Clinical Information

Development of Traumatic Synovitis

running horseTraumatic synovitis occurs after multiple, repeated episodes of trauma from everyday use, training, or performance. In its early stages it is associated with synovitis and is very common in the high motion joints such as the fetlock and carpus. It is a major cause of early retirement in equine athletes. Because it is rather insidious in onset, it is not unusual to have insult to the soft tissues of the joint before we can see any outward clinical signs such as swelling, heat or pain. As this repetitive trauma continues over time damage will occur to the joint capsule, synovial lining, cartilage and even the subchondral bone, which eventually can lead to osteoarthritis.

Osteoarthritis is a multifactorial disease influenced by mechanical overload during high-impact physical activity, joint instability, and repeated trauma, and the metabolic processes associated with aging, body mass index related to obesity and hereditary factors.

Healthy Joint

Joint with SynovitisThis image illustrates the structures of the joint that are affected by traumatic joint disease. Osteoarthritis is characterized by progressive loss of joint function, pain, cartilage destruction, subchondral bone remodeling, thickening of joint capsules, and increased synovial effusion. The synovial fluid is an ultra-filtrate from blood plasma and is produced by the synovial membrane. The high hyaluronic acid (HA) content of this fluid comes from the synoviocytes and gives the joint fluid its characteristic, thick, viscous consistency. This fluid, with its high HA content helps lubricate the soft tissues which surround the joint and to a lesser degree helps lubricate the articular cartilage itself. Another major function of this specialized fluid is to provide nourishment to the cartilage as well as remove waste products from the joint because cartilage does not have a direct blood supply.

With an inflammatory process such as synovitis you will see the release of inflammatory mediators. This is a direct result of insult to these tissues. There are many different chemicals which are produced when tissues become inflamed, some of the primary ones with respect to equine joint disease are cytokines (IL-1 and TNF-alpha), a number of different proteolytic enzymes (MMPs or matrix metalloproteinases) and proinflammatory substances (especially prostaglandin E2, free radicals such as nitric oxide and leukotrienes).

Prostaglandins can cause vasodilation of blood vessels, enhanced pain perception and cause degradation of the protoglycan content (building blocks) of cartilage. Free radicals such as nitric oxide can have damaging effects on almost any type of tissue but it is known that they can directly damage cartilage as well as break-down or "cleave" HA molecules in the joint fluid.

There are a number of different enzymes which can have damaging effects on the cartilage and on the surrounding soft tissues. Some of the more prominent enzymes include stromelysin, gelatinase and collagenase and matrix metalloproteinases.

It is important to understand that these chemicals are released for a reason when tissues become insulted or damaged. This occurs constantly in the normal, healthy balance of tissue use and remodeling or replenishment.

cycle of inflammation
This graphic summarizes the cycle of inflammation in joints with Type I joint trauma or disease.
The goal of treatment is to stop this before osteoarthritis develops, where we have boney changes that are permanent.

When there is more inflammation and tissue damage occurring than healthy tissue replacement, joint disease will occur in its earliest stages. The problem is that these chemicals can't tell the difference between healthy tissue and damaged tissue. What happens is that the production of these chemicals can then lead directly to further tissue insult and inflammation—a "cycle" of inflammation can result.

As this cycle of inflammation continues there is additional release of inflammatory mediators and enzymes which further initiates inflammation and at this point clinical signs appear such as joint swelling, pain and lameness. If the inflammation continues and worsens, eventually direct damage to the cartilage occurs. This is to be avoided if at all possible.

The cells that make up the synovial membrane are a rich source of several proinflammatory molecules that can incite and perpetuate articular deterioration, if the underlying cause of the inflammation cannot be controlled.

Release of Inflammatory Mediators Damaged Articular Cartilage

The inflammation can negatively affect the chondrocytes. If the cartilage damage becomes severe, then the disease process can progress to osteoarthritis. These osteoarthritic boney changes are permanent

In summary, arthritis results from an imbalance between the substances that promote healthy cartilage growth and those substances that cause the remodeling or destruction of these cartilage components. The effects of the catabolic substances (damaging) overpower the effects of the anabolic (healing promoting) substances. Collectively these catabolic substances perpetuate synovitis, initiate articular cartilage damage and induce remodeling of subchondral bone.

Early recognition and intervention is essential to prevent permanent joint damage.

IMPORTANT SAFETY INFORMATION:
Click here to view the complete label and usage instructions.

Federal law restricts this drug to use by or on the order of a licensed veterinarian. For use only in horses. Do not use in horses intended for human consumption.

LEGEND 4 mL and LEGEND® Multi dose 20 mL are approved only for I.V. use. LEGEND 2 mL is approved for I.V. and I.A. use. The intra-articular safety of LEGEND Multi Dose with benzyl alcohol has not been evaluated.

The safety of LEGEND has not been evaluated in breeding stallions or in breeding, pregnant or lactating mares.

Not for use in humans. Keep this and all other drugs out of reach of children. Strict aseptic techniques should be observed when administering by intra-articular injection.

Post-Approval Experience: While all adverse reactions are not reported, the following adverse reactions are based on voluntary post-approval reporting for Legend Injectable Solution: Following intravenous use: Occasional depression, lethargy and fever. Following intra-articular (Legend Injectable Solution - 2 mL only) use:lameness, joint effusion, joint or injection site swelling, and joint pain.

1. Kawcak, CE; Frisbie, DD; Trotter, GW; McIlwraith, CW; Gillette, SM; Powers, BE; Walton, RM: Effects of intravenous administration of sodium hyaluronate on carpal joints in exercising horses after arthroscopic surgery and osteochondral fragmentation. AJVR, Vol. 58, No.110, October 1997.

2. Freedom of Information NADA #140-883