Progression of Osteoarthritis 

Updated: Dec 01, 2015
Author: Carlos J Lozada, MD; Chief Editor: Herbert S Diamond, MD 

Stages of Osteoarthritis

The etiopathogenesis of osteoarthritis has been divided into 3 stages.

Stage 1

In stage 1, proteolytic breakdown of the cartilage matrix occurs. Chondrocyte metabolism is affected, leading to an increased production of enzymes, which includes metalloproteinases (eg, collagenase, stromelysin) that destroy the cartilage matrix. Chondrocytes also produce protease inhibitors, including tissue inhibitors of metalloproteinases (TIMP) 1 and 2, but in amounts insufficient to counteract the proteolytic effect.

Stage 2

Stage 2 involves the fibrillation and erosion of the cartilage surface, with a subsequent release of proteoglycan and collagen fragments into the synovial fluid.

Stage 3

In stage 3, the breakdown products of cartilage induce a chronic inflammatory response in the synovium. Synovial macrophage production of metalloproteinases, as well as cytokines such as interleukin (IL) 1, tumor necrosis factor (TNF)-alpha, occurs. These can diffuse back into the cartilage and directly destroy tissue or stimulate chondrocytes to produce more metalloproteinases. Other proinflammatory molecules (eg, nitric oxide [NO], an inorganic free radical) may also be a factor in stage 3.

Further progression

Eventually, the above events alter the joint architecture, and compensatory bone overgrowth occurs in an attempt to stabilize the joint. As the joint architecture is changed and further mechanical and inflammatory stress occurs on the articular surfaces, the disease progresses unchecked.

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Subsets of Primary Osteoarthritis

Certain diseases are often categorized as subsets of primary osteoarthritis. These include primary generalized osteoarthritis (PGOA), erosive osteoarthritis, and chondromalacia patellae.

Primary generalized osteoarthritis

Kellgren and Moore described PGOA in 1952.[1, 2] The disease is characterized by familial and often premature development of Heberden and Bouchard nodes, as well as the precocious degeneration of the articular cartilage at multiple joints, including the first carpometacarpal joints, knee joints, hip joints, and spine articulations. The radiographic appearance of PGOA is indistinguishable from that of nonfamilial primary osteoarthritis, although the disease typically progresses relatively rapidly and has a severe appearance on images.[3, 4, 5]

Erosive osteoarthritis

Erosive (ie, inflammatory) osteoarthritis is a form of primary osteoarthritis marked by a greater degree of inflammation, with erosive abnormalities and, in some cases, osseous ankylosis. The disease most commonly occurs in postmenopausal women, and it may be hereditary. Laboratory findings are generally uninformative.

Erosive osteoarthritis is typically bilateral and symmetrical, and it occurs in the interphalangeal joints (particularly the distal interphalangeal [DIP] joints) of the hands (see the image below). In rare cases, patients have erosive osteoarthritis at the base of the first metacarpal or even in the feet.[6]

Close-up posteroanterior (PA) radiograph of the ha Close-up posteroanterior (PA) radiograph of the hand reveals narrowing and osteophytes affecting multiple interphalangeal joints. Note the "gull-wing" configuration of the distal interphalangeal joint of the middle finger due to central erosion. There is also ankylosis of the distal interphalangeal joint of the index finger.

Radiographically, the erosions are centrally located, in contrast to the marginal erosions in rheumatoid arthritis. In addition, osteophytes are present in erosive osteoarthritis; consequently, interphalangeal joints may assume a gull-wing configuration, with central erosions flanked by raised lips of bone (see the first image below). Periarticular soft-tissue swelling is evident. Osseous fusion, which severely limits joint motion, may occur (see the second image below).[7]

Close-up radiograph of the fifth digit shows osteo Close-up radiograph of the fifth digit shows osteophytes and central erosions resulting in a "gull wing" appearance.
Close-up radiograph shows fusion of the distal int Close-up radiograph shows fusion of the distal interphalangeal (DIP) joint of the fifth finger; this finding is compatible with advanced erosive osteoarthritis.

Chondromalacia patellae

Chondromalacia patellae is a syndrome of crepitus and pain at the anterior knee that most commonly occurs in young adults. Conventional radiographs provide little information, and although arthrography enables a more direct assessment of cartilaginous integrity, many consider magnetic resonance imaging (MRI) to be the initial imaging study of choice. Chondromalacia patellae is associated with cartilaginous changes along the undersurface of the patella (see the following image).

Oblique projection demonstrates gradual narrowing Oblique projection demonstrates gradual narrowing and sclerosis of the facet joints as one progresses down the lumbar spine.

Radiologic Classification of Osteoarthritis

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 full-thickness irregularity with or without underlying subchondral bone change) is generally sufficient and prevents confusion that occurs with numeric grading systems. Radiographic findings may be normal in the early stages of the disease, because cartilage is not directly visualized. Eventually, cartilage loss manifests as joint-space narrowing.

In patients with osteoarthritis not related to previous trauma, diffuse cartilaginous thinning is often noted; early in the disease, this affects the medial compartment more so than the lateral or patellofemoral compartments. Later, tricompartmental cartilaginous thinning may be appreciated (see the images below).

Transverse, fast spin-echo, T2-weighted, fat-satur Transverse, fast spin-echo, T2-weighted, fat-saturated magnetic resonance imaging (MRI) scan of the knee reveals increased signal intensity within the articular cartilage of the patella reflecting degeneration.
Transverse fat-suppressed fast spin-echo T2-weight Transverse fat-suppressed fast spin-echo T2-weighted magnetic resonance image reveals a fissure of the patellar cartilage filling with joint fluid.

Kellgren-Lawrence grading system

The Kellgren-Lawrence grading system is the most universally accepted method of classifying radiographic osteoarthritis and uses the following 4 radiographic features:

  • Joint space narrowing

  • Osteophytes

  • Subchondral sclerosis

  • Subchondral cysts

Examples of the radiographic grade of osteoarthritis according to this system are seen below.

Osteoarthritis of the bilateral knees, Kellgren st Osteoarthritis of the bilateral knees, Kellgren stage II.
Osteoarthritis of the right knee, Kellgren stage I Osteoarthritis of the right knee, Kellgren stage II.
Osteoarthritis of the left knee, Kellgren stage II Osteoarthritis of the left knee, Kellgren stage II.
This radiograph demonstrates osteoarthritis of bil This radiograph demonstrates osteoarthritis of bilateral knees. Radiographic findings of osteoarthritis are often graded using the Kellgren-Lawrence Grading System. These knees would be classified as Kellgren grade III.
Osteoarthritis of the knee, Kellgren stage III. Osteoarthritis of the knee, Kellgren stage III.
Osteoarthritis of the knee, Kellgren stage III. Osteoarthritis of the knee, Kellgren stage III.

Outerbridge classified articular cartilage damage based on the arthroscopic findings in patients affected with osteoarthritis.[8] The 4 grades are as follows:

  • Grade I – Softening and swelling

  • Grade II – Fragmentation and fissuring of less than 0.5 inches

  • Grade III – Fragmentation and fissuring of greater than 0.5 inches

  • Grade IV – Erosion down to the subchondral bone