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Review of the Scientific Basis for Use of Intra-Articular Corticosteroids in the Horse

Take Home Message

Intra-articular corticosteroids are potent anti-inflammatory agents with prolonged effectiveness for traumatic joint disease in the horse. Generalizations about harmful effects of intra-articular corticosteroids are inappropriate, and research has defined differences in beneficial and deleterious effects. There is also no evidence that intra-articular corticosteroids cause harm to subchondral bone or promote catastrophic injury. Sound evidence linking laminitis to corticosteroid injection of normal doses of corticosteroids is lacking.

Introduction

The Thoroughbred horse-racing industry has come under renewed scrutiny in recent years in the United States because of horses suffering from catastrophic injury during high-profile events. Consequently the public outcry from these events has led to Congressional oversight and investigation into the industry, which has led to significant scrutiny of medications that are used in sport. Anabolic steroids were banned in 2009 and now, other medications are also being critically reviewed. Intra-articular use of corticosteroids has recurred as a focus of attention. Proponents of intra-articular corticosteroid treatment argue that such therapy is needed to decrease inflammation and musculoskeletal pain, which is common in Thoroughbred racehorses, and more importantly, to avoid overloading of the other limbs, possibly leading to catastrophic injury. However, opponents of corticosteroid use feel that it is merely masking pain and results in joint deterioration. Much of this perception of harm is based on opinion and has been passed down through the literature.1
 
This paper was a review of the clinical use and scientific basis of intra-articular corticosteroid administration that was generated by a request to Dr. McIlwraith by the American Association of Equine Practitioners Racing Committee and the Racing Medication and Testing Consortium (RMTC) to critically review the scientific data regarding intra-articular corticosteroids. After doing this review Dr. McIlwraith has published a full review in Equine Vet Journal2 and it was also presented at the Annual Meeting of AAEP in December 2010.3

Summary of Important Points

  • The use of hydrocortisone in the treatment of a variety of musculoskeletal conditions in 94 horses and cattle was first reported in 1955 by Wheat. The author cited profound improvements in clinical signs in most cases but also cautioned treated animals should be rested after injection to allow healing of affected animals.
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  • This report was followed by multiple investigations that showed positive effects by Van Pelt and colleagues.
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  • The first paper indicting corticosteroids as harmful in the horse was written in 1968 and was based on an anonymous paper in the human literature. The statement, "an endless destructive cycle is set into motion which, if continued, will produce a steroid arthropathy which can render the horse useless" was referenced and the reference was an abstract written by an anonymous author. In a subsequent textbook chapter on drugs in the performance horse a number of statements were made regarding corticosteroids and their harmful effect on joints.
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  • Early studies evaluating the effect of methylprednisolone acetate (MPA) injected into normal joints showed deleterious effects.
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  • Based on observations of the lack of secondary cartilage damage when doing arthroscopic surgery for joints with osteochondral fragmentation, research projects were commenced at the ORC at Colorado State University.
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  • The initial project was done with betamethasone esters and there were no harmful side effects observed in an experimental model in which a chip fragment was created and horses exercised on the treadmill.
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  • Subsequent evaluation of MPA showed definite deleterious side effects using the osteochondral fragment model that was modified and has been used in multiple studies since then. This led to recommendation of caution using MPA.
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  • Triamcinolone acetonide (TA) was then evaluated using the osteochondral fragment model and protective effects to the cartilage as well as good clinical effects in lowering inflammation were found.
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  • There had been a long fear of the use of TA potentiating development of laminitis. Early work had recommended that a total body dose of 18 mg not be exceed. Subsequent to that a clinical paper showed use of doses up to 40 mg were not associated with laminitis. More recently a report of intra-articular injection of corticosteroids in 2,000 cases revealed laminitis being associated with this treatment in three cases. The majority of the time TA was used at higher dose rates ranging from 20-45 mg.
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  • A traditional concept has been that a load is better not to use MPA in high motion joints, but its use in low motion joints (such as the distal tarsal joints) is appropriate. There certainly has been decreased use of TA by sport horse veterinarians even in low motion joints, but the use persists in racehorses but there is no evidence either way that this practice needs to be continued. While MPA is believed to be longer acting there is questionable logic to selective harm to articular cartilage.
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  • There is no association of intra-articular use of triamcinolone acetonide or methylprednisolone acetate causing harm to the bone and predisposition to fracture and catastrophic injury based on controlled studies in horses.
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  • Anti-inflammatory actions of corticosteroids are mediated through cytoplasmic receptors which lead to gene-regulation changes and consequent changes in protein expression through signaling pathways. The anti-inflammatory effects are quite long acting and the pharmacologic presence in the joint. There are a number of pharmacokinetic studies being done with corticosteroids but it is difficult to directly transpose pharmacokinetic data into biologic potency or activity. Measuring gene expression using pharmacogenomic methods provides the potential of more global assessment or pharmacodynamics responses after intra-articular corticosteroid injection.
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  • There is no current evidence that combination therapy with HA can mitigate the negative effects associated with MPA but recent work shows that HA does have chondroprotective effects in combination therapy with TA or betamethasone esters is appropriate.

References

  1. McIlwraith C.W. The usefulness and side effects of intra-articular corticosteroids – What do we know? In Proceedings, 38th Annual Meeting of the American Association of Equine Practitioners 1992;21-30.
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  3. McIlwraith C.W. The use of intra-articular corticosteroids in the horse – what do we know on a scientific basis? Equine Vet J 2010;42:563-571.
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  5. McIlwraith C.W. Review of the scientific basis for use of intra-articular corticosteroids in the horse. In Proceedings, 56th Annual Meeting of the American Association of Equine Practitioners 2010;56:19-23.
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