Nutrition in Orthopedics

Bone is a specialized form of connective tissue with a complex chemical and physical composition. Apart from its cellular fraction and the water phase (10%), it is composed of an organic matrix and a mineral phase. The cellular fraction includes osteoblasts (organic-matrix forming cells), osteoclasts (calcified-matrix resorbing cells), and osteocytes (embedded osteoblasts with bone-resorbing capacity). The organic matrix, which is about 20% of the bone volume, is composed of 90% collagen fibers with a high content of hydroxyproline and 10% aminopolysaccharides, noncollagen proteins, and a small quantity of lipids. The mineral phase encompasses about 70% of the bone volume, mainly in the form of hydroxyapatite crystals and amorphous calcium phosphate, as well as small quantities of other elements. The total amounts of body calcium and phosphorus, 99% and 80%, respectively, are present in the skeleton. Although zinc, copper, manganese, and other elements may influence the development of skeletal abnormalities,1 they seem of minor significance in small animal practice. The availability of calcium, phosphate, and vitamins A and D has direct and indirect influences on skeletal mineralization. This will be discussed later in the chapter.

This chapter is limited to the recognition and management of orthopedic problems that are significant in small animal practice in which nutritional management is either a causative or a therapeutic factor. The quantity and quality of the food (including the main minerals and vitamins) are discussed in relation to skeletal diseases in growing, and in adult dogs and cats. In addition, nutrition is reviewed in relation to osteoarthrosis and fractures.

Nutrition and Skeletal Growth

Skeletal growth includes cartilage maturation as part of enchondral ossification and osteoid formation and mineralization, as well as bone modeling influenced by skeletal homeostasis and calcium homeostasis. The latter is under the influence of parathyroid hormone (PTH), calcitonin, and vitamin D metabolites.

A food of good quality and palatability that has been shown to be nutritionally adequate for growth should be given. Requirements for a number of nutrients are listed in Table 114-1. Young dogs and cats should have sufficient food during the growth phase to meet their needs, which can be two-and-one half to three times the adult maintenance value [1]. Optimal nutrition in an otherwise satisfactory environment permits optimal growth as ordained by the genotype.

In the following sections the orthopedic consequences of deficient or excessive intake of protein, energy, minerals, and vitamins for young dogs and cats are described.

Restricted Caloric Intake

Slight underfeeding may slow the growth of puppies but will not influence the adult size of the dog. In a controlled study of Great Dane dogs raised on a mixture of balanced complete commercial diets, the animals fed ad libitum had early skeletal maturation and advanced growth, but at 7 months of age the length of long bones of litter-mates fed a restricted diet (two-thirds of the caloric intake) was identical [2]. After a period of inhibited growth owing to malnutrition or illness of short duration, the animal will grow at a greater rate than average for its age (i.e., catch-up growth). Influences of growth factors other than nutrition must be considered when judging an animal that is small for its age [3], including the extent of variation in growth patterns of normal healthy animals. From different studies of young dogs raised on food with carbohydrate content of 0 to 62%, protein 20% to 48%, and fat 13% to 76% as percentage of metabolizable energy, it was concluded that, so long as adequate protein and essential fatty acids exist in a palatable diet, it does not appear to matter in growing dogs what proportion of energy comes from carbohydrate, fat, or protein [1]. A study revealed that in 3 groups of Great Danes each fed iso-energetic diets only differing in their dietary protein levels (i.e., 15%, 23%, or 32% protein on dry matter base[dmb]), with carbohydrates exchanged for proteins, and diets fed in equal energetic amounts to all dogs, the 32%-protein-fed dogs had significantly higher body weight without a difference in length of the antebrachial bones than the dogs fed the 15%-protein diet at half a year of age. This leads to the conclusion that a high quality and quantity content of proteins in the diet stimulates soft tissue growth in young dogs, but does not increase skeletal growth or increase the risk for developmental orthopedic diseases [4].

Low Calcium Intake

Young animals have a great need for calcium to mineralize newly formed cartilage and osteoid. Depending on the dietary regimen and hormonal status, 225 to 900 mg/kg body weight (bw) per day is deposited in the growing skeleton of young dogs, of which 100 to 225 mg/kg per day should be absorbed from the intestine [1,5,6]. The minimal requirement for dietary calcium in growing dogs is 0.4 to 0.6% on dmb in small breed dogs, 0.5% on dmb for growing kittens, and 0.7 to 1.2% for fast-growing dogs of large breeds [1]. Low calcium absorption, either from low calcium content of the food or poorly available calcium (complexes with phytic acid or oxalate, high phosphate content of the food, inadequate vitamin D status), can cause a decrease in the circulating calcium concentration.

This situation can be created by feeding an all-meat diet. The decrease in circulating calcium concentration will be counteracted by the increase in PTH secretion, with eventually increased osteoclasia and increased synthesis of the active vitamin D metabolite 1,25-dihydroxycholecalciferol (or 1,25(OH)2 vitamin D3). The latter stimulates calcium (and phosphate) absorption with a total efficiency of up to approximately 80 to 90% of the digested amount in puppies and kittens [5-7]. Subsequently, the high PTH and vitamin D metabolite levels will stimulate calcium and phosphate resorption from bone. When this situation continues for weeks, massive osteoclasia will weaken the skeleton to such an extent that it can withstand neither body weight nor muscle forces. The result is the development of skeletal deformities, which include bowing of long bones and calcaneus, compression fractures in cancellous bone (metaphyseal and epiphyseal areas), deformation of the pelvis and vertebrae, and greenstick fractures of long bones (Fig. 114-1B and Fig. 114-2). No changes occur at the growth plates (Fig. 114-1B). Compression fractures of the vertebrae can result in compression of the spinal cord that may be severe enough to cause posterior paresis or paralysis in the acute phase.

Figure 114-1. Radiographs of the left radius and ulna of five different young dogs used as a diagnostic aid for nutritionally induced skeletal abnormalities by evaluation of the growth plate (gp) width, the metaphyseal (m) aspect, cortical (c) thickness, and length of ulna when compared with the radius (position of styloid process (sp)).

Figure 114-2. Low-calcium diet. Skeleton of a cat fed all-meat food on a long-term basis. The cat has had severe skeletal abnormalities and recurrent constipation. Note the abnormal alignment of the long bones (especially the femurs), the calcanei, the vertebral column, and pelvis.

The bones cannot withstand the stress or load of a splint or cast, and additional greenstick fractures may result proximal to the cast or splint. Therefore, therapy is limited to good nursing care and a diet that fulfills the requirements according to the nutrient requirements of dogs [1] without any injections of vitamin D. This allows the skeleton to become sufficiently mineralized within 3 weeks. Corrective osteotomies of long bones or symphysis pelvis can be considered once the skeleton has become mineralized to acceptable levels. For example, narrowing of the pelvic canal by deformation may result in chronic constipation (Fig. 114-2). Failure of the obstipation to respond to medical management may require pelvic osteotomy at a later date.

Low Vitamin D Intake

Vitamin D metabolites stimulate increased plasma levels of calcium and phosphate to mineralize newly formed osteoid and cartilage. Vitamin D is absorbed by the intestine, hydroxylated in the liver to 25OH vitamin D, and then further hydroxylated in the kidney to 24,25(OH)2 vitamin D3 or to the most active metabolite, 1,25(OH)2 vitamin D3. Puppies fed a semi-purified balanced dry dog food without added vitamin D did not synthesize sufficient vitamin D when they were irradiated daily with ultraviolet (sun) light under controlled circumstances. This is in contrast to other species, including herbivores and omnivores [8]. Biochemical, radiographic, and histologic evidence showed that these dogs developed rickets within 3 months. Thin cortices and broad physeal growth plates (Fig. 114-1C) returned to normal when a commercial dog food was given.

Clinical cases of rickets in dogs and cats are exceedingly uncommon and can be diagnosed by measuring circulating vitamin D3 metabolites [8], or by determining the width of the growth plates as seen radiologically and histologically. An increase in width is not seen with low-calcium-high-phosphate diets, but is a strong indication of rickets. In rickets, the bowing of the legs predominates over the number of pathologic fractures.

Dietary therapy consists of commercial food with adequate amounts of calcium, phosphate, and vitamin D3. No injections of vitamin D3 are indicated, especially because commercial pet foods may contain more than the minimal recommended amounts [9]. When indicated, corrective surgery can be considered later.

High Energy Intake

Young animals have less tendency to become obese with excessive energy intake before 30 weeks of age than do older animals. Free-choice feeding of young dogs coincides with higher plasma levels of thyroid hormone, and thus stimulation of metabolic processes including heat production [10]. Young Great Danes overfed with a palatable, balanced, complete commercial diet did not show evidence of obesity, but rather advanced increases in weight and height when compared with their littermates fed a restricted diet. The dogs fed restricted diets reached the identical length of long bones at 7 months of age [2]. In another study, Great Danes had an even higher energy intake and a greater growth rate, but again without signs of obesity [11]. These Great Danes, as well as German shepherd dogs and retrievers, suffered from more severe developmental orthopedic diseases (including osteochondrosis, panosteitis, and hip dysplasia) when raised on a high caloric intake, in comparison with littermates raised on a restricted energy intake [11-13]. Dogs grow slower and have less fat deposition when fed a low density food with 8% instead of 24% fat, both offered free of choice [10]. Overweight owing to high energy intake may cause biomechanical stress, which, preceding or following cartilaginous lesions, may be held responsible for these orthopedic diseases [10].

The owner of a young dog should monitor growth rate rather than body fat deposition and compare this with the average for that breed. The owner should realize that rapid growth will not lead to a larger adult dog, but will probably increase the risk of orthopedic problems, including hip dysplasia.

High Mineral Intake

To avoid the classic skeletal diseases that are a result of lack of calcium, too much phosphate, or too little vitamin D (as described previously), some owners, as well as some dog food manufacturers, tend to over-supplement with calcium, with or without a proportional addition of phosphate [9]. A high calcium content increases the circulating calcium concentration and eventually increases calcitonin secretion and decreases PTH secretion (for details see Metabolic, Nutritional, and Endocrine Bone Disorders). A chronic hypercalcitoninemic state causes decreased activity of osteoclasts, which are of utmost importance for skeletal modeling during growth. Bony foramina should be widened by the osteoclasts in proportion to growth of soft tissues, such as the spinal cord and nutritional vessels of bones. In several studies, Great Danes fed a diet with a high calcium content (2 g/1000 kJ), with or without excess of other constituents such as protein or phosphate) developed an inadequately expanded cervical vertebral canal in proportion to the growth of the cervical cord [5,11]. This causes compression of the cord with clinical, radiographic, and pathologic signs of canine wobbler syndrome.

Decreased diameter and alteration in the course of the nutritional foramina in the diaphyses restrict venous return, leading to edema in the medullary cavity and subperiosteal. Ultimately, this edema leads to intramedullary fibrosis and bone formation, as well as subperiosteal edema and new bone formation. This entity is known as panosteitis.

Disturbance in enchondral ossification, termed osteochondrosis, was more frequent and more severe in young Great Danes receiving a supplementation of calcium when compared with Great Danes with a calcium intake of 0.8 to 1.1% on dmb [5,11,14]. Not only was the weight-bearing cartilage affected, but also the non-weight-bearing growth plates of ribs; therefore, microtrauma owing to overweight could be excluded. Severe signs of osteochondritis dissecans in the proximal humeral head and retained cartilage cones in metaphyseal growth plates (Fig. 114-1D), with eventual radius curvus syndrome (Fig. 114-3) and deviation of the hind legs [8,11,14] were observed in the dogs whose calcium intake was high. In less severe cases, nutritional correction may restore normal position of the legs (Fig. 114-3); more severe cases may have to be treated surgically.

Figure 114-3. A. A 25-week-old Great Dane with both front legs in valgus position and with radiologic evidence of retained cartilage cones. B. The position of both front legs at age 1 year is normalized after the dog was fed a controlled amount of a balanced diet.

Hypertrophic osteodystrophy (HOD) can be characterized as a massive disturbance of enchondral ossification of growth plates. Typical is the osseous discontinuity in the metaphyseal area of many long bones, close to and parallel with the growth plates. This zone is composed of remnants of cartilage and bone trabeculae, blood, fibrin, and debris. This area becomes visible on radiographs when it is surrounded by mineralized tissue (Fig. 114-1E). At a later stage, a superfluous periosteal reaction becomes visible on clinical and radiographic evaluation, as evidenced by bulging (Fig. 114-1F). Pathologic signs of this disease were found in different controlled studies in well vaccinated Great Danes (a breed with a high prevalence for HOD) but all raised on food with a high mineral content [5,11,15]. Vitamin C supplementation may be expected to aggravate HOD more than to cure it [16]. Owners of young, fast-growing dogs should be aware of the severe consequences of high mineral intake on skeletal development.

Vitamin D Excess

The first hydroxylation of vitamin D3 to 25OH vitamin D3 in the liver is relatively poorly controlled, whereas the second hydroxylation to 1,25(OH)2 vitamin D3 in the kidney is under exquisite control. The allowance for vitamin D3 is 500 IU/kg food on dmb for dogs (growth and maintenance alike) and 750 IU/kg food for kittens (but possibly as low as 250 IU/ kg food) and 500 IU/kg food for adult cats for maintenance [1]. In case of over supplementation of vitamin D3, 25OH vitamin D3 will be metabolized into the less biologically effective 24,25(OH)2 vitamin D3 and is the formed 1,25(OH)2 vitamin D3 quickly hydroxylated into the non-effective 1,24,25(OH)3 vitamin D3 [17]. In a controlled study in Great Danes, vitamin D excess of 100 times the recommended level of 500 IU per kg food, given during a 5-month period, caused plasma concentrations of 1,25(OH)2 vitamin D3 lower than controls, coinciding with severe osteochondrosis with radius curvus syndrome [17] with a similar radiologic appearance as in Fig. 114-1D. Massive intakes of vitamin D3 (or even more so of its metabolites) can cause hypercalcemia together with hyperphosphatemia, anorexia, polydipsia, polyuria, vomiting, muscle weakness, and lameness [1]. The circulating high levels of calcium and phosphate are a result of increased bone resorption, increased absorption from the gastrointestinal tract, and eventually, tubular mineralization. Vitamin D intoxication in dogs and cats is marked by mineralization of soft tissues, including blood vessels, alveoli, and renal tubules, together with pathologic changes in the gastrointestinal tract and the heart [1].

Pet foods can contain from 2 to more than 10 times the NRC-recommended amount of vitamin D [9]. Extra supplementation with vitamin D can cause increased calcium and phosphate absorption with deleterious effects on skeletal development (see Chapter 99) and probably on kidney function [9]. Owners of young dogs and cats should be aware of the severe effects of clinical and subclinical vitamin D3 intoxication with cumulative effects owing to vitamin over-supplementation.

Excessive Vitamin A Intake

Because development of hypervitaminosis A demands prolonged intake of vitamin A-rich food stuffs such as raw liver, intoxication is rarely seen clinically in young animals. Metabolism of an excess of vitamin A is more complete in cats than in dogs, so hypervitaminosis A is more likely to occur in kittens than in puppies (see Metabolic, Nutritional, and Endocrine Bone Disorders).

Experimentally, massive doses of vitamin A given for several weeks caused profound depression of bone growth, owing to degenerative changes of the growth plates, in addition to decreased osteoblast activity and osteoporosis in both kittens and puppies [9]. Osteophyte formation and periosteal reactions are present but of minor importance in these young animals [9]. The recommendation for vitamin A is 5000 IU/kg of food dmb for dogs (both for growth and for maintenance) and 3333 IU/kg food dmb for kittens and 6000 IU/ kg food for adult cats [1]; supplementation of commercial pet food with a vitamin additive can result in giving 100 times the normal requirement [9]. Owners of young companion animals, especially kittens, should be aware of the severe skeletal abnormalities that can result from over-supplementation with vitamin A.

Nutrition and Skeletal Maintenance

Permanent bone turnover occurs in the adult dog and cat and consists of bone resorption as well as new bone formation. In the adult dog, calcium deposition and resorption are equal in magnitude: approximately 4 to 8 mg/kg bw per day. Daily losses of calcium by endogenous fecal and urinary excretion (i.e., 10 to 30 and 1 to 7 mg/kg bw per day, respectively) can easily be compensated for by a balanced diet.

Natural menopause and other causes of estrogen deficiency in women are characterized by bone loss leading to pathologic fractures of the vertebrae, proximal femur, and wrist. This explains the extensive concern for nutrition in elderly women. Although ovariectomy is a common practice in female cats and dogs, and some osteoporotic changes are noticeable 17 to 36 weeks after surgery [17,18], this practice does not result in a problem of practical significance in companion animal orthopedics (see Metabolic, Nutritional, and Endocrine Bone Disorders).

Feeding adult animals a diet based on some variation of the dietary requirements prescribed for growing animals usually does not result in serious problems. The major clinical problems in relation to orthopedics in adult companion animals are excessive energy intake, low vitamin D or excessive phosphorus intake together with decreased renal function, and excessive vitamin A intake, especially in cats.

Excessive Energy Intake

Superfluous energy content will increase the risk of obesity for the normally active companion animal. In addition to high energy intake, the following factors may underlie an abnormal gain in body weight: the dietary composition (protein-energy ratio), breed and strain differences, hormonal status, the number of adipocytes present, and changes in household circumstances. Between 24% and 44% of dogs and at least 9% and 25% of cats are said to be overtly obese [1]. The females of the species are more frequently obese. About 25% of obese dogs have orthopedic problems, whereas only 10% of all dogs seen in 11 veterinary practices had orthopedic problems [19]. These problems included arthritis, herniated intervertebral disks, and ruptured anterior cruciate ligaments. In a risk assessment study for hip dysplasia in German shepherd dogs, golden retrievers, Labrador retrievers, and Rottweilers, high body weight was shown to be an important risk factor [20] (see "Osteoarthrosis" later in this chapter). No known dietary aberration is responsible for these diseases, but rather the mechanical effect of the increased weight on the skeleton [19].

Excessive Mineral Intake

The calcium and phosphate content of ordinary commercial pet foods can significantly exceed the recommended levels, and although this may not have deleterious effects on healthy adults, it is certainly unnecessary [9]. In dogs and cats with severe loss of kidney function, phosphate will accumulate and thereby decrease circulating calcium concentrations. Hyperphosphatemia can go together with decreased 1-α hydroxylation of 25OH vitamin D, resulting in diminished production of 1,25(OH)2 vitamin D3 and thus in decreased active calcium absorption. As a result, the parathyroid glands will secrete more PTH (renal secondary hyperparathyroidism), causing an increase in osteoclastic activity to normalize circulating calcium concentrations, with eventual development of osteodystrophy and loosening of teeth in the mandible and maxilla. Of greater clinical significance are the systemic effects of renal failure. Renal osteodystrophy is characterized microscopically by increased osteoclast and osteocyte activity and inadequate mineralization of normal osteoid. High phosphate intake will aggravate the situation by (1) promoting mineral depositions in soft tissues, not only the kidney but also periarticular tissue, tendon sheaths, and foot pads; and (2) decreasing circulating calcium concentrations and subsequently boosting hyperparathyroidism [21].

Low Vitamin D Intake

Because young dogs are not able to fulfill their need for vitamin D by biosynthesis in the skin via stimulation by ultraviolet light, it seems reasonable to suggest that adults also need dietary vitamin D. Hypovitaminosis D, causing osteomalacia in adult dogs and cats and characterized by increased osteoclasia and unmineralized osteoid layers, is seldom recognized clinically. The deleterious effects of vitamin D intoxication are the same as those previously described for young animals.

Excessive Vitamin A Intake

Hypervitaminosis A is seen more frequently in cats than in dogs, especially at an older age (2 to 9 years). Radiologically, hypervitaminosis A is characterized by new bone formation rather than by osteoporosis or bone loss. New bone formation starts at the points of insertion of ligaments, muscles, and joint capsules, causing narrowing of intervertebral foramina in the cervical area and ankylosis of vertebral, shoulder, elbow, hip, and stifle joints (rarely carpal and tarsal joints). In addition to lethargy, pain on palpation, and changes in character, such changes as stiffness of the neck or of one or more large joints can be the first clinical signs. For further details and treatment see Metabolic, Nutritional, and Endocrine Bone Disorders.

Nutrition and Osteoarthrosis

Cartilage contains chondroblasts, proteoglycans, and collagen. Proteoglycans are built out of glycosaminoglycans (GAGs) and a core protein. Aggrecan is an important proteoglycan in joint cartilage, with keratin sulphate and chondroitin sulphate as GAGs. About 200 aggrecan molecules are bound via a glycoprotein to a hyaluronan molecule, binding a large quantity of extracellular water, determining the compressibility of cartilage. Collagen molecules in cartilage contain large amounts of hydroxyproline and hydroxylysine. The molecules form a triple helix structure, bound to fibrils and these to fibers, with great strength against pull and which form a labyrinth holding proteoglycans in its place. During aging, the length of GAGs decreases, the proteoglycan content decreases, and thus the water content and the flexibility to withstand loading decrease. GAGs may be damaged by reactive oxygen species (ROS), i.e., free radicals formed during different metabolic processes, trauma, infection, and irradiation.

Regeneration of cartilage can occur after microtrauma by proliferation of undamaged chondrocytes and by de novo synthesis of proteoglycans and collagen. Severe cellular damage will lead to a scar without cells, a fibrotic cartilage scar with a low content of proteoglycans.

Under normal circumstances proteolytic enzymes, mainly matrix metalloproteinases (MMPs), will be suppressed by tissue inhibitors of MMPs (TIMPs). In osteoarthrosis (OA), however, MMPs will be formed under the influence of cytokines interleukin-I (IL-I) and tumor necrosis factor-α, released by synovial membrane cells, monocytes, macrophages, and T-cells. These cytokines also stimulate chondrocytes and osteoclasts to produce MMPs as soon as their surrounding cartilage has been destroyed. In addition, IL-I stimulates the release of arachidonic acid (AA) metabolites including prostaglandin PGE2 from chondrocytes and synovial membrane as well as leukotriene B4 (LTB4) [5].

Causative Role of Nutrition

Osteoarthrosis (OA) can be divided into primary OA, i.e., without any other cause than aging, and secondary OA, which has a variety of causes, including incongruency or loose bodies in the joint, joint instability, and infection, immune disease, or hemarthrosis. This wide variety of diseases will eventually result in clinical OA. The age of onset and severity of occurrence of primary OA may depend on the breed (Patronek et al, 1997). Many orthopedic developmental diseases have a low h2 (as in elbow dysplasia, h2 = 0.4-0.7), leaving a large influence on the environment. Fragmented coronoid process (FCP) and osteochondrosis of the elbow joint have been explained by Olsson [22] as a disturbance of endochondral ossification and, as such, expressions of the same disease. Osteochondrosis is seen more frequently in certain breeds and subpopulations and can be aggravated by high food intake and excessive calcium intake, [5,8] as well as by over-supplementation of balanced food with vitamin D [23]. Rations rich in protein will not have a disturbing influence on skeletal development [4], however, Great Danes raised on food with an increased calcium and phosphorous intake but with the same Ca:P ratio (3.3 Ca and 3.0% P versus controls on 1.1% Ca and 0.9% P) also developed disturbances in endochondral ossification in the growth plates of the distal radius or ulna (Fig. 114-1D) [14]. As a consequence, elbow incongruity developed, owing either to a severe disturbance of growth in length of the radius or to a severe radius curvus syndrome with disturbed growth in length of the ulna (Fig. 114-3) [8,14]. The latter may coincide with an ununited anconeal process or the painful distraction cubiti; both will lead to OA of the elbow joint. In studies in Labradors [2,13], Great Danes [11] and German shepherds [12] it has been demonstrated that OA develops in hip joints in overweight dogs and less frequently in restricted-fed dogs. The frequency and severity of the occurrence of OA can thus be prevented by dietary management, including a food with a lowered calcium-to-energy ratio, or a quantitative restriction of food intake, and without adding minerals or vitamin D to a balanced diet.

Therapeutic Role of Nutrition

The nonsurgical therapy of OA includes adaptations and medications. First the body weight of the patient should be adapted. Decrease of weight, gained during the period of decreased mobilization but not with a simultaneous adaptation of energy intake, will be the primary goal. A significant improvement was recorded by Impellizeri et al., in dogs with HD, following a decrease in body weight by 11 to 18% [24]. This clinical finding was supported by the objective score by force-plate analysis by Burkholder et al. [25]. Adaptation to the amount and the kind of activity that does the least possible harm to the joint, preferably hydrotherapy (i.e., swimming), should coincide with the weight reduction program.

Corticosteroids suppress phospholipase activity, consequentially with stabilization of blood vessel walls and lysosomes. The joints will be less painful and less synovia is produced. Because regeneration of cartilage will be decreased under the influence of corticosteroids, long-lasting or repetitive use of corticosteroids, especially intraarticular and at higher doses, is contraindicated. Nonsteroidal anti-inflammatory drugs (NSAIDs) have actions against cyclooxygenase (COX) enzymes; COX1 stimulates the production of prostaglandins (PGs), which protect the body, whereas COX2 stimulates the production of PGE2, which is responsible for clinical signs such as pain and hyperemia (with resultant warm joint and overproduction of joint fluid). Selective COX2 inhibitors with or without suppressive action on lipoxygenase are claimed to be available for dogs, with fewer side effects than most inhibitors of COX1 and COX2. NSAIDs with low incidence of side effects will be prescribed for a prolonged period, not to mask pain but to improve the metabolic condition of the diseased joint [26].

In order to support regeneration of joint cartilage and to shorten or lower the dosage of NSAIDs, a search continues for nutritional support of patients with OA. These supplements or diseases-modifying osteoarthritis agents (DMOAs) include chondroitin sulphate, glucosamines, polyunsaturated fatty acids, and antioxidants.

Chondroitin sulphate increases in vitro the production of proteoglycans and, therefore, the regeneration of cartilage [27]. When given prophylactically in rabbits, it prevents synthesis of MMPs by IL-3 and thus cartilage damage.

Glucosamines, precursors of GAGs, will stimulate synthesis of GAGs, prostaglandins, and collagen by chondrocytes in vitro [27]. In case of substitution of glucosamines in the medium of chondrocytes, mRNA content for aggrecan increased, and for MMPs decreased and synthesis of proteoglycan increased [28]. In rabbits with a cranial cruciate ligament (CCL) rupture, 120 mg/kg body weight of prophylactic glucosamine decreased the amount of chondropathy in comparison with controls [29]. In a study in dogs with CCL rupture as a model, it has been demonstrated that these dogs had less cartilage swelling, less total and active metalloproteinase (MMP), and lower pathologic scores when injected with 4 mg/kg bw glycosaminoglycan polysulfuric acid (GAGPS) twice weekly for 4 to 8 weeks, starting 4 weeks after the CCL rupture [30]. It is suggested by Altman et al that GAGPS suppress proteoglycan breakdown by MMPs or by directly inhibiting MMP in cartilage, rather than by increasing synthesis of proteoglycans by chondrocytes [30]. De Haan et al demonstrated in a clinical double-blind, placebo-controlled trial that, in dogs with hip dysplasia, 4.4 mg GAGPS per kg bw (IM for 3 to 5 days) revealed an improvement in lameness score, range of motion, and joint pain and no side effects after 8 injections, with only small improvement in the placebo group of dogs [31].

Combinations of chondroitin sulphate and glucosamines given to dogs with OA subjectively allowed for more normal locomotion and joint movement than in untreated controls [32]. Prophylactically provided, this combination decreased inflammation in dogs with induced arthritis [33], possibly owing to a modulated metabolism of the articular cartilage. The latter was suggested to occur in dogs with CCL ruptures, supplemented with a mixture of chondroitin sulphate, glucosamine hydrochloride, and manganese ascorbate [34].

The polyunsaturated free fatty acid (PUFA) component of mussels or plant seeds has a potentially beneficial role in immune-related disorders and OA [35]. Leukotrienes are formed out of arachidonic acid (AA; 20:4Ω -6) and eicosapentaenoic acid (EPA; 20:6Ω-3), originating from cellular membranes, under the influence of the enzyme 5-lipoxygenase. Pro-inflammatory LTB4 originates from AA, anti-inflammatory LTB5 originates from EPA. The amount and type of these eicosanoids are determined by the availability of the PUFA precursor. A higher Ω–3 intake results in decreased membrane AA levels and thus a decreased synthesis of eicosanoids from AA and an increase in eicosanoids derived from EPA. In joints with OA, the LTB4 content is increased [36]. In 36 dogs with elbow OA owing to elbow dysplasia, a double-blind efficacy study was performed by feeding balanced foods with increased Ω-3 content (Ω-3 of 4%, and Ω-6 of 20%) versus a high Ω-6 content (Ω-3 of 0.8%, and Ω-6 of 38%) revealed significant increase in plasma LTB5 concentrations in the former group, although ground reaction forces did not differ between the two groups of dogs [37]. A clinical trial including force-plate analysis performed in two groups of dogs fed either a control food or an EPA-supplemented diet for a 90-day period revealed that 31% of the controls and 82% of the EPA-supplemented group improved their weight-bearing ability [38]. In addition, in vitro studies of canine cartilage indicated that cartilage exposed to EPA stopped further degradation [39].

Antioxidants may decrease the damage of synovial cells by reactive oxygen species (ROS). For this purpose, vitamins A, C, and E and β-carotene content in the diet can be increased [40].

Combinations of chondroitin, glucosamine and PUFAs are present in green-lipped mussels (GLM). The flesh part of the GLM, separated from the shell, contains saturated, monounsaturated, and polyunsaturated fatty acids. Of the latter, a large amount is Ω-3 fatty acid, mainly EPA, and docosahexaenoic acid (DHA), with a final ratio of Ω-6: Ω-3= 1: 10. GLM powder is claimed to be a 5-lipoxygenase-pathway inhibitor. Freeze-dried GLM powder contains in addition a variety of nutrients that may have a beneficial effect on joint health, including amino acids (glutamine, methionine), vitamins C and E, and minerals (zinc, copper, and manganese). The combination of Ω-3, PUFA, and other ingredients may have the synergistic potential to limit the progression of OA. In a double-blind, randomized, controlled trial in dogs with OA, 17 dogs were given GLM supplement powder and 15 dogs were given GLM supplement oil (both in a daily dosage of 1000 mg when bw was more than 34 kg; 750 mg when bw was 34 to 25 kg; 450 mg when bw was less than 25 kg) and both groups were compared with 15 controls. A non-objectivated score of arthritic signs grading from no signs to severe was given for mobility and for all major joints individually before the start of the study and at 6 weeks. Joint swelling, pain, and crepitus were reported to improve in only the GLM-powder supplemented group in comparison with the controls [41]. In addition, Bierer and Bui reported on a dose-response in alleviating arthritis score in 4 groups of dogs: 3 dosage groups (1:2:4) receiving GLM-power and 1 control group [41]. All 3 doses resulted in a similar improvement in total arthritic score and all significantly different from the controls. However, no significant effects were observed with regard to mobility and range of joint movement with the addition of GLM in any of the groups. Longer study period and more sensitive assessment methods may be helpful in detecting any possible effects in these parameters [41].

There is great interest in the discovery of natural products to be used as DMOAs, based on the aversion to "chemical substances" (i.e., NSAIDs) that exist among many dog owners, as well as on the less restricted efficacy-control of supplements in terms of dosage and purity, and the approval to add these substances to dog food. There is a growing need to double-blind clinical-efficacy studies with objectivated criteria to demonstrate the evidence gathered in vitro that these DMOAs, "neutraceuticals" and "supplements" may be beneficial to patients suffering from OA. Meta-analyses of the efficacy of glucosamine and chondroitin sulphate for treatment of OA in humans, led to different conclusions: supplementation with glucosamine or chondroitin sulphate demonstrated some efficacy in some symptom-relieving parameters, but the ability to modify the structure of articular cartilage was not confirmed [42]. Research is scarcely available to demonstrate a direct therapeutic effect in support of the treatment of OA in dogs at the level these substances are included in most pet foods [32,38]. Claims for different levels or different combinations of neutraceuticals, or the period before efficacy can be expected, the use in particular breeds or sizes of dogs, or the indication for their use in different joints with OA or at certain stages of OA will be a matter of debate until the onus of proof is laid in the hands of those who claim the efficacy.

Nutrition and Fractures

The skeleton is under the influence of calcium homeostasis. Low calcium or high phosphate intake or low vitamin D intake can cause pathologic fractures owing to poor mineralization of the skeleton (Fig. 114-1). These pathologic fractures include compression fractures of cancellous bone and greenstick fractures of cortical bone. In the latter, the abnormal alignment (Fig. 114-2) can be corrected only after the bone has achieved normal mineralization. Therefore, the first phase should consist of good nursing and feeding of a balanced diet. Because a great deal of osteoid (and cartilage, in the case of hypovitaminosis D) has to be mineralized in this first phase of treatment, this "bone hunger" can be compensated for by supporting the balanced food with calcium salts (i.e., bone meal) up to 0.7 g calcium and 0.5 g phosphorus per 1000 kJ. Radiographic evaluation (Fig. 114-3) will demonstrate dramatic improvement. If the improvement does not occur, other rarer causes of abnormal skeletal development, including osteogenesis imperfecta (see Chapter 99), should be considered. When posterior paralysis or paresis occurs, the prognosis for improvement is guarded.

Spontaneous fractures, especially of the mandibles, in old dogs can be the first sign of severe renal dysfunction and they require treatment.

When properly treated in a healthy animal, traumatic fractures heal via the process of primary or secondary bone healing. The latter has much in common with enchondral ossification and thus needs the same nutritional support. Optimal circumstances can be reached with a balanced commercial pet food containing optimal levels of calcium, phosphate, vitamin A, and vitamin D. Excessively high doses of these nutrients have been demonstrated to retard enchondral ossification [39] and bone healing [40]. Pain owing to trauma or surgery may cause distress, which depletes reserves of protein and diminishes immune competence. In addition, the dietary requirements of ascorbic acid and probably of other nutrients are increased [1]. In surgical patients, the fasting period before and after anesthesia may be detrimental. Therefore, a palatable food formulated to meet the needs of young, growing animals must be considered. Even obese patients should be kept in a positive energy balance, although this demands special management of fracture treatment and postoperative mobilization.