Skipping past steroids to enhance joint health in horsesResearch work continues on how to minimize cartilage injury on horses with OA. | Photo: Nichole ChiricoVeterinarians and researchers have made, and continue to make, remarkable progress in understanding osteoarthritis (OA, degenerative joint disease) in horses. We now know, for example, that the horses joint is an organ, and OA affects all the associated tissues. This includes the joints synovial lining, the articular cartilage lining the bones, the layer beneath the articular cartilage called the subchondral bone, as well as the supporting joint capsules and ligaments. Scientists have also described many of the key players involved in the pathogenesis of equine OA that lead to inflammation and degeneration of the joint tissues, such as interleukin-1 (IL-1), tumor necrosis factor- (TNF), and matrix metalloproteinases (MMPs), among myriad others.Regenerative therapies, along with oral non-steroidal anti-inflammatory drugs (NSAIDs, e.g., Bute) and intra-articular (IA) corticosteroids, help manage OA pain while keeping horses comfortable and in competition. Interleukin-1 receptor antagonist protein (IRAP), autologous protein solution, stem cell therapy (from either adipose tissue or bone marrow), and platelet-rich plasma now are all widely available for supporting horses diagnosed with OA.Despite these advances, no treatment has yet halted the progression of equine OA. Researchers, however, continue to explore novel approaches. In the past year multiple groups have tested creative strategies to address this persistent problem in horses, and here well highlight some of the most promising findings.Next-Level Stem-Cell TherapiesWhile using stem cells for OA is not new, Ontario Veterinary College researchers looked at using pooled, ready-to-use equine umbilical-cord-derived (eCB) mesenchymal stromal cells (MSCs). In that study, led by Judith Koenig, Dr med vet, DVSc, Dipl. ACVS, ACVSMR, professor of clinical studies, researchers combined pooled eCB-MSCs with hyaluronic acid (HA; Munevar Luque et al., 2024) to evaluate symptom-modifying effects of this treatment in client-owned horses with naturally occurring OA of the carpus (knee) or fetlock.They cultured and cryopreserved eCB-MSCs collected from healthy Thoroughbred and Standardbred foals. Then they mixed 1 milliliter of cryopreserved eCB-MSCs containing either 10 or 20 million cells with 2 mL HA and injected them into the affected joint of each horse. Control horses received only 3 mL of the HA.Evidence suggests that combining cells from several donors may better reduce inflammation than using cells from just one donor, Koenig says. Recent studies, including our own, have shown that injecting 10 to 20 million umbilical-cordderived stem cells into horse joints is safe, with the higher dose even linked to fewer signs of inflammation. Stem cell treatments for joints can be prepared in different solutions, such as HA or saline. Because HA is routinely used to treat OA in horses and other species, we wanted to compare if adding MSCs to HA can improve outcomes compared to HA alone.Researchers included horses with lameness localized to a single fetlock or carpus by blocking (diagnostic analgesia) and radiographs (X rays). They assessed baseline joint effusion (swelling) and lameness immediately prior to injection and again 24 to 72 hours and three and six weeks after treatment. Owners completed a satisfaction survey 18 weeks after treatment. In total, the team included nine in each of three groups: 10 million eCB-MSCs + 2 mL HA; 20 million eCB-MSCs + 2 mL HA; and 3 mL HA.No significant differences in lameness were observed between treatment groups at either three or six weeks following treatment; however, lameness improved significantly over time within each treatment group, says Koenig. Additionally, lameness grade improved by 0.5 grades in the HA group, and by one full grade in both the 10 and 20 million eCB-MSC groups, she adds.By 18 weeks, eight of the nine horses in the 10 million + HA group returned to the same or higher level of exercise, and seven out of nine in the 20 million + HA group returned to exercise. Only five of nine horses in the HA group returned to exercise. While this difference was not statistically significant, Koening says the small number might have limited interpretation of the results.In addition to improving lameness compared with HA alone, pooled and cultured eCB-MSCs appear safe. Only three horses had minor adverse reactions following treatment, with the most serious occurring in the HA group. All three horses responded to treatment with an NSAID and cryotherapy.In sum, both HA alone and HA plus eCB-MSCs reduced lameness in horses with naturally occurring OA, but horses treated with both HA and MSCs had higher rates of return to athleticism than HA alone. The researchers saw no differences in using 10 vs. 20 million eCB-MSCs.Based on the results of this study, we treated an additional 30 client-owned horses with either 10 million activated (treated to enhance function) cord blood (CB)-MSCs in HA, 10 million CB-MSCs without HA, or HA alone. Koenig says, referring to data that will be published soon. Horses that received 10 million CB-MSCs were four times more likely to return to exercise, while those treated with 10 million CB-MSCs plus HA were 1.5 times more likely than the HA-alone group to return to exercise 18 weeks after treatment.Koenig explains that the main goal of this research is to develop ready-to-use allogeneic CB-MSCs harvested and pooled in the spring when foals are born. Those cells are then expanded, thoroughly tested for bacteria, fungi, and viruses, and frozen in standardized doses of 10 million or smaller. When certain OA cases arise, veterinarians can thaw and inject the cells immediately, avoiding delays in treatment.Anti-TNF- TherapyEmilio De Simone, MV, PhD, professor of animal physiology in the Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, in Argentina, and colleagues recently reported on the beneficial clinical and biochemical effects of using anti-TNF- antibodies in sport horses with OA (Perrone et al., 2025).TNF- stimulates a variety of cells within the joint to release MMPs, which are a group of degradative enzymes, he explains. MMP-2 and MMP-9, in particular, contribute to the breakdown of gelatin and other matrix components, amplifying cartilage destruction. Other MMPs are also involved in this degradative cascade. Thus, treating horses with an antibody that binds to TNF- may mitigate damage to articular cartilage by reducing the activity of these enzymes. Further, studies suggest that anti-TNF- therapy inhibits other proinflammatory molecules such as IL-1.In the first study evaluating the use of anti-TNF- antibodies for treating OA in horses, De Simone created llama-derived anti-TNF- antibodies to inject IA. He hypothesized this therapy would significantly reduce clinical scores, decrease activity of MMPs, and increase concentrations of glycosaminoglycans (GAGs, structural components of connective tissue) in the synovial fluid of horses with OA.He recruited 50 sport horses20 healthy horses and 30 with OA of the intercarpal or intertarsal (hock) joints. He and his team treated the affected joint in the 30 OA horses with 10 milligrams anti-TNF- antibody and assessed lameness and synovial fluid at baseline and on Day 30 of the study.Key findings included:Lameness decreased significantly in the treated horses over the 30-day study period, though the lameness grade remained higher in the treated group than the control group. These results suggest anti-TNF- therapy has potent anti-inflammatory effects in articular tissues.The horses treated generally had chronic OA with mild to moderate clinical signs, adds De Simone. While clinical improvement was evident, the lameness scores of the treated horses never matched those of the control group, which mostly consisted of horses without a history of lameness or OA.Therefore, although anti-TNF- therapy appears to be a very effective anti-inflammatory treatment, it likely does not reverse the existing structural bone or cartilage damage in the joint, he explains. For this reason, combining anti-TNF- therapy with regenerative approaches could be of interest to enhance clinical outcomes.They found GAGs were significantly lower at baseline in OA joints compared to healthy joints. They increased significantly by Day 30 to similar levels as the control horses, suggesting GAGs are preserved in synovial fluid following treatment.They also noted MMP levels decreased significantly in OA horses following anti-TNF- treatment, supporting the hypothesis that anti-TNF- inhibits MMPs.These results suggest that early treatment with anti-TNF- antibodies can reduce the activity of proteases involved in joint degradation in sport horses, says De Simone. This therapy is particularly interesting because, unlike commonly used anti-inflammatory drugs such as corticosteroids, it does not appear to have harmful effects on joint metabolism. In fact, corticosteroids, especially when administered repeatedly or intra-articularly over long periods, can inhibit the synthesis of key cartilage components such as type II collagen and proteoglycans, potentially accelerating cartilage deterioration. Therefore, anti-TNF- therapy offers a promising alternative that may control inflammation without contributing to cartilage damage.In terms of next steps, he says, At this stage, more research is needed before clinical use can be widely recommended. The current findings are promising and support the potential of anti-TNF- therapy as a novel anti-inflammatory approach for managing equine joint disease. However, further studies are necessary to validate and homogenize the results, and efforts should be directed toward reducing production costs to develop an accessible, commercially viable treatment.In parallel, we are currently evaluating the combined use of this therapy with regenerative approaches such as platelet-rich plasma, aiming to enhance both the anti-inflammatory response and tissue repair, De Simone adds.BiomaterialsIA Biomaterials Polymeric biomaterials have garnered great interest in the field of equine OA. In the past few years manufacturers introduced two polyacrylamide hydrogels (PAAG, one 2.5% and one 4%) to the equine market, and both continue to gain popularity. While both are hydrogels, they have two different mechanisms of action. The 2.5% hydrogel has been shown to integrate into the synovial membrane, whereas the 4% product provides surface and boundary lubrication (Pluim and Frippiat, 2025). Researchers on multiple studies have shown positive effects of these products and, according to a recently published survey, eight out of 10 veterinarians reported satisfaction with using these biomaterials (Pluim and Frippiat, 2025).Given the positive results, other groups are looking into additional IA biopolymers to support pain-free movement. For example, in a study out of the University of Bologna, in Italy, Rinnovati et al. (2025) explored using a carboxymethylcellulose (CMC) hydrogel, composed of cellulose gum crosslinked with croscarmellose in a physiologic buffer.The study included 30 horses with lameness due to OA of one fetlock joint. Half the horses received a single IA injection of CMC, while the remaining horses were treated IA with a combination of 12 mg of the corticosteroid triamcinolone and 20 mg HA. Horses underwent lameness evaluations and flexion tests on Days 15, 30, and 90 of the study.The researchers defined treatment success as a minimum of one lameness grade improvement (using the five-point AAEP lameness scale) compared to baseline. Using that definition they saw treatment success of 20%, 75%, and 75% in the CMC group at 15, 30, and 90 days, which means little improvement in the short term but a marked improvement as time passed. In the controls (triamcinolone/HA), treatment success was 90%, 75%, and 8% at 15, 30, and 90 days, suggesting only a transient improvement.The research team reports that CMC appears to act primarily as a mechanical barrier and joint lubricant that might modify the IA environment over time. This could explain the observed lag in treatment effect.Overall, the researchers concluded that the small study has limitations but offers promising clinical results and encourages additional studies.Lauren K. Luedke, DVM, Dipl. ACVS-LA, assistant professor of equine surgery and lameness at Colorado State Universitys Equine Orthopaedic Research Center, in Fort Collins, and her colleagues recently examined a biolubricant called pMPC (poly2) that functions to augment the extracellular matrix of cartilage. They evaluated pMPC using a well-established post-traumatic model of OA in 16 horses.Researchers simulated joint trauma by inducing an osteochondral chip fracture in the middle knee joint of one limb in 16 horses. The other knee served as the control. Fourteen days later they treated eight horses with 6 mL pMPC in the traumatized knee, while they treated the other eight with 6 mL saline. They performed lameness exams and synovial fluid analyses at baseline and then intermittently during the 70-day study. The team obtained radiographs at baseline and again on Day 70 and performed microscopic analyses of the joints on Day 70.OA joints treated with pMPC had mild increases in lameness, effusion, and flexion scores, says Luedke. Further, synovial fluid analyses showed inflammation, and radiographs had significantly higher osteophyte scores in the pMPC treated joints, an indicator of OA. The studied biolubricant, however, did show some chondroprotective effects on microscopy, with lower erosion scores and higher cartilage GAGs.Although the results werent as promising as those of other biopolymers on the market, Luedke says, I think its important to realize that while we collectively refer to these biopolymers as the same, their chemical composition varies significantly, which is why they may have differing mechanisms of action. The pMPC showed significant promise in early murine (mice or rat) models; however we did not appreciate the same response in horses. This may indicate the dose used may need to change, or the chemical composition altered slightly to accommodate different joint environments. The product did demonstrate some chondroprotective effects.Other Uses of Biomaterials In addition to intrasynovial lubricants, biomaterials might also be used in a variety of ways to benefit horses with OA as described by Kim et al. (2025). For example, biopolymers can be synthesized in nanoparticle format to deliver therapeutic drugs or even genes to affected joints.These nanoparticles are most commonly derived from poly(lactic-co-glycolic) acid (PLGA) which is a combination of lactic acid and glycolic acid, Luedke explains. By creating microspheres of PLGA, therapeutics can be impregnated into the nanoparticles. The PLGA degrades over time, therefore the particles slowly release drugs over time, resulting in sustained drug release and long-term effects (e.g., anti-inflammatories).As an example of using the biopolymer PLGA for drug delivery in horses, Luedke referred to a study by Katzman et al. (2024). Researchers at the University of California, Davis, injected horses IA with PLGA microparticles containing 122 micrograms of flavopiridol, a cyclin-dependent kinase-9 inhibitor (stops cells from dividing). The authors reported that horses tolerated the microparticles well, with detectable flavopiridol in the synovial fluid for four weeks after administration.The extended-release microparticle formulation promotes intra-articular retention of the drug, and it may be an alternative to other intra-articular medications for treatment of equine joint disease, the researchers reported.Take-Home MessageCurrent therapies for OA help veterinarians manage the clinical signs such as heat, pain, and swelling. Stem cells, cell-less therapies (e.g., PAAG), combination therapies (e.g., stem cells with HA), and various biomaterials still need further study. Other areas of researchomitted here for space, not importanceinclude microfragmented adipose tissue therapy, mitotherapy, and gene therapy.Cartilage loss is a major challenge in treating OA, as current therapies cannot restore its original structure. So, while therapies support horses with OA and slow progression, they neither fully stop the disease nor restore the joint to its previous level of health.One of our most significant challenges with OA is the loss of cartilage, says Luedke. Cartilage is important to the joint because it offers a smooth gliding surface and impact protection/shock absorption to the weight-bearing portion of the joint. There are no therapies that can regenerate or repair cartilage to its previous structural integrity. With cartilage damage, the inflammatory cascades become predominant, which in turn compromises the cartilage. Therefore, our primary efforts are to mitigate the inflammatory process within the joint to minimize further cartilage injury.This article is from the Research Roundup 2025 issue ofThe Horse: Your Guide to Equine Health Care. 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