Progression of Osteoarthritis

Osteoarthritis (OA) results from an imbalance between breakdown and repair of the tissues in the synovial joints. Risk factors include trauma, overuse, obesity, and genetic predisposition. The etiopathogenesis of osteoarthritis has been divided into 3 stages.

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

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.

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

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The following diseases are often categorized as subsets of primary osteoarthritis:

• Primary generalized osteoarthritis (PGOA)
• Erosive osteoarthritis
• 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. Articular cartilage lesions can increase the risk and rate of progression to end-stage disease. The radiographic appearance of PGOA is indistinguishable from that of nonfamilial primary osteoarthritis, although PGOA 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]

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]

Patellofemoral pain (PFP)

A variety of factors may alter the mechanics of the patellofemoral joint and increase joint stress, potentially leading to OA. Knee OA research has mainly focused on the tibiofemoral compartment, yet evidence suggests that the patellofemoral compartment is at least as commonly affected by OA. ^[8]

Different terms have been used to describe a syndrome of crepitus and pain at the anterior knee, such as chondromalacia patellae, anterior knee pain and/or syndrome, patellofemoral pain syndrome, PFP, patellofemoral anthropathy, and runner's knee. In 2016, a consensus statement from the Fourth International Patellofemoral Pain Research Retreat recommended patellofemoral pain (PFP) as the preferred term. People with patellofemoral OA exhibit similar patterns of pain and functional limitation to those with PFP. ^[8]  

PFP is most common in young adults and is defined by pain around or behind the patella that is aggravated by at least one activity that loads the patellofemoral joint during weight bearing on a flexed knee (eg, squatting, stair ambulation, jogging/running, hopping/jumping). An annual prevalence of PFP in the general population of 22.7% has been reported. ^[9]  Higher body mass index (BMI) appears to be a risk factor for PFP and patellofemoral osteoarthritis in the general adult population. ^[10]

Additional criteria includes ^[8] :

• Crepitus or grinding sensation emanating from the patellofemoral joint during knee flexion movements
• Tenderness on patellar facet palpation
• Small effusion
• Pain on sitting, rising on sitting, or straightening the knee following sitting

Diagnosis has historically been based on detailed subjective and objective assessments, with pain on a number of special tests including the patellofemoral compression test, palpation of the patella and pain of resisted knee extension. ^[9]  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. Cartilage loss and subchondral sclerosis, edema and cystic changes at the patellar and trochlea surfaces are the main findings in patellofemoral osteoarthritis on MRI. ^[11]  

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).

Kellgren-Lawrence grading system

The Kellgren-Lawrence (KL) 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

Based on the data presented in their original work, the Kellgren-Lawrence classification is typically applied within the context of knee OA. Based on the radiographic features, the severity of OA is given a grade from 0 to 4, with grade 0 signifying no presence of OA and grade 4 signifying severe OA. Although it is unclear whether the radiographic descriptions were presented with the intent of demonstrating a linear disease progression of OA that begins with the formation of osteophytes and culminates in the altered shape of bone ends, the KL system has been criticized on the basis of this assumption. ^[12]

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

Wright and collegues reevaluated the interobserver reliability of the KL system in addition to five other OA radiographic classification schemes. The group used radiographs from 632 patients enrolled in the Multicenter ACL Revision Study (MARS) consortium. Weightbearing AP and/or Rosenberg radiographs  were graded using the six radiographic classification schemes. The radiographic findings were also compared with arthroscopic evidence of tibiofemoral chondral disease. The KL system was the most studied among the different classification systems and had an interobserver reliability intraclass correlation coefficient of 0.51 to 0.89 from studies since its original publication. This large range may be due to the various techniques used, the broad range of patient age groups, and the wide variation in the degree of osteoarthritis. ^[13]

The investigators reported interobserver reliability intraclass correlation coefficients of 0.54 (95% confidence interval [CI], 0.48–0.59) for Rosenberg radiograph and 0.38 (95% CI, 0.33–0.43) for AP radiographs, which they characterized as moderate and poor, respectively. No radiographic classification system had very good (intraclass correlation coefficient of 0.8 to 1.0) interobserver reliability; the scores ranged from moderate (0.4 to 0.6) to good (0.6 to 0.8) reliability for classifying tibiofemoral osteoarthritis of the knee. The International Knee Documentation Committee classification (IKDC) assessed with use of 45° posteroanterior flexion weight-bearing radiographs had the most favorable combination of reliability and correlation. The IKDC system, which places more emphasis on joint space narrowing than does the more traditional Kellgren-Lawrence system. ^[13]

Outerbridge classified articular cartilage damage based on the arthroscopic findings in patients affected with osteoarthritis. ^[14] The 5 grades are as follows:

• Grade 0 – Normal articular cartilage
• 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