic knee pain as soon as 1 week after injection. The effect

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may last, on average, anywhere from 4 to 6 weeks per injection, but the benefit is unlikely to continue beyond that time frame. View full drug information

Methylprednisolone (Depo-Medrol, Medrol, Solu-Medrol)

Methylprednisolone decreases inflammation by suppressing migration of polymorphonuclear leukocytes (PMNs) and reversing increased capillary permeability. View full drug information

Betamethasone (Celestone Soluspan)

Betamethasone decreases inflammation by suppressing migration of PMNs and reversing increased capillary permeability. It affects the production of lymphokines and has an inhibitory effect on Langerhans cells. View full drug information

Triamcinolone (Aristospan Intra-Articular)

Triamcinolone decreases inflammation by suppressing migration of PMNs and reversing capillary permeability.

Intra-articular Agents
Class Summary
Intra-articular injections of these agents are used to treat patients with osteoarthritic knee pain that is unresponsive to conservative nonpharmacologic therapy and simple analgesics (eg, acetaminophen). View full drug information

Sodium hyaluronate (Euflexxa, Hyalgan, Orthovisc, Supartz, Synvisc, Synvisc-One)

Sodium hyaluronate is a hyaluronic acid derivative that supports the lubricating and shockabsorbing properties of articular cartilage.

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