DEVELOPMENTAL ORTHOPAEDIC DISEASE AND NUTRITION S ROLE

Transcription

1 Vet Times The website for the veterinary profession DEVELOPMENTAL ORTHOPAEDIC DISEASE AND NUTRITION S ROLE Author : CATHERINE DUNNETT Categories : Vets Date : October 6, 2008 CATHERINE DUNNETT explains how, with up to 80 per cent of some horse breeds affected by this condition, diet can be critical factor in managing treatment DEVELOPMENTAL orthopaedic disease (DOD) is not a single disease process this umbrella term was introduced during the mid-1980s to describe a number of potentially related conditions that were commonly seen in growing horses. DOD encompasses: physitis; angular limb deformities; subchondrial cystic lesions; flexural limb deformities; cuboidal bone abnormalities; osteochondritis dissecans (OCD); and juvenile osteoarthritis. 1 / 13

2 Incidence and genetic influence It is likely that there is a familial component to many of the equine developmental orthopaedic diseases, and this has certainly been identified in regard to OCD, both in standardbred totters (Grøndahl et al, 1993) and warmbloods (Hoppe, 1984). To date, no comparable work has been carried out in thoroughbreds to establish a similar genetic basis to this condition, although this does not rule out its implication. There does appear to be clear differences in the susceptibility of different breeds to DOD (Lepeule et al, 2008). In a study of 392 foals (from a total of 21 stud farms with similar management regimes), 66.3 per cent of foals were radiographically confirmed as having a form of DOD. It was also apparent that warmblood foals experienced the highest incidence of DOD (80.6 per cent) compared to standardbreds (62.7 per cent) and thoroughbreds (60.1 per cent). In this particular survey, osteochondral fragmentation and physitis were the most common manifestations of DOD in all breeds, although the relative severity differed between breeds. While genetic and breed differences appear to impact on the incidence of DOD, other factors (such as mechanical stress and trauma, defects in vascularisation, growth rate and body size, and endocrine effects) have also all been implicated in the aetiology of one or more developmental orthopaedic diseases. Nutrition has provided a focus for research into the cause of DOD, as it impacts either directly or indirectly on many of the previously implicated factors. The importance of diet is emphasised by its influence on the overall hormonal milieu in the body and specific effects on hormones, including insulin, thyroxine, growth hormone, parathyroid hormone and calcitonin, which are all involved in endochondral ossification. Energy intake and rate of growth Early on, OCD was associated with large-framed and rapidly growing horses. The incidence of OCD in the fetlock, hock, shoulders and stifle in a group of 271 thoroughbred foals was described by Pagan (1998). With the exception of early fetlock lesions, OCD was generally associated with increased bodyweight and a faster rate of growth. This reported association with growth rate and bodyweight was linked with over-nutrition, in terms of either protein or digestible energy (DE) intake. In reality, growth rate reflects a combination of genetics and diet over-supply of energy has been demonstrated to increase the incidence of OCD. The previously hypothesised causal link with excessive protein intake, however, has not been proven. In the studies of Savage et al (1993), reviewed by Jeffcott et al (1996), foals fed a ration that 2 / 13

3 provided 129 per cent of the National Research Centre (NRC) requirements for DE consistently resulted in clinical and radiographical signs of OCD, with 50 per cent of the foals affected. In contrast, OCD was not found in a group of foals that were fed 126 per cent of the NRC requirements for protein, or in a control group where 100 per cent of the NRC requirements for both energy and protein were provided. Energy source Latterly, this early work has led to further studies to examine the importance of energy sources to the incidence of OCD. The hydrolysable carbohydrate (starch and sugars) content of the diet became the focus of attention for researchers interested in OCD due to its close relationship to insulin metabolism. The involvement of insulin and insulin-like growth factors (IGF) in the differentiation of cartilage chondrocyte cells has previously been reported (Henson et al, 1997). These authors demonstrated that insulin was able to suppress the differentiation of equine chondrocytes and, hence, has been previously implicated in the pathogenesis of OCD (Henson et al, 1997). Research supports this, as diets with a high glycaemic nature, such as those with a high starch and sugar content (typical of the more traditional stud and youngstock rations) appear to be more likely to trigger OCD. A higher glucose and insulin response to feeding a cereal-rich feed was observed in young standardbred horses with OCD lesions relative to healthy foals (Ralston, 1996). These results were supported by Pagan et al (2001) in a study of 218 thoroughbred weanlings, where a higher glucose and insulin response to a cereal-based concentrate meal was also associated with an increased incidence of OCD. This exaggerated glucose and insulin response to feeding has been suggested to be mediated by insulin resistance, which appears to be related to both current feeding practice and previous dietary history. However, the ultimate development of DOD is still likely to depend on the underlying susceptibility of individual animals, which may have a genetic basis. Insulin resistance Insulin resistance is apparent when a normal concentration of insulin fails to elicit a normal physiological response. Decreased sensitivity or resistance to insulin has been demonstrated in healthy thoroughbred weanlings following adaptation to a pasture-based diet, in conjunction with two discrete highstarch and sugarcontaining meals being fed daily (49 per cent NSC). In this study, insulin sensitivity was 37 per cent less than in the control group fed a contrastingly highfibre and oil 3 / 13

4 feed, in combination with pasture (12 per cent NSC; Treiber et al, 2005). Similar findings were also reported in mares maintained on a mixed diet of pasture and either a high-starch and sugar or high-fibre and oil-containing concentrate ration (Staniar et al, 2007a). In addition, although the significance remains unclear, the circulating level of IGF-1 was reported to be higher in yearlings fed a high-starch and sugar diet in conjunction with grazing during a period of rapid spring growth, in comparison to those at pasture and supplemented with a highfibre and oil diet (Staniar et al, 2007b). The work of George et al (2007) does not support the suggestion that insulin insensitivity in youngsters and adult horses could be due to metabolic programming during foetal or neonatal growth in response to maternal diet. In this study, foals exhibited high sensitivity to insulin in comparison to adult horses, and although wide individual variation was found, this could not be attributed to the glycaemic nature of the maternal diet (George et al, 2007). Despite this, diets that produce high post-prandial glycaemic peaks in genetically susceptible individuals may be significant, with reference to OCD and other developmental orthopaedic diseases. Research continues to develop appropriate diagnostic indicators of susceptibility to OCD, in particular using assessment of insulin sensitivity in horses (Firshman et al, 2007). Other endocrine factors The potential role of other endocrine factors, including the glucocorticoids that can be affected by the composition of the diet (Mills et al, 1979), remain to be investigated fully in horses. Long-term administration of dexamethasone to horses has been reported to induce osteochondrosis-type lesions (Glade et al, 1983). In the review by Mcllwraith (2005), glucocorticoid involvement in DOD is postulated, given its known effects on parathyroid hormone activity, glycosamino glycan formation, capillary penetration of cartilage, vitamin D metabolism and collagen crosslinking. However, there is a paucity of data in this area. One study carried out by Vervuert et al (2004) found no significant difference in the level of markers of bone formation (osteocalcin, carboxyterminal propeptide of type-one collagen), bone resorption (carboxyterminal telopeptide of type-one collagen) or of parathyroid hormone between normal Hanoverian warmblood foals and those that developed OCD lesions. Mineral imbalances Many mineral imbalances in the diet, including high calcium, high phosphorus and low copper and high zinc, have also been implicated as causative factors in OCD in particular, but few have any equivocal evidence to support their involvement. 4 / 13

5 For example, OCD lesions have been reproduced experimentally in foals maintained on a diet where phosphorus intake was five times the current recommended NRC level (Savage et al, 1993). However, in the same study, feeding calcium at three times the NRC recommended level failed to produce OCD lesions. Practically, a highphosphorus diet could arise inadvertently by feeding straight cereals, such as oats, without a suitable balancer or complementary feed, such as alfalfa, to redress the low calcium-tophosphorus ratio in the grain. Less extreme versions of this diet can occur through excessive top dressing of a balanced coarse mix or cubes with additional cereals, such as oats or barley, which is still common practice. Copper has received particular attention with regards to DOD due to its functional role in the activity of the key enzymes lysyl oxidase and superoxide dismutase (SOD), both of which are involved in either cartilage formation or turnover. Low copper status, either directly as the result of reduced intake or as the result of a secondary deficiency, has been previously implicated in the incidence of OCD and other developmental orthopaedic disorders, as reviewed by Harris et al (2004). For example, in a blinded randomised trial where both diets containing high copper (25mg/kg) and low copper (7mg/kg) were fed to foals, those in the lower copper group had declining liver copper concentrations and exhibited OCD lesions, physitis and other limb deformities. This was in contrast to the high copper group, where these abnormalities were essentially absent (Hurtig et al, 1993). Copper status in the foal is related to maternal dietary intake during gestation, but does not appear to be improved by supplementation of the mare post-partum (Pearce et al, 1998a; Pearce et al, 1998b). The effectiveness of copper administration, however, may depend on the route of intake as intramuscular administration in the ninth and 10th month of pregnancy failed to elicit a similar increase in liver copper concentration in the resultant foals at birth (Gee et al, 2000). The copper content of mares milk is low and unresponsive to copper supplementation of the mare (Pearce et al, 1998a). In contrast, direct supplementation of foals does, however, appear to increase their liver copper stores (Pearce et al, 1998b). Molybdenum effects In grazing youngsters, a secondary copper deficiency could arise through excessive molybdenum levels in pasture. In cattle, bacteria in the rumen form complexes between molybdenum and sulphur. These thiomolybdate complexes can bind copper within the gutand, when absorbed, will bind further copper, either circulating in the blood, or in association with copper-dependent enzymes. This can impair the activity of some key enzymes that are involved in growth processes and cartilage turnover, such as SOD (Ward et al, 1997). However, given the anatomical and spatial differences in the horse s digestive tract, there is 5 / 13

6 theoretically less opportunity for these thiomolybdates to be absorbed. It has been largely accepted from previous studies that molybdenum-derived copper deficiency in horses is not significant, as copper status measured by liver, plasma, blood cell and plasma trichloroacetic acid-insoluble copper concentrations, as well as the enzyme activities of plasma caeruloplasmin and red blood cell SOD, were unchanged with increased dietary molybdenum intake (Pearce et al, 1999; Rieker et al, 2000). However, molybdenum toxicosis in horses as a cause of death has been reported (Ladefoged et al, 1995) and an in-field analysis of SOD in a larger number of animals grazing pasture with high levels of molybdenum suggests that copper status may be affected by dietary molybdenum intake (Telfer, personal communication). While there is evidence to support the role of copper in the aetiology of DOD, it should not be regarded as a panacea for these conditions, as its effects are likely to be dependent on other factors. It has been suggested that the reduced copper status may be a secondary effect due to marginal copper intake on the capacity for repair of early lesions (Harris et al, 2004). Other trace minerals, including manganese and zinc, may be important during a foal s development, as they are also necessary co-factors for SOD enzymes involved in regulating cartilage metabolism. Certainly, the effects of excess zinc intake and the zinc-to-copper ratio of the diet on the incidence of DOD have been investigated. These studies, however, primarily highlight the issue of antagonism between zinc and copper in the digestive tract and the potential for an induced or secondary copper deficiency (Bridges et al, 1990; Cymbaluk et al, 1993). The effect of diet on the incidence of OCD and other developmental orthopaedic diseases is, therefore, not straightforward and is likely to be highly influenced by hereditary factors. A large epidemiological study carried out in Germany to establish the practical feeding practices in Hanoverian warmblood mares and foals (629 foals from 83 farms) revealed that the diets of both were often deficient in digestible energy, digestible crude protein, calcium, phosphorus, copper and zinc. However, despite these findings, there was no clear link between feeding status, mineral intake and the incidence of OCD lesions in the foals (Coenen et al, 2004). However, in this study, the dietary intake was examined post-partum and, as discussed, dietary composition and balance during the latter stages of gestation may be the more significant period, with reference to the future incidence and capacity for recovery from DOD. References Bridges C H and Moffitt P G (1990). Influence of variable content of dietary zinc on copper metabolism of weanling foals, American Journal of Veterinary Research 51(2): Coenen M, Vervuert I, Granel M, Winkelsett S, Borchers A, Christmann L, Bruns E, Distl O and Hertsch B (2004). Feeding practices in Hanoverian warmblood mares and foals with regard to the incidence of osteochondrose, European Association for Animal Production (EAAP): The Growing Horse: Nutrition and Prevention of Growth Disorders, Wageningen Academic Publishers, Dijon, France. 6 / 13

7 Cymbaluk N F and Smart M E (1993). A review of possible metabolic relationships of copper to equine bone disease, Equine Vet J 16 (Suppl): Firshman A M and Valberg S J (2007). Factors affecting clinical assessment of insulin sensitivity in horses, Equine Veterinary Journal 39(6): Gee E K, Grace N D, Firth E C and Fennessy P F (2000). Changes in liver copper concentration of thoroughbred foals from birth to 160 days of age and the effect of prenatal copper supplementation of their dams, Australian Veterinary Journal 78(5): George L, Staniar W B, Harris P and Geor R (2007). Insulin sensitivity and glucose dynamics in neonatal foals, FASEB J 21(6): A1420-b-. Glade M J, Krook L, Schryver H F and Hintz H F (1983). Morphologic and biochemical changes in cartilage of foals treated with dexamethasone, The Cornell Veterinarian 73(2): Grøndahl A M and Dolvik N I (1993). Heritability estimations of osteochondrosis in the tibiotarsal joint and of bony fragments in the palmar and/or plantar portion of the metacarpo and metatarsophalangeal joints of horses, Journal of the American Veterinary Medical Association 203(1): Harris P A, Staniar W B and Ellis A D (2004). Effect of exercise and diet on the incidence of DOD, EAAP: The Growing Horse: Nutrition and Prevention of Growth Disorders, Wageningen Academic Publishers, Dijon, France. Henson F M D, Davenport C, Butler L, Moran I, Shingleton W D, Jeffcott L B and Schofield P N (1997). Effects of insulin and insulin-like growth factors I and II on the growth of equine fetal and neonatal chondrocytes, Equine Veterinary Journal 29(6): Hoppe F (1984). Radiological investigations of osteochondrosis dissecans in Standardbred Trotters and Swedish Warmblood horses, Equine Veterinary Journal 16(5): Hurtig M, Green S L, Dobson H, Mikuni-Takagaki Y and Choi J (1993). Correlative study of defective cartilage and bone growth in foals fed a low copper diet, Equine Vet J 16 (Suppl): Jeffcott L B and Savage C J (1996). Nutrition and the development of osteochondrosis (dyschondroplasia), Pferdeheilkunde 12(3): Ladefoged O and Sturup S (1995). Copper deficiency in cattle, sheep and horses caused by excess molybdenum from fly ash: a case report, Veterinary and Human Toxicology 37(1): Lepeule J, Bareille N, Valette J P, Seegers H, Jacquet S, Denoix J M and Robert C (2008). Developmental orthopaedic disease in limbs of foals: Between-breed variations in the prevalence, location and severity at weaning, Animal 2(2): Mcllwraith C W (2005). What are the major problems associated with growth and how important are they really? The 1st Waltham International Breeding Symposium, Newmarket, UK. Mills S E and Jenny B F (1979). Effects of high concentrate feeding and fasting on plasma glucocorticoids in dairy heifers, Journal of Animal Science 48(4): Pagan J D (1998). The incidence of developmental orthopaedic disease (DOD) on a Kentucky thoroughbred farm, Advances in Equine Nutrition, Nottingham University Press I: 7 / 13

8 Pagan J D, Geor R J, Caddel S E, Pryor P B and Hoekstra K E (2001). The relationship between glycemic response and the incidence of OCD in thoroughbred weanlings: a field study. 47th Annual American Association of Equine Practitioners Convention, San Diego, California. Pearce S G, Firth E C, Grace N D and Fennessy P F (1999). The effect of high pasture molybdenum concentrations on the copper status of grazing horses in New Zealand, New Zealand Journal of Agricultural Research 42(1): Pearce S G, Grace N D, Firth E C, Wichtel J J, Holle S A and Fennessy P F (1998b). Effect of copper supplementation on the copper status of pasture-fed young thoroughbreds, Equine Veterinary Journal 30(3): Pearce S G, Grace N D, Wichtel J J, Firth E C and Fennessy P F (1998a). Effect of copper supplementation on copper status of pregnant mares and foals, Equine Veterinary Journal 30(3): Ralston S L (1996). Hyperglycemia/ hyperinsulinemia after feeding a meal of grain to young horses with osteochondritis dissecans (OCD) lesions, Pferdeheilkunde 12(3): Rieker J M, Cooper S R, Topliff D R, Freeman D W and Teeter R G (2000). Copper balance in mature geldings fed supplemental molybdenum, Journal of Equine Veterinary Science 20(8): Savage C J, McCarthy R N and Jeffcott L B (1993). Effects of dietary phosphorus and calcium on induction of dyschondroplasia in foals, Equine Vet J, 16(suppl): Staniar W B, Cubitt T A, George L A, Harris P A and Geor R J (2007a). Glucose and insulin responses to different dietary energy sources in thoroughbred broodmares grazing cool season pasture, Livestock Science 111(1-2): Staniar W B, Kronfeld D S, Akers R M and Harris P A (2007b). Insulin-like growth factor I in growing thoroughbreds, Journal of Animal Physiology and Animal Nutrition 91(9-10): Telfer S (personal communication). Dr Stuart Telfer is based at the University of Leeds department of animal physiology and nutrition. Treiber K H, Boston R C, Kronfeld D S, Staniar W B and Harris P A (2005). Insulin resistance and compensation in thoroughbred weanlings adapted to high-glycemic meals, Journal of Animal Science 83(10): 2,357-2,364. Vervuert I, Coenen M, Winkelsett S, Christmann L, Distl O, Bruns E and Hertsch B (2004). Changes in bone markers and intact parathyroid hormone with regard to the incidence of osteochondrosis in growing Hanoverian warmblood foals, EAAP: The Growing Horse: Nutrition and Prevention of Growth Disorders, Wageningen Academic Publishers, Dijon, France. Ward J D and Spears J W (1997). Long-term effects of consumption of low-copper diets with or without supplemental molybdenum on copper status, performance, and carcass characteristics of cattle, Journal of Animal Science 75(11): 3,057-3, / 13

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11 A high-phosphorus diet could arise inadvertently by feeding straight cereals, such as oats or alfalfa. Photo: SIMON CURTIS. 11 / 13

12 Nutrition has provided a focus for research into the cause of DOD, as it impacts on many previously implicated factors. 12 / 13

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