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Immune-Mediated Polyarthritis (IMPA)

Veterinary Resources

Idiopathic, non-infectious, non-erosive arthritis in a bitch. C.R. Hutchings, G.A. Verkerk, K.J. Kissling. New Zealand Vet. J. 1980;28(5). Quote: A 2 1/2-year-old Cavalier King Charles Spaniel bitch was examined because of recurring episodes of lameness and joint swelling over a period of 2 years. Clinical examination, radiography, serology, joint-fluid analysis and histopathology of the joint capsule led to a diagnosis of idiopathic, non-infectious, non-erosive arthritis. Combination therapy with prednisolone, cyclophosphamide and azothioprine produced a rapid improvement in the dog's condition. The features of this disease and its relationship to rheumatoid arthritis and systemic lupus erythematosis are discussed.

Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. Roush JK, Cross AR, Renberg WC, Dodd CE, Sixby KA, Fritsch DA, et al. J. Am. Vet. Med. Assn. Jan. 2010; doi: 10.2460/javma.236.1.67. Quote: Objective: To evaluate the effects of a food supplemented with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. Design: Randomized, double-blinded, controlled clinical trial. Animals: 38 client-owned dogs with osteoarthritis examined at 2 university veterinary clinics. Procedures: Dogs were randomly assigned to receive a typical commercial food (n = 16) or a test food (22) containing 3.5% fish oil omega-3 fatty acids. On day 0 (before the trial began) and days 45 and 90 after the trial began, investigators conducted orthopedic evaluations and force-plate analyses of the most severely affected limb of each dog, and owners completed questionnaires to characterize their dogs' arthritis signs. Results: The change in mean peak vertical force between days 90 and 0 was significant for the test-food group (5.6%) but not for the control-food group (0.4%). Improvement in peak vertical force values was evident in 82% of the dogs in the test-food group, compared with 38% of the dogs in the control-food group. In addition, according to investigators' subjective evaluations, dogs fed the test food had significant improvements in lameness and weight bearing on day 90, compared with measurements obtained on day 0. Conclusions and Clinical Relevance: At least in the short term, dietary supplementation with fish oil omega-3 fatty acids resulted in an improvement in weight bearing in dogs with osteoarthritis.

Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. Roush JK, Dodd CE, Fritsch DA, Allen TA, Jewell DE, Schoenherr WD, et al. J. Am. Vet. Med. Assn. January 2010; doi: 10.2460/javma.236.1.59. Quote: Objective: To assess the effect of food containing high concentrations of fish oil omega-3 fatty acids and a low omega-6–omega-3 fatty acid ratio on clinical signs of osteoarthritis in dogs. Design: Randomized, double-blinded, controlled clinical trial. Animals: 127 client-owned dogs with osteoarthritis in 1 or more joints from 18 privately owned veterinary clinics. Procedures: Dogs were randomly assigned to be fed for 6 months with a typical commercial food or a test food containing a 31-fold increase in total omega-3 fatty acid content and a 34-fold decrease in omega-6–omega-3 ratio, compared with the control food. Dog owners completed a questionnaire about their dog's arthritic condition, and investigators performed a physical examination and collected samples for a CBC and serum biochemical analyses (including measurement of fatty acids concentration) at the onset of the study and at 6, 12, and 24 weeks afterward. Results: Dogs fed the test food had a significantly higher serum concentration of total omega-3 fatty acids and a significantly lower serum concentration of arachidonic acid at 6, 12, and 24 weeks. According to owners, dogs fed the test food had a significantly improved ability to rise from a resting position and play at 6 weeks and improved ability to walk at 12 and 24 weeks, compared with control dogs. Conclusions and Clinical Relevance: Ingestion of the test food raised blood concentrations of omega-3 fatty acids and appeared to improve the arthritic condition in pet dogs with osteoarthritis.

Progressive lameness in a Cavalier King Charles Spaniel. Mark Longley, Kinley Smith. BSAVA Companion. April 2011; doi: 10.22233/20412495.0411.10. Quote: An 8-year-old Cavalier King Charles Spaniel presented with a 6-month history of progressive forelimb lameness. The diagnosis and treatment of rheumatoid arthritis is described.

Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate. Gupta RC, Canerdy TD, Lindley J, Konemann M, Minniear J, Carroll BA, et al. J. Anim. Physiol. Anim. Nutr. (Berl). May 2011; doi: 10.1111/j.1439-0396.2011.01166.x. Quote: The investigation was conducted on client-owned moderately arthritic dogs with two objectives: (i) to evaluate therapeutic efficacy of type-II collagen (UC-II) alone or in combination with glucosamine hydrochloride (GLU) and chondroitin sulphate (CHO), and (ii) to determine their tolerability and safety. Dogs in four groups (n = 7-10), were treated daily for a period of 150 days with placebo (Group-I), 10 mg active UC-II (Group-II), 2000 mg GLU + 1600 mg CHO (Group-III), and UC-II + GLU + CHO (Group-IV). On a monthly basis, dogs were evaluated for observational pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using different numeric scales. Pain level was also measured objectively using piezoelectric sensor-based GFP for peak vertical force and impulse area. Dogs were also examined every month for physical, hepatic (ALP, ALT and bilirubin) and renal (BUN and creatinine) functions. Based on observations, significant (p < 0.05) reduction in pain was noted in Group-II, III, and IV dogs. Using GFP, significant increases in peak vertical force (N/kg body wt) and impulse area (N s/kg body wt), indicative of a decrease in arthritis associated pain, were observed in Group-II dogs only. None of the dogs in any group showed changes in physical, hepatic or renal functions. In conclusion, based on GFP data, moderately arthritic dogs treated with UC-II (10 mg) showed a marked reduction in arthritic pain with maximum improvement by day 150. UC-II, GLU and CHO operate through different mechanisms of action, and were well tolerated over a period of 150 days.

Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain. Daniela Impellizzeri, Giuseppe Bruschetta, Marika Cordaro, Rosalia Crupi, Rosalba Siracusa, Emanuela Esposito, Salvatore Cuzzocrea. Neuroinflammation. August 2014; doi: 10.1186/s12974-014-0136-0. Quote: Background: The fatty acid amide palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory and neuroprotective actions. The lipidic nature and large particle size of PEA in the native state may limit its solubility and bioavailability when given orally, however. Micronized formulations of a drug enhance its rate of dissolution and reduce variability of absorption when orally administered. The present study was thus designed to evaluate the oral anti-inflammatory efficacy of micronized/ultramicronized versus nonmicronized PEA formulations. Methods: Micronized/ultramicronized PEA was produced by the air-jet milling technique, and the various PEA preparations were subjected to physicochemical characterization to determine particle size distribution and purity. Each PEA formulation was then assessed for its anti-inflammatory effects when given orally in the carrageenan-induced rat paw model of inflammation, a well-established paradigm of edema formation and thermal hyperalgesia. Results: Intraplantar injection of carrageenan into the right hind paw led to a marked accumulation of infiltrating inflammatory cells and increased myeloperoxidase activity. Both parameters were significantly decreased by orally given micronized PEA (PEA-m; 10 mg/kg) or ultramicronized PEA (PEA-um; 10 mg/kg), but not nonmicronized PeaPure (10 mg/kg). Further, carrageenan-induced paw edema and thermal hyperalgesia were markedly and significantly reduced by oral treatment with micronized PEA-m and ultramicronized PEA-um at each time point compared to nonmicronized PeaPure. However, when given by the intraperitoneal route, all PEA formulations proved effective. Conclusions: These findings illustrate the superior anti-inflammatory action exerted by orally administered, micronized PEA-m and ultramicronized PEA-um, versus that of nonmicronized PeaPure, in the rat paw carrageenan model of inflammatory pain.

Nerve Growth Factor: A Focus on Neuroscience and Therapy. Luigi Aloe, Maria Luisa Rocco, Bijorn Omar Balzamino, Alessandra Micera. Curr. Neuropharmacol. May 2015; doi: 10.2174/2F1570159X13666150403231920 Quote: Nerve growth factor (NGF) is the firstly discovered and best characterized neurotrophic factor, known to play a critical protective role in the development and survival of sympathetic, sensory and forebrain cholinergic neurons. NGF promotes neuritis outgrowth both in vivo and in vitro and nerve cell recovery after ischemic, surgical or chemical injuries. Recently, the therapeutic property of NGF has been demonstrated on human cutaneous and corneal ulcers, pressure ulcer, glaucoma, maculopathy and retinitis pigmentosa. NGF eye drops administration is well tolerated, with no detectable clinical evidence of systemic or local adverse effects. The aim of this review is to summarize these biological properties and the potential clinical development of NGF.

Clinical features and pathological joint changes in dogs with erosive immune-mediated polyarthritis: 13 cases (2004–2012). Magen L. Shaughnessy, Susannah J. Sample, Carter Abicht, Caitlin Heaton, Peter Muir. JAVMA. November 2016;249(10):1156-1164. Quote: Objective: To evaluate the clinical features and pathological joint changes in dogs with erosive immune-mediated polyarthritis (IMPA). Design: Retrospective case series. Animals: 13 dogs with erosive IMPA [including two cavalier King Charles spaniels (15.4%)] and 66 dogs with nonerosive IMPA. Procedures: The medical record database of a veterinary teaching hospital was reviewed to identify dogs with IMPA that were examined between October 2004 and December 2012. For each IMPA-affected dog, information extracted from the medical record included signalment, diagnostic test results, radiographic findings, and treatments administered. Dogs were classified as having erosive IMPA if review of radiographs revealed the presence of bone lysis in multiple joints, and descriptive data were generated for those dogs. All available direct smears of synovial fluid samples underwent cytologic evaluation. The synovial fluid total nucleated cell count and WBC differential count were estimated and compared between dogs with erosive IMPA and dogs with nonerosive IMPA. Results: 13 of 79 (16%) dogs had erosive IMPA. Dogs with erosive IMPA had a mean ± SD age of 7.1 ± 2.4 years and body weight of 8.3 ± 3.4 kg (18.3 ± 7.5 lb). All 13 dogs had erosive lesions in their carpal joints. (See left carpus of an 8-year-old spayed female Cavalier King Charles Spaniel with subjectively moderate subchondral bone lysis accompanied by severe synovial swelling -- in x-ray at right).The estimated median synovial fluid lymphocyte count for dogs with erosive IMPA was significantly greater than that for dogs with nonerosive IMPA. All dogs received immunosuppressive therapy with leflunomide (n = 9), prednisone (3), or prednisone-azathioprine (1). Conclusions & Clinical Relevance: Results indicated erosive IMPA most commonly affected the carpal joints of middle-aged small-breed dogs. Further genetic analyses and analysis of lymphocyte-subsets are warranted for dogs with erosive IMPA.

Prevalence, duration and risk factors for appendicular osteoarthritis in a UK dog population under primary veterinary care. Katharine L. Anderson, Dan G. O’Neill, David C. Brodbelt, David B. Church, Richard L. Meeson, David Sargan, Jennifer F. Summers, Helen Zulch, Lisa M. Collins. Sci. Repts. April 2018;8:5641. Quote: Osteoarthritis is the most common joint disease diagnosed in veterinary medicine and poses considerable challenges to canine welfare. This study aimed to investigate prevalence, duration and risk factors of appendicular osteoarthritis in dogs under primary veterinary care in the UK. The VetCompassTM programme collects clinical data on dogs attending UK primary-care veterinary practices. The study included all VetCompassTM dogs under veterinary care during 2013. Candidate osteoarthritis cases were identified using multiple search strategies. A random subset was manually evaluated against a case definition. Of 455,557 study dogs, 16,437 candidate osteoarthritis cases were identified; 6104 (37%) were manually checked and 4196 (69% of sample) were confirmed as cases. Additional data on demography, clinical signs, duration and management were extracted for confirmed cases. Estimated annual period prevalence (accounting for subsampling) of appendicular osteoarthritis was 2.5% (CI95: 2.4–2.5%) equating to around 200,000 UK affected dogs annually. Risk factors associated with osteoarthritis diagnosis included breed (e.g. Labrador, Golden Retriever), being insured, being neutered, of higher bodyweight and being older than eight years. Duration calculation trials suggest osteoarthritis affects 11.4% of affected individuals’ lifespan, providing further evidence for substantial impact of osteoarthritis on canine welfare at the individual and population level. ... Prevalence estimate. The estimated annual period prevalence of osteoarthritis diagnosis in dogs under primary veterinary care in the UK during 2013 was 2.5% (CI95: 2.4–2.5%). Prevalence of the most frequently affected breeds was also calculated with the most prevalent breeds being large breeds, specifically: Golden Retriever (7.7% of all Golden retrievers), Labrador Retriever (6.1% of all Labradors), Rottweiler (5.4% of all Rottweilers) and German Shepherd Dog (4.9% of all German Shepherds). ... Cavalier King Charles (2.42%).

Spontaneous Septic Arthritis of Canine Elbows: Twenty-One Cases. Ben Mielke, Eithne Comerford, Kate English, Richard Meeson. Vet Comp Orthop Traumatol. November 2018;31(6):488-493. Quote: Objective: This study provides information on clinical features, diagnosis, treatment and associated risk factors of spontaneous septic elbow arthritis in the dog. Methods: Medical records between March 2007 and June 2015 were searched for cases of spontaneous septic elbow arthritis with a diagnosis based on clinical signs, arthrocentesis, cytological and microbiological analysis of elbow joint synovial fluid, radiography and outcome following treatment. Results: Twenty-one cases of septic arthritis were identified [including one cavalier King Charles spaniel]. Pre-existing osteoarthritis was present in 14/15 elbows for which diagnostic imaging was available. Although all cases had increased neutrophil count on synovial fluid cytology, culture was only positive in 12/21. Despite initial improvement in lameness scores (pre-treatment 9/10 [range: 1-10] versus post-treatment 3/10 [range: 1-5]), 11/12 had residual long-term lameness. Recurrence of infection was noted in 3/12 elbows for which long-term (>8 weeks) follow-up was available. There was an acute mortality rate of 2/21 associated with severe systemic sepsis. Clinical significance: Septic arthritis, even in the absence of pyrexia, should be considered as a major differential diagnosis in middle aged, large breed dogs, with pre-existing elbow arthritis, that suffer an acute onset lameness, with elbow joint effusion and discomfort. Antibiotic therapy alone was effective for treatment with high initial response rates. Chronic lameness post-treatment was common, and a high rate of recurrence was seen with 3/12 dogs suffering more than one episode.

Evaluation of the effects of undenatured type II collagen (UC-II) as compared to robenacoxib on the mobility impairment induced by osteoarthritis in dogs. Stabile M, Samarelli R, Trerotoli P, Fracassi L, Lacitignola L, Crovace A, et al. Vet. Sci. September 2019; doi: 10.3390/vetsci6030072. Quote: Osteoarthritis (OA) is a chronic disease that requires a multimodal therapeutic approach. The aim of this study was to evaluate the effects of undenatured type II collagen (UC-II) as compared to robenacoxib in dogs affected by OA. Our hypothesis was that the two compounds would be similar (non-inferiority) in improving mobility. To test this hypothesis, a complete orthopedic examination, x-ray and the Liverpool Osteoarthritis in Dogs (LOAD) survey were performed in dogs affected by OA before and after the treatments. The study was designed as a clinical, randomized, controlled and prospective study. Sixty client-owned dogs were randomized in the R group (n = 30, robenacoxib 1 mg/kg/day for 30 days) and in the UC-II group (n = 30, UC-II 1 tablet/day for 30 days). Thirty days after the beginning of the treatment (T30), the dogs were reassessed for the LOAD, MOBILITY and CLINICAL scores. Based on the data obtained from the study, a significant reduction in LOAD and MOBILITY scores was recorded between T0 and T30 with a similar magnitude among the two groups (R = 31.5%, p < 0.001; UC-II = 32.7%, p = 0.013). The results of this study showed that UC-II and robenacoxib were able to similarly improve mobility of dogs affected by OA.

The Use of Cannabidiol-Rich Hemp Oil Extract to Treat Canine Osteoarthritis-Related Pain: A Pilot Study. Lori Kogan, Peter Hellyer, Robin Downing. AHVMA J. March 2020;58(Spring):42-45. Quote: The objective of this 90-day pilot clinical trial was to assess the impact of a full-spectrum product containing hemp extract and hemp seed oil on dogs with chronic mal adaptive pain. A total of 37 dogs diagnosed with chronic maladaptive pain primarily as a result of osteoarthritis were enrolled in the study. The dogs were given an initial physical examination that included systematic pain palpation, mapping of pain patterns, informal gait analysis, metabolic profile, and owner interview. The same palpa tions and mappings were performed during each biweekly assessment to identify trends, chart progress, and inform dose adjustments. ... Among these 30 dogs, the dose of CBD needed to achieve a positive effect ranged from 0.3 up to 4.12 mg/kg BID. The 2 dogs in the study requiring the highest dose of the CBD product were both Cavalier King Charles spaniels (not related to one another), and neither of these dogs experienced any changes/elevations in liver enzymes. It is unclear why some patients responded to a very small dose of the CBD product (0.3 mg/kg per dose), whereas the majority required dosing in the range of 1 to 2 mg/kg per dose. ... The metabolic parameters were repeated at the end of the study. Of the 32 dogs that completed the study, 30 dogs demonstrated improved pain support. Of the 23 dogs in the study that were taking gabapentin at the time of enrollment, 10 dogs were able to discontinue the gabapentin, and an additional 11 dogs were able to have their daily dose reduced with the addition of the cannabidiol (CBD) oil. Conclusion: The addition of a hemp- derived CBD oil appears to positively affect dogs with chronic maladaptive pain by decreasing their pain, thereby improving their mobility and quality of life. The reduction in gabapentin dose may be the result of changes in analgesia and/or sedation with the addition of the hemp oil extract.

Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis. Federica Alessandra Brioschi, Federica Di Cesare, Daniela Gioeni, Vanessa Rabbogliatti, Francesco Ferrari, Elisa Silvia D’Urso, Martina Amari, Giuliano Ravasio. Animals. August 2020; doi: 10.3390/ani10091505. Quote: The aim of this study was to evaluate the efficacy of oral transmucosal (OTM) cannabidiol (CBD), in addition to a multimodal pharmacological treatment for chronic osteoarthritis-related pain in dogs. Twenty-one dogs were randomly divided into two groups: in group CBD (n = 9), OTM CBD (2 mg kg−1 every 12 h) was included in the therapeutic protocol (anti-inflammatory drug, gabapentin, amitriptyline), while in group C (n = 12), CBD was not administered. Dogs were evaluated by owners based on the Canine Brief Pain Inventory scoring system before treatment initiation (T0), and one (T1), two (T2), four (T3) and twelve (T4) weeks thereafter. Pain Severity Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0043) and T3 (p = 0.016). Pain Interference Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0007) and T4 (p = 0.004). Quality of Life Index was significantly higher in CBD group at T1 (p = 0.003). The addition of OTM CBD showed promising results. Further pharmacokinetics and long-term studies in larger populations are needed to encourage its inclusion into a multimodal pharmacological approach for canine osteoarthritis-related pain.

A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Chris D. Verrico, Shonda Wesson, Vanaja Konduri, Colby J. Hofferek, Jonathan Vazquez-Perez, Emek Blair, Kenneth Dunner Jr, Pedram Salimpour, William K. Decker, Matthew M. Halpert. Pain. September 2020; doi: 10.1097/j.pain.0000000000001896. Quote: Over the last 2 decades, affirmative diagnoses of osteoarthritis (OA) in the United States have tripled due to increasing rates of obesity and an aging population. Hemp-derived cannabidiol (CBD) is the major nontetrahydrocannabinol component of cannabis and has been promoted as a potential treatment for a wide variety of disparate inflammatory conditions. Here, we evaluated CBD for its ability to modulate the production of proinflammatory cytokines in vitro and in murine models of induced inflammation and further validated the ability of a liposomal formulation to increase bioavailability in mice and in humans. Subsequently, the therapeutic potential of both naked and liposomally encapsulated CBD was explored in a 4-week, randomized placebo-controlled, double-blinded study in a spontaneous canine model of OA. In vitro and in mouse models, CBD significantly attenuated the production of proinflammatory cytokines IL-6 and TNF-α while elevating levels of anti-inflammatory IL-10. In the veterinary study, CBD significantly decreased pain and increased mobility in a dose-dependent fashion among animals with an affirmative diagnosis of OA. Liposomal CBD (20 mg/day) was as effective as the highest dose of nonliposomal CBD (50 mg/day) in improving clinical outcomes. Hematocrit, comprehensive metabolic profile, and clinical chemistry indicated no significant detrimental impact of CBD administration over the 4-week analysis period. This study supports the safety and therapeutic potential of hemp-derived CBD for relieving arthritic pain and suggests follow-up investigations in humans are warranted.

Undenatured type II collagen mitigates inflammation and cartilage degeneration in healthy Labrador retrievers during an exercise regimen. Varney JL, Fowler JW, Coon CN. Transl. Anim. Sci. May 2021; doi: 10.1093/tas/txab084. Quote: The aim of this experiment was to evaluate the effect of undenatured type II collagen supplementation on inflammation and cartilage degeneration after exercise in healthy dogs. Forty healthy Labrador Retrievers (20 male/20 female; range 5-12 yr; average 8 yr) were sorted into two groups: undenatured type II collagen group receiving 40 mg UC-II (10 mg collagen type II/min. 3% undenatured type II collagen; Lonza Consumer Health, Inc.) and placebo group receiving 40 mg maltodextrin daily by capsule. After 2-wk loading, all dogs began an 11-wk endurance exercise regimen consisting of two weekly runs, starting at 5 km and increasing incrementally to 8 km, with one final 16 km run. Blood samples were collected at baseline, pre and post first 5 km run, and pre- and post-16 km run. Activity per kilometer was greater in male undenatured type II collagen vs. male placebo over all runs (P = 0.004), and average moving speed was greater in all undenatured type II collagen dogs compared with placebo over all runs (P < 0.001). Hematology analysis indicated that during the first insult, undenatured type II collagen dogs had a greater lymphocyte count (P < 0.001) and lymphocyte percentage (P = 0.001) vs. placebo dogs. Undenatured type II collagen dogs had a lesser neutrophil percentage (P = 0.042) and neutrophil to lymphocyte ratios (P = 0.001) compared to placebo dogs. For the final insult, undenatured type II collagen dogs had greater lymphocyte percentage (P = 0.013) and lesser mean corpuscular hemoglobin concentration (P = 0.043) compared with placebo dogs. Both groups had significant changes between timepoints for several hematological parameters. Biomarker IL-6 was lesser in undenatured type II collagen dogs compared with placebo at post 5 km (P = 0.037). Cartilage oligomeric matrix protein (COMP) was lesser in undenatured type II collagen dogs at post 16 km (P = 0.023), and only the placebo dogs had a significant increase in COMP from pre to post 16 km (P = 0.021). In summary, Labrador Retrievers supplemented with undenatured type II collagen had decreased inflammation and cartilage degeneration compared with nonsupplemented dogs during exercise.

The effect of oral administration of undenatured type II collagen on monosodium iodoacetate-induced osteoarthritis in young and old rats. Sahin E, Orhan C, Erten F, Saiyed Z, Azari EK, Durkee S, et al. Sci. Rep. April 2023; doi:
10.1038/s41598-023-33763-2. Quote: We investigated whether different doses of undenatured type II collagen (undenatured collagen, UC-II) help improve monosodium iodoacetate (MIA)-induced (osteoarthritis) OA in young and old rats. A total of 70 rats were divided into five groups: (1) control; (2) MIA (a single intra-articular injection of MIA); (3)–(5) MIA+ Undenatured Collagen with various oral doses (0.66, 1.33, and 2 mg/kg). The results showed that all doses of undenatured collagen in both age groups reduced knee diameter, while the two higher doses (1.33 mg/kg and 2 mg/kg) reduced the Mankin score and increased most gait measurements as early as day 14 compared to the MIA rats. However, the 2 mg/kg dose showed the best efficacy in improving Mankin score and gait measurements by 28 days post-OA induction. In young but not old rats, all doses of undenatured collagen reduced the Kellgren-Lawrence score compared to the MIA group. Undenatured collagen reduced the levels of most inflammatory and cartilage breakdown markers in serum and knee joint cartilage in both age groups. In conclusion, this data suggests that while all doses of undenatured collagen supplementation may ameliorate MIA-induced OA symptoms, the higher doses showed faster improvement in gait measurements and were more efficacious for overall joint health in rats.

Efficacy and safety of cannabidiol for the treatment of canine osteoarthritis: a systematic review and meta-analysis of animal intervention studies. Chanthawat Patikorn, Osot Nerapusee, Kumpanart Soontornvipart, Kanta Lawonyawut, Kachapong Musikpodok, Kanisorn Waleethanaphan, Puree Anantachoti. Front. Vet. Sci. September 2023; doi: 10.3389/fvets.2023.1248417. Quote: Introduction: Canine osteoarthritis (OA) is a degenerative disease with chronic inflammation of internal and external joint structures in dogs. Cannabis spp. contains cannabidiol (CBD), a substance known for various potential indications, such as pain relief and anti-inflammatory in various types of animals, including dogs with OA. As CBD is increasingly in the spotlight for medical use, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and safety of CBD in treating canine OA. Methods: We searched PubMed, Embase, Scopus, and CAB Direct for animal intervention studies investigating the effects of CBD for canine OA from database inception until February 28, 2023. Study characteristics and findings were summarized. A risk of bias in the included studies was assessed. Meta-analyses were performed using a random-effects model to estimate the effects of CBD on pain scores (0–10), expressed as mean difference (MD) and 95% confidence interval (95% CI). Certainty of evidence was assessed using GRADE. Results: Five articles were included, which investigated the effects of CBD in 117 dogs with OA. All studies were rated as having a high risk of bias. CBD products varied substantially, i.e., oral full-spectrum CBD oil in four studies, and isolated CBD oil and liposomal CBD oil in another study. Treatment duration varied from 4–12 weeks. Meta-analyses of three studies found that, in dogs with OA, treatment with oral full-spectrum CBD oil may reduce pain severity scores (MD; −0.60, 95% CI; −1.51 to 0.31, I2 = 45.64%, p = 0.19) and pain interference scores (MD; −1.52, 95% CI; −3.84 to 0.80, I2 = 89.59%, p = 0.20) but the certainty of evidence was very low. CBD is generally considered safe and well-tolerated in the short-run, with few mild adverse events observed, such as vomiting and asymptomatic increase in alkaline phosphatase level. Conclusion: CBD is considered safe for treating canine OA. CBD may reduce pain scores, but the evidence is very uncertain to conclude its clinical efficacy. High-quality clinical trials are needed to further evaluate the roles of CBD in canine OA.

Librela (Beransa) – Wonder Drug Or Disaster In The Making? Edward Bassingthwaighte. Dogs Naturally. October 2023. Quote: In my professional opinion, there is no way that Librela should ever be considered as a first treatment or intervention for arthritis in dogs.

A blinded, randomized and controlled multicenter field study investigating the safety and efficacy of long-term use of enflicoxib in the treatment of naturally occurring osteoarthritis in client-owned dogs. Josep Homedes, Marion Ocak, Sebastian Riedle, Marta Salichs. Frontiers in Vet. Sci. February 2024; doi: 10.3389/fvets.2024.1349901. Quote: Background Enflicoxib is a COX-2 selective NSAID shown to be efficacious and safe in the treatment of pain and inflammation associated with canine osteoarthritis (OA) in clinical studies of 6 weeks duration. Objective This prospective, multisite, blinded, randomized, placebo-controlled, parallel-group field study aimed to confirm the safety and efficacy of enflicoxib in long-term canine OA treatments. Animals A total of 109 client owned dogs with clinical and radiographic signs of OA for at least 3 weeks were enrolled with 78 dogs completing all study visits. Methods Dogs were randomized at a 3:1 ratio to receive enflicoxib (n = 83) or placebo (n = 26) once weekly during 6 months. Dogs underwent veterinary assessments from Day 0 to Day 189 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). Safety was assessed clinically and by repeated blood and urine sample analysis. The efficacy outcome measure was the treatment response according to the CSS and secondarily the treatment response according to the CBPI. The primary safety outcome was the incidence of adverse events (AEs) and secondarily the evolution of the clinical pathology parameters. Results Percentages of CSS responders for enflicoxib were 71.6; 74.6 and 71.6% on Days 44, 135 and 189 respectively, always showing statistically significant differences (p < 0.05) vs. placebo (41.7, 33.3, and 20.8% respectively). Treatment response according to owner assessments followed the same pattern, achieving significant differences compared to placebo after 2 weeks of treatment. The incidence and type of AEs were as described in previous enflicoxib studies of shorter duration and as for other NSAIDs, with no tendency to increase over time. No relevant changes in hematology, biochemistry or urine parameters were observed. Conclusions and clinical relevance Enflicoxib safety and efficacy profile is maintained after a long-term treatment, which together with its weekly administration, makes it a good alternative for the chronic treatment of dogs with naturally occurring OA.

Cannabidiol plus krill oil supplementation improves chronic stifle osteoarthritis in dogs: A double-blind randomized controlled trial. K. Soontornvipart, P. Wongsirichatchai, A. Pongphuwanun, K. Chatdarong, S. Vimolmangkang. Vet. J. August 2024; doi: 10.1016/j.tvjl.2024.106227. Quote: Osteoarthritis (OA) is the most common orthopedic disorder characterized by chronic inflammation and pain in dogs and cats. Cannabis spp. contains cannabidiol (CBD), a substance with pain relief and anti-inflammatory properties in different animals including dogs with OA. The use of CBD supplements has been increasingly intertwining in veterinary medicine. This study aimed to evaluate the clinical efficacy of CBD + krill oil-supplemented biscuit against canine OA. In total, 30 dogs with stifle OA were randomized and divided into the placebo, krill oil, and CBD + krill oil groups. The Canine Brief Pain Inventory questionnaire was used to evaluate the efficacy of each treatment against pain. Stifle temperature was monitored to identify degrees of stifle inflammation. Two and one dogs in the placebo group were excluded from the study due to worsening lameness and increased pain interference score (PIS) and pain severity score (PSS) at days 14 and 28, respectively. The PIS and PSS scores of the krill oil and CBD + krill oil groups gradually and significantly improved after two weeks of treatment. The CBD + krill oil group had better PIS and PSS scores than the placebo and krill oil groups. However, there was no statistically significant difference in the PIS and PSS scores between the krill oil and CBD + krill oil groups. The stifle temperature of the three groups at different periods did not significantly differ. In conclusion, CBD + krill oil supplements are safe against canine OA. CBD can reduce pain and inflammation. Highlights: • CBD + krill oil-supplemented biscuit significantly reduced pain and inflammation in OA dogs. • Krill oil or CBD + krill oil biscuits both reduced pain, with the latter showing slightly better results. • No side effects were observed when giving the dog the CBD + krill oil-supplemented biscuit.

A proposed framework for practical multimodal management of osteoarthritis in growing dogs. Denis J. Marcellin-Little, Donald A. Hulse, Janice L. Huntingford, Tamara Grubb, Matthew W. Brunke, Arielle Pechette Markley, Bethany Frank. Front. Vet. Sci. April 2025; doi: 10.3389/fvets.2025.1565922. Quote: Osteoarthritis (OA) is a ubiquitous problem affecting dog joints, particularly the hip, elbow, stifle, and spine. OA most often results from developmental orthopedic problems such as hip dysplasia, elbow dysplasia, and patellar luxation and from injuries to the cranial cruciate ligament. Several management approaches have been proposed to manage OA, including steps to modulate growth, physical activity, and exercise, nutrition and nutritional supplementation, medications, physical rehabilitation, and surgical procedures. This article is the first in a series of articles that propose steps for practical OA management in dogs at various life stages. The review presented here focuses on growing dogs. The text describes the early pathophysiology and diagnosis of OA. The physical, nutritional, analgesic, and surgical management options of OA in growing dogs are presented. The application of these management options is described for three dogs. The overall approach to the management of OA in growing dogs is discussed.

Musculoskeletal adverse events in dogs receiving bedinvetmab (Librela). Mike Farrell, Felix W. A. Waibel, Ines Carrera,  Giliola Spattini, Louise Clark, Robert J. Adams, Dirsko J. F. Von Pfeil, Ricardo J. R. De Sousa, Diego Bobis Villagrà, Maria Amengual-Vila, Annalisa Paviotti, Rob Quinn, Justin Harper, Stephen P. Clarke, Christopher J. Jordan, Michael Hamilton, Andy P. Moores, Mark Irwin Greene. Front. Vet. Sci. May 2025; doi: 10.3389/fvets.2025.1581490. Quote: Objectives: To conduct a specialist-led disproportionality analysis of musculoskeletal adverse event reports (MSAERs) in dogs treated with bedinvetmab (Librela™) compared to six comparator drugs with the same indication. Furthermore, to report the findings from a subset of dogs whose adverse event (AE) data underwent independent adjudication by an expert panel. Study design: Case–control study and case series analysis. Sample population: The European Medicines Agency’s EudraVigilance database (2004–2024) and 19 client-owned dogs. Methods: An EBVS® Veterinary Specialist in Surgery individually reviewed all MSAERs to Librela™, Rimadyl®, Metacam®, Previcox®, Onsior®, Galliprant®, and Daxocox® (2004–2024). The primary null hypothesis was that Librela’s MSAER rate would not exceed that of comparator drugs by more than 50%. The secondary hypothesis was that MSAER would surge and taper following the launch of new drugs. Results: The disproportionality analysis did not support the hypotheses. Ligament/tendon injury, polyarthritis, fracture, musculoskeletal neoplasia, and septic arthritis were reported ~9-times more frequently in Librela-treated dogs than the combined total of dogs treated with the comparator drugs. A review of 19 suspected musculoskeletal adverse events (MSAEs) by an 18-member expert panel unanimously concluded a strong suspicion of a causal association between bedinvetmab and accelerated joint destruction. Conclusion: This study supports recent FDA analyses by demonstrating an increased reporting rate of musculoskeletal adverse events in dogs treated with Librela. Further investigation and close clinical monitoring of treated dogs are warranted. Impact: Our findings should serve as a catalyst for large-scale investigations into bedinvetmab’s risks and pharmacovigilance.

Commentary: Musculoskeletal adverse events in dogs receiving bedinvetmab (Librela). Matthew Warren Brunke, Curtis Wells Dewey. Front. Vet. Sci. July 2025; doi: 10.3389/fvets.2025.1628681.

Rapidly progressive osteoarthritis (RPOA) in companion animals treated with bedinvetmab (Librela™): an expected pathophysiological phenomenon or a cause for concern? Ali Mobasheri, Peter Hanson, Jonathan Larkin. Front. Vet. Sci. August 2025; doi: 10.3389/fvets.2025.1640217.  Quote: The advent of anti-nerve growth factor (NGF) monoclonal antibodies, such as bedinvetmab (Librela™), has marked a significant advancement in the management of osteoarthritis (OA) pain in dogs. First approved for use in October 2020 (EU) and May 2023 (U.S.), bedinvetmab offers a novel mechanism of action by targeting NGF, a key mediator in pain pathways, thereby providing relief for canine OA patients.While clinical trials have demonstrated the efficacy and safety of bedinvetmab, post-marketing surveillance has brought to light reports of adverse events, including neurological signs such as ataxia, seizures, and paresis, as well as musculoskeletal issues like lameness. Similar observations have been made in humans with OA treated with NGF neutralizing antibodies such as Tanezumab, which was originally developed for the treatment of human OA (6). These observations have collectively raised concerns about the potential for rapidly progressive OA (RPOA) in dogs undergoing treatment with bedinvetmab and humans receiving Tanezumab.The term RPOA has recently become a focal point in OA drug development, particularly following its association with the anti-NGF class of analgesics. RPOA is characterized by an accelerated deterioration of joint structures, leading to severe pain and functional impairment. In human medicine, RPOA has been associated with anti-NGF therapies, particularly when used concomitantly with nonsteroidal anti-inflammatory drugs (NSAIDs). The pathophysiology is thought to involve the suppression of pain signals, resulting in increased joint usage and subsequent structural damage. In veterinary medicine, the occurrence of RPOA in dogs treated with bedinvetmab remains a subject of investigation, monitoring and scrutiny. Recent case reports have reported rapid joint deterioration in dogs with elbow OA, following the initiation of bedinvetmab therapy. While case reports do not establish causality, they underscore the need for vigilance and further safety monitoring. The potential for RPOA in canine patients necessitates a cautious approach, especially regarding the concurrent use of NSAIDs, despite previous reports of acceptable safety. Although the safety of combining bedinvetmab with NSAIDs has not been fully established, some practitioners have employed short-term NSAID therapy during the initiation of bedinvetmab treatment. Given the experiences in human medicine, it may be prudent to limit or closely monitor such combinations until more definitive data are available.The identification of RPOA in dogs is unfortunately complicated by the lack of standardized diagnostic criteria and the variability in clinical presentations. Advanced imaging modalities and longitudinal structural studies are essential to differentiate RPOA from the natural progression of OA and to elucidate any potential links to anti-NGF therapies. This reminds us of the crucially important work that was carried out by the Nobel Prize winner Dr Rita Levi-Montalcini 1 and her colleagues almost 30 years ago, following the discovery of NGF, warning that NGF must be viewed as a multifactorial mediator that modulates more than pain responses, and is involved in neuroimmune-endocrine functions of vital importance to the regulation of physiological homeostatis, with potential involvement in pathological processes deriving from dysregulation of either local or systemic homeostatic balances (12). Any treatment that blocks the production and the signal of this vital growth factor requires long-term safety monitoring in humans and in companion animals.In conclusion, while bedinvetmab represents a promising option for managing OA pain in dogs, the emergence of adverse events resembling RPOA warrants careful consideration. Veterinarians should remain alert to signs of rapid joint deterioration in companion animals receiving bedinvetmab and they must report such cases to appropriate pharmacovigilance systems. Case reports are generally regarded as week in terms of scientific and medical evidence and we need better processes for integrating them into scientific and medical knowledge. The number of adverse cases associated with bedinvetmab use are generally low, but they do occur. Therefore further research is imperative to determine the incidence, risk factors, and pathogenesis of RPOA in canine patients, thereby ensuring the safe and effective use of anti-NGF therapies in veterinary practice.