Intra-articular steroids have long been the therapy of choice for arthritic equine joints. Because of steroids’ potential ramifications on long-term cartilage and joint health, metabolic effects, and associated laminitis risks, however, many veterinarians have turned to orthobiologics as an alternative joint therapy—particularly in the growing senior horse population that’s prone to not only osteoarthritis (OA) but also insulin dysregulation and pituitary pars intermedia dysfunction.
During the Dec. 8 Sunrise Session “Healing With Horsepower,” presented by Zoetis, at the 2024 American Association of Equine Practitioners (AAEP) Convention, a panel of distinguished researchers reviewed recent study results on autologous blood-based products and their effects on equine joints and metabolic parameters. Here are their main take-homes.
APS and its Potential Disease-Modifying Effects
This summer, Kyla Ortved, DVM, PhD, Dipl. ACVS, ACVSMR, associate professor of large animal surgery at University of Pennsylvania’s New Bolton Center, and colleagues published a study in Equine Veterinary Journal investigating autologous protein solution’s (Pro-Stride® APS) effects on synovial fluid parameters and joint pathology scores in 18 horses with induced synovitis—a precursor to OA. The goal is to identify intra-articular therapies veterinarians can use to intervene early in the progression of joint disease.
While APS did not alter synovial fluid parameters or decrease lameness or joint circumference in treated horses compared with controls, it did significantly decrease their gross and synovial membrane histopathology scores.
Based on these results, said Ortved, “APS may have disease-modifying effects within the synovium that could have significant, long-lasting downstream effects on the joint.”
In a second study, Ortved compared four autologous blood-based devices she uses in her practice: Alpha2EQ (alpha-2-macroglobulin, or A2M), Pro-Stride APS, Restigen® PRP, and Arthrex ACP (autologous conditioned plasma).
“We’re using them for the purpose of trying to inhibit pro-inflammatory pathways and promote pro-healing pathways, and they obviously have this effect on various cell types, including all the cells in the joint,” she explained. “We’re looking for them to be chondroprotective and then also promote tissue proliferation and regeneration.”
In this study, her team set out to quantify A2M, immunomodulatory cytokines, and the growth factor TGFβ-1 for each product in six healthy study horses. “We hypothesized that Alpha2EQ would have higher concentrations of A2M and lower concentrations of cytokines and growth factors compared to APS, PRP, and ACP,” Ortved said.
What they found is that APS had the highest concentration of A2M. They also found high concentrations of IL-1Ra, a potent anti-inflammatory cytokine, in APS and PRP but not in the other products. There were no significant differences between other cytokine levels in any of the products. They found the highest concentration of TGFβ-1 in Restigen PRP, which Ortved said is not surprising because that growth factor is high in platelets.
“This tells us that blood-based products do have different immunomodulatory and growth factor profiles, and that’s probably a reflection of the different concentration of platelets and white blood cells, and the different processing between all of the products,” Ortved summarized. “It’s something moving forward that we still have to be mindful of.”
APS and ACS Safe for Horses With PPID
If a veterinarian uses orthobiologics to help manage joint disease in a PPID horse, is that condition going to affect the product’s anti-inflammatory and, thus, beneficial properties? To answer this question, Valerie Moorman, DVM, PhD, DACVS-LA, clinical professor in the University of Georgia College of Veterinary Medicine’s Department of Large Animal Medicine, and colleagues recently conducted a study evaluating PPID horses’ cytokine profiles in the final product of Pro-Stride APS and autologous conditioned serum (ACS).
They compared pro- and anti-inflammatory cytokine concentrations from six PPID and six non-PPID horses before and after processing blood for ACS and APS and found no statistically significant differences in any of the cytokines between the two study groups. Moorman said this suggests PPID does not alter the cytokine profile of ACS and APS preparations.
“These products could be effective (in PPID horses), but we still don’t know because of inter-horse variability,” she concluded. “A horse with PPID may be able to produce a beneficial orthobiologic, at least.”
APS Does Not Have Metabolic Effects
Intra-articular (IA) corticosteroids remain popular therapies for equine joint pain despite published research on these drugs’ metabolic effects. So, could orthobiologics be a safer alternative? In a recent study, Allen Page, DVM, PhD, assistant professor at the University of Kentucky’s Gluck Equine Research Center, and his team aimed to find out.
They compared the metabolic effects of IA triamcinolone acetonide (TA), APS, and a saline control on five metabolically normal study horses and hypothesized that “compared to the saline and the Pro-Stride treated groups, a single 9-milligram dose of intra-articular triamcinolone will elicit changes in a variety of different parameters, including ACTH, cortisol, insulin, glucose, as well as some thyroid hormones,” said Page. “We also wanted to look at what the effects of those different treatments would be on the oral sugar test (OST) for insulin dysregulation and the thyrotropin-releasing hormone (TRH) test for PPID.”
His team found that TA had significant effects on ACTH, cortisol, glucose, and insulin levels, while APS did not. In particular, he noted a significant increase in insulin, even in the metabolically normal study horses. “If you take horses that already have much higher resting basal insulin levels, like insulin dysregulated horses, we could be increasing their chances of hyperinsulinemia-associated laminitis,” he said.
“Use intra-articular triamcinolone with caution in insulin dysregulated horses due to induced hyperinsulinemia,” Page concluded. “Pro-Stride might be a safer alternative for insulin dysregulated horses.” He urged practitioners to perform OST and TRH testing on horses before administering IA corticosteroids.
