J O U R N A L O F B L O O D G R O U P S E R O L O G Y A N D E D U C A T I O NV O L U M E 1 6 , N U M B E R 3 , 2 0 0 0J O U R N A L O F B L O O D G R O U P S E R O L O G Y A N D E D U C A T I O N A review: modification of the red blood ce ll membrane and its application in blood group serology Key Words: red cell antigens,enzymes,modification of able for use in the blood bank. These incl
Doi:10.1016/j.cvsm.2006.08.007Vet Clin Small Anim 36 (2006) 1307–1323 Nutrition and Osteoarthritis in Dogs:Does It Help? Steven C. Budsberg, DVM, MS,Joseph W. Bartges, DVM, aDepartment of Small Animal Medicine and Surgery, College of Veterinary Medicine,University of Georgia, Athens, GA 30602, USAbDepartment of Small Animal Clinical Sciences, Veterinary Teaching Hospital,College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37996-4544, USA Osteoarthritis(OA)isacommonsyndromehavingmultiplecausesand characterized by pathologic change of the synovial or diarthrodialjoint accompanied by clinical signs of pain and disability. Confusion about the definition of OA has arisen over the years; recently, the AmericanAcademy of Orthopaedic Surgeons proposed the following consensus defini-tion: osteoarthritic diseases are a result of mechanical and biologic events thatdestabilize the normal coupling of degradation and synthesis of articular carti-lage chondrocytes, extracellular matrix (primarily collagen and aggrecan), andsubchondral bone. Although they may be initiated by multiple factors, includ-ing genetic, developmental, metabolic, and traumatic factors, osteoarthritic dis-eases involve all the tissues of the diarthrodial joint. Ultimately, osteoarthriticdiseases are manifested by morphologic, biochemical, molecular, and biome-chanical changes of cells and matrix that lead to softening, fibrillation, ulcera-tion, articular cartilage loss, sclerosis and subchondral bone eburnation, andosteophyte production. When clinically evident, osteoarthritic diseases arecharacterized by joint pain, tenderness, limitation of movement, crepitus, occa-sional effusion, and variable degrees of inflammation without systemic effects. OA has been estimated to affect as many as 20% of dogs older than 1 yearof age . For years, the discussion of OA and nutrition in small animal med-icine has centered around nutrition and developmental orthopedic disease orthe association between obesity and OA. The enormous public interest inthe relation between diet supplements and OA has recently taken over centerstage when discussing OA and nutrition, however. Physicians and veterinar-ians are constantly asked about these well-advertised supplements. Purely spec-ulative information on nutritionally based therapies to treat OA has permeatedevery form of media available to the public. Unfortunately, few well-designedscientific studies have been initiated to explore these treatments in clinical *Corresponding author. E-mail address: (S.C. Budsberg).
ª 2006 Elsevier Inc. All rights reserved.
patients. Thus, this article focuses solely on the evidence for dietary modifica-tion, including nutraceuticals formulated into diets, in patients with chronicOA.
Our initial discussion focuses on the use of evidence-based medicine. Evi- dence is defined as ‘‘the data on which a judgment or conclusion may be based,or by which proof or probability may be established’’ . Evidence-based med-icine is the integration of best research evidence with clinical expertise and pa-tient values . There are many ways in which to analyze and integrateevidence into the practice of veterinary medicine and several schemes by whichto rank the strength of evidence. In this article, we review results of randomizedplacebo-controlled studies, and, where none exist, clinical trials or controlledexperimental studies. Searches were performed on PubMed, setting the searchlimits to include only ‘‘clinical trial’’ and ‘‘randomized controlled trial.’’ Thesesearches were limited to ‘‘dogs’’ or ‘‘humans.’’ The final search using ‘‘dogAND (arthritis OR osteoarthritis OR degenerative joint disease) AND (dietOR nutrition OR nutrient OR nutraceutical OR supplement),’’ supplementedwith a search of bibliographies of articles that discussed the management of ca-nine OA, yielded seven articles, of which five were randomized controlled stud-ies. These studies varied in quality and type of design, limiting the strength ofevidence they can provide to the clinician. The studies are briefly abstracted togive the reader some idea of the different studies done and their limitations.
The most striking limitation shown here is the sheer lack of the number of stud-ies and the number of dogs involved.
STUDY RESULTSStudy by Bui and BiererBui and Bierer evaluated the efficacy of green-lipped mussel (GLM; Pernacanaliculus), added to a complete dry diet, for alleviating clinical signs of arthritisin dogs. A blind, randomized, longitudinal study design was used, with 31 dogsexhibiting varying degrees of arthritis. Each dog was evaluated by a veterinar-ian, and joints were individually scored for degree of pain, swelling, crepitus,and reduction in range of movement. Summation of all scores for an individualdog comprised its total score. Both groups were fed the same base dry diet, towhich 0.3% GLM powder was added in the test group. The change in totalscore, by the end of 6 weeks, showed a significant improvement (P < .05) inthe test group versus the control group. Significant improvements were also ob-served in joint pain and swelling scores in the test group. Changes in joint crep-itus and range of joint movement were not significantly different between thetest and control groups.
Study by Dobenecker and colleaguesThe objective of the study by Dobenecker and colleagues was to com-pare dog owners’ perceptions of the effects of chondroitin sulfate (CS) or NewZealand GLM extract with a placebo in a double-blind field study in dogs witha chronic degenerative joint disease. Seventy dogs of different breeds, ages, and genders were included in the study. Patients were randomized into threegroups: the first group was given CS, the second group received mussel extract(GLM powder), and the third group was fed a placebo. The supplements weremixed into the normal diet of the patients. Changes in clinical symptoms duringthe 12-week oral application period were verified separately by dog owners andthe attending veterinarians using standardized questionnaires at the beginningand end of the study. Fifty-eight dogs (83%) finished the trial. An important resultof this study is that none of the tested substances led to a distinct improvement inthe recorded symptoms or even to total recovery in general. The evaluation of thequestionnaires of the attending veterinarians revealed good correspondence be-tween the judgment of owners and experts. Both groups reported a slight im-provement of the symptoms regarding the means of all three treatment groups,including that fed a placebo.
Study by Innes and colleaguesP54FP is an extract of Indian and Javanese turmeric, Curcuma domestica and Cur-cuma xanthorrhiza, respectively, that contains a mixture of active ingredients, in-cluding curcuminoids and essential oils. Innes and colleagues conducteda randomized, blind, placebo-controlled, parallel-group clinical trial of P54FPas a treatment for OA of the canine elbow or hip. Sixty-one client-owneddogs with OA were recruited for the study at a single center. After a 2-weekwash-out period, they were randomly allocated to receive P54FP or a placeboorally twice daily for 8 weeks and were re-examined after 4, 6, and 8 weeks oftreatment. The effectiveness of the treatment was assessed in terms of the peakvertical force (PVz) and vertical impulse of the affected limbs, as measured witha force platform, by clinical assessments of lameness and joint pain by the in-vestigators and overall assessment of the response to treatment by the investi-gators and owners. The results from 25 P54FP-treated dogs and 29 placebo-treated dogs showed that there was no statistically significant difference be-tween the groups in terms of the PVz of the affected limb. The investigators’overall assessment showed a statistically significant treatment effect in favorof P54FP (P ¼ .012), but the owners’ assessment failed to reach statisticalsignificance (P ¼ .063). No serious adverse effects were recorded, but 2 P54FP-treated dogs and 4 placebo-treated dogs were withdrawn from the studybecause their condition deteriorated.
Study by Reichling and colleaguesReichling and colleagues conducted an open multicenter clinical trial com-paring conditions before and after treatment with a natural resin extract of Bos-wellia serrata. Twenty-nine dogs with manifestations of chronic joint and spinaldisease were enrolled. OA and degenerative conditions were confirmed radio-logically in 25 of 29 cases. The resin extract (BSB108; Bogar AG, Wallisellen,Switzerland) was administered with the regular food at a dose of 400 mg per10 kg of body weight once daily for 6 weeks. A statistically significant reductionof severity and resolution of typical clinical signs in individual animals, such asintermittent lameness, local pain, and stiff gait, were reported after 6 weeks. In 5 dogs, reversible brief episodes of diarrhea and flatulence occurred, but onlyonce was a relation to the study preparation suspected.
Study by Gingerich and StrobelGingerich and colleagues designed a questionnaire method for dog ownersto monitor the orthopedic disabilities of their pets for evaluation of a nutraceut-ical with joint health claims. Fifty large-breed dogs presented with signs of OAwere randomly allocated to placebo and active treatment groups. Degree of dis-ability was assessed by physical examination, a standard questionnaire on dailyactivities, and a case-specific questionnaire that monitored specific impairmentsof each dog. The test product was a special milk protein concentrate (SMPC;Microlactin, Stolle Milk Biologics, Cincinnati, Ohio). Only 35 of the dogs com-pleted the study. Overall improvement was noted in 68% and 35% of theSMPC and placebo groups, respectively. A significant (P < .05) improvementin mean standardized and patient-specific questionnaire scores and in ownerglobal assessments was detected in the SMPC group but not in the placebogroup. Compared with the placebo group, the treatment response was signifi-cantly better in the SMPC group with regard to case-specific scores (P < .001)and owner global assessments (P ¼ .004).
Study by Moreau and colleaguesThe efficacy, tolerance, and ease of administration of a nutraceutic agent, car-profen, or meloxicam were evaluated in a prospective double-blind study byMoreau and colleagues in 71 dogs with OA. The client-owned dogswere randomly assigned to one of the three treatments or to a placebo controlgroup. The influence of OA on the dogs’ gait was described by comparing theground reaction forces of the arthritic dogs and 10 normal dogs. Additionally,subjective assessments were made by the owners and by the orthopedic sur-geons. Changes in the ground reaction forces were specific to the arthritic jointand were significantly improved by carprofen and meloxicam but not by thenutraceutic agent; the values returned to normal only with meloxicam. The or-thopedic surgeons assessed that there had been an improvement with carprofenand meloxicam, but the owners considered that there had been an improve-ment only with meloxicam. The treatments were well tolerated, except fora case of hepatopathy in a dog treated with carprofen.
Study by Impellizeri and colleaguesImpellizeri and colleagues conducted a study on the effect of weight reduc-tion on clinical signs of lameness among overweight dogs with clinical and ra-diographic signs of hip OA. This was a nonblind prospective clinical trial. Nineclient-owned dogs with radiographic signs of hip OA that weighed 11% to 12%greater than their ideal body weight and were examined because of hind limblameness were included in the study. Baseline body condition, hind limb lame-ness, and hip function scores were assigned. Severity of lameness was scoredusing a numeric rating scale and a visual analog scale. Dogs were fed a re-stricted-calorie diet, with the amount of diet fed calculated to provide 60% of the calories needed to maintain the dogs’ current weight. Evaluations were re-peated midway through and at the end of the weight loss period. Dogs lost be-tween 11% and 18% of their initial body weight. Body weight, body conditionscore, and severity of hind limb lameness were all significantly decreased at theend of the weight loss period.
OA is the most common form of arthritis recognized in dogs Hip dys- plasia, cruciate instability, and osteochondritis dissecans are common causes ofcanine OA (degenerative joint disease). As previously described, degenerativeOA is characterized as a slowly progressive condition in which two primarypathologic processes occur: articular cartilage degeneration and subchondralbone changes. A low-grade synovitis often occurs. Inflammation is present inthese joints, and steroidal or nonsteroidal anti-inflammatory drugs may modu-late this inflammation. Although nutritional imbalances may result in develop-mental skeletal disease (see the article by Lauten elsewhere in this issue), which,in turn, may lead to degenerative joint disease, the role of nutrition in the man-agement of degenerative joint disease is less clear. Nutrition may aid in treat-ment of degenerative joint disease through optimizing body condition andbody weight (managing obesity), by modifying degenerative or inflammatoryprocesses (specific nutrient effects), and by influencing pharmacologic therapy(drug-nutrient interaction).
OBESITYObesity can be defined as accumulation of body fat in excess of what is neces-sary to maintain optimum condition and health. This may be obvious ina grossly obese individual, particularly when obesity-related disease is present;however, it is less obvious in a patient that is overweight and otherwise clini-cally healthy but is at risk for obesity-related disease, such as degenerativeOA. Quantitatively, obesity in dogs is generally defined as exceeding idealbody weight by 15% to 20% or more. One technique that is useful in the man-agement of patients is a body condition score. The advantage of assigning abody condition score is that it uses information additional to body weight. Itis a measure of the appearance of the animal, of fat stores that are identified, ofmuscle mass and tone, and of general health.
Obesity may result in OA as a result of excess forces placed on joints and articular cartilage, which may lead to inactivity and further development ofobesity; thus, a vicious cycle ensues. Additionally, adipose tissue is recognizedas being metabolically active and proinflammatory; therefore, obesity may con-tribute to inflammation .
Several studies have demonstrated a relation between obesity and OA ; however, a cause and effect mechanism has not been found . A long-term study was performed in 48 Labrador Retrievers from seven litters dividedinto two dietary groups: one group was fed an adult maintenance dog food at0.27 kJ of metabolizable energy per kilogram of body weight per day, and thesecond group was fed the same diet at 75% of the amount (0.2025 kJ of metab-olizable energy per kilogram of body weight per day) Restricted fed dogs lived, on average, 2 years longer, weighed less, had better body conditionscores, and had longer delay to treatment of chronic disease, including OA Therefore, maintaining an optimal or slightly lean body condition may be as-sociated with lower risk of development of OA, development of less severeOA, and delay of onset of clinical signs of OA in dogs.
Weight reduction from an obese state is beneficial in the management of OA in human beings In addition to improvement in mobility, weight re-duction was associated with better quality-of-life scores in human beings withknee OA Two uncontrolled clinical studies of obese dogs with OA dem-onstrated improvement in mobility . In one study of 9 dogs with a bodycondition score of 5 of 5 and coxofemoral OA, obesity management resulted inloss of 11% to 18% of body weight, a decrease in body condition to optimalcondition, and improvement in the severity of subjective hind limb lamenessscores . In a second study of 16 dogs with coxofemoral OA, weight lossof 13% to 29% of body weight and decrease of body condition to optimal re-sulted in improvement of ground reactive force as well as improvement in sub-jective mobility and clinical signs of OA Although these are uncontrolledclinical trials in a small number of dogs, results suggest that weight reductionmay be beneficial in dogs with OA.
x-3 FATTY ACIDSDegenerative OA involves an inflammatory component; thus, it may be possi-ble to modify the inflammation by nutritional components, specifically x-3 (n3)fatty acids. Arachidonic acid (an x-6 [n6] fatty acid) is incorporated into cellmembranes; when metabolized, it yields prostaglandins, leukotrienes, andthromboxanes of the 2 and 4 series. Many drugs used to treat degenerativeOA inhibit conversion of arachidonic acid to these eicosanoids. These n6-de-rived eicosanoids have, for the most part, vasoactive and proinflammatory ef-fects. Substituting an n3 fatty acid in the membrane may decrease theseresponses. Metabolism of n3 fatty acids results in eicosanoids of the 3 and 5series, which are less vasoactive and less proinflammatory.
Several studies have been published that demonstrate a beneficial response to n3 fatty acid incorporation into diets of human beings with rheumatoid ar-thritis although other studies have not demonstrated a benefit There is a growing body of data showing positive effects of n3 fatty acids oncartilage and its metabolism in the face of degradative enzymes. Recent workhas provided direct evidence that n3 fatty acid supplementation can reduceor abrogate the inflammatory and matrix degradative response elicited bychondrocytes during OA progression Unfortunately, there are no ran-domized controlled clinical trials published of n3 fatty acids and OA in dogs.
An unpublished study has been performed in dogs evaluating n3 fatty acidsand experimentally induced stifle arthritis . Eighteen dogs were randomlyassigned to one of three isocaloric diet groups containing 21.4% fat (dry matterbasis) differing only in their fatty acid composition: a diet with an n6-to-n3 fattyacid ratio of 28.0:1.0 (high-n6 diet), a diet with an n6-to-n3 fatty acid ratio of 8.7:1.0 (control diet), and a diet with an n6-to-n3 fatty acid ratio of 0.7:1.0(high-n3 diet). Diets were fed for a total of 21 months. Initially, the dogswere started on their assigned diet 3 months before surgical transection ofthe left cranial cruciate ligament, continued until surgical repair 6 months later,and maintained for an additional 12 months after repair. When compared withthe high-n6 and control diets, consumption of the high-n3 diet was associatedwith lower serum concentrations of cholesterol, triglycerides, and phospho-lipids; lower synovial concentrations of prostaglandin E2; better ground reac-tion forces; and fewer radiographic changes of OA. Synovial membrane fattyacid composition mirrored the fatty acid composition of the diets consumedby the dogs. Recently, a randomized study was presented in abstract form,where 38 dogs with naturally occurring OA were placed on a commerciallyavailable therapeutic food formulated to contain an n6-to-n3 ratio of 0.7:1.0(Prescription Diet J/d; Hill’s Pet Nutrition, Topeka, Kansas) or a typical drydog food . Ground reaction forces as well as owner and veterinarian clinicalevaluations were collected at days 0, 45, and 90. Ground reaction forces in-creased and weight bearing increased in the dogs fed the therapeutic dietwhen compared with the control diet. It should be noted that the two diets dif-fered in more than just the fatty acid composition, but this was the major dif-ference. Finally, one study in dogs reported results of observations of dogowners who perceived improvement in their pet’s arthritic symptoms whentreated with fatty acids for various dermatologic problems .
ANTIOXIDANTSThe formation of free radicals as a consequence of cellular metabolism occursconstantly, but the potential deleterious effects are minimized by antioxidants.
The balance between free radicals and antioxidant defenses is a key factor inpreventing development of noxious processes at the cellular and tissue levels.
Recent evidence supports the theory that excessive production of free radicalsor the imbalance between concentrations of free radicals and antioxidant de-fenses may be related to such processes as aging, cancer, diabetes mellitus, lu-pus, and arthritis . Progressive hypoxia resulting in the production ofreactive oxygen species may play a role in rheumatoid arthritis . Thus, an-tioxidant therapy may be of benefit in the treatment of OA Most studies of antioxidant therapy for arthritis in human beings involve rheumatoid arthritis, although several studies of knee OA have been published.
An early pilot study of vitamin E (tocopherol) demonstrated improvement inclinical signs and pain scores in 52% of 29 patients with knee OA comparedwith 4% receiving a placebo . In another placebo-controlled study of humanbeings with OA of the coxofemoral or knee joint, high-dose tocopherol was asefficacious as diclofenac in reducing pain and improving mobility Thiswas also found in studies of human beings with rheumatoid arthritis .
Other studies have not demonstrated a benefit of vitamin E for rheumatoid ar-thritis or OA . Likewise, the efficacy of vitamin C in human beings withOA has been difficult to determine because of contradictory results of studies Selenium was not shown to be beneficial in human beings with rheu-matoid arthritis . Methyl-sulfonyl-methane (MSM) is a derivative of di-methyl sulfoxide and has been suggested as an agent for the management ofpain and inflammation and as an antioxidant. The rationale for its use lies inthe possibility of a dietary sulfur deficiency, with a resultant deficiency of sul-fur-containing compounds in the body, such as antioxidants and CS Cur-rently, there are no randomized controlled clinical trials evaluating MSM inhuman beings; however, in a recent pilot clinical trial involving a placebo con-trol, MSM reduced the Western Ontario and McMaster University Osteoar-thritis Index visual analog scale scores and pain and improved physicalfunction when compared with placebo . There are no controlled studiesevaluating or documenting a benefit of vitamin C, MSM, or selenium indogs with OA, although they may be recommended Dogs do not re-quire exogenous vitamin C because they are capable of synthesizing it endog-enously; therefore, its use is not encouraged.
CHONDROMODULATING AGENTSChondromodulating agents are purported to slow or alter the progression ofOA. These agents are considered to be slow-acting drugs in osteoarthritis(SADOAs) and can be subdivided into symptomatic slow-acting drugs in oste-oarthritis (DMOADs). Beneficial effects may include a positive effect on cartilage matrixsynthesis and hyaluronan synthesis by synovial membrane as well as an inhib-itory effect on catabolic enzymes in osteoarthritic joints Compounds fallinto two different categories. One group is agents that are approved by theUS Food and Drug Administration and can have label claims of clinical effects,such as polysulfated glycosaminoglycan (Adequan; Luitpold Pharmaceuticals,Shirley, New York). The second group comprises products that are consideredto be nutritional supplements, which are not regulated and legally cannot claimany medical benefits. Examples of this group include glucosamine and CS (Gly-coflex; Vetri-Science Laboratories, Essex Junction, Vermont and Cosequin;Nutramax Laboratories, Baltimore, Maryland). Although many of these prod-ucts are administered as a supplement or alternative treatment, some, such asglucosamine and GLM, are incorporated into pet foods.
Glucosamine and Chondroitin SulfateGlucosamine is an amino sugar that is a precursor for biochemical synthesis ofglycosylated proteins and lipids. D-glucosamine is made naturally in the formof glucosamine-6-phosphate and is the biochemical precursor of all nitrogen-containing sugars Specifically, glucosamine-6-phosphate is synthesizedfrom fructose-6-phosphate and glutamine as the first step of the hexos-amine biosynthesis pathway. The end product of this pathway is uridinediphosphate (UDP)-N-acetylglucosamine, which is then used for making gly-cosaminoglycans, proteoglycans, and glycolipids. Because glucosamine is aprecursor for glycosaminoglycans and glycosaminoglycans are a major component of joint cartilage, supplemental glucosamine may help to rebuildcartilage, and there are in vitro data to support this claim There areconflicting data on evidence of any clinical effect of glucosamine in veterinarymedicine, however . Commonly used forms of glucosamine includeglucosamine sulfate and glucosamine hydrochloride, and it is often combinedwith CS and MSM. A review of studies of pharmacologic dosages of glucos-amine is beyond the scope of this article; however, glucosamine, with CS, isincluded in dog foods at low concentrations.
When evaluating glucosamine and CS inclusion in a manufactured dog food, two questions might be asked. Are the glucosamine and CS in the food stableand bioavailable? Is the amount of glucosamine and CS in the food enough toprovide a beneficial effect? It is difficult to find the amount of glucosamine andCS in pet foods. Many dog foods formulated and marketed for adult dogs, ge-riatric dogs, and large-breed growth contain glucosamine and CS, but theamounts are not readily available from the manufacturer or from electronicor print information. These compounds are not recognized by the AmericanAssociation of Feed Control Officials, and thus are not included in dog nutrientprofiles. Furthermore, they are not considered as ‘‘generally regarded as safe’’(GRAS) ingredients.
New Zealand Green-Lipped MusselNew Zealand GLM is a rich source of glycosaminoglycans, although its pro-posed benefit is thought to be from the anti-inflammatory effects of tetraenoicacid of the n3 series In 1986, dried mussel extracts that were stabilizedwith a preservative became available. The earlier studies that found no benefi-cial effect of GLM on arthritis all used preparations that had not been stabi-lized, which is a point that may help to explain some of the discrepancies inthe research. A stabilized lipid extract (Lyprinol, Pharmalink International,Lancashire, England) is more effective than a nonstabilized extract at inhibitinginflammation In an uncontrolled clinical trial, Lyprinol administration re-sulted in an 80% improvement in human beings with rheumatoid arthritis .
In a randomized controlled clinical study of 31 dogs with arthritis, GLM pow-der (0.3%) was added to the diet during processing of one group of dogs .
Compared with the control group, which was fed the same diet without addedGLM powder, there was significant improvement in subjective arthritis scores,joint swelling, and joint pain in the treated group. These data must not be over-interpreted, however. In a systematic review of agents used to treat canine OA,the data regarding the benefits of GLM extract in dogs were promising but un-certainties existed relating to the scientific quality of the data, and no definitiverelation has been proven between clinical improvements and the therapy .
OTHER DIETARY COMPOUNDSThere are many other dietary supplements, including herbs and other nutra-ceutic agents, that are recommended. Few, if any, have been evaluated in a con-trolled manner. Because of limitations of space, only a few are discussed.
P54FPP54FP is an extract of Indian and Javanese turmeric, C domestica and C xanthor-rhiza, respectively, which contains a mixture of active ingredients, including cur-cuminoids and essential oils There is evidence that these active ingredientspossess anti-inflammatory activity. Specifically, curcumin has been shown toinhibit prostaglandin E2 and cyclooxygenase-2 as well as nuclear factor-jBOne randomized blind study in dogs with OA found no differencein objective ground reaction forces but did see some improvements in certainsubjective outcome measures .
Avocado/SoyAvocado/soybean unsaponifiables (ASUs) are composed of the unsaponifiablefractions of avocado and soybean oils in a 1:3 to 2:3 proportion, respectivelyIn vitro data show that ASUs have antiosteoarthritic properties by in-hibiting interleukin-1 and stimulating collagen synthesis in cartilage culturesIn vivo, there is one report in an ovine meniscectomy model of OA pro-viding some support for disease-modifying capabilities Human clinical tri-als have shown some beneficial effects of ASUs on clinical symptoms ofsymptoms of OA and suggest that ASUs may have some structure modificationcapabilities. There are, however, some conflicting data, because one studyfound no long-term benefits ASUs have not yet been evaluated indogs with OA.
BoronBoron deficiency in food may be part of the cause of some arthritides Ep-idemiologic studies suggest that human beings in countries with low boron in-take (less than 1.0 mg/d) have a higher risk of development of arthritis whencompared with human beings in countries in which boron intake is higher(3–10 mg/d) . In a double-blind placebo/boron supplementation trial in20 subjects with OA, a significantly favorable response to a boron supplementat 6 mg/d was found; 50% of subjects receiving supplement improved com-pared with 10% receiving placebo . Whether boron deficiency occurs inpet dogs is unknown. Furthermore, whether boron supplementation andwhat dosage of boron would be best are unknown. Until studies are performed,supplementation cannot be recommended.
Boswellia ResinBoswellia, also known as Boswellin or Indian frankincense, comes from the In-dian Boswellia serrata tree. Resin from the bark of this tree is purported to haveanti-inflammatory properties. Boswellia resin has been shown to improve clin-ical signs and pain in human beings in controlled studies . Boswelliaresin has been evaluated in 24 dogs in an open multicenter study . Improve-ment in clinical signs, lameness, and pain was found in 17 of 24 dogs. In 5 dogs,diarrhea and flatulence occurred. Further controlled clinical trials are needed tovalidate these findings.
Cat’s ClawCat’s claw, an Amazonian medicinal plant, has anti-inflammatory and antioxi-dant effects and has been shown to decrease clinical signs of knee arthritis andrheumatoid arthritis in human beings . It has not been evaluated in dogswith OA.
CreatineCreatine is used in muscle for production of ATP, which provides energy formuscle contraction. Creatine is sometimes used by body builders and peoplewho exercise with the intent to increase muscle mass and muscular energy;however, some recommend its use with arthritis, especially rheumatoid arthri-tis in human beings. In rheumatoid arthritis, skeletal muscle weakness often ac-companies the arthropathy. In one study, creatine supplementation in humanbeings with rheumatoid arthritis increased serum and skeletal muscle creatinecontent but failed to increase skeletal muscle creatine phosphate concentrationor strength . In another study of human beings undergoing total knee re-placement, creatine supplementation did not improve body composition orskeletal muscle strength No randomized controlled studies have been per-formed in dogs with OA.
Special Milk Protein ConcentrateMilk contains a number of biologically active compounds, including immuno-globulins, cytokines, enzymes, hormones, and growth factors. These com-pounds impart anti-inflammatory properties that have been recognized inhuman breast milk and milk from hyperimmunized cows AnSMPC prepared from milk of hyperimmunized cows (Microlactin) exertsanti-inflammatory properties . The anti-inflammatory properties do notseem to be caused by inhibition of arachidonic acid metabolism but by suppres-sion of neutrophil migration from the vascular space A randomized con-trolled clinical trial has been performed evaluating the SMPC in dogs withnaturally occurring OA In this study, dogs receiving the SMPC had im-provement in subjective clinical signs of OA and owner global assessment com-pared with dogs receiving placebo. Further studies need to be completed tovalidate these findings.
CURRENTLY AVAILABLE VETERINARY DIETSMany over-the-counter dog foods contain claims of being ‘‘joint friendly’’ be-cause they contain glucosamine, CS, and perhaps other ingredients theorizedto be beneficial for joint health. There are four diets specifically formulatedand marketed for dogs with arthritis: CNM Joint Mobility JM (Ralston Purina,St. Louis, Missouri), Prescription Diet J/d (Hill’s Pet Nutrition), Mobility Sup-port JS 21 (Royal Canin, St. Charles, Missouri), and Mobility Support JS 21Large Breed (Royal Canin). Nutritional characteristics are presented in .
Most adult maintenance dog foods have n6-to-n3 ratios of greater than8.0:1.0; therefore, these diets are higher in n3 fatty acids relative to mainte-nance adult dog foods.
Table 1Average nutrient content for CNM Joint Mobility, Prescription Diet J/d, Mobility Support JS 21, and Mobility Support JS 21 Large Breed Abbreviations: Ca/P, calcium-to-phosphorous ratio; J/d, Prescription diet J/d canine diet (Hill’s Pet Nutrition, Topeka, Kansas); JM, CNM Joint Mobility JM canine diet (RalstonPurina, St. Louis, Missouri); JS, Mobility Support JS 21 canine diet (Royal Canin, St. Charles, Missouri); JS LB, Mobility Support JS 21 Large Breed (Royal Canin); ME, metaboliz-able energy.
Recent research supports a role of nutrition and nutritional modification in the management of OA in dogs. Furthermore, weight management, includingweight reduction and prevention of obesity, has a positive impact on the inci-dence and clinical signs of OA in dogs. Feeding diets that contain increased n3fatty acids and GLM has been shown to help dogs with OA. Whether otherdietary ingredients provide benefit has yet to be determined.
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2 Sterling Avenue Manurewa, Auckland Tel: 09 270 4157 Fax: 09 270 4159 www.nufarm.co.nz EMERGENCY INFORMATION AND STORAGE GUIDE / DANGEROUS GOODS DECLARATION 3 566 Insecticide Substance: Bright yellow liquid, (emulsifiable concentrate) containing 475g/L pirimiphos-methyl (CAS No. 29232-93-7 )and 25g/L permethrin (CAS No. 52645-53-1) Proper shipping name : FLAMMABLE LIQUID, N.O.S. (