© 2023 MJH Life Sciences™ and dvm360 | Veterinary News, Veterinarian Insights, Medicine, Pet Care. All rights reserved.
Advances in musculoskeletal medications (Proceedings)
Selection of treatments for joint disease in horses is complicated by the fact that there are so many options to choose from.
Selection of treatments for joint disease in horses is complicated by the fact that there are so many options to choose from. Consequently, the decision for use of a specific medication or group of medications is often dictated by subjective decision making and word of mouth. With this in mind, the goals of using medication for management of joint disease are:
1. Relieve pain and inflammation in and around the joint
2. Restore the normal anabolic/catabolic balance within the joint
3. Improve strength and conditioning
4. Preemptively manage the disease process
Intraarticular corticosteroid use in horses is widespread and used in all breeds and disciplines. Information concerning the use of corticosteroids for treating joint pain in horses has been in the literature for over 50 years. Since that time there have been numerous objective studies, both clinical and experimental, that have evaluated the use of the medication. In vivo studies have shown that betamethasone (BM) had no detrimental effects in an osteochondral fragment model of osteoarthritis. However, it is only available at this time in compounded form, leading exposure of veterinarians to potential liability claims. Methylprednisolone acetate (MPA) has been shown to cause a nonsignificant reduction in lameness in the same model, but also to cause significant reduction in synovial fluid PGE2, and intimal hyperplasia and vascularity in the synovial membrane. However, articular cartilage damage was worse in treated joints. Using these data, and data obtained from other studies, it has been concluded that MPA causes articular cartilage damage in high-motion joints with repeated use. Triamcinolone acetanide (TA) has also been studied using the OA model, and induced significant decrease in lameness, decrease in synovial fluid total protein, increase in synovial fluid hyaluronan and glycosaminoglycan concentrations, and significant synovial membrane and articular cartilage benefits both in treated and remote joints. This has lead to the conclusion that TA may actually be chondroprotective. However, the biggest drawback to the use of TA is its perceived potential for causing laminitis, limiting its use for treatment of multiple joints in a single horse.
Corticosteroid-induced laminitis is thought to result from the ability of glucocorticoids to induce insulin resistance in cells. This has been shown experimentally in horses treated with systemic TA at a dose of 0.05 mg/kg, specifically resulting in hyperglycemia, hyperinsulinemia and hypertriglyceridemia. The reduction in glucose use by the peripheral tissues has been shown to induce separation between basal epidermal cells and their basement membrane, which is classic for hoof separation in laminitis. However, a review of clinical cases in one hospital showed that for horses without a history of laminitis, 40 – 80 mg of TA per horse did not induce laminitis in 205 horses. Until publication of this paper, 18 mg per horse was the recommended dose, which was based on review of clinical cases in which no incidence of laminitis resulted in 1500 doses of TA when given at or below that dose. Regardless of these reports, however, there are still anecdotal reports of laminitis occurring shortly after doses of TA are given, and widespread use of high doses. It is uncertain whether the McCluskey, et al paper has dictated that the standard of care for TA dosing be raised.
Another contentious point often raised is the ability of MPA to induce ankylosis in low motion joints, specifically the distal intertarsal and tarsometatarsal joints. Objective studies have repeatedly shown that MPA can induce significant articular cartilage erosion in high motion joints. However, it is unknown whether the same can occur in low motion joints. There is no clinical or experimental evidence to show that MPA induces ankylosis in low motion joints, and in fact, facilitated ankylosis is often necessary due to failure of intra-articular medication to control joint pain.
Both clinical and experimental evidence has shown that doses lower than those used in the past are common and effective for treating joint disease. Use of these lower doses and selection of type of corticosteroid based on age, use and type of joint have improved effective management of horses with joint pain. As an example, stifle pain in western performance horses, namely cutting horses, is common. It is now common to treat those horses with shorter acting preparations such as TA, and save MPA for later in life if needed. The same has been reported for Standardbred racehorses, in which Isoflupredone Acetate is commonly used in young horses in order to prolong an effective career. It is also becoming common in sport horses to treat with relatively short acting preparations, but in combination with hyaluronic acid. In addition, with the clinical benefits of autologous conditioned serum being realized, therapies can be staged in order to best control pain in performance horses. Although general guidelines can be given, the use and staging of these various medications is best based on clinical experience.
NSAIDs are used most commonly to control inflammation and pain for musculoskeletal pain. Medications in this classification are very effective for controlling Prostaglandin E2, a major factor in the progression of synovitis and osteoarthritis. Most NSAIDs also inhibit cyclooxygenase at varying levels, thus reducing the production of PGE2. Other biochemical actions may also be at work with some NSAIDs, such as the ability of Ketoprofen to reduce lipoxygenase. Therefore, specific NSAIDs have varying effects on inflammation and pain. It is becoming apparent that effectiveness of the medication can be easily influenced by several factors in addition to dose. For instance, the peak plasma concentration can be delayed if the horse has access to hay. Therefore, effectiveness and withdrawal times should be considered in light of feed schedules. There is also concern that NSAIDs can have a deleterious effect on articular cartilage. The data however are controversial, as both degradative and beneficial effects have been seen in vitro and in vivo when the literature is reviewed. Therefore, the current recommendations are to use NSAIDs as needed for symptomatic control of pain and inflammation.16
Hyaluronic acid (HA) is commonly used both systemically and intraarticularly. Systemic use of HA showed strong anti-inflammatory benefits up to 56 days after the start of treatment at 40 mg IV once weekly for 3 weeks. It is also commonly used once or twice monthly during competition. It is difficult to determine its affect, but some trainers and owners feel that some horses do very well with it regardless of the type of injury or the joint involved. HA is used intraarticularly as well, with variable results. HA can be used alone for cases of synovitis, but in most instances it is used in combination with CS for maximal effect. It appears that the combination of medications can have an additive effect and work towards managing joint pain by 2 different means. The other location where HA alone can be beneficial is in the management of tendon sheath adhesions, and it is commonly used postoperatively in sheaths where adhesions and damage have been found.
Polysulfated glycosaminoglycans (PSGAG) are also used systemically and intraarticularly. Systemic use of PSGAG has shown beneficial effects on articular cartilage and clinical signs of joint disease in several species. The clinical improvement may be a result of anti-inflammatory effects of the medication, which including inhibition of PGE2, and general cytokine release. There are several forms of PSGAG on the market, but the only form that has been studied extensively is Adequan. Other forms of PSGAG for injectable use are compounded and veterinarians must assume all liability for their use. Doses for Adequan vary, and range from 500 mg IM every 4 days for 8 treatments, to every 5 days for 5 treatments. It can also be used once or twice monthly. Intraarticular treatment using PSGAG is commonly done, but with caution. PSGAG can potentiate infection, so must be administered with 125 mg Amikacin. We commonly use IA PSGAG for joints with severe articular cartilage erosive lesions, and in cases of severe OA it is often used combined with HA.