Joint Medication: Part 4 - Systemic joint therapy

So far we have looked into what makes up a joint, joint communication and medication which is injected directly into the joint. Many horses suffer from discomfort in multiple joints. In these cases, there is often a need to treat the horse systemically, therefore treating all the joints simultaneously. This can be done through systemic medication or dietary supplements. A detailed supplement blog will soon follow.

Systemic medication

• Oral

  • Non-steroidal anti-inflammatories

    • Equipalazone (Bute)

    • Danilon

  • Paracetamol

• Intravenous

  • Hyaluronic acid

• Intramuscular

  • Polysulfated glycosaminoglycans

    • Adequan

  • Pentosan Polysulfate Sodium

    • Cartrophen

    • Osteopen

    • Arthropen

• Intravenous or intramuscular

  • Bisphosphonates

    • Osphos

    • Tildren

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Non-Steroidal Anti-inflammatories (NSAIDs)

The basic nonsteroidal anti-inflammatory drugs (NSAIDs) function is to stop pain. There are 3 different classes of NSAIDs, based on which part of the inflammation pathway they actually stop, however, this also has a knock on effect in terms of side effects.

The most commonly used NSAIDs for musculoskeletal diseases are:

• Phenylbutazone - ‘Bute’ - most commonly sold as Equipalazone - this is within the 1st group, called the COX-1 inhibitors.

• Suxibuzone - Most commonly sold as Danilon - this is a prodrug of Bute, meaning that it is transformed into phenylbutazone once it is absorbed.

Danilon is considered to be more palatable than Bute (1), and have less side effects (2). Bute is mainly associated with the potential to cause gastric ulcers, however, long term use at high levels can also cause kidney disease.

Most importantly, both Bute and Danilon are considered to have the same pain relieving effect (1). Bute has a withdrawal period of 7 days as per the FEI List of Detection Times.

Other, safer NSAIDs also exist. Meloxicam can also be used to treat chronic musculoskeletal disease (3), however, it is not as effective as Bute (4).

Paracetamol

The actual drug in paracetamol is called acetaminophen. This drug does not work through COX inhibitors (unlike the NSAID group). It can therefore be used at the same time as NSAIDs to control discomfort, especially in episodes of acute (sudden) pain (5). Repeated dosing with paracetamol is considered to be safe, with mild changes in liver parameters and no increase in gastric ulceration (6).

Most cases of arthritis and joint pain are not acute and sudden lameness should be discussed with your vet. Paracetamol, however, can be part of your horse’s pain management plan.

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Hyaluronic Acid (HA)

HA is a non-sulfated glycosaminoglycan. The 3rd part of the blog series showed that intra-articular medication (direct injection into the joint) with hyaluronic acid did not result in significant improvement. Another method of administering HA is intravenously, meaning that it is injected directly into the vein.

Injection of HA into the vein leads to an increase in its concentration in the blood for less than 3 hours (7). Different formulations of HA are commercially available, based on how heavy (the molecular weight) the HA compound is. Heavier HA formulations (above 5 x10ʌ5) are much more effective (8).

This doesn’t seem like a long time, however, scientific studies show that three weekly injections of 40 mg HA decreased lameness and improved the synovial membrane (9).

This also takes us back to the study mentioned in the 3rd part of this blog series:

‘A 2021 study (10) of TB horses with middle carpal joint lameness showed that horses which received PAAG (Arthramid) had an 83% chance of being lameness free at 6 weeks, as opposed to 27% that received TA and 40% that received HA. This is a great case study as all the horses were in flat race training and the lameness was localized to the same joint in every horse.’

Within this study, the horses in the HA portion also received two intravenous doses of 40 mg of HA at weekly intervals, and not just a one-off dose into the joint.

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Polysulfated glycosaminoglycans (PSGAGs) - Adequan

A course of Adequan treatment consists of 7 injections, 4 days apart. A 1993 study (11) showed that it doubles the HA concentration in joints within 48 hours. This has been shown to decrease lameness and improve joint flexibility (12).

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Pentosan polysulfate sodium (PPS) - Cartrophen/ Arthropen/ Osteopen

A course of PPS consists of 4 injections, 5-7 days apart. PPS has been shown to positively improve the structural integrity of joints (13) by decreasing articular cartilage damage and increasing chondroitin (a vital building block of cartilage) within the joint (14).

Some horses subsequently receive monthly PPS injections as maintenance. A number of products are available.

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Bisphosphonates - Tildren/ Osphos

Tildren and Osphos are the bisphosphonates currently used in horses.

• Tildren - the active ingredient is called tiludronate - administered intravenously, slowly as a drip.

• Osphos - the active ingredient is called clodronate - administered intramuscularly, generally into 3 different muscles.

These drugs regulate bone activity to restore normal bone function, leading to improved bone remodeling, decreased mineral loss and reduction of pain caused by abnormal bone changes. It should not be used in young horses (under the age of 36-48 months) as it may predispose to stress fractures, decrease the ability to repair microcracks (which occur due to normal stress of workload) and potentially worsen sesamoid diseases and palmar osteochondral disease (POD - fetlock disease) (15).

So which conditions scientifically improve after administration of these drugs?

• Lower hock pain - Tildren (16).

• Navicular disease - Osphos (17) and Tildren (18).

• Back pain - Tildren (19).

Potential side effects are uncommon and should be discussed with your vet before treatment.

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Conclusion

A number of treatment options which improve joint quality all around the body are available and worth utilising. Every vet is going to be guided by their own success experience when deciding which additional therapy would suit your horse. This guide has hopefully provided an understanding of how some of the most common joint modifying drugs work.

References

1. Sabaté, D., Homedes, J., Salichs, M., Sust, M. and Monreal, L. (2009). Multicentre, controlled, randomised and blinded field study comparing efficacy of suxibuzone and phenylbutazone in lame horses. Equine Veterinary Journal, 41(7), pp.700-705.

2. Monreal, L., Sabaté, D., Segura, D., Mayós, I. and Homedes, J. (2004). Lower gastric ulcerogenic effect of suxibuzone compared to phenylbutazone when administered orally to horses. Research in Veterinary Science, 76(2), pp.145-149.

3. Olson, M., Nagel, D., Custead, S., Wise, W., Penttila, K., Burwash, L., Ralston, B., Schatz, C. and Matheson-Bird, H. (2016). The Palatability and Comparative Efficacy of Meloxicam Oral Suspension for the Treatment of Chronic Musculoskeletal Disease in Horses. Journal of Equine Veterinary Science, 44, pp.26-31.

4. Banse, H. and Cribb, A. (2017). Comparative efficacy of oral meloxicam and phenylbutazone in 2 experimental pain models in the horse. Canadian Veterinary Journal, 58, pp.157-167.

5. Taylor, P. and Senior, M., 2018. Update in advances in pain management for the equine practitioner. Equine Veterinary Education, 31(7), pp.340-342.

6. Mercer, M., McKenzie, H., Davis, J., Wilson, K., Hodgson, D., Cecere, T. and McIntosh, B., 2019. Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses. Equine Veterinary Journal, 52(1), pp.120-125.

7. Popot, M., Bonnaire, Y., Guechot, J. and Toutain, P., 2010. Hyaluronan in horses: physiological production rate, plasma and synovial fluid concentrations in control conditions and following sodium hyaluronate administration. Equine Veterinary Journal, 36(6), pp.482-487.

8. Smith, M. and Ghosh, P., 1987. The synthesis of hyaluronic acid by human synovial fibroblasts is influenced by the nature of the hyaluronate in the extracellular environment. Rheumatology International, 7(3), pp.113-122.

9. Kawcak, C., Frisbie, D., Trotter, G., McIlwraith, C., Gillette, S., Powers, B. and Walton, R., 1997. Effects of intravenous administration of sodium hyaluronate on carpal joints in exercising horses after arthroscopic surgery and osteochondral fragmentation. American Journal of Veterinary Research, 58(10), pp.1132-40.

10. ​​de Clifford, L., Lowe, J., McKellar, C., McGowan, C. and David, F., 2021. A Double-Blinded Positive Control Study Comparing the Relative Efficacy of 2.5% Polyacrylamide Hydrogel (PAAG) Against Triamcinolone Acetonide (TA) And Sodium Hyaluronate (HA) in the Management of Middle Carpal Joint Lameness in Racing Thoroughbreds. Journal of Equine Veterinary Science, 107, p.103780.

11. Burba, D., Collier, M., Default, L., Hanson-Painton, O., Thompson, H. and Holder, C., 1993. In vivo kinetic study on uptake and distribution of intramuscular tritium-labeled polysulfated glycosaminoglycan in equine body fluid compartments and articular cartilage in an osteochondrial defect model. Journal of Equine Veterinary Science, 13(12), pp.696-703.

12. Verde, C., Ferrante, M., Simpson, M., Babusci, M., Broglia, G. and Landoni, M., 2010. Efficacy of intramuscular polysulfated glycosaminoglycan in a controlled study of equine carpitis. Journal of Veterinary Pharmacology and Therapeutics,.

13. Ghosh, P., 1999. The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment. Seminars in Arthritis and Rheumatism, 28(4), pp.211-267.

14. McIlwraith, C., Frisbie, D. and Kawcak, C., 2012. Evaluation of intramuscularly administered sodium pentosan polysulfate for treatment of experimentally induced osteoarthritis in horses. American Journal of Veterinary Research, 73(5), pp.628-633.

15. McLellan, J., 2017. Science-in-brief: Bisphosphonate use in the racehorse: Safe or unsafe?. Equine Veterinary Journal, 49(4), pp.404-407.

16. Gough, M., Thibaud, D. and Smith, R., 2010. Tiludronate infusion in the treatment of bone spavin: A double blind placebo-controlled trial. Equine Veterinary Journal, 42(5), pp.381-387.

17. Frevel, M., King, B., Kolb, D., Boswell, R., Shoemaker, R., Janicek, J., Cole, R., Poole, M. and Longhofer, S., 2014. Multi-Centre Field Trial to Evaluate the Effectiveness of Clodronic Acid for Navicular Syndrome. Equine Veterinary Journal, 46, pp.5-6.

18. Denoix, J., Thibaud, D. and Riccio, B., 2010. Tiludronate as a new therapeutic agent in the treatment of navicular disease: a double-blind placebo-controlled clinical trial. Equine Veterinary Journal, 35(4), pp.407-413.

19. Coudry, V., Thibaud, D., Riccio, B., Audigié, F., Didierlaurent, D. and Denoix, J. (2007). Efficacy of tiludronate in the treatment of horses with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column. American Journal of Veterinary Research, 68(3), pp.329-337.