Updated January 05, 2015.

Written or reviewed by a board-certified physician. See About.com's Medical Review Board.

Rheumatoid arthritis is a chronic, inflammatory disease characterized by progressive joint damage, physical limitations, and functional disability.  When I was first diagnosed with rheumatoid arthritis (in 1974 at age 19) and initially learned about my treatment options, the goal became quickly apparent -- control inflammation, slow disease progression, and relieve pain and other rheumatoid arthritis symptoms.

Sounded like an appropriate plan to me. As a newbie arthritis patient, I was eager to begin treatment and stop the disease process.

I learned that there was the possibility of remission, too, which made me feel even more encouraged. What I didn't fully realize at the time was that even with treatment, arthritis can progressively worsen. Joint damage can worsen. Yes, it's true. Even if a patient is in remission, as defined by established criteria, they can still exhibit radiographic progression (i.e., x-ray evidence of increasingly worse joint damage). 

Treatment Geared Towards Controlling Inflammation

For decades, disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate, plaquenil, and sulfasalazine, were used to slow or dampen down disease activity associated with rheumatoid arthritis. With the availability of biologic drugs (Enbrel [etanercept] was the first in 1998), the targets became more specific at the molecular level. And now, there is a new strategy unfolding, referred to as Treat-to-Target therapy.

Treat-to-Target pins down a treatment strategy based on an individual patient's level of disease activity. The goal is to achieve a low level of disease activity or remission in a specified period of time -- and each plan is individualized. To put it in the most simple of terms, treatment changes are made if disease activity goals are not met. How well Treat-to-Target would effectively prevent joint damage remains to be seen. Disease activity-targeted treatments (i.e., anti-inflammatory treatments) do not have prevention of joint damage in its cross-hairs. It has been suggested that even after inflammation is controlled, synovial tissue activity in rheumatoid arthritis patients can mediate cartilage and bone destruction. To better understand, let's look more closely at how joint damage develops and progresses.   

Understanding How Joint Damage Occurs

Joint damage can be observed within months of rheumatoid arthritis onset. Early cartilage loss and bone erosions are associated with the accumulation of inflammatory cell populations in the synovial membrane and development of pannus (thickened synovial tissue that can invade the bone). There is a synovial sublining layer that contains several cell populations of macrophages, T cells, B cells, dendritic cells, and polymorphonuclear leukocytes, as well as a synovial lining layer consisting of macrophages and fibroblast-like synoviocytes (synovial cells). There are populations of activated macrophages and synoviocytes that can secrete enzymes (proteinases) involved in the process of tissue degradation. Understanding synovial activity, specifically the mechanisms and pathways involved at the level where there is secretion of the tissue degrading enzymes, is imperative if joint damage is to be controlled or prevented. For example, at the molecular level, what causes the fibroblasts to become aggressive and damaging? 

According to Kelley's Textbook of Rheumatology, proteinases from three sources destroy cartilage in rheumatoid arthritis: surfaces of articular cartilage are destroyed by proteinases present in synovial fluid; through direct contact between articular cartilage and and proteolytic (i.e., capable of breaking down proteins) synovium or pannus tissue or both; or intrinsic destruction (i.e., destruction from within) by proteinases derived from chondrocytes.

As researchers work to find the answers, we inch closer and closer to better treatments -- with the hope of eventually finding a way to prevent joint damage. Over the course of rheumatoid arthritis, joint damage may progress slowly and consistently. In late or advanced rheumatoid arthritis, a strong correlation exists between x-ray evidence of joint damage and disability. Reducing joint damage would help preserve joint function.

The process of joint damage in osteoarthritis is a bit different. A mechanically triggered event (e.g., injury or wear-and-tear) is typically associated with the cartilage degradation process. Inflammation occurs, but it is secondary in most cases of osteoarthritis. IL-1 (interleukin-1), a cytokine, may play a significant role in cartilage degeneration associated with osteoarthritis. Chondrocytes (cells found in cartilage) produce significant amounts of IL-1 and synovial inflammation adds to the activity of IL-1. While no significant inflammatory changes usually occur in the synovium in early osteoarthritis, there is increased production of enzymes by the chondrocytes which contribute to cartilage destruction.  There does, however, appear to also be a specific phenotype of osteoarthritis that exists as well, a more erosive type of osteoarthritis, characterized by joint destruction that is driven primarily by inflammation.

<sub>Sources:

Progression of joint damage despite control of inflammation in rheumatoid arthritis: a role for cartilage damage driven synovial fibroblast activity. Floris PJG Lafeber, Willemijn H Van der Laan. Annals of the Rheumatic Diseases 2012;71:793-795 doi:10.1136/annrheumdis-2011-200950
http://ard.bmj.com/content/71/6/793.full

Pathogenesis of joint damage in rheumatoid arthritis. Bresnihan B. Journal of Rheumatology. 1999.
http://www.ncbi.nlm.nih.gov/pubmed/10090189

The links between joint damage and disability in rheumatoid arthritis. Rheumatology. 2000.
http://rheumatology.oxfordjournals.org/content/39/2/122.abstract

Kelley's Textbook of Rheumatology. Ninth edition. Volume I. Pages 111-113.</sub>