Mild and moderate osteoarthritis can be managed effectively using nutritional supplements, delaying the need for treatment with NSAIDs. Osteoarthritis is a painful condition that can severely impact the mobility and quality of life for man and his best friend. Approximately 90 percent of dogs five years of age and older suffer from some degree of osteoarthritis.1 Veterinarians commonly manage it with non-steroidal anti-inflammatory drugs (NSAIDs). However, it is well known the long-term use of NSAIDs can lead to kidney and liver damage. Mild and moderate osteoarthritis can be managed effectively using nutritional supplements, delaying the need for treatment with NSAIDs. When managing severe cases, the veterinarian can combine an NSAID with a nutritional supplement enabling the dose of NSAID needed to be minimized. This article addresses several nutritional supplements that can be used by veterinarians to manage canine osteoarthritis. Omega-3 fatty acids Roush et al., studied the use of fish oil omega-3 fatty acids to manage canine osteoarthritis in a randomized, double-blind, placebo-controlled clinical trial involving 38 client-owned, osteoarthritic dogs.2 Over a 90-day period, 16 dogs received a conventional commercial diet, while 22 dogs received a diet comprising 3.5 percent fish oil omega-3 fatty acids. The most important finding of the study was dogs that received a diet enriched with omega-3 fatty acids experienced a statistically significant improvement in peak vertical force generation (p=0.01), while dogs that received the control diet did not experience any improvement in this parameter (p=0.85). Clinical metrology instruments, such as Liverpool osteoarthritis in dogs (LOAD),3 canine brief pain inventory (CBPI),4 and Helsinki chronic pain index (HCPI)5 are used extensively by clinicians to diagnose canine osteoarthritis, but are inherently subjective in nature while peak vertical force is a highly objective parameter. Dogs receiving omega-3 fatty acid supplementation also experienced improvements in subjective parameters such as lameness and weight bearing capacity, and trends toward improvements in pain and reluctance to hold up the contralateral limb were also observed. Green-lipped mussel Green-lipped mussel (GLM) is a shellfish native to New Zealand and has been consumed by the coastal-dwelling Maori for centuries. GLM is a rich source of omega-3 fatty acids with powerful anti-inflammatory properties, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and eicosatetraenoic acid (ETA). In addition, GLM is also an abundant source of glycosaminoglycans (GAGs), such as chondroitin sulfate, that play an instrumental role in chondrogenesis. In a prospective, double-blinded, longitudinally controlled study involving 23 osteoarthritic dogs, it was reported that GLM supplementation did lead to improvements in peak vertical force (p=0.003).6 Hielm-Björkman, et al., reported in a veterinary clinical trial, GLM was able to alleviate chronic orthopedic pain in osteoarthritic dogs when compared with placebo treatment, although GLM was less effective than carprofen.7 After 56 days of GLM treatment, Pollard et al. reported osteoarthritic dogs experienced improvements in clinical signs (p=0.018) and musculoskeletal scores (p=0.053) when compared with dogs in the placebo group.8 Fortetropin, fertilized, chicken egg yolk powder Fortetropin is a fertilized, chicken egg yolk powder that is produced using a patented, low- temperature manufacturing process.9 It is well recognized that quadriceps muscle atrophy is a significant risk factor for osteoarthritis.10 White et al.,11 studied the impact of fertilized, chicken egg yolk powder on dogs undergoing TPLO surgery in a randomized, double-blind, placebo- controlled clinical trial. Dogs that received daily supplementation of Fortetropin following TPLO surgery did not experience statistically significant losses in quadriceps muscle tissue when examined after eight weeks. In contrast, dogs receiving supplementation with a macronutrient-matched placebo did experience statistically significant losses in quadriceps muscle tissue on the affected (p=0.03) and unaffected limb (p=0.02) when examined after eight weeks following surgery. In a randomized, double-blind, placebo-controlled clinical trial conducted at Kansas State University that examined that impact of Fortetropin on geriatric dogs, it was observed dogs that received Fortetropin supplementation experienced statistically significant decreases in LOAD scores, indicating improved mobility and quality of life when they were examined after six and 12 weeks of supplementation.12 Dogs that were part of the placebo group did not experience any significant changes in LOAD scores when examined at these time points. Eggshell membrane Muller et al., reported results from a randomized, double-blind, placebo-controlled clinical study involving 27 osteoarthritic dogs to evaluate the impact of an eggshell membrane-based nutritional supplement over a duration of 12 weeks.13 A trend toward a decrease in the inflammatory cytokine, IL-2 was observed in dogs that were supplemented when compared with the dogs in the placebo group (p=0.069). Upon completion of the study at day 84, dogs that received the eggshell membrane supplement did experience a statistically significant decrease in LOAD scores when compared with dogs in the placebo group (p=0.034). Undenatured, type II collagen A randomized, positive-controlled clinical study involving 60 client-owned dogs was conducted by Stabile et al., to examine the impact of undenatured, type II collagen (UC-II) supplementation on dogs with osteoarthritis.14 Approximately 90 percent of dogs with any form of osteoarthritis are five years of age or older. Because NSAIDs are considered the “gold standard” for managing canine osteoarthritis, one group of dogs (n=30) was treated with the NSAID robenacoxib while the other group of dogs was treated with UC-II. At the start of the study, all dogs were required to undergo a radiographic exam and each X-ray was scored from 1-4 by a veterinary radiologist and categorized into “at risk” (1), “mild” (2), “moderate” (3), and “severe” (4). The distribution of dogs in each of the two groups (UC-II, Robenacoxib) was equivalent at baseline with respect to X-ray scores (p=0.998). The dogs were also required to undergo a clinical examination by a veterinarian and were also scored from 1 to 4 and categorized into (1) pre-clinical, (2) mildly abnormal, (3) moderately abnormal, and (4) severely abnormal. The two groups of dogs were not equivalent with respect to clinical scores (p=0.0169). 50.1 percent of dogs that received UC-II were assessed to be “severely abnormal” while only 8.3 percent of dogs that received robenacoxib were assessed to be “severely abnormal.” The authors found dogs with more severe clinical scores (3 and 4) responded better to robenacoxib than UC-II but both UC-II and robenacoxib were effective for dogs with mild and moderate scores (1 and 2). Glucosamine HCl/chondroitin sulfate McCarthy et al.,15 conducted a randomized, positive-controlled clinical study involving 35 dogs with osteoarthritis to evaluate the impact of glucosamine HCl and chondroitin sulfate (Glu/CS) in comparison to a positive control, the NSAID carprofen. Dogs were assessed at days 14, 42, and 70. Glu/CS was effective in terms of addressing pain, weight-bearing capacity, and severity of osteoarthritis in dogs by day 70, albeit the onset of significant improvements occurred more slowly in dogs that received Glu/CS relative to the dogs treated with carprofen. As discussed earlier, when reviewing the management of canine osteoarthritis with UC-II, the combination of an NSAID, such as carprofen, with a nutritional supplement, such as Glu/CS, may enable the veterinarian to reduce the dose of NSAID necessary to manage the dog’s condition, which will minimize the risk of long-term liver and kidney damage. Summary Nutritional supplements, such as those above, can effectively manage canine osteoarthritis based on veterinary clinical research. Nutritional supplements, such as those mentioned earlier, enable the veterinarian to delay treatment with NSAIDs and minimize the dose needed to effectively manage canine osteoarthritis. Such a therapeutic approach will help avoid long-term damage to the liver and kidneys. Neerav D. Padliya, PhD, serves as the vice president of R&D at MYOS Corporation. He manages the group’s human and veterinary clinical programs in addition to preclinical studies with leading universities and CROs to study the impact of nutrition products on sarcopenia, muscle disuse atrophy, and cancer cachexia in humans and animals. References 1 Johnson, Karie A., Anne H. Lee, and Kelly S. Swanson. Nutrition and nutraceuticals in the changing management of osteoarthritis for dogs and cats. Journal of the American Veterinary Medical Association 256.12 (2020): 1335-1341. 2 Roush, James K., et al. Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. Journal of the American Veterinary Medical Association 236.1 (2010): 67-73. 3 Hercock, C. A., et al. Validation of a client-based clinical metrology instrument for the evaluation of canine elbow osteoarthritis. Journal of Small Animal Practice 50.6 (2009): 266-271. 4 Brown, Dorothy Cimino, et al. Ability of the canine brief pain inventory to detect response to treatment in dogs with osteoarthritis. Journal of the American Veterinary Medical Association 233.8 (2008): 1278-1283. 5 Hielm-Björkman, Anna K., Hannu Rita, et al. Psychometric testing of the Helsinki chronic pain index by completion of a questionnaire in Finnish by owners of dogs with chronic signs of pain caused by osteoarthritis. American journal of veterinary research 70.6 (2009): 727-734. 6 Rialland, Pascale, et al. Effect of a diet enriched with green-lipped mussel on pain behavior and functioning in dogs with clinical osteoarthritis. Canadian Journal of Veterinary Research 77.1 (2013): 66-74. 7 Hielm-Björkman, Anna, et al. Evaluating complementary therapies for canine osteoarthritis part I: green-lipped mussel (Perna canaliculus). Evidence-Based Complementary and Alternative Medicine 6 (2009). 8 Pollard, B., et al.”Clinical efficacy and tolerance of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease. New Zealand Veterinary Journal 54.3 (2006): 114-118. 9 Buxmann, Waldemar, et al. Process for producing a composition containing active follistatin. U.S. Patent #8,815,320. August 26, 2014. 10 Ikeda, Shinichi, Hiroshi Tsumura, and Takehiko Torisu. “Age-related quadriceps-dominant muscle atrophy and incident radiographic knee osteoarthritis.” Journal of Orthopaedic Science 10.2 (2005): 121-126. 11 White, Dana A., et al. Fortetropin inhibits disuse muscle atrophy in dogs after tibial plateau leveling osteotomy. Plos one 15.4 (2020): e0231306. 12 https://www.prnewswire.com/news-releases/myos-corp-announces-positive-results-from-mobility-and-quality-of-life-study-in-geriatric-and-arthritic-dogs-at-kansas-state-university-301189586.html 13 Muller, C., et al. Placebo-controlled pilot study of the effects of an eggshell membrane-based supplement on mobility and serum biomarkers in dogs with osteoarthritis. The Veterinary Journal 253 (2019): 105379. 14 Stabile, Marzia, et al. Evaluation of the effects of undenatured type II collagen (UC-II) as compared to robenacoxib on the mobility impairment induced by osteoarthritis in dogs. Veterinary sciences 6.3 (2019): 72. 15 McCarthy, Grainne, et al. Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis. The Veterinary Journal 174.1 (2007): 54-61.