"Relationship of Nutrition to Developmental Skeletal Disease in Young Dogs" for Veterinary Clinical Nutrition, Volume 4, Number 1, 1997, Published by Veterinary Practice Publishing Company, P.O. Box 4457, Santa Barbara, CA 93140, Phone - 805-965-1028, Fax - 805-965-0722.

Relationship of Nutrition to Developmental Skeletal Disease in Young Dogs

Daniel C. Richardson¹

Phillip W. Toll¹

Developmental skeletal disease is common in large and giant-breed puppies. One manifestation, hip dysplasia, affects millions of dogs. Genetics, environment, and nutrition all contribute to developmental skeletal disease. Of the nutritional components, rate of growth, specific nutrients, food amounts consumed, and feeding methods influence skeletal disease. Excess energy and calcium are known risk factors; therefore, the level of these nutrients in the food should be near the Association of American Feed Control Officials minimum requirement. Puppies should be fed a growth-type food using a food-limiting technique. All puppies should be weighed and evaluated at least every two weeks. Amounts fed should be increased or decreased based on weight and body condition score.

Key Words: Developmental skeletal disease, calcium, energy, hip dysplasia, electrolyte balance, osteochondrosis, body condition, feeding method.

Introduction

The musculoskeletal system changes constantly throughout life. These changes are most rapid during the first few months of life and slow with skeletal maturity (about 12 months for most breeds). The skeletal system is most susceptible to physical and metabolic insult during the first 12 months of life because of the heightened metabolic activity. The physical manifestation of these results can be lameness and/or altered growth. Both can affect locomotion and/or soundness of adult dogs.

Developmental skeletal disease is a multifactorial process that has genetic, environmental, and nutritional components. These skeletal abnormalities primarily affect fast growing, large-breed dogs. Lack of careful genetic monitoring can introduce and propagate disorders (e.g., hip dysplasia, osteochondrosis) that are difficult to eliminate. Trauma, whether obvious (e.g., hit by a car) or subtle (e.g., excessive weight) can adversely affect relatively weak growth centers and cause skeletal disease (e.g., angular limb deformities). Nutrient excesses (e.g., excess calcium supplementation) often exacerbate musculoskeletal disorders.^1-4 This article reviews the role of nutrition in developmental skeletal disease in young dogs.

Nutrition and Skeletal Disease

The role of nutrition in developmental skeletal disease is complex. Rate of growth, specific nutrients, food consumption, and feeding methods have all been shown to influence skeletal disease. Large and giant breeds are most susceptible to developmental skeletal disease, presumably because of their accelerated growth rate.^4,5 Dietary deficiencies are rare in young, growing dogs fed commercial growth foods.⁶ Problems associated with dietary excess are far more likely, especially if a high quality growth food is supplemented with minerals, vitamins, and energy.⁶ The following review discusses some of the more critical nutrients in developmental skeletal disease.

Energy

The energy needed for any individual depends on breed, age, neuter status, and activity levels. In general, growing puppies require twice as much dietary energy as adults for body maintenance, activity, and growth. The need is greatest right after birth and decreases as the dog grows and matures. Rapid growth in large and giant-breed dogs increases the risk of skeletal disease.^4,5 Excessive dietary energy may support a growth rate that is too fast for proper skeletal development and results in a higher frequency of skeletal abnormalities in large and giant-breed dogs.⁷ Because fat has twice the caloric density of protein or carbohydrate, dietary fat is the primary contributor to excess energy intake.

Excess energy leads to rapid growth. Dietary energy in excess of a puppy's needs will be stored as body fat. Body condition scoring evaluates body fat stores and therefore correctness of energy intake. Maintaining appropriate body condition during growth not only avoids excess body fat storage, but also helps control excess growth rate. Limiting intake to maintain a lean body condition will not impede a dog's ultimate genetic potential. It will only reduce food intake, fecal production, obesity, and lessen the risk of skeletal disease.⁸ Energy or food-dose calculations can only be used as general guidelines or starting points that must be modified based on frequent clinical evaluation of each puppy because individual needs can vary widely. (Fig. 1). Physical evaluation or body condition scoring should be done at least every two weeks (See Evaluation of Feeding Methods and Scoring to follow).

Protein

Unlike other species, protein excess has not been demonstrated to negatively affect calcium metabolism or skeletal development in dogs. Protein deficiency, however, has more impact on the developing skeleton. In Great Dane puppies, a protein level of 14.6% (dry matter basis) with 13% of the dietary energy derived from protein can result in significant decreases in bodyweight and plasma albumin and urea concentrations.^9,10 The minimum adequate level of dietary protein depends on digestibility, amino acids, and their availability from protein sources. A growth food should contain > 22% protein (dry matter basis) of high biologic value (Table 1).¹¹ The dietary protein requirements of normal dogs decrease with age.

Calcium

The absolute level of calcium in the diet, rather than an imbalance in the calcium/phosphorus ratio, influences skeletal development.² Young, giant-breed dogs fed a food containing excess calcium (3.3% dry matter basis) with either normal phosphorus(0.9% dry matter basis) or high phosphorus(3% dry matter basis, to maintain a normal calcium/phosphorus ratio) had significantly increased incidence of developmental bone disease.² These puppies apparently were unable to protect themselves against the negative effects of chronic calcium excess.³ Further, chronic high calcium intake increased the frequency and severity of osteochondrosis.⁷

Often puppies are switched from growth to maintenance-type foods to avoid calcium excess and skeletal disease. However, because some maintenance foods have much lower energy density than growth foods, the puppy must consume more dry matter volume to meet its energy requirement. If the calcium levels are similar (dry matter basis) between the two foods, the puppy will actually consume more calcium when fed the maintenance food. This point is exemplified in the case of switching a 15-week-old, 15-kg male Rottweiler puppy from a growth food containing, on an as fed basis, 4.0 kcal/g metabolizable energy and 1.35% calcium (1.5% on a dry matter basis) to a maintenance food containing the same amount of calcium but at a lower, 3.2 kcal/g energy density. The puppy would require approximately 1,600 kcal/day. In order to meet this energy need the puppy would consume approximately 400g of the growth food (containing 5.4g of calcium) vs. 500g of the maintenance food (containing approximately 6.7g of calcium).

Feeding treats containing calcium and/or providing calcium supplements further increases daily calcium intake. Two level teaspoons of a typical calcium supplement (calcium carbonate) added to the growth food of the 15-week-old, 15-kg Rottweiler puppy would more than double its daily calcium intake. This calcium intake is well beyond the levels shown to increase the risk for developmental bone disease. A recent review article best sums up the need for calcium supplements: "Because virtually all dog foods contain more calcium than is needed to meet the requirement, the use of a calcium supplement certainly is unnecessary. Now that the deleterious effects of excess dietary calcium have been delineated, we can say that the feeding of calcium supplements not only is unnecessary, but, in fact, contraindicated!"⁸

Because these studies demonstrate the safety and adequacy of 1.1% calcium (dry matter basis) and the Association of American Feed Control Officials (AAFCO) minimum recommendation is 1% (dry matter basis, Table 1), we recommend that calcium levels for a growth food be within this range for at risk puppies, with no supplementation.

Other Nutrients

L-ascorbic acid (Vitamin C) is necessary for hydroxylation of proline and lysine during biosynthesis of collagen, a major component of ligaments and bones. Food devoid of Vitamin C fed to puppies for 147 to 154 days neither affected growth nor caused skeletal lesions.¹² There are no known dietary requirements for Vitamin C in the dog.¹¹

Vitamin C supplementation in pigs elevates plasma levels of Vitamin C without changing articular concentrations of hydroxyproline.¹³ Similar studies in dogs demonstrated transient elevation of plasma Vitamin C concentrations; however, long-term supplementation did not increase concentrations much above normal.¹⁴ Even though Vitamin C has been recommended, the relationship between Vitamin C and developmental skeletal disorders in dogs such as osteochondrosis and hip dysplasia is unproven.¹⁵

Vitamin D metabolites regulate calcium metabolism and therefore skeletal development in dogs. These metabolites aid in the absorption of calcium and phosphorus from the gut, increase bone cell activity, and influence endochondral ossification and calcium excretion.¹⁶ Unlike other omnivores, the dog seems dependent on dietary Vitamin D sources from plants (Vitamin D₂) or animals (Vitamin D₃). Commercial pet foods contain from two to 10 times the AAFCO recommended amounts of Vitamin D.⁶ Diagnosis of Vitamin D deficiency can be made by measuring circulating levels of Vitamin D metabolites and by measuring growth plate width. Clinical cases of Vitamin D deficiency (rickets) are extremely rare in animals eating commercial foods.⁶ Increased growth plate width is not associated with low calcium/high phosphorus foods but is a strong indicator of rickets.¹⁶ Excess Vitamin D can cause hypercalcemia, hyperphosphatemia, anorexia, polydipsia, polyuria, vomiting, muscle weakness, generalized soft tissue mineralization, and lameness. In growing dogs, supplementation with Vitamin D can markedly disturb normal skeletal development due to increased calcium and phosphorus absorption.¹⁶

The trace minerals copper and zinc are involved in normal skeletal development. Supplementing a mare's dietary copper intake during the late stages of pregnancy, and supplementing the foal's diet from 90 to 180 days of age has been shown to reduce the prevalence and severity of developmental cartilage lesions.¹⁷ Copper deficiency in dogs has been associated with hair depigmentation, hyperextension of the distal phalanges, and decreased copper levels in the hair, liver, kidney, and heart muscle.¹⁸ However, bone copper concentration was not influenced by dietary treatment and developmental skeletal abnormalities associated with a deficiency of dietary copper were not described. Similarly, long-term studies of dietary zinc on canine growth and reproduction showed no significant clinical influence on the skeletal development.¹⁹ The role of these two nutrients in the development of skeletal disease in the dog remains unclear at this time.

Two of the most common skeletal diseases of growing dogs are hip dysplasia and osteochondrosis. The balance of this section will review the relationship between these diseases and critical nutrients.

Canine Hip Dysplasia (CHD)

Canine hip dysplasia (CHD) is the most frequently encountered orthopedic disease in veterinary medicine (Fig. 2). The actual number of cases is estimated to be in the millions.²⁰ This extremely common heritable disorder of large and giant-breed dogs can be influenced by nutrition during growth. Early developmental findings of CHD, including joint laxity and coxofemoral anatomical changes, have been documented within 2 weeks of birth. Rapid weight gain in German Shepherd dogs during the first 60 days after birth has been associated with CHD at a later age. The importance of this early influential time period was demonstrated in a study comparing cesarean-section, hand reared puppies to vaginal birth, bitch-fed puppies. Cesarean section and hand rearing markedly reduced growth and the incidence of CHD in these puppies. Vaginally born, bitch-fed puppies that grew "optimally" or somewhat "suboptimally" had a higher incidence of CHD.²¹ The period from 3 to 8 months of age is important in the development of CHD, with the first 6 months generally regarded as the most critical. Frequency and severity of CHD was influenced by weight gain in growing dogs that were offspring of parents with CHD or parents with a high incidence of CHD in their offspring. Dogs with weight gain that exceeded breed standards had a higher frequency and more severe CHD than dogs with weight gain below breed standards.²²

In one colony of fast growing Labrador Retriever dogs, the triradiate growth plates of the acetabula fused at 5 months as determined by conventional radiography. These growth plates normally close at 6 months in puppies growing at conventional rates. The investigators speculated that early fusion in the acetabulum may result in bone/cartilage disparities in the future and predispose to dysplastic changes.²³ Limiting food intake in growing Labrador Retriever puppies has been associated with less subluxation of the femoral head and fewer signs of hip dysplasia.²⁴

Palpation of the hip is of little to no value in predicting development of hip joints. However, the combination of physical and radiographic examination are important diagnostic methods for evaluating the hips (Orthopedic Foundation for Animals, Columbus, MO; Penn HIP, Malvern, PA). A recent review of nutritional influences on CHD contains more information and a more complete reference list.²⁵

Electrolyte Balance and CHD

Control of dietary electrolytes has been proposed as a preventative for CHD.²⁶ Investigators have associated the dietary anion gap (DAG) with the radiographic changes of subluxation in the coxofemoral joints in several canine breeds. A food with a DAG (Na⁺ + K⁺ - Cl^-) < 23 mEq/100g of food was fed to large-breed puppies and resulted in less femoral head subluxation, on average, at 6 months of age. The slowed progression of subluxation was also observed in dogs fed a food with a reduced DAG from 35 to 45 weeks of age.²⁸ Hip joint laxity was determined using the Norberg hip score computed from radiographs. Significant correlation between radiographic findings (e.g., Norberg hip scores)and progression of CHD, either radiographic or clinical was not proven. The authors propose the balance of anions and cations in the food (specifically sodium, potassium, and chloride) influence the electrolytes and osmolality in joint fluid. The joint fluid of dysplastic dogs has higher osmolality and is increased in volume when compared to that of disease-free hips from dogs of the same breed.²⁹ The changes in osmolality and fluid volume could be a result rather than a cause of CHD. Changes in synovial fluid osmolality and electrolyte concentrations were not reported. These studies suggest an association between DAG and joint laxity without proving a mechanism of action.

Osteochondrosis (OCD)

Osteochondrosis is a focal disruption in endochondral ossification. OCD is manifested clinically by pain and lameness. Physical examination results can be confirmed radiographically. Figure 3 shows a classic inoperative lesion on the proximal humerus. Acute inflammatory joint disease begins when the subchondral bone is exposed to synovial fluid. Inflammatory mediators and cartilage fragments are released into the joint and perpetuate the cycle of degenerative joint disease.²⁷ OCD occurs in the physis and/or epiphysis of growth cartilage, and is a generalized or systemic disease. When OCD affects the physis, it may cause growth abnormalities in long bones. OCD is wide-spread among young, rapidly growing, warm-blooded, domesticated species and humans. In all species, the etiology is considered multifactorial. In dogs, risk factors for OCD are age, gender, breed, rapid growth and nutrient excesses (primarily calcium).^1,5,25,29

All large and giant-breed dogs are at increased risk for OCD. Great Dane, Labrador Retriever, Newfoundland, and Rottweiler breeds are at highest risk.²⁹ Males have an increased risk of OCD in the proximal humerus but gender relationships are not found with OCD involving other joints.²⁸

At least two schools of thought exist concerning the pathogenesis of OCD. In the first, cartilage lesions develop secondary to excessive biomechanical stresses. This may be termed an "outside-in" development. Over-nutrition, such as ad libitum feeding, stimulates skeletal growth, cancellous bone remodeling, and weight gain in breeds already having inherent capacity for rapid growth.⁵ Rapid growth combined with remodeling results in weakened subchondral regions to support the cartilage surface. If osteopenic and biomechanically weak subchondral spongiosa develops, there is inadequate bony support to the articular cartilage. The increasing body mass exerts excessive biomechanical forces on the cartilage and secondarily disturbs chondrocyte nutrition, metabolism, function, and viability. An outside-in development suggests OCD results when nutritional effects initiate a biomechanical disease.

An "inside-out" pathogenesis has also been proposed. Here, abnormalities of the cartilage canal vessels and chondrocyte necrosis are thought to precede degenerative changes in the articular cartilage matrix.³⁰ Focal lesions of dead and nectrotic chondrocytes develop, and subsequently, biomechanical stresses disrupt the lesion. Osteochondrosis lesions are routinely found in pigs as young as 25 days of age, when rapid growth and weight gain are much less of a factor. These findings support a localized, primary effect on the chondrocyte rather than secondary effects of biomechanical force.

Regardless of the pathogenesis of OCD, nutrition is still an underlying factor. In growing puppies, overnutrition can result in a mismatch between body weight and skeletal growth, which can overload skeletal structures.⁷ Nutrition of the mother may also play a role in the development of OCD in the offspring.

Feeding techniques

The nutrient profile of the food and how it is fed control nutritional risk factors for developmental skeletal disease. There are three basic methods of feeding growing dogs: free-choice (ad libitum), time-limited, or food-limited.

Free-choice feeding

Free-choice feeding is relatively effortless and may reduce abnormal behavior such as barking at feeding time. Frequent trips to the food bowl help reduce boredom, timid or unthrifty animals have less competition when eating, coprophagy may be decreased, and frequent small meals may result in a more constant blood level of nutrients and hormones. Disadvantages of ad libitum feeding include food wastage, only dry forms of pet food can be fed, and competition or boredom may stimulate overeating. The most serious disadvantage is increased risk of developmental bone disease because of overconsumption in the large and giant breeds.^1-4,24 In general, free-choice feeding in contraindicated in "at risk" dogs until they have reached skeletal maturity (about 12 months of age or at least 80 to 90% adult weight).

Time-limited feeding

Time-limited feeding can be used for most large and giant breeds. Making food available for a set period of time, two to three times per day, may help control intake and help in discipline and housetraining young puppies. The owner interacts with the puppy during this time and is able to observe general condition and behavior. This may lead to earlier detection of health problems. A routine of feeding a puppy then taking it outdoors can enforce housetrainng by taking advantage of the gastrocolic reflex.

Some researchers have proposed that puppies fed on a time-limited basis consumed less food, had slightly reduced growth rates, but achieved similar adult size and lean body mass when compared to puppies eating free-choice.⁸ Other studies have shown that feeding 15 minutes twice a day did not result in decreased food intake between ad libitum and time-restricted groups.³¹ Many variables (e.g., breed, temperament, housing, etc.) influence these results and account for the varied findings. If time-restricted feeding is used, 5 to 10 minute feeding periods (3x per day for the first month after weaning, then 2x per day) may be required to decrease food intake in some puppies.

Food-limited feeding

The method of choice for feeding puppies is limiting food intake to maintain growth rate and body condition. Food-limited feeding requires feeding a measured amount of food based on calculated energy requirement or as recommended by the manufacturer. Energy requirement is most easily calculated by using resting energy requirement (RER) as a base on which to build. RER can be calculated using either of the following two equations:

RER (kcal/day) - 70 (Wtkg)^0.75

or

RER (kcal/day) = 30 (Wtkg) + 70

As a starting point use 3x RER for the first 4 months of life and 2x RER from 4 months of age to skeletal maturity (about 12 months for most breeds). Most large and giant-breed dogs will continue to increase bodyweight and muscle mass after 12 months, but the growth rate is reduced and most if not all growth plates are closed. At 12 months they can be fed as adults (1.6x RER).

Once daily caloric requirement has been calculated (kcal/day), divide this number by the energy density of the food (kcal/cup or kcal/can) to determine the number of cups or cans to feed per day. Remember, these calculations and manufacturers' recommendations are only starting points. Clinical evaluation of the growing puppy and adjustment of food offered is crucial. Rapidly growing, large and giant-breed dogs have a very steep growth curve and their intake requirements can change dramatically over short time periods. These puppies should be weighed, evaluated, and their daily feeding amount adjusted at least once every 2 weeks (Fig. 1). Most of the studies that have demonstrated the beneficial effects of limiting food intake of puppies have fed the limited group 25 to 30% less food then their counterparts ate when fed free-choice. Unfortunately, this is not a practical approach to feeding most puppies in a home environment.

Evaluation of feeding methods and body condition scoring

Regardless of a food's nutrient profile and how it is fed, the ultimate measurement of appropriate intake is the physical condition of the puppy. The only way to reduce potentially harmful nutritional risk factors that may affect skeletal development is to assess body condition and adjust the amount fed to ensure lean, healthy growth. We recommend that at risk puppies be evaluated at least every 2 weeks. Figure 4 reviews body condition scoring and physical findings. A more in-depth discussion follows.³²

A body condition score of 1 is characterized as very thin. The ribs are easily palpable with no fat cover. The tailbase has a prominent raised bony structure with no tissues between the skin and the bone. The bony prominences are easily felt with no overlying fat. In animals over 6 months, there is a severe abdominal tuck when viewed from above.

An underweight condition is categorized as a 2 in the scoring system. The ribs are easily palpable with minimal fat cover. The tailbase has a raised bony structure with little tissues between the skin and the bone. The bony prominences are easily felt with minimal overlying fat. In animals over 6 months, there is an abdominal tuck when viewed from the side and a marked hourglass shape when viewed from above.

The ideal body condition of a puppy is represented by a score of 3. The ribs are palpable with a thin layer of fat between the skin and the bone. The bony prominences are easily felt with a significant amount of overlying fat. In animals over 6 months, there is an abdominal tuck when viewed from the side and a well proportional lumbar waist when viewed from above.

A score of 4 is defined as overweight. The ribs are difficult to feel with moderate fat cover. The tailbase has some thickening with moderate amounts of tissue between the skin and the bone. The bony structures can still be felt. The bony prominences are covered by a moderate layer of fat. In animals over 6 month, there is little or no abdominal tuck of the waist when viewed from the side. The back is slightly broadened when viewed from above.

An obese condition is represented as a 5 on the scale. The ribs are very difficult to feel under a thick fat cover. The tailbase appears thickened and is difficult to feel under a prominent layer of fat. The bony prominences are covered by a moderate to thick layer of fat. In animals over 6 months, there is a pendulous ventral bulge and no waist when viewed from the side. The back is markedly broadened when viewed from above.

Conclusion

Large and giant-breed dogs are the most susceptible to developmental skeletal disease. Genetics, environment, and nutrition play key roles. Nutritionally, rate of growth, food consumption, specific nutrients, and feeding methods influence our ability to optimize skeletal development and minimize skeletal disease. Maximizing the growth rate in young, growing puppies does not correlate to maximal adult size. It does, however, increase the risk of skeletal disease. The growth phase of 3 to 8 months, and possibly the phases before weaning, are vital to ultimate skeletal integrity. The large and giant breeds may be limited in their ability to cope with excesses of minerals such as calcium.

Overnutrition from overconsumption and oversupplementation increases the frequency of developmental bone disease in large and giant-breed dogs. Energy and calcium are the nutrients of greatest concern. Often, owners feeding highly palatable, energy-dense growth foods switch to maintenance type foods in an attempt to reduce developmental disorders. As shown earlier, this practice may worsen total calcium intake. It is not only important to feed the appropriate food, but to feed the food appropriately.

Table 1 lists the minimum requirement of some nutrients of concern for growing puppies. These values represent the minimum and in some cases the maximum AAFCO recommendations for these nutrients. Foods for large and giant-breed puppies should meet these recommendations. Because energy (primarily from fat) and calcium are nutrients known to be risk factors for developmental skeletal disease, the level of these nutrients should be near the minimum requirement. Meeting but not exceeding the requirement for these nutrients ensures proper growth while minimizing risk factors for skeletal disease.

Nutritional management alone will not completely control developmental bone diseases. Skeletal diseases can be influenced during growth by feeding technique and nutrient profile. Dietary deficiencies are minimal concern in this age of commercial foods specifically prepared for young, growing dogs. The potential for harm is in overnutrition from excess consumption and oversupplementation.

References

1. Hedhammer A, et al; Overnutrition and Skeletal Disease: An Experimental Study in Growing Great Dane Dogs, Cornell Vol 64 (suppl 5): 11-60, 1974

2. Hezewinkel HAW, et al; Calcium Metabolism in Great Dane Dogs Fed Diets With Various Calcium and Phosphorus Levels, J Nutr 121:599-S106, 1991.

3. Hezwinkel HAW, et al; Influences of Chronic Calcium Excess on the Skeletal Development of Growing Great Danes, JAAHA 21: 377-391, 1985

4. Meyer H, Zentek J; Energy Requirements of Growing Geat Danes, J Nitr 121: 335-838, 1991.

5. Daminnich K; Relationship Between Nutrition and Bone Growth in large and Giant Dogs, J Nutr 121:8114-8121, 1991.

6. Kaltfalz FA, Ozanis DA; Overnutrition: An Epidemic Problem in Pet Animal Practices, Vet Clinic North Am Small Anim Pract 19(3): 433-446, 1989.

7. Nap RC, Hezwinkel HAW; Growth and Skeletal Development in the Dog in Relation to Nutrition: A Review, Vet Quarterly 1:50-59, 1994.

8. Alexander JE, WOOD LL; Growth Studies in Labrador Retrievers Fed a Caloric-Dense Diet: Time-Restricted Versus Free-Choice Feeding, Companion Animal 14 (2): 41-47, 1987.

9. Nap RC, et al; Growth and Skeletal Development in Great Dane Pups Fed Different levels of Protein Intake, J Nutr 121:8107-8113, 1991.

10. Nap RC, et al; The Influence of the Diet Protein Content on Growth in Giant Breed Dogs, j Vet Comp Orthop Trauma 6:1-8, 1993.

11. Ozanis DA; The AAFCO Dog and Cat Food Nutrient Profiles, In Current Veterinary Therapy XII, Ed by JD Bongura, Philadelphia, WS Saunders, 1995, pp 1418-1421.

12. National Research Council Nutrient Requirements of Dogs, Washington, DC, National Academy Press, 1995.

13. Nakano T, Aheme FX, Thmopson JR; Effect of Dietary Supplementation of Vitamin C on Pig Performance and the Incidence of Osteochondrosis in Elbow and Stifle Joints in Young Growing Swine, Can j Anim Sci 63:421-428, 1983

14. Teare JA, et al; Ascorbic Acid Deficiency and Hypertrophic Osteodystrophy in the Dog: A Renuttal, Cornell Vet 69:384-401, 1979.

15. Bennet D; Hip Dysplasia and Ascorbate Therapy: Fact or Fancy? Semin Vet Med Surg (small Anim) 2 (2): 152-157, 1997.

16. Hazewinkel HAW; Nutrition in Orthopedics, In: Disease Mechanisms in Small Animal Surgery, ed 2. Ed by MJ Bojrab, Philadelphia, Lea & Febiger, 1993, pp 1119-1128.

17. Knight DA. Et al; The Effects of Copper Supplementation on the Prevalence of Cartilage Lesions in Foals, Equine Vet j 22 (8): 426-432, 1990.

18. Zeniek J, Meyer H; Investigations on Copper Deficiency in Growing Dogs, j Nutr 121:883-884, 1991.

19. Booles D, et al; Effects of Two levels of Zinc Intake on Growth ands Trace Element Status in Labrador Puppies, J Nutr 121:879-880, 1991.

20. Corley EA, Hogan PM; Trends in Hip Dysplasia Control: Analysis of Radiographs Sybmitted to the Orthopedic Foundation for Animals, 1974 to 1984, JAVMA 187:805-809, 1985.

21. Lust G, Geary JO, Shelly BE, Development of Hip Dysplasia in Dogs, Am J Vet Res 34:87-91, 1973.

22. Kaastrom, H; Nutrition, Weight Gain and Development of Hip Dysplasia \, Acta Radiologies 334(suppl): 135-179, 1975.

23. Lust G, et al; Canine Hip Dysplasia: Concepts and Diagnosis, JAVMA 187:838-840, 1985

24. Kealy RD, et al; Effects of Limited Food Consumption on the Incidence of Hip Dysplasia in Growing Dogs, JAVMA 201:857-863, 1992.

25. Richardson DC; The Role of Nutrition in Canine Hip Dysplasia, Vet Clin North Am Small Anim Pract 22(3): 529-540, 1992.

26. Kealy, RD, etal; Effects of Dietary Electrolyte Balance on Submuxation of the Femoral Head in Growing Dogs, Am J Vet Res 64(4): 556-582, 1993.

27. Hill MA, et al; Dyschondroplasias, Including Osteochondrosis of Boars Between 25 and 169 Days of Age: Historical Changes, Am J Vet Res 45 (5): 903-926, 1984.

28. Slater MR., et al; Breed, Genderand Age as Risk Facotrs for Canine Osteochondritis Dissecans, J Vet Comp Ortho Trauma 4:100, 1991.

29. Slater MR, et al; Diet and Exercise as potential Risk Factors for Osteochondritis Dissecans in Dogs, Am J Vet Res 53 (11):2119-2124, 1992.

30. Carlson OS, et al; Ischemic Necrosis of Cartilage in Spontaneous and Experimental Lesions of Osteochondrosis, J Ortho Res 9(3):317-329, 1991.

31. Richardson DC; Developemental Orthopedics: Nutritional Influences in the Dog, In: Textbook of Veterinary Internal Medicine, ed 4. Ed by SJ Ettinger, EC Feldman, Philadelphia, WE Saunders, 1995, pp 252-257.

32. Armstrong pj, Lund Bm; Changes in Body Composition and Energy Balance With Aging health and Nutrition of Geriatric Cats and Dogs, proceedings of a Symposium, 11-15.

1 Science & Technology Center, Hill's Pet Nutrition, Inc., P.O. Box 148, Topeka, KS 66601