Evaluating treatment options for equine tendon, ligament and joint disease

EDITOR'S NOTE

This is the first of two parts on the array of treatment choices available to equine practitioners dealing with tendon and ligament injuries or joint problems in the horse. The next article will discuss why specific treatments are more likely to be chosen for specific injuries.

There are many treatment options available to equine practitioners dealing with injuries to tendons and ligaments and an equally large number of drugs, techniques and modalities that can be used to help manage joint problems in the athletic horse.

Photo 1: Endurance horses and other equine athletes are subject to repetitive compression injury and bone bruising at the joint surfaces. Treatments such as intra-articular injections, extracorporeal shock-wave therapy and IRAP can provide pain relief and improved healing. But scientists struggle with recommend- ations for the "best" therapy choice for each individual.

That is a benefit because somewhere in the potions and procedures is usually something that will bring at least some relief to each patient. On the other hand, the array of choices is a problem because clients and practi- tioners often are confused about which is best.

Clients hear about the various treatments, some only recently removed from experimental stages, or read about them on Web sites and question why their horse was treated with one drug and not another or given one procedure instead of something else.

Practitioners may find themselves debating as well — shock-wave therapy or Acell? Stem cells or platelet-rich plasma (PRS)? Tildren or IRAP? Even referral cases do not provide clarity. Equine veterinarians often find that very similar cases with the same diagnosis sent to different clinical centers or veterinary universities receive different treatments.

Photo 2: This is a thermographic scan of a horse with an injury to the inside of the right knee (the scan is taken from behind the horse). The white areas indicate more heat and inflammation, and the inside right knee shows much more heat than the similar area on the left. This horse suffered damage to the collateral knee ligaments of the inside right leg and is now a prime candidate for treatments that will accelerate ligament repair. But which treatment is best?

These instances leave DVMs and clients asking, "Why"?

Making informed decisions

Education, familiarity and experience all factor into the treatment choices that veterinarians make every day. They're certainly at work in the way an individual clinician chooses to treat a torn tendon, a strained ligament or an arthritic joint. Essentially you use what you were taught to use, what you have tried and had success with and what you are comfortable with.

But this doesn't ensure that the appropriate or best treatment, out of the many available, is used on each case. Many of the treatments in these instances have been available just long enough, however, for us to take a closer, more scientific look and to evaluate their successes and failures. A look at what we now know about these ways of dealing with specific injuries will provide a better basis on which to make a clinical decision.

This evaluation will make it easier for practitioners to recognize strengths and weaknesses of individual drugs and procedures and to educate their clients on choices made.

Photo 3: Horses working at speed or jumping uneven surfaces are more prone to tendon and ligament damage. Treatments such as PRP, Tildren and stem-cell use can significantly improve healing.

Allowing sufficient rest

Even with all the treatments available, there is one part of almost all equine soft-tissue injury protocols that is universally accepted: "Rest must be an integral part of any potentially successful tendon or ligament-treatment program," says Dr. Mark Revenaugh of the Equine Performance Institute of Mulino, Ore.

Some practitioners believe rest may be the most important part. Dr. Rodger Smith, of the Department of Veterinary Clinical Sciences at the Royal Veterinary College, University of London, states, "a multitude of treatments have been advocated for the management of tendon over-strain injuries, but there is little evidence in any species that any is more effective than a prolonged period of rehabilitation with carefully controlled exercise."

Attempting any other treatments without incorporating adequate rest into the protocol generally is unrewarding.

There are a number of topical creams (such as diclofenac liposomal cream) and rubs for treating tendon and ligament inflammation. A reduction in edema and in the damaging secondary cellular effects of inflammation can lessen initial injury and shorten recovery time. These products are relatively inexpensive, easy to use and apply, and most have a proven effectiveness.

If damage to the tendon or ligament is severe and involves fiber disruption, the action of these topicals is limited to reducing inflammation, so an accelerated healing time will not be as likely as with various other, more aggressive, treatments.

Diclofenac liposomal cream has been shown to decrease the histological progression of osteoarthritis when applied to joints and provides better pain relief and anti-inflammatory response than standard anti-inflammatory drug choices (phenylbutazone).

Shock-wave therapy

It has been almost 10 years since Extracorporeal Shock Wave Therapy (ESWT) was first used in horses. This technique uses a machine (extracorporeal; from outside the body) to produce high-intensity shock or pressure waves that are directed, often with ultrasound, to a specific site within injured tissue.

After initially being pointed at any and all injuries in the horse, ESWT has found success treating conditions varying from suspensory ligament desmitis, navicular disease and bucked shins, to bowed tendons, saucer, sesamoid and stress fractures, and some conditions of the equine spine.

The exact manner in which ESWT works remains largely unknown, and whether it primarily produces pain relief or stimulates healing is still in debate.

Researchers at the Institute of Biomedical Engineering at the National Yang-Ming University in Taiwan investigated ESWT on rat Achilles-tendon preparations and documented cellular evidence of shock-wave treatment.

They found "positive stimulatory effects," including up-regulation of proliferating cell nuclear antigen, collagen types I and III, transforming growth factor and increases in nitric-oxide production. They concluded "ESWT can stimulate tenocyte proliferation and collagen synthesis."

In the cases and areas where ESWT is effective, it is very beneficial, but in many other instances has little better than a 50/50 chance of success. ESWT seems to be most effective on front-leg suspensory desmitis but for hind-leg suspensory problems and for navicular disease it works about half the time.

In joint therapy, ESWT has been shown to improve clinical lameness and synovitis but does not improve the progression of arthritis.

The analgesia produced by this modality may lead to joint damage if the treated animal becomes more animated and active during its recovery.

Tissue engineering

Twenty years ago the concept of "tissue engineering" emerged from the field of regenerative medicine. This area of study and investigation applied the principles of engineering to the field of medicine with the goal of repairing and restoring damaged or missing tissue and organs.

The ACell product that was developed from this tissue approach is a "resorbable bioscaffold" made into a sheet or powder and derived from porcine urinary bladder tissue. ACell provides a matrix for cell growth, promotes new blood-vessel formation and constructive remodeling of damaged tissue, because cells around the Acell implant grow into it and begin a cycle of growth, degradation and replacement by tissues that are needed in that location.

Essentially, placing Acell into a tendon or ligament defect allows cells to grow into that area and to differentiate into tendon cells rather than traditional healing where tendon defects fill with some version of fibrosis or scar tissue.

The loss of strength and elasticity with fibroblastic healing of tendons and ligaments is believed to account for the decrease in performance post-injury for many equine athletes. Any product that can promote more normal cell healing in these structures will greatly potentiate their athletic lives.

Acell is fairly expensive, however, and cannot be used with the following: alcohol, detergents and/or soaps, iodine products, silver nitrate, hydrogen peroxide and cortisone. It must be injected into soft-tissue injuries and carries a somewhat higher risk of infection because of the invasive nature of the procedure.

With less than 10 years of clinical availability, Acell already has become a popular choice of therapy for many clinicians.

There are no studies testing it against similar products, however, and bone-marrow cells can provide scaffolding for tendon and ligament repair as well.

Stem cells

Regenerative medicine has given practitioners the option of using stem cells for tendon and ligament repair. "The definition/identification of stem cells is constantly evolving," according to Dr. Lisa Fortier of the Department of Veterinary Clinical Sciences at the New York State College of Veterinary Medicine at Cornell University.

This evolution adds to the confusion as to which type of stem cell practitioners might choose for various tendon and ligament injuries.

Stem cells can be embryonic (derived from the umbilical cord and able to differentiate into any cell types), or adult-derived (obtained from fat, muscle, bone marrow and other tissues and having a restricted number of cell lineages into which they can differentiate).

There is fairly strong clinical evidence for the use of stem cells in tendon and ligament repair.

A study of 168 national hunt horses in the U.K. showed that re-injury following stem-cell therapy for superficial digital flexor tendon injuries in the three years following repair was 24 percent, compared to 56 percent in horses getting tendon treatment.

There are two techniques currently available that produce two different populations of stem cells for tendon and ligament repair.

Bone-marrow-derived stem cells have been the most studied and currently are favored because of their superior performance.

To produce them, marrow is collected from the sternum of the standing, anesthetized horse. The cells are cultured over a period of weeks and then suspended in a bone-marrow supernatant.

These cultured bone-marrow cells derive benefits from the rich growth factors in the supernatant. This mix of cells and nutrient broth is then injected into the structural lesion via ultrasound.

Research shows these cells perform well and have an ability to differentiate more readily into known cell types (more tendon-like, less fibrosis-like).

Disadvantages include the need for bone-marrow sampling surgery, a relatively lengthy culturing period, ultrasound-guided implantation and the expense of the procedures.

Fat-derived stem cells are surgically harvested from the tail head of the horse. They are not cultured, and are then implanted via ultrasound.

This technique provides a large number of stem cells but without the differentiation potential of cultured bone-marrow cells.

This procedure is quicker, contains no culturing period so it is shorter, and it is less expensive.

Though the results with fat-derived stem cells are not as good as with cultured cells, there is still significant improvement with this treatment over more standard tendon and ligament treatments.

In a review article on the future of stem-cell treatment, Dr. (Rodger) Smith writes, "This technology (stem cell) has shown encouraging, but not yet proven, efficacy for treating acute tendon lesions in horses."

He cites the relatively small number of horses in the study and the difficulty in doing controlled studies in a working equine environment (training track or racing barn) as a weakness in conclusions reached.

Further studies are under way, and more information and recommendations on the use of stem cells should be available soon.

Platelet-rich plasma

Platelets contain many growth factors that can be released upon activation.

Transforming growth factor from platelets helps promote new blood-vessel growth, formation of new connective tissue (fibroplasia) and the re-growth of skin.

Platelet-rich plasma (PRP) therefore has been used to improve healing and help regenerate damaged tissue.

It has been shown to enhance early bone healing.

This blood component is a potent activator of collagenase, which promotes tissue strength and of TGF-b, which stimulates the deposition of collagen within the wound as a step toward tissue repair.

PRP is prepared by drawing the horse's blood into a specially prepared bag. The blood is processed and eventually a syringe of PRP is produced.

This preparation can then be injected into the tendon or ligament injury.

Research results are encouraging, but there are no head-to-head comparative studies involving these products. Clients and DVMs need more information to evaluate and choose these therapies properly.

"Evaluation of clinical cases is ongoing," according to Dr. Andris Kaneps of the New England Medical and Surgical Center in Dover, N.H., "but our initial results indicate that PRP treatment of tendon and ligament injuries is a tremendous improvement over other current techniques."

IRAP

Research shows that one of the main substances responsible for cartilage destruction is interleukin-1 (IL-1). Antibodies against this destructive substance are known to have a beneficial effect in arresting cartilage damage.

IRAP, or interleukin receptor antagonist protein, is the term for this technology that requires that blood be drawn in a special tube.

The blood tube is then incubated, resulting in a high level of interleukin antibodies. The syringe is centrifuged and the serum harvested and later injected into the joint in question.

This technique is only minimally invasive. The risks are the same as for any type of joint injection, with infection and scar formation topping the list.

IRAP is relatively expensive but has no negative effect on cartilage. Because no prohibited substances are administered, there is no withdrawal time for competition.

Dr. Andrew McDiarmid of Clyde Vet Group in the U.K. say, "Although use of this treatment is still in its early stages, preliminary results are encouraging and IRAP represents an exciting addition to our therapeutic range in the management of equine lameness." He adds that most veterinarians in England currently use IRAP on refractory cases that have not responded to conventional therapy.

Tildren

Tildren is another newer drug that is being used for equine joint problems. It is licensed in Europe but not currently in England or the United States.

Tildren works by regulating bone destruction as it reduces the activity of osteoclasts (bone destroyers) and activates osteoblasts (bone producers).

Competition horses often have sufficient bone stress to force remodeling into an activated state as the body attempts to thicken and protect some areas and to lighten and thin others. Tildren slows this overactive process and leads to better overall joint health. Some horses may experience a mild to more severe colic while receiving Tildren, so caution is warranted and appropriate treatment should be started if needed.

Tildren is shown to be effective for treating navicular disease but there is some debate about its use in hock arthritis relief.

Confusing array

Overall, it is easy to see why clients and clinicians become overwhelmed and confused as to treatment choices for tendon, ligament and joint disease in the horse.

Many good practitioners have used PRP, developed a certain comfort level with it and are likely to recommend it to their clients over other modalities.

An equal number facing similar cases will recommend Acell, Tildren or stem cells.

The follow-up article will feature discussions with surgeons and clinicians.

They will share their clinical experiences with these drugs, techniques and modalities.

And some will discuss the process they use in making their treatment choices.

Marcella is an equine practitioner in Canton, Ga.