Tendon and Ligament Injuries

Photo: Erica Larson, News Editor

Tendon and ligament injuries are notoriously difficult to treat. Are new therapies realistic treatment options?

Soft tissue injuries involving ligaments and tendons have long been recognized as an important source of lameness in horses. Injuries involving these delicate structures are an important cause of lost performance time and a major source of economic losses. To add insult to injury, after losing valuable training days and performance dates, paying veterinary fees, and hours of TLC, there is a high rate of recurrence.

This article describes the common types of injuries athletic horses incur, explains why these injuries are problematic, and reviews the treatment options currently available for returning athletic horses to their intended function.

Common Injuries

The commonly injured soft tissue structures of the limb are the deep digital flexor tendon (DDFT), superficial digital flexor tendon (SDFT), suspensory ligament and its associated branches, and accessory ligaments of the DDFT (the check ligaments).

Soft tissue injuries of the distal limb are also thought to predispose horses to other injuries. For example, suspensory ligament injury is believed to predispose horses to catastrophic injury and fracture of the lateral metacarpal condyle--the distal part of the cannon bone.

Congratulations, It's a Bow!

Why are tendon and ligament injuries such a clinical challenge?

According to Jennifer Barrett, DVM, PhD, Dipl. ACVS, assistant professor of equine surgery at the Virginia-Maryland Regional College of Veterinary Medicine's Marion DuPont Scott Equine Medical Center in Leesburg, Va., "The frustrations associated with tendon and ligament injuries stem from the fact that healing rarely results in completely normal structure, leaving these structures prone to re-injury."

Part of the problem is the exact mechanisms involved in tendon repair in the horse remain unclear, and even less is known about the repair process in ligament injuries. Without knowing how the damage occurs or how the body responds to a damaged tendon or ligament, finding an effective treatment is like finding the proverbial needle in a haystack.

"It is currently thought that subsequent to a tendon injury, there is an inflammatory reaction, which results in swelling, con-striction of the blood vessels, and release of cytokines (inflammatory mediators) that break down and call in the cells that help healing of the tissue," says Barrett.

"A tendon strain creates a lesion with breakdown of the collagenous structure in the center core of the tendon during the early inflammatory phase of the injury," she continues. "The debris incites an inflammatory reaction, and swelling ensues early in the process, with an enlarged tendon, and enlargement of the centrally damaged region."

Scar tissue slowly forms in the injured area of the tendon. In addition, there is an increase in the cross-sectional area of the tendon. "While new tendon fibers are formed following an injury, disorganized scar tissue persists and limits the fiber and fascicle (bundle of skeletal muscle fibers surrounded by connective tissue) movement," notes Barrett. "Instead of replacing the normal tendon matrix with the same type of matrix, the new scarred matrix is less organized, and the biomechanical properties are not the same as the uninjured tendon. There can be a lack of elasticity in the 'healed' tendon, which is thought to result in future injury during tendon loading."

Therapies: A Shot in the Dark?

Suggestions and advice regarding the ideal management solution for tendon and ligament injuries are ubiquitous; however, experts attest that existing treatment modalities for tendon and ligament injuries have shown equivocal or even deleterious effects on healing.

At the 2008 American Association of Equine Practitioners' annual convention, Roger Smith, MA, VetMB, PhD, DEO, Dipl. ECVS, MRVS, a professor of equine orthopaedics at the Royal Veterinary College in the United Kingdom, presented an in-depth review of literature on tendon and ligament injuries. Smith stated there are really only a handful of treatments that have a valid basis for use. According to Smith, of the available treatment methods, none appears to be more or less effective than another for returning horses to athletic function without re-injury.

Biologic Therapies

An ideal treatment for tendon and ligament injuries should avoid excessive scar tissue formation and be able to regenerate normal tendon matrix. In the quest to find this "deal" therapy and based on the positive results in human medicine, research involving stem cells and platelet-rich plasma (PRP) has been advancing in equine medicine to the point where both technologies are widely available clinically.

Stem cell therapy Stem cell-based therapies for the management of various soft tissue injuries have become a popular treatment option. Stem cells can be harvested either from the patient's bone marrow or adipose (fat) tissue, processed, then injected directly into the injured tendon or ligament to facilitate the healing process.

Alan J. Nixon, BVSc, MS, Dipl. ACVS, and colleagues from Cornell University have studied the use of bone marrow-derived mesenchymal stem cells (i.e., the stem cells harvested from the injured horse's own bone marrow that have the capability to transform into tendon cells). Specifically, the researchers created tendonitis in the SDFT in both front limbs of 12 horses. Six days after inciting inflammation in the tendons, the scientists injected stem cells they had isolated and cultured from bone marrow into one of the SDFT lesions in each horse, while they injected each control limb with saline. Six of the horses had stem cells injected that were also carrying a growth factor gene to determine whether this gene therapy approach might drive better healing than stem cells only. The researchers performed follow-up ultrasound examinations of the tendons at two-week intervals for eight weeks post-treatment. In addition, they conducted mechanical, biomechanical, and microscopic evaluation of the tendons eight weeks after intralesional injection with stem cells.

"While no difference in the biochemical composition of the treated and untreated tendons was noted, tendons injected with mesenchymal stem cells derived from the horse's own bone marrow had significantly improved histology scores (compared to) the untreated tendons," explains Nixon. "Gene-enhanced stem cells improved healing better than simple stem cells. This means that the microscopic appearance of the treated tendons was closer to 'normal' than the untreated tendons."

Nixon concluded, "Intralesional injection of stem cells appears to be beneficial to horses with injured superficial digital flexor tendons."

Despite these positive results, Nixon says, "More research is needed to confirm these results and identify the optimal dose of stem cells for treating tendon injuries."

Platelet-rich plasma Another novel therapy for tendon and ligament injuries in horses is PRP. This is a fraction of whole blood that contains a concentrated source of platelets. These platelets are a "hot commodity" because they are natural reservoirs for growth factors (and other proteins), such as transforming growth factor-β and platelet-derived growth factor, that stimulate the healing process.

Typically, PRP is produced by collecting a sample of the injured horse's blood at the time of diagnosing the injury and either filtering or centrifuging the blood (to separate the components). The resultant platelet-rich plasma contains approximately five times as many platelets as normal blood, and this concentrated platelet product is then injected directly into the soft tissue injury.

"Since this is a patient-side, autologous procedure--one that uses a biologic product derived from the patient's own body--it is a very safe technique," says Barrett.

In addition, platelet-rich plasma can be used either as a stand-alone therapy or in combination with stem cell therapy or even one or more of the traditional therapies, such as surgery, conservative care, and/or rehabilitation.

Most of the research on platelet-rich plasma has been generated by the research groups of Alicia Bertone, DVM, PhD, Dipl. ACVS, Trueman Chair in Equine Clinical Medicine and Surgery at The Ohio State University's Comparative Orthopedic Re-search Laboratory, and Lisa Fortier, DVM, PhD, Dipl. ACVS, associate professor of large animal surgery at Cornell University in Ithaca, N.Y.

Bertone's research group used PRP in nine racehorses diagnosed with moderate to severe injuries of the suspensory ligament. All horses were treated with a single injection of PRP followed by a controlled, gradual return to exercise. All nine horses returned to racing after treatment in a median time of 32 weeks. Specifically, all of the treated horses had as many race starts during their first two years after returning to racing as compared to a group of nontreated horses racing at the same time. The researchers suggested that "horses treated by a single injection of platelet-rich plasma followed by a program of gradually increased exercise had an excellent prognosis for return to racing."

The full-length manuscript of this study was published in the May 15, 2008, edition of the Journal of the American Veterinary Medical Association.

Fortier's research group has primarily studied platelet-rich plasma in the laboratory setting using ligament and tendon explant cultures.

Fortier says, "Our results, (funded by the Harry M. Zweig Memorial Fund for Equine Research), indicate that platelet-rich plasma stimulates the generation of new tendon and ligament in horses."

She notes, however, that there are several ways to make platelet-rich plasma, and the resultant products are not the same with respect to contents or their effects on tendon or ligament regeneration.

"One of the focuses of our laboratory is to determine what the optimal contents of a platelet-rich plasma mixture would be to treat acute vs. chronic lesions of tendons and ligaments in horses," Fortier says.

Take-Home Message

Despite the many options available for managing tendon and ligament injuries, many horses continue to suffer from chronic and recurrent soft tissue injuries that don't respond to most available treatments. As a result, injuries to tendons and ligaments in athletic horses remain an important cause of lameness and wastage.

About the Author

Stacey Oke, DVM, MSc

Stacey Oke, MSc, DVM, is a practicing veterinarian and freelance medical writer and editor. She is interested in both large and small animals, as well as complementary and alternative medicine. Since 2005, she's worked as a research consultant for nutritional supplement companies, assisted physicians and veterinarians in publishing research articles and textbooks, and written for a number of educational magazines and websites.

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