SEARCHING FOR A COMPLIMENT FOR OSTEOARTHRITIS

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SEARCHING FOR A COMPLIMENT FOR OSTEOARTHRITIS Part 1 Osteoarthritis & Nutrition Donna M. Raditic DVM, DACVN, CVA Clinical Assistant Professor Integrative Medicine Nutrition Service The University of Tennessee College of Veterinary Medicine C247 Veterinary Teaching Hospital 2407 River Drive Knoxville, TN 37996 draditic@utk.edu In order to integrate appropriate nutritional recommendations for patient management, a two-step process is undertaken: a nutritional assessment phase (based on the Circle of Nutrition by the American College of Veterinary Nutrition (http://www.acvn.org)) and an analysis, interpretation, and action phase. In the assessment phase, three sets of factors are assessed: animal-specific factors, diet-specific factors, and feeding management and environmental factors. Animalspecific factors include age, physiological status, disease processes, and activity of the patient. Diet-specific factors include safety and appropriateness of diet fed and nutrients of interest. Feeding factors include frequency, timing, location, and method of feeding, and environmental factors include living space and quality of the patient s surroundings. An important part of the assessment phase is obtaining body weight, body condition score, and muscle condition score. Body condition score evaluates body fat. There are 2 commonly used body condition scoring systems, a 5-point and a 9-point scale. In either scale, the middle number represents optimal condition with a body fat content of 15-25%; higher numbers on the scale represent various degrees of over-condition and body fat content > 25% and lower numbers on the scale represent various degrees of under-condition and body fat content < 15%. The goal for most patients is a body condition of 2.5-3.0 out of 5 or a 4-5 out of 9, which is associated with decreased health problems including musculoskeletal conditions. Muscle condition score evaluates muscle mass, which can be independent from body fat content assessed by body condition score. Evaluation of muscle mass includes visual examination and palpation over temporal bones, scapulae, lumbar vertebrae, and pelvic bones. The scale is from 1 to 3 with 3 being well-muscled and 1 corresponding to severe sarcopenia. Sarcopenia is seen with decreased weight bearing, decrease in nerve/vascular supply, and/or aging. After collecting information from the assessment phase, information is analyzed and interpreted and an action plan is implemented; the patient undergoes repeated assessment and adjustment of the plan. ROLE OF NUTRITION IN THE PREVENTION OF MUSCULOSKELETAL DISEASE Prevalence of musculoskeletal disorders for all dogs at multicenter referral practices has been reported to be approximately one in four. In dogs less than one year of age, prevalence is 22%, with 20% of these possibly having a nutrition-related cause. Data is not currently available on the incidence of OA in the feline patients, but a current study has identified biomarkers that may become useful in assessment. 1

Developmental Orthopedic Disease (DOD) DOD refers to a group of skeletal abnormalities (e.g. osteochondrosis dissecans, hip dysplasia, wobblers syndrome, ligamentous laxity, and hypertrophic osteodystrophy) that affect primarily rapidly growing, large- and giant-breed dogs. Nutrient excess (calcium and energy) and rapid growth (overfeeding and excess energy) are known risk factors for DOD in dogs that have genetic risk. Restricting food intake during growth slows growth rate without significantly reducing adult body size and is associated with decreased incidence of DOD. If a puppy s growth is restricted with an inappropriate diet such an adult maintenance diet, other nutrient deficiencies may be created with lower this lower intake. Dietary calcium greater than 3% on a dry matter basis is associated with increased risk despite an appropriate calcium-to-phosphorous ratio. Even if the diet contains less calcium than this, excess calcium intake can occur if owners provide supplemental calcium. Limited meal-feeding and limiting rate of growth also decrease DOD. For large- and giant-breed dogs during growth, recommended dietary composition includes: Energy: 3.2-4.1 kcal/kg of diet (lower end of range if at risk for DOD or if clients use free-choice feeding); Crude fat: 8.5-11% on a dry matter basis; Docosahexaenoic acid: 0.02% on a dry matter basis; Protein: 27% on a dry matter basis; Calcium: 0.8-1.2% ( 3% on a dry matter basis) with a calcium-to-phosphorous ratio of 1.1-2.0:1.0. The diet of a DOD predisposed puppy should be evaluated to be sure these nutrient parameters are met for optimal development. Obesity Obesity can be defined as accumulation of body fat in excess of what is necessary to maintain optimum condition and health. Quantitatively, obesity is defined generally as exceeding ideal body weight by 15-20% or more. One technique that is useful in the management of clinical patients is a body condition score and muscle condition score as discussed previously. Obesity may contribute to the development and progression of OA because of excess forces placed on joints and articular cartilage, which may lead to inactivity and further development of obesity. Current literature notes that adipose tissue is recognized as being metabolically active and pro-inflammatory; therefore, obesity may contribute to inflammation. Several studies have demonstrated a relationship between obesity and OA; however, a direct cause and effect has not been determined. A long term study was performed of 48 Labrador retrievers from 7 litters divided into 2 dietary groups. One group was fed an adult maintenance dog food and the second group was fed the same diet at 75% of the amount. Restricted fed dogs lived on average 1.8 years longer, weighed less, had better body condition scores and had longer delay to treatment of chronic disease including OA. Maintaining optimal or slightly lean body condition may be associated with lower risk of developing OA, development of less severe OA if it occurs, and delay of onset of clinical signs of OA in dogs. A study to identify proteins with differential expression between healthy dogs and dogs with stifle joint osteoarthritis secondary to cranial cruciate ligament (CCL) disease evaluated serum 2

and synovial fluid samples from dogs with stifle joint osteoarthritis before (n = 10) and after (8) surgery and control dogs without osteoarthritis (9). No proteins had significantly different expression between serum samples of control dogs versus those of dogs with stifle joint osteoarthritis whereas eleven proteins had significantly different expression (> 2.0-fold) between synovial fluid samples obtained before surgery from dogs with stifle joint osteoarthritis versus those obtained from control dogs. Of these results complement component 3 was strongly expressed in all (5/5) synovial membrane samples of dogs stifle osteoarthritis and weakly expressed in 3 of 5 synovial membrane samples of dogs without arthritis. These results that the complement system and proteins involved in lipid and cholesterol metabolism may have a role in stifle joint osteoarthritis, CCL disease, or both; therefore, the consideration of the role of obesity in osteoarthritis. ROLE OF NUTRITION IN THE TREATMENT OF MUSCULOSKELETAL DISEASE Nutrition and Surgery Non-traumatized surgical patients Patients undergoing surgery that are healthy and in optimal body and muscle condition require no further intervention nutritionally other than to continue feeding the current diet at the same amount and frequency. Patients are not fed 8-12 hours prior to anesthesia and surgery, but can resume normal feeding pattern once recovered from the procedure. It may be necessary to add flavoring agents or feed a different diet to stimulate appetite in the post-operative period. Patients should be assessed daily following surgery to insure they are eating adequately and that no adverse events occur either from the procedure or from post-operative medications such as analgesics and sedatives. As the patient becomes more active or as a rehabilitation program is initiated, energy requirements will increase. In many instances, surgery in these patients is elective; therefore, depending on the urgency of the surgical procedure, consideration should be given to weight reduction prior to surgery in patients that are obese. Reducing body weight to the optimal weight decreases anesthetic risk, improves immune function, and allows patients to more easily undergo post-surgical physical rehabilitation. The timing of weight loss with surgery and rehabilitation should be a consideration in every orthopedic surgery patient. Assessing the patient s weight, BCS, muscle condition score, and current activity level will be needed to optimize a nutritional program for an elective orthopedic condition. Traumatized surgical patients Patients with surgical musculoskeletal disease associated with trauma may or may not have increased nutritional requirements depending on the degree of trauma. If the trauma is less severe, then energy requirements are similar to non-traumatized surgical patients, and energy requirements approximate resting energy requirements. Severely injured patients or those with closed head injuries typically have energy requirements exceeding resting energy requirements due to the extent of the injuries or to activation of the sympathetic nervous system, in part. In these patients, energy requirements may exceed two times the estimated resting energy requirements. Likewise, protein requirements may exceed that required for maintenance in order to facilitate recovery, immune function, and wound healing. With trauma or strenuous exercise, protein requirements may exceed these by 50-100%. 3

Some patients may require facilitated nutritional support enterally or parenterally. Nutritional support in these patients should be individualized and intensive monitoring is required in order to maximize recovery and response to supportive care. Convalescent diets that are formulated to contain higher levels of protein and fat, are more calorically dense, highly palatable, and have a homogeneous texture suitable for feeding tubes are available. Nutrition and Rehabilitation Research into nutritional needs of patients undergoing various rehabilitation programs is nonexistent. Individuals developing rehabilitation programs should have knowledge of nutrition. Rehabilitation can include simple strengthening to extensive long-term physical rehabilitation; therefore, the nutritional plan for a patient must adjunctively meet the goals set during therapy and after goals are met. Nutritional plans should be included as part of the rehabilitation therapy. Obesity Three uncontrolled clinical studies of obese dogs with OA demonstrated improvement in mobility. In one study of nine dogs, with body condition score of 5 out of 5 and coxofemoral OA, obesity management resulted in loss of 11-18% of body weight, a decrease in body condition to optimal, and improvement in severity of subjective hind limb lameness scores. In the second study of 16 dogs with coxofemoral OA, weight loss of 13-29% of body weight and decrease of body condition to optimal resulted in improvement of ground reactive forces and improvement in subjective mobility and clinical signs of OA. In the third study, 14 client-owned dogs with clinical and radiographic signs of OA participated in an open prospective clinical trial. Results indicate that body weight reduction causes a significant decrease in lameness with a weight loss of 6.10% or more. Kinetic gait analysis supported the results with a body weight reduction of 8.85% or more. These results confirm that weight loss should be presented as an important treatment modality to owners of obese dogs with OA and that noticeable improvement may be seen after modest weight loss of 6.10-8.85% body weight. Weight loss is beneficial when used in combination with rehabilitation and physical rehabilitation in dogs. In a non-blinded prospective randomized clinical trial, 29 adult dogs that were overweight or obese (body condition score of 4/5 or 5/5) having clinical and radiographic signs of OA were evaluated. All dogs underwent weight loss. One group received caloric restriction and a home-based physical rehabilitation program and the other group received an identical dietetic protocol and an intensive physical rehabilitation program including transcutaneous electrical nerve stimulation. Significant weight loss and improved mobility were achieved in both groups; however, greater weight reduction and better mobility was obtained in the group receiving intensive physical rehabilitation. DIETS FOR OSTEOARTHRITIS IN DOGS AND CATS There are several commercially available diets formulated for management of dogs with OA. These diets contain higher levels of omega-3 fatty acids and may contain chondromodulators and antioxidants. A controlled experimental study in dogs where the cruciate ligament was transected demonstrated a beneficial effect of pre-feeding a diet containing high omega-3 fatty acids with less severe radiographic and functional joint disease. Available joint diets also contain antioxidants that may be beneficial in decreasing free radical induced injury with OA. Chondromodulating agents are also often included in joint diets. The amount of these 4

compounds in commercial diets is less than recommended for treatment of OA; therefore, they may be beneficial in prevention or management of early disease but probably less effective in more advanced disease. OA occurs commonly in cats; however, there is a paucity of information regarding nutrition or nutritional compounds in management. In a prospective, blinded, parallel group study evaluating a diet high in n-3 fatty acids and supplemented with green-lipped mussel extract and glucosamine/chondroitin fed to cats with OA over 9 weeks, there was an improvement in mobility of cats fed the supplemented diet and a decline in cats fed the control diet. Although other nutritional compounds are used in cats with OA, none have been evaluated in a controlled manner. THE FUTURE OF NUTRITION AND OSTEOARTHRITIS IN DOGS AND CATS Traditional nutrition research has dealt with providing nutrients to nourish populations; it now focuses on improving the health of individuals through diet. Modem nutritional research aims at health promotion, disease prevention, and performance improvement. The concept of developing nutritionally enhanced or functional food requires an understanding of the mechanisms of prevention and protection, identification of the biologically active molecules, and demonstration of the efficacy of these molecules. The disciplines "nutrigenetics" and "nutrigenomics" have evolved. Nutrigenetics asks how individual genetic disposition affect susceptibility to diet whereas nutrigenomics addresses the inverse relationship (i.e., how diet influences gene transcription, protein expression, and metabolism). A major methodologic challenge of nutrigenomics is integrating genomics (gene analysis), transcriptomics (gene expression analysis), proteomics (global protein analysis), and metabolomics (metabolite profiling) to define a healthy phenotype. The long-term goal should be to personalized nutrition for maintenance and improvement of individual health and the prevention of disease. These major challenges for "-omics" in nutrition and health are still to be met. Some of these challenges apply to omic disciplines in general, and others are specific for -omic discovery in nutrition and disease states: Integration of gene and protein expression profiles with metabolic fingerprints is still in its early stages. Health and wellness are poorly understood compared with our understanding of many diseases. Omics in nutrition may be particularly sensitive. It has to reveal many weak signals rather than a few abundant signals to detect early deviations from normal. Metabolomic and proteomic studies in veterinary nutrition may be the future for developing nutritional interventions for diseases states in our patients. Metabolomics is the comprehensive analysis of metabolites in urine or plasma but also applicable to tissues and other biological fluids using mass spectrometry, HPLC, and other specialized techniques. The advantage of this type of research is the quantitative, noninvasive analysis of easily accessible body fluids. Genomics and proteomic applications were used in a feline and canine study and these will be discussed as examples of the future of veterinary clinical nutrition. 5

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