Causes

The biologic factors leading to the deterioration of cartilage in osteoarthritis are not entirely understood. Many experts believe that osteoarthritis results from a genetic susceptibility that causes some biologic response to injuries to the joint, which in turn leads to progressive deterioration of cartilage. In addition, the ability to make repairs becomes progressively limited as cartilage cells age.

Aging Cells

Although osteoarthritis generally accompanies aging, osteoarthritic cartilage is chemically different from normal aged cartilage. As chondrocytes (the cells that make up cartilage) age, they lose their ability to make repairs and produce more cartilage. This process may play an important role in the development and progression of osteoarthritis.

Genetic Factors

Researchers report a high correlation of osteoarthritis between parents and children or between siblings. Genetic factors are thought to be involved in about half of osteoarthritis cases in the hands and hips and a somewhat lower percentage of cases in the knee. A number of genes are under investigation that might contribute to an inherited risk.

For example, mutations in the ank gene may be important in some cases. The ank gene regulates pyrophosphate, a chemical that inhibits the formation of mineral deposits, and may protect the cartilage in joints. Mutations in the ank gene then may result in lower pyrophosphate levels in the joint, leading to accumulation of mineral deposits and arthritis. (About 60% of people with osteoarthritis have mineral deposits in their cartilage.)

Another gene, called the osteoprotegerin gene, is important in regulating bone and cartilage formation. Mutations in this gene may play a role in osteoarthritis.

Inflammatory Response and Matrix Metalloproteinases

The inflammatory response is an overreaction of the immune system to an injury or other assault in the body, such as an infection. This response causes specific immune factors, called cytokines, to gather in injured areas and cause inflammation and damage to body tissue and cells. The inflammatory response plays an important role in rheumatoid arthritis and other muscle and joint problems associated with autoimmune diseases. It has generally been believed that inflammation plays at most a minor role in osteoarthritis and is more likely to be a result -- not a cause -- of the disease.

However, recent studies suggest that inflammation may play an important role in the progression of osteoarthritis and its chronic nature. For example, a 2003 study found evidence of severe inflammation in the lining of the joints in 30% of patients with osteoarthritis. Still, the effects of the inflammatory response in osteoarthritis are likely to be different from those in rheumatoid arthritis and less severe.

Some theories on how this response may contribute to osteoarthritis involve overproduction of enzymes called matrix metalloproteinases or MMPs (also called collagenases). In large amounts they break down collagen, the building blocks of cartilage. Some studies suggest that immune factors called vascular endothelial growth factor (VEGF) are overproduced during the inflammatory response and in turn increase production of MMPs.

Another theory suggests that the inflammatory response is triggered by the changes and injuries in the bone that occur during osteoarthritis. According to this theory, immune factors released in this process diffuse into the cartilage, where they suppress cartilage cell growth and activate MMPs.

Injuries

Joint injuries are the starting point in the disease process. Osteoarthritis sometimes develops years after a single traumatic injury to or near a joint. One large study found that by age 65, osteoarthritis developed in almost 14% of those who had joint injuries as young adults, compared to just 6% in those without earlier injuries. Patients with knee injuries were five times more likely to have osteoarthritis in the injured knee than those without injuries, and patients with hip injuries were more than three times more likely to develop arthritis in the injured hip. Proper treatment of injuries, such as surgical repair of ligament tears in the knee with a strong rehabilitation approach, may help to prevent the development of osteoarthritis.

Other Medical Conditions that Can Cause Osteoarthritis

• Bleeding disorders such as hemophilia that cause bleeding to occur in the joint
• Disorders such as avascular necrosis that block the blood supply near the joint
• Complications of persistent, inflammatory arthritic conditions, particularly chronic gout, pseudogout, or rheumatoid arthritis
• Conditions that cause iron build-up in the joints such as hemochromatosis

Review Date: 12/21/2006
Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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