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osteoarthritis

Thursday 25 September 2003

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Definition: Osteoarthritis (OA, also known as degenerative arthritis, degenerative joint disease), is a group of diseases and mechanical abnormalities entailing degradation of joints, including articular cartilage and the subchondral bone next to it.

Osteoarthritis is the most common type of joint disease and is one of the most disabling conditions in developed nations. It is characterized by the progressive erosion of articular cartilage. It is estimated that over $33 billion are spent annually in the United States for its treatment and for lost days of work.

The term osteoarthritis implies an inflammatory disease. However, although inflammatory cells may be present, osteoarthritis is considered to be an intrinsic disease of articular cartilage in which biochemical and metabolic alterations result in its breakdown.

In the great majority of instances, osteoarthritis appears insidiously, without apparent initiating cause, as an aging phenomenon (idiopathic or primary osteoarthritis). In these cases, the disease usually affects few joints (oligoarticular) but may be generalized.

In about 5% of cases, osteoarthritis may appear in younger individuals having some predisposing condition, such as previous macrotraumatic or repeated microtraumatic injuries to a joint, a congenital developmental deformity of a joint(s), or some underlying systemic disease such as diabetes, ochronosis, hemochromatosis, or marked obesity.

In these settings, the disease is called secondary osteoarthritis and often involves one or several predisposed joints-witness the shoulder or elbow involvements in baseball players and knees in basketball players.

Gender has some influence on distribution. The knees and hands are more commonly affected in women and the hips in men.

Clinical symptoms of OA may include joint pain, tenderness, stiffness, inflammation, creaking, and locking of joints.

In OA, a variety of potential forces (hereditary, developmental, metabolic, and mechanical) may initiate processes leading to loss of cartilage, a strong protein matrix that lubricates and cushions the joints.

As the body struggles to contain ongoing damage, immune and regrowth process can accelerate damage. When bone surfaces become less well protected by cartilage, subchondral bone may be exposed and damaged, with regrowth leading to a proliferation of ivory-like, dense, reactive bone in central areas of cartilage loss, a process called eburnation.

The patient increasingly experiences pain upon weight bearing, including walking and standing. Due to decreased movement because of the pain, regional muscles may atrophy, and ligaments may become more lax.

OA is the most common form of arthritis, and the leading cause of chronic disability in the United States.

Osteoarthritis is the most common human joint disease, characterized by loss and/or remodeling of joint synovium, cartilage, and bone.

Osteoarthritis (OA) demonstrates considerable clinical heterogeneity, generating heated debate over whether OA is a single disease or a complex mix of disparate diseases and concerning which tissues are principally involved in disease initiation and progression.

Epidemiology

OA affects nearly 21 million people in the United States, accounting for 25% of visits to primary care physicians, and half of all NSAID (Non-Steroidal Anti-Inflammatory Drugs) prescriptions.

It is estimated that 80% of the population will have radiographic evidence of OA by age 65, although only 60% of those will be symptomatic.

Clinical synopsis

Osteoarthritis is an insidious disease. Patients with primary disease are usually asymptomatic until they are in their fifties. If a young patient has significant manifestations of osteoarthritis, a search for some underlying cause should be made.

Characteristic symptoms include deep, achy pain that worsens with use; morning stiffness; crepitus; and limitation of range of movement. Impingement on spinal foramina by osteophytes results in cervical and lumbar nerve root compression with radicular pain, muscle spasms, muscle atrophy, and neurologic deficits.

Typically, only one or a few joints are involved, except in the uncommon generalized variant. The joints commonly involved include the hips, knees, lower lumbar and cervical vertebrae, proximal and distal interphalangeal joints of the fingers, first carpometacarpal joints, and first tarsometatarsal joints of the feet.

Characteristic in women, but not in men, are Heberden nodes in the fingers, representing prominent osteophytes at the distal interphalangeal joints. The wrists, elbows, and shoulders are usually spared. There are still no satisfactory means of preventing primary osteoarthritis, and there are no methods for halting its progression.

The disease may stabilize for years at any stage but more often is slowly progressive over the remaining years of life; osteoarthritis is second only to cardiovascular diseases in causing long-term disability.

Morphology

In the early stages of osteoarthritis, the chondrocytes proliferate. This process is accompanied by biochemical changes as the water content of the matrix increases and the concentration of proteoglycans decreases.

Subsequently, vertical and horizontal fibrillation and cracking of the matrix occur as the superficial layers of the cartilage are degraded. Gross examination at this stage reveals a granular articular surface that is softer than normal.

Eventually, full-thickness portions of the cartilage are sloughed, and the exposed subchondral bone plate becomes the new articular surface. Friction smoothes and burnishes the exposed bone, giving it the appearance of polished ivory (bone eburnation).

Concurrently, there is rebuttressing and sclerosis of the underlying cancellous bone. Small fractures through the articulating bone are common, and the dislodged pieces of cartilage and subchondral bone tumble into the joint, forming loose bodies (joint mice).

The fracture gaps allow synovial fluid to be forced into the subchondral regions in a one-way, ball-valve-like mechanism. The loculated fluid collection increases in size, forming fibrous walled cysts.

Mushroom-shaped osteophytes (bony outgrowths) develop at the margins of the articular surface and are capped by fibrocartilage and hyaline cartilage that gradually ossify. The synovium shows minor alterations in comparison to the destruction of the articular surface and is congested and fibrotic and may have scattered chronic inflammatory cells.

In severe disease, a fibrous synovial pannus covers the peripheral portions of the articular surface.

Etiology

Some investigators believe that mechanical stress on joints underlies all osteoarthritis, with many and varied sources of mechanical stress, including misallignments of bones due to congenital or pathogenic causes; mechanical injury; being overweight; loss of strength in muscles supporting joints; and impairment of peripheral nerves, leading to sudden or uncoordinated movements that overstress joints.

Although it commonly arises from trauma, osteoarthritis often affects multiple members of the same family, suggesting that there is hereditary susceptibility to this condition.

Genetics

Genetic factors also appear to play a role in susceptibility to osteoarthritis, particularly in cases involving the hands and hips. The specific gene or genes responsible for this have not been identified, although linkage to chromosomes 2 and 11 has been suggested in some cases.

A number of studies have shown that there is a greater prevalence of the disease between siblings and especially identical twins, indicating a hereditary basis. Up to 60% of OA cases are thought to result from genetic factors.

- mutation in the MATN3 gene encoding the noncollagenous cartilage extracellular matrix protein matrilin-3 (12736871)

Pathogenesis

Articular cartilage is the major target of degenerative changes in osteoarthritis. Normal articular cartilage is strategically located at the ends of bones to perform two functions:

- (1) bathed in synovial fluid, it ensures virtually friction-free movements within the joint;
- (2) in weight-bearing joints, it spreads the load across the joint surface in a manner that allows the underlying bones to absorb shock and weight without being crushed.

These functions require the cartilage to be elastic (i.e., to regain normal architecture after being compressed) and for it to have unusually high tensile strength.

These attributes are provided by the two major components of the cartilage: a special type of collagen (type II) and proteoglycans, both secreted by chondrocytes. As is the case with adult bones, articular cartilage is not static; it undergoes turnover in which "worn out" matrix components are degraded and replaced.

This balance is maintained by chondrocytes, which not only synthesize the matrix but also secrete matrix-degrading enzymes. Thus, the health of the chondrocytes and their ability to maintain the essential properties of the cartilage matrix determine joint integrity. In osteoarthritis, this process is disturbed by a variety of influences.

Perhaps the most important of these influences are aging and mechanical effects. Although osteoarthritis is not exclusively a wear-and-tear process, there is little doubt that mechanical stresses on the joint play a major role in its development.

Evidence for this includes the increasing frequency of osteoarthritis with advancing age; its occurrence in weight-bearing joints; and an increase in the frequency of the disease in conditions that predispose the joints to abnormal mechanical stresses, such as obesity and previous joint deformity.

The risk of osteoarthritis is increased in direct proportion to bone density, and high levels of estrogens have also been associated with an increased risk of the disease. The overall role played by hormones in the pathogenesis of osteoarthritis remains unclear, however.

References

- Wieland HA, Michaelis M, Kirschbaum BJ, Rudolphi KA. Osteoarthritis - an untreatable disease? Nat Rev Drug Discov. 2005 Apr;4(4):331-44. PMID: 15803196

- Peach CA, Carr AJ, Loughlin J. Recent advances in the genetic investigation of osteoarthritis. Trends Mol Med. 2005 Apr;11(4):186-91. PMID: 15823757