ArticleLiterature Review

Systematic Review of Efficacy of Nutraceuticals to Alleviate Clinical Signs of Osteoarthritis

Wiley
Journal of Veterinary Internal Medicine
Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Various treatments of osteoarthritis (OA) have been described, including use of nutraceuticals. To review systematically the literature about the effects of nutraceuticals on clinical signs of pain or abnormal locomotion in horses, dogs, and cats, and to discuss methodological aspects of trials and systematic reviews. A systematic search of controlled trials evaluating the impact of nutraceuticals on OA in horses, dogs, and cats was performed, using Medline, CAB Abstracts, and Google Scholar. Scientific evidence was evaluated by means of criteria proposed by the Food and Drug Administration (FDA), and a scoring system adapted from both the CONsolidated Standards of Reporting Trials (CONSORT) statement and recommendations for assessing trials by the Center of Evidence Based Medicine of Oxford. Twenty-two papers were selected and reviewed, with 5 studies performed in horses, 16 in dogs, and 1 in cats. The strength of evidence was low for all nutraceuticals except for omega-3 fatty acid in dogs. There were limited numbers of rigorous randomized controlled trials and of participants in clinical trials. The evidence of efficacy of nutraceuticals is poor, with the exception of diets supplemented with omega-3 fatty acids in dogs. Greater access to systematic reviews must be part of the objectives of the veterinary science in the future. Their reporting would be improved by internationally agreed-upon criteria for standards and guidelines.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Three previous systematic reviews on the treatment of animal OA revealed a disappointing quantity and quality of scientific evidence regarding fortified therapeutic diets and nutraceuticals [12][13][14]. The evidence from these three systematic reviews on the use of these products was not strong enough to adopt or support meaningful recommendations. ...
... A meta-analysis scale "analgesic efficacy" was also constructed in the form of a simple categorisation (see below) of the effect of the treated group vs. control group, temporal (within-group) improvement and non-effect. The assessment grids were developed based on the models used in three previous systematic reviews [12][13][14], in compliance with ARRIVE recommendations (Animal Research: Reporting In Vivo Experiments; [15]), CONSORT (Consolidated Standards of Reporting Trials; [16]) and CAMARADES (Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies; [17,18]). Finally, the study was registered on the international prospective register of systematic reviews PROSPERO (www.crd.york.ac.uk/prospero/; accessed on 4 February 2022, CRD42021279368) whose educational tools guide the systematic review process. ...
... Both scales were established following the review of methodologies presented in previous articles, including three systematic reviews assessing the benefits of enriched therapeutic diets and nutraceuticals in canine OA [12][13][14] (Materials and Methods). They were subsequently successful for face, content and construct validity. ...
Article
Full-text available
With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.
... It causes joint pain, swelling, stiffness, and restricted movement of the joint. It is a prevalent cause of lameness in equine species and is also common in dogs and older cats (Vandeweerd et al. 2012;Corbee et al. 2013). In cats, dogs, and horses, nonsteroidal anti-inflammatory drugs (NSAIDs) are the basic treatment for OA. ...
... In cats, dogs, and horses, nonsteroidal anti-inflammatory drugs (NSAIDs) are the basic treatment for OA. Corticosteroids, polysulfated glycosaminoglycans, or hyaluronic acid (a nonsulfated glycosaminoglycan) injections are also employed in horses and dogs (Vandeweerd et al. 2012). ...
... Based on a review of scientific literature, Vandeweerd et al. (2012) concluded that omega-3 fatty acids significantly alleviate the clinical signs of OA in dogs, unlike other nutraceuticals, whose evidence of efficacy is poor. Dogs fed diets containing a total of 0.8% (baseline therapeutic food), 2.0%, and 2.9% EPA and DHA on a dry matter (DM) basis were evaluated for the symptomatic relief of OA . ...
Chapter
Nutraceuticals are bioactive compounds that may be used to prevent and treat diseases and to promote health. They include vitamins, minerals, and other bioactive chemical compounds, such as omega fatty acids. This chapter discusses the potential benefits of omega fatty acids to animals, including their use in treating osteoarthritis, atopy, inflammatory bowel disease and other inflammatory conditions, renal and cardiovascular diseases, lipid and metabolic disorders, and cancer. Additionally, the effects of omega fatty acids on neurological development, behavior, and cognitive function are summarized along with recommended dosing levels and potential adverse effects such as immune function impairment, platelet dysfunction, and altered glucose and lipid metabolism.
... The term "nutraceutical" is defined as "a substance produced in purified or extracted form, which, when administered orally to patients, provides them the necessary elements for their structure and normal function to better their health and well-being" (Boothe 1997). Many nutraceuticals are marketed towards the prevention or treatment of canine OA; however, they are not subject to any regulation due to the lack of evidentiary efficacy reported (Vandeweerd et al. 2012, Comblain et al. 2017. Two previous systematic reviews of veterinary nutraceuticals concluded that there was evidence for clinical efficacy of omega-3 fatty acids in the treatment of canine OA (Vandeweerd et al. 2012, Barbeau-Grégoire et al. 2022, and the more recent of these also found a weak efficacy of collagen (Barbeau-Grégoire et al. 2022). ...
... Many nutraceuticals are marketed towards the prevention or treatment of canine OA; however, they are not subject to any regulation due to the lack of evidentiary efficacy reported (Vandeweerd et al. 2012, Comblain et al. 2017. Two previous systematic reviews of veterinary nutraceuticals concluded that there was evidence for clinical efficacy of omega-3 fatty acids in the treatment of canine OA (Vandeweerd et al. 2012, Barbeau-Grégoire et al. 2022, and the more recent of these also found a weak efficacy of collagen (Barbeau-Grégoire et al. 2022). Neither found evidence that glucosamine hydrochloride and chondroitin sulphate provided any beneficial effects in the treatment of canine OA. ...
Article
Full-text available
Osteoarthritis is a progressive degenerative disease process that affects a significant proportion of the canine population, impacting these animals' quality of life. Currently, there is no cure and treatment consists of managing the clinical signs of pain and reduced mobility. There are many treatments for canine osteoarthritis and in this review we discuss the evidence base behind non‐pharmaceutical, non‐surgical treatments of this disease. These treatments include weight management, nutraceuticals, acupuncture, physiotherapies such as therapeutic exercise, hydrotherapy as well as other therapeutic modalities including photobiomodulation therapy, electromagnetic field therapy and others.
... First, many of these articles were review or systematic review articles, not clinical studies. 4,8,[11][12][13][45][46][47] Second, 4 studies were excluded because the test treatments contained multiple ingredients (mixed with turmeric/curcumin) and hence these studies could not conclude effects on only turmeric/curcumin extracts. [48][49][50][51] Other studies were disqualified due to lack of standardized treatment or control groups on which to base conclusions on efficacy of turmeric/curcumin extracts. ...
... Studies reviewed noted changes in gait or ground reactive forces but the use of standardized grading systems for canine OA was lacking. 45 The safety of using turmeric/curcumin in OA canine patients also needs further study. Dejonckheere listed several contraindications in certain breeds and co-morbidities. ...
Article
Full-text available
The objective of this systematic review was to determine the efficacy of using turmeric (Curcuma longa) in veterinary patients for control of osteoarthritis (OA). The literature search was conducted using three electronic databases and a university library. Keywords searched included “turmeric”, “curcumin” and “osteoarthritis”. There were 24 experimental model studies in laboratory species that used turmeric as a treatment for OA and met inclusion criteria. These studies compared a turmeric/curcumin treated group to placebo (or no treatment) control group. The meta-analysis based on the reported statistical significance (p-values) concluded an overall p-value of 3.0×10-28, which demonstrated turmeric/curcumin was highly effective in improving OA in these studies for the parameters measured. Meta-analysis using random-effects model on the four most reported outcome measurements (TNF-α, IL-1β, NF-kβ, MMG) also concluded effectiveness of turmeric/curcumin in improving OA conditions (all p-values < 0.001). The positive results in animal model studies from this systematic review and meta-analysis suggest that turmeric/curcumin may be of benefit for companion animals with OA, and supports further investigation of its use as part of food therapy and/or herbal formulations with randomized controlled clinical studies.
... Unfortunately, it is very hard to evaluate the evidence provided by these studies as they report different therapy durations, sometimes include other active ingredients, and the drugs used are produced by different manufacturers, thereby having different compositions. Consequently, the evidence of nutraceutical efficacy in alleviating DJD-related clinical signs in dogs is poor, with the exception of omega-3 fatty acids (Bhathal et al., 2017, Vandeweerd et al., 2012. With regards to GLM, three studies reported an improvement whilst one study did not; however, since GLM contains ETA, it was suggested that part of its effect was due to that (Vandeweerd et al., 2012). ...
... Consequently, the evidence of nutraceutical efficacy in alleviating DJD-related clinical signs in dogs is poor, with the exception of omega-3 fatty acids (Bhathal et al., 2017, Vandeweerd et al., 2012. With regards to GLM, three studies reported an improvement whilst one study did not; however, since GLM contains ETA, it was suggested that part of its effect was due to that (Vandeweerd et al., 2012). Interestingly, a later study also reported an objectively-assessed beneficial effect of a GLMenriched diet using objective primary outcomes (Rialland et al., 2012), however the evidence regarding GLM is still controversial. ...
Thesis
Full-text available
Degenerative joint disease (DJD) is one of the most common causes of chronic pain in cats. Two studies were designed to identify risk factors for DJD in 6-year-old cats by examining prospective data from a longitudinal cohort study, and compare the activity profiles and quality of life of cats with (cases) and without (controls) early owner-reported signs of impaired mobility using orthopaedic examination, accelerometry and owner-completed questionnaires (Feline Musculoskeletal Pain Index (FMPI), VetMetrica). Binomial logistic regression using backwards elimination identified four risk factors for increased owner- reported mobility impairment score in 6-year-old cats: entire neuter status at six months of age (OR=1.97, 95%CI 1.26–3.07), sustained trauma before six years of age (OR=1.85, 95%CI 1.3–2.6), outdoor access at six years of age (OR=1.67, 95%CI 0.96–2.9), and overweight/obese status at six years of age (OR=1.62, 95%CI 1.13–2.33). Case cats scored significantly lower than control cats for the FMPI (p=0.003) and the VetMetrica domain of comfort (p=0.002), but not vitality (p=0.009) or emotional wellbeing (p=0.018). Total pain (p<0.0001), crepitus (p=0.002) and thickening (p=0.003) scores were higher in case cats. Accelerometry differentiated cases from controls with a 90.9% accuracy. Risk factor analysis demonstrated that obesity, outdoor access, and a history of trauma predispose cats to developing DJD, whereas neutering appears to decrease that risk. Changes in joint health as detected by orthopaedic examination and accelerometry reflected owner-reported mobility changes, differentiating cats with early DJD-related signs from healthy cats, whilst the VetMetrica comfort domain score indicated an impaired quality of life of cats with early DJD compared to healthy cats. Being able to recognise signs of mobility impairment earlier would allow interventions aimed at slowing DJD progression, thereby improving feline health and welfare. These findings have identified that orthopaedic examination, FMPI and accelerometry are effective in identifying early DJD-related mobility changes in cats.
... < Glucosamine-chondroitin There is a paucity of good quality evidence to support glucosamine-chondroitin supplementation in cats. 87 One double-blinded, placebocontrolled trial has been published comparing the efficacy of meloxicam and glucosaminechondroitin in the management of cats with OA. 34 The product used in this study (glucosamine 225 mg; chondroitin sulphate 175 mg; N acetyl glucosamine 25 mg; ascorbic acid 2 mg; zinc sulphate 15 mg) was administered q12h for 6 weeks and then reduced to q24h for 4 weeks. 34 This study was under powered (n = 30) so significant conclusions could not be made about the results, but there was a trend for owner assessment scores to be maintained after the cats were started on the placebo and the glucosamine-chondroitin supplement was stopped. ...
... 93 There is, at this time, greater evidence for the benefit of EPA supplementation compared with glucosamine-chondroitin products in companion animals. 87,94,95 Two small studies have suggested some benefit for the use of omega-3 fatty acid supplementation in cats with DJD/OA. ...
Article
Practical relevance An understanding of the process of musculoskeletal ageing – which all senior and geriatric cats will experience – is vital to maintaining the health and welfare of our ageing cat population. Clinical challenges Assessment of the feline musculoskeletal system is not always straightforward. Diagnosis of impairment relies on input from owners and veterinarians in terms of visual observation, and clinical and orthopaedic examination, in addition to diagnostic imaging Audience This review is written for the primary care veterinary team. Aims The goals are to raise awareness and improve clinical diagnosis of musculoskeletal impairment as a result of ageing. The article also reviews therapeutic options and considers the evidence available for the prevention/deceleration of musculoskeletal ageing and impairment. Evidence base There is good evidence of a high prevalence of osteoarthritis (OA) and degenerative joint disease (DJD) in older cats. There is also good evidence to indicate that functional impairment and chronic pain are sequelae of musculoskeletal disease. However, there is a paucity of information for what is best practice for the management and treatment of musculoskeletal impairment in a clinical situation. There is also a lack of evidence on how prevention of central stimulation of the nervous system caused by musculoskeletal impairment and, in turn the development of chronic pain, can be avoided.
... OA is a common joint disease in veterinary clinics. It often occurs in horses, cattle and dogs, seriously affecting animal health and quality of life, and causing huge economic losses [2]. OA is very common in overweight and large breed dogs and lameness caused by OA is also the main reason for the early retirement of police dogs [3]. ...
... In recent years, studies have found that dietary supplements and herbs have played some positive and bene cial effects through anti-catabolic and anti-in ammatory effects [10,11]. They have attracted much attention because of their high safety, no adverse reactions, convenient management and prevention of the occurrence and development of diseases [2]. paragraph 3 ...
Preprint
Full-text available
Background Lameness caused by osteoarthritis (OA) is one of the main causes of disability in elderly dogs. Non-steroidal anti-inflammatory drugs (NSAIDs) are important tools in the treatment of canine OA. In recent years, due to the many side effects of NSAIDs, patients cannot tolerate or do not want to take the risk of NSAIDs. People are becoming more and more interested in new treatments for canine OA, and so-called nutritional supplements have emerged. Puerarin has a wide range of pharmacological activities and is often used as a clinical prescription drug and dietary supplement in China. However, the effect of puerarin on canine OA has not been evaluated. Therefore, the purpose of this study is to evaluate the anti-inflammatory and anti-cartilage degradation effects of puerarin in a canine OA model induced by anterior cruciate ligament transection (ACLT), and to detect the serum inflammatory factor interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels and cartilage degradation biomarker C-terminal telopeptides of collagen type II (CTX-II), cartilage oligomeric matrix protein (COMP) and chondroitin sulfate 846 epitope (CS 846) levels in serum and synovial fluid at different periods of puerarin administration. ResultsEight weeks after the administration, the veterinarian performed clinical and imaging evaluations to comprehensively evaluate the protective effect of puerarin on canine OA. Daily oral administration of 20 mg/kg puerarin can significantly inhibit the expression of IL-1β, IL-6 and TNF-α in serum within 8 weeks ( P < 0.05), and its anti-inflammatory effect is similar to oral celecoxib (negative control group). Puerarin has a certain protective effect on articular cartilage and can reduce the level of biomarkers CTX-II, COMP and CS 846 in serum and synovial fluid in the early stage of OA ( P < 0.05). In addition, the clinical scores and radiographs scores were significantly reduced after 8 weeks of puerarin treatment ( P < 0.05). Conclusions Canine OA cartilage may be mediated through anti-inflammatory, anti-metabolism and anabolic effects, and strongly down-regulate the inflammatory factors IL-1β, IL-6 and TNF-α and cartilage degradation biomarkers CTX-II, COMP and CS 846 are related, providing a good alternative therapy for OA.
... The use of nutraceuticals is becoming more and more common in veterinary medicine for prevention and treatment of common diseases, including OA [104,33,82,65,67,32,35,36,25]. New nutraceuticals or new use of old nutraceuticals are being evaluated for efficacy and safety in dogs with OA. ...
... PUFAs (EPA and DHA) protect activation of autophagy in chondrocytes by modulating mammalian targets of rapamycin (mTOR) signaling pathway, thereby exerting an anti-OA effect [106,32,35]. In a number of clinical studies, omega-3 fatty acids, singly or in combination with other anti-OA nutraceuticals, have been shown to improve OA in dogs and cats without side effects [21,104,30,84,85,64]. ...
... Although there has been no research demonstrating the definitive need for ALA, EPA, or DHA for maintenance in adult dogs, cats, or horses, the anti-inflammatory effects of n-3 FA have been of interest in helping manage osteoarthritis across all three species (Vandeweerd et al., 2012). A meta-analysis consisting of 72 canine and feline trials investigated the efficacy of several therapeutic diets and nutraceuticals for their effectiveness in the pain management of dogs and cats with osteoarthritis, and presented evidence for clinical analgesic efficacy of dietary n-3 FA (Barbeau-Grégoire et al., 2022). ...
Article
Both n-6 and n-3 fatty acids (FA) have numerous significant physiological roles for mammals. The interplay between these families of FA is of interest in companion animal nutrition due to the influence of the n-6:n-3 FA ratio on the modulation of the inflammatory response in disease management and treatment. As both human and animal diets have shifted to greater consumption of vegetable oils rich in n-6 FA, the supplementation of n-3 FA to canine, feline, and equine diets has been advocated for. Although fish oils are commonly added to supply the long-chain n-3 FA eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), a heavy reliance on this ingredient by the human, pet food, and equine supplement industries is not environmentally sustainable. Instead, sustainable sourcing of plant-based oils rich in n-3 α-linolenic acid (ALA), such as flaxseed and camelina oils, emerges as a viable option to support an optimal n-6:n-3 FA ratio. Moreover, ALA may offer health benefits that extend beyond its role as a precursor for endogenous EPA and DHA production. The following review underlines the metabolism and recommendations of n-6 and n-3 FA for dogs, cats, and horses and the ratio between them in promoting optimal health and inflammation management. Additionally, insights into both marine and plant-based n-3 FA sources will be discussed, along with the commercial practicality of using plant oils rich in ALA for the provision of n-3 FA to companion animals.
... The exclusion criteria were dogs which were receiving pain relief medication (for example non-steroidal anti-inflammatory drugs (NSAIDs)) for mobility or other health-related problems which prevented any mobility impairments, that would otherwise be expected to be evident on veterinary examination or gait analysis, from being masked. However, any dogs receiving nutraceuticals were included in the study as it has been previously suggested that this would not disguise any mobility impairments [20,57]. Specific questions regarding if dogs were receiving any medication, which could potentially hide mobility impairments, were included in the GenPup-M questionnaire. ...
Article
Full-text available
Objective To use a previously validated veterinary clinical examination sheet, Liverpool Osteoarthritis in Dogs (LOAD) questionnaire, combined with kinetic and kinematic gait analysis in dogs with/without mobility problems to demonstrate the capacity of a novel clinical metrology instrument (“GenPup-M”) to detect canine mobility impairments. Design Quantitative study. Animals 62 dogs (31 with mobility impairments and 31 without mobility impairments). Procedure The dogs’ clinical history was obtained from owners and all dogs underwent a validated orthopaedic clinical examination. Mobility impairments were diagnosed in the mobility impaired group based on clinical history and orthopaedic examination. Owners were asked to complete GenPup-M along with a previously validated mobility questionnaire (Liverpool Osteoarthritis in Dogs (LOAD)) to identify construct validity. As a test of criterion validity, the correlation between instrument scores and the overall clinical examination scores, along with force-platform obtained peak vertical forces (PVF) were calculated. GenPup-M underwent internal consistency and factor analysis. Spatiotemporal parameters were calculated for dogs with/without mobility impairments to define the gait differences between these two groups. Results Principal Component Analysis identified GenPup-M had two components with Eigenvalues >1 (“stiffness/ease of movement” and “willingness to be active/exercise”). Cronbach’s α was used to test internal consistency of GenPup-M and was found to be “good” (0.87). There was a strong, positive correlation between GenPup-M and LOAD responses (r² = 0.69, p<0.001) highlighting construct validity. Criterion validity was also shown when comparing GenPup-M to clinical examination scores (r² = 0.74, p<0.001) and PVF (r² = 0.43, p<0.001). Quantitative canine gait analysis showed that there were statistically significant differences between peak vertical forces (PVF) of mobility impaired and non-mobility impaired dogs (p<0.05). Analyses of PVF showed that non-mobility impaired dogs more evenly distributed their weight across all thoracic and pelvic limbs when compared to mobility impaired dogs. There were also consistent findings that mobility impaired dogs moved slower than non-mobility impaired dogs. Conclusion and clinical relevance GenPup-M is a clinical metrology instrument (CMI) that can be completed by dog owners to detect all mobility impairments, including those that are early in onset, indicating the versatility of GenPup-M to assess dogs with and without mobility impairments. Results of the study found that GenPup-M positively correlated with all three objective measures of canine mobility and consequently showed criterion and construct validity. Owner-reported CMIs such as GenPup-M allow non-invasive scoring systems which veterinary surgeons and owners can use to allow communication and longitudinal assessment of a dog’s mobility. It is anticipated that GenPup-M will be used by owners at yearly vaccinations/health checks, allowing identification of any subtle mobility changes, and enabling early intervention.
... A meta-analysis study suggested an association between more complications when using lipid emulsion infusion whose main component was PUFA O-6 in critically ill human patients [25]. In veterinary medicine, the benefits of using O-3 have been reported in animals with different diseases [9,[26][27][28]. Despite the limited number of studies about O-3 on animals with cancer, there are positive results such as longer survival times of dogs with stage III lymphoma treated with doxorubicin that were supplemented with O-3 and arginine [29]. ...
Article
Full-text available
A high-protein hypercaloric diet enriched with glutamine and omega-3 polyunsaturated fatty acids was called an onco-diet. The goal was to verify the modulation of the inflammatory response and body composition of female dogs with mammary tumor after mastectomy, during onco-diet consumption, using a randomized, double-blinded, clinical trial. Six bitches (average age of 8.6 years) were allocated into Control Group—diet without glutamine, EPA and DHA supplementation; and six bitches (10.0 years) were allocated into Test—diet enriched with glutamine and omega-3. Serum measurements of TNF-α, IL-6, IL-10, IGF-1, C-reactive protein and determination of body composition were performed at pre- and post-surgical times. Statistical tests were used to compare the nutrient intake and dietary effects on inflammatory variables between the diets. No differences in concentrations of different cytokines (p>0.05) and C-reactive protein (CRP) (p = 0.51) were observed between the groups. The test group had a higher concentration of IGF-1 (p<0.05), higher percentage of muscle mass (p<0.01) and lower body fat (p<0.01), but the difference was present from initial and throughout the study. Onco-diet, enriched with glutamine and omega-3, in the amounts evaluated in this study, was not sufficient to modulate the inflammation and body composition of female dogs with mammary tumors submitted to unilateral mastectomy.
... This musculoskeletal disease results in lameness, loss of joint function and mobility, chronic pain, and reduced quality of life [10]. The management of OA in dogs is a lifetime commitment, involving a multimodal approach based on relieving the symptoms of the disease by treating pain and inflammation, improving mobility and hence quality of life, whilst protecting joints from OA [11][12][13][14][15]. Non-steroidal anti-inflammatory drugs (NSAIDs) have been the medical cornerstone for the management of pain and inflammation in canine OA for many years [16,17] and preferential and selective cyclooxygenase-2 (COX-2) inhibitors have been developed to potentially reduce the risk of unwanted side effects caused by the inhibition of COX-1 [18,19]. ...
Article
Full-text available
Background This prospective, multisite, blinded, randomized, non-inferiority clinical study aimed to confirm the efficacy and safety of enflicoxib in the treatment of pain and inflammation associated with canine osteoarthritis. A total of 180 dogs were randomized to receive enflicoxib (n = 78), mavacoxib (n = 80) or placebo (n = 22). Dogs underwent veterinary assessments from day 0 to day 42 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). The primary efficacy endpoint was the overall CSS from day 0 to day 42. Results The overall CSS expressed as area under the curve demonstrated non-inferiority of enflicoxib compared to mavacoxib, and both showed superiority over placebo. At the end of the study, average CSS, and the percentage of CSS responders for enflicoxib (3.64 and 74%) and mavacoxib (4.49 and 68%), was superior to placebo (7.15 and 29%). A faster onset of action was observed for enflicoxib as superiority over placebo was evidenced from the first efficacy assessment (day 7) onwards for both parameters, whereas mavacoxib was only significantly different from day 14 onwards. According to the owner assessment, the percentage of CBPI responders was 90%, 79%, and 43% for dogs treated with enflicoxib, mavacoxib and placebo, respectively, and superiority over placebo was demonstrated for both active treatments. In all secondary parameters, non-inferiority of enflicoxib versus mavacoxib was confirmed. The dog’s quality of life improved in all groups, but only enflicoxib showed superiority versus placebo. When assessing severely affected dogs only, results were similar, thus confirming the efficacy of enflicoxib in all stages of canine OA. There were no differences between groups in the frequency of adverse events, which were most frequently mild affecting the gastrointestinal tract and recovered without treatment. Conclusions Enflicoxib is efficacious and safe for the treatment of pain and inflammation in any stage of canine osteoarthritis with a faster onset of action compared to mavacoxib.
... They took into account several treatments of osteoarthritis commonly used for treatment in horses, dogs, and cats. They reported low strength of evidence in most of the nutraceuticals [127]. Also, a common drawback with most of the studies was limited numbers of rigorous randomized controlled trials. ...
... With the recognition that pet owners are increasingly looking for botanical and "more natural" treatment options, as well as an increase in interest from the scientific veterinary community in the nutritional and medicinal use of herbal medicinal products, the expert group felt it important to include products and ingredients that have appropriate studies and evidence for OA treatment (101,102). The list is not complete but includes some of the more common product groups. ...
Article
Full-text available
The Canadian consensus guidelines on OA treatment were created from a diverse group of experts, with a strong clinical and/or academic background in treating OA in dogs. The document is a summary of the treatment recommendations made by the group, with treatments being divided into either a core or secondary recommendation. Each treatment or modality is then summarized in the context of available research based support and clinical experience, as the treatment of OA continues to be a multimodal and commonly a multidisciplinary as well as individualized approach. The guidelines aim to help clinicians by providing clear and clinically relevant information about treatment options based on COAST defined OA stages 1–4.
... Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association of efficacy in canine OA. Therefore, its management is based on relieving the symptoms of the disease by treating pain and inflammation, improving mobility and hence quality of life, whilst protecting joints from OA. [8][9][10][11] Nutritional supplementation, physiotherapy and weight management are essential to alleviate the symptoms of the disease, however, non-steroidal antiinflammatory drugs (NSAIDs) are still considered the medical cornerstone for the management of canine OA. 12,13 The pain associated with osteoarthritis is chronic 14 and long-term continuous NSAID treatment has been shown to be more efficacious than short-term treatment periods, with no evidence of any increase in NSAID-related side effects. 15 However, although the incidence is low in comparison to NSAID frequency of use, 16 gastrointestinal, hepatic and renal side effects may occur and should be monitored. ...
Article
Full-text available
Background: Enflicoxib is a new COX-2 selective NSAID intended for the treatment of pain and inflammation associated with canine osteoarthritis. Methods: A prospective, multisite, blinded, randomised, controlled, parallel-group field study was performed to determine the efficacy and safety of enflicoxib in canine osteoarthritis. A total of 242 dogs were randomised to receive enflicoxib at 4 or 2 mg/kg, mavacoxib at 2 mg/kg or placebo, orally. Enflicoxib and placebo were administered once weekly from day 0 to day 35. Mavacoxib was administered on D0 and day 14. Veterinarians assessed efficacy with a numerical rating scale and owners used the Canine Brief Pain Inventory. Results: After 6 weeks, enflicoxib at 4 mg/kg showed the highest percentage of responders as assessed by the veterinarians (68%) and the owners (84%), followed by mavacoxib (62and 83%, respectively), and enflicoxib at 2 mg/kg (57 and 80%, respectively). All treatments reached statistical significance versus placebo, which obtained success rates of 37% and 53%, respectively. No differences in the incidence of adverse reactions were detected among the different groups. Conclusions: Enflicoxib administered weekly for 6 weeks, at 4 mg/kg PO with an initial loading dose of 8 mg/kg, is efficacious and safe for the treatment of canine osteoarthritis.
... Dogs with mild to moderate OA were randomly allocated into Groups 1, 2, and 3. Dogs with severe OA were allocated into Group 4. These dogs required immediate medication with a known anti-inflammatory effect, and it would have not been ethical to place them in a trial with a one in three chance of receiving a placebo. The testing of many natural products/nutraceuticals is generally restricted to the use of dogs with mild to moderate clinical signs of OA [20,58,31,17,12,43,60]. The allocation of dogs to Group 4 provided an opportunity to compare responses in dogs with severe OA to mild or moderate OA in regards to severity of disease and responses of dogs to treatment. ...
... At present, there are multiple reviews focusing on the effects of dietary supplements in clinical signs of companion animal OA, as an attempt to clarify their effectiveness in the OA management [4,[19][20][21]. In this context, a previous literature review studied some nutraceutical effects in different OA animal models [22]. ...
Article
Full-text available
Glucosamine and chondroitin sulfate have been proposed due to their physiological and functional benefits in the management of osteoarthritis in companion animals. However, the scientific evidence for their use is still controversial. The purpose of this review was to critically elucidate the efficacy of these nutraceutical therapies in delaying the progression of osteoarthritis, evaluating their impact on the synovial knee joint tissues and biochemical markers in preclinical studies by systematically reviewing the last two decades of peer-reviewed publications on experimental osteoarthritis. Three databases (PubMed, Scopus and, Web of Science) were screened for eligible studies. Twenty-two articles were included in the review. Preclinical studies showed a great heterogeneity among the experimental designs and their outcomes. Generally, the evaluated nutraceuticals, alone or in combination, did not seem to prevent the subchondral bone changes, the synovial inflammation or the osteophyte formation. However, further experimental studies may be needed to evaluate their effect at those levels. Regarding the cartilage status and biomarkers, positive responses were identified in approximately half of the evaluated articles. Furthermore, beneficial effects were associated with the pre-emptive administrations, higher doses and, multimodality approaches with some combined therapies. However, additional studies in the long term and with good quality and systematic design are required.
... There are several published clinical and experimental studies evaluating the effect of nutraceuticals in either clinically healthy or sick dogs and cats, although a systematic evaluation is lacking in veterinary medicine. Only one systematic review evaluates the effect of various nutraceuticals on a particular disease (9), not the effect of a single nutraceutical on different disorders. ...
Article
Full-text available
Background/aim: The aim of this study is to identify and describe randomized controlled studies evaluating the therapeutic effect of EPA and DHA supplementation in companion animal diseases. Materials and methods: A systematic search was conducted in PubMed database and the information collected was summarized and evaluated according to the risk of bias, using the revised Cochrane tool (RoB2). Results: Twenty-three studies were eligible for inclusion: twenty performed in dogs and three in cats. A therapeutic benefit was found in canine allergic dermatitis, haircoat disorder, keratoconjunctivitis sicca, valvular disease, and canine and feline osteoarthritis. Dogs diagnosed with chronic heart failure and lymphoma and cats with allergic dermatitis also seem to benefit from supplementation with omega-3 fatty acids, but studies with improved methodological quality are needed to strengthen this evidence. Conclusion: EPA and DHA supplementation has proven benefits in the adjuvant treatment of various neoplastic and non-neoplastic diseases in dogs and cats.
... On the treatment side, one of the most up-to-date and clinically relevant issues consists in the multimodal approach to pain management, i.e., a combination of different therapeutic weapons, like analgesic drugs, acupuncture and physiotherapy techniques, as well as dietary interventions [29][30][31][32][33]. With regard to the last measure, calorie restriction and omega-3 fatty acids are the most investigated approaches to chronic pain in pets, particularly osteoarthritis pain [34,35]. ...
Article
Full-text available
The management of chronic pain is an integral challenge of small animal veterinary practitioners. Multiple pharmacological agents are usually employed to treat maladaptive pain including opiates, non-steroidal anti-inflammatory drugs, anticonvulsants, antidepressants, and others. In order to limit adverse effects and tolerance development, they are often combined with non-pharmacologic measures such as acupuncture and dietary interventions. Accumulating evidence suggests that non-neuronal cells such as mast cells and microglia play active roles in the pathogenesis of maladaptive pain. Accordingly, these cells are currently viewed as potential new targets for managing chronic pain. Palmitoylethanolamide is an endocannabinoid-like compound found in several food sources and considered a body’s own analgesic. The receptor-dependent control of non-neuronal cells mediates the pain-relieving effect of palmitoylethanolamide. Accumulating evidence shows the anti-hyperalgesic effect of supplemented palmitoylethanolamide, especially in the micronized and co-micronized formulations (i.e., micro-palmitoylethanolamide), which allow for higher bioavailability. In the present paper, the role of non-neuronal cells in pain signaling is discussed and a large number of studies on the effect of palmitoylethanolamide in inflammatory and neuropathic chronic pain are reviewed. Overall, available evidence suggests that there is place for micro-palmitoylethanolamide in the dietary management of chronic pain in dogs and cats.
... Currently, there are no disease-modifying therapies with strong evidence of efficacy in canine OA; therefore, its management is based on relieving symptoms and improving function [5,6]. Non-steroidal anti-inflammatory drugs (NSAIDs) produce analgesic, anti-inflammatory and antipyretic effects primarily by the inhibition of the expression of cyclooxygenase (COX) enzymes in cell membranes that are responsible for the synthesis of inflammatory mediators. ...
Article
Full-text available
Background This study aimed to evaluate the safety and efficacy of reduced-dosage ketoprofen with or without tramadol in dogs. Five healthy dogs receiving standard-dosage ketoprofen (2 mg/kg SC, then 1 mg/kg PO daily) comprised Group A. Twenty dogs with osteoarthritis were randomized to receive reduced-dosage ketoprofen (0.5 mg/kg SC once; 0.25 mg/kg PO daily) alone (Group B) or in combination with tramadol (5 mg/kg/day PO) (Group C). Treatments were administered for 28 days. Platelet aggregation time (PAT), gastrointestinal (GI) endoscopy and glomerular filtration rate (GFR) were performed up to 60 days after treatment initiation. Pain was scored using a validated clinical metrology instrument up to D120. Data were analyzed with general linear mixed model for repeated measures (α = 0.05). Results PAT was not different between groups but was increased with time for all groups. GI lesion scores were higher in Group A than Groups B and C (day 28; P = 0.005) and were increased with time for Group A (P = 0.005). GFR was lower in Group A than Groups B and C (day 28; P < 0.01) and were decreased with time for group A (P < 0.001). Standard-dosage ketoprofen administration resulted in clinically relevant adverse effects. Pain score decreased in both treated groups (B and C) from D0 to D28. Need of rescue analgesia from D29 to D120 was higher in Group B than in Group C (P = 0.039). Conclusions The long-term safety profile of reduced-dosage ketoprofen is similar whether the drug is administered alone or in combination with tramadol to dogs with osteoarthritis. Analgesic efficacy of the combination looks attractive.
... Among the treatment modalities, surgical and conservative ones are described. This second one is restricted to weight control, exercise restriction, physical rehabilitation, pain management and administration of nutraceutical supplements [17][18][19][20][21]. The surgical procedures described in animals are juvenile pubic sinfisiodesis [19,22], colocephalectomy [16], triple pelvic osteotomy [23], total hip replacement [19,24] and capsular denervation [3]. ...
Article
Osteoarthritis (OA) is a common disease in dogs with severe impact on their welfare. The multimodal management of OA includes feeding therapeutic diets and nutraceuticals to slow down OA progression. Collagen hydrolysates (CH) are a nutritional supplement that may exert anabolic effects on osteoarthritic joint cartilage as well as disease-modifying effects. After oral intake, CH is absorbed, mainly as amino acids, di- and tripeptides that are transported amongst others to the joint. In addition to reducing cartilage degradation, CH metabolites may reduce synovial inflammation and subchondral bone sclerosis during OA. Preliminary evidence in dogs suffering from the consequences of OA support the clinical efficacy of CH with reported reductions in lameness. However, effects on biomarker level of cartilage metabolism and inflammation are inconclusive. Additionally, current studies show a lack of standardised dosing regimens and the use of not validated outcomes. Future work should therefore elucidate further on the bioavailability of CH in dogs in order to establish adequate dosing recommendations. Furthermore, high-quality placebo-controlled randomised controlled trials are essential to dstudies have evaluated the cetermine the clinical efficacy of CH to reduce lameness, prevent OA progression and thereby improve the level of evidence.
Article
Full-text available
Background – Musculoskeletal diseases (MSDs) are an increasing issue as the lifespan of captive animals increases. Extracts of green-lipped mussels have been linked to alleviation of MSDs in domestic carnivores. Understanding their efficacy in non-domestic felids could provide another tool in improved welfare of aged individuals in collections. Methods – A within subject study design quantified steps per minute in each of 18 cats of 13 species before and after addition of AntinolTM to their diets. The age structure of four commonly kept subspecies of non-domestic cats was quantified to provide a demographic context to the need for managing aged individuals. Results – Each of the 18 cats exhibited a higher rate of steps per minute after addition of Antinol in their diet. A paired t-test showed that at the group level the rate of steps after uptake was significantly higher than before addition of Antinol to the diet. Limitations –While our results showed a strong significant increase, further studies that incorporate a placebo, more individuals, and more detailed metrics of mobility would provide a more detailed evidence-base for practitioners. Conclusion – Nutraceuticals may yield benefits to aged individual felids including species kept widely in European collections. Their use warrants further, detailed research in collections.
Chapter
Aging wild animals undergo many physiological changes that are not visible to their keepers. Changes in their digestive system render them less efficient at absorbing nutrients, changes in their brain reduce mental acuity and inflammation builds up throughout the body, especially the joints. Eventually symptoms will be observed such as muscle loss, decreased activity and longer reaction times, thereby impacting their welfare and eventually their quality of life. Some of these changes may be prevented or delayed by meaningful changes to the diet when an animal reaches 70% of their life span in captivity. Protein, vitamins and omega-3 fatty acids have shown high potential in the maintenance and improvement of the welfare and quality of life of geriatric wild animals.
Article
Full-text available
The recent global wave of organic food consumption and the vitality of nutraceuticals for human health benefits has driven the need for applying scientific methods for phytochemical testing. Advanced in vitro models with greater physiological relevance than conventional in vitro models are required to evaluate the potential benefits and toxicity of nutraceuticals. Organ-on-chip (OOC) models have emerged as a promising alternative to traditional in vitro models and animal testing due to their ability to mimic organ pathophysiology. Numerous studies have demonstrated the effectiveness of OOC models in identifying pharmaceutically relevant compounds and accurately assessing compound-induced toxicity. This review examines the utility of traditional in vitro nutraceutical testing models and discusses the potential of OOC technology as a preclinical testing tool to examine the biomedical potential of nutraceuticals by reducing the need for animal testing. Exploring the capabilities of OOC models in carrying out plant-based bioactive compounds can significantly contribute to the authentication of nutraceuticals and drug discovery and validate phytochemicals medicinal characteristics. Overall, OOC models can facilitate a more systematic and efficient assessment of nutraceutical compounds while overcoming the limitations of current traditional in vitro models.
Article
Full-text available
Background and objective: NXT15906F6 (TamaFlexTM) is a proprietary herbal composition containing Tamarindus indica seeds and Curcuma longa rhizome extracts. NXT15906F6 supplementation has been shown clinically effective in reducing knee joint pain and improving musculoskeletal functions in healthy and knee osteoarthritis (OA) subjects. The objective of the present study was to assess the possible molecular basis of the anti-OA efficacy of NXT15906F6 in a monosodium iodoacetate (MIA)-induced model of OA in rats. Methods: Healthy male Sprague Dawley rats (age: 8-9 wk body weight, B.W.: 225-308 g (n = 12) were randomly assigned to one of the six groups, (a) vehicle control, (b) MIA control, (c) Celecoxib (10 mg/kg B.W.), (d) TF-30 (30 mg/kg B.W.), (e) TF-60 (60 mg/kg B.W.), and (f) TF-100 (100 mg/kg B.W.). OA was induced by an intra-articular injection of 3 mg MIA into the right hind knee joint. The animals received either Celecoxib or TF through oral gavage over 28 days. The vehicle control animals received intra-articular sterile normal saline. Results: Post-treatment, NXT15906F6 groups showed significant (p < 0.05) dose-dependent pain relief as evidenced by improved body weight-bearing capacity on the right hind limb. NXT15906F6 treatment also significantly reduced the serum tumor necrosis factor-α (TNF-α, p < 0.05) and nitrite (p < 0.05) levels in a dose-dependent manner. mRNA expression analyses revealed the up-regulation of collagen type-II (COL2A1) and down-regulation of matrix metalloproteinases (MMP-3, MMP-9 and MMP-13) in the cartilage tissues of NXT15906F6-supplemented rats. Cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) protein expressions were down-regulated. Decreased immunolocalization of NF-κβ (p65) was observed in the joint tissues of NXT15906F6-supplemented rats. Furthermore, microscopic observations revealed that NXT15906F6 preserved MIA-induced rats' joint architecture and integrity. Conclusion: NXT15906F6 reduces MIA-induced joint pain, inflammation, and cartilage degradation in rats.
Article
Full-text available
Veterinary professionals are taught to recognize that “old age is not a disease.” However, clients may have the perception that older dogs and cats undergo an unavoidable physical, mental, and behavioral decline attributable simply to old age. The veterinary team’s role includes providing medical care and support to senior pets to maintain their quality of life, as well as supporting and educating clients on proper senior animal care and addressing any misconceptions about the aging process. These Guidelines describe a systematic approach to the healthcare of the senior pet that is based on an evidence-guided assessment of both healthy and unhealthy canine and feline patients. By using evidence-guided medicine, which may include conventional and integrative approaches as well as environmental management for the senior pet, the patient’s quality of life can be enhanced and potentially extended during this vulnerable life stage. Developing a senior program for the veterinary practice requires appropriate training of the entire healthcare team and includes a robust client education program that focuses on the wellbeing of the senior pet. Palliative and hospice care should be included in the education and information provided for both the veterinary team and the families of senior pets.
Article
Osteoarthritis of the elbow joint secondary to elbow dysplasia is common in dogs. Intraarticular radionuclide injection is thought to suppress both synovitis and inflammatory pain mediators in the joint which are not directly addressed by current treatments. This dose‐finding investigation was a longitudinal, prospective, experimental parallel group, post‐test study with repeated measures. Forty‐four dogs, with low to intermediate‐grade osteoarthritis, received a single injection into their most clinically affected elbow joint and were randomized into three treatment cohorts; 37 MBq, 64.75 MBq, or 92.5 MBq (normalized to the body surface area of a 22 kg dog) of 117mSn radiocolloid. Dogs were assessed monthly by owners, using the canine Brief Pain Inventory (cBPI), and at 1, 3, 6, 9, and 12 months intervals by investigators. Positive responses to treatment were observed by both owners and clinicians in all dose groups with the medium dose group having the highest and most durable response rate based on cBPI scores. The results of this study support the use of 117mSn radiocolloid as a primary treatment of osteoarthritis in low to intermediate‐grade osteoarthritis of the canine elbow.
Article
Animal sentience refers to the capacity of animals to feel both positive and negative emotions including that of pain. As veterinary health professionals, we have a medical and ethical duty to mitigate suffering from pain to the best of our ability. In 2014, the first Global Pain Council World Small Animal Veterinary Association (WSAVA) Guidelines for the Recognition, Assessment and Treatment of Pain was published and remains to this day one of the most relevant and widespread documents of its kind. The 2022 WSAVA Global Pain Management Guidelines evolves from the first document with updated scientific information reflecting major advances in veterinary pain medicine in the last decade. This document is designed to provide the user with easy‐to‐implement, core fundamentals on the successful recognition and treatment of pain in the day‐to‐day small animal clinical practice setting. It provides basic and practical information with an extensive reference list to guide those who want to further their knowledge on pain management. The 2022 WSAVA Global Pain Management Guidelines should be easily implemented regardless of practice setting and/or location for the promotion and advance of pain management and animal welfare.
Article
Full-text available
Background Lameness is one of the major causes of reduced physical performance and early retirement in working horses. TamaFlex™ (NXT15906F6) is a standardized synergistic anti‐inflammatory botanical formulation containing Tamarindus indica seed extract and Curcuma longa rhizome extract at a 2:1 ratio. Methods We conducted a 12‐week single‐center, randomized, blinded, placebo‐controlled trial demonstrating the efficacy of NXT15906F6 in horses with lameness grade 2–4 on the American Association of Equine Practitioners (AAEP) scale. Twenty‐two lame horses were supplemented with NXT15906F6 (2.5 gram/day) or placebo over a period of 84 days. Improvement in lameness over placebo was the primary endpoint, and changes in the levels of rheumatoid factor (RF), anti‐nuclear antibody (ANA), and anti‐cyclic citrullinated peptide (ACC‐peptide) in serum, and pro‐inflammatory cytokines including interleukin (IL‐1β and IL‐6), tumor necrosis factor‐α (TNF‐α) and prostaglandin‐E2 (PGE2) in serum and synovial fluid were the secondary endpoints. Results NXT15906F6 exhibited significant relief from lameness in a time‐dependent manner. NXT15906F6 also reduced levels of ANA, PGE2, IL‐1β, TNF‐α and IL‐6. Moreover, NXT15906F6 supplementation is safe and tolerable in alleviating joint pain in lame horses, and protects the joints from further degradation by reducing pro‐inflammatory mediators. Conclusion NXT15906F6 significantly reduces the lameness during walking and trotting, leading to an improvement in their joint flexibility, health, and working performances.
Article
The typical canine rehabilitation patient with orthopedic disease may differ in its nutritional needs, with the assumption that most patients will be on a complete and balanced commercial dog food that is not enriched with agents for ameliorating their condition. For a significant number of rehabilitation patients, obesity is a major issue where hypocaloric diet plans are often implemented and are covered extensively elsewhere (VCNA Small Animal Practice May 2021). The focus of this article will be implementation of physical activity or structured physical exercise protocols and how they might be used in combination with a typical hypocaloric diet plan, a diet low in calories. Considering the limited information regarding physical activity or structured exercise programs in dogs, a human comparative assessment of efficacy is fundamental as a baseline of information regarding typical interventions. In addition, many of these long-term rehabilitation cases typically exhibit osteoarthritis (OA) and as part of case management, there is a need to implement nutrient or nutraceutical intervention to either diminish the progression of OA or help with pain control measures, particularly for the nonsteroidal anti-inflammatory intolerant patient. Nutraceutical intervention comes in many forms from botanicals to nutritional enhancement; botanicals will be covered elsewhere in this issue. This overview of nutraceuticals will cover nonbotanical interventions including fish oil, glucosamine/chondroitin, avocado/soybean unsaponifiables, undenatured collagen, green lipped mussel, and egg shell membrane supplementation.
Article
These updated guidelines present a practical and logical approach to the assessment and management of acute and chronic pain in canine and feline patients. Recognizing pain is fundamental to successful treatment, and diagnostic guides and algorithms are included for assessment of both acute and chronic pain. Particularly for chronic pain, capturing owner evaluation is important, and pain-assessment instruments for pet owners are described. Expert consensus emphasizes proactive, preemptive pain management rather than a reactive, “damage control” approach. The guidelines discuss treatment options centered on preemptive, multimodal analgesic therapies. There is an extensive variety of pharmacologic and nonpharmacologic therapeutic options for the management of acute and chronic pain in cats and dogs. The guidelines include a tiered decision tree that prioritizes the use of the most efficacious therapeutic modalities for the treatment of acute and chronic pain.
Article
Full-text available
Osteoarthritis is a common and debilitating disease affecting horses across breeds and disciplines. Although the cornerstone of therapy among equine practitioners remains systemic and local anti-inflammatory medications, this approach only addresses the symptoms of osteoarthritis, rather than modifying the progression of the disease itself. There has been great interest in various biologic and cell-based therapies, such as autologous conditioned serum, platelet-rich plasma, and mesenchymal stem cells, as potentially being disease-modifying osteoarthritis drugs. In vitro and experimental results for these novel modalities are promising. However, although the use of these therapies is now widespread, scientific evidence supporting their efficacy in clinical cases is limited to date. Gene therapy for delivery of anti-inflammatory cytokines or growth factors has also been investigated experimentally with good results but has not entered widespread clinical practice. Standardized definitions of disease and large randomized controlled trials, organized across institutions, are needed improve evidence-based recommendations for osteoarthritis treatment. This review provides a brief overview of what is known about the pathophysiology of osteoarthritis and addresses the current literature for medical treatment of osteoarthritis in the horse.
Article
Objectives The purpose of this study was to evaluate the pain-alleviating and activity-enhancing effects of glucosamine/chondroitin sulfate (Dasuquin) in cats that had degenerative joint disease (DJD) and owner-noted mobility/activity impairment. We hypothesized that the nutritional supplement would produce pain-relieving and activity-enhancing effects in cats with painful DJD. Methods In this prospective, randomized, stratified, double-blind, placebo-controlled clinical trial, 59 cats with DJD pain were assigned to receive a placebo (n = 30) or supplement (n = 29) for 6 weeks after 2 weeks of placebo. Outcome measures (at-home accelerometry and client-specific outcome measures [feline (CSOMf); Feline Musculoskeletal Pain Index (FMPI); quality of life (QoL)]; and veterinarian examination) were collected at days 14, 28, 42 and 56. Results Twenty-seven cats in the treatment group and 30 in the placebo group completed the trial. Within the first 2 weeks (placebo administration to all cats), 78% of all cats had an improvement in CSOMf scores. Both groups showed significant improvement at most time points in CSOMf, FMPI, QoL and pain scores, with the placebo group showing greater improvement than the supplement group (significant for CSOMf [ P = 0.01]). Overall, no differences in activity were seen between the groups. Cumulative distribution function analysis indicated that for most levels of activity, the placebo-treated cats were more active; however, the least active cats were more active on the supplement ( P = 0.013). Conclusions and relevance This study showed a strong placebo effect. The glucosamine/chondroitin sulfate supplement did not show pain-relieving effects when compared with placebo.
Article
The guidelines are the first comprehensive consensus report on veterinary healthcare recommendations for working, assistance, and therapy dogs. This category of canine patients includes a broad assortment of animals, some with well-defined functions and others that provide a more generalized support role. The guidelines discuss recommendations for dogs trained for protection, odor/scent detection, service functions for people with diagnosed disabilities or physical limitations, emotional support, and therapeutic intervention. Although the term is often used to describe dogs providing animal-assisted activities, true therapy dogs provide goal-directed therapy, often under the supervision of a healthcare professional such as an occupational therapist or psychologist. Many working dogs undergo extensive training and have rigorous physical demands placed upon them. These factors make working, assistance, and therapy dogs inherently valuable and impose a need for a high level of primary veterinary care as described in the guidelines. Because working dogs have a particularly close relationship with their handlers, a trust relationship between the practice team and the working-dog client is imperative.
Article
Osteoarthritis is prevalent in the UK canine population and has a clear impact on animal welfare. Treatment of osteoarthritis is advised to be multimodal, with nutraceuticals becoming a popular part of this approach. However, veterinary nutraceuticals are not subject to any regulation and systematic reviews are still uncommon in the veterinary field, which makes evaluating these products difficult. This article looks at the most commonly used veterinary supplements and how to critically evaluate the evidence of their efficacy. Evidence is promising for omega-3 fatty acids but is limited for other common ingredients. There are limited numbers of rigorous, randomised controlled trials and veterinary studies are often hampered by small sample sizes. Standardisation of reporting, as performed in human medicine, is needed to allow more robust systematic reviews of nutraceuticals to subsequently enable vets to make more informed decisions.
Article
Small breed dogs (<15 kg) affected by cranial cruciate ligament rupture secondary to cranial cruciate ligament disease are usually middle‐aged (mean age at presentation: 5.4 to 9.8 years); terrier breeds, miniature and toy poodles are over‐represented. Small breed dogs have a different morphology of the proximal tibia compared to medium and large breed dogs with a steep tibial plateau angle (mean tibial plateau angle 28.8° to 36.3°), absent base of the flare of the tibial tuberosity and a caudally bowed fibula. There is a lack of evidence regarding the optimal management of cranial cruciate ligament rupture in small dogs. The treatment options consist of conservative management, extracapsular stabilisation, cranial closing wedge ostectomy, tibial plateau levelling osteotomy and tibial tuberosity advancement. The limited evidence available shows that conservative management is likely to result in prolonged recovery time (average time to recovery approximately 4 months). There is paucity of reports focussing on extracapsular stabilisation in small breed dogs, and questions have been raised regarding the early failure of the extracapsular suture subject to higher loads due to the steep tibial plateau angle of small breed dogs. Cranial closing wedge ostectomy and tibial plateau levelling osteotomy have been reported to have low major complication rates and good subjective outcomes. It is controversial whether tibial tuberosity advancement is a suitable technique in dogs with steep tibial plateau angle, which includes most small breed dogs.
Article
Working dogs are athletes, but have a wide variety of work types and durations that impact their dietary needs. Their basic nutritional needs do not change: all dogs need a complete and balanced diet, fed in proper proportions to maintain optimal body condition. However, with increasing muscle work and endurance, the amounts of specific nutrients (particularly the macronutrients, protein, fat, and carbohydrates) must be adjusted. This article provides an overview of the key aspects of working canine nutrition and provides the nutritional science behind the recommendations made.
Article
Full-text available
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 5-12yrs; Avg 8yrs) were sorted into two groups: undenatured type II collagen group receiving 40mg UC-II (10mg Collagen Type II/Min. 3% Undenatured Type II Collagen; Lonza Consumer Health, Inc.) and placebo group receiving 40mg maltodextrin daily by capsule. After 2-weeks loading, all dogs began an 11-week endurance exercise regimen consisting of two weekly runs, starting at 5km and increasing incrementally to 8km, with one final 16km run. Blood samples were collected at baseline, pre and post first 5km run, and pre and post 16km 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 5km (P=0.037). Cartilage oligomeric matrix protein (COMP) was lesser in undenatured type II collagen dogs at post 16km (P=0.023), and only the placebo dogs had a significant increase in COMP from pre to post 16km (P=0.021). In summary, Labrador Retrievers supplemented with undenatured type II collagen had decreased inflammation and cartilage degeneration compared with non-supplemented dogs during exercise.
Chapter
This chapter discusses osteoarthritis (OA) in dogs and cats. OA is a syndrome that affects synovial or diarthrodial joints and may manifest its presence by causing pain in association with degeneration of articular cartilage and changes in periarticular soft tissues. It can occur in two forms: primary and secondary, with secondary OA being the more common form presenting clinically in veterinary medicine. Primary OA is considered a “wear and tear” phenomenon of joint degeneration occurring in older patients. Secondary OA is due to an underlying or secondary cause for the development of the disease. Diagnostics are initially directed towards orthogonal view radiographs of the affected joint and should include the contralateral joint for comparative assessment. Nonimaging modalities can be used for more detailed joint evaluation, including computed tomography and magnetic resonance imaging. Current treatment strategies used to treat OA patients are multimodal medical management, surgery or, more commonly, the integration of both treatment modalities.
Chapter
This chapter deals with the various of forms of therapies given for treating equine lameness. The treatment types include systemic and parenteral therapies, topical and local therapies, intrasynovial therapies, intralesional therapies, oral and nutritional therapies, corrective shoeing and therapeutic shoeing, acupuncture treatments, manual therapies, and rehabilitation and physical therapy. Systemic administration of medications to treat musculoskeletal diseases in the horse mainly encompasses intravenous nonsteroidal anti‐inflammatory drugs (NSAIDS), intramuscular polysulfated glycosaminoglycans, and intravenous hyaluronan. The most commonly used IV NSAIDs are phenylbutazone and flunixin meglumine. The need for systemic NSAID therapy can be reduced and associated edema and tissue damage minimized with effective use of topical therapy. Equine practitioners currently have several options available to treat intrasynovial inflammation. Intrasynovial therapies, specifically corticosteroids, are used frequently in horses to minimize or control pain associated with synovitis and osteoarthritis.
Chapter
Full-text available
O presente capítulo aborda os métodos avaliativos mais comumente utilizados, bem como a reabilitação dos desajustes laríngeos presentes na disfonia.
Article
Veterinary pet supplements and nutraceuticals are widely used by dog, cat and horse owners across the United States, generating millions of dollars in revenue for manufacturers. Despite the widespread use of these veterinary products, oversight and regulation remain limited as compared to human dietary supplement regulations. This review describes the current regulation, quality control, safety and efficacy of pet supplements and nutraceuticals targeted towards the dog, cat and horse.
Book
Full-text available
Escrever sobre reabilitação enquanto campo de prática clínica e sua integração com a pesquisa é uma tarefa mais complexa do que pode parecer. O livro que ora apresentamos nasceu de uma iniciativa dos organizadores, a partir da busca por um enfoque da reabilitação clínica e da integração com a pesquisa realizada no PPG Ciências da Reabilitação da Universidade Federal de Ciências da Saúde de Porto Alegre. A tarefa, que parecia simples, de coadunar colegas especialistas em diferentes áreas da reabilitação para escreverem sobre tema de sua produção teórica e científica mostrou-se um trabalho extenso. O trabalho compreendeu vastas revisões dos especialistas em cada um dos temas. O cuidado dos autores dos capítulos apresentados neste livro é típico de pesquisadores, cientistas de um campo com aplicações clínicas de amplo espectro e que têm visualização clara sob a matéria. Nos dezesseis capítulos são exploradas temáticas presentes nas três linhas de pesquisa do programa: reabilitação musculoesquelética, reabilitação cardiorrespiratória e reabilitação neurológica. No primeiro capítulo, as autoras Michele Rocha e Maria Cristina Cardoso apresentam os métodos de avaliação dos distúrbios da deglutição e exploram a prática clínica aliada à pesquisa, através da comparação dos diferentes processos de avaliação das disfagias que, quando presentes, podem desencadear quadros clínicos de desidratação, desnutrição e distúrbios pulmonares aspirativos. No mesmo caminho, no segundo capítulo, Camila Lucia Etges, Lisiane de Rosa Barbosa e Maria Cristina Cardoso tratam do diagnóstico de distúrbios de deglutição em pediatria no ambiente hospitalar, apresentando uma atualização dos dados para o diagnóstico de distúrbios de deglutição em pediatria, tema constantemente carente de informações empíricas e ensaios clínicos. No terceiro capítulo, Camila Maria de Paula da Silva, Cecília Cristine Pohren Dhein, Eveline de Lima Nunes, Patrícia Keitel da Silva, Samara Regina Fávero e Maria Cristina Cardoso apresentam a aplicabilidade clínica da auscultação cervical, indicando uma atualização quanto ao uso da auscultação cervical nas avaliações de beira de leito nos distúrbios da deglutição, cujo perfil é subjetivo, mas com possibilidades objetivas. No quarto capítulo, Bruno Barcellos Hervé, Janice Luisa Lukrafka Tartari, Mariane Borba Monteiro, Fernanda Machado Balzan, Wagner da Silva Naue, Paulo Roberto Stefani Sanches, Danton Pereira da Silva Junior e André Frotta Müller discutem dados sobre a exploração da avaliação da assincronia paciente-ventilador na Doença Pulmonar Obstrutiva Crônica (DPOC) em ventilação não invasiva (VNI), visto que a assincronia é uma das complicações decorrentes da interação entre o paciente e o ventilador. No quinto capítulo, Isadora de Oliveira Lemos, Gabriela da Cunha Pereira e Mauriceia Cassol discorrem sobre a avaliação e a reabilitação frente aos quadros clínicos de distúrbio voz, que são tão frequentes quanto debilitantes. No sexto capítulo, Giesse Albeche Duarte e Maria Cristina Cardoso propõem ações fonoaudiológicas nas fissuras labiopalatinas, que são exploradas através de uma visão geral das possibilidades clínicas junto a uma das malformações mais frequentes que acometem o ser humano e que comprometem o indivíduo como um todo. No sétimo capítulo, as autoras Chenia Caldeira Martinez e Mauriceia Cassol apresentam evidências científicas sobre ansiedade e depressão relacionadas aos distúrbios vocais em pacientes com problemas de saúde mental (ansiedade e depressão), comuns em nossa sociedade. Na sequência, as autoras do oitavo capítulo, Thayse Steffen Pereira, Fabiana de Oliveira e Maria Cristina Cardoso, abordam a saúde bucal a partir da interferência dos hábitos orais viciosos continuados e de difícil eliminação. No nono capítulo, Sabrina Braga dos Santos e Mauriceia Cassol exploram o uso de uma técnica específica para distúrbios de voz, junto a uma população crescente na nossa sociedade, a de idosos. No décimo capítulo, as principais intervenções em escrita e leitura na perspectiva da saúde coletiva e da atenção primária focando a prevenção e a promoção de saúde são abordadas por Caroline Tozzi Reppold, Léia Gonçalves Gurgel e Flavia Amaral Machado. Os modelos das intervenções neuropsicológicas no processo de aprendizagem de crianças em idade escolar são o foco do décimo primeiro capítulo. Caroline Tozzi Reppold, Flavia Amaral Machado e Léia Gonçalves Gurgel, novamente, fazem uma análise voltada para o aprimoramento e para a reabilitação da aprendizagem em âmbito escolar, além de discutirem a importância das funções executivas nesse processo. A elaboração de instrumentos de avaliação do desenvolvimento motor em crianças com paralisia cerebral é o tema do décimo segundo capítulo. Esse é um campo dominado por escalas que concedem pouca ou nenhuma atenção às habilidades motoras finas. Priscilla Pereira Antunes, Daniela Centenaro Levandowski, Fabiana Rita Camara Machado e Alcyr Alves de Oliveira Jr. exploram outras escalas motoras e sua utilização na avaliação de pacientes com paralisia cerebral. No décimo terceiro capítulo, são apresentados os avanços e a aplicação da tecnologia computacional interativa de videogames para o tratamento de habilidades motoras através de jogos interativos na reabilitação de crianças com paralisia cerebral. Os autores Fabiana Rita Camara Machado, Daniela Centenaro Levandowski e Alcyr Alves de Oliveira Jr. revisam o tema considerando a facilidade de acesso aos equipamentos e aos jogos, aliada ao baixo custo, o que torna possível uso desses aparatos como ferramentas domésticas para o treinamento motor de crianças com paralisia cerebral. A qualidade de vida dos cuidadores de crianças com paralisia cerebral é o foco do décimo quarto capítulo, já que o nível de sobrecarga encontrada nas famílias desses pacientes é considerável. Os autores Jandara de Moura Souza, Daniela Centenaro Levandowski e Alcyr Alves de Oliveira Jr. tratam do desenvolvimento neuromotor dessas crianças durante o processo de reabilitação. Um dos pontos importantes da temática é a expectativa parental sobre o filho recém-chegado e a sobrecarrega advinda quando a criança não atende às expectativas. No décimo quinto capítulo, Juliana de Lima Cordeiro e Alcyr Alves de Oliveira Jr. apresentam um breve levantamento bibliográfico sobre a doença de Parkinson, enfocando nas características motoras e em suas influências no comprometimento cognitivo. Concluem que o rendimento das funções cognitivas na doença de Parkinson pode ser um fator tão importante quanto os visíveis prejuízos motores. Por fim, no décimo sexto capítulo, Marlon Francys Vidmar, Verônica Bidinotto Brito, Gilnei Lopes Pimentel, Carlos Rafael de Almeida, Luis Henrique Telles da Rosa e Marcelo Faria Silva tratam da suplementação com ômega-3 em processos inflamatórios e do estresse oxidativo em processos pós-lesões do joelho. Abordam as possíveis alterações no metabolismo celular produzido pelo estresse oxidativo que podem conduzir ao agravamento de lesões de joelho e a um maior dano nas estruturas articulares. Assim, nesses dezesseis capítulos, os autores apresentam brevemente uma série de produtos, frutos de pesquisas conduzidas por profissionais e acadêmicos atuantes no PPG em Ciências da Reabilitação e em outros programas parceiros.
Article
Osteoarthritis (OA) is a debilitating disease in dogs. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat OA; however, many dogs do not obtain adequate pain relief with an NSAID alone. This pilot study evaluated the systemic anti-inflammatory and mobility enhancing effects of an eggshell membrane-based nutritional supplement in dogs with OA-associated pain and mobility impairment. Twenty-seven dogs with OA-associated pain were enrolled into a randomized, double-masked, placebo-controlled, proof of principle pilot study and received either placebo or an eggshell membrane-based nutritional supplement over a 12-week period. Inflammatory biomarkers (IL-2, IL-6, IL-8, tumor necrosis factor-α, C-reactive protein, S100A12, and N-methylhistamine) were measured at Day 0 and Day 84. Owner questionnaires (CBPI and LOAD) were completed at Day 0, Day 42, and Day 84. Differences between groups over time were calculated. Twenty-two dogs completed the pilot study. Inflammatory biomarker IL-2 decreased in the supplement group, compared to the placebo group. Although small, the difference was statistically significant at an alpha of 0.1 (P = 0.069). LOAD scores were numerically lower in the supplement group, but not significantly different from the placebo group at Day 0. Day 84 LOAD scores were significantly lower in the supplement group compared to the placebo group (P = 0.034). CBPI results did not show the same pattern. The changes in biomarkers and LOAD scores were small, and do not provide definitive evidence of positive effects. However, these pilot results provide a rationale for performing a larger placebo-controlled study of the potential effects of the eggshell membrane-based nutritional supplement.
Article
Full-text available
Concerns about the completeness and accuracy of reporting of randomized clinical trials (RCTs) and the impact of poor reporting on decision-making have been documented in the medical field over the past several decades. Experience from RCTs in human medicine would suggest that failure to report critical trial features can be associated with biased estimated effect measures, and there is evidence to suggest similar biases occur in RCTs conducted in livestock populations. In response to these concerns, standardized guidelines for reporting RCTs were developed and implemented in human medicine. The Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996 with a revised edition published in 2001. The CONSORT statement consists of a 22-item checklist for reporting a RCT and a flow diagram to follow the number of participants at each stage of a trial. An explanation and elaboration document not only defines and discusses the importance of each of the items, but also provides examples of how this information could be supplied in a publication. Differences between human and livestock populations necessitate modifications to the CONSORT statement to maximize its usefulness for RCTs involving livestock. These have been addressed in an extension of the CONSORT statement titled the REFLECT statement: Methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety. The modifications made for livestock trials specifically addressed the common use of group housing and group allocation to intervention in livestock studies, the use of a deliberate challenge model in some trials, and common use of non-clinical outcomes, such as contamination with a foodborne pathogen. In addition, the REFLECT statement for RCTs in livestock populations proposed specific terms or further clarified terms as they pertained to livestock studies.
Article
Full-text available
The CONSORT (Consolidated Standards of Reporting Trials) statement is used worldwide to improve the reporting of randomized, controlled trials. Schulz and colleagues describe the latest version, CONSORT 2010, which updates the reporting guideline based on new methodological evidence and accumulating experience.
Article
Full-text available
Problem statement: There are indications that the intake of gelatin hydrolysate has a beneficial impact on the clinical signs of osteoarthritis in dogs. Data from a controlled trial were required to substantiate these indications. Approach: A double-blind, placebo-controlled trial with privately owned dogs was carried out to assess the efficacy of a preparation of gelatin hydrolysate in the treatment of osteoarthritis. With the use of a questionnaire, the clinical signs were evaluated by the owners. For a period of 8 weeks, the test dogs daily received 10 g of gelatin hydrolysate; as a placebo, soya protein isolate was used. The supplements were mixed with the diet; all dogs were fed on the same dry food. There were 15 dogs per treatment group. Results: The administration of gelatin hydrolysate significantly improved activity (vitality) and significantly reduced stiffness and lameness. Conclusion: Gelatin hydrolysate is commonly used as a component of human foods and is generally considered as safe. It is suggested that a dose of about 2.5% in a dry food would be beneficial for dogs with osteoarthritis.
Article
Full-text available
Problem statement: There are indications for a beneficial effect of beta-1,3/1,6-glucans on the clinical signs of dogs with osteoarthritis. Data from a controlled trial were necessary to prove or disprove the indications. Approach: A double-blind, placebo-controlled trial with privately owned dogs was carried out to assess the efficacy of a preparation of beta-1,3/1,6-glucans in the treatment of osteoarthritis. With the use of a questionnaire, the clinical signs were evaluated by the owners. For a period of 8 weeks, the test dogs daily received a complete dry food without or with 800 ppm beta-1,3/1,6-glucans. There were 23 dogs per experimental group. Results: When compared with the baseline values, the administration of beta-1,3/1,6-glucans significantly improved activity (vitality) and significantly reduced stiffness, lameness and pain. In the placebo group there only was a significant change in the clinical signs of stiffness. When the changes over time for the two groups were compared, there were no statistically significant differences, but the test group showed greater numerical improvement as to the scores for activity, stiffness, lameness and pain. Conclusion: Beta-1,3/1,6-glucans can be considered safe and it is suggested that a dose of 800 ppm in a dry food would be beneficial for dogs with osteoarthritis.
Article
Full-text available
Food supplemented with fish oil improves clinical signs and weight bearing in dogs with osteoarthritis (OA). Determine whether increasing the amount of fish oil in food provides additional symptomatic improvements in OA. One hundred and seventy-seven client-owned dogs with stable chronic OA of the hip or stifle. Prospective, randomized clinical trial using pet dogs. Dogs were randomly assigned to receive the baseline therapeutic food (0.8% eicosopentanoic acid [EPA] + docosahexaenoic acid [DHA]) or experimental foods containing approximately 2- and 3-fold higher EPA+DHA concentrations. Both veterinarians and owners were blinded as to which food the dog received. On days 0, 21, 45, and 90, serum fatty acid concentrations were measured and veterinarians assessed the severity of 5 clinical signs of OA. At the end of the study (day 90), veterinarians scored overall arthritic condition and progression of arthritis based on their clinical signs and an owner interview. Serum concentrations of EPA and DHA rose in parallel with food concentrations. For 2 of 5 clinical signs (lameness and weight bearing) and for overall arthritic condition and progression of arthritis, there was a significant improvement between the baseline and 3X EPA+DHA foods (P=.04, .03, .001, .0008, respectively) but not between the baseline and the 2X EPA+DHA foods. Increasing the amount of fish oil beyond that in the baseline food results in dose-dependent increases in serum EPA and DHA concentrations and modest improvements in the clinical signs of OA in pet dogs.
Article
Full-text available
To determine the effects of feeding a diet supplemented with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. Randomized, controlled, multisite clinical trial. 131 client-owned dogs with stable chronic osteoarthritis examined at 33 privately owned veterinary hospitals in the United States. In all dogs, the dosage of carprofen was standardized over a 3-week period to approximately 4.4 mg/kg/d (2 mg/lb/d), PO. Dogs were then randomly assigned to receive a food supplemented with fish oil omega-3 fatty acids or a control food with low omega-3 fatty acid content, and 3, 6, 9, and 12 weeks later, investigators made decisions regarding increasing or decreasing the carprofen dosage on the basis of investigator assessments of 5 clinical signs and owner assessments of 15 signs. Linear regression analysis indicated that over the 12-week study period, carprofen dosage decreased significantly faster among dogs fed the supplemented diet than among dogs fed the control diet. The distribution of changes in carprofen dosage for dogs in the control group was significantly different from the distribution of changes in carprofen dosage for dogs in the test group. Results suggested that in dogs with chronic osteoarthritis receiving carprofen because of signs of pain, feeding a diet supplemented with fish oil omega-3 fatty acids may allow for a reduction in carprofen dosage.
Article
Full-text available
To evaluate the effects of a food supplemented with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. Randomized, double-blinded, controlled clinical trial. 38 client-owned dogs with osteoarthritis examined at 2 university veterinary clinics. 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. 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. 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.
Article
Full-text available
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. Randomized, double-blinded, controlled clinical trial. 127 client-owned dogs with osteoarthritis in 1 or more joints from 18 privately owned veterinary clinics. 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. 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. 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.
Article
Full-text available
What do we do if different studies appear to give different answers? When applying research to questions for individual patients or for health policy, one of the challenges is interpreting such apparently conflicting research. A systematic review is a method to systematically identify relevant research, appraise its quality, and synthesize the results. The last two decades have seen increasing interest and developments in methods for doing high quality systematic reviews. Part I of this book provides a clear introduction to the concepts of reviewing, and lucidly describes the difficulties and traps to avoid. A unique feature of the book is its description, in Part II, of the different methods needed for different types of health care questions: frequency of disease, prognosis, diagnosis, risk, and management. As well as illustrative examples, there are exercises for each of the sections. This is essential reading for those interested in synthesizing health care research.
Article
Full-text available
This review assesses the evidence for the efficacy of therapies used in the management of osteoarthritis in dogs on the basis of papers published in peer-reviewed journals in English between 1985 and July 2007. Sixty-eight papers were identified and evaluated. They considered four alternative therapies, one use of functional food, two intra-articular agents, six nutraceutical agents, 21 pharmacological agents, two physical therapies, three surgical techniques and two combinations of weight control. There was a high level of comfort (strong evidence) for the efficacy of carprofen, firocoxib and meloxicam, and a moderate level of comfort for the efficacy of etodolac in modifying the signs of osteoarthritis. There was a moderate level of comfort for the efficacy of glycosaminoglycan polysulphate, licofelone, elk velvet antler and a functional food containing green-lipped mussel for the modification of the structures involved in the disease. There was weak or no evidence in support of the use of doxycycline, electrostimulated acupuncture, extracorporeal shockwave therapy, gold wire acupuncture, hyaluronan, pentosan polysulphate, P54FP (extract of turmeric), tiaprofenic acid or tibial plateau levelling osteotomy.
Article
Full-text available
Collagen metabolism in osteoarthritic human articular cartilage was compared to that in normal cartilage and was also correlated with the degree of severity of the osteoarthritic lesion as determined by a histological-histochemical grading system. No correlation was apparent between the concentrations of DNA, hydroxyproline, and hydroxylysine and the degree of severity of the osteoarthritic lesion (except in far-advanced lesions). Similarly, there was no correlation in levels of these components in tissues from the normal vs. osteoarthritic group. The similarity of the values of the ratio hydroxylysine/hydroxyproline in osteoarthritic tissue compared with normal, and the lack of variation in these with increasing severity of the disease process argues against the possibility that osteoarthritis is associated with a major shift in the synthesis of type II collagen to type I. [3H]Proline incorporation into osteoarthritic cartilage was increased fourfold as compared to normal cartilage and varied with advancing histological-histochemical grade. Measurement of the specific activity of insolubilized hydroxyproline-containing material of the cartilage matrix, as an index of the turnover of collagen, showed a sixfold increase in osteoarthritic cartilage which also varied with grade. These data suggest that collagen synthesis in these tissues is substantially greater than in nonosteoarthritic tissues and varies directly with the severity of the disease process up to a point and then varies inversely as the lesion becomes more severe.
Article
Full-text available
This study describes specific molecular mechanisms by which supplementation with n-3 fatty acids (i.e. those present in fish oils) can modulate the expression and activity of degradative and inflammatory factors that cause cartilage destruction during arthritis. Our data show that incorporation of n-3 fatty acids (but not other polyunsaturated or saturated fatty acids) into articular cartilage chondrocyte membranes results in a dose-dependent reduction in: (i) the expression and activity of proteoglycan degrading enzymes (aggrecanases) and (ii) the expression of inflammation-inducible cytokines (interleukin (IL)-1α and tumor necrosis factor (TNF)-α) and cyclooxygenase (COX-2), but not the constitutively expressed cyclooxygenase COX-1. These findings provide evidence thatn-3 fatty acid supplementation can specifically affect regulatory mechanisms involved in chondrocyte gene transcription and thus further advocate a beneficial role for dietary fish oil supplementation in alleviation of several of the physiological parameters that cause and propogate arthritic disease.
Article
Full-text available
Glucosamine and chondroitin preparations are widely touted in the lay press as remedies for osteoarthritis (OA), but uncertainty about their efficacy exists among the medical community. To evaluate benefit of glucosamine and chondroitin preparations for OA symptoms using meta-analysis combined with systematic quality assessment of clinical trials of these preparations in knee and/or hip OA. We searched for human clinical trials in MEDLINE (1966 to June 1999) and the Cochrane Controlled Trials Register using the terms osteoarthritis, osteoarthrosis, degenerative arthritis, glucosamine, chondroitin, and glycosaminoglycans. We also manually searched review articles, manuscripts, and supplements from rheumatology and OA journals and sought unpublished data by contacting content experts, study authors, and manufacturers of glucosamine or chondroitin. Studies were included if they were published or unpublished double-blind, randomized, placebo-controlled trials of 4 or more weeks' duration that tested glucosamine or chondroitin for knee or hip OA and reported extractable data on the effect of treatment on symptoms. Fifteen of 37 studies were included in the analysis. Reviewers performed data extraction and scored each trial using a quality assessment instrument. We computed an effect size from the intergroup difference in mean outcome values at trial end, divided by the SD of the outcome value in the placebo group (0.2, small effect; 0.5, moderate; 0.8, large), and applied a correction factor to reduce bias. We tested for trial heterogeneity and publication bias and stratified for trial quality and size. We pooled effect sizes using a random effects model. Quality scores ranged from 12.3% to 55.4% of the maximum, with a mean (SD) of 35.5% (12%). Only 1 study described adequate allocation concealment and 2 reported an intent-to-treat analysis. Most were supported or performed by a manufacturer. Funnel plots showed significant asymmetry (P< or =.01) compatible with publication bias. Tests for heterogeneity were nonsignificant after removing 1 outlier trial. The aggregated effect sizes were 0.44 (95% confidence interval [CI], 0.24-0.64) for glucosamine and 0.78 (95% CI, 0.60-0.95) for chondroitin, but they were diminished when only high-quality or large trials were considered. The effect sizes were relatively consistent for pain and functional outcomes. Trials of glucosamine and chondroitin preparations for OA symptoms demonstrate moderate to large effects, but quality issues and likely publication bias suggest that these effects are exaggerated. Nevertheless, some degree of efficacy appears probable for these preparations.
Article
Health providers face the problem of trying to make decisions in situations where there is insufficient information and also where there is an overload of (often contradictory) information. Statistical methods such as meta-analysis have been developed to summarise and to resolve inconsistencies in study findings-where information is available in an appropriate form. Consensus methods provide another means of synthesising information, but are liable to use a wider range of information than is common in statistical methods, and where published information is inadequate or non-existent these methods provide a means of harnessing the insights of appropriate experts to enable decisions to be made. Two consensus methods commonly adopted in medical, nursing, and health services research-the Delphi process and the nominal group technique (also known as the expert panel)-are described, together with the most appropriate situations for using them; an outline of the process involved in undertaking a study using each method is supplemented by illustrations of the authors' work. Key methodological issues in using the methods are discussed, along with the distinct contribution of consensus methods as aids to decision making, both in clinical practice and in health service development.
Article
Context Glucosamine and chondroitin preparations are widely touted in the lay press as remedies for osteoarthritis (OA), but uncertainty about their efficacy exists among the medical community.Objective To evaluate benefit of glucosamine and chondroitin preparations for OA symptoms using meta-analysis combined with systematic quality assessment of clinical trials of these preparations in knee and/or hip OA.Data Sources We searched for human clinical trials in MEDLINE (1966 to June 1999) and the Cochrane Controlled Trials Register using the terms osteoarthritis, osteoarthrosis, degenerative arthritis, glucosamine, chondroitin, and glycosaminoglycans. We also manually searched review articles, manuscripts, and supplements from rheumatology and OA journals and sought unpublished data by contacting content experts, study authors, and manufacturers of glucosamine or chondroitin.Study Selection Studies were included if they were published or unpublished double-blind, randomized, placebo-controlled trials of 4 or more weeks' duration that tested glucosamine or chondroitin for knee or hip OA and reported extractable data on the effect of treatment on symptoms. Fifteen of 37 studies were included in the analysis.Data Extraction Reviewers performed data extraction and scored each trial using a quality assessment instrument. We computed an effect size from the intergroup difference in mean outcome values at trial end, divided by the SD of the outcome value in the placebo group (0.2, small effect; 0.5, moderate; 0.8, large), and applied a correction factor to reduce bias. We tested for trial heterogeneity and publication bias and stratified for trial quality and size. We pooled effect sizes using a random effects model.Data Synthesis Quality scores ranged from 12.3% to 55.4% of the maximum, with a mean (SD) of 35.5% (12%). Only 1 study described adequate allocation concealment and 2 reported an intent-to-treat analysis. Most were supported or performed by a manufacturer. Funnel plots showed significant asymmetry (P≤.01) compatible with publication bias. Tests for heterogeneity were nonsignificant after removing 1 outlier trial. The aggregated effect sizes were 0.44 (95% confidence interval [CI], 0.24-0.64) for glucosamine and 0.78 (95% CI, 0.60-0.95) for chondroitin, but they were diminished when only high-quality or large trials were considered. The effect sizes were relatively consistent for pain and functional outcomes.Conclusions Trials of glucosamine and chondroitin preparations for OA symptoms demonstrate moderate to large effects, but quality issues and likely publication bias suggest that these effects are exaggerated. Nevertheless, some degree of efficacy appears probable for these preparations.
Article
THE final article of this three-part series discusses a key skill required for the practice of evidence-based veterinary medicine (EBVM) - the ability to appraise the evidence presented in scientific papers. Having identified information needs and searched for evidence - processes discussed in Parts 1 and 2 - the clinician needs to evaluate the usefulness of the evidence by asking questions such as, 'Is it true?' and 'Is it relevant to my patient?'. Clearly, an understanding of study design and methods of analysing the results is required in order to determine the validity and relevance of clinical studies.
Article
The U.S. Congress, in the Dietary Supplement Health and Education Act (DSHEA) established a framework for regulation of dietary supplements by the U.S. Food and Drug Administration. For dietary supplements, the FDA regulates labeling to limit health claims, but is not empowered to insist on rigorous studies establishing safety before marketing (as would be required for drugs or food additives). This creates a substantial potential risk to the health of the public, and serious adverse effects have been reported from some dietary supplements that are currently being marketed. The author recommends that a new category of dietary supplements, called "nutraceuticals," be established for supplements to be administered at doses that exceed normal human exposure to these agents in foods. Regulations should require that these nutraceuticals be judged safe before they are marketed.
Article
Osteoarthritis (also known as osteoarthrosis or degenerative joint disease) is a term covering a broad spectrum of poorly understood joint disorders. Although it is preferable to think of osteoarthritis as a disease process with a variety of initiating factors, it may, for the purposes of this article, be defined as a disorder of synovial joints characterised by aberrant repair and eventual degeneration of articular cartilage and also by the formation of new bone at the articular margins, sclerosis of subchondral bone and variable low grade synovial inflammation. While the apophyseal joints of the spine can also be affected, the association between osteoarthritis of these joints, disc disease and the clinical signs is unclear. Discussion will, therefore, be limited to the joints of the appendicular skeleton.
Article
Cetyl myristoleate was isolated from National Institutes of Health, general purpose, Swiss albino mice that were immune to the polyarthritis induced in rats with Freund's adjuvant. This substance, or material synthesized from cetyl alcohol and myristoleic acid, afforded good protection against adjuvant-induced arthritic states in rats. In limited comparisons, cetyl oleate, also found in Swiss albino mice, gave lesser protection, whereas cetyl myristate and cetyl elaidate, the trans-isomer of cetyl oleate, appeared to be virtually ineffective. Dosage of the protective compound as well as the site of injection of Freund's adjuvant was important.
Article
The CONSORT statement is used worldwide to improve the reporting of randomised controlled trials. Kenneth Schulz and colleagues describe the latest version, CONSORT 2010, which updates the reporting guideline based on new methodological evidence and accumulating experience. To encourage dissemination of the CONSORT 2010 Statement, this article is freely accessible on bmj.com and will also be published in the Lancet, Obstetrics and Gynecology, PLoS Medicine, Annals of Internal Medicine, Open Medicine, Journal of Clinical Epidemiology, BMC Medicine, and Trials.
Article
The present investigation evaluated arthritic pain in horses receiving daily placebo, undenatured type II collagen (UC-II) at 320, 480, or 640 mg (providing 80, 120, and 160 mg active UC-II, respectively), and glucosamine and chondroitin (5.4 and 1.8 g, respectively, bid for the first month, and thereafter once daily) for 150 days. Horses were evaluated for overall pain, pain upon limb manipulation, physical examination, and liver and kidney functions. Evaluation of overall pain was based upon a consistent observation of all subjects during a walk and a trot in the same pattern on the same surface. Pain upon limb manipulation was conducted after the walk and trot. It consisted of placing the affected joint in severe flexion for a period of 60 sec. The limb was then placed to the ground and the animal trotted off. The response to the flexion test was then noted with the first couple of strides the animal took. Flexion test was consistent with determining clinically the degree of osteoarthritis in a joint. Horses receiving placebo showed no change in arthritic condition, while those receiving 320 or 480 or 640 mg UC-II exhibited significant reduction in arthritic pain (P < 0.05). UC-II at 480 or 640 mg dose provided equal effects, and therefore, 480 mg dose was considered optimal. With this dose, reduction in overall pain was from 5.7 +/- 0.42 (100%) to 0.7 +/- 0.42 (12%); and in pain upon limb manipulation from 2.35 +/- 0.37 (100%) to 0.52 +/- 0.18 (22%). Although glucosamine and chondroitin treated group showed significant (P < 0.05) reduction in pain compared with pretreated values, the efficacy was less compared with that observed with UC-II. In fact, UC-II at 480 or 640 mg dose was found to be more effective than glucosamine and chondroitin in arthritic horses. Clinical condition (body weight, body temperature, respiration rate, and pulse rate), and liver (bilirubin, GGT, and ALP) and kidney (BUN and creatinine) functions remained unchanged, suggesting that these supplements were well tolerated.
Article
Feline degenerative joint disease (DJD) is common and there are no approved therapies for the alleviation of the associated pain. To test a diet high in eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) content and supplemented with green-lipped mussel extract and glucosamine/chondroitin sulfate (test-diet) for its pain-relieving and activity-enhancing effects in cats with painful, mobility-impairing DJD over a 9-week period. Forty client-owned cats. Randomized, controlled, blinded, parallel group, prospective clinical study. Cats with no detectable systemic disease, and with at least 1 appendicular joint with radiographic evidence of DJD where manipulation elicited an aversive response were included. Cats were randomly allocated to the test-diet or control diet (C-diet). Outcome measures were subjective owner and veterinarian assessments, and objective activity monitoring (accelerometry). Nonparametric statistics were used to evaluate changes within and between groups for both subjective and objective data, and locally weighted scatterplot smoothing regression analysis was used to predict activity changes. The primary objective outcome measures indicated that activity declined significantly (P < .001) in the C-diet group, significantly increased (P < .001) in the test-diet group and there was a significant difference between the groups (P < .001). A diet high in EPA and DHA and supplemented with green-lipped mussel extract and glucosamine/chondroitin sulfate improved objective measures of mobility. Dietary modulation might be 1 method to use to improve mobility in cats with DJD-associated pain.
Article
Concerns about the completeness and accuracy of reporting of randomized clinical trials (RCTs) and the impact of poor reporting on decision-making have been documented in the medical field over the past several decades. Experience from RCTs in human medicine would suggest that failure to report critical trial features can be associated with biased estimated effect measures, and there is evidence to suggest similar biases occur in RCTs conducted in livestock populations. In response to these concerns, standardized guidelines for reporting RCTs were developed and implemented in human medicine. The Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996 with a revised edition published in 2001. The CONSORT statement consists of a 22-item checklist for reporting a RCT and a flow diagram to follow the number of participants at each stage of a trial. An explanation and elaboration document not only defines and discusses the importance of each of the items, but also provides examples of how this information could be supplied in a publication. Differences between human and livestock populations necessitate modifications to the CONSORT statement to maximize its usefulness for RCTs involving livestock. These have been addressed in an extension of the CONSORT statement titled the REFLECT statement: Methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety. The modifications made for livestock trials specifically addressed the common use of group housing and group allocation to intervention in livestock studies, the use of a deliberate challenge model in some trials, and common use of non-clinical outcomes, such as contamination with a foodborne pathogen. In addition, the REFLECT statement for RCTs in livestock populations proposed specific terms or further clarified terms as they pertained to livestock studies.
Article
Nutraceuticals are increasingly applied to the management of equine arthritis and joint disease, particularly those based upon glucosamine and chondroitin sulphate. While the first report of using glucosamine in horses appeared more than 25 years ago, it was not until 1992 that isolated studies began to be reported. Since that time, 15 in vivo papers have been published in the equine literature, usually on products already commercially available and often seeking evidence for efficacy. These studies demonstrate an encouraging trend to manufacturers of these products investing in research, but most do not meet a quality standard that provides sufficient confidence in the results reported. This review discusses the entirety of published in vivo research on glucosamine-based nutraceuticals (GBN) for horses, including that on Cosequin, Cortaflex, Synequin, Sasha's EQ, Myristol, chondroitin sulphate, glucosamine sulphate and glucosamine hydrochloride; and considers experimental limitations of this research along with their impact on interpretation of results. A quality score was calculated for each paper according to preset quality criteria. A minimum quality standard of 60% was set as the threshold for confidence in interpretation of results. Of the 15 papers reviewed, only 3 met the minimum quality standard. Experimental limitations of each research paper are discussed. It is concluded that the quality of studies in this area is generally low, prohibiting meaningful interpretation of the reported results. New high quality research on GBN for horses is needed and recommendations for future research are discussed.
Article
Contents The objective of this study was to evaluate the quality of published literature on reproduction in dogs. A systematic search in online databases revealed 287 papers that met the inclusion criteria. For evaluation a questionnaire comprising 40 criteria regarding materials and methodology, study design, statistics, presentation and information content, applicability and conclusions was developed. In a pre‐test including seven independent scientists the applicability and explanatory power of the questionnaire and its results were validated. Out of 287 publications evaluated, 90 (31.4%) were classified as clinical trials. The remaining 197 publications were case reports or contained information based on personal experience. Not a single meta‐analysis was found. Sixty (66.7%) of the 90 clinical trials included a control group. Randomization was conducted in 23 and blinding in eight articles respectively. In total five articles were determined as randomized, controlled and blinded clinical trials. Information content of the publications was variable concerning details on included animals, type or dosage of used remedies or conducted interventions. For example, in 99.7% of the articles, the exact number of animals was given, but in 79.8%, housing and feeding of the animals were not described. Statistical procedures of clinical trials were determined adequate in 55.6%. However, the data of 67.9% of the articles were evaluated to be not sufficient to draw valid conclusions. This study revealed evidence of deficits in the field of canine reproduction. The demand for more high quality clinical research is obvious. Requisite for the further implementation of the evidence‐based veterinary medicine is an improvement of the quantity and the quality of well‐designed, conducted and reported clinical trials. The practitioner should always assess the quality of information before implementing results into practice to provide best available care for the animals.
Article
This paper describes a collaborative project, conducted under the auspices of the British Equine Veterinary Association's survey section and financed by the Horserace Betting Levy Board, with the objective of collecting relevant data from breeding and racing statistics and evaluating losses (areas of wastage) that occur in the Thoroughbred racing industry. The investigation, which was carried out between 1977 and 1980, was divided into 2 parts. In Phase 1 the available statistics showed that considerable wastage existed from the time of covering to the appearance of the progeny on the flat, but that losses were closely consistent each year. Of the active mares in the General Stud Book for the seasons 1973 to 1979, 11.8 per cent were eliminated because no covering return was received and a further 10.1 per cent were either not covered, were covered by halfbreds or foaled abroad. The remaining mares, which were confirmed to have been covered (ie, applicable covered returned mares) were used to base the estimates of wastage. These were failure to conceive, 22.5 per cent, aborted or had a non‐surviving foal, 10.1 per cent, live progeny not named, 13.9 per cent, named animals not trained (2 to 4) years), 20.1 per cent and trained animals that did not run at 2 to 4 years, 6.2 per cent. This gave an overall figure for wastage of 72.8 per cent. Data on the numbers of outings as well as the numbers of animals imported and exported are quoted. An estimate of the cost of these losses was made under the following categories: lost stallion fees, keep of mares, keep of unnamed foals and keep of named animals that did not run. The cumulative losses for the 1974 season and its progeny was calculated to be at least £15.2 million. Phase 2 examined more specifically some of the areas of wastage caused by breeding losses and the reasons for an unsatisfactory number of racing appearances. The most substantial reason for not competing or competing less than the average number of times was horses showing little or no ability to race. In a survey of 762 horses, 26.5 per cent did not race up to the age of 4 years; of these just over one third were being kept as “store” animals for National Hunt racing. The final part of the survey examined the veterinary reasons for wastage. In 314 horses in Newmarket, lameness was the most significant factor. There was an incidence of lameness of 53 per cent at some periods during the season and in 20 per cent of cases the lameness was sufficient to prevent racing afterwards. Résumé Cet article produit les résultats d'une étude menée sous les auspices de la commission d'enquète de la BEVA, étude financée par le British Horserace Betting Levy Board. L'objectif de cette étude était de réunir des informations utilisables à partir des statistiques des courses et de l'elevage afin d'évaluer les pertes et les points faibles de l'industrie des courses de pur sang. Les recherches ont été conduites entre 1977 et 1980. Les résultats sont exposés en deux parties. Dans la première, les statistiques disponibles ont montré qu'un déficit considérable se produit entre la période de monte et l'apparition de la production sur l'hippodrome; les pertes sont du même ordre chaque année. 11.8% des poulinières répertoriées au General Stud Book ont étéécartées de l‘étude parce qu'aucun renseignement sur la monte n'a été renvoyé. En outre 10% des poulinières furent ou bien non saillies ou bien saillies par des demi sang, d'autres mettant bas à l’étranger. On a donc retenu pour servir de base à l'estimation le reliquat, c'est‐à‐dire celles des poulinières dont les résultats de saillie furent officiellement confirmés (renseignements effectivement “retournés”). Les résultats furent les suivants: — vides (n'ayant pas conçu): 22.5% — avortées ou ayant eu un produit qui n'a pas vécu: 10% — production vivante non nommée: 13.9% (anonymes) — animaux nommés qui n'ont pas étéà l'entraînement entre deux et quatre ans: 20.1% — animaux entraînés qui n'ont pas couru entre 2 et 4 ans: 6.2% Au total le déficit s'élève à 72.8% Les données se rapportant au nombre d'animaux importés et exportés sont fournies. Une estimation du montant des pertes ainsi constatées a été faite sous les rubriques suivantes: pertes sur les coûts de saillie — pertes sur l'entretien des juments — pertes sur l'entretien des poulains anonymes — pertes sur l'entretien des chevaux qui n'ont pas couru. Cumulées, les pertes pour la saison 1974 et pour ceux des animaux nés cette année lâ ont été estimés à plus de 15.2 millions de livres sterling. Dans la seconde partie, on examine plus particulièrement quelques unes des sources de déficit et les raisons du nombre insuffisant des sorties en course. La raison la plus importante pour ne pas courir ou pour courir moins souvent que la moyen ne est l'inaptitude pure et simple à la compétition. Pour 762 chevaux on constate que 26.5% d'entre eux n'ont pu courir avant l‘âge de 4 ans. Parmi ceux‐ci un peu plus d'un tiers fut conservé pour les programmes de courses à obstacles. La dernière partie de cette enquête étudie les raisons “vétérinaires” du déficit. A Newmarket, pour 314 chevaux on a trouvé que la boiterie était le facteur le plus important. A un certain moment, on a constaté 53% de boiteries durant la saison et dans 20% des cas les boiteries ont empêché le retour à la compétition. Zusammenfassung Dieser Beitrag beschreibt eine gemeinsame Untersuchung, die von der BEVA überwacht und vom Horserace Betting Levy Board finanziert worden ist. Es wurde die Absicht verfolgt, relevante Angaben aus Zucht‐ und Rennstatistiken zu sammeln und die Verluste, die im Vollblut‐Rennbetrieb sich einstellen, auszuwerten. Die Untersuchung erstreckte sich über die Jahre 1977 bis 1980 und wurde in zwei Teilen vorgenommen. Die zugänglichen Statistiken zeigten, dass in Phase 1 ein erheblicher Verschleiss sich bemerkbar macht zwischen der Deckzeit und dem Erscheinen des Nachwuchses in Flachrennen. Diese Verluste veränderten sich von Jahr zu Jahr kaum. Von den “aktiven” Stuten im General Stud Book wurden zwischen 1973 und 1979 11.8 Prozent eliminiert, weil das Deckergebnis nicht gemeldet wurde und weitere 10.1% wurden entweder nicht belegt oder durch Warmbluthengste gedeckt, oder sie fohlten ins Ausland ab. Die verbleibenden Stuten (Stuten mit bekannten Deckangaben und Abfohler‐gebnissen) dienten zu einer Verschleissschätzung: Keine Konzeption 22.5% Abort oder nichtüberlebendes Fohlen 10.1% lebendes, namenloses Fohlen 13.9% Tiere mit Namen, aber nicht im Training zwischen 2 bis 4 Jahren 20.1% Im Training, aber nicht im Rennen zwischen 2 bis 4 Jahren 6.2% Das ergibt eine Verschleissrate von 72.8%. Es werden auch Angaben gemacht über die Anzahl der bestrittenen Rennen und über die Zahl importierter, beziehungsweise exportierter Pferde. Eine Schätzung der durch diesen Verschleiss verursachten Kosten wurde in den folgenden Kategorien angestellt: verlorene Sprunggelder; Kosten der Stutenhaltung; Kosten der Haltung namenloser Fohlen; Haltungskosten für nicht in Rennen eingesetzte Pferde. Die kumulierten Verluste für die Decksaison 1974 und für die Produktion aus dieser Saison wurden auf mindestens 15.2 Mio Pfund geschätzt. In Phase 2 der Untersuchung wurden bestimmte Aspekte dieser Zuchtverluste spezifischer ausgewertet und die Gründe für die unbefriedigende Anzahl bestrittener Rennen erforscht. Der wichtigste Grund dafür, dass viele Pferde überhaupt nie auf die Rennbahn kommen oder nur an einer unterdurch‐schnittlichen Anzahl von Rennen teilnehmen, besteht in einer fehlenden oder ungenügenden Eignung als Rennpferd. Von 762 Pferden bestritten 26.5% bis zu einem Alter von 4 Jahren überhaupt keine Rennen; davon wurde nur etwas mehr als ein Drittel für den Einsatz in Hindernisrennen “aufgespart”. Im letzten Teil der Untersuchung wurden die tierärztlichen Gründe für die Verluste unter die Lupe genommen. Bei 314 Pferden in Newmarket wurde Lahmheit als weit wichtigster Grund festgestellt. Während der Rennsaison ergaben sich Perioden mit einer Lahmheitsfrequenz von 53%, wobei 20% der lahmen Pferde auch später nicht mehr in Rennen eingesetzt werden konnten.
Article
Designer foods provide benefits for both consumers and the food-processing industry, and represent a significant opportunity for biotechnology companies. But are they also blurring the definition of a drug?
Article
The basic science immunology community is quite accepting of the phenomenon of oral tolerance induction in animals; however, in contradistinction, the clinical community is somewhat agnostic regarding oral tolerance. Progress in multiple sclerosis has not been definitive and outcomes in RA have been modest at best. Recent reports in animal models have suggested that oral ingestion of autoantigen can have deleterious effects on the host. Although those experiments have had a highly artificial framework, they are consistent with the possibility that oral antigen therapy in human disease may be: (1) beneficial; (2) of no consequence; or (3) detrimental. An extremely open mind will hopefully be applied to future research efforts.
Article
Effects of hyperimmune milk factor (HIMF), an anti-inflammatory factor from milk of hyperimmunised cows, on tight junction permeability and cell growth were studied in vitro. Mammary (HC11) and kidney (MDCK) epithelial cell lines were used. HIMF was used at a final concentration of 2 mg/ml. Tight junction permeability was assessed by measuring transepithelial electrical resistance (TER) across confluent monolayers, following the addition of HIMF with or without an inflammatory challenge. Cell growth was assessed by measuring total DNA of cultures with and without HIMF. Data were analysed by analyses of variance. HIMF promoted tight junction formation and prevented loss of TER following a challenge in both epithelia. Post-challenge recovery of TER was also faster with HIMF. HIMF inhibited cell growth. HIMF stimulates tight junction maintenance and formation, and its previously reported anti-inflammatory properties may be mediated by restricting the extravasation of white blood cells through tight junctions.
Article
Objective: Avocado and soya unsaponifiables (ASU) have been reported to exert beneficial effects in the treatment of periodontal and osteoarticular diseases. They are supposed to stimulate deposition and repair of extracellular matrix components, but the mechanisms underlying their action are not well understood. In view of the repair potential of osteoarthritic (OA) cartilage and the role that the transforming growth factor beta (TGFbeta) system could play in that process, we carried out in vitro studies to determine the mechanism of action of ASU on articular chondrocytes that may account for the beneficial effects on cartilage metabolism. Methods: Cultured bovine articular chondrocytes were treated with various concentrations of ASU, and the expression of both TGFbeta isoforms, 1 and 2, and their receptors (TGFbetaRI and TGFbetaRII) was determined by Northern blot and reverse transcriptase-polymerase chain reaction. Cell transfection with TGFbeta1 promoter constructs was also used to delineate the cis-acting sequences mediating ASU responsiveness in chondrocytes. The level of plasminogen activator inhibitor 1 (PAI-1) was also evaluated by Northern blotting and protein radiolabeling. Results: The data indicated that ASU stimulate the expression of TGFbeta1, TGFbeta2, and PAI-1 by articular chondrocytes. In contrast, the levels of TGFbetaRI and TGFbetaRII were not significantly affected by the compound. Treatment of bovine articular chondrocytes transiently transfected with TGFbeta1 promoter constructs suggested that the effect on TGFbeta1 expression is mediated by the region located between -732 and -1132 bp. Conclusion: The results indicate that the ASU-induced stimulation of matrix synthesis previously reported in cultured articular chondrocytes could be explained by the ability to enhance TGFbeta expression in these cells. Further, ASU increase the production of PAI-1, an effect that could help in blocking the plasmin cascade that leads to metalloprotease activation. These data suggest that the compound has properties that might promote TGFbeta-induced matrix repair mechanisms in articular cartilage.
Article
To evaluate the effects of orally administered glucosamine hydrochloride (GlAm)-chondroitin sulfate (CS) and GlAm-CS-S-adenosyl-L-methionine (SAMe) on chemically induced synovitis in the radiocarpal joint of dogs. 32 adult mixed-breed dogs. For 21 days, all dogs received a sham capsule (3 groups) or GlAm-CS (prior treatment group) in a double-blinded study. Unilateral carpal synovitis was induced by injecting the right radiocarpal joint with chymopapain and the left radiocarpal joint (control joint) with saline (0.9% NaCl) solution. Joints were injected on alternate days for 3 injections. After induction of synovitis, 2 groups receiving sham treatment were given GlAm-CS or GlAm-CS-SAMe. Another group continued to receive sham capsules (control group). Joint inflammation was quantified, using nuclear scintigraphy, before injection of joints and days 13, 20, 27, 34, 41, and 48 after injection. Lameness evaluations were performed daily. Dogs given GlAm-CS before induction of synovitis had significantly less scintigraphic activity in the soft-tissue phase 48 days after joint injection, significantly less uptake in the bone phase 41 and 48 days after joint injection, and significantly lower lameness scores on days 12 to 19, 23, and 24 after injection, compared with other groups. Analysis of results of this study suggest that prior treatment with GlAm-CS for 21 days had a protective effect against chemically induced synovitis and associated bone remodeling. Prior treatment with GlAm-CS also reduced lameness in dogs with induced synovitis.
Article
Supplements of glucosamine hydrochloride, low molecular weight chondroitin sulfate, and manganese ascorbate were tested separately and in combination for their ability to retard progression of cartilage degeneration in a rabbit instability model of osteoarthrosis. Computerized quantitative histologic evaluation of safranin O stained sections of the medial femoral condyles measured the grade and extent of tissue involvement of lesions. Severe lesions (Mankin grade greater than 7) were absent in all animals supplemented with a dietary mixture of glucosamine, chondroitin sulfate, and manganese ascorbate. Total linear involvement (mm of lesioned surface) and total grade (mean grade x number of lesions per animal) were reduced significantly in animals given the combination compared with controls (59% and 74% respectively). Animals supplemented with glucosamine, chondroitin sulfate, or manganese ascorbate alone had less moderate and severe tissue involvement than controls but not to the extent of the combined group. In vitro, a combination of glucosamine hydrochloride and chondroitin sulfate acted synergistically in stimulating glycosaminoglycan synthesis (96.6%). Chondroitin sulfate and manganese ascorbate but not glucosamine were effective in inhibiting degradative enzyme activity. These data suggest that the disease modifying effect (the ability to retard progression of cartilage degeneration) of a mixture of glucosamine, chondroitin sulfate, and manganese ascorbate is more efficacious than either agent alone.
Article
To evaluate effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate (CS-G-M) on articular cartilage metabolism in dogs with cranial cruciate ligament (CCL) deficient and reconstructed knees, as reflected by concentrations of synovial fluid 3B3, 7D4 and total sulfated glycosaminoglycan (GAG). Sixteen adult dogs that underwent unilateral CCL transection were randomized into four groups. Thereafter, group I (N=3) had a sham CCL reconstruction, group II (N=3) had CS-G-M and sham CCL reconstruction, group III (N=5) had CCL reconstruction, and group IV (N=5) had CS-G-M and CCL reconstruction. Synovial fluid collected at 0, 1, 3 and 5 months was examined by ELISA for 3B3 and 7D4 epitope, and by DMMB assay for total GAG. Synovial fluid from CCL transected knees of CS-G-M treated dogs contained significantly elevated concentrations of 3B3 (P=0.029), 7D4 (P=0.036) and 7D4/GAG (P=0.007) in comparison to controls, in a cross-sectional analysis at 3 months. Furthermore, 7D4 and 7D4/GAG concentrations remained significantly elevated (P=0.012) in CCL transected knees of CS-G-M treated dogs over the 5 month period. However, when epitope concentrations were expressed as a ratio of CCL-transected to contralateral non-operated knee, treatment effect of CS-G-M was no longer significant. Reconstruction of the CCL had no significant effect on synovial fluid epitope. Administration of CS-G-M was associated with altered concentrations of 3B3 and 7D4 epitope in synovial fluid, suggesting that these compounds may act to modulate articular cartilage matrix metabolism in vivo.
Article
Rheumatoid arthritis is characterized by infiltration of T lymphocytes, macrophages and plasma cells into the synovium, and the initiation of a chronic inflammatory state that involves overproduction of proinflammatory cytokines and a dysregulated T-helper-1-type response. Eicosanoids synthesized from arachidonic acid and cytokines cause progressive destruction of cartilage and bone. The n-6 polyunsaturated fatty acid gamma-linolenic acid is the precursor of di-homo-gamma-linolenic acid. The latter and the n-3 polyunsaturated fatty acid eicosapentaenoic acid, which is found in fish oil, are able to decrease the production of arachidonic acid-derived eicosanoids and to decrease the production of proinflammatory cytokines and reactive oxygen species, and the reactivity of lymphocytes. A number of double-blind, placebo-controlled trials of gamma-linolenic acid and fish oil in rheumatoid arthritis have shown significant improvements in a variety of clinical outcomes. These fatty acids should be included as part of the normal therapeutic approach to rheumatoid arthritis. However, it is unclear what the optimal dosage of the fatty acids is, or whether there would be extra benefit from using them in combination.
Article
The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.