CHAPTER 115 Management of Tendon Injuries
Treatment of tendon and ligament injuries caused by overuse in the horse is an important challenge for veterinarians, owners, and trainers. Tendonitis and desmitis are common injuries in sport and racing horses and result in significant economic loss to the equine industry. In recent years, an increased awareness of the early signs of injury and improved means of diagnosis and treatment have developed; however, the incidence of injuries remains high. The incidence of tendon and ligament injuries in performance horses has been estimated at 11% to 46%. The superficial digital flexor (SDF) tendon is the most frequently injured soft tissue structure of the lower limb, accounting for an estimated 8% to 30% of all racing injuries in Thoroughbreds. Recurrence of tendonitis following return to full work has been reported to be as high as 43% to 93%.
Tendons transfer the forces generated by muscle contraction into skeletal movement, provide skeletal support, and increase the efficiency of locomotion by storing and releasing energy. As a result, tendons are required to withstand high tensile forces and are characterized histologically by a highly organized ultrastructure that permits plastic deformation under these high tensile loads. Tendons and ligaments are dense connective tissues with a relatively small number of highly differentiated fibroblasts embedded in a collagen-rich extracellular matrix (ECM). Tendon fibroblasts are responsible for the critical task of maintaining the integrity of the surrounding matrix. Normal tendon and ligament exist in a finely tuned equilibrium between anabolic and catabolic processes. Under conditions of physiologic exercise, fibroblasts within the tendon or ligament parenchyma maintain a homeostatic balance between breakdown of damaged ECM and production of replacement proteins. When exercise levels exceed the yield point of the tissue or when the repetitive nature of loads creates damage to the ECM at a rate that exceeds that at which the cells can keep up with repair, damage accumulates and becomes clinically apparent.
Tendon and ligament heal via three overlapping phases of repair that are a specialized version of those described for generalized wound healing: (1) acute inflammation, (2) proliferation, and (3) remodeling. As healing progresses, collagen synthesis increases, and collagen becomes increasingly organized and cross-linked, resulting in improved tensile strength and the ability to withstand escalating loads over time. Tendon is inherently slow to heal because of its high collagen content and low cell numbers. The rehabilitation program must be designed to match the phase of healing and the associated tensile strength of the tissues.
Traditional treatments for tendonitis include both medical and surgical approaches aimed at decreasing inflammation and preventing further damage within the tendon, releasing the strain on the injured tendon, and increasing vascularity within the core lesion. Widespread availability of high-resolution portable diagnostic ultrasound equipment has greatly improved the management of horses with tendon injuries; however, few major medical breakthroughs have improved the prognosis for return to athletic soundness or have decreased the risk of recurrence. Injured tendon heals by formation of scar tissue that is mechanically and biochemically inferior to normal tendon and lacks the elasticity and strength to withstand repetitive high tensile forces.
In recent years, there has been a notable increase in the interest, time, and dollars invested in research directed at elucidating the pathophysiology of tendon and ligament injury, cellular and molecular responses of tendon and ligament to injury, and development of novel therapies aimed at improving the quality of the healed tissues. Despite major advances, there is a great deal more to learn. Tissue engineering is an emerging field devoted to the use of a combination of cells, engineering materials and methods, and suitable biochemical and physiochemical factors to improve or replace biological functions. Regenerative medicine is a synonymous term that emphasizes the use of stem cells in the healing process. Three individual components are critical to the successful regeneration of tendon following injury: (1) a biocompatible scaffold suitable for cell attachment and migration and capable of directing the three-dimensional reconstruction of the injured tissue, (2) a source of precursor cells capable of recruiting endogenous stem cells and differentiating into tendon fibroblasts, and (3) a physiologic combination of growth factors and cytokines to orchestrate the formation of organized tendon matrix on the scaffold provided. The field of tendon healing is focused on all three of these aspects of tissue regeneration in an effort to develop novel therapies that will increase the quality of repair tissue.
This review provides equine practitioners with an overview of the therapeutic options available at present and those in development for treatment of tendon and ligament injuries in the horse. The field is expanding rapidly, with new information being published regularly. An understanding of the theoretical basis for each treatment, as well as knowledge of the current literature, will enable practitioners to educate clients about treatment choices for horses with tendonitis or desmitis.
Early, aggressive anti-inflammatory therapy is critical to reducing ongoing tissue damage that can occur following injury. Horses should be confined to strict stall rest without turnout. Hand walking on a level, smooth, firm surface is suggested for horses that are sound at the walk. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is recommended for the first 1 to 10 days, depending on the severity of the lesion. The treatment duration should be minimized because most NSAIDs have detrimental effects on wound healing. Initial loading doses may be higher but should be tapered to the lowest effective dose and discontinued as early as possible. Topical NSAIDs, such as diclofenac sodium (Surpass, IDEXX Pharmaceuticals Inc, Greensboro, NC) may be a useful adjunct to systemic therapy and may reduce the risk of toxic effects from systemic NSAIDs.
Cold therapy is a cornerstone of treatment after acute tendon or ligament injury and may include all or some combination of ice therapy, cold hosing, and commercial cold therapy units. Standing the horse in ice water, either still or turbulent, is the simplest, most effective means of transferring heat from the limb and cooling the deeper structures. Commercial units vary in their effectiveness. One of the newest commercial units operates on the concept of cyclic compression in conjunction with the circulating ice water to maximize the efficacy of the treatment (Game Ready, Inc, Berkeley, CA, www.gamereadyequine.com/). The cyclic compression stimulates lymphatic drainage and helps drive the cold into the deeper tissues.
Bandaging is important in the acute phase of injury to control swelling and provide support. Generally a simple padded standing bandage consisting of a leg quilt and a track bandage is recommended. The bandage may be changed daily or more frequently to allow reapplication of cold therapy. A mild sweat or poultice may be added to the bandaging routine; however, caution should be used to avoid scalding the skin. Scalding perpetuates the inflammatory cascade and precludes the use of injectable therapeutic agents until the skin is fully healed.
Despite the advances that have been made in the treatment of exercise-induced tendonitis and desmitis in the horse, the cornerstones of therapy continue to be a controlled exercise program and patience. Carefully controlled increases in exercise, determined on the basis of serial clinical and ultrasound examinations, is essential to a successful outcome. Swim therapy and hyperbaric oxygen therapy (see Chapter 201, Hyperbaric Oxygen Therapy) are potential adjuncts to the therapies described in this review.
STEM CELL THERAPY
Stem cells are undifferentiated cells that have the ability to undergo differentiation into specific cell lineages and are capable of self-renewal. Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from bone marrow, muscle, tendon, and adipose tissue and can differentiate into cells such as osteoblasts, myocytes, chondrocytes, adipocytes, and tendon fibroblasts. Adult stem cells can exert a regenerative response by differentiating into mature cells in the tissue into which they are implanted and producing tissue-appropriate ECM products. They may also contribute to healing via production of bioactive proteins (growth factors and cytokines) that exert signaling effects locally through recruitment of endogenous stem cells and inducing anabolic effects in newly recruited cells and mature tissue-specific cells already present in the tissue. The potential for cell differentiation, growth factor production, and cell recruitment has made adult stem cell technology one of the hottest topics in medicine.
Autogenous Bone Marrow Injection
Literature on the efficacy of using MSCs to enhance tendon healing is expanding rapidly. Interest in these multipotent cells is gaining momentum, and MSCs are the subject of numerous research projects focused on tendon and ligament healing. The concept of using MSCs for treatment of tendon and ligament injuries in the horse originated when Dr. Doug Herthel began collecting bone marrow aspirate from the sternum of horses and injecting it into injured ligament. A published case series reported improved clinical lameness outcomes in horses with high suspensory desmitis treated with injection of bone marrow aspirate. This technique has become widely used by equine veterinarians without apparent adverse effects.
The potential beneficial effects of autologous bone marrow injection are twofold. The injected MSCs may differentiate into mature fibroblasts under the signaling influences of the tissue and produce the appropriate matrix products for repair. In addition, bone marrow reportedly contains high concentrations of growth factors, several of which improve the healing of tendons and ligaments in several models. Rabbit patellar tendons injected with autologous blood were mechanically stronger than normal patellar tendon in one study. Blood is known to contain high concentrations of growth factors, and bone marrow, when harvested via needle aspiration, is largely composed of blood. This indirect evidence supports the idea that marrow supernatant may enhance the healing process. In an Achilles tendon laceration model in the rabbit, MSCs seeded onto a bioabsorbable suture material via a contracted collagen gel significantly improved the biomechanics and structural properties of the repair.