Osteoarthritis 

Osteoarthritis is the most common type of joint disease, affecting over 20 million individuals in the United States alone (see Epidemiology). It represents a heterogeneous group of conditions that result in common histopathologic and radiologic changes. It is a degenerative disorder that results from the biochemical breakdown of articular (hyaline) cartilage in the synovial joints. However, the current concept holds that osteoarthritis involves not just the articular cartilage but 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) and proximal interphalangeal (PIP) joints of the hands. This article primarily focuses on osteoarthritis of the hand, knee, and hip joints (see Pathophysiology).

For more information, see Glenohumeral Arthritis, Wrist Arthritis, Lateral Compartment Arthritis, and Medial Compartment Arthritis.

Although osteoarthritis is thought to be largely due to excessive wear and tear, secondary nonspecific inflammatory changes may also affect the joints. Therefore, the term degenerative joint disease is no longer appropriate when referring to osteoarthritis.

Historically, osteoarthritis has been divided into primary and secondary forms, although this division is somewhat artificial. Secondary osteoarthritis is conceptually easier to understand. It refers to degenerative disease of the synovial joints that results from some predisposing condition, usually trauma, that has adversely altered the articular cartilage and/or subchondral bone of the affected joints. Secondary osteoarthritis often occurs 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 primary osteoarthritis is related to the aging process and typically occurs in older individuals, in the broadest sense of the term, it is an idiopathic phenomenon, occurring in previously intact joints and having no apparent initiating factor.

Some clinicians limit primary osteoarthritis to the joints of the hands (specifically the DIP and PIP joints and joints at the base of the thumb), whereas others include the knees, hips, spine (apophyseal articulations), and hands as potential sites of involvement. 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; it is typically diagnosed on the basis of clinical and radiographic findings (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 patient education, temperature modalities, weight loss, exercise, physical therapy, occupational therapy, and joint unloading in certain joints (eg, knee, hip). (See Treatment Strategies and Management)

Intra-articular pharmacologic therapy includes corticosteroid injection and viscosupplementation, which may provide pain relief and have an anti-inflammatory effect on the affected joint.

Begin treatment with acetaminophen for mild or moderate pain without apparent inflammation; if the clinical response to acetaminophen is not satisfactory or if the clinical presentation is inflammatory, consider nonsteroidal anti-inflammatory drug (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 of osteoarthritis 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.)

Joints can be classified as synovial, fibrous, or combination joints, based on the presence or absence of a synovial membrane and the amount of motion that occurs in the joint. 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 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 the major protein component of synovial fluid, hyaluronic acid (also known as hyaluronate). 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.

Primary and secondary osteoarthritis are not separable on a pathologic basis, although bilateral symmetry is often seen in cases of primary osteoarthritis, particularly when the hands are affected.^{[12, 13]}

As mentioned above, although osteoarthritis was traditionally thought to affect primarily the articular cartilage of synovial joints, pathophysiologic changes also occur in the synovial fluid, as well as in the underlying (subchondral) bone and in the overlying joint capsule (see Workup).^{[14, 15, 16, 17]}

Even though osteoarthritis has always been classified as a noninflammatory arthritis, increasing evidence has shown that inflammation occurs as cytokines and metalloproteinases are released into the joint. Theses agents are involved in the excessive matrix degradation that characterizes cartilage degeneration in osteoarthritis.^[18] Therefore, as previously noted, the term degenerative joint disease is no longer appropriate when referring to osteoarthritis.

In early osteoarthritis, swelling of the cartilage usually occurs, due to 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, thereby further compromising joint surface integrity.

Microscopically, as flaking and fibrillations (vertical clefts) develop along the normally smooth articular cartilage on the surface of an osteoarthritic joint, the loss of cartilage results in the loss of the joint space.

In major weight-bearing joints of persons with osteoarthritis, a greater loss of joint space occurs at those areas subjected to the greatest pressures; this effect contrasts with that of inflammatory arthritides, in which uniform joint-space narrowing is the rule. In the osteoarthritic knee, for example, one commonly observes the greatest loss of joint space in the medial femorotibial compartment, although 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, due to either 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. These lesions are generally 2-20 mm in diameter. Osteoarthritic cysts in the acetabulum are termed Egger cysts, one of which is seen in the image below.

At nonpressure 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 the joint damage noted above, osteoarthritis may also lead to pathophysiologic changes in ligaments and the neuromuscular apparatus.

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
• 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)

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. Spinal stenosis is caused by facet arthritic changes that result in compression of the nerve roots. The occurrence of an acquired spondylolisthesis is a common denominator of arthritis of the lumbar spine.

The daily stresses applied to the joints, especially the weight-bearing joints (eg, ankle, knee, 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 disrupt the cartilaginous matrix.^{[20, 21, 22, 23]}

Risk factors for osteoarthritis include the following^{[24, 25, 26, 27]} :

• Age
• Obesity (increases mechanical stress)^{[28, 29, 30]}
• Trauma
• Genetics
• Sex hormones
• Muscle weakness^[31]
• Repetitive use (ie, jobs requiring heavy labor and bending)^[32]
• Infection
• Crystal deposition
• Acromegaly
• Previous rheumatoid arthritis (ie, burnt-out rheumatoid arthritis)
• Heritable metabolic causes (eg, alkaptonuria, hemochromatosis, Wilson disease)
• Hemoglobinopathies (eg, sickle cell disease, thalassemia)
• Neuropathic disorder leading to a Charcot joint (eg, syringomyelia, tabes dorsalis, diabetes)
• Underlying orthopedic disorders (eg, congenital hip dislocation, slipped femoral capital epiphysis)
• Disorders of bone (eg, Paget disease, avascular necrosis)

Advancing age

With advancing age, cartilage volume, proteoglycan content, cartilage vascularization, and cartilage perfusion are reduced and may result in certain characteristic radiologic features, including narrowed joint space and the presence of 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. Using logistic regression, one study evaluated the associations between body mass index (BMI) over 14 years and knee pain at year 15 in 594 women. A greater BMI at year 1 and a significant increase in BMI over 15 years were predictors of knee pain at year 15. These results suggest that a higher BMI may be predictive of knee pain at year 15, independently of radiographic changes; this association was significant in bilateral but not unilateral knee pain.^[30]

Trauma

Traumatic insults to the articular cartilage, ligaments, or menisci lead to abnormal biomechanics in the joints and enhance their premature degeneration.

Menopause

Menopause often increases the progression of osteoarthritis; however, estrogen replacement therapy lowers the expected rate of radiographic and clinical findings in the knees and hips.

Muscle dysfunction

Muscle dysfunction compromises the body's 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 to prevent muscle dysfunction.

Genetics

In addition to the above factors, a hereditary component to the disease has long been recognized, particularly in generalized osteoarthritis; indeed a specific gene for osteoarthritis has been identified. One should not confuse environmental factors as causes of osteoarthritis, because these factors actually cause traumatic arthritis on a macrotraumatic or microtraumatic basis. This is especially true of individuals whose lifestyles require squatting, climbing stairs, or excessive kneeling.

United States statistics

Osteoarthritis affects over 20 million individuals in the United States, although statistical figures are influenced by whether the condition is defined epidemiologically (ie, using radiographic criteria) or clinically (eg, using radiographic findings plus clinical symptoms). Based on the radiographic criteria for osteoarthritis, more than half of adults older than age 65 years are affected by the disease.

International statistics

Internationally, osteoarthritis is the most common articular disease. Estimates vary among different populations. The prevalence of osteoarthritis differs among different ethnic groups.^[33] 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. 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.

Age- and sex-related prevalence

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 primary osteoarthritis.^[34] Patients with symptoms usually do not notice them until after age 50 years. The prevalence of the disease increases dramatically among persons over age 50, 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.^[34]

In individuals older than age 55 years, the prevalence of osteoarthritis is higher among women than men.^[34] Women are especially susceptible to osteoarthritis in the DIP joints of the fingers. Women also have osteoarthritis of the knee joints more frequently than do men, 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.

At age 18-24 years, 7% of men and 2% of women show signs of osteoarthritis in the hands. At age 55-64 years, 28% of men and women show signs of osteoarthritis in the knee, and 23% show signs of osteoarthritis in the hip. At age 65-74 years, 39% of men and women show signs of osteoarthritis in the knee and 23% show signs of osteoarthritis in the hip. At age 75-79 years, approximately 100% of men and women show some signs of osteoarthritis.

The prognosis of osteoarthritis depends on the joints involved and the severity of the condition. No proven disease/structure-modifying drugs for osteoarthritis are currently known; thus, the medication-based regimen is directed at symptom relief.

Nevertheless, a recent systematic review of the literature has noted several clinical features associated with more rapid knee osteoarthritis (OA) progression. These include age, body mass index, varus deformity, and multiple involved joints, and their presence may help identify those more likely to have knee OA progression.^[35]

The prognosis is good for patients with osteoarthritis who have undergone joint replacement, with success rates for hip and knee arthroplasty being generally more than 90%. However, a joint prosthesis may need revision 10-15 years after its installation, depending on the patient's activity level. Younger and more active patients will require revisions, whereas the majority of older patients will not. (See Treatment Strategies and Management.)

Educate patients on the natural history of and management options for osteoarthritis. 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 institute ways to reduce pain and increase joint function. Emphasize the need for physician follow-up visits.

For excellent patient education resources, visit eMedicine's Arthritis Center. Also, see eMedicine's patient education article Osteoarthritis.