Pathology
reprinted from Primer on the Rheumatic Diseases, edition 12

Osteoarthritis can be defined as a gradual loss of articular cartilage, combined with thickening of the subchondral bone; bone outgrowths (osteophytes) at joint margins; and mild, chronic nonspecific synovial inflammation. The difference between “physiologic” aging of the cartilage and OA cartilage is not sharp. However, three cartilage stages can be identified: stage I, normal cartilage; stage II, aging cartilage; stage III, OA cartilage.

Normal Cartilage
Normal cartilage has two main components. One is the extracellular matrix, which is rich in collagens (mainly types II, IX, and XI) and proteoglycans (mainly aggrecan). Aggrecan is a central cor eprotein bearing numerous glycosaminoglycan chains of condroitin sulfate and keratan sulfate, all capable of retaining molecules of water. The second component consists of isolated chondrocytes, which lie in the matrix. The matrix components are responsible for the tensile strength and resistance to mechanical loading of the articular cartilage.

Passage of Normal Cartilage to Aging Cartilage
Several structural and biochemical changes involving the non collagenous component of the matrix occur during aging. These changes alter biochemical properties of the cartilage that are essential for the distribution of forces in the weight-bearing zone. Glycosaminoglycans are modified qualitatively; they become shorter as the cartilage ages. The concentration of type 6 keratan sulfate (KS) increases during aging, to the detriment of type 4 KS. These quantitative and qualitative changes in proteoglycan reduce the capacity of the molecules to retain water. Thus, aging cartilage contains less water, which alters the biochemical properties of the cartilage. Fissures that develop in cartilage during aging are due mainly to stress fractures of the collagen network.

Osteoarthritic Joints
Osteoarthritic joints have abnormal cartilage and bone, with synovial and capsular lesions (8). Marcroscopically, the most characteristic elements are reduced joint space; formation of osteophytes (protrusions of bone and cartilage) mostly at the margins of joints; and sclerosis of the subchondral bone. These changes are the result of several histologic phases.

Phase 1: edema and microcracks. The first recognizable change in OA is edema of the extracellular matrix, principally in the intermediate layer. The cartilage loses its smooth aspect, and microcracks appear. There is a focal loss of chondrocytes, alternating with areas of chondrocyte proliferation.

Phase 2: fissuring and pitting. The microcrack deepen perpendicularly in the direction of the forces of tangential cutting and along fibrils of collagen. Vertical clefts form in the subchondral bone cartilage. Clusters of chondrocytes appear around these clefts and at the surface.

Phase 3: erosion. Fissures cause fragments of cartilage to detach and “fall” into the articular cavity, creating osteocartilaginous loose bodies and uncovering the subchondral bone. Subchondral microcysts develop. These fragments caus the mild synovial inflammation of OA. The resulting inflammation often is more focal than inflammation that occurs during rheumatoid synovitis. Histologically , OA synovitis is characterized by mild, nonspecific lymphoplasmocytic and histiocytic infiltration.

There is sclerosis of the subchrondral bone, due to the apposition of small strips of new bone. Osteophytes form around the zone, their surface covered with fibrilar cartilage. Subchondrol sclerosis increases with disease progression. Specific changes in architechture of he subchondral trabecular bone are due to accelerated bone turnover.