Plasma concentration of thrombopoietin in dogs with immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is a common cause of severe thrombocytopenia in dogs. The pathogenesis of nonassociative, primary ITP (pITP) appears complex, with ill-defined thrombopoietic response. OBJECTIVES: Develop an immunoassay to measure plasma canine thrombopoietin (TPO) concentration and characterize TPO concentrations in dogs with pITP. ANIMALS: Forty-one healthy dogs, 8 dogs in an induced ITP model (3 control, 5 ITP), and 58 pITP dogs. METHODS: Recombinant canine TPO (rcTPO) was purchased and its identity confirmed by mass spectrometry. Monoclonal antibodies were raised to rcTPO and used to configure a sandwich ELISA using streptavidin-biotin detection. Assay performance, coefficients of variability, and healthy dog plasma TPO reference interval (RI) were determined, followed by assay of ITP samples. RESULTS: Assay dynamic range was 15 pg/mL (lower limit of detection) to 1000 pg/mL TPO, with limit of quantitation of 62 pg/mL. Plasma TPO RI was 0 to 158 pg/mL, with plasma TPO <62 pg/mL for 35/41 healthy dogs. All dogs with induced ITP developed marked increases in plasma TPO concentration. Peak values ranged from 515 to >6000 pg/mL. In contrast, only 2/58 pITP dogs had TPO values above RI. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma TPO concentration is paradoxically low at diagnosis for most dogs with pITP. This finding suggests that ineffective thrombopoiesis contributes to thrombocytopenia in pITP dogs and supports evaluating TPO receptor agonist treatment as used for pITP in humans. The TPO assay provides a new tool to study thrombopoiesis in pITP and other thrombocytopenic syndromes in dogs.

Prevalence of antibiotic use for dogs and cats in United States veterinary teaching hospitals, August 2020.

BACKGROUND: Awareness of prescribing practices helps identify opportunities to improve antibiotic use (AU). OBJECTIVES: To estimate AU prevalence in dogs and cats in U.S. veterinary teaching hospitals (VTHs) and identify antibiotic drugs commonly prescribed, indications for use, and evidence of bacterial infection. ANIMALS: Medical record data were collected from dogs and cats examined at 14 VTHs. METHODS: Data were collected from VTH medical records of dogs and cats examined by primary care, urgent care, emergency and critical care, internal medicine, and surgery services on a single day during August 13-September 3, 2020. Data included signalment; clinical service; inpatient or outpatient status; clinical conditions; diagnostic tests; evidence of bacterial infection; intended reason for AU; name and route of antibiotics prescribed. RESULTS: Of 883 dogs and cats, 322 (36.5%) were prescribed at least 1 antibiotic. Among 285 antibiotics administered systemically intended for treatment of infection, 10.9% were prescribed without evidence of infection. The most common class of antibiotics presribed for systemic administration was potentiated penicillin for dogs (115/346, 33.3%) and cats (27/80, 33.8%). For dogs and cats, first-generation cephalosporins (93/346, 26.9% and 11/80, 13.8%, respectively) and fluoroquinolones (51/346, 14.7% and 19/80, 23.8%, respectively) was second or third most-prescribed. Common AU indications included skin, respiratory, and urinary conditions, and perioperative use. CONCLUSIONS AND CLINICAL IMPORTANCE: Collaborative data collection provides a sustainable methodology to generate national AU prevalence estimates and bring attention to areas requiring additional research and detailed data collection. These efforts can also identify practice improvement opportunities in settings where future veterinarians are trained.

Evaluation of cytokine concentrations in a trehalose-stabilised lyophilised canine platelet product: a preliminary study.

BACKGROUND: Platelet transfusion is indicated for haemorrhage due to severe thrombocytopenia and for trauma associated coagulopathy. Febrile non-haemolytic transfusion reactions are a common complication of platelet transfusions in people and may be due to accumulated inflammatory cytokines. The present study aimed to determine the cytokine profile of a novel canine lyophilised platelet product following reconstitution, to assess the lyophilised platelets' activation response to physiological platelet agonists and to compare the cytokine profiles of basal and stimulated canine lyophilised platelets. METHODS: Cell counts and biochemical analyses were conducted following reconstitution. Cytokine concentrations were measured with a canine-specific multiplex immunocapture assay and with an electrochemiluminescent ELISA. Aliquots of reconstituted product from three separate vials were activated for 10 minutes under non-stirred conditions using adenosine diphosphate, thrombin or convulxin and their cytokine concentrations compared with unactivated samples. Flow cytometry and light-transmission aggregometry were used to evaluate the product's ability to express a procoagulant surface, degranulate and aggregate. Fresh platelet-rich plasma was used as a positive control. RESULTS: The product had a mean±SD particle count of 1.23±0.2×109/ml, contained platelets that expressed surface phosphatidylserine before agonist stimulation and was capable of aggregation in response to thrombin stimulation suggesting that the product may have haemostatic potential following in vivo administration. Cytokine concentrations measured by the immunocapture assay were generally low, while twofold to threefold increases relative to published intervals were noted for several cytokines using the ELISA. Concentrations of chemokine (C-X-C) motif ligand 8 and tumour necrosis factor-α were significantly increased as measured by the ELISA, but not by the immunocapture assay, while concentrations of KC-like were significantly increased as measured by the immunocapture assay. Stimulation with platelet agonists did not affect measured cytokine concentrations. CONCLUSION: Further study of the effects of administration of this lyophilised platelet product is warranted.

A Novel Microchip Flow Chamber (Total Thrombus Analysis System) to Assess Canine Hemostasis.

Hemorrhagic diseases are common in dogs. Current coagulation assays do not model all aspects of in vivo hemostasis and may not predict bleeding risk. The Total-Thrombus Analysis System (T-TAS) is a novel hemostasis assay system in which whole blood flows through microfluidic channels at defined shear rates to provide qualitative and quantitative evaluation of platelet function (PL-chip) and coagulation function (AR-chip). The present study evaluated the T-TAS in dogs with hereditary bleeding disorders and with acquired hemorrhagic syndromes (Group 1), and healthy controls (Group 2). Hereditary defects included von Willebrand's disease (VWD; n = 4), hemophilia A (n = 2), and canine Scott syndrome (n = 2). Acquired hemorrhagic disorders included neoplastic hemoperitoneum (n = 2) and acute hemorrhagic diarrhea syndrome (n = 1). Citrate anticoagulated samples were collected from diseased dogs (Group 1, n = 11) and controls (Group 2, n = 11) for coagulation screening tests, fibrinogen analyses, D-dimer concentration, antithrombin activity, von Willebrand Factor antigen, PFA-100 closure time (PFA-CT), and thromboelastography (TEG). Citrate and hirudin anticoagulated samples were used for T-TAS analyses at two shear rates. Qualitative thrombus formation in each chip was recorded using the T-TAS video camera. Numeric parameters, derived from the instrument software, included occlusion start time (OST; time to 10 kPa), occlusion time (OT; time to 60 kPa (PL-chip) or 80 kPa (AR-chip)), and area under the pressure curve (AUC). Correlations between continuous variables were evaluated by Spearman's rank. Continuous variables were compared between groups by Student's t-test or the Mann-Whitney U-test. Alpha was set at 0.05. In combined analyses of all dogs, significant correlations were identified between T-TAS variables, between the PFA-CT and PL-chip parameters and between TEG variables and AR-chip parameters. The prothrombin time correlated with the AR-chip AUC at both shear rates. In Group 1 dogs, the AR-chip AUC at low shear was significantly reduced compared with Group 2 dogs. Aberrant thrombus formation was seen in video images recorded from dogs with VWD and hemophilia A. The T-TAS AR-chip analysis distinguished dogs with bleeding risk compared to healthy controls. Initial evaluations of the T-TAS suggest it may aid characterization of hemostasis in patients at-risk of bleeding and assist with delineating bleeding phenotypes.

Effect of sample type on plasma concentrations of cell-free DNA and nucleosomes in dogs.

Cell-free DNA (cfDNA) and nucleosomes are two biomarkers of cell death and neutrophil extracellular trap formation that are increased in dogs with sepsis, immune-mediated haemolytic anaemia, cancer and following trauma and have diagnostic and prognostic values. cfDNA and nucleosomes are typically measured in plasma samples using DNA-specific fluorophores and ELISA assays, respectively, but their concentrations may be affected by pre-analytical variables such as sample type. The present study aimed to investigate the influence of sample type on the plasma cfDNA and nucleosome concentrations of a heterogeneous group of dogs presenting to an emergency room. Triplicate samples were collected into K2-ethylenediamine tetraacetic acid, 3.2% citrate and a specialised DNA stabilisation tube (Streck BCT), processed rapidly and frozen for batch analysis. Biomarker concentrations were compared between sample types by calculation of Spearman's correlation coefficients, and with Deming regression, Bland-Altman plots and the Friedman test. Overall, biomarker concentrations were highly correlated between the three sample types. The most concordant results were obtained using citrate samples and the DNA stabilisation tube. Matched cfDNA concentrations between the different sample types were significantly different but there was no significant difference between the nucleosome concentrations in any of the sample types. The present study suggests that cfDNA and nucleosomes can be successfully measured in various sample types, but distinct sample types do not produce interchangeable results. This argues for use of a consistent sample type within studies and suggests standardisation may be useful for the field.

Severity of Ionized Hypercalcemia and Hypocalcemia Is Associated With Etiology in Dogs and Cats.

Background: Calcium disorders are common in small animals, but few studies have investigated the etiology of ionized hypercalcemia and hypocalcemia in large populations. This study aimed to determine the incidence of ionized calcium disorders in dogs and cats treated at a tertiary referral clinic and to describe the associated diseases. Methods: An electronic database of electrolyte analyses conducted at the Cornell University Hospital for Animals from 2007 to 2017 was searched. Dogs and cats with ionized hypercalcemia or hypocalcemia were identified based on institution reference intervals. Duplicate case entries were removed. Medical records were reviewed to identify the cause of the calcium abnormality. Chi-squared analysis with Bonferroni adjustment was performed to compare frequencies of disease processes between mild and moderate-severe disturbances. Results: The database included 15,277 dogs and 3,715 cats. Hypercalcemia was identified in 1,641 dogs and 119 cats. The incidence of canine and feline hypercalcemia was 10.7 and 3.2%, respectively. Hypocalcemia was identified in 1,467 dogs and 450 cats. The incidence of canine and feline hypocalcemia was 9.6% and 12.1%, respectively. The most common pathologic causes of hypercalcemia in dogs were malignancy-associated (12.9%), parathyroid-dependent (4.6%) and hypoadrenocorticism (1.7%). In cats, malignancy-associated hypercalcemia (22.7%), kidney injury (13.4%) and idiopathic hypercalcemia (12.6%) were most common. Dogs presenting with moderate-severe hypercalcemia vs. mild hypercalcemia were significantly more likely to have hyperparathyroidism, malignancy-associated hypercalcemia or hypervitaminosis D, whereas cats were significantly more likely to have malignancy-associated hypercalcemia or idiopathic hypercalcemia. The most common pathologic causes of hypocalcemia in dogs were critical illness (17.4%), kidney injury (10.4%) and toxicity (7.5%). In cats, kidney injury (21.6%), urethral obstruction (15.1%), and critical illness (14.7%) were most frequent. Dogs presenting with moderate-severe hypocalcemia were significantly more likely to have hypoparathyroidism, kidney injury, eclampsia or critical illness, whereas cats were significantly more likely to have kidney injury, soft tissue trauma or urethral obstruction. Conclusions: Mild calcium disturbances are most commonly associated with non-pathologic or transient conditions. Malignancy-associated hypercalcemia is the most common cause of ionized hypercalcemia in dogs and cats. Critical illness and kidney injury are frequent causes of ionized hypocalcemia in both species.

ACVIM consensus statement on the diagnosis of immune-mediated hemolytic anemia in dogs and cats.

Immune-mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune-mediated erythrocyte destruction, and adverse consequences of long-term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence-based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.

Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 1-Defining populations at risk.

OBJECTIVES: Thrombosis is a well-recognized phenomenon in dogs and cats with a significant impact on morbidity and mortality. Despite growing awareness of thrombosis and increased use of antithrombotic therapy, there is little information in the veterinary literature to guide the use of anticoagulant and antiplatelet medications. The goal of Domain 1 was to explore the association between disease and thrombosis in a number of conditions identified as potential risk factors in the current veterinary literature, to provide the basis for prescribing recommendations. DESIGN: A population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. Revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines. Diseases evaluated included immune-mediated hemolytic anemia, protein-losing nephropathy, pancreatitis, glucocorticoid therapy, hyperadrenocorticism, neoplasia, sepsis, cerebrovascular disease, and cardiac disease. SETTINGS: Academic and referral veterinary medical centers. RESULTS: Of the diseases evaluated, a high risk for thrombosis was defined as dogs with immune-mediated hemolytic anemia or protein-losing nephropathy, cats with cardiomyopathy and associated risk factors, or dogs/cats with >1 disease or risk factor for thrombosis. Low or moderate risk for thrombosis was defined as dogs or cats with a single risk factor or disease, or dogs or cats with known risk factor conditions that are likely to resolve in days to weeks following treatment. CONCLUSIONS: Documented disease associations with thrombosis provide the basis for recommendations on prescribing provided in subsequent domains. Numerous knowledge gaps were identified that represent opportunities for future study.

Multicenter in vitro thromboelastography and thromboelastometry standardization.

OBJECTIVE: To establish and compare the repeatability and reproducibility of activated thromboelastography (TEG) and thromboelastometry (ROTEM) assays. DESIGN: Multicenter in vitro test standardization. SETTING: Veterinary academic centers. ANIMALS: Test samples were obtained from normal, healthy dogs. Sixty identical 5 mL aliquots of canine platelet-rich plasma collected by apheresis, frozen in 6% dimethyl sulfoxide, were tested initially. Sixty identical 6 mL aliquots of canine fresh frozen plasma with admixed cryoprecipitate were subsequently evaluated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Frozen study samples, quality controls, reagents, and consumables were distributed to participating centers (7 TEG and 3 ROTEM). TEG centers analyzed study samples with kaolin and tissue factor activated assays; ROTEM centers ran proprietary ellagic acid activated and tissue factor activated assays. All machines underwent quality control prior to sample analysis. Within- and between-center coefficients of variation (CVs) were calculated and compared using Mann-Whitney tests and calculation of intraclass correlation coefficients. Within and between centers, individual parameters for both TEG and ROTEM assays were comparable. Both within-center and between-center CVs varied markedly (0.7-120.5% and 1.4-116.5%, respectively) with assay type, instrument, and parameter. CVs for equivalent parameters were not significantly different between the 2 platforms. Intraclass correlation coefficients suggested moderate agreement between centers. In general, individual parameter CVs for platelet-rich plasma samples were lower in TEG centers, while CVs for canine fresh frozen plasma with admixed cryoprecipitate samples were lower in ROTEM centers. CONCLUSIONS: More variation within and between centers was identified than anticipated, but some parameters such as alpha angle were repeatable and reproducible. Sample types for future multicenter standardization efforts will require further optimization and may need to be adapted separately to each platform. Individual centers using viscoelastic tests for evaluation and management of clinical patients should take steps to minimize preanalytical and analytical sources of variation.

Multivariable analysis of the association between electrolyte disturbances and mortality in cats.

OBJECTIVES: Electrolyte disorders have been individually associated with mortality in small populations of cats with specific conditions, but the associations and interactions between electrolyte disturbances and outcome have not been evaluated in a large, heterogeneous population. It was hypothesized that abnormalities of sodium, chloride, potassium and calcium concentrations would be independently and proportionately associated with death from natural causes and with all-cause mortality in cats. METHODS: An electronic database containing 7064 electrolyte profiles was constructed to assess the association between disorders of sodium, potassium, corrected-chloride and ionized calcium concentrations with non-survival by multivariable modelling. A second database containing 2388 records was used to validate the models constructed from the first database. RESULTS: All four electrolytes assessed had non-linear U-shaped associations with case fatality rates, wherein concentrations clustered around the reference interval had the lowest case fatality rates, while progressively abnormal concentrations were associated with proportionately increased risk of non-survival (area under the receiver operator characteristic curve [AUROC] 0.689) or death (AUROC 0.750). CONCLUSIONS AND RELEVANCE: Multivariable modelling suggested that these electrolyte disturbances were associated with non-survival and with death from natural causes independent of each other. The present study suggests that measurement of electrolyte concentrations is an important component of the assessment of cats in emergency rooms or intensive care units. Future studies should focus on confirming these associations in a prospective manner accounting for disease severity.

Measurement of plasma cell-free DNA concentrations in dogs with sepsis, trauma, and neoplasia.

OBJECTIVES: To determine if cell-free DNA (cfDNA) was identifiable in canine plasma, to evaluate 3 techniques for the measurement of plasma cfDNA concentrations in dogs presented to an emergency service, and to compare the plasma cfDNA concentrations of healthy dogs to those with sepsis, trauma, and neoplasia. DESIGN: Retrospective study of banked canine plasma samples collected between May 2014 and December 2014. SETTING: Dogs presented to the emergency service of a university veterinary teaching hospital. ANIMALS: Plasma cfDNA was measured on residual plasma samples obtained from 15 dogs with sepsis, 15 dogs with moderate-severe trauma, 15 dogs diagnosed with a sarcoma. Plasma cfDNA was also measured in 15 healthy dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Assay linearity, repeatability, and reproducibility were evaluated. Quantification of cfDNA was performed in duplicate on diluted citrated plasma and following DNA purification using 2 fluorescence assays (SYBR-Gold; Quant-iT) and by ultraviolet absorbance spectroscopy. Fluorescence intensities (FIs) were converted to cfDNA concentrations using standard curves. Median FI values and cfDNA concentrations were compared to healthy controls using the Kruskal-Wallis test, with adjustment for multiple comparisons. Alpha was set at 0.05. Both assays had excellent linearity, and acceptable repeatability and reproducibility. Compared to controls, plasma cfDNA concentrations were significantly increased in dogs with sepsis or moderate-severe trauma with both assays (P ≤ 0.003). Dogs with neoplasia had significantly increased cfDNA concentrations with the Quant-iT assay only (P = 0.003). When measurements were performed on purified DNA, only dogs with moderate-severe trauma had significantly increased cfDNA concentrations (P < 0.001; SYBR-Gold assay). CONCLUSIONS: cfDNA can be readily identified in canine plasma using 2 fluorescence assays. DNA extraction offers no advantage over direct measurement. Compared to healthy controls, dogs with sepsis or moderate-severe trauma have significantly increased plasma cfDNA concentrations.

Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs.

Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher's exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.

Syntaxin 8 regulates platelet dense granule secretion, aggregation, and thrombus stability.

Platelet secretion not only drives thrombosis and hemostasis, but also mediates a variety of other physiological and pathological processes. The ubiquitous SNARE machinery and a number of accessory proteins have been implicated in regulating secretion in platelet. Although several platelet SNAREs have been identified, further members of the SNARE family may be needed to fine-tune platelet secretion. In this study we identified expression of the t-SNARE syntaxin 8 (STX8) (Qc SNARE) in mouse and human platelets. In mouse studies, whereas STX8 was not essential for α-granule or lysosome secretion, Stx8(-/-) platelets showed a significant defect in dense granule secretion in response to thrombin and CRP. This was most pronounced at intermediate concentrations of agonists. They also showed an aggregation defect that could be rescued with exogenous ADP and increased embolization in Stx8(-/-) mice in vivo consistent with an important autocrine and paracrine role for ADP in aggregation and thrombus stabilization. STX8 therefore specifically contributes to dense granule secretion and represents another member of a growing family of genes that play distinct roles in regulating granule release from platelets and thus platelet function in thrombosis and hemostasis.

RhoG protein regulates platelet granule secretion and thrombus formation in mice.

Rho GTPases such as Rac, RhoA, and Cdc42 are vital for normal platelet function, but the role of RhoG in platelets has not been studied. In other cells, RhoG orchestrates processes integral to platelet function, including actin cytoskeletal rearrangement and membrane trafficking. We therefore hypothesized that RhoG would play a critical role in platelets. Here, we show that RhoG is expressed in human and mouse platelets and is activated by both collagen-related peptide (CRP) and thrombin stimulation. We used RhoG(-/-) mice to study the function of RhoG in platelets. Integrin activation and aggregation were reduced in RhoG(-/-) platelets stimulated by CRP, but responses to thrombin were normal. The central defect in RhoG(-/-) platelets was reduced secretion from α-granules, dense granules, and lysosomes following CRP stimulation. The integrin activation and aggregation defects could be rescued by ADP co-stimulation, indicating that they are a consequence of diminished dense granule secretion. Defective dense granule secretion in RhoG(-/-) platelets limited recruitment of additional platelets to growing thrombi in flowing blood in vitro and translated into reduced thrombus formation in vivo. Interestingly, tail bleeding times were normal in RhoG(-/-) mice, suggesting that the functions of RhoG in platelets are particularly relevant to thrombotic disorders.

Nutraceutical therapies for degenerative joint diseases: a critical review.

There is growing recognition of the importance of nutritional factors in the maintenance of bone and joint health, and that nutritional imbalance combined with endocrine abnormalities may be involved in the pathogenesis of osteoarthritis (OA) and osteochondritis dissecans (OCD). Despite this, dietary programs have played a secondary role in the management of these connective tissue disorders. Articular cartilage is critically dependent upon the regular provision of nutrients (glucose and amino acids), vitamins (particularly vitamin C), and essential trace elements (zinc, magnesium, and copper). Therefore, dietary supplementation programs and nutraceuticals used in conjunction with non-steroidal, anti-inflammatory drugs (NSAIDs) may offer significant benefits to patients with joint disorders, such as OA and OCD. This article examines the available clinical evidence for the efficacy of nutraceuticals, antioxidant vitamin C, polyphenols, essential fatty acids, and mineral cofactors in the treatment of OA and related joint disorders in humans and veterinary species. This article also attempts to clarify the current state of knowledge. It also highlights the need for additional targeted research to elucidate the changes in nutritional status and potential alterations to the expression of plasma membrane transport systems in synovial structures in pathophysiological states, so that current therapy and future treatments may be better focused.