Intraarticular Medications for the Horse
There are several products currently available for intravenous and/or intraarticular use in horses with arthritis. These products are considered forms of SHORT-TERM arthrotherapy.
All short-term arthrotherapeutic medications are designed to alleviate joint inflammation, block degradative enzyme release and function, hasten the production of hylauronan from the synovial membrane, and inhibit cartilage degeneration. They all have a common goal of returning an abnormal joint environment to homeostasis.
We have implemented all of the follwoing products at The Atlanta Equine Clinic and have formed opinions of each. Client impression was a contributing factor in all of our evaluations.
Corticosteroids. Intraarticular corticosteroids have been utilized as part of our treatment strategy for equine synovitis/ arthritis for many years. Their potent antiinflammatory effects are well-documented and undoubtedly responsible for reestablishing comfort and soundness in thousands of joints that we've treated. Of course, the potential for the development of deleterious side effects within joints treated with corticosteroids has prompted us to implement their use with some degree of caution.
Common intraarticular corticosteroid preparations include Triamcinilone Acetonide (Vetalog®), Methylprednisolone Acetate (Depo-Medrol®) and Betamethasone (Celestone®).
Anabolic-Androgenic Steroids (AASs). Stanozolol increases the production of collagen and other fundamental protein substances of the cartilage matrix, thereby improving the condition of cartilaginous tissue. Increased multiplication of synoviocytes and chondrocytes in addition to regeneration/repair of articular cartilage and synovial membrane demonstrate the drug's combined antiinflammatory and anabolic actions.
Administration of Sungate® in arthritic joints has also been shown to increase synovial fluid viscosity. This increase can be attributed to enhanced synoviocyte metabolism which results in increased synthesis, production and concentration of high-molecular-weight sodium hyaluronate.
Hyaluronan. Sometimes referred to as "hyaluronic acid", this molecule is a normal constituent of synovial fluid and is responsible for maintaining its viscosity and lubricating properties within the joint. Although injection of a synthetic version of this molecule is very healthy for any joint, it (by itself) is not considered to have very potent antiinflammatory effects. It is therefore often administered in combination with other medications (such as steroids) to prolong their effect and improve overall synovial integrity.
Preparations of this molecule include Hylartin-V®, Hyvisc®, and MAP®-5. Two forms of hyaluronate sodium (Legend® and MAP®-5) are discussed individually below.
We have observed good results with this product over the past 10 years and have had no complications pursuant to using it on our clients' horses.
Unfortunately, however, inflammatory joint reactions and septic arthritis (joint infection) have been reported following administration of Adequan® I.A. Studies suggest that Adequan IA potentiates joint infection, which is a rare but potentially life threatening complication.
To reduce the likelihood of complication, most veterinarians infuse Adequan IA in combination with antibiotic (usually Amikacin) into the joint. Although this approach dramatically decreases the risk of developing post-treatment septic arthritis, we have found that the presence of intraarticular antibiotic can result in synovial irritation/ inflammation. Therefore, the addition of antibiotic to the treatment regimen actually diminishes the positive effect of the injection.
It is for this reason that we typically select a different product for intraarticular use in the horse.
It should be noted that there is no correlation between administration of Adequan IM (the intramuscular form) and septic arthritis (joint infection). We frequently use Adequan IM as part of our long-term arthrotherapeutic strategy.
Legend® (hyaluronate sodium) is the only FDA approved intravenous and intraarticular therapy designed to treat equine non-infectious synovitis associated with osteoarthritis. It is a preparation of pure hyaluronate sodium, the same glycosaminoglycan present in normal joint fluid. Legend is produced by a patented biofermentation process, resulting in such purity that it can be given intravenously for immediate bioavailability.
We have observed excellent results when using Legend intravenously in our practice. The effect of IV injection peaks in about 48 hours and lasts for approximately 2 weeks.
Since there are preparations of hyaluronan available with higher molecular weight at comparable expense, we usually do NOT implement Legend in our joint injections.
MAP®-5 (hyaluronate sodium) is a patented salt of hyaluronic acid in normal saline for use in the collection, handling, culture and cryopreservation of embryo, ova, sperm and other cells. Although this product is licensed for use as a cryopreservative, it has proven to be very effective as an off-label treatment for equine arthritis.
We often recommend MAP-5 for IV use in place of Legend, as it seems to have a comparable effect and is considerably less expensive. It can be administered both intravenously and intraarticularly.
Polyglycan is a highly viscous aqueous solution of defined fractions of purified Hyaluronic acid, Chondroitin sulfates A-and-C in a 10% solution of N-acetyl-D-glucosamine. Some clients consider this product to be a combination of Adequan and Legend. Although this is not exactly accurate, Polyglycan does contain components that are representative of both.
Polyglycan was initially developed as a post surgical joint lavage with the goal of quickly reestablishing synovial physiology following arthroscopic or arthrotomic surgery. Polyglycan contains naturally occurring components of synovia that play a central role in maintaining the homeostatic environment of the joint.
Soon after it's introduction into the equine market, however, off-label intraarticular and intravenous applications quickly popularized.
In our experience, Polyglycan has comparable benefit to Legend with respect to both intravenous and intraarticular administration. Some clients think that it works better than Legend when administered intravenously (IV), although this comprises the minority of opinions.
We do implement Polyglycan intraarticularly for post-surgical cases, although typically elect to use high-vicosity hyaluronan (i.e. Hylartin® or Hyvisc®) as part of our intraarticular protocol in horses with chronic joint disease.
Some lay-people (not our clients) have complained of excessive hemorrhage/ bleeding as a result of Polyglycan administration, although these reports are highly-speculative and there has been no clinical observations to this effect.
Sodium Pentosan Polysulfate (PPS) is a linear polymer prepared from xylan, a complex hemicellulose extract of plant (Beechwood) origin. PPS is one of the sulfated heparinoid compounds. The heparin-like anti-coagulant effects have been reduced and the anti-inflammatory, fibrinolytic, and tissue trophic effects have been enhanced.
It is administered both intramuscularly (IM) and intraarticularly (IA) in the horse.
In addition to promoting synovial intergrity and inhibiting enzymal degradation of the joint, Pentosan may have increased antiinflammatory effect as compared to other products. This quality may obviate the need for concurrent use of intraarticular corticosteroids, upon which which many veterinarians rely for their potent antiinflammatory properties. The potential deleterious effects of intraarticular corticosteroids on articular cartilage have been well-documented.
In our experience, Pentosan alone does not produce a positive clinical effect comparable to that of a hyaluronan/steroid combination. The antiinflammatory effects of corticosteroid appear to be much stronger. This observation coupled with our current ability to use relatively "safe" (non-deleterious) articular steroids (such as Betamethasone) usually prompts us to implement a hyaluronan/ steroid combination during our initial treatment of equine arthritis.
Subjective opinions of Pentosan vary considerably among our clients. Some think that is makes a tremendous difference in their horse's performance; others do not observe any positive effect. Lack of effect may in lieu of the recommended dose of 3mg/kg being inadequate (too low). It is for this reason that we typically offer Pentosan as a second-line strategy to our clients that are willing to try it.
We should note that if a combination of hyaluronan and steroid has already been implemented unsuccessfully, it is unlikely that intraarticular Pentosan will prove to be effective.
Autologous Conditioned Serum (ACS) is marketed as "IRAP" by Arthrex Vet Systems. The exploration of interleukin-1 receptor antagonist protein (IL-1Ra or IRAP) as a treatment for synovitis, osteoarthritis and rheumatoid arthritis began shortly after its first published characterization in 1984. The ability of this molecule to act as both a symptom- and disease-modifying agent in various species (including horses and humans) has prompted its clinical application as a treatment for joint disease. The goal behind IRAP treatment is to use the body's own inflammation-fighting cells to reduce arthritis rather than the synthetically-produced antiinflammatory medications that we buy in a bottle. Because antiinflammatory cells are produced by the host body itself, we can often expect an improved degree of response as well as a longer duration of response.
At The Atlanta Equine Clinic, we generally reserve IRAP & IRAP II use for those joint refractory to corticosteroid treatment.
Mesenchymal Stem Cells (MSC) are receiving a great deal of scientific attention as well as coverage in the lay press. The primary reason for the attention is the potential ability of stem cells to regenerate tissues without the production of scar tissue that is generally associated with healing processes. The goal through stem cell use, therefore, is to replace damaged tissue with something comparable to the original tissue rather than with scar tissue.
At The Atlanta Equine Clinic, we typically reserve stem cell use for those joint with relatively deep subchondral lesions.
Platelet-Rich Plasma (PRP). Numerous growth factors have been used in the horse with the intention of enhancing synthesis and reducing breakdown of tendon/ ligament tissue pursuant to injury. Historically, these growth factors have been harvested from bone marrow and/or fat aspirates, which also contain increased concentrations of stem cells.
More recently, platelet-rich plasma (PRP) has been gaining popularity as a treatment designed to augment equine tissue repair.
Platelet-rich plasma (PRP) is an autologous concentration of platelets in a small volume of plasma. Plasma is the straw-colored liquid in which blood cells are suspended. PRP is generated through relatively simple centrifugation of blood. Because it is a concentration of platelets, it is also a concentration of 7 fundamental protein growth factors known to be secreted by platelets in response to wound healing. PRP also contains proteins known to promote cell adhesion during tissue rebuilding.
Platelets perform many functions in the body, including formation of blood clots and release of growth factors into wounds. The rationale for the use of PRP as a treatment strategy for tendonitis (tendon damage) and desmitis (ligament damage) stems from the increased platelet release of multiple growth factors in response to an injury. Two additional incentives for using PRP include its relative ease of collection and the unlikelihood that it will result in immune rejection since it is autologous (produced from the patient's own blood).
At The Atlanta Equine Clinic, PRP has been used to successfully treat the following soft tissue injuries: tendon strain, muscle strain, ligament strain, and joint capsular laxity. PRP has also been used to treat intraarticular injuries. Examples include arthritis, arthrofibrosis, articular cartilage defects, meniscal injury, and chronic synovitis (joint
Diagnostic & Surgical Arthroscopy. Direct visualization of the joint's interior can be performed using an arthroscope. In many cases, abnormalities not readily visible radiographically (upon x-ray) or ultrasonographically will be apparent through the arthroscope. Once isolated, certain lesions (such as meniscal tears, bone chips or subchondral cysts) can be debrided under arthroscopic guidance. "Cleaning up" the joint in this fashion may help to reestablish the horse's soundness. Diagnostic/ surgical arthroscopy requires general anesthesia, however, and therefore must be performed in a hospital environment. Cost for the procedure varies depending on the type and location of lesion(s).
Please review our Postoperative Arthroscopy Notes HERE.