2012 - The Role of Diet in The Prevention and Management of Several Equine Diseases 1

Animal Feed Science and Technology 173 (2012) 86101
Contents lists available at SciVerse ScienceDirect
Animal Feed Science and Technology

journal homepage: www.elsevier.com/locate/anifeedsci
The role of diet in the prevention and management of several equine

diseases
Cristy J. Secombe, Guy D. Lester
Division of Health Sciences, School of Veterinary and Biomedical Sciences, Murdoch University, South Street, Murdoch, Western Australia, 6150, Australia
a r t i c l e
i n f o
Keywords:
Horse
Diet
Equine metabolic syndrome
Laminitis
Exertional myopathy
Selenium
a b s t r a c t
Modern feeding and housing practices of horses are typically directed at achieving a high
level of athletic performance. There are some unfortunate consequences including an
increased incidence of disease. Some of these diseases can be directly linked to dietary practices, while in others diet contributes as an important co-factor. Breeding practices to select
for specic traits have also inadvertently resulted in the preferential selection of horses
with genetic mutations within several breeds. In several of these genetic disorders specic
dietary management is required for affected horses to achieve an acceptable level of performance. Diseases in which diet has a signicant inuence are discussed including equine
metabolic syndrome, laminitis, diseases attributed to deciency of vitamin E and/or selenium, exertional myopathies, nutritional secondary hyperparathyroidism, hyperkalaemic
periodic paralysis, and the developmental orthopaedic disease complex.
2011 Elsevier B.V. All rights reserved.
1. Introduction
Diet plays a pivotal role in both the genesis and the management of several common diseases of horses. Animals involved in
modern horse activities commonly receive a diet that differs markedly from that consumed by horses during recent evolution
of the species, where the diet was typically bre-rich and low in starch and was consumed slowly and continuously with
little day-to-day variability in feed type or quality (Janis, 1976; Durham, 2009). In contrast modern diets commonly include
large high starch meals that are interspersed with variable amounts of roughage. Changes in the type and quality of feed can
vary widely and may predispose horses to a range of problems.
Modern feeding practices are commonly associated with problems of the gastrointestinal tract. For example, sudden
changes in diet have been identied as the most important risk factor in the development of abdominal pain (colic) in horses
(Archer and Proudman, 2006). The risk appears to be increased for up to 14 days after a diet change (Cohen et al., 1999). The
sudden, and typically accidental, consumption of a large amount of starch, often grain, has long been identied as a cause of
colic, abdominal bloat, diarrhoea, toxaemia, and laminitis. Diet has also been recognised as a contributing factor to several
infectious intestinal diseases of horses, including salmonellosis and clostridiosis (Traub-Dargatz et al., 1990).
Abbreviations: AST, aspartate aminotransferase; Ca, calcium; CK, creatine phosphokinase; DE, digestible energy; DM, dry matter; DOD, developmental
orthopaedic disease complex; EDM, equine degenerative myeloencephalopathy; EMND, equine motor neuron disease; EMS, equine metabolic syndrome;
FFA, free fatty acid; GYS1, glycogen synthetase enzyme; HYPP, hyperkalaemic periodic paralysis; IR, insulin resistance; MJ, megajoule; NSC, non-structural
carbohydrates; Na, sodium; NSH, nutritional secondary hyperparathyroidism; OC, osteochondrosis; P, phosphorus; PSSM, polysaccharide storage myopathy; PTH, parathyroid hormone; QH, Quarter Horse; RER, recurrent exertional myopathy; RYR1, ryanodine receptor; WMD, white muscle disease; WSC,
water-soluble carbohydrate.
This paper is part of the special issue entitled Nutrition and Pathology of Non-Ruminants, Guest Edited by V. Ravindran.
Corresponding author. Tel.: +61 893607676; fax: +61 893602603.
E-mail address: G.Lester@murdoch.edu.au (G.D. Lester).
0377-8401/$ see front matter 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.anifeedsci.2011.12.017
C.J. Secombe, G.D. Lester / Animal Feed Science and Technology 173 (2012) 86101
87
Continuous access to pasture is considered to be protective with the incidence of colic less in this population than in
horses that are predominately stabled (Hudson et al., 2001). Horses at pasture are not immune from colic and can develop
problems with hindgut fermentation when large amounts of fructan-rich pasture are consumed (AlJassim and Andrews,
2009). Overstocking in sandy regions commonly leads to consumption of sand and an associated risk of intestinal obstruction
and colic (Ragle et al., 1989).
The focus of this review is examination of the relationship between diet and several important diseases of horses.
These include the equine metabolic syndrome (EMS), laminitis, diseases attributed to deciency of vitamin E and/or selenium, exertional myopathies, nutritional secondary hyperparathyroidism, hyperkalaemic periodic paralysis (HYPP), and the
developmental orthopaedic disease (DOD) complex.
2. Equine metabolic syndrome
A disease with similarities to human metabolic syndrome is recognised in the horse and is termed equine metabolic
syndrome (Frank et al., 2010). Obesity and insulin resistance (IR) are factors shared by both syndromes (Johnson et al., 2006).
The presence of, or history of laminitis is also characteristic of the EMS phenotype (Treiber et al., 2006). Hypertriglyceridaemia
(Frank et al., 2006), hyperleptinaemia (Cartmill et al., 2003), arterial hypertension (Bailey et al., 2008), increased systemic
markers associated with obesity (Vick et al., 2007), and altered reproductive cycling (Vick et al., 2006) are also associated
with EMS.
The domestication of horses led to feeding practices that often differed signicantly from the diets consumed in a natural
state. Before domestication the genetic predisposition of thrifty genes conferred an evolutionary advantage. The accumulation of fat, development of transient IR and a proinammatory state was benecial for survival during times of limited feed
availability. These changes abated when fat stores were depleted, typically at the end of winter (Johnson et al., 2006). The
subsequent domestication and propensity to overfeed horses has led to year round persistence of adipose tissue with continual IR and its associated consequences. Adipose tissue is hormonally active and produces adipokines and adipocytokines
(Rasouli and Kern, 2008). More than 100 different adipokines have been identied and it is the inappropriate secretion of
these products over time that results in the pathophysiological consequences of obesity (Hutley and Prins, 2005). Specic
adipokines that have been implicated in EMS include leptin, adiponectin, and resistin. Adipocytokines released by the adipose tissue or from macrophages within fat are pro-inammatory and lead to a chronic state of low-level inammation
(Wisse, 2004; Vick et al., 2007; Rasouli and Kern, 2008). Similar to humans it is suspected that specic regions of adipose
tissue in horse may be more hormonally active than other regions. One area is the accumulation of adipose tissue in the
crest of the neck. A neck crest scoring system (the cresty neck score) has been developed to help distinguish horses that
have developed regional rather than generalised obesity (Carter et al., 2009).
Insulin resistance is caused by defective insulin signalling at the cellular level leading to defects in a range of insulindependent metabolic and vascular processes, including insulin-mediated glucose transport (Kashyap and Defronzo, 2007).
There is a compensatory increase in insulin secretion from the pancreas. As described earlier obesity and IR are clearly
linked in EMS (Frank et al., 2006; Treiber et al., 2006; van Weyenberg et al., 2008). The link between IR and obesity may be
due to the adipokine- or adipocytokine-induced down-regulation of insulin signalling pathways and/or the accumulation of
intracellular lipids in insulin-sensitive tissues, such as skeletal muscle, a process termed lipotoxicity (Slawik and Vidal-Puig,
2006). Horses like humans vary in their genetic ability to develop IR; for this reason some obese horses do not exhibit IR
(Frank, 2009).
The common signalment of the equid affected with EMS is the horse or pony between 5 and 15 years of age. The most
common clinical signs at presentation include laminitis and prolonged generalised or regional obesity. It has recently been
shown that supraphysiologic hyperinsulinaemia can induce laminitis in horses (Asplin et al., 2007). It is postulated that
physiologic hyperinsulinaemia is a signicant trigger factor in the development of laminitis (Johnson et al., 2010). The
underlying effect of high insulin levels on the sensitive laminae tissues of the hoof is yet to be fully elucidated, but is
suspected to be mediated by disruption to insulin-mediated vasoregulatory properties (Frank et al., 2010). It is reported that
IR promotes a state of vasoconstriction due to decreased endogenous production of nitrous oxide (Muniyappa et al., 2007).
The diagnosis of EMS requires consideration of the patient signalment, history, physical examination including body
scoring or neck crest measurement, and appropriate laboratory screening tests. Radiographic evaluation of the feet may also
be indicated. The laboratory diagnosis of EMS is typically centred on the single measurement of blood insulin and glucose
concentrations. Testing should be performed between 8 am and 10 am in the morning after a minimum of 6 h of grain and
pasture deprivation. A small amount of highly structured carbohydrate can be fed and is useful in horses that become stressed
with feed deprivation (Frank, 2009).
Horses with EMS tend to have a resting blood glucose concentration in the upper end of the normal range rather than
being hyperglycaemic. Type 2 diabetes mellitus should be considered in older horses with persistently elevated resting
glucose when external inuences cannot account for the increased glucose. A serum insulin concentration greater than
20 U/mL is consistent with IR, although there may be variability between laboratories (Frank et al., 2010). Test specicity
can be affected in a variety of situations; false positives may occur when animals are stressed or experiencing pain, such as
those experiencing laminitis. Testing should only occur when the animal is acclimatised to the environment and is without
lameness or concurrent disease. Sensitivity of the test is affected when the horse is in the early stages of the disease or
if pancreatic insufciency has occurred due to cell exhaustion resulting in diabetes mellitus type 2 (Frank, 2009; Frank
88
et al., 2010). If a false negative result is suspected dynamic testing using the combined glucoseinsulin test is strongly
recommended (Eiler et al., 2005).
The mainstay of management of EMS involves dietary modication and increasing physical activity. Pharmacological
intervention may be used to enhance the response to management changes, but if used alone is unlikely to result in a
successful response. Horses should be fed low quantities of non-structural carbohydrates (NSC) in order to attenuate the
insulinaemic response to meals. Pasture access should be denied or tightly controlled as the digestible energy (DE) from this
source is difcult to quantify and can contribute a signicant amount to total daily intake. It has recently been recognised
that dietary fructan, a component of many pasture types, undergoes signicant hydrolysis before the large intestine, thereby
contributing to the glycaemic response to a meal (Longland and Byrd, 2006). In addition equids exhibiting IR mount an insulin
response to dietary fructan (Bailey et al., 2007). Non-structural carbohydrates can be calculated by adding starch and watersoluble carbohydrate (WSC) percentages and should be below 100 g/kg of dry mater (DM) intake in affected animals (Frank
et al., 2010). The practice of soaking hay in cold water for 60 min to reduce WSC cannot be relied upon to consistently remove
WSC from roughage (Longland et al., 2009).
Weight loss is essential for successful management of EMS, but horses should not be starved. This may worsen IR or cause
pathologic mobilisation of fat stores. Horses should be fed hay at a recommended rate of 1.5% of body weight daily for the
rst 30 days of management, and then further reduced to 1% of body weight daily. Those horses that exhibit IR and regional
adiposity rather than generalised obesity are more challenging to manage and often require the addition of higher energy
but low NSC feedstuffs, such as beet pulp or vegetable oils. It is also recommended to feed regularly spaced small meals
(Frank et al., 2010).
Exercise has been clearly shown to be effective in improving insulin sensitivity in people with IR (Goodyear and Kahn,
1998; Crandall et al., 2008). A similar response to exercise has been documented in horses with IR (Pratt et al., 2006). The
primary limitation to exercise in equids with EMS is the frequent episodes of laminitis. Although the amount of exercise
required to improve insulin sensitivity has been determined in humans, this is not the case in the horse (Bajpeyi et al., 2009).
The current recommendations in laminitis-free equids are to begin with 23 exercise sessions a week of 2030 min duration,
and slowly increase both the number and intensity of sessions over time (Frank et al., 2010).
Pharmacological management of EMS includes levothyroxine sodium, insulin-sensitising drugs such as metformin, or
supplements such as magnesium and chromium. Levothyroxine has been shown to induce weight loss and improve insulin
sensitivity in horses over the short- and long-term without any reported adverse effects (Frank et al., 2005). There are
conicting data on metformin improvement in insulin sensitivity in horses (Vick et al., 2006). This may be due in part to the
drugs apparent low bioavailability in horses (Hustace et al., 2009).
3. Laminitis
Laminitis is one of the most common diseases of horses. The condition, also known as founder, has a range of inciting
causes, but all result in a common pathologic consequence and consistent clinical signs. The most frequently identied form
of laminitis seen is pasture-induced (Hinckley and Henderson, 1996; USDA-NAHMS, 2000). Although this form has a clear
nutritional basis the exact mechanism that triggers the pathways resulting in laminitis have not been denitely determined.
A digestive and/or metabolic disturbance is postulated (Geor, 2009).
The delivery of a large amount of poorly digested but rapidly fermentable substrate to the caecum and large colon
initiates changes in bacterial ora and mucosal permeability (Krueger et al., 1986; Milinovich et al., 2006). This occurs
classically when large amounts of grain are consumed spontaneously, or when carbohydrate is administered experimentally,
typically in the form of starch. The pathophysiology of pasture-induced laminitis differs from the experimental model of
starch overload. Recently, a model of laminitis has been established using oligofructose, a storage carbohydrate of grasses
in climatic conditions that favour photosynthesis over plant growth (Longland et al., 1999). Such climatic conditions are
associated with an increase in the incidence of pasture-induced laminitis (Hinckley and Henderson, 1996).
Fructans are the primary storage carbohydrate of pasture grasses grown in temperate regions and are located in the
plant stem (Longland and Byrd, 2006). Starch is the storage carbohydrate of the seed of temperate grasses. Starch is also
the primary carbohydrate in the vegetative tissue and seeds of legumes and warm season grasses (Longland, 2007). There
are numerous environmental factors that inuence the accumulation of fructans in pasture, including seasonal and diurnal
factors. Fructan concentration is highest in spring in the afternoon of any particular day (Longland and Byrd, 2006). In horses
with 24-h access to pasture it is possible to reach a NSC intake equivalent to or greater than that used to create laminitis in
an experimental model, but this typically would occur over the entire period rather than as a single bolus, thereby sparing
the majority of animals from becoming clinically affected. It is likely that horses with a predisposition to pasture-induced
laminitis will be affected by smaller doses of fructans consumed over relatively short periods of ingestion (Geor, 2009).
It has been observed that a particular phenotype of equid is predisposed to pasture-induced laminitis. There is now a
substantial body of evidence that links obesity, IR, and hyperinsulinaemia as predisposing factors for the development of
pasture-induced laminitis (Johnson et al., 2004; Treiber et al., 2006; Frank, 2009). Grazing of pastures with high NSC (134 g/kg
DM) compared to other times of the year have been shown to exacerbate IR and hyperinsulinaemia in ponies (Treiber et al.,
2008), and recent research has demonstrated that hyperinsulinaemia alone can result in clinical laminitis (Asplin et al.,
2007). Insulin resistance may lower the threshold for induction of laminitis from carbohydrates due to the vasoconstrictive
and pro-inammatory state it potentiates (Geor, 2009).
89
The clinical signs, diagnosis and treatment of laminitis are reviewed elsewhere (Floyd, 2007a, 2007b; van Eps, 2010).
The focus in horses predisposed to founder is to prevent initial occurrence or to limit exacerbation in animals currently or
recently affected. This revolves around the identication and correction of underlying metabolic abnormalities and limiting
dietary NSC intake. The most common metabolic abnormalities associated with pasture-induced laminitis are EMS and
pituitary pars intermedia dysfunction, the latter condition often incorrectly referred to as Equine Cushings disease.
Fructans are believed to pose the greatest risk of laminitis, but other NSC may also be important and should be included
in a feed analysis (Longland and Byrd, 2006). Forage analysis of hay and other feedstuffs is easily performed and highly
recommended in order to develop a feeding regimen for these animals. Unfortunately, due to the dynamic nature of carbohydrate storage within pasture, single point analysis may not accurately reect the range of NSC throughout a 24-h period
(Longland and Byrd, 2006). This limitation usually results in conservative recommendations regarding access to pasture, for
example, animals with active laminitis should have no pasture exposure and horses that are identied as being of high risk
should have highly restricted pasture access. This advice can be tempered through knowledge of geographical, diurnal, and
seasonal variability in NSC content of pasture. Estimates of the amount of pasture that is ingested during pasture access have
been reported (Ince et al., 2005). The current recommendations are that at risk animals should have no access to pasture
during the growing season, but if this is not possible then restriction should be instituted, with animals having access late
at night or early in the morning before fructans reach daily peak concentrations (Longland and Byrd, 2006). Horses should
not be grazed on mature grasses with high stem NSC content and grazing in conditions that favour photosynthesis rather
than growth should be avoided due to preferential fructan accumulation. Recently harvested stubble and pastures that have
gone to seed should also be avoided (Longland and Byrd, 2006). Horses can be managed successfully using grazing muzzles
to limit pasture intake at times of high fructan content, but consideration should be given to changes in social dynamics that
may occur with muzzle use (Harris et al., 2006).
The presence of rapidly fermentable material in the hindgut results in preferential growth of Gram positive bacteria over
Gram negative organisms (Garner et al., 1975, 1978). In a study where horses were fed pelleted diets containing 830 g/kg
ground maize, at rate greater than 20 MJ DE per 100 kg bodyweight daily, the antibiotic virginiamycin prevented selective
overgrowth of Gram positive bacteria (Rowe et al., 1994). Antibiotic efcacy has been supported by in vitro data with the
maximal benet reported in starch models and a lesser degree of benet in response to dietary fructans (Bailey et al., 2002).
Anecdotally prophylactic administration of virginiamycin has not been efcacious in all cases prompting investigation of
other agents (Harris et al., 2006). The results thus far have been disappointing leaving dietary control as the fundamental
preventative strategy (Bailey et al., 2002).
In those animals that have limited or no access to pasture safe dietary alternatives need to be provided. Ideally feed
should be tested for NSC content, with less than 100 g/kg content the ideal. As a general rule mature grass hays will contain
less NSC than immature hays and therefore should be chosen for the at-risk animal. Horses require 2% of body weight of
forage daily to maintain body weight, but forage alone will not provide sufcient mineral, vitamins or protein. Therefore
supplementation should be provided (Geor, 2009).
4. Diseases associated with a deciency in vitamin E/selenium
There are 3 equine conditions where deciencies of vitamin E and/or selenium have been implicated. Nutritional myodegeneration is most commonly expressed clinically as rhabdomyolysis in young, rapidly growing foals and is due primarily
to a deciency of selenium. A deciency of vitamin E is postulated to be involved in the pathogenesis of 2 other neurologic
diseases of equids, equine degenerative myeloencephalopathy (EDM) and equine motor neuron disease (EMND). Equine
degenerative myeloencephalopathy is a chronic disease seen in younger horses that causes symmetric ataxia and paresis, more pronounced in the hind limbs and spasticity. Equine motor neuron disease is a neurodegenerative disease of the
somatic lower motor neurons affecting mature horses. Although vitamin E and selenium deciency is not thought to be
involved in the aetiology of atypical myopathy they may be protective against a potential oxidative stress involved in the
pathophysiology of this disease (Galen et al., 2008).
4.1. Nutritional myodegeneration in foals
Nutritional myodegeneration, or as it is more commonly known white muscle disease (WMD), is a non-inammatory,
degenerative disease of skeletal and cardiac muscle caused by a deciency of selenium, and to some degree vitamin E (Higuchi
et al., 1989; Lofstedt, 1997). The disease has been reported in both hemispheres (Dill and Rebhun, 1985; Radostits et al.,
1994) and occurs in areas with selenium decient soils. Selenium decient soils are often acidic and volcanic in nature and
produce crops that are also decient in selenium. A contributing factor is the presence of sulphur, either natively within the
soil or through fertilisation with sulphur-containing fertilisers. Dietary sulphur hinders selenium absorption in animals and
uptake in plants. Rapidly growing plants, in particular legumes, tend to be the most selenium decient (Maas and Valberg,
2009).
Selenium has a variety of functions within the body including inhibition of lipid peroxidation and incorporation into some
important amino acids and enzymes (Koller and Exon, 1986). From the perspective of the aetiology of WMD perhaps the
most important enzyme is glutathione peroxidase, which in conjunction with vitamin E, serves to act as an antioxidant and
protect lipid containing organelles and cellular membranes from damage caused by free radicals or highly reactive oxygen
90
metabolites (Lofstedt, 1997). Vitamin E scavenges compounds that form reactive metabolites while glutathione peroxidase
destroys formed free radicals and reactive oxygen species. Vitamin E and glutathione peroxidase work synergistically, but
the latter is considered more important, illustrating a critical role for selenium (Lofstedt, 1997). Selenium is also important
in effecting an adequate humoral immune response, a role that has been demonstrated in the horse (Baalsrud and Overnes,
1986; Knight and Tyznik, 1990).
White muscle disease in equids is without breed and gender predilection and clinical signs usually occur within 60 days
of birth, but have been reported at up to 1 year of age and in aborted foetuses (Dill and Rebhun, 1985). The disease may
occur acutely, quickly progressing to cardiovascular collapse and death due to cardiac muscle involvement. A subacute form
of WMD is characterised by signs of profound muscular weakness due to involvement of skeletal muscle (Moore and Kohn,
1991). Dysphagia is a common clinical sign that is often seen in this group of animals and is attributed to involvement of
the pharyngeal and masticatory muscles (Dill and Rebhun, 1985). Although rare in adult horses, the only presenting sign
of nutritional myodegeneration in this age group is dysphagia (Ludvikova et al., 2007). It is important to recognise that
low serum levels of selenium are present in many outwardly healthy foals when reared in selenium decient areas. Other
compounding factors such as excessive exercise, stress, vitamin E deciency, or excessive dietary fats may induce clinical
disease (Lofstedt, 1997).
The diagnosis of WMD is based on clinical signs of profound muscular weakness, palpably rm muscles, or signs of dysphagia. An antemortem diagnosis is conrmed through a variety of biochemical and electrolyte abnormalities and measurement
of whole blood selenium and glutathione peroxidase activity (Dill and Rebhun, 1985; Moore and Kohn, 1991). Biochemical
and electrolyte abnormalities include markedly elevated muscle-derived enzymes creatine phosphokinase (CK) and aspartate aminotransferase (AST), and hyponatraemia, hypochloraemia, hyperkalaemia, and azotaemia. A mixed metabolic and
respiratory acidosis may be present (Dill and Rebhun, 1985). The measurement of whole blood selenium is thought to
accurately reect the current selenium status of the animal, whereas erythrocyte glutathione peroxidase activity is a good
indicator of selenium status in the months prior to sample collection as selenium is incorporated into the erythrocyte at cell
formation only (Lee et al., 1995). A postmortem diagnosis of WMD typically reveals bilaterally symmetric white streaks in a
variety of muscle groups. Histologically the muscle has hyaline degeneration and fragmentation with lysis of the myobrils
in acute cases, and calcication and histiocyte inltration in more long-standing cases (Dill and Rebhun, 1985; Moore and
Kohn, 1991).
Treatment involves minimising physical exertion and stress, supportive therapy, and administration of parenteral selenium and vitamin E (Dill and Rebhun, 1985). Mildly affected animals should improve rapidly after selenium injections
although there is a delay in increase erythrocyte glutathione peroxidase activity. Platelet glutathione peroxidase activity
increases within hours of selenium administration and this may be more reective of changes that occur within the muscles
after supplementation (Lofstedt, 1997). Despite treatment the prognosis is often guarded, with mortality rates of up to 95%
in the cardiac form and up to 45% in the skeletal form (Combs and Combs, 1986).
The assessment of herd selenium status, ideally performed in the last trimester of pregnancy, should provide the rationale
for prophylactic supplementation of selenium. This is most efcacious when administered during the prepartum period (Dill
and Rebhun, 1985; Moore and Kohn, 1991). Selenium status of newborn foals is dependent on the mare, and blood levels
are usually lower than the dams if the mares selenium status is normal (Lee et al., 1995). The prevention of WMD is through
ensuring the mare has an appropriate selenium intake of 1 mg/day for a 500 kg horse (National Research Council, 2007). Daily
oral supplementation or annual parenteral selenium administration to the mare may be required if her existing dietary intake
does not meet requirements (Wichtel et al., 1998), or given to the foal after birth, although this does not prevent in utero
acquired WMD (Lofstedt, 1997).
4.2. Equine degenerative myeloencephalopathy
EDM is a neurologic disease of horses with an incompletely understood pathophysiology. Vitamin E deciencies in isolation or in combination with a familial tendency, or exposure to wood preservatives have all been postulated as contributory
factors (Dill et al., 1990). Copper deciency has been shown to cause degenerative myelopathy in other species but this
appears not to occur in horses (Dill and Hintz, 1989). The case for vitamin E deciency is supported in part by data collected
from other species where uncomplicated vitamin E deciency results in axonal degenerative disease in juvenile animals
(Mohammed et al., 2007). The pathological nervous system lesions seen in EDM are similar to those seen in vitamin E deciency in a variety of other species (Blythe and Craig, 1992a). Vitamin E acts as an antioxidant and prevents abnormal lipid
peroxidation, in the case of deciency there is excessive membrane lipid peroxidation and an abnormal spinal cord vascular
accumulation of lipopigment (Cummings et al., 1995). This is supported by histological ndings of a larger amount vascular
endothelium lipopigment in horses with EDM versus controls (Cummings et al., 1995). The source of the reactive oxygen
metabolites is thought to be endothelial mitochondria, which may explain why lesions are more marked in the spinal grey
matter rather than the spinal roots, as the mitochondria are far more abundant in the cord (Cummings et al., 1995).
Serum vitamin E concentrations are not always decreased in affected animals (Dill et al., 1989) and in those farms where a
problem has been identied it has been clearly shown that supplementation with vitamin E (10002000 IU/day) has reduced
disease incidence (Mayhew et al., 1987; Dill et al., 1990).
The aetiology of the low alpha-tocopherol levels in affected horses is unknown but several hypotheses have been put
forward, with the inadequate dietary vitamin E being the most favoured (Miller and Collatos, 1997). It has been demonstrated
91
that raising foals on dirt lots rather than vitamin E-rich green pastures is a risk factor for the development of the disease
(Dill et al., 1990).
Histopathological lesions of EDM are consistent with a neuronal dystrophy and occur in the brain stem and throughout
the spinal cord (Blythe and Craig, 1992a). The most common clinical presentation is that of a horse less than 1 year of
age presenting with symmetrical ataxia and paresis more pronounced in the pelvic limbs (Dill et al., 1990; Blythe and
Craig, 1992a). There is usually hyporeexia, manifest as a failure to elicit the cutaneous trunci reex or reduced or absent
thoracolaryngeal adductor response (aka slap test) (Mayhew et al., 1987). Clinical signs are often self-limiting and if a
horse survives, the neurological decits often remain stable for the duration of the animals life (Blythe and Craig, 1992a).
The diagnosis of EDM is often one of exclusion, with cervical vertebral compressive myelopathy, equine herpes myeloencephalopathy, and in some geographical locations, equine protozoal myeloencephalitis being the main differential diagnoses.
Serum vitamin E or alpha-tocopherol levels should be measured, but a low value should not lead to a denitive diagnosis
EDM; the only denitive diagnostic test is histopathology (Blythe and Craig, 1992b).
Once clinical signs of EDM develop a full recovery is unlikely, even with vitamin E supplementation, although some
improvement may be achievable. Clinical improvement should begin within 34 weeks and may continue for up to a year
following supplementation (6000 IU/day) (Blythe and Craig, 1992b). Foals that exhibit risk factors, i.e., familial history, minimal access to green pasture, high incidence of the disease on the farm, and exposure to wood preservatives should receive
vitamin E prophylactically (10002000 IU/day) (Mayhew et al., 1987).
4.3. Equine motor neuron disease
EMND was rst reported in 1990 and has many similarities to progressive spinal atrophy of man (Cummings et al., 1990).
The disease is a neurodegenerative disorder of somatic lower motor neurons and occurs independently of geographic region,
although the northeast of the USA appears over-represented in cases (Hahn and Mayhew, 1993; Sustronck et al., 1993; Gruys
et al., 1994; Kuwamura et al., 1994; De la Rua-Domenech et al., 1997). There have been several EMND epidemiologic studies
performed (Mohammed et al., 1994; De la Rua-Domenech et al., 1995a, 1995b) and risk factors typically include an isolated
mature horse, of either Quarter Horse or Thoroughbred breed, that has been kept in a dry lot with little to no pasture access.
Although pasture access may not be as an important factor as previously thought (McGorum et al., 2006).
The underlying pathophysiology of EMND involves damage and death of somatic ventral motor neuronal cells (Divers
et al., 2001). A neuronal loss of 30% is required before clinical signs are evident (Weber Polack et al., 1998). The loss of the
parental motor neuron cells results in degeneration of the myelinated axons in the ventral roots, peripheral nerves and
muscles with a predominance of type 1 bres. These muscles, often the postural muscles, are more highly oxidative than
other muscle groups and therefore are more severely affected (Valentine et al., 1994). All brainstem cranial nerve somatic
motor nuclei, except those of cranial nerves 3,4 and 6 are affected, although cranial nerve decits are rarely appreciated
clinically (Divers et al., 2006b). Lipopigment deposition is seen in both the endothelial cells of the spinal cord capillaries
and retina and occasionally in the liver and the gut; this reects increased lipid peroxidation, a consequence of widespread
oxidative stress (Cummings et al., 1995; Verhulst et al., 2001).
The aetiology of the disease is again likely to be multifactorial with oxidative stress due to hypovitaminosis E being a
major contributor. This is supported by the experimental induction of the disease by chronic dietary vitamin E deciency
(Divers et al., 2006a; Mohammed et al., 2007) with the loss of the antioxidant activity of vitamin E (both systemically and
in nervous tissue) and accumulation of oxidative free radicals within tissue. There is more rapid induction of disease when
decient animals are fed pro-oxidants (Divers et al., 2006a). Deciency of other antioxidants is not thought to result in
disease (Mohammed et al., 2007). It is likely that additional factors are required to induce disease, as the classic lesions
associated with vitamin E deciency in other mammals are not present and the disease was not identied until the 1990s,
well after vitamin E deciency was rst recognised in horses (Divers et al., 1994; Mohammed et al., 2007). Interestingly in 3
horses with histologically conrmed EDM, there was concurrent histological evidence of EMND although clinical signs were
absent (Divers et al., 2006b). In addition in the experimental models not all horses fed a vitamin E decient diet went on to
develop clinical EMND, although ante-mortem diagnostic tests were suggestive of early disease (Mohammed et al., 2007).
It remains unknown if low vitamin E is a consequence of the disease rather than a cause (Wijnberg, 2006). Further work is
required to determine other aetiologic factors.
Antioxidant status depends on a multitude of factors including nutrition, time of year, age and activity (McGorum et al.,
2003). Antioxidant status may be better assessed by repeatedly measuring vitamin E, glutathione peroxidase and selenium
before concluding that a true deciency exists (Wijnberg, 2006). In addition reference values for each lab should be established, as they are notoriously variable (Wijnberg, 2006). This may help explain those sporadic cases in which the disease is
diagnosed post-mortem but vitamin E status is within normal limits (Syrja et al., 2006).
Equine motor neuron disease clinical signs are dependent on the stage of the disease at the time of presentation and are
categorised as subacute or chronic (Divers et al., 1994). Horses suffering from the subacute form often demonstrate muscle
fasciculations, trembling, frequent shifting of weight, abnormal sweating, and spend a large amount of time lying down.
Head carriage is usually low and tail head is usually elevated due to atrophy of the tail head muscles (sacrocaudalis dorsalis).
Appetite is appropriate or increased. Owners often report a loss in muscle mass over the preceding month (Divers et al.,
1994). Around 30% of horses will demonstrate a pigment retinopathy, but vision is usually not affected (Riis et al., 1999).
The chronic form of the disease is usually seen after stabilisation of the subacute stage, but some horses may present in the
92
chronic disease state. Clinical signs seen at this stage include fatigue, poor athletic performance, and an unusual gait. Muscle
atrophy resulting in weight loss is usually present and will vary from mild to severe. Muscles most severely affected are
those involved with the stay apparatus (Valentine et al., 1994) and may explain why these horses have extreme difculty
standing still. Around 40% of horses will deteriorate quickly in around 1 month after diagnosis, 40% will show improvement
within a similar time period with environmental change and/or vitamin E supplementation (200010,000 U/day), and the
remaining 20% of animals will have permanent muscle atrophy. Each outcome is dictated by the extent of motor neuron
death (Divers et al., 2006b).
Laboratory ndings often found in EMND cases are mild increases in CK and AST, and reduced plasma vitamin E concentrations <1 g/mL (Divers et al., 1994). Spinal cord concentrations of copper have been elevated (Polack et al., 2000) and
vitamin E levels low (unpublished data cited from Divers et al., 2006b). Most cases have abnormal intestinal glucose absorption (Divers et al., 1994), but the only intestinal pathology reported is occasional lipopigment accumulation (Cummings et al.,
1995). The link between abnormal glucose absorption and EMND remains unknown but it is hypothesised that increased
glucose metabolism may be due to increased GLUT-4 translocation and may actually lead to decreased plasma vitamin E
concentration (van der Kolk et al., 2005).
An antemortem diagnosis of EMND is usually based on the clinical signs, the presence of dened risk factors, and laboratory
data. An electromyographic study may be performed in the standing animal and motor unit action potentials indicative of a
generalised neuropathy are strongly supportive of a diagnosis of EMND (Wijnberg, 2006). Invasive diagnostic tests include
histopathology of the sacrocaudalis dorsalis muscle and/or the ventral branch of the spinal accessory nerve. When examined
by an experienced pathologist both tests have a sensitivity and specicity of around 90% (Divers et al., 2001).
The most consistent nding in horses with EMND is a low plasma vitamin E concentration; consequently the current
recommendations are to supplement with vitamin E at 50007000 IU/horse/day (Divers et al., 1997, 2001). In treated horses
there are increased systemic levels of vitamin E but the extent of the increase is variable, suggesting unpredictable absorption
(Divers et al., 2001). In animals with likely inadequate dietary intake vitamin E supplementation at 200010,000 IU/horse/day
is recommended (Divers, 2005).
5. Exertional myopathies including polysaccharide storage myopathy and recurrent exertional myopathy
Polysaccharide storage myopathy (PSSM) and recurrent exertional myopathy (RER) are heritable conditions that result
in episodes of exertional rhabdomyolysis. Both disorders can be controlled through dietary modication. Polysaccharide
storage myopathy is a glycogen storage disorder characterised by accumulation of amylase-resistant polysaccharide within
2a and 2b skeletal muscle bres (Valberg et al., 1992). Horses with PSSM exhibit enhanced blood glucose uptake and insulin
sensitivity (Annandale et al., 2004). Affected horses have accelerated clearance of blood glucose after consumption of a
carbohydrate meal or administration of glucose as part of a tolerance test (De La Corte et al., 1999a, 1999b). Submaximal
exercise results in an energy decit state within myobres (Annandale et al., 2005). Unlike humans with gylcogenoses horses
with PSSM have normal glycogenolytic and glycolytic enzyme activities and they are able to use glycogen and produce lactate
with anaerobic exercise (Valberg et al., 1992, 1998).
Polysaccharide storage myopathy is most prevalent in Quarter Horse and Draft Horse breeds with 612% and 36% of
horses affected within each breed, respectively (Firshman et al., 2005; McCue and Valberg, 2007). Affected Quarter Horses
have increased insulin sensitivity and clinical evidence of rhabdomyolysis typically by 6 months of age, with subclinical
rhabdomyolysis evident as early as 4 weeks of age. Accumulation of abnormal polysaccharide is not usually evident within
muscle biopsies until 712 months of age (De La Corte et al., 2002). Interestingly, Draft Horses with PSSM do not exhibit
heightened insulin sensitivity (Firshman et al., 2008). Recently PSSM has been classied into those cases with a known
genetic mutation, type 1, and those without a known genetic mutation, type 2 (McCue et al., 2008a). Type 1 PSSM is caused
by an autosomal dominant mutation in the gene that encodes the skeletal muscle glycogen synthetase enzyme (GYS1) and
may be found in either a heterozygous or homozygous forms (McCue et al., 2008a, 2008b).
Clinical signs associated with PSSM vary between breeds, but all relate to skeletal muscle dysfunction. Signs include pain,
stiffness, muscle spasm, atrophy or segmental bre necrosis, or any combination of signs (Valentine, 2003). Affected Quarter
Horses tend to develop typical signs of exertional rhabdomyolysis with mild exercise with signs exacerbated in horses that
are unt or following unfamiliar connement (McCue et al., 2006). The severity of signs is variable and is thought to be due
to the heterozygosity or homozygosity of the GYS1 mutation (McCue et al., 2008a). Clinical signs seen in Warmbloods, a
breed that more commonly exhibits type 2 PSSM, also includes exertional rhabdomyolysis, but signs are more subtle and
may be limited to subtle gait abnormalities and/or muscle fasciculations (Hunt et al., 2008). Draft breeds tend to present
in manner similar to Warmbloods but may also exhibit weakness and recumbency (Valentine, 2003). In showjumpers and
dressage horses the disease may present with sign of back pain (Quiroz-Rothe et al., 2002).
Recurrent exertional myopathy is most commonly seen in exercising Thoroughbreds, but can also be seen in other breeds,
including Standardbreds and Arabians (Valberg, 2009). The genetic basis for the disease in Thoroughbreds is believed to be
a fault in intracellular calcium regulation resulting in exercise-induced excessive muscle contraction and necrosis (Lentz
et al., 1999a, 1999b). Animals at greatest risk are the 2-year-old racing females (McGowan et al., 2002). Stressful episodes
and a nervous temperament appear to predispose affected horses to episodes of RER. Episodes tend to occur during training
rather than racing, becoming more frequent as tness increases (MacLeay et al., 1999). The diagnosis of chronic exertional
93
rhabdomyolysis requires collection of a thorough history, including a detailed description of the clinical complaint, ration
composition, exercise schedule and temperament of the horse (McKenzie and Firshman, 2009).
Horses with PSSM will often have a persistent elevation in serum CK at rest, especially if they are conned (Finno et al.,
2009), but horses with RER typically have a normal serum CK concentration if they have not exercised recently. Creatinine
kinase should be assessed within 46 h of 220 min of trotting exercise, with a greater than a 34 fold increase in serum
activity or a total CK concentration greater than 1000 IU/L being abnormal (Valberg et al., 1993; De La Corte and Valberg,
2000). In some horses with RER submaximal exercise testing may not result in a reliable increase in CK (McKenzie and
Firshman, 2009). Muscle biopsies may also provide valuable information with both RER and PSSM having consistent but
different ndings. The recent discovery of the genetic mutation associated with PSSM allows for genetic testing. Current
recommendations are for Quarter Horses and QH-based breeds to be tested for both the GYS1 mutation and the ryanodine
receptor (RYR1) mutation, which can be done via blood or hair prior to muscle biopsy. The RYR1 mutation is responsible for
a third type of PSSM and is uncommon in QH with an estimated incidence of 0.5%. This is a more severe and possible fatal
PSSM phenotype and is associated with malignant hyperthermia (McCue et al., 2009). A muscle biopsy is recommended in
those horses that have clinical signs of rhabdomyolysis but are negative for the genetic abnormalities to conrm a diagnosis
of non-GYS1 (type 2) PSSM (McKenzie and Firshman, 2009).
Long before a more thorough understanding of chronic exertional rhabdomyolysis and its subtypes were achieved it has
been appreciated that nutritional modication is important in the management of the condition. Regardless of the aetiology,
horses that exhibit rhabdomyolysis are more likely to encounter muscle necrosis on diets high in NSC (McKenzie et al.,
2003b; Ribeiro et al., 2004). In horses with PSSM high NSC may result in enhanced glucose uptake and glycogen storage in
muscle (McKenzie and Firshman, 2009). In horses with RER a high NSC within the diet has been linked with excitability, a
strong triggering factor for the expression of clinical signs (MacLeay et al., 1999).
Horses with PSSM should receive a diet that reduces glucose load and encourages the supply of fat-based substrate to
exercising muscle. The diet should provide 10% or less of the daily energy requirements as starch and a minimum of 13% DE
as fat (McKenzie and Firshman, 2009). Implementation of a regular exercise regimen in horses with PSSM is also benecial
(Firshman et al., 2003; Ribeiro et al., 2004). It is believed that a low starch, fat-supplemented diet decreases both insulin
concentration and glucose uptake, and by increasing plasma free fatty acids (FFAs) concentrations FFA oxidation is favoured
over glucose metabolism (Ribeiro et al., 2004). Although some authors believe that increasing the fat supplementation to 20%
DE is benecial (Valentine et al., 2001) an increase to this level often exceeds caloric requirements, may create unpalatable
rations, and could reduce the digestibility of other feedstuffs within the ration (McKenzie and Firshman, 2009). Improvement
of clinical signs with dietary modication in horses with PSSM without the inclusion of partial connement (less than 12 h
per day) and an exercise regimen appears to be very limited (Firshman et al., 2003).
Horses that have RER appear to only benet from fat supplementation when the total DE intake is high, exceeding
88 MJ/DE/day (McKenzie and Firshman, 2009). Serum CK levels were signicantly lower when horses were fed a high energy
ration where 20% of the DE was supplied as fat, contrasted with a starch-based equivalent energy ration (McKenzie et al.,
2003b). The horses were subjectivity better to handle, had lower resting heat rates and lower packed cell volumes (haematocrit). As there is close relationship between nervousness and RER the addition of fat at the expense of starch, but not energy,
may make horses calmer and therefore less predisposed to an episode of rhabdomyolysis (MacLeay et al., 1999; McKenzie
et al., 2003b).
The current recommendations for feeding horses with RER is to limit starch sources to less than 20% of daily DE and include
fat at 1520% of energy requirements (McKenzie et al., 2003a). Clinical improvement with dietary modication in RER horses
has been shown to occur in less than a week and is attributed to neurohormonal changes that reduce anxiety in susceptible
animals (McKenzie et al., 2003b). Exercise modication and other management strategies, including pharmaceuticals, have
an important role as well (McKenzie and Firshman, 2009).
6. Nutritional secondary hyperparathyroidism
This disease is colloquially been known as bran disease, Millers disease or big head, and has been well recognised
in horses for centuries (Manning, 1882). The disease tends to occur when horses are fed diets that are low in calcium and
high in phosphorus (e.g., rice bran) or have access to pastures that have a high content of oxalates (Walthall and McKenzie,
1976; Bertone, 1992; Toribio, 2009).
The pathophysiology of the disease is related to the homeostatic need to maintain total serum and ionised serum calcium
within a very narrow range. If a dietary imbalance of high phosphorus, low calcium, or a P:Ca ratio exceeding 3:1 is not
corrected then physiological compensatory mechanisms are activated (Toribio, 2004). Consumption of grasses with a calcium:oxalate ratio less than 0.5, usually occurring in grasses containing more than 0.5% oxalate DM, while typically not high
enough in oxalate to cause oxalate toxicity, will chelate calcium within the gastrointestinal tract and therefore reduce intestinal absorption causing disease (Blaney et al., 1981). Grasses that are commonly oxalate-rich are tropical grasses including
Setaria, Cenchrus, Panicum, Pennisetum clandestinum and Brachiaria species (Walthall and McKenzie, 1976; McKenzie, 1988;
Bertone, 1992).
Extracellular ionised calcium is maintained by a homeostatic system involving three hormones: parathyroid hormone
(PTH); calcitonin; and 1,25-dihydroxyvitamin D3 , and three body systems: renal; gastrointestinal; and musculoskeletal, and
a calcium sensing receptor (Mundy and Guise, 1999; Toribio et al., 2001; Toribio, 2004). The calcium receptors in the chief
94
cells of the parathyroid detect changes in the calcium concentration; low calcium and/or elevated phosphorus stimulate
PTH secretion while elevated calcium results in increased calcitonin secretion. PTH increases renal calcium resorption in the
distal nephron, decreases phosphate resorption in the proximal tubules, stimulates renal calcitrol synthesis in the proximal
tubules and stimulates osteoclastic bone resorption. Calcitrol increases intestinal absorption of calcium and increases renal
resorption of calcium and phosphorus and inhibits PTH secretion (Toribio, 2004). Hyperphosphataemia stimulates PTH secretion and inhibits renal 1,25 hydroxy vitamin D synthesis, causing parathyroid cell hyperplasia and increased PTH secretion.
Hyperphosphataemia also results in calcium phosphate precipitates and this further contributes to a reduction in serum
calcium (Argenzio et al., 1974). The condition is slowly progressive and as the homeostatic mechanisms are highly effective
in maintaining blood calcium within a normal range horses do not present with the classic clinical signs of hypocalcaemia
(Toribio, 2009).
As the disease causes increased bone resorption clinical signs include ill thrift, a stiff gait, and shifting limb lameness
(Walthall and McKenzie, 1976; Bertone, 1992; Toribio, 2009). The lameness is thought to be due to loss of bony support of
the articular cartilage as a consequence of subchondral bone resorption, microfractures of the subepiphyseal region of long
bones, focal periosteal avulsion fractures, and insertional tendinopathies or desmopathies (Krook, 1968). The classic clinical
sign of NSH is brous dystrophy of the facial bones, colloquially known as big head. This is more commonly seen in younger
horses due to a higher rate of bone metabolism (Bertone, 1992; Ronen et al., 1992). Fibrous tissue replaces bone and horses
may develop masticatory difculties and loose teeth (Walthall and McKenzie, 1976; Bertone, 1992; Toribio, 2009).
The diagnosis of NSH is based on dietary history, clinical signs, and the outcome of diagnostic tests. Dietary history includes
diets that are high in phosphorus (P:Ca > 3:1) (Toribio, 2009) such as bran or concentrates, or horses that are grazing heavily
on oxalate-rich pastures (David et al., 1997). An inappropriate dietary Ca:P ratio may also cause disease in the absence of
an overtly phosphorus-abundant diet (Little et al., 2000). Osteoporosis is evident radiographically with the lamina durae
dentes demonstrating the earliest change of bone mineral density as they have a high rate of osseous turnover and a thin
discrete radiographic appearance. A decrease of 30% in bone mineral density is required before a subjective decrease can
be appreciated radiographically (Krook, 1968). Facial bones will often be the next radiographically affected and will have
evidence of brous proliferation and nally the long bones (Toribio, 2009).
Laboratory testing involves determining calcium and phosphorus serum concentrations and urinary fractional excretion
of key electrolytes, the serum concentration of PTH, and the Ca:P ratio in faeces. Serum concentrations of both calcium
and phosphorus are often normal or there may be a slight increase in phosphorus (David et al., 1997), if this is the case
then urinary fractional excretion is necessary and is considered a sensitive indicator of the disease (Bertone, 1992). Urinary
fractional excretion of phosphorus exceeding 0.5% is consistent with NSH (Bertone, 1992). Measurement of urinary excretion
of calcium is controversial, but if low is also consistent with NSH (Bertone, 1992; Toribio, 2009). Horses with NSH have an
abnormally elevated PTH and measurement has been found to be most accurate using the immunoradiometric assay of
which there are several generations. The third generation assay has now been validated in the horse (Estepa et al., 2003).
The ratio of Ca:P in faeces is often elevated if the horse has been consuming oxalate containing pastures and a ratio of greater
than 2.35:1 is considered signicant (Walthall and McKenzie, 1976; Bertone, 1992).
The treatment of NSH involves limiting exercise, providing a ration to correct the Ca:P ratio and reduce the inappropriate
secretion of PTH. The aim is to increase the dietary Ca:P ratio to greater than 4:1 (Toribio, 2009). This can be achieved by
reducing grain intake and increasing hay, in particular lucerne (alfalfa) hay due to high calcium content. Supplementation
with either dicalcium phosphate (Ca:P ratio 22:1.5) and or calcium carbonate (350 g/kg calcium) is also useful (McKenzie
et al., 1981; Toribio, 2009). Feeding a ration with a high Ca:P ratio should continue until the radiographic signs have returned
to normal and clinical signs have resolved, this process may take up to 1 year. In some cases the facial swelling may not
regress and lameness may improve but not resolve (Krook, 1968; Bertone, 1992; Toribio, 2009). Prevention of the disease is
easily achieved by ensuring horses have a diet with an adequate Ca:P ratio, especially in young growing animals.
7. Hyperkalaemic periodic paralysis
Hyperkalaemic periodic paralysis is a genetic disease affecting horses descended from the prominent Quarter Horse sire
Impressive (Impressive was a cross between a QH and Thoroughbred). Dietary modication is a critical aspect of disease
management (Naylor, 1994b). The disease is characterised as a myopathy and is attributed to a defect in skeletal sodium
(Na) muscle channels (Rudolph et al., 1992; Naylor, 1994b; Meyer et al., 1999). Horses with the genetic mutation were
preferentially selected due to their prominent muscular phenotype (Naylor, 1994a). The disease is well recognised as a
genetic defect and mandatory genetic testing is required before registration with the American Quarter Horse Association
(Groves, 1996).
Hyperkalaemic periodic paralysis is caused by an autosomal dominant point mutation that results in a
phenylalanineleucine substitution at the voltage-dependent skeletal muscle Na channel alpha subunit (Rudolph et al.,
1992; Naylor, 1997). Sodium channels are usually closed in resting muscle but are triggered to open as the membrane
potential moves toward threshold. The resultant rapid inux of Na leads to membrane depolarisation giving rise to the early
phase of the cell action potential. Once the membrane is fully depolarised the Na channels close and the potassium channels
open, potassium leaves the cell leading to cell repolarisation. In HYPP horses the Na channels remain open following membrane depolarisation resulting in a permanent reduction of membrane potential causing involuntary muscle contraction,
followed by fatigue and weakness (Naylor, 1997). Involuntary contraction occurs when the bres are sufciently depolarised
95
to reach the threshold for contraction. The simultaneous contraction of groups of bres appears as visible muscular spasm
or fasciculation and is a feature of mild to moderate attacks. In sustained severe attacks there is muscle fatigue and this
is reected clinically as weakness (Naylor, 1997). Affected horses maintain a muscle resting membrane potential that is
less negative and therefore closer to reaching the electrical threshold potential (Pickar et al., 1991). Although the mutation
results in a Na channel defect the prominent electrolyte abnormality is hyperkalaemia, which is only present during attacks.
There are some horses that will continue to maintain a normal serum potassium concentration in the face of an HYPP clinical episode (Stewart et al., 1993). Raising extracellular potassium can trigger opening of Na channels and during attacks
there is increased potassium efux from cells that also contributes to the measurable hyperkalaemia (Naylor, 1997). There
is variation in individual horses susceptibility to attacks, which appears to be due to differential rates of transcription of the
normal and abnormal genes (Zhou et al., 1994).
Clinical signs range from the horse being clinically asymptomatic to daily exhibition of periodic attacks. Heterozygotes
(single loci positive for defect) tend to show signs that occur less frequently and are less severe than homozygotes. In heterozygotes the most common and earliest clinical sign is muscle fasciculation that can be misinterpreted as either shivering
or anxiousness (Naylor et al., 1993). Other common clinical signs in heterozygotes include tachypnoea, sweating, and weakness. Less common signs, more likely to be seen in homozygotes, include prolapse of the third eyelid, respiratory stridor,
colic-like signs, recumbency, arrhythmia, or rarely death (Naylor, 1997). During the attack and immediately afterwards
serum potassium is elevated, but in some instances may be normal, more so in homozygotes (Stewart et al., 1993). The
majority of affected heterozygote horses begin to exhibit clinical signs between 2 and 3 years of age and are apparently
normal between episodes (Rudolph et al., 1992; Naylor, 1994b), whereas homozygotes tend to display clinical signs as foals
(Naylor, 1997). Precipitating factors that increase the risk of an attack include diets high in potassium, sudden changes in diet,
transportation, anaesthesia, exposure to cold, co-existent disease, pregnancy, and rest after exercise. Exercise alone does not
cause clinical signs (Reynolds et al., 1998; Spier, 2006). During mild attacks horses usually remain standing with episodes
usually last between 15 and 60 min (Spier, 2006). Although horses are clinically normal between episodes electromyographic
examination is abnormal (Naylor, 1994b).
Historically the diagnosis of HYPP has been based on pedigree analysis, clinical signs, and documentation of hyperkalaemia
during an episode (Naylor, 1997). HYPP was the rst veterinary disease to utilise DNA probes for genetic diagnosis (Rudolph
et al., 1992), and since 1998 all Quarter Horses from an Impressive lineage must have genetic testing prior to registration
and from 2007 homozygous HYPP horses could no longer be registered (Spier, 2006). This addendum was likely due to
persistence of the genetic mutation within the breed after mandatory testing was introduced.
Most acute attacks will often pass without requiring any medical intervention. If the event is mild then light exercise may
be sufcient to resolve the episode (Spier, 2006). Corn syrup, grain or glucose may be given to stimulate insulin secretion,
which facilitates intracellular movement of potassium. This along with the administration of adrenalin or the diuretic acetazolamide may reduce the signs associated with mild episodes (Spier, 2006). More severe attacks require more aggressive
treatment and commonly include the intravenous administration of potassium free uids to dilute and encourage renal
excretion of potassium, the administration of sodium bicarbonate, or intravenous glucose to enhance cellular uptake of
potassium, and intravenous calcium which will reduce membrane threshold (Leitch and Paterson, 1994; Spier, 2006).
The longer term control of the disease is focused around the reduction of potassium in the diet, increasing renal excretion
of potassium, and avoiding stressful events or sudden environmental change (Naylor, 1997; Spier, 2006). High potassium
feeds that should be avoided include lucerne/alfalfa (1424 g/kg potassium DM), electrolyte and kelp supplements, soyabean
meal, molasses, and some sweet feeds. Feeds that are low in potassium include beet pulp, oats, barley and wheat, and most
pasture grasses (Spier, 2006). Horses that suffer repeated episodes should be fed a diet with between 6 and 11 g/kg potassium
DM and meals should contain less than 33 g of total potassium (Reynolds et al., 1998). Some horses will experience recurrent
episodes even in the face of dietary management and may require medical therapies that increase renal potassium excretion.
Potassium wasting diuretics such as acetazolamide and hydrochlorothiazide are often useful (Naylor, 1997; Spier, 2006).
8. Developmental orthopaedic disease

Developmental orthopaedic disease (DOD) is a non-specic term to describe an assortment of manifestations of bone
disease including osteochondrosis, subchondral bone cysts, physitis, angular limb deformities, exural deformities and
cervical vertebral compressive myelopathy. Although all of these diseases occur in young growing horses and involve the
musculoskeletal system it remains speculative that they all share a common underlying aetiology (Jeffcott, 1991). Even
the aetiopathogenesis of the most researched manifestation of DOD, osteochondrosis (OC), remains provisional rather than
denitive at this time (Jeffcott and Henson, 1998; Ytrehus et al., 2007). It is universally agreed that aetiology of both OC and
DOD are multifactorial and that the contribution of various risk factors is open to debate.
These DOD risk factors include genetic predisposition, nutrition, growth rate/body size, exercise, biomechanical loading,
and endocrinologic factors (Jeffcott, 1991). Inheritance and the accompanying conformational characteristics are important
contributors to the development of OC in humans, dogs, pigs and horses (Ytrehus et al., 2007). Biomechanical inuences
aid in the explanation of the consistent predilection sites of disease, particularly for OC (van Weeren, 2006). Excessive or
inadequate levels of exercise in foals have both been shown to increase the incidence of OC (van Weeren and Barneveld,
1999) and appropriate levels of exercise in the immature horse is important for optimal skeletal development and bone
96
growth (Rogers et al., 2008a, 2008b; van Weeren et al., 2008) and may enhance resistance to injury (Barneveld and van
Weeren, 1999).
Nutritional factors that contribute to the aetiopathogenesis of DOD include mineral deciencies, excesses, or relative
imbalances. Deciencies of calcium, phosphorus, copper, and zinc have all been postulated to predispose to DOD (Knight
et al., 1985; Lawrence and Pagan, 2005). The role of copper deciency in DOD is controversial with some literature supportive
of dietary supplementation with copper to decrease the incidence of DOD (Hurtig et al., 1993; Pearce et al., 1998). However
the role of copper in maintenance of skeletal integrity and therefore DOD remains to be fully elucidated. It has been speculated
that copper may be important in the repair and resolution of early cartilage lesions rather than in disease prevention (van
Weeren et al., 2003). Copper supplementation to dams in late gestation or high liver copper levels in foals is not protective
against the development of cartilage lesions (Gee et al., 2007).
Mineral excesses have also been associated with DOD and include excesses in calcium, phosphorus, zinc, iodide, uoride,
lead, and cadmium (Lawrence and Pagan, 2005). It was proposed that a high rate of calcium supplementation interferes with
trace mineral absorption and could lead to an increase in DOD cases (Krook and Maylin, 1988), but this has been found not
to be the case (Savage et al., 1993a). Excessive dietary phosphorus supplementation will result in the reduction of calcium
absorption and this has been shown to increase the incidence of DOD lesions (Savage et al., 1993b). Excessive zinc intake
has been shown to result in a secondary copper deciency (Eamens et al., 1984; Cymbaluk and Smart, 1993). Balancing
rations to ensure that appropriate mineral requirements are met has failed as a single strategy to reduce the incidence of
DOD (Lawrence and Pagan, 2005).
Excessive energy intake resulting in rapid growth within a specic time period is postulated to result in an increased
incidence of DOD (van Weeren et al., 1999; Donabedian et al., 2006). It is proposed that excessive energy intake leads to a
strong and sustained postprandial hyperinsulinaemia that is induced by a meal containing a high amount of easily digestible
carbohydrates (van Weeren, 2006). Insulin as well as insulin growth factors 1 and 2 directly impact endochondral ossication
and insulin removes thyroid hormones from circulation, which also adversely impacts cartilage differentiation (Jeffcott and
Henson, 1998). Horses with OC lesions have been shown to have higher insulin and glucose responses to high grain diets
than normal horses (Ralston, 1996; Pagan et al., 2001), but the effect of insulin on thyroid hormones may only occur within
a narrow age range (Glade and Reimers, 1985). Although it is possible to induce OC lesions in horses due to dietary energy
manipulation (Savage et al., 1993a) the lesions produced are not often seen in naturally occurring cases of OC (Glade and
Belling, 1986), giving rise to the belief that although excessive energy intake plays a key role in the development of DOD the
exact mechanism through which this occurs remains to be determined.
Ration evaluation is essential to determine if nutrition is a causative factor in cases of DOD and there are multiple common
feeding scenarios that may potentiate DOD. Overfeeding of young horses is a common problem that results in excessive intake
and growth rates, both of which have been shown to result in DOD (Savage et al., 1993a; Pagan et al., 1996; Lepeule et al.,
2009). Principles have been developed to minimise the incidence of DOD.
Preventative feeding strategies should begin during pregnancy. Many horse owners overfeed their brood mares during
early pregnancy and underfeed them in lactation; these feeding practices have the propensity to lead to overweight broodmares (Lawrence and Pagan, 2005). There is anecdotal evidence that over-conditioned brood mares will produce foals that
are at increased risk of DOD, particularly angular limb deformities (Mason, 1981). If a mare is fed appropriately throughout
pregnancy it is unnecessary to supplement a foal until 90 days of age, at which time it can be introduced to grain. A gradual
introduction should be undertaken or there may be the risk of an excessive growth at this time (Lawrence and Pagan, 2005).
The period from weaning to 12 months of age is the most important time in regards to dietary management to prevent DOD.
Weanlings should be having adequate mineral supplementation and be grown at a moderate rate. Often the nutritional
content of pasture is underestimated, again leading to excessive growth rates (Lawrence and Pagan, 2005). Recent research
indicates that feeding concentrates that initiate a low glycaemic response may also be prudent (Pagan et al., 2001). Once
a horse reaches 12 months of age the risk of new DOD lesions is greatly reduced, but it may be an important period for
pre-existing DOD lesions to become clinically apparent.
In young horses that develop DOD nutritional modication can be used to reduce the severity of disease. The rationale of
dietary modication is a slowing of skeletal growth rate through a reduction in energy intake, while maintaining appropriate
levels of protein and minerals to promote healthy bone development.
9. Conclusion
Modern equine breeding, feeding and management practices have tended to focus on achieving rapid growth and maximising athletic performance. The feeding of concentrate-based diets is an important factor in achieving these outcomes. As
a consequence there are several diseases of horses that may have a direct or indirect causal relationship with diet. It is likely
that dietary modication will be an important tool in the management and prevention of such diseases.
Conict of interest
None.
97
References
AlJassim, R.A.M., Andrews, F.A., 2009. The bacterial community of the horse gastrointestinal tract and its relation to fermentative acidosis, laminitis, colic
and stomach ulcers. Vet. Clin. North Am. Equine Pract. 25, 199215.
Annandale, E.J., Valberg, S.J., Mickelson, J.R., Seaquist, E.R., 2004. Insulin sensitivity and skeletal muscle glucose transport in horses with equine polysaccharide storage myopathy. Neuromuscul. Disord. 14, 666674.
Annandale, E.J., Valberg, S.J., Essen-Gustavsson, B., 2005. Effects of submaximal exercise on adenine nucleotide concentrations in skeletal muscle bers of
horses with polysaccharide storage myopathy. Am. J. Vet. Res. 66, 839845.
Archer, D.C., Proudman, C.J., 2006. Epidemiological clues to preventing colic. Vet. J. 172, 2939.
Argenzio, R.A., Lowe, J.E., Hintz, H.F., Schryver, H.F., 1974. Calcium and phosphorus homeostasis in horses. J. Nutr. 104, 1827.
Asplin, K.E., Sillence, M.N., Pollitt, C.C., McGowan, C.M., 2007. Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies. Vet. J. 174,
530535.
Baalsrud, K.J., Overnes, G., 1986. Inuence of vitamin E and selenium supplement on antibody production in horses. Equine Vet. J. 18, 472474.
Bailey, S.R., Rycroft, A., Elliott, J., 2002. Production of amines in equine cecal contents in an in vitro model of carbohydrate overload. J. Anim. Sci. 80,
26562662.
Bailey, S.R., Menzies-Gow, N.J., Harris, P.A., Habershon-Butcher, J.L., Crawford, C., Berhane, Y., Boston, R.C., Elliott, J., 2007. Effect of dietary fructans and
dexamethasone administration on the insulin response of ponies predisposed to laminitis. J. Am. Vet. Med. Assoc. 231, 13651373.
Bailey, S.R., Habershon-Butcher, J.L., Ransom, K.J., Elliott, J., Menzies-Gow, N.J., 2008. Hypertension and insulin resistance in a mixed-breed population of
ponies predisposed to laminitis. Am. J. Vet. Res. 69, 122129.
Bajpeyi, S., Tanner, C.J., Slentz, C.A., Duscha, B.D., McCartney, J.S., Hickner, R.C., Kraus, W.E., Houmard, J.A., 2009. Effect of exercise intensity and volume on
persistence of insulin sensitivity during training cessation. J. Appl. Physiol. 106, 10791085.
Barneveld, A., van Weeren, P.R., 1999. Conclusions regarding the inuence of exercise on the development of the equine musculoskeletal system with
special reference to osteochondrosis. Equine Vet. J. Suppl. 11, 2119.
Bertone, J.J., 1992. Nutritional secondary hyperparathyroidis. In: Robinson, N.E. (Ed.), Current Therapy in Equine Medicine 3. WB Saunders Co., Philadelphia,
pp. 119122.
Blaney, B.J., Gartner, R.J.W., McKenzie, R.A., 1981. The effects of oxalate in some tropical grasses on the availability to horses of calcium, phosphorus and
magnesium. J. Agric. Sci. 97, 507514.
Blythe, L.L., Craig, A.M., 1992a. Equine degenerative myeloencephalopathy. Part I. Clinical signs and pathogenesis. Compend. Contin. Educ. Pract. Vet. (USA)
14, 12151221.
Blythe, L.L., Craig, A.M., 1992b. Equine degenerative myeloencephalopathy. Part II. Diagnosis and Treatment. Compend. Contin. Educ. Pract. Vet. (USA) 14,
16331637.
Carter, R.A., Geor, R.J., Burton Staniar, W., Cubitt, T.A., Harris, P.A., 2009. Apparent adiposity assessed by standardised scoring systems and morphometric
measurements in horses and ponies. Vet. J. 179, 204210.
Cartmill, J.A., Thompson, D.L., Storer, W.A., Gentry, L.R., Huff, N.K., 2003. Endocrine responses in mares and geldings with high body condition scores grouped
by high vs. low resting leptin concentrations. J. Anim. Sci. 81, 23112321.
Cohen, N.D., Gibbs, P.G., Woods, A.M., 1999. Dietary and other management factors associated with colic in horses. J. Am. Vet. Med. Assoc. 215, 5360.
Combs, G.F., Combs, S.B., 1986. Biochemical functions of selenium. In: The Role of Selenium in Nutrition. Academic Press, Orlando, p. 205.
Crandall, J.P., Knowler, W.C., Kahn, S.E., Marrero, D., Florez, J.C., Bray, G.A., Haffner, S.M., Hoskin, M., Nathan, D.M., 2008. The prevention of type 2 diabetes.
Nat. Clin. Pract. Endocrinol. Metab. 4, 382393.
Cummings, J.F., De Lahunta, A., George, C., Fuhrer, L., Valentine, B.A., Cooper, B.J., Summers, B.A., Huxtable, C.R., Mohammed, H.O., 1990. Equine motor
neuron disease; a preliminary report. Cornell Vet. 80, 357379.
Cummings, J.F., De Lahunta, A., Mohammed, H.O., Divers, T.J., Summers, B.A., Valentine, B.A., Jackson, C.A., 1995. Endothelial lipopigment as an indicator of
-tocopherol deciency in two equine neurodegenerative diseases. Acta Neuropathol. 90, 266272.
Cymbaluk, N.F., Smart, M.E., 1993. A review of possible metabolic relationships of copper to equine bone disease. Equine Vet. J. Suppl. 16, 1929.
David, J.B., Cohen, N.D., Nachreiner, R., 1997. Equine nutritional secondary hyperparathyroidism. Compend. Contin. Educ. Pract. Vet. (USA) 19, 13801387.
De La Corte, F.D., Valberg, S.J., MacLeay, J.M., Williamson, S.E., Mickelson, J.R., 1999a. Glucose uptake in horses with polysaccharide storage myopathy. Am.
J. Vet. Res. 60, 458462.
De La Corte, F.D., Valberg, S.J., Mickelson, J.R., Hower-Moritz, M., 1999b. Blood glucose clearance after feeding and exercise in polysaccharide storage
myopathy. Equine Vet. J. Suppl. 30, 324328.
De La Corte, F.D., Valberg, S.J., 2000. Treatment of polysaccharide storage myopathy. Compend. Contin. Educ. Pract. Vet. 22, 782788.
De La Corte, F.D., Valberg, S.J., MacLeay, J.M., Mickelson, J.R., 2002. Developmental onset of polysaccharide storage myopathy in 4 Quarter Horse foals. J. Vet.
Intern. Med. 16, 581587.
De la Rua-Domenech, R., Mohammed, H.O., Atwill, E.R., Cummings, J.F., Divers, T.J., Summers, B.A., De Lahunta, A., Jackson, C., 1995a. Epidemiologic evidence
for clustering of equine motor neuron disease in the United States. Am. J. Vet. Res. 56, 14331439.
De la Rua-Domenech, R., Mohammed, H.O., Cummings, J.F., Divers, T.J., De Lahunta, A., Valentine, B.A., Summers, B.A., Jackson, C.A., 1995b. Incidence and
risk factors of equine motor neuron disease: an ambidirectional study. Neuroepidemiology 14, 5464.
De la Rua-Domenech, R., Mohammed, H.O., Cummings, J.F., Divers, T.J., De Lahunta, A., Summers, B.A., 1997. Intrinsic, management, and nutritional factors
associated with equine motor neuron disease. J. Am. Vet. Med. Assoc. 211, 12611267.
Dill, S.G., Rebhun, W.C., 1985. White muscle disease in foals. Compend. Contin. Educ. Pract. Vet. (USA) 7, S627S634.
Dill, S.G., Hintz, H.F., 1989. Plasma and liver copper values in horses with equine degenerative myeloencephalopathy. Can. J. Vet. Res. 53, 2932.
Dill, S.G., Kallfelz, F.A., deLahunta, A., Waldron, C.H., 1989. Serum vitamin E and blood glutathione peroxidase values of horses with degenerative myeloencephalopathy. Am. J. Vet. Res. 50, 166168.
Dill, S.G., Correa, M.T., Erb, H.N., De Lahunta, A., Kallfelz, F.A., Waldron, C., 1990. Factors associated with the development of equine degenerative myeloencephalopathy. Am. J. Vet. Res. 51, 13001305.
Divers, T.J., Mohammed, H.O., Cummings, J.F., Valentine, B.A., De Lahunta, A., Jackson, C.A., Summers, B.A., 1994. Equine motor neuron disease: ndings in
28 horses and proposal of a pathophysiological mechanism for the disease. Equine Vet. J. 26, 409415.
Divers, T.J., Mohammed, H.O., Cummings, J.F., 1997. Equine motor neuron disease. Vet. Clin. North Am. Equine Pract. 13, 97105.
Divers, T.J., De Lahunta, A., Hintz, H.F., Riis, R.C., Jackson, C., Mohammed, H., 2001. Equine motor neuron disease. Equine Vet. Educ. 13, 6367.
Divers, T.J., 2005. Equine motor neuron disease. J. Equine Vet. Sci. 25, 238.
Divers, T.J., Cummings, J.E., De Lahunta, A., Hintz, H.F., Mohammed, H.O., 2006a. Evaluation of the risk of motor neuron disease in horses fed a diet low in
vitamin E and high in copper and iron. Am. J. Vet. Res. 67, 120126.
Divers, T.J., Mohammed, H.O., Hintz, H.F., De Lahunta, A., 2006b. Equine motor neuron disease: a review of clinical and experimental studies. Clin. Tech.
Equine Pract. 5, 2429.
Donabedian, M., Fleurance, G., Perona, G., Robert, C., Lepage, O., Trillaud-Geyl, C., Leger, S., Ricard, A., Bergero, D., Martin-Rosset, W., 2006. Effect of fast vs.
moderate growth rate related to nutrient intake on developmental orthopedic disease in the horse. Anim. Res. 55, 471486.
Durham, A., 2009. The role of nutrition in colic. Vet. Clin. North Am. Equine Pract. 25, 6778.
Eamens, G.J., Macadam, J.F., Laing, E.A., 1984. Skeletal abnormalities in young horses associated with zinc toxicity and hypocuprosis. Aust. Vet. J. 61, 205207.
Eiler, H., Frank, N., Andrews, F.M., Oliver, J.W., Fecteau, K.A., 2005. Physiologic assessment of blood glucose homeostasis via combined intravenous glucose
and insulin testing in horses. Am. J. Vet. Res. 66, 15981604.
98
Estepa, J.C., Gara, B., Gao, P.R., Cantor, T., Rodriguez, M., Aguilera-Tejero, E., 2003. Validation and clinical utility of a novel immunoradiometric assay
exclusively for biologically active whole parathyroid hormone in the horse. Equine Vet. J. 35, 291295.
Finno, C.J., Spier, S.J., Valberg, S.J., 2009. Equine diseases caused by known genetic mutations. Vet. J. 179, 336347.
Firshman, A.M., Valberg, S.J., Bender, J.B., Finno, C.J., 2003. Epidemiologic characteristics and management of polysaccharide storage myopathy in Quarter
Horses. Am. J. Vet. Res. 64, 13191327.
Firshman, A.M., Baird, J.D., Valberg, S.J., 2005. Prevalences and clinical signs of polysaccharide storage myopathy and shivers in Belgian draft horses. J. Am.
Vet. Med. Assoc. 227, 19581964.
Firshman, A.M., Valberg, S.J., Baird, J.D., Hunt, L., DiMauro, S., 2008. Insulin sensitivity in Belgian horses with polysaccharide storage myopathy. Am. J. Vet.
Res. 69, 818823.
Floyd, A.E., 2007a. Grading the laminitic horse. In: Floyd, A.E., Mansmann, R.A. (Eds.), Equine Podiatry. Saunders, Missouri, pp. 320327.
Floyd, A.E., 2007b. An approach to the treatment of the laminitic horse. In: Floyd, A.E., Mansmann, R.A. (Eds.), Equine Podiatry. Saunders, Missouri, pp.
347358.
Frank, N., Sommardahl, C.S., Eiler, H., Webb, L.L., Denhart, J.W., Boston, R.C., 2005. Effects of oral administration of levothyroxine sodium on concentrations
of plasma lipids, concentration and composition of very-low-density lipoproteins, and glucose dynamics in healthy adult mares. Am. J. Vet. Res. 66,
10321038.
Frank, N., Elliott, S.B., Brandt, L.E., Keisler, D.H., 2006. Physical characteristics, blood hormone concentrations, and plasma lipid concentrations in obese
horses with insulin resistance. J. Am. Vet. Med. Assoc. 228, 13831390.
Frank, N., 2009. Equine metabolic syndrome. J. Equine Vet. Sci. 29, 259267.
Frank, N., Geor, R.J., Bailey, S.R., Durham, A.E., Johnson, P.J., 2010. Equine metabolic syndrome. J. Vet. Intern. Med. 24, 467475.
Galen, G., Serteyn, D., Amory, H., Votion, D.M., 2008. Atypical myopathy: new insights into the pathophysiology, prevention and management of the
condition. Equine Vet. Educ. 20, 234238.
Garner, H.E., Coffman, J.R., Hahn, A.W., Hutcheson, D.P., Tumbleson, M.E., 1975. Equine laminitis of alimentary origin: an experimental model. Am. J. Vet.
Res. 36, 441444.
Garner, H.E., Moore, J.N., Johnson, J.H., Clark, L., Amend, J.F., Tritschler, L.G., Coffmann, J.R., Sprouse, R.F., Hutcheson, D.P., Salem, C.A., 1978. Changes in the
caecal ora associated with the onset of laminitis. Equine Vet. J. 10, 249252.
Gee, E., Davies, M., Firth, E., Jeffcott, L., Fennessy, P., Mogg, T., 2007. Osteochondrosis and copper: histology of articular cartilage from foals out of copper
supplemented and non-supplemented dams. Vet. J. 173, 109117.
Geor, R.J., 2009. Pasture-associated laminitis. Vet. Clin. North Am. Equine Pract. 25, 3950.
Glade, M.J., Reimers, T.J., 1985. Effects of dietary energy supply on serum thyroxine, tri-iodothyronine and insulin concentrations in young horses. J.
Endocrinol. 104, 9398.
Glade, M.J., Belling, T.H., 1986. A dietary etiology for osteochondrotic cartilage. J. Equine Vet. Sci. 6, 151155.
Goodyear, L.J., Kahn, B.B., 1998. Exercise, glucose transport, and insulin sensitivity. Annu. Rev. Med. 49, 235261.
Groves, L., 1996. HYPP: Someone elses problem? Quarter Horse J. (January), 5259.
Gruys, E., Beynen, A.C., Binkhorst, G.J., van Dijk, S., Koeman, J.P., Stolk, P., 1994. Neurodegenerative disorders of the central nervous system in horses. Tijdschr.
Diergeneeskd. 119, 561567.
Hahn, C.N., Mayhew, I.G., 1993. Does equine motor neuron disease exist in the United Kingdom. Vet. Rec. 132, 133134.
Harris, P., Bailey, S.R., Elliott, J., Longland, A., 2006. Countermeasures for pasture-associated laminitis in ponies and horses. J. Nutr. 136, 2114S2121S.
Higuchi, T., Ichijo, S., Osame, S., Ohishi, H., 1989. Studies on serum selenium and tocopherol in white muscle disease of foal. Nippon Juigaku Zasshi 51,
5259.
Hinckley, K., Henderson, I., 1996. The epidemiology of equine laminitis in the UK. In: 35th Congress of the British Equine Veterinary Association, Warwick,
UK, p. 62.
Hudson, J.M., Cohen, N.D., Gibbs, P.G., Thompson, J.A., 2001. Feeding practices associated with colic in horses. J. Am. Vet. Med. Assoc. 219, 14191425.
Hunt, L.M., Valberg, S.J., Steffenhagen, K., McCue, M.E., 2008. An epidemiological study of myopathies in Warmblood horses. Equine Vet. J. 40, 171177.
Hurtig, M., Green, S.L., Dobson, H., Mikuni-Takagaki, Y., Choi, J., 1993. Correlative study of defective cartilage and bone growth in foals fed a low-copper
diet. Equine Vet. J. Suppl. 16, 6673.
Hustace, J.L., Firshman, A.M., Mata, J.E., 2009. Pharmacokinetics and bioavailability of metformin in horses. Am. J. Vet. Res. 70, 665668.
Hutley, L., Prins, J.B., 2005. Fat as an endocrine organ: relationship to the metabolic syndrome. Am. J. Med. Sci. 330, 280289.
Ince, J., Longland, A., Moore-Colyer, M., Harris, P., 2005. A pilot study to estimate the intake of grass by ponies with restricted access to pasture. In: British
Society of Animal Science Conference, Cirencester, UK (abstract 109).
Janis, C., 1976. The evolutionary strategy of the equidae and the origins of rumen and cecal digestion. Evolution 30, 757774.
Jeffcott, L.B., 1991. Osteochondrosis in the horsesearching for the key to pathogenesis. Equine Vet. J. 23, 331338.
Jeffcott, L.B., Henson, F.M.D., 1998. Studies on growth cartilage in the horse and their application to aetiopathogenesis of dyschondroplasia (osteochondrosis).
Vet. J. 156, 177192.
Johnson, P.J., Ganjam, S.K., Turk, J.R., Buff, P.R., 2006. Obesity paradigm: an introduction to the emerging discipline of adipobiology. In: American Association
of Equine Practitioners 52nd Annual Convention, pp. 4150.
Johnson, P.J., Messer, N.T., Slight, S.H., Wiedmeyer, C., Buff, P., Ganjam, V.K., 2004. Endocrinopathic laminitis in the horse. Clin. Tech. Equine Pract. 3, 4556.
Johnson, P.J., Weidmeyer, C.E., LaCarrubba, A., Ganjam, V.K., Messer, N., 2010. Laminitis and the equine metabolic syndrome. Vet. Clin. North Am. Equine
Pract. 26, 239255.
Kashyap, S.R., Defronzo, R.A., 2007. The insulin resistance syndrome: physiological considerations. Diab. Vasc. Dis. Res. 4, 1319.
Knight, D.A., Gabel, A.A., Reed, S.M., Embertson, R.M., Tyznik, W.J., Bramlage, L.R., 1985. Correlation of dietary mineral to incidence and severity of metabolic
bone disease in Ohio and Kentucky. In: Proceedings of the Annual Convention of the American Association of Equine Practitioners (USA), pp. 445461.
Knight, D.A., Tyznik, W.J., 1990. The effect of dietary selenium on humoral immunocompetence of ponies. J. Anim. Sci. 68, 13111317.
Koller, L.D., Exon, J.H., 1986. The two faces of selenium-deciency and toxicityare similar in animals and man. Can. J. Vet. Res. 50, 297306.
Krook, L., 1968. Dietary calcium-phosphorous and lameness in the horse. Cornell Vet. 58, 5973.
Krook, L., Maylin, G.A., 1988. Fractures in Thoroughbred race horses. Cornell Vet. 78 (suppl. 11), 746.
Krueger, A.S., Kinden, D.A., Garner, H.E., Sprouse, R.F., 1986. Ultrastructural study of the equine cecum during onset of laminitis. Am. J. Vet. Res. 47, 18041812.
Kuwamura, M., Iwaki, M., Yamate, J., Kotani, T., Sakuma, S., Yamashita, A., 1994. The rst case of equine motor neuron disease in Japan. J. Vet. Med. Sci. 56,
195197.
Lawrence, L.A., Pagan, J.D., 2005. The role of nutrition in developmental orthopedic disease in the equine. In: Mid-Atlantic Nutrition Conference, pp. 185196.
Lee, J., McAllister, E.S., Scholz, R.W., 1995. Assessment of selenium status in mares and foals under practical management conditions. J. Equine Vet. Sci. 15,
240245.
Leitch, S.P., Paterson, D.J., 1994. Role of Ca2+ in protecting the heart from hyperkalemia and acidosis in the rabbit: implications for exercise. J. Appl. Physiol.
77, 23912399.
Lentz, L.R., Valberg, S.J., Balog, E.M., Mickelson, J.R., Gallant, E.M., 1999a. Abnormal regulation of muscle contraction in horses with recurrent exertional
rhabdomyolysis. Am. J. Vet. Res. 60, 992999.
Lentz, L.R., Valberg, S.J., Mickelson, J.R., Gallant, E.M., 1999b. In vitro contractile responses and contracture testing of skeletal muscle from Quarter Horses
with exertional rhabdomyolysis. Am. J. Vet. Res. 60, 684688.
Lepeule, J., Bareille, N., Robert, C., Ezanno, P.J.P., 2009. Association of growth, feeding practices and exercise conditions with the prevalence of Developmental
Orthopaedic Disease in limbs of French foals at weaning. Prev. Vet. Med. 89, 167177.
99
Little, D., Redding, W.R., Spaulding, K.A., Dupree, S.H., Jones, S.L., 2000. Unusual presentation of nutritional secondary hyperparathyroidism in a Paint colt.
Equine Vet. Educ. 12, 297302.
Lofstedt, J., 1997. White muscle disease of foals. Vet. Clin. North Am. Equine Pract. 13, 169185.
Longland, A.C., Cairns, A.J., Humphreys, M.O., 1999. Seasonal and diurnal changes in fructan concentration in Lolium perenne: implications for the
grazing management of equines predisposed to laminitis. In: Proceedings of the 16th Equine Nutrition and Physiology Society Symposium,
pp. 258259.
Longland, A.C., Byrd, B.M., 2006. Pasture nonstructural carbohydrates and equine laminitis. J. Nutr. 136, 2099S2102S.
Longland, A.,2007. Starch, sugar and fructans: what are they and how important are they in diets for horses. In: The Latest Findings in Laminitis Research.
The First Waltham Royal Veterinary College Laminitis Conference. Equine Veterinary Journal Limited, Suffolk (UK), pp. 714.
Longland, A.C., Barfoot, C., Harris, P.A., 2009. Loss of water-soluble carbohydrate and soluble protein from nine different hays soaked. J. Equine Vet. Sci. 29,
383384.
Ludvikova, E., Jahn, P., Lukas, Z., 2007. Nutritional myodegeneration as a cause of dysphagia in adult horses: three case reports. Vet. Med. (Czech) 52,
267272.
Maas, J., Valberg, S., 2009. Nutritional myodegeneration. In: Smith, B.P. (Ed.), Large Animal Internal Medicine. Mosby, St Louis, pp. 14051409.
MacLeay, J.M., Sorum, S.A., Valberg, S.J., Marsh, W.E., Sorum, M.D., 1999. Epidemiologic analysis of factors inuencing exertional rhabdomyolysis in
Thoroughbreds. Am. J. Vet. Res. 60, 15621566.
Manning, J.R., 1882. Diseases of the bones. In: The Illustrated Stock Doctor. Pacic Publishing, Sydney, pp. 435437.
Mason, T.A., 1981. A high incidence of congenital angular limb deformities in a group of foals. Vet. Rec. 109, 9394.
Mayhew, I.G., Brown, C.M., Stowe, H.D., Trapp, A.L., Derksen, F.J., Clement, S.F., 1987. Equine degenerative myeloencephalopathy: a vitamin E deciency
that may be familial. J. Vet. Intern. Med. 1, 4550.
McCue, M.E., Ribeiro, W.P., Valberg, S.J., 2006. Prevalence of polysaccharide storage myopathy in horses with neuromuscular disorders. Equine Vet. J. Suppl.,
340344.
McCue, M.E., Valberg, S.J., 2007. Estimated prevalence of polysaccharide storage myopathy among overtly healthy Quarter Horses in the United States. J.
Am. Vet. Med. Assoc. 231, 746750.
McCue, M.E., Valberg, S.J., Lucio, M., Mickelson, J.R., 2008a. Glycogen synthase 1 (GYS1) mutation in diverse breeds with polysaccharide storage myopathy.
J. Vet. Intern. Med. 22, 12281233.
McCue, M.E., Valberg, S.J., Miller, M.B., Wade, C., DiMauro, S., Akman, H.O., Mickelson, J.R., 2008b. Glycogen synthase (GYS1) mutation causes a novel skeletal
muscle glycogenosis. Genomics 91, 458466.
McCue, M.E., Valberg, S.J., Jackson, M., Borgia, L., Lucio, M., Mickelson, J.R., 2009. Polysaccharide storage myopathy phenotype in quarter horse-related
breeds is modied by the presence of an RYR1 mutation. Neuromuscul. Disord. 19, 3743.
McGorum, B.C., Wilson, R., Pirie, R.S., Mayhew, I.G., Kaur, H., Aruoma, O.I., 2003. Systemic concentrations of antioxidants and biomarkers of macromolecular
oxidative damage in horses with grass sickness. Equine Vet. J. 35, 121126.
McGorum, B.C., Mayhew, I.G., Amory, H., Deprez, P., Gillies, L., Green, K., Mair, T.S., Nollet, H., Wijnberg, I.D., Hahn, C.N., 2006. Horses on pasture may be
affected by equine motor neuron disease. Equine Vet. J. 38, 4751.
McGowan, C.M., Fordham, T., Christley, R.M., 2002. Incidence and risk factors for exertional rhabdomyolysis in thoroughbred racehorses in the United
Kingdom. Vet. Rec. 151, 623626.
McKenzie, E.C., Valberg, S., Pagan, J.D., 2003a. In: Robinson, N.E. (Ed.), Nutritional Management of Exertional Rhabdomyolysis. Saunders, St Louis (MO), pp.
727734.
McKenzie, E.C., Valberg, S.J., Godden, S.M., Pagan, J.D., MacLeay, J.M., Geor, R.J., Carlson, G.P., 2003b. Effect of dietary starch, fat, and bicarbonate content on
exercise responses and serum creatine kinase activity in equine recurrent exertional rhabdomyolysis. J. Vet. Intern. Med. 17, 693701.
McKenzie, E.C., Firshman, A.M., 2009. Optimal diet of horses with chronic exertional myopathies. Vet. Clin. North Am. Equine Pract. 25, 121135.
McKenzie, R.A., Gartner, R.J.W., Blaney, B.J., Glanville, R.J., 1981. Control of nutritional secondary hyperparathyroidism in grazing horses with calcium plus
phosphorus supplementation. Aust. Vet. J. 57, 554557.
McKenzie, R.A., 1988. Purple pigeon grass (Setaria incrassata): a potential cause of nutritional secondary hyperpharathyroidism of grazing horses. Aust.
Vet. J. 65, 329330.
Meyer, T.S., Fedde, M.R., Cox, J.H., Erickson, H.H., 1999. Hyperkalemicperiodic paralysis in horses: a review. Equine Vet. J. 31, 362367.
Milinovich, G.J., Trott, D.J., Burrell, P.C., van Eps, A.W., Thoefner, M.B., Blackall, L.L., Al Jassim, R.A.M., Morton, J.M., Pollitt, C.C., 2006. Changes in equine
hindgut bacterial populations during oligofructose-induced laminitis. Environ. Microbiol. 8, 885898.
Miller, M.M., Collatos, C., 1997. Equine degenerative myeloencephalopathy. Vet. Clin. North. Am. Equine Pract. 13, 4352.
Mohammed, H.O., Cummings, J.F., Divers, T.J., de la Rua-Domenech, R., de Lahunter, A., 1994. Epidemiology of equine motor neuron disease. Vet. Res. 25,
275278.
Mohammed, H.O., Divers, T.J., Summers, B.A., de Lahunta, A., 2007. Vitamin E deciency and risk of equine motor neuron disease. Acta Vet. Scand. 49, 1726.
Moore, R.M., Kohn, C.W., 1991. Nutritional muscular dystrophy in foals. Compend. Contin. Educ. Pract. Vet. (USA) 13, 476489.
Mundy, G.R., Guise, T.A., 1999. Hormonal control of calcium homeostasis. Clin. Chem. 45, 13471352.
Muniyappa, R., Montagnani, M., Koh, K.K., Quon, M.J., 2007. Cardiovascular actions of insulin. Endocr. Rev. 28, 463491.
National Research Council, 2007. Nutrient Requirements of Horses, 6th revised edition. National Academies Press, Washington, DC.
Naylor, J.M., Jones, V., Berry, S.L., 1993. Clinical syndrome and diagnosis of hyperkalemicperiodic paralysis in quarter horses. Equine Vet. J. 25,
227232.
Naylor, J.M., 1994a. Selection of quarter horses affected with hyperkalemic periodic paralysis by show judges. J. Am. Vet. Med. Assoc. 204, 926928.
Naylor, J.M., 1994b. Equine hyperkalemic periodic paralysis: review and implications. Can. Vet. J. 35, 279285.
Naylor, J.M., 1997. Hyperkalemic periodic paralysis. Vet. Clin. North Am. Equine Pract. 13, 129144.
Pagan, J.D., Jackson, S.G., Caddel, S., 1996. A summary of growth rates of thoroughbreds in Kentucky. Pferdeheilkunde 12, 285289.
Pagan, J.D., Geor, R.J., Caddel, S.E., Pryor, P.B., Hoekstra, K.E., 2001. The relationship between glycemic response and the incidence of OCD in Thoroughbred
weanlings: a eld study. In: Proceedings of the 47th Proceedings of the American Association Equine Practitioners, San Diego, pp. 323325.
Pearce, S.G., Firth, E.C., Grace, N.D., Fennessy, P.F., 1998. Effect of copper supplementation on the evidence of developmental orthopedic disease in pasture-fed
New Zealand Thoroughbreds. Equine Vet. J. 30, 211218.
Pickar, J.G., Spier, S.J., Snyder, J.R., Carlsen, R.C., 1991. Altered ionic permeability in skeletal muscle from horses with hyperkalemic periodic paralysis. Am.
J. Physiol. Cell Physiol. 260, C926C933.
Polack, E.W., King, J.M., Cummings, J.F., Mohammed, H.O., Birch, M., Cronin, T., 2000. Concentrations of trace minerals in the spinal cord of horses with
equine motor neuron disease. Am. J. Vet. Res. 61, 609611.
Pratt, S.E., Geor, R.J., McCutcheon, L.J., 2006. Effects of dietary energy source and physical conditioning on insulin sensitivity and glucose tolerance in
standardbred horses. Equine Vet. J. Suppl. 57, 9584.
Quiroz-Rothe, E., Novales, M., Aguilera-Tejero, E., Rivero, J.L.L., 2002. Polysaccharide storage myopathy in the M. longissimus lumborum of showjumpers
and dressage horses with back pain. Equine Vet. J. 34, 171176.
Radostits, O.M., Blood, D.C., Gay, C.C., 1994. Diseases caused by nutritional deciencies. In: Veterinary Medicine. Bailliere Tindall, London, p. 1368.
Ragle, C.A., Meagher, D.M., Lacroix, C.A., Honnas, C.M., 1989. Surgical treatment of sand colic; results in 40 horses. Vet. Surg. 18, 4851.
Ralston, S.L., 1996. Hyperglycaemia/hyperinsulinaemia after feeding a meal of grain to young horses with osteochondrosis dissecans (OCD) lesions.
Pferdeheilkunde 12, 320322.
Rasouli, N., Kern, P.A., 2008. Adipocytokines and the metabolic complications of obesity. J. Clin. Endocrinol. Metabol. 93, 64S73S.
100
Reynolds, J.A., Potter, G.D., Greene, L.W., Wu, G., Carter, G.K., Martin, M.T., Peterson, T.V., Murray-Gerzik, M., Moss, G., Erkert, R.S., 1998. Genetic-diet
interactions in the hyperkalemic periodic paralysis syndrome in quarter horses fed varying amounts of potassium. II. Symptoms of HYPP. J. Equine Vet.
Sci. 18, 591600.
Ribeiro, W.P., Valberg, S.J., Pagan, J.D., Gustavsson, B.E., 2004. The effect of varying dietary starch and fat content on serum creatine kinase activity and
substrate availability in equine polysaccharide storage myopathy. J. Vet. Intern. Med. 18, 887894.
Riis, R.C., Jackson, C., Rebhun, W., Katz, M.L., Loew, E., Summers, B., Cummings, J., de Lahunta, A., Divers, T., Mohammed, H., 1999. Ocular manifestations of
equine motor neuron disease. Equine Vet. J. 31, 99110.
Rogers, C.W., Firth, E.C., McIlwraith, C.W., Barneveld, A., Goodship, A.E., Kawcak, C.E., Smith, R.K., van Weeren, P.R., 2008a. Evaluation of a new strategy to
modulate skeletal development in racehorses by imposing track-based exercise during growth: the effects on 2- and 3-year-old racing careers. Equine
Vet. J. 40, 119127.
Rogers, C.W., Firth, E.C., McIlwraith, C.W., Barneveld, A., Goodship, A.E., Kawcak, C.E., Smith, R.K., van Weeren, P.R., 2008b. Evaluation of a new strategy to modulate skeletal development in Thoroughbred performance horses by imposing track-based exercise during growth. Equine Vet. J. 40,
111118.
Ronen, N., van Heerden, J., van Amstel, S.R., 1992. Clinical and biochemistry ndings, and parathyroid hormone concentrations in three horses with secondary
hyperparathyroidism. J. S. Afr. Vet. Assoc. 63, 134136.
Rowe, J.B., Lees, M.J., Pethick, D.W., 1994. Prevention of acidosis and laminitis associated with grain feeding in horses. J. Nutr. 124, 2742S2744S.
Rudolph, J.A., Spier, S.J., Byrns, G., Rojas, C.V., Bernoco, D., Hoffman, E.P., 1992. Periodic paralysis in quarter horses: a sodium channel mutation disseminated
by selective breeding. Nat. Genet. 2, 144147.
Savage, C.J., McCarthy, R.N., Jeffcott, L.B., 1993a. Effects of dietary energy and protein on induction of dyschondroplasia in foals. Equine Vet. J. Suppl. 16,
7479.
Savage, C.J., McCarthy, R.N., Jeffcott, L.B., 1993b. Effects of dietary phosphorus and calcium on induction of dyschondroplasia in foals. Equine Vet. J. Suppl.
16, 8083.
Slawik, M., Vidal-Puig, A.J., 2006. Lipotoxicity, overnutrition and energy metabolism in aging. Ageing Res. Rev. 5, 144164.
Spier, S.J., 2006. Hyperkalemic periodic paralysis: 14 years later. In: Proceedings of the 52nd Annual Conference of the American Association of Equine
Practitioners, pp. 15.
Stewart, R.H., Bertone, J.J., Yvorchuk-St Jean, K., Reed, S.M., Neil Jr., W.H., 1993. Possible normokalemic variant of hyperkalemic periodic paralysis in two
horses. J. Am. Vet. Med. Assoc. 203, 421424.
Sustronck, B., Deprez, P., Roy, M., Muylle, E., Roels, S., Thoonen, H., 1993. Equine motor neuron disease: the rst conrmed cases in Europe. Vlaams
Diergeneeskundig Tijdschr. 62, 4044.
Syrja, P., Cizinauskas, S., Sankari, S.M., Makela, O., Tulamo, R.M., de Lahunta, A., 2006. Equine motor neuron disease (EMND) in a horse without vitamin E
deciency: a sequela of iron excess? Equine Vet. Educ. 18, 122126.
Toribio, R.E., Kohn, C.W., Chew, D.J., Sams, R.A., Rosol, T.J., 2001. Comparison of serum parathyroid hormone and ionized calcium and magnesium concentrations and fractional urinary clearance of calcium and phosphorus in healthy horses and horses with enterocolitis. Am. J. Vet. Res. 62, 938947.
Toribio, R., 2004. Calcium disorders. In: Reed, S.M., Bayly, W.M., Sellon, D.C. (Eds.), Equine Internal Medicine. Saunders, St Louis, p. 1295.
Toribio, R., 2009. Endocrine and metabolic diseases. In: Smith, B.P. (Ed.), Large Animal Internal Medicine. Mosby, St Louis, pp. 13551363.
Traub-Dargatz, J.L., Salman, M.D., Jones, R.L., 1990. Epidemiologic study of salmonellae shedding in the feces of horses and potential risk factors for
development of the infection in hospitalized horses. J. Am. Vet. Med. Assoc. 196, 16171622.
Treiber, K.H., Kronfeld, D.S., Hess, T.M., Byrd, B.M., Splan, R.K., Staniar, W.B., 2006. Evaluation of genetic and metabolic predispositions and nutritional risk
factors for pasture-associated laminitis in ponies. J. Am. Vet. Med. Assoc. 228, 15381545.
Treiber, K.H., Carter, R.A., Harris, P.A., Geor, R.J., 2008. Seasonal changes in energy metabolism of ponies coincides with changes in pasture carbohydrates:
implications for laminitis. J. Vet. Intern. Med. 22, 735736.
USDA-NAHMS, 2000. Lameness and Laminitis in US Horses. USDA: APHIS: VS, CEAH, National Animal Health Monitoring System, Fort Collins, CO
(#N318.0400).
Valberg, S.J., Cardinet, G.H., Carlson, G.P., DiMauro, S., 1992. Polysaccharide storage myopathy associated with recurrent exertional rhabdomyolysis in
horses. Neuromuscul. Disord. 2, 351359.
Valberg, S., Jonsson, L., Lindholm, A., Holmgren, N., 1993. Muscle histopathology and plasma aspartate aminotransferase, creatine kinase and myoglobin
changes with exercise in horses with recurrent exertional rhabdomyolysis. Equine Vet. J. 25, 1116.
Valberg, S.J., Townsend, D., Mickelson, J.R., 1998. Skeletal muscle glycolytic capacity and phosphofructokinase regulation in horses with polysaccharide
storage myopathy. Am. J. Vet. Res. 59, 782785.
Valberg, S., 2009. Exertional myopathies in horses. In: Smith, B.P. (Ed.), Large Animal Internal Medicine. Mosby, St Louis, p. 1414.
Valentine, B.A., de Lahunta, A., George, C., Summers, B.A., Cummings, J.F., Divers, T.J., Mohammed, H.O., 1994. Acquired equine motor neuron disease. Vet.
Pathol. 31, 130138.
Valentine, B.A., Van Saun, R.J., Thompson, K.N., Hintz, H.F., 2001. Role of dietary carbohydrate and fat in horses with equine polysaccharide storage myopathy.
J. Am. Vet. Med. Assoc. 219, 15371544.
Valentine, B.A., 2003. Equine polysaccharide storage myopathy. Equine Vet. Educ. 15, 254262.
van der Kolk, J.H., Rijnen, K.E., Rey, F., de Graaf-Roelfsema, E., Grinwis, G.C., Wijnberg, I.D., 2005. Evaluation of glucose metabolism in three horses with
lower motor neuron degeneration. Am. J. Vet. Res. 66, 271276.
van Eps, A.W., 2010. Acute laminitis: medical and supportive therapy. Vet. Clin. North Am. Equine Pract. 26, 103114.
van Weeren, P.R., Barneveld, A., 1999. The effect of exercise on the distribution and manifestation of osteochondrotic lesions in the Warmblood foal. Equine
Vet. J. Suppl. 1, 625.
van Weeren, P.R., Sloet van Oldruitenborgh-Ooste, Barneveld, A., 1999. The inuence of birth weight, rate of weight gain and nal achieved height and sex
on the development of osteochondrotic lesions in a population of genetically predisposed Warmblood foals. Equine Vet. J. Suppl., 2630.
van Weeren, P.R., Knaap, J., Firth, E.C., 2003. Inuence of liver copper status of mare and newborn foal on the development of osteochondrotic lesions.
Equine Vet. J. 35, 6771.
van Weeren, P.R., 2006. Etiology, diagnosis, and treatment of OC (D). Clin. Tech. Equine Pract. 5, 248258.
van Weeren, P.R., Firth, E.C., Brommer, B., Hyttinen, M.M., Helminen, A.E., Rogers, C.W., Degroot, J., Brama, P.A., 2008. Early exercise advances the maturation
of glycosaminoglycans and collagen in the extracellular matrix of articular cartilage in the horse. Equine Vet. J. 40, 128135.
van Weyenberg, S., Hesta, M., Buyse, J., Janssens, G.P., 2008. The effect of weight loss by energy restriction on metabolic prole and glucose tolerance in
ponies. J. Anim. Physiol. Anim. Nutr. 92, 538545.
Verhulst, D., Barnett, K.C., Mayhew, I.G., 2001. Equine motor neuron disease and retinal degeneration. Equine Vet. Educ. 13, 5967.
Vick, M.M., Sessions, D.R., Murphy, B.A., Kennedy, E.L., Reedy, S.E., Fitzgerald, B.P., 2006. Obesity is associated with altered metabolic and reproductive
activity in the mare: effects of metformin on insulin sensitivity and reproductive cyclicity. Reprod Fertil. Dev. 18, 609617.
Vick, M.M., Adams, A.A., Murphy, B.A., Sessions, D.R., Horohov, D.W., Cook, R.F., Shelton, B.J., Fitzgerald, B.P., 2007. Relationships among inammatory
cytokines, obesity, and insulin sensitivity in the horse. J. Anim. Sci. 85, 11441155.
Walthall, J.C., McKenzie, R.A., 1976. Osteodystrophia brosa in horses at pasture in Queensland: eld and laboratory observations. Aust. Vet. J. 52, 1116.
Weber Polack, E., King, J.M., Cummings, J.F., de Lahunta, A., Divers, T.J., Mohammed, H.O., 1998. Quantitative assessment of motor neuron loss in equine
motor neuron disease (EMND). Equine Vet. J. 30, 256259.
Wichtel, J.J., Grace, N.D., Firth, E.C., 1998. The effect of injectable barium selenate on the selenium status of horses on pasture. N.Z. Vet. J. 46, 186190.
Wijnberg, I.D., 2006. Equine motor neuron disease. Equine Vet. Educ. 18, 126129.
101
Wisse, B.E., 2004. The inammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J. Am. Soc. Nephrol. 15,
27922800.
Ytrehus, B., Carlson, C.S., Ekman, S., 2007. Etiology and pathogenesis of osteochondrosis. Vet. Pathol. Online 44, 429448.
Zhou, J., Spier, S.J., Beech, J., Hoffman, E.P., 1994. Pathophysiology of sodium channelopathies: correlation of normal/mutant mRNA ratios with clinical
phenotype in dominantly inherited periodic paralysis. Hum. Mol. Genet. 3, 15991603.

2012 - The Role of Diet in The Prevention and Management of Several Equine Diseases 1

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

2012 - The Role of Diet in The Prevention and Management of Several Equine Diseases 1

Uploaded by

Copyright:

Available Formats

Animal Feed Science and Technology 173 (2012) 86101

Contents lists available at SciVerse ScienceDirect

Animal Feed Science and Technology

The role of diet in the prevention and management of several equine

8. Developmental orthopaedic disease

You might also like