Arthritis of the Knee

Arthritis of the knee is a family of disorders characterized by pain and loss of function, progressive deterioration of the articular surface, and pathological change in the bones and nearby soft tissues. The most common form of knee arthritis is osteoarthritis, a wear and tear condition, which usually appears without any specific known cause beyond aging. Osteoarthritis can also appear (especially in relatively younger patients) after peri-articular fractures, or tears of ligaments and menisci that can alter the normal biomechanics. Less frequently, damage of the knee joint is caused by rheumatoid arthritis or systemic diseases. Osteoarthritis cannot be cured, but only palliated; the advancement of rheumatoid arthritis can be controlled with medication.



Structure and Function

The knee comprises two separate articulations within one synovial compartment. First, there is a modified hinge joint between the distal femur and the proximal tibia. This joint has medial and lateral articulations, with a greater share of the load borne medially. It is a “modified hinge” in that there is a small amount of rotation, too. The second articulation is between the patella and the femur’s trochlear groove.


The knee is surrounded by a synovial membrane, which produces a fluid that nourishes and lubricates the cartilage and reduces friction. Each knee has two menisci that stabilize the knee, absorb shock and distribute load-bearing forces. The articulation of the femur with the tibia has been likened to “two match sticks (the femur and tibia) held together by rubber bands (the ligaments).” That is, the knee joint, unlike the hip, for example, has little inherent bony stability.


There are four main ligaments: the anterior and posterior cruciate ligaments (to prevent anterior and posterior displacement of the tibia relative to the femur) and the medial and lateral collateral ligaments (to provide side to side stability). The joint surfaces are lined with articular cartilage, a specialized structure whose top layer is particularly smooth, with layers below that constructed to absorb load.


A more detailed discussion of the patellofemoral jointmeniscicollateral and cruciate ligaments, and the chondral surface of the knee are presented in chapters dedicated to each.


Arthritis of the knee is typically osteoarthritis, a disease of “wear and tear” or trauma that produces a deterioration of the articular cartilage and reactive changes in the bone. Often osteoarthritis of the knee is asymmetric, affecting the medical compartment preferentially. As noted, people tend to bear more weight on the medial compartment of the knee and thus the cartilage wears out there first. Rheumatoid arthritis, by contrast, is manifest by an autoimmune inflammatory reaction against the synovium that leads to the body’s destruction of its own articular cartilage. Among other differences, rheumatoid arthritis thus symmetrically damages the joint. (The basic differences in pathophysiology between rheumatoid arthritis and osteoarthritis produce important differences in clinical presentation, as discussed below.)


With the advancement of osteoarthritis, the articular cartilage loses proteoglycans (e.g., chondroitin sulfate) and its collagen becomes disorganized. There can be inflammatory changes in the synovium, though these are an effect, not a cause of the disease. The bone attempts to compensate, one might say, with the only trick it has: proliferation. There is, accordingly, subchondral sclerosis (bone grown below the articular cartilage) and osteophyte formation (bone growth extending out of the edges of the bone, into the soft tissue nearby or within spaces inside the joint itself).


The characteristic pathology of rheumatoid arthritis is synovial infiltration by leukocytes and the initiation of an inflammatory cascade. This inflammation produces hyperplastic synovium, cartilage damage, and chondrocytes cell death. The inflammation also stimulates osteoclasts and suppresses osteoblasts leading to periarticular bone loss, especially at points where the synovial membrane inserts into the bone’s periosteum.



Patient Presentation

Patients with osteoarthritis of the knee present with pain, worse after prolonged activity and improved with rest. Stiffness and mechanical symptoms such as locking and catching sensations are common. In rheumatoid arthritis, stiffness is reported to be worse after rest (e.g., upon wakening) but improves with activity.


Examination abnormalities might include a limp, malalignment, atrophy, effusions and restricted motion. There may be a flexion contracture (an inability to fully extend the knee) which effectively shortens the length of the leg (i.e., the effective limb length is the hypotenuse of a triangle whose other limbs are the femur and tibia). This may produce hip or back pain.


The history should determine if any other joints are symptomatic and whether there was a history of prior injury. Rheumatoid arthritis usually affects hands and feet; the neck, elbows, ankles, and shoulders are often involved too.


The physical examination should note any abnormalities in the following domains:

  • Inspection to assess for erythema, scarring, atrophy, and deformity.
  • Palpation to assess for tenderness and effusion. Important points to look for tenderness are the medial and lateral joint lines, the patella and its tendons, the prepatellar bursa, and the pes anserine bursa (just medial and proximal to the tibial tubercle).
  • Stability test to assess the integrity of the cruciate and collateral ligaments. Note that patients with knee arthritis can have a pseudo-laxity of the medical collateral ligament, and that loss of cartilage in the medial compartment may create more room for the tibia to move when the knee is stressed, falsely suggesting that the MCL is damaged.


Objective Evidence

Weight-bearing radiographs are routine. Antero-posterior, lateral and a sunrise view of the patellofemoral joint should be obtained. In patients with rheumatoid arthritis, there is symmetric joint space loss, with osteopenia (see Figure 1).


Figure 1: Knee with rheumatoid arthritis, showing symmetric medial and lateral narrowing, and “washed out” bone quality. (Courtesy of Radiopedia)

Osteoarthritis has four characteristic radiographic findings, the so-called ‘cardinal signs’ (see Figure 2) as follows:

  • Asymmetric joint space narrowing, representing the loss of cartilage. The medial side is often more severely affected than the lateral (leading to the characteristic varus, or bow-legged, deformity).
  • Subchondral sclerosis, manifest as a white line under the surface of the tibial plateau. Areas are excessively stimulated to form bone, whose density produces this sign.
  • Osteophytes/bone spurs growing adjacent to the joint (as contrasted with subchondral sclerosis, where the growth is directly under the area that is loaded.)
  • Subchondral cysts, which form when synovial fluid in a joint affected by osteoarthritis seeps through cracks in the cartilage and into the bone.


Figure 2: Knee radiograph, center, showing the four cardinal signs of osteoarthritis: joint space narrowing (orange box), subchondral sclerosis (the dense bone, appearing white on x-ray, denoted by the red arrow), osteophyte formation (bone spurring from the medial tibia, yellow bracket) and a subchondral cyst (blue circle). (Case courtesy of Dr Ian Bickle,, rID: 51665)

There is only a very limited role for MRI once the diagnosis of osteoarthritis is established. A meniscal tear seen on MRI in the setting of arthritis is almost certainly part and parcel of the overall degenerative condition. Indeed, a meniscal tear can be assumed to be present if there is significant joint space narrowing. Likewise, any ligament deficiency that might show up on MRI should be detectable on exam, and likely would not be treated distinctly anyway. An MRI might be useful to exclude osteonecrosis, to characterize loose bodies seen on radiographs, or, if x-rays are mildly abnormal at most, to determine if marrow edema or other intraosseous processes are responsible for the reported pain (see Figure 3). In short, when an MRI is unlikely to affect management of the arthritic knee, it should be omitted.


Figure 3: Two MRI images of the same 55-year-old female patient with normal x-rays, taken four months apart. The image at left was obtained after presentation with knee pain, showing diffuse bone marrow edema of the medial tibial plateau (red arrow). The image at right, taken after symptom resolution, shows resolution of the edema (white arrow). (Images courtesy of


There are no laboratory tests for osteoarthritis, but testing may be performed to exclude other diagnoses.


Laboratory studies may be helpful for suspected rheumatoid arthritis, but the diagnosis of rheumatoid arthritis is not made conclusively on the basis of any one laboratory test. Blood test abnormalities associated with rheumatoid arthritis include an elevated rheumatoid factor or antibodies against cyclic citrullinated peptides. Abnormalities of the inflammatory markers, c-reactive protein and erythrocyte sedimentation rate, are common but not specific.


The single most useful laboratory test in rheumatoid arthritis is perhaps the aspiration of the joint fluid and its examination. This is done not so much to make the diagnosis of rheumatoid arthritis, but to exclude two other conditions which may mimic it: infectious arthritis or gout. In those cases, one would see either bacteria or urate crystals, respectively.




Knee osteoarthritis, the most common type of arthritis, is more prevalent in women than men, as well as people over the age of 50. The incidence rate is 240 per 100,000 people every year and is rising due to both an aging population and an increase in obesity. More than 250 million people are affected worldwide.


The prevalence of rheumatoid arthritis in the United States is estimated to be 0.5 to 1%. Rheumatoid arthritis is more likely to affect women by a factor of two.



Differential Diagnosis

Pain in the knee can be caused by spinal stenosis or radiculopathy.


Gout/pseudogout, Lyme disease, and septic arthritis can co-exist with other types of arthritis.


A patient could have medial knee pain from pes bursitis, or pain laterally from iliotibial band syndrome. These are highly amenable to non-operative treatment and should be excluded on exam.



Red Flags

Acute worsening of symptoms, especially associated with an effusion and painful passive motion is worrisome for infection.


Treatment Options and Outcomes

First line of treatment of osteoarthritis is non-operative. Non-operative treatment includes patient education about the natural history of the condition (which may improve coping), physical therapy (for range of motion and strengthening), and mild analgesics. Opioids are not indicated. Weight loss should be for patients with an elevated body mass index, but enduring weight reduction is very difficult to achieve.

Intra-articular injections with corticosteroid may reduce pain, albeit temporarily, in some patients. Intra-articular injections of hyaluronic acid may be tried, though this treatment is a bit controversial, primarily owing to its cost. The theory is that because people with osteoarthritis have a deficiency of hyaluronic acid – a natural lubricant found in normal synovial fluid – an injection to replenish it will reduce symptoms.


Surgical treatment should be considered when non-surgical measures have failed and symptoms are severe and disabling. Bear in mind, though, that a failure to respond to non-operative treatment is not in and of itself a reason to have surgery. (“Some pain is likely to persist in many patients regardless of what we do with the meniscus or the articular cartilage, but with good coaching from an empathic surgeon, many of those patients can accommodate to their condition. - Seth S. Leopold, MD [doi: 10.1097/CORR.0000000000002068]) 


For many years, arthroscopic lavage/debridement was a popular surgical option for arthritis. In 2002, Moseley and colleagues published a paper in The New England Journal of Medicine (see Figure 4) reporting a “controlled trial involving patients with osteoarthritis of the knee [whose] outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure.”


Figure 4: The appearance of the paper, “A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee” in the New England Journal of Medicine in 2002 was big news, as evidenced by the placement of a related story “above the fold” on the front page of the New York Times.

In the years that followed, arthroscopic lavage/debridement has remained a popular surgical option for arthritis, for reasons that can only be surmised. Arthroscopic lavage/debridement of course does nothing to the bone outside the joint (subchondral sclerosis, for example), and trimming the edges of the damaged articular cartilage does not normalize the remaining tissue (see Figure 5). Arthroscopy can be useful for treating mechanical symptoms such as locking and for removing symptomatic loose bodies.


Figure 5: Histological section of articular cartilage, showing that the surface zone, shown by the black bracket, is clearly distinct from the middle zone below it. As such, “smoothing” an articular lesion does not merely leave behind less cartilage, but cartilage that is qualitatively different and abnormal. (Courtesy of Tsai, et al

If the arthritis is limited to a single compartment (usually the medial side) high tibial osteotomy may be helpful. In this operation, the tibia is cut and realigned, allowing more weight to be carried by the healthier side of the joint. Alternatively, partial (uni-compartmental) knee replacement can be tried (see Figure 6).


Figure 6: Preoperative x-ray, left, showing severe arthritis of the medial compartment and postoperative x-ray, right, showing uni-compartmental knee replacement. (Image courtesy of Kurien et al, The Knee Journal,

The mainstay treatment of end-stage arthritis is total knee arthroplasty (see Figure 7). In this procedure, the ends of the femur and tibia are removed and are then prepared to accept metal components. A plastic spacer is inserted between the femoral and tibial components, to create a gliding surface. The undersurface of the patella can also be resurfaced, though many surgeons elect not to.


Figure 7: Postoperative x-rays of a total knee replacement (with skin staples still in place). The polyethylene surface atop the tibial component is outlined in pink. Note that the patellar surface was not replaced. (Image courtesy of Mikael Häggström,

Total knee arthroplasty is an effective operation, but approximately 20% of patients will be disappointed with their results. Also, about 1% will suffer a severe complication (such as infection, blood clot or cardiovascular event); and about 0.1% will die. And to be sure, even a perfect result will not endure forever, as the prosthetic device is subject to mechanical failure and loosening over time. Taken together, total knee arthroplasty should be reserved for older patients with end-stage arthritis, realistic expectations, and a willingness to assume the risks inherent in the operation.


The treatment of rheumatoid arthritis is beyond the scope of this volume and the interested reader is directed to the 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis []. In brief, there are many effective medications, and patients who are treated early on in their course have fewer systematic complications and less joint damage. Beyond the traditional use of NSAID and corticosteroids, so-called disease-modifying antirheumatic drugs (DMARDs) can markedly suppress the disease. The knee arthritis itself can be treated with local injection, topical medicines, and physical therapy.



Risk Factors and Prevention

Risk factor for knee osteoarthritis include trauma, obesity and genetics. In general, these are not modifiable. Activity is not a risk factor, except to the extent that activity might be construed as a risk factor for trauma, which it turn can lead to arthritis.  (Aging is a risk factor for arthritis, but dying before aging is worse.)

Exercise to increase flexibility and strength can help foster a sense of wellbeing, even when irreversible damage to the articular surface is present.


Abstaining from smoking is good advice for all, but especially those with rheumatoid arthritis, as smoking may enhance antibody formation.




The use of circulating rheumatoid factor to screen for rheumatoid arthritis is not justified even if the sensitivity and specificity are relatively high. That is because the prevalence is low. Assume that sensitivity is 80% and a specificity of 90%. In a population with a 1% prevalence, Bayes theorem tells us that a positive test will raise the probability of rheumatoid arthritis to only 13%.


Key Terms

Osteoarthrosis, knee, degenerative joint disease, knee osteotomy, knee replacement




Obtain a comprehensive medical history. Perform a skillful physical examination. Interpret radiographs. Formulate a treatment plan based on patient preferences in context of the natural history of disease and the strengths and limitations of the various interventions.



 Meg's Notes:

see Red Text, please clarify