If you've been around horses, particularly performance horses, for even a short while, you've probably met someone who's had a horse's joints injected. The procedure--which involves injecting medication directly into the joint to combat such problems as synovitis, osteoarthritis, and arthrosis--is now commonplace. Despite prominent use and continuing research, though, disagreement and debate remain, particularly regarding the effectiveness and safety of the products used and the method of treatment. In this article, we'll outline the primary pro and con points currently being made in regard to joint injections. Certain joint injections, such as nerve blocks, can also be used for diagnostic purposes, but in this article we'll focus on therapeutic uses.

An Overview

There are three main categories of medication currently used in joint (intra-articular) injections--hyaluronic acid (HA, also known as sodium hyaluronate), polysulfated glycosaminoglycans (PSGAG), and corticosteroids (also called cortisone or steroid). At the most basic level, these medications aim to decrease inflammation in a damaged or diseased joint, explains Elizabeth Davidson, DVM, Dipl. ACVS, an assistant professor of equine sports medicine at the University of Pennsylvania's New Bolton Center.

By reducing inflammation, the medications also relieve heat and pain, allowing the horse to feel and perform better. In addition, since inflammation releases substances that damage cartilage, eliminating the inflammation helps to slow or even stop the cartilage degeneration that's at the heart of many joint diseases.

While cited by many veterinarians as highly effective joint treatments, the injections do come with risks. "Anytime you do a needle puncture into a joint, that's trauma," says Mark Rick, DVM, a practitioner with Alamo Pintado Equine Medical Center in Los Olivos, Calif. He notes that blood from the injection site could enter the joint area, causing your horse pain.

More significantly, he continues, "There is the potential for contamination, and contamination leads to infection." It doesn't take much contamination to cause trouble, either. Research at Colorado State University has shown that it takes just 100 organisms to infect a joint, compared to one million to infect a skin laceration, says C. Wayne McIlwraith, BVSc, PhD, FRCVS, Dipl. ACVS, Dipl. ECVS, Director of the Orthopaedic Research Center and Barbara Cox Anthony Endowed University Chair at Colorado State University.

However, adds Rick, "If (the injection) is done with good prep, good handling of the horse, and aseptic (sterile) conditions, the chances (of infection) are minimal." To further reduce that risk, many veterinarians include a small amount of antibiotic with the joint injection, "not in place of good prep, but as a tiny bit of extra insurance," he says.

Joint injections can cause problems even if they don't cause infection. These "sterile" problems (called flares) occur when the horse's body reacts adversely to the injected medication, causing painful inflammation at the site and possibly lameness, says Rick. Luckily, flares are fairly uncommon and can usually be treated with basic first-aid measures, such as cold-hosing, wrapping, and oral anti-inflammatory drugs.

Besides the general pros and cons that apply to all forms of joint injections, each specific medication carries its own advantages and drawbacks. We'll address those, drug by drug, in the rest of this article.

PSGAG: Focus on Prevention

Adequan is the best-known PSGAG product; others include Cartophen (pentosan polysulfate) and Rumalon (glycosaminoglycan peptide complex). Cartophen and Rumalon are not licensed in the United States.

Research has shown that PSGAG structure is similar to that of heparin--a naturally occurring polysaccharide (complex carbohydrate) with anticoagulant (anti-blood-clotting) properties. But its importance has nothing to do with blood clots. Instead, PSGAG is believed to help prevent cartilage degeneration.

PSGAG works on the collagen fibers and intercollagenous tissues that comprise the matrix, or origination point, of joint cartilage, says Rick. Specifically, adds McIlwraith, "PSGAG has been shown to inhibit the effects of various enzymes associated with cartilage degeneration, including both collagenase and stromelysin, serine proteinases, and others."

While PSGAG is considered by many to be an effective means of preventing cartilage degeneration in a joint, it doesn't heal joint defects, says McIlwraith. What's more, he adds, not everyone believes that the drug can even protect cartilage, and some studies have shown PSGAG to have little beneficial effect on cartilage degeneration.

In addition, says Rick, there is some evidence that intra-articular (within the joint) use of PSGAG results in a higher incidence of infection and sterile flare than is found with other joint products. Although CSU research showed that using an antibiotic in conjunction with the PSGAG prevented infection, many veterinarians now opt for the newer, less problematic intramuscular version of Adequan rather than its intra-articular form. However, McIlwraith feels that intramuscular Adequan has less dramatic effects than intra-articular Adequan.

Hyaluronic Acid (HA)

HA is a normal constituent of synovial fluid, explains McIlwraith. It's part of what's normally found in the body and is produced by the synovial membrane. It provides some lubrication to the cartilage, and there is pretty good evidence that it inhibits the action of inflammatory mediators that potentially degrade the cartilage.

Legend is the best-known HA product; others include Hyvisc and Hylartin V. Davidson notes there are different grades of HA product based on molecular weight, with higher weights considered more effective.

Specifically, Jerry Black, DVM, senior partner and president of Pioneer Equine Hospital in Oakdale, Calif., noted in "Joint Disease" (www.TheHorse.com/ViewArticle.aspx?ID=2813) that HAs work largely by counteracting metalloproteinases and prostaglandin E2--products involved in the inflammatory processes and the perception of pain.

It's not uncommon for veterinarians to prescribe both HA and PSGAG, says Rick. The two drugs complement each other well, as PSGAG works deeper in the joint structures and is more effective at chondroprotection (protection of the cartilage), while HA works on the more superficial areas of the joint and is more effective against mild to moderate synovitis (inflammation of a synovial membrane).

Unlike the PSGAGs, intra-articular use of HAs has thus far proven safe, with few side effects or reactions, says McIlwraith. Nonetheless, an intravenous (IV) form of Legend is also available that might prove as good as the intra-articular drug, and it is often used in conjunction with the intra-articular drug. Studies at CSU support this idea and hint that IV administration could cause the HA to work through receptors in the cells, stimulating positive effects even after the initial dose of medication has left the system. Plus, while HA products typically are the most expensive joint medications, the IV use of Legend would allow multiple joints to be treated with a single injection, potentially saving money.

Corticosteroids: Inflammation's Enemy

"Corticosteroids are the most potent anti-inflammatories you can put in a joint," says Rick, who notes that they're also the least expensive joint medication. "They eliminate some damage that can be caused by inflammation and take away heat, pain, and swelling so the horse feels better and can perform better."

In technical terms, McIlwraith explains, "Corticosteroid effects are exerted through an interaction with steroid-specific receptors in the cellular cytoplasm of steroid-responsive tissues. The corticosteroid binds to the receptor and induces changes in the transcription of genes coding various proteins that produce the hormonal effects."

Corticosteroids, he continues, are known to act against a number of deleterious products produced by synovitis, including collagenase, proteoglycanase (stromelysin), prostaglandin, and synovial membrane-induced interleukin-1.

Perhaps most significant to joint disease treatment is the drug's ability to inhibit the movement of inflammatory cells (including neutrophils and monocyte-macrophages) into an inflamed area. "They (corticosteroids) greatly inhibit prostaglandin E2 production by cells, and this may be the dominant mechanism for their anti-inflammatory effects," says McIlwraith. "And they exert their effect on the prostaglandin cascade above the level of where NSAIDs affect it."

On the downside, corticosteroids--used in horses since at least the 1950s--have received bad press over the years and remain a controversial treatment in some circles. The major argument against them is based on reports (or, in some experts' opinions, rumors) that they do nothing more than mask pain. Thus, the theory goes, they allow horses to continue performing in relative comfort on joints that perhaps aren't up to the task, and the horses could be further damaged by the level of exercise.

McIlwraith dismisses this notion as inaccurate, saying, "The insinuation that corticosteroids 'deaden' the joint is dangerous and has caused considerable alarm."

Rick, however, adds that it is possible for a horse being treated with corticosteroids to "outperform what it should be doing." After all, he notes, inflammation can have a protective effect--discouraging a horse from using an injured limb until it heals. Unless you're also properly diagnosing and addressing the initial cause of the inflammation, he says, you could be putting the horse in a position where he no longer feels the need to protect the joint in question, and so continues to use it when perhaps he should be resting.

McIlwraith noted that the corticosteroid methylprednisolone acetate can adversely affect cartilage if it is used inappropriately, resulting in decreased cartilage cells and decreased rates of proteoglycan and collagen synthesis, according to one study. Another study showed that high doses of the drug decreased amounts of proteoglycans. For more information, see "Corticosteroids: The Big Three" on page 127.

To help modulate the potential side effects of a corticosteroid, says Rick, it's often used in combination with HA in a single intra-articular injection, a mix sometimes referred to as "white acid" for the white coloring of the corticosteroid. This option gives the horse the best of all worlds--a high-potency anti-inflammatory, plus added lubrication and possible healing properties.

Just One Part of the Program

So what's the bottom line on joint injection therapy? Davidson perhaps sums it up best when she says, "Certainly it is invasive, but it can be very beneficial. You have to weigh the benefits and the negatives, then use some common sense and get a good program established with your veterinarian."

Whichever joint injection option you and your veterinarian end up selecting, if any, it's a good idea not to think of it as a stand-alone treatment. When you combine periodic intra-articular medication with other therapies--such as non-steroidal anti-inflammatory medication (i.e., phenylbutazone), oral joint supplements, cold hosing, massage, and thoughtful conditioning/exercise regimens--you can create a comprehensive program that gives your horse the best chance of maintaining a high level of comfort and performance for as many years as possible.


 GENE THERAPY: New Hope On the Horizon

The biggest buzz word in any medical circle these days is "gene therapy," and the world of equine joint disease treatment is no different. Alan J. Nixon, BVSc, a professor of clinical sciences at Cornell University's Veterinary Medical Center, is one of the many researchers studying the subject. Nixon has already cloned growth factor molecules (IGF-I) using viral vectors and transplanted chondrocytes to carry them into equine joints. Once there, the genetically engineered IGF-I has actually stimulated cartilage cell metabolism. While the treatment seems effective, it's unfortunately short-lived. However, with Nixon and other researchers continuing research along these lines, we might some day be able to offer our horses a permanent solution to joint disease.

David Frisbie, DVM, who is working on his PhD at Colorado State, did the first demonstration of the clinical usefulness of a gene therapy protocol in osteoarthritis in any species. He put the gene for interleukin-1 receptor antagonist (IL-1Ra) into equine joints and shut down osteoarthritis with a single injection.--Sushil Dulai Wenholz


CORTICOSTEROIDS: THE BIG THREE

There are three primary corticosteroids used for intra-articular injections in horses, each with potent anti-inflammatory properties, but with differing durations of effectiveness. Here's an overview:

Methylprednisolone acetate (Depo-Medrol)--Longest-lasting of the three; typically used in low-motion joints for degenerative joint disease. Colorado State University (CSU) research has shown that this drug does have negative effects on articular cartilage.

Triamcinolone acetate (Vetalog)--Moderate duration of effectiveness; used in high-motion joints at low dosages. Work at the CSU Orthopaedic Research Laboratory showed no negative effects and an increase in the synthesis of essential articular cartilage elements. Triamcinolone acetate might be chondroprotective (protective of the cartilage).

Betamethasone phosphate (Betavet Soluspan, Celestone)--Shortest-acting of the three; used to reduce synovitis and joint inflammation; a CSU study uncovered no deleterious side effects of the drug.--Sushil Dulai Wenholz

About the Author

Sushil Dulai Wenholz

Sushil Dulai Wenholz is a free-lance writer based in Lakewood, Colo. Her work appears in a number of leading equine publications, and she has earned awards from the American Horse Publications and the Western Fairs Association.

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