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A multi-center study of the effect of a therapeutic food supplemented with fish oil omega-3 fatty acids on the carprofen dosage in dogs with osteoarthritis. Fritsch DA, Allen TA, Dodd CE, et al. J Am Vet Med Assoc. 2010. In press. Background Osteoarthritis (OA) or degenerative joint disease is a chronic, progressive disease characterized by pathological changes of movable joints accompanied by clinical signs of pain and disability. OA is associated with degeneration of articular cartilage, loss of proteoglycan and collagen, proliferation of new bone, and a variable inflammatory response. OA has been estimated to affect up to 20% of the canine population over 1 year of age. The goals of managing OA include: 1) prevention or risk factor management, 2) managing progression of the disease, and 3) controlling clinical signs. Proper nutrition, weight control, controlled exercise, physical therapy, anti-inflammatory and analgesic medication, and other disease-modifying agents are often incorporated into all three categories to manage OA. Previous studies demonstrated that a food containing high levels of eicosapentaenoic acid (EPA) helped improve the clinical signs of osteoarthritis in pet dogs, especially in the context of rising from a resting position, walking, running and playing with their owners. The mechanisms likely for the potential clinical benefits of omega-3 fatty acids include controlling inflammation and reducing the expression and activity of cartilage proteoglycan degrading enzymes. The primary objective of this study was to determine if a therapeutic food alters the dose of a non-steroidal anti-inflammatory drug (NSAID) required to manage clinical signs in dogs with OA. Study Details The investigation was conducted as a 90-day prospective, randomized (dietary treatments), double-masked, controlled study in 33 veterinary hospitals in the United States. OA was diagnosed based on compatible history, clinical signs and radiographic evidence of arthritis in one or more joints on the clinically affected limb. To be eligible for inclusion, dogs also had to be a least 1 year of age, weigh 25 pounds or more, consume dry food and be free of systemic disease as determined by history, physical examination, complete blood count (CBC), serum biochemistry analysis and urinalysis. Exclusion criteria included acute traumatic injuries, complicating disease conditions, preexisting conditions for which corrective surgery was anticipated during the feeding period, and recent intra-articular injection or arthrocentesis. Dogs satisfying the inclusion/exclusion criteria were randomly assigned to receive either a typical commercial dog food (control food) or a test food for 12 weeks. The test food (Hill s Prescription Diet j/d Canine) contained a 39-fold increase in EPA concentration (0.4% EPA dry matter basis), compared to the control food (<0.01% EPA, dry matter basis). Owners could feed either a dry food or a combination of dry plus canned foods of the control or test formulas. Pet owner and veterinary clinical evaluations were completed at 0, 3, 6, 9 and 12 weeks. The pet owner evaluation consisted of a standardized questionnaire that included assessments of the frequency and severity of the following signs: difficulty rising from rest, limping, stiffness, soreness when touched, vocalizing in pain, aggression, lagging behind on walks, and reluctance in running, walking, jumping, climbing stairs, playing and general activity. Based on these activities, pet owners were also asked to provide an overall assessment of the severity of their pets pain. The veterinary clinical assessment consisted of careful evaluation of the following parameters: reluctance to bear weight, lameness, reduced range of motion, pain on palpation of the affected joint and reluctance to hold up the contralateral limb. All dogs were being administered the NSAID carprofen to help manage clinical signs of OA. At each evaluation period, the veterinarian considered the results of the orthopedic examination and the pet owner s assessment to determine if lowering the dose of carprofen was feasible.

Carprofen dose reductions were possible in 46% of dogs consuming j/d Canine vs. 32% of dogs eating the control food. Carprofen dose increases were necessary in 5% of the dogs consuming the control food and in only 2% of dogs consuming j/d Canine. For the group receiving j/d Canine, the mean carprofen dose reduction was 25.6%. Significantly greater reductions in carprofen dose (mg/lb. body weight) were possible in the dogs consuming j/d Canine, compared with the control group (p=0.025). Clinical Impact This study indicates that nutritional management using a food with high levels of total omega-3 fatty acids and EPA helps improve the clinical signs of osteoarthritis in dogs. Furthermore, doses of NSAID can often be reduced in dogs with osteoarthritis consuming j/d Canine. / Trademarks owned by Hill s Pet Nutrition, Inc. 2009 Hill s Pet Nutrition, Inc. CER0838-1

A MULTI-CENTER VETERINARY PRACTICE ASSESSMENT OF THE EFFECTS OF OMEGA-3 FATTY ACIDS ON CANINE OSTEOARTHRITIS. Roush JK, Dodd CE, Fritsch DA, et al. J Am Vet Med Assoc. 2010. In press. Background Osteoarthritis (OA) or degenerative joint disease is a chronic, progressive disease characterized by pathological changes of movable joints accompanied by clinical signs of pain and disability. OA is associated with degeneration of articular cartilage and loss of proteoglycan and collagen, proliferation of new bone and a variable inflammatory response. OA has been estimated to affect up to 20% of the canine population over 1 year of age. The goals of managing OA include the following: 1) prevention or risk factor management, 2) managing progression of the disease, and 3) controlling clinical signs. Proper nutrition, weight control, controlled exercise, physical therapy, anti-inflammatory and analgesic medication, and other disease-modifying agents are often incorporated into all three categories to manage OA. A relatively new concept in the management of animals with OA is the use of omega-3 fatty acids. The mechanisms likely for the potential clinical benefits of omega-3 fatty acids include controlling inflammation and reducing the expression and activity of cartilage proteoglycan degrading enzymes. The objective of this study was to determine the effect of a food containing high levels of omega-3 fatty acids on clinical signs of OA in dogs. Study Details The investigation was conducted as a six-month prospective, randomized, double-masked, controlled study in 18 veterinary hospitals in the United States. OA was diagnosed based on compatible history, clinical signs and radiographic evidence of arthritis in one or more joints on the clinically affected limb. To be eligible for inclusion, dogs also had to be at least 1 year of age, weigh 25 pounds or more, consume dry dog food and be free of systemic disease as determined by history, physical examination, complete blood count (CBC), serum biochemistry analysis and urinalysis. Exclusion criteria included acute traumatic injuries, complicating disease conditions, preexisting conditions for which corrective surgery was anticipated during the feeding period and recent intra-articular injection or arthrocentesis. Dogs were randomly assigned to receive either a typical commercial dog food (Purina Dog Chow / Pedigree Choice Cuts ) or a test food (Hill s Prescription Diet j/d Canine) for six months. The test food contained a 31-fold increase in total omega-3 fatty acid concentration (3.47 vs. 0.11% on dry matter basis), a 41-fold increase in eicosapentaenoic acid (EPA) concentration [0.41 vs. <0.01% on dry matter basis] and a 97% decrease in the omega-6:omega-3 ratio (0.7:1 vs. 24.3:1) compared to the control food. Pet owners could feed either a dry food or a combination of dry plus canned foods of the control or test formulas. For baseline purposes, pet owners completed a questionnaire that detailed their dogs arthritic condition. Baseline assessments included the frequency with which dogs exhibited the following signs: difficulty in rising from rest, limping, stiffness, soreness when touched, vocalizing in pain, aggression, lagging behind on walks, reluctance in running, walking, jumping, climbing stairs, playing and general activity level. Variables were assessed at the beginning of the study and at 6, 12 and 24 weeks after onset of feeding the control or test food. Additionally, veterinary clinical evaluations were conducted at each time interval. These consisted of an orthopedic examination with a specific emphasis on lameness, pain on palpation of the affected joint(s), limitation in weight-bearing ability, range of motion of the affected joint(s) and willingness to bear weight on the most affected limb when the contralateral limb was elevated. Samples for CBC, serum biochemistry and serum fatty acid determinations were also obtained at each time interval.

Of 169 dogs starting the study, 127 dogs completed six months of feeding (71 received test food, 56 received control food). Baseline mean body weights, mean body condition score, age, gender, overall arthritic condition and frequency of clinical signs were not significantly different between treatment groups. Both groups maintained body weight and condition over the course of the study. Dogs fed the test food had significantly higher serum concentrations of total omega-3 fatty acids, significantly higher serum concentrations of EPA, significantly lower serum concentrations of arachidonic acid and significantly lower omega-6:omega-3 fatty acid ratios at 6, 12 and 24 weeks (Figure 1). Dogs fed the test food had significantly improved ability to rise from a resting position and in playing at six weeks and improvements in walking at 12 and 24 weeks compared to control dogs. In contrast, dogs fed the control food showed no significant improvement in the 13 clinical variables assessed by dog owners when compared to dogs fed the test food. The mean scores for veterinary clinical evaluation of both groups improved over the course of the study; however, the differences between groups were not significant. Clinical Importance This study indicates that nutritional management using a food with high levels of omega-3 fatty acids helps improve clinical signs of OA in dogs, especially in the context of rising from a resting position, walking, and playing. Mean Serum EPA Concentrations 25 20 * 15 EPA mg/dl * * 10 5 0 0 Days 45 Days 90 Days 180 Days Control 1.1 0.9 0.7 0.9 Experimental 1.3 16.4 18.7 20.1 *P<0.0001 Figure 1. Mean serum eicosapentaenoic acid (EPA) concentrations in dogs fed either a control (<0.01% EPA on dry matter basis) or test (0.38% EPA on dry matter basis) food for 180 days (*p<0.0001). Note that serum EPA concentrations rise rapidly within 45 days of feeding a food with enhanced EPA levels. / Hill s, Prescription Diet and j/d are trademarks owned by Hill s Pet Nutrition, Inc. Purina and Dog Chow are trademarks owned by Société Des Produits Nestlé, S.A. Pedigree and Choice Cuts are trademarks owned by Mars, Incorporated and its affiliates. 2009 Hill s Pet Nutrition, Inc. CER0838-2

Effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. Roush JK, Cross AR, Renberg WC, et al. J Am Vet Med Assoc. 2010. In press. Background Osteoarthritis (OA) or degenerative joint disease is a chronic, progressive disease characterized by pathological changes of movable joints accompanied by clinical signs of pain and disability. OA is associated with degeneration of articular cartilage and loss of proteoglycan and collagen, proliferation of new bone and a variable inflammatory response. OA has been estimated to affect up to 20% of the canine population over 1 year of age. The goals of managing OA include the following: 1) prevention or risk factor management, 2) managing progression of the disease, and 3) controlling clinical signs. Proper nutrition, weight control, controlled exercise, physical therapy, anti-inflammatory and analgesic medication, and other disease-modifying agents are often incorporated into all three categories to manage OA. A relatively new concept in the management of animals with OA is the use of omega-3 fatty acids. The mechanisms likely for the potential clinical benefits of omega-3 fatty acids include controlling inflammation and reducing the expression and activity of cartilage proteoglycan degrading enzymes. The objective of this study was to determine the effect of food containing high levels of omega-3 fatty acids for ameliorating clinical signs in dogs with OA by using force plate analysis as an objective measurement of the dogs weight bearing abilities. Study Details The investigation was conducted as a 90-day prospective, randomized, double-masked, controlled study in two veterinary teaching hospitals in the United States. OA was diagnosed based on compatible history, clinical signs and radiographic evidence of arthritis in one or more joints on the clinically affected limb. To be eligible for inclusion, dogs also had to be at least 1 year of age, weigh 25 pounds or more, consume dry dog food and be free of systemic disease as determined by history, physical examination, complete blood count (CBC), serum biochemistry analysis and urinalysis. Exclusion criteria included acute traumatic injuries, complicating disease conditions, preexisting conditions for which corrective surgery was anticipated during the feeding period and recent intra-articular injection or arthrocentesis. Dogs were randomly assigned to receive either a typical commercial dog food (Purina Dog Chow / Pedigree Choice Cuts ) or a test food (Hill s Prescription Diet j/d Canine) for 90 days. The test food contained a 31-fold increase in total omega-3 fatty acid concentration (3.47 vs. 0.11% on dry matter basis), a 41-fold increase in eicosapentaenoic acid (EPA) concentration (0.38 vs. <0.01% on dry matter basis) and a 97% decrease in the omega-6:omega-3 ratio (0.7:1 vs. 24.3:1) compared to the control food. Pet owners could feed either a dry food or a combination of dry plus canned foods of the control or test formulas. For baseline purposes, pet owners completed a questionnaire that detailed their dogs arthritic condition. Baseline assessments included the frequency with which dogs exhibited the following signs: difficulty in rising from a resting position, limping, stiffness, soreness when touched, vocalizing in pain, aggression, lagging behind on walks, reluctance in running, walking, jumping, climbing stairs, playing and general activity level. Variables were assessed at the beginning of the study and at 45 and 90 days after onset of feeding the control or test food. Additionally, veterinary clinical evaluations were conducted at each time interval. These consisted of an orthopedic examination with a specific emphasis on lameness, pain on palpation of the affected joint(s), limitation in weight bearing ability, range of motion of the affected joint(s) and willingness to bear weight on the most affected limb when the contralateral limb was elevated. Samples for CBC, serum biochemistry and serum fatty acid determinations were also obtained at each time interval.

Gait analyses using a computerized biomechanical force plate were also conducted at the same time intervals. For each dog, five valid force plate trials were obtained during each test period for the most severely affected and ipsilateral limb. Orthogonal ground reaction forces of peak vertical force, vertical impulse, braking and propulsion peak force, and braking and propulsive force were measured and recorded. All forces were normalized with respect to body weight in kilograms and data from valid trials for each limb were averaged to obtain a mean value at each time period. Of 44 dogs starting the study, 38 dogs (22 received test food, 16 received control food) completed 90 days of feeding. Baseline mean body weights, mean body condition score, age, gender, overall arthritic condition and frequency of clinical signs were not significantly different between treatment groups. Both groups maintained body weight and condition over the course of the study. Dogs fed the test food had significantly higher serum concentrations of total omega-3 fatty acids, significantly higher serum concentrations of EPA, significantly lower serum concentrations of arachidonic acid and significantly lower omega-6:omega-3 fatty acid ratios at 45 and 90 days. On clinical orthopedic examination, dogs consuming the test food were reported to have decreased lameness (p=0.02) and improved weight bearing (p=0.001). Vertical peak force was the key parameter measured to determine weight bearing of affected limbs. There was no significant change in mean peak force over the duration of the 90-day feeding trial for the control group. The mean vertical peak force increased significantly (p=0.01) for the test group over the same time interval. In the study, 82% of dogs in the test group increased weight bearing, compared to 38% of dogs in the control group. CLINICAL IMPORTANCE This study indicates that nutritional management using a food with high levels of omega-3 fatty acids helped improve the clinical signs of OA in dogs as measured by clinical orthopedic examination and gait analysis of ground reaction forces. / Hill s, Prescription Diet and j/d are trademarks owned by Hill s Pet Nutrition, Inc. Purina and Dog Chow are trademarks owned by Société Des Produits Nestlé, S.A. Pedigree and Choice Cuts are trademarks owned by Mars, Incorporated and its affiliates. 2009 Hill s Pet Nutrition, Inc. CER0838-3