Treating Joint Disease in the Equine Athlete

Kyla Ortved | DVM, PhD, DACVS, DACVSMR | Published: Issue 3, 2023

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Joint disease is common in the equine athlete and osteoarthritis (OA) remains the leading cause of lameness in the equine industry, affecting approximately 60% of the equine population.
Posttraumatic OA (PTOA), which occurs secondary to acute or chronic joint trauma, is likely the most
common type of OA in the horse. Trauma can be caused by such things as repetitive loading, intraarticular fractures, osteochondritis dissecans (OCD), and soft tissue injuries (e.g., meniscal tears, collateral ligament tears). Secondary to trauma, global posttraumatic inflammation of the articular environment is caused by increased synthesis of catabolic cytokines and degradative enzymes that lead to unregulated, progressive degeneration of the articular cartilage.¹,²

Currently, there are no effective disease-modifying drugs that halt or reverse OA in the horse with treatment regimens being aimed at reducing the clinical signs associated with OA. Unfortunately, joint disease often leads to early retirement or euthanasia. The two main goals of treatment for joint disease are:

1. Decrease pain and lameness

2. Minimize the progression of joint degeneration

Standard medical treatments for OA have included systemic therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and other medications aimed at supporting joint health (e.g., polysulfated glycosaminoglycans (PSGAGs), hyaluronic acid); intra-articular therapy with corticosteroids, hyaluronic acid, and PSGAGs; and controlled exercise. During the past decade, significant research and clinical focus has been on the use of orthobiologics in the horse with the goal of limiting further degeneration by -orthobiologics used in equine joint disease. Other newer treatments include intra-articular polyacrylamide hydrogels. Many horses with joint disease can also be treated surgically. Options for surgical intervention may include stabilization of intra-articular fractures, removal of osteochondral fragments, cartilage repair, facilitated ankylosis, and arthrodesis.

Certainly, here’s the text in a format that you can easily copy and paste without any coding:

Use of Orthobiologics in the Horse with the Goal of Limiting Further Degeneration by Orthobiologics Used in Equine Joint Disease. Other newer treatments include intra-articular polyacrylamide hydrogels. Many horses with joint disease can also be treated surgically. Options for surgical intervention may include stabilization of intra-articular fractures, removal of osteochondral fragments, cartilage repair, facilitated ankylosis, and arthrodesis.

Medical Treatment of Joint Disease

Corticosteroids
Intra-articular corticosteroids have been the mainstay of joint disease treatment for many decades and, despite some of the negative connotations associated with this class of drugs, can be very effective in treating joint disease in many horses. Corticosteroids act as potent anti-inflammatories by inhibiting the arachidonic acid cascade by blocking phospholipase A2. They have been shown to decrease expression and synthesis of IL-1β, TNF-α, MMP-3, and MMP-13 in cartilage, thereby impeding the degradative processes in the joint. Currently, the three main corticosteroids used by equine practitioners include methylprednisolone acetate (Depo-Medrol), triamcinolone acetonide (Vetalog), and betamethasone acetate (Betavet). Previous studies have shown that while all formulations have beneficial effects on lameness, triamcinolone also has some protective effects on cartilage, while methylprednisolone actually has some detrimental effects on chondrocytes and the ECM. These findings led to the AAEP suggestion that triamcinolone be used in high-motion joints, while methylprednisolone be reserved for low-motion joints. Despite the beneficial clinical effects of corticosteroids, a recent trend away from them is notable, likely due to a combination of potential detrimental effects on the joint and stricter withdrawal periods imposed by racing authorities. Additionally, although the reported incidence of corticosteroid-induced laminitis in the literature is quite low (0.15-0.5%), there are rising concerns about laminitis post-corticosteroid administration in horses with pre-existing endocrinopathies such as pituitary pars intermedia dysfunction (PPID; Equine Cushing’s Disease) or insulin dysregulation. Further research is needed in this rapidly growing population of horses.

Hyaluronic Acid
Hyaluronic acid (HA), a disaccharide of D-glucuronic acid and N-acetyl-D-glucosamine, is a major component of synovial fluid and aggrecan. When administered intra-articularly, HA plays a role in lubrication and has anti-inflammatory effects, particularly on white blood cells, in the joint. It is also believed to increase endogenous production of HA by synoviocytes. High molecular weight HA is reported to be more effective; however, it is also associated with higher costs. Hyaluronic acid is likely more effective for treatment of mild synovitis or capsulitis versus more severe cases of OA. Combination therapy of HA and corticosteroids is common, although a recent study found that lameness was decreased more in horses treated with triamcinolone alone compared to HA + triamcinolone. At this time, the jury is still out on the effectiveness of combination therapy.

Polysulfated Polysaccharides
Polysulfated polysaccharides, including polysulfated glycosaminoglycan (PSGAG; Adequan) and pentosan polysulfate, have been shown to inhibit catabolic cytokines and degradative enzymes in the joint. Both products can be administered intramuscularly (IM) or intra-articularly (IA); however, only Adequan is FDA-approved, and this approval is only limited to IM administration. Intramuscular PSGAG administered every four days for seven treatments have been shown to slightly decrease lameness in an experimental OA study when compared to placebo; although, when the study was repeated with IA PSGAG administered once a week for two weeks, more significant improvements were noted. It should be noted that there is evidence that IA administration of Adequan lowers the bacterial inoculation dose of Staphylococcus such that co-administration of amikacin (125mg) is recommended. There is little evidence in the literature to support the use of pentosan polysulfate; although, anecdotal reports are favorable.

Bisphosphonates
Bisphosphonates are a class of drug that inhibit osteoclastic activity in bone, thereby slowing bone loss. Currently, clodronate (OsPhos) and tiludronate (Tildren) are available for use in the horse. Although neither drug is approved for use in horses with OA, several studies have suggested beneficial effects in horses with distal tarsal OA and axial skeleton OA. Because bisphosphonates have a remarkably long half-life in bone (up to 10 years), the long-term effect of osteoclastic inhibition requires careful consideration.

Polyacrylamide Hydrogels
Polyacrylamide hydrogels (PAAG) have been recently introduced for use in synovial joints. PAAGs are synthetic, non-degradable, and biocompatible injectable gels that can be used for viscosupplementation in joints. They have been shown to integrate into the host’s soft tissues, specifically into the sub-synovial layer of rabbit and horse joints, and persist for at least 2 years. This integration is believed to alter the biologic and/or mechanical properties of the synovium, supporting joint health and decreasing pain. Further studies are necessary to fully elucidate the mechanism of action of PAAGs and to determine if there are any long-term side effects associated with the non-degradable substance. Preliminary studies in horses demonstrated analgesic benefits in OA joints up to 2 years post-injection. Currently, Noltrex (4% PAAG) and Arthramid (2.5% PAAG) are approved for use in the US.

Orthobiologics


Platelet Rich Plasma (PRP)
Platelet-rich plasma (PRP) is defined as a volume of plasma with a platelet count above that of whole blood. Commercial systems are available to prepare PRP, and the therapeutic effect is due to degranulation of platelet α-granules that release growth factors that modulate the healing response. PRP has been shown to be safe to inject into equine joints, with minimal, transient increases in nucleated cell count. PRP has also been shown to improve lameness scores in horses with naturally occurring fetlock arthritis.

Autologous Conditioned Serum (ACS)
Autologous conditioned serum (ACS) contains concentrated interleukin-1 receptor antagonist (IL-1Ra or IRAP) and other cytokines. IL-1Ra is an endogenous protein produced by immune cells and is a competitive antagonist of interleukin-1 (IL-1). IRAP II and Orthokine are two commercially available products that concentrate IL-1Ra. ACS is injected into the affected joint, with the excess stored at -20ºC for future injections.

IRAP (Interleukin-1 Receptor Antagonist Protein)
IRAP therapy neutralizes IL-1, a proinflammatory cytokine responsible for cartilage and joint degradation. It utilizes a two-syringe system to extract and inject the IRAP-rich serum into the affected joint. Studies have shown similar results in treatment efficacy and anti-inflammatory properties between IRAP and ACS.

Autologous Conditioned Serum (ACS)
Autologous conditioned serum (ACS) contains concentrated interleukin-1 receptor antagonist (IL-1Ra or IRAP) and other cytokines. IL-1Ra is an endogenous protein produced by immune cells, mainly monocytes, and is a competitive antagonist of interleukin-1 (IL-1), a central mediator of inflammation and degradation in joints. IRAP II (Arthrex Vet Systems) and Orthokine (Dechra Veterinary Products) are two commercially available products that rely on a 24-hour incubation of autologous blood in a specialized syringe to concentrate IL-1Ra. Following incubation, the conditioned serum is collected and used for IA injections, with the excess being stored at -20ºC for future injections. A common treatment regimen includes injection of the affected joint every seven to ten days for three to five treatments. Few studies have been performed evaluating the effect of ACS; however, Frisbie et al. have demonstrated improved clinical outcomes in horses with experimentally induced OA treated with ACS.

Autologous Protein Solution (APS)
Autologous protein solution (APS) is a newer patient-side product that contains concentrated platelets and increased concentrations of IL-1Ra. Marketed as ProStride, this product was recently acquired by Zoetis. The combination of growth factors from platelets and IL-1Ra is suggested to have a synergistic effect in the joint. The system does not require incubation and can be used patient-side. One study has shown improved lameness scores in osteoarthritic horses treated with Pro-Stride.

Alpha-2-Macroglobulin (A2M)
Alpha-2-macroglobulin (A2M) is an endogenous protease inhibitor that can be concentrated during processing of autologous blood. A2M binds several catabolic cytokines, including IL-1β and TNF-α, and appears to neutralize MMP activity. Although there are currently no studies evaluating the clinical effect of A2M in the horse, anecdotal reports are favorable. Additionally, A2M has been shown to protect the ECM in rats with anterior cruciate ligament transection.

Amnion
Equine amnion-based products are available for treating joints (AniCell Biotech). Amnion is collected and decellularized to create an off-the-shelf bioscaffold. Support for the use of amnion in equine joint disease is mainly anecdotal.

Stem Cells
Stem cells are undifferentiated cells capable of self-renewal and differentiation into different cell types. Adult-derived mesenchymal stem cells (MSCs) are commonly used in equine medicine, obtained from bone marrow and adipose tissue. The therapeutic effect of MSCs is attributed to their immunomodulatory effects and ability to recruit endogenous progenitor cells. Intra-articular MSCs have been shown to improve healing and alleviate clinical signs associated with OA and meniscal tears. The number of cells for injection depends on the size of the joint, generally ranging from 10-50 million cells per joint. Several equine studies have also reported the resurfacing of full-thickness cartilage lesions with MSCs.

Surgical Treatment of Joint Disease

Many horses with joint disease can be treated with surgery, either alone or in combination with medical treatment. Surgical treatment is indicated for articular fractures with the goal of reconstruction and stabilization of the articular surface. Horses with osteochondral fragments, including chip fractures and OCD, benefit from arthroscopic removal of loose cartilage flaps and free-floating fragments. Focal chondral lesions can be repaired with advanced cartilage repair techniques. In more severely affected joints, joint fusion, facilitated ankylosis, or arthrodesis may become the goal, depending on the joint and the horse’s intended use.

Physical Therapies
Physical therapies, including extracorporeal shock wave (ESWT), cryotherapy, therapeutic shoeing, therapeutic ultrasound, therapeutic laser therapy, and pulsed electromagnetic field (PEMF), may benefit horses with joint disease. Controlled exercise is essential for horses with joint disease, as they benefit from movement versus stall rest and confinement. Hopefully as the field of equine physical therapy and rehabilitation expands, we will have more evidence-based medicine on which to make recommendations.

References

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About the Author

Kyla Ortved, DVM, PhD, DACVS, DACVSMR

Dr. Kyla Ortved is an Assistant Professor of Large Animal Surgery at New Bolton Center, University of Pennsylvania in Kennett Square, PA. She received her DVM degree from the University of Guelph in 2006 and completed her large animal surgical residency training at Cornell University in 2010. Kyla became boarded with the American College of Veterinary Surgeons in 2011. Following her residency, Kyla went on to obtain a PhD in gene therapy for equine cartilage repair at Cornell. In February 2016, Kyla became boarded with the American College of Veterinary Sports Medicine and Rehabilitation. She joined the large animal surgery faculty at New Bolton Center in 2016 as an equine orthopedic surgeon and was named the Jacques Jenny Endowed Term Chair of Orthopedic Surgery in 2019. Her research program focuses on understanding the pathophysiology of equine osteoarthritis and developing gene and cell-based therapies to improve cartilage repair and prevent osteoarthritis.


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