The osteoarthritic knee

Peter C. Vitanzo, Jr, MD; John M. McShane, MD

From A Special Report: Osteoarthritis of the Knee

Keeping Aging Adults Active

Preview: Osteoarthritis of the knee is a complex, multifactorial process. It can be a major cause of pain and disability, and it has a substantial impact on functioning and activities of daily living. The evaluation of signs and symptoms consistent with osteoarthritis of the knee includes careful history taking as well as physical and radiographic examinations. Some risk factors are consistent, but others, such as physical activity, are controversial. Identification of these factors can help physicians manage patients with arthritis as well as reduce the burden this condition imposes on healthcare costs.

Osteoarthritis of the knee is a common problem, especially in elderly people, but it should not be considered an inevitable feature of aging.1 Although the prevalence varies among different populations, it is a major cause of pain and disability and can impose significant financial costs on society. Osteoarthritis of the knee often has a substantial impact on functioning and activities of daily living.

The estimated population prevalence varies from 4% to 30% depending on age, gender, and disease definition.1 The risk of osteoarthritis of the knee is comparable in men and women up to about 50 years of age. However, after 50 years of age, the incidence and prevalence of osteoarthritis of the knee increases more rapidly in women than in men.2 This is especially evident in African-American women compared with other women.3

Despite the fact that clinicians may know what constitutes osteoarthritis, outcome and epidemiologic studies have been hindered by disparity over a precise definition.1 Furthermore, different studies have been inconsistent about the impact of lifestyle and constitutional factors on the development and progression of osteoarthritis of the knee.4

The goal of this article is to clarify and enhance clinicians' understanding of osteoarthritis of the knee, especially in older people. We will focus on the pathophysiological characteristics of the disease process, cause, diagnosis, and evaluation of patients.

Pathophysiology of the disease process

Osteoarthritis is predominantly a disease of articular cartilage, which is composed mainly of water, collagens, and proteoglycans. Chondroitin sulfate and keratin sulfate (glycosaminoglycan side chains) are attached to a protein core forming proteoglycans. These in turn bind with hyaluronic acid (glycosaminoglycan) and proteins, contributing to cartilage stability and strength. Collagens, especially type II (the major type in hyaline cartilage), also play a key role in the structural integrity and functional capabilities of cartilage.3

Grossly, the first manifestation of osteoarthritis is cartilage irregularity. This is followed by erosion of the cartilage surface and ultimately, by cartilage loss, which can result in bone-to-bone contact within the joint.3,5

Microscopically, fibrillation (irregularity) occurs in the early stages, preceding the eventual depletion of glycosaminoglycans. This leads to the development of vertical fissures and clefts and inevitably, loss of cartilage. Inflammatory cells may transiently proliferate early in the process, but inflammation is not a significant component of osteoarthritis of the knee.3

As a result of the depletion of glycosaminoglycans, the water content of cartilage increases secondary to increased diffusion capacity. There is also an increase in matrix metalloproteinase enzyme activity, which plays a major role in the degradation of the extracellular matrix of cartilage and facilitates the breakdown of both proteoglycans and collagen.3

At the cellular level, in early osteoarthritis chondrocytes undergo transient proliferation and produce increased quantities of various enzymes and growth factors. This results in an imbalance between the degradation and the synthesis of the cartilage matrix. When this imbalance occurs, osteoarthritic changes develop.3

Crystal deposition has also been implicated in the pathogenesis of osteoarthritis. The progression of osteoarthritis is often parallel with calcium phosphate crystal, calcium pyrophosphate, or hydroxyapatite accumulation in the joint fluid. This is even more common in severely osteoarthritic joints.6 One implication of crystal deposition in osteoarthritis is hypothesized to be crystal endocytosis by synovial lining cells. This leads to release of enzymes (collagenases, stromelysin, and other proteases) and other factors (prostaglandin E2) that can augment cartilage degeneration.3,6,7

After initiation, osteoarthritis develops into a self-perpetuating process that continues unchecked. Progression of the disease is inevitably accompanied by a change in cartilage architecture, which alters the mechanical stresses within the joint. This leads to further joint damage and degradation.6 Several theories have been proposed to clarify the degradation of cartilage in osteoarthritis. Mechanical stress seems to be the inciting event, leading to alterations in chondrocyte metabolism and matrix properties as well as increased production of proteolytic enzymes. It appears that resultant multiple microfractures eventually lead to degradation and gradual loss of the articular cartilage, which alters joint architecture and promotes osteophyte production.3

The pathophysiology of pain in osteoarthritis is multifactorial. Periostitis may develop at sites of bone remodeling with resultant pain. Other pain generators include subchondral microfractures, irritation of sensory nerve endings in the synovium from osteophytes, periarticular muscle spasm, and bone angina from diminished blood flow and elevated intraosseous pressure. Synovial inflammation with associated release of prostaglandins, leukotrienes, and various cytokines can also cause pain, but extensive histological changes of synovial inflammation are lacking in osteoarthritis of the knee.5


Osteoarthritis of the knee is a universal problem caused by multiple factors, including genetic (which may account for up to 40% to 60% of osteoarthritis), metabolic, biochemical, enzymatic, and biomechanical properties, as well as environmental factors.8,9 The literature suggests that the pathogenesis of osteoarthritis of the knee is different between men and women. In women, osteoarthritis tends to have a stronger association with obesity and is frequently bilateral; in men it tends to be related to prior trauma or injury and is often unilateral.10 Established risk factors include older age, female sex, osteoarthritis at other sites, obesity, and previous injury or surgery (table 1). Obesity and previous injury seem to have a greater impact on initiation than on progression.11 There is also evidence that a certain level of physical activity may have the same effect, but some investigators have not been convinced of this relationship.11,12 In all age groups, "normal" joints appear to tolerate prolonged, vigorous exercise without adverse outcomes or accelerated onset of osteoarthritis of the knee.9

Table 1. Risk factors for osteoarthritis of the knee
Established Controversial
Obesity Physical activity
Sex (female) Genetics
Age Estrogen deficiency
Osteoarthritis at other sites Smoking
Previous knee trauma or injury  
Previous knee surgery  

As part of the Framingham study, McAlindon et al12 demonstrated a strong association with heavy physical activity and the incidence of osteoarthritis of the knee, especially in elderly patients. This may be related to physiologic impairment (muscle weakness, proprioceptive defects, meniscal degeneration, or ligamentous tears) in the skeletal response to physical activity in older people.7,12 These biomechanical stresses may permit transmission of an increased load across affected osteoarthritic joints, leading to accelerated joint damage. Repetitive joint loading may influence joint degeneration,9 but this has not been well studied.7 Biomechanical and biochemical factors, age, sex, characteristics of the playing surface, duration and intensity of the sport, and history of joint injury or trauma (sudden or repetitive) are risk factors that most physicians would consider important in the development of exercise-related osteoarthritis of the knee.

Factors such as ligamentous instability and abnormal motion may also contribute to premature osteoarthritis of the knee. Running is a good example of these concepts. Despite the evidence that a moderate amount of running does not seem to augment the development of osteoarthritis of the knee in most people, it has a different effect on people who have sustained previous trauma or injury or have joints with significant anatomical variances.9 Unfortunately, the literature on the association between osteoarthritis of the knee and leisurely physical activity is controversial, especially in people with normal joints.11 Low-impact activities do not seem to promote an increased risk of osteoarthritis of the knee, but high-impact or high-intensity activities do.11,12

Controlled joint loading and motion may actually stimulate repair of damaged cartilage and promote maintenance of the normal synovial joint structure, composition, and function. This is evident after a prolonged decrease in joint use (ie, after injury or trauma), when cartilage changes frequently occur. It is well known that protracted immobilization of the joints eventually causes irreversible damage to articular cartilage. This often includes contracture of periarticular dense fibrous tissues, muscles that act across the joint, articular cartilage loss, and infiltration of fibrofatty tissue into the joint cavity. This beneficial effect is mainly limited to the loss of matrix proteoglycans because there is little evidence that joint use promotes repair of enzymes that disrupt the cartilage alone.9 Up to a certain threshold, this increased loading and motion of the joint may increase matrix synthesis relative to matrix degeneration and promote healthier cartilage.9,12 Above this threshold, activities may become deleterious, possibly because of repetitive subclinical injuries.12

Another consistent risk factor for osteoarthritis of the knee is obesity, especially in middle-aged or older women compared with men.4,8,13 Cross-sectional and longitudinal studies have repeatedly demonstrated this.13 In a case-controlled study of 625 subjects (men and women) in Sweden, Sandmark et al4 found a strong association with obesity (or elevated body mass index [BMI]) and osteoarthritis of the knee, primarily in women 40 to 50 years of age. This was also confirmed in the Framingham study12 and in a case-controlled study by Oliveria et al,13 which also accounted for estrogen use, height, smoking status, and healthcare contacts. Furthermore, body weight and BMI are consistent predictors of osteoarthritis of the knee.13

As previously mentioned, age plays a critical role in the prevalence and incidence as well as the progression of osteoarthritis of the knee.7 In the Chingford study,8 investigators found a 2-fold increase in the risk of osteoarthritis of the knee in older women compared with women 20 years younger, and in moderately overweight women compared with thin or normal-weight women. In addition, age and obesity appear to have the most significant effect on the incidence of knee osteophytes.8 The Framingham study12 did not report such a close correlation with age and incidence. A case-controlled study of 452 subjects (40 to 80 years old) by Lanyon et al1 found no significant decline in joint space width in any compartment with increasing age among asymptomatic men and women with osteophytes. Furthermore, these authors did not find a significant correlation between joint space and height, weight, or BMI in normal subjects. These findings contrast with other studies which suggest that joint space width diminished with age until an apparent symptomatic pain threshold was attained. However, the findings are consistent with the concept that osteoarthritis is a specific process and not simply a normal part of aging.

Finally, sex is another critical factor for osteoarthritis of the knee. Based on the Chingford and Framingham studies8,12 approximately 2% to 3% of middle-aged women will develop new knee osteophytes and joint space narrowing each year.8 In a prospective cohort study by Slemenda et al,10 an increase in body weight was associated with osteoarthritis of the knee in women but was not statistically significant in men. Reduced quadriceps muscle strength relative to body weight may be a risk factor for osteoarthritis of the knee in women.10 Quadriceps strength was found to be about 15% to 18% less among women with radiographic evidence of osteoarthritis of the knee compared with normal subjects.10,14 This relationship did not hold true for men.10

A prospective cohort study by Zhang et al2 found that estrogen deficiency may also play a role in the development of osteoarthritis in women. In fact, postmenopausal estrogen replacement therapy may have a moderately protective effect on the incidence and progression of radiographic osteoarthritis of the knee in elderly women. The Chingford and Framingham studies8,12 also found a protective relationship of current estrogen use on the prevalence of osteoarthritis of the knee. However, this effect was not significant for the incidence of new-onset disease.8

Diagnosis and evaluation

The history, physical examination, and radiographic examination help establish the diagnosis of arthritis of the knee.

HISTORY—The diagnosis of osteoarthritis of the knee can almost always be made by taking the history and performing a physical examination. Although the typical age distribution of people with osteoarthritis is middle-aged and elderly, certain groups of people are more likely to develop osteoarthritis at a younger age. These include people who have had trauma to their knees and African-American women.3 The reasons the latter group is more susceptible are not clear.

The insidious onset with gradual progression of aching pain is usually the initial symptom of osteoarthritis, but patients may remain asymptomatic. The pain may be localized to the knee or radiate widely. It is often aggravated by weight-bearing or increased use (ie, walking or other exercise).6 Patients may also complain of anterior knee pain that is worse with prolonged sitting (theater sign), climbing stairs, jumping, squatting, or kneeling, which may indicate patellofemoral joint involvement. Initially, the pain improves with rest, but with disease progression, the pain may occur both at rest and at night. Weather patterns tend to alter the level of pain in osteoarthritis of the knee. People often note increased pain with damp, cool, or rainy conditions. This is probably caused by a change in intra-articular pressure associated with changes in atmospheric pressure.5

Other symptoms include stiffness and limitation of function, with or without a sensation of crepitus. Compared with rheumatoid arthritis, morning stiffness associated with osteoarthritis usually lasts for 15 to 20 minutes or less. Patients also describe the "gel phenomenon" (stiffness with rest and inactivity) that resolves within a few minutes of activity. As osteoarthritis of the knee progresses, patients complain of sensations of instability with buckling or giving out and diminished range of motion. Patients may even report locking or catching of the knee secondary to intra-articular loose bodies from degenerative pieces of cartilage shed into the joint.6 Patients may also note a deformity that is manifested in the affected lower extremity (often a varus or bowleg deformity). It is not uncommon for patients with severe osteoarthritis of the knee to develop a limp or report episodes of falling. Last, varying amounts of both soft-tissue swelling and joint effusion can develop with disease progression.

PHYSICAL EXAMINATION—The physical examination is extremely important in diagnosing osteoarthritis of the knee. However, in the early stages, there may be no physical findings.6 The physical examination should always begin with gross visual inspection of the patient's general appearance (thin or obese?) and gait (limp?). Alignment changes can occur in the Q-angle (figure 1). At full extension, this angle should be less than 22° in women and less than 18° in men; at 90° of flexion it should be less than 9° in women and less than 8° in men.5,15 About half of people with osteoarthritis of the knee have genu varum (bowleg) secondary to medial tibiofemoral joint cartilage loss and resultant narrowing.3,5 However, it is not unusual to see genu valgum (knock-knee) with lateral tibiofemoral joint involvement. Further visual inspection may demonstrate swelling or even bony enlargement of the knee joint. Soft-tissue swelling usually occurs in the more advanced stages of osteoarthritis.6 There may even be atrophy of the quadriceps, especially the vastus medialis obliques. A Baker's cyst (a fluid-filled sac located in the medial border of the popliteal fossa) may also develop.

Palpation of the knee can elicit significant findings. More than 90% of people with osteoarthritis have some level of pain with associated crepitus on passive range of motion, especially extreme flexion.3 This crepitus is probably secondary to joint surface irregularities and incongruities of opposing cartilaginous surfaces.3,6 This crepitation can be exaggerated with patellofemoral joint compression.6 Range of motion may be limited. It is important to palpate for joint effusions. Compared with other joints affected with osteoarthritis, the knee has a higher tendency to develop effusion, especially in more advanced cases.6

The next step is examination of the medial and lateral joint lines and the patella facets. We routinely perform patella inhibition and compression tests. Occasionally palpation of these areas elicits pain, but joint-line pain may be absent. Furthermore, bony enlargement and irregularities (osteophytes) may be present. We always check for instability of the joint by examining for pathologic ligamentous laxity on varus and valgus stress testing and specific tests such as Lachman's and anterior drawer. Finally, warmth of the knee can occur secondary to local irritation and inflammation.

RADIOGRAPHIC EXAMINATION—The radiographic examination is a key component of the diagnostic work-up for osteoarthritis of the knee. At least 50% to 75% of people older than age 65 demonstrate some radiographic evidence of osteoarthritis of the knee on plain x-ray films. This number approaches 100% in people older than age 75.9 However, only 40% to 60% of these people may be clinically symptomatic.1,9 Therefore, knee pain is not a predictor of radiographic disease and there is no strong correlation between the clinical outcome of osteoarthritis of the knee and its radiographic course.7,8

Osteoarthritis is the most common form of knee arthritis and can affect any or all 3 compartments: medial tibiofemoral joint, lateral tibiofemoral joint, or patellofemoral joint.5,15

Osteoarthritis of the knee has a tendency to be asymmetric. The detection of pathologic abnormalities by radiographs depends on the type of examination ordered. Routine films (anteroposterior and lateral) can be limited in their ability to detect early osteoarthritic changes.5 Additional views are often required, including anteroposterior weight-bearing, "tunnel", and patella ("skyline," "sunrise," and "Merchant") (figures 2 and 3). Each of these views is more sensitive for a particular pathologic finding. Standing tunnel views with 30° to 45° of flexion may demonstrate osteoarthritis changes—especially on the posterior aspect of the femoral condyles—that routine films may miss.5 Weight-bearing or "stress" views with full extension often give a better assessment of cartilage loss because the joint space collapses under body weight.1 These films also depict femoral and tibial subluxation in addition to varus and valgus angulation more accurately.5 Patella views with moderate flexion are ideal for identifying osteoarthritis of the patellofemoral joint, particularly joint space narrowing, as well as patella subluxation.1

In osteoarthritis of the knee, involvement is more likely to be unicompartmental (especially medial tibiofemoral joint) or bicompartmental (medial tibiofemoral joint and patellofemoral joint or lateral tibiofemoral joint and patellofemoral joint) than tricompartmental. In fact, medial tibiofemoral joint changes are probably the most consistent with osteoarthritis of the knee. The patellofemoral compartment, which includes the medial, lateral, and odd facets (medial to the medial facet and separated by a ridge) is frequently affected in osteoarthritis, but disease usually occurs in association with changes in the tibiofemoral joint. It is unusual to see isolated joint involvement.5

There is still some controversy in the literature as to which radiographic finding is most sensitive for osteoarthritis of the knee (table 2). Joint space narrowing, subchondral sclerosis, osteophytes, and bone remodeling are common features no matter what compartment is involved. Subchondral cysts, although not as prevalent, can also occur, mainly in the tibia.5 Bone demineralization and marginal erosions are not common features and one should consider other inflammatory arthritides.3

Table 2. Radiographic findings in osteoarthritis of the knee
Osteophytes ("central" or "marginal")
Joint space narrowing (especially medial tibiofemoral compartment)
Subchondral cysts
Subchondral sclerosis
Intra-articular osseous debris (loose bodies or "joint mice")
Varus or valgus angulation
Patella subluxation
Bone remodeling

Joint space narrowing corresponds with erosion (mild to severe) and is a sensitive predictor of osteoarthritis of the knee when it affects the medial tibiofemoral joint or the lateral patellofemoral joint.1,5 Men usually have a larger joint space width than women.1 Subchondral sclerosis more frequently occurs in the tibia or in both the tibia and femur but can also involve the patella. Isolated sclerosis of the femur is unusual. It occurs predominantly in the immediate subchondral regions and consistently in areas of joint space narrowing.5 Osteophytes also occur frequently, especially at the articular margins ("marginal") of the femur and tibia as well as at the superior and inferior poles of the patella. Interior ("central") osteophytes can occur, especially on the femoral condyles and tibial spines. The literature seems to support the finding of osteophytes as the most sensitive and efficient finding for radiographic osteoarthritis of the knee.1,8 In a case-controlled study of 452 patients, Lanyon et al1 found a significant association between pain and the presence of osteophytes, but this association was weaker with joint space narrowing of any compartment. However, there does not seem to be a biological threshold for joint space width below which the likelihood of symptoms markedly increases. Patella subluxation, when it occurs, has a tendency to move toward the side of the affected facet (mainly the lateral one). This may be related to the large articular surface and the lateral vector of forces resulting from physiologic valgus angulation.5

Intra-articular osseous debris (loose bodies or "joint mice") is common and results from disintegration of the articular surfaces. This debris must be distinguished from marginal and central osteophytes and normal sesamoid bones (fabella). Arthrography, conventional tomograms, computed tomography, and magnetic resonance imaging are quite useful is this respect. However, plain tunnel views may be adequate.

A fabella is a sesamoid bone, found in about 11% to 13% of the normal population, that is embedded in the tendinous portion of the lateral head of the gastrocnemius muscle immediately posterior to the lateral femoral condyle. It is reported with increased frequency in people with osteoarthritis of the knee and is often bilateral. It, too, has a surface with hyaline cartilage that articulates with the posterior condylar region and is subject to osteoarthritic changes.5


Osteoarthritis of the knee is a complex, multifactorial process. Some risk factors are consistent while others, such as physical activity, are controversial. Extended studies are needed to further delineate these risk factors and their importance. We hope that this article helps to serve as a basis for the initial approach and evaluation of a patient with signs and symptoms consistent with osteoarthritis of the knee. If preventive factors continue to be identified, there is the potential to favorably affect the disability and medical costs that can result from this disease.

Peter C. Vitanzo, Jr, MD is a primary care sports medicine fellow, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia. Dr Vitanzo declares that he has no relationships with companies that manufacture products used to treat the patients under discussion.
Address correspondence to Peter C. Vitanzo, Jr, MD, Department of Family Medicine, Thomas Jefferson University Hospital, 1015 Walnut St, Curtis Bldg, Suite 401, Philadelphia, PA 19107.

John M. McShane, MD is director of primary care sports medicine and the primary care sports medicine fellowship, Thomas Jefferson University Hospital, Philadelphia, and director of sports medicine, Riddle Memorial Hospital, Media, Philadelphia, Pennsylvania. Dr McShane declares that he has no relationships with companies that manufacture products used to treat the patients under discussion.


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