A scoping review of the analytical literature concerning nonambulatory dairy cattle.

Nonambulatory dairy cattle pose a complex problem due to the challenges associated with prevention, appropriate treatment and management, and arriving at an accurate prognosis. There is a breadth of literature regarding this topic, of which there is currently no formal synthesis. The objective of this scoping review was to describe and characterize the literature investigating risk factors, sequela, preventions, treatments, and prognostic factors for nonambulatory conditions in dairy cattle, with the intent of qualitatively synthesizing knowledge of the topic and identifying gaps in the literature. A literature search was conducted in 6 databases and 2 conference proceeding archives, which returned 7,568 unique articles. Initial screening of abstracts resulted in 1,544 articles reviewed at the full-text stage, of which 379 were included for data extraction. Over 75% of the included literature was published after 1980, and the most common countries in which these studies took place were the United States (n = 72), Canada (18), Sweden (17), and Germany (17). Common eligibility criteria used for inclusion were geographic region (97) and parity (92). Of the 379 studies included in this review, 144 were randomized controlled trials and 235 were observational studies. The majority of the controlled trials assessed prevention of nonambulatory conditions (116), most commonly through supplementation of vitamin D (27) and calcium (25) or the provision of anionic salts (22). Of the 28 studies focusing on treatment of nonambulatory conditions, 26 focused on calcium administration. Becoming nonambulatory was evaluated as an outcome in 165 of the observational studies. Frequently measured risk factors for becoming nonambulatory included hematological variables, such as blood calcium (73), phosphorus (53) and magnesium (42), and other factors such as parity (35) and breed (22). Recovery from a nonambulatory condition was the outcome in 31 of the observational studies, with commonly measured prognostic indicators being calcium (9), phosphorus (9), and duration of recumbency (7). Nonambulatory disorders were measured as risk factors in 53 of the observational studies, with the most commonly assessed outcomes including disorders of the transition period (11), and death or euthanasia (11). The most common terms used to describe nonambulatory conditions were "milk fever" (199) and "parturient paresis" (147). These terms were only further defined with explicit symptomatic criteria in 193 of the 379 studies in this review. Recumbency was the most commonly used of these criteria (144), followed by inability to rise (55). Potential gaps in the literature concerning nonambulatory dairy cattle that were identified in the present review included investigation of prognostic indicators for recovery from nonambulatory conditions that are applicable on farm, treatment alternatives to calcium administration, and guidance regarding the appropriate usage of terms meant to categorize nonambulatory dairy cattle.

[Etiology, therapy and prophylaxis of bovine parturient paresis (hypocalcaemia)]. / Wesen, Ursachen, Therapie und Prophylaxe der hypokalzämischen Gebärparese beim Rind.

Due to the sudden increase of calcium demand at the onset of lactation many high yielding dairy cows experience a certain level of hypocalcaemia following parturition. The incidence of hypocalcaemia (parturient paresis) increases with age but also depends on many other factors such as the acid-base status and the availability of calcium as well as other minerals and trace elements. Hypocalcaemia can easily be treated by supplementation of calcium parenterally or orally, nonetheless, prophylaxis of the condition should be the main focus in modern dairy farming, in order to avoid its negative effects. Oral administration of calcium around parturition is the simplest way of prophylaxis, but results in a high work load and requires exact knowledge of the date of parturition. The latter also applies for the parenteral administration of vitamin D3, which should be injected 1 week before parturition. Additionally, repeated treatment with vitamin D increases the risk for calcinosis. Reducing the calcium concentration of the ration fed during the late dry period also decreases the risk for hypocalcaemia by activating the mechanisms for calcium homeostasis within the body. The induction of a mild (compensated) metabolic acidosis to increase the sensitivity of parathormone receptors and enhance intestinal calcium uptake may also be employed to prevent milk fever. For this purpose, a DCAD (dietary cation anion difference) diet is fed during the late dry period, in which the concentrations of strong cations (potassium and sodium) as well as strong anions (sulfate and chloride) are altered. This may either be achieved by reducing the potassium concentration (partial-DCAD) or by adding anionic salts (full-DCAD). This method, especially the full-DCAD variant, requires a substantial level of surveillance and monitoring. Suitable prophylactic measures for the prevention of hypocalcaemia must be chosen individually for each farm, depending on the incidence of hypocalcaemia as well as personnel and structural resources.

Hypocalcemia-Cow-level prevalence and preventive strategies in German dairy herds.

Hypocalcemia around calving is considered a gateway disease that can lead to health disorders and decreased milk production. The objective of this cross-sectional study was to evaluate the prevalence of clinical and subclinical hypocalcemia 0 to 48 h after calving. Blood samples were drawn from 12 animals of each dairy farm (n = 115) and analyzed for serum calcium, magnesium, and phosphorus concentration. Cows not affected clinically but with a serum calcium concentration below 2.0 mmol/L were characterized as subclinical hypocalcemic animals. Recumbent cows with a serum calcium concentration below 2.0 mmol/L were defined as cows suffering from clinical milk fever. Herds were classified into negative (0 to 2/12), borderline (3 to 5/12), and positive (≥6/12) according to the number of animals with hypocalcemia. Strategies to control hypocalcemia were documented. Prevalence of clinical milk fever was 1.4, 5.7, and 16.1% for second, third, and ≥fourth parity cows, respectively. None of the cows in first lactation were suffering from clinical milk fever. Based on the threshold of 2.0 mmol/L, 5.7, 29.0, 49.4, and 60.4% of cows in first, second, third, and ≥fourth lactation were suffering from subclinical hypocalcemia, respectively. Fourteen, 51, and 50 herds were classified as negative, borderline, and positive, respectively. A positive association was observed between serum calcium and serum phosphorus concentration. Serum calcium and magnesium concentration were negatively associated. Only 50 of 115 farms had a control strategy implemented to avoid hypocalcemia. Most common was the use of oral calcium products (40/115 herds), followed by feeding of anionic salts in the close-up diet (10/115 herds). These results indicate that the prevalence of clinical and subclinical hypocalcemia in German dairy herds was high and that an active control strategy was not implemented on all farms. The negative association between calcium and magnesium warrants further research regarding the physiological regulation of these 2 minerals around parturition.

[Diagnosis, therapy and prophylactic measures of parturient paresis in dairy cattle: results of an online survey for Swiss veterinarians]. / Diagnose, Therapie und prophylaktische Massnahmen der Gebärparese beim Rind: Ergebnisse der Online-Umfrage bei Schweizer Tierärzten.

INTRODUCTION: The aim of this study was to obtain the diagnostic, therapeutic and prophylactic approach among Swiss veterinary practitioners in cows with parturient hypocalcemia. All members of the Association for Ruminant Health were contacted per e-mail. The survey was completed by 108 (28%) of 393 that were contacted. According to the questionnaire responses, the typical presentation of a parturient paresis cow is a pluriparous middle-yielding dairy cow one day post-partum in sternal recumbency with normal consciousness. The diagnosis is usually based upon the medical history. Therapy of parturient paresis consists of mixed infusions (with calcium, phosphorus, magnesium or glucose) as well as oral preparations with calcium. The veterinarians estimate that 25-50% of the cows treated for parturient paresis need more than one treatment and that one case of parturient paresis costs CHF 200-300. Prophylactic treatments are usually used for cows, which have suffered from parturient paresis in the previous lactation, elder cows (≥ 3 lactations) as well as cows with a high body condition score (> 3.25). Prophylactic measures used by the veterinarians are vitamin D3 injections and oral preparations with calcium. They recommended a special diet, for example a low calcium diet ante-partum.

INTRODUCTION: Le but de la présente enquête en ligne était de relever les méthodes de diagnostic, de traitement et de prophylaxie utilisées en pratique en matière de parésie puerpérale hypocalcémique. Tous les membres de l'Association suisse pour la santé des ruminants ont été contactés par courriel. Sur les 393 questionnaires envoyés, 108 (28%) ont été remplis complètement et exploités. L'anamnèse typique est un animal pluripare avec une production de parésie puerpérale, il est mentionné des animaux pluripares avec une production laitière moyenne, incapables de se lever un jour après le vêlage et présentant un état de conscience normal. Le diagnostic est fréquemment posé sur la base de l'anamnèse. Les vaches laitières concernées sont traitées avec des perfusions mixtes (produits à base de calcium et de phosphore, parfois avec du magnésium et du glucose) et des préparations de calcium orales. Les vétérinaires estiment que 25 à 50% des vaches nécessitent plusieurs traitements et que les coûts totaux par animal de l'ordre de CHF 200 à 300. Du point de vue prophylactique, ce sont principalement les animaux ayant déjà souffert d'une parésie lors de la lactation précédente ainsi que les vaches plus âgées (3ème lactation et plus) et celles présentant un indice de condition élevé (> 3.25) qui sont traitées. Les vétérinaires utilisent pour cette prophylaxie des injections de vitamine D3 ainsi que des préparations orales de calcium et/ou conseillent aux propriétaires une alimentation pauvre en calcium ante partum.

Effects of a sustained release formulation of 1,25-dihydroxyvitamin D3-glycosides for milk fever prevention on serum 1,25-dihydroxyvitamin D3, calcium and phosphorus in dairy cows.

Milk fever (MF) is a metabolic disease in dairy cows around parturition. The clinical lead sign is muscular paresis leading in severe cases to paralysis of the affected animal. Multiparturient animals of high performing dairy breeds are most likely to be affected and have a high probability of recurrence. An acute drop in blood calcium levels causes the disease when the demand for calcium at the onset of lactation exceeds the ability to replete blood calcium levels through mobilization from bone and intestinal uptake. With the understanding of the underlying mechanism, calcium supply management and vitamin D supplementation became prime candidates for MF prevention and therapy. Several strategies have been developed for MF prevention. Application of the active form of Vitamin D, 1,25(OH)2D3, was found to prevent MF effectively. In order to prevent a delayed hypocalcemia, which was occasionally seen after stopping the treatment with 1,25(OH)2D3, a new approach was chosen by applying Solanum glaucophyllum extract (SGE), which contains 1,25(OH)2D3-glycosides, as instant-release (irSGE) in combination with slow-release (srSGE) tablets. In a first study, non-lactating cows were treated with a single bolus of either synthetic 1,25(OH)2D3, irSGE, or srSGE and the results were compared to a control group without treatment. Blood serum levels of 1,25(OH)2D3 (1,25D), calcium (Ca), phosphate (P) and magnesium (Mg) were followed for 11days and the area under the curve (AUC) was calculated. Calcium and phosphate excretion in urine were determined during 15days. While serum concentration of 1,25(OH)2D3 was back to pre-treatment level in the irSGE, srSGE and 1,25(OH)2D3 treated group within 3days, calcium and phosphate levels remained elevated for up to 9days. AUC of serum 1,25(OH)2D3 was 2.89 (1,25D), 3.13 (irSGE) and 4.21 (srSGE) times higher than control. Serum calcium levels were 1.07* (for 1.25D); 1.08* (for irSGE) and 1.12* (for srSGE) times higher than control. Serum phosphate levels were 1.20* (for 1,25D); 1.30* (for irSGE) and 1.41* (for srSGE) times higher than control, with * p<0.05. In a second field study calving cows treated with one bolus containing ir- and sr- tablets of SGE were compared to an untreated control group and to a group treated with 4 boli of commercial calcium salts. As a result, calcium serum levels increased (+19% compared to baseline) around calving after treatment with the single bolus of SGE. The single bolus of SGE lead also to an increase of serum phosphate (+31% compared to baseline). These calcium and phosphate increases were statistically significant (p<0.001) 0-24h after calving compared to the control group and to the group treated with calcium salts. The sample size of the study was too small to draw a conclusion on the effect on MF prevention. In conclusion, application of a single bolus of a SGE extract lead to an increase of serum calcium and phosphate for up to 9days and may thus have the potential to prevent a hypocalcemia and -phosphatemia, an important cause for clinical milk fever.

Calcium and magnesium physiology and nutrition in relation to the prevention of milk fever and tetany (dietary management of macrominerals in preventing disease).

Dairy cows may suffer events of hypocalcemia and hypomagnesemia, commonly known as milk fever and tetany. Milk fever is characterized by hypocalcemia at parturition as a consequence of a sudden increase in Ca demand and an unavoidable delay in Ca metabolism adaptation. Tetany is due to impaired Mg absorption from the rumen that cannot be compensated by absorptive or excretory adaptation, resulting in a net nutritional shortage of Mg and culminating in hypomagnesemia. Prevention strategies require triggering the activation of Ca gastrointestinal absorption and avoiding factors limiting ruminal Mg absorption.

Survey on the occurrence of milk fever in dairy cows and the current preventive strategies adopted by farmers in New South Wales, Australia.

OBJECTIVE: The aim of this study was to investigate general and specific strategies adopted by New South Wales (NSW) farmers to prevent milk fever (MF) and its occurrence at calving within their dairy herds. DESIGN AND METHODS: Of 300 dairy farmers in NSW randomly chosen and sent questionnaires, descriptive analysis of the returned data was performed for 102 questionnaires. To identify the various strategies used to prevent MF and its incidence, farms were classified as having a low (<3%) or high (>3%) incidence of MF. The data were analysed using a multivariable logistic regression model and backwards stepwise elimination to identify significant preventive strategies adopted by farmers having a low or high incidence of MF. RESULTS: Based on the 102 responses, the median incidence of MF in the NSW dairy region was 3% (range 0-30%). The farms with low MF incidence practised specific MF control strategies, such as feeding dry cows separately, grain supplementation and feeding a low-potassium ration before calving and using a commercial ration mix immediately after calving. The time to first milking post-calving was on average 13.6 h on the low-incidence farms compared with 21.1 h on the high-incidence farms. CONCLUSIONS: The low median incidence of MF (3%) in NSW was probably related in part to awareness of the importance of feeding a low-potassium, high-grain diet before calving. However, the incidence of MF was high on the farms not practising specific MF preventive methods.

Effects of folic acid and vitamin B12 supplementation on culling rate, diseases, and reproduction in commercial dairy herds.

This study was undertaken to determine the effect of a combined folic acid and vitamin B12 supplement given in early lactation on culling rate, metabolic disorders and other diseases, and reproduction in commercial dairy herds. A total of 805 cows (271 primiparous and 534 multiparous cows) in 15 commercial dairy herds were involved. Every 2mo from February to December 2010 and within each herd, cows were assigned according to parity, previous 305-d milk production, and calving interval to 5mL of either (1) saline 0.9% NaCl (control group) or (2) 320mg of folic acid + 10mg of vitamin B12 (vitamin group). Treatments were administered weekly by intramuscular injections starting 3wk before the expected calving date until 8wk after parturition. A total of 221 cows were culled before the next dry period. Culling rate was not affected by treatment and was 27.5%; culling rate was greater for multiparous (32.2%) than for primiparous cows (18.8%). Within the first 60d in milk (DIM), 47 cows were culled, representing 21.3% of total culling, and no treatment effect was noted. Ketosis incidence based on a threshold ≥100µmol/L of ß-hydroxybutyrate in milk was 38.3±2.9% for the vitamin group and 41.8±3.0% for the control group and was not affected by treatment. The combined supplement of folic acid and vitamin B12 did not decrease incidence of retained placenta, displaced abomasum, milk fever, metritis, or mastitis. However, the incidence of dystocia decreased by 50% in multiparous cows receiving the vitamin supplement, although no effect was observed in primiparous cows. The first breeding postpartum for multiparous cows occurred 3.8d earlier with the vitamin supplement compared with controls, whereas no treatment effect was seen for primiparous cows. Days open, first- and second-breeding conception rates, number of breedings per conception, and percentage of cows pregnant at 150 DIM were not affected by treatment. The reduced percentage of dystocia combined with the earlier DIM at first breeding for multiparous cows receiving the combined supplementation in folic acid and vitamin B12 indicates that the vitamin supplement had a positive effect in older cows.

[The effect of oral calcium lactate in postpartum cows]. / Untersuchungen zur Wirkung von Kalziumlaktat bei Kühen post partum.

The oral administration of calcium lactate for prophylaxis of bovine parturient paresis has been promoted for a number of years. The goal of the present study was to investigate the effect of this treatment on the serum concentrations of calcium, inorganic phosphorus and magnesium in parturient cows. Five fresh calved cows were given a drench containing calcium lactate and 5 control cows received the same drench but without calcium lactate. There were no significant differences in the serum concentrations of total and ionised calcium and magnesium between treated and control cows within 24 hours of treatment. Because the calcium lactate drench did not significantly affect calcium concentrations in the blood of fresh cows, it appears highly questionable whether the administration of calcium lactate decreases the risk of bovine parturient paresis. Based on our results, the oral administration of calcium lactate can not be recommended for prophylaxis of bovine parturient paresis.

Urinary calcium excretion in non-lactating dairy cows in relation to intake of fat-coated rice bran.

At calving, many older cows fail to compensate the sudden demand of calcium by an adequate activation of intestinal absorption. This results in a variable degree of hypocalcaemia. Reducing intestinal availability of calcium during the close-up period can prevent milk fever. Fat-coated rice bran (FCRB) was investigated for its potential to reduce Ca availability in pre-calving cows. Fat-coated rice bran was incubated in situ to estimate ruminal degradation of dry matter and phytic acid. Also, seven dry multiparous dairy cows were used for a feeding trial in three periods of approximately 1 week each: P1: adaptation; P2: feeding of 2 kg of FCRB and P3: withdrawal of FCRB. Feed intake was recorded and daily urine samples were analysed for pH, Ca and creatinine. The bypass fraction of phytic acid (passage rate: 5%/h) was 30%. Fat-coated rice bran depressed dry matter intake in P2, resulting in a lower Ca intake. In P2 urine pH and calcium excretion were lower. Daily calcium excretion decreased after introduction of FCRB, peaked after withdrawal and dropped 2 days later. Changes in urinary Ca excretion by feeding FCRB indicate that FCRB affected Ca homeostasis in dry multiparous dairy cows.

The effect of various anionic salts on ruminant pH and short-chain fatty acids in non-pregnant and non-lactating cows.

AIM: To evaluate whether the different anionic salts used in the prevention of parturient paresis have an impact on the ruminal pH and the production of short-chain fatty acids (SCFA) in mature non-pregnant, non-lactating cows. METHODS: Eleven Holstein-Friesian crossbred cows were administered 2,000 mEq of either one of three chloride salts, viz CaCl2, MgCl2, or NH4Cl; four sulphate salts, viz CaSO4, CaSO4 with a grain size of 10 microm, MgSO4, or (NH4)2SO4; two combinations of anionic salts, viz CaCl2+MgSO4, or CaSO4+NH4Cl; NaCl; or water, via a ruminal cannula over a 14-day treatment period. The salts and controls were assigned in an 11 x 11 Latin square, and the cows were distributed randomly. Ruminal fluid was collected four times in each treatment period for monitoring the ruminal pH, and four times a day at Days 7 and 14 for monitoring any changes in the concentrations of SCFA. RESULTS: Feeding anionic salts did not change the ruminal pH, total concentration of SCFA, or distribution pattern of the main SCFA acetic acid, propionic acid, butyric acid or valeric acid (p>0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Feeding anionic salts has no negative side effect on the ruminal pH and concentrations of SCFA in mature non-pregnant, non-lactating cattle. Impaired function of the rumen due to the feeding of anionic salts is not likely.

Historical and current perspectives on the treatment, control and pathogenesis of milk fever in dairy cattle.

Milk fever has been recognised in cattle for about 215 years and its clinical signs have not changed since they were described by Victorian veterinary surgeons in the mid-nineteenth century. It was only 80 years ago that abnormal parathyroid gland function was associated with the pathogenesis of the hypocalcaemia characteristic of the disease, and the current basis for its treatment with intravenous calcium salts was established. Although this treatment is effective, most recent research has focused on preventing the disease through an understanding of the endocrine control of extracellular calcium homeostasis. In the 1970s the synthetic vitamin D analogue 1alpha-hydroxycholecalciferol was developed for intramuscular injection before a cow calved, but variable results encouraged other preventive strategies to be considered, including restricting the dietary intake of calcium, and manipulating the dietary cation-anion balance of cows before they calved. Currently, the role of extracellular calcium receptors in the parathyroid gland is under investigation as a preliminary step to devising more effective treatments and/or preventive methods for milk fever.

[Efficacy of oral calcium and/or sodium phosphate in the prevention of parturient paresis in cows]. / Untersuchungen zur Prophylaxe der Gebärparese mit Kalzium und Natriumphosphat per os.

The goal of this study was to investigate the efficacy of calcium chloride, sodium phosphate or a combination of these two substances administered orally immediately postpartum for the prevention of parturient paresis in cows. Thirty-two cows that had had parturient paresis at the previous calving, and in which serum biochemistry had shown hypocalcaemia and hypophosphataemia, were used in the study. The cows were transferred to the Department of Farm Animals, University of Zurich, five days before their expected due dates. On a randomized trial, the cows were given calcium chloride, sodium phosphate, both substances or no treatment (controls) via a stomach tube immediately postpartum and 12 hours later. The cows were monitored for 96 hours during which time blood was collected on a regular basis for the determination of total calcium, ionized calcium, inorganic phosphorus and magnesium concentrations. Of the 32 cows treated, 19 (59%) had parturient paresis and 13 (41%) did not. The incidence of parturient paresis did not differ significantly among the groups although there was a tendency for a lower incidence in cows treated with both calcium chloride and sodium phosphate. The various treatments had no apparent effect on serum calcium concentration. The concentration of inorganic phosphorus increased significantly in cows treated with sodium phosphate compared with the controls. The results of this study showed that cows treated with both calcium chloride and sodium phosphate orally tended to have a lower incidence of parturient paresis. Further investigation into multiple administrations of oral calcium chloride and sodium phosphate, started before parturition, for the prevention of parturient paresis is required.

The role of dietary calcium concentration in the use of anionic salts to prevent parturient paresis in dairy cows.

The role of dietary calcium concentration during the feeding of anionic salts (AS) was reviewed. Hypocalcaemia is still the major cause of parturient paresis in dairy cows. Feeding AS is an established method for preventing severe hypocalcaemia by activating the calcium metabolism in the last two to three weeks before parturition by inducing a metabolic acidosis. In compensation for this acidosis, the organism increases the concentrations of ionised Ca [Ca2+] in the blood. This increase leads to an increasing excretion of calcium via the urine, which is ensued by an increased calcium absorption in the intestine. The ongoing metabolic acidosis changed the flux of Ca. The size of the Ca pool, however, remained unchanged. As the calcium metabolism is activated by AS, it seems necessary to increase the amount of calcium that is fed to the cows. Several studies examined the impact of different dietary calcium concentrations on the acid-base balance and the calcium metabolism in cows fed anionic salts. The study designs vary concerning the amounts of calcium fed and the use of pregnant or non-pregnant cows. Only one study combined the feeding of AS with a very low amount of calcium, which fell below the daily requirements of pregnant cows in the last three weeks before parturition. In this study, the calcium balance post partum was better in the cows that were administered AS and a high calcium diet. In the other studies, the amount of calcium in the different experimental groups and the difference between the amounts of calcium fed varied greatly. As far as it was monitored in the studies, the calcium concentration of the diet did not have a significant impact on the degree of acidosis induced by AS. In pregnant cows, no significant differences in the calcium concentration in serum or urine occurred before parturition. Some of the researchers found a lower incidence of parturient paresis when cows were fed a combination of AS and a higher amount of calcium, but some other researches did not. Interestingly, the parameters of bone metabolism did not change between experimental groups. According to what is currently known, the feeding of AS to transition cows should not be combined with a dietary calcium concentration that falls below the requirement of cows in this stage of lactation. On the other hand, there is no need to increase the Ca concentration. When AS are used the dietary calcium concentration should be between 9 g and 12 g/kg dry matter. Further research is needed to investigate the role of dietary calcium regarding the use of AS for improving Ca metabolism in dairy cows around parturition.

The monitoring, prevention, and treatment of milk fever and subclinical hypocalcemia in dairy cows.

The periparturient cow undergoes a transition from non-lactating to lactating at calving. The animal is tremendously challenged to maintain calcium homeostasis. Those that fail can develop milk fever, a clinical disorder that is life threatening to the cow and predisposes the animal to a variety of other disorders. Guidelines for monitoring the incidence of hypocalcemia and methods for treating milk fever are reviewed. The physiological factors that cause milk fever and strategies for prevention of milk fever are discussed, focusing on the effects diet cation-anion difference can have on tissue sensitivity to parathyroid hormone. Another major risk factor for milk fever is hypomagnesemia, which is observed when animals are fed inadequate amounts of magnesium, or some factor is present in the diet that prevents adequate absorption of magnesium. Moderate hypomagnesemia impairs the ability of the cow to maintain calcium homeostasis and hypocalcemia occurs.

Milk fever in dairy cows: a review of pathophysiology and control principles.

The periparturient or transition period of 4 weeks before and 4 weeks after calving is characterised by a greatly increased risk of disease. Hypocalcaemia around calving is a risk factor for many of these diseases and is an indirect risk factor for increased culling. The incidence of clinical hypocalcaemia (milk fever) in the field generally ranges from 0-10%, but may exceed 25% of cows calving. In research trials conducted on milk fever the incidence has approached 80% of cows calving. Homeostasis of calcium (Ca) is regulated by calcitonin, parathyroid hormone and 1,25(OH)(2) vitamin D(3). Age increases the risk of milk fever by approximately 9% per lactation. Control of milk fever has revolved around stimulation of homeostatic mechanisms through feeding a pre-calving diet low in Ca. More recently, the role of the dietary cation anion difference (DCAD) in the prevention of Ca disorders has been examined, both by field research and meta-analysis. The most appropriate form of the DCAD equation has been contentious, but recent meta-analyses have shown that the equation (Na(+)+K(+))-(Cl(-)+S(2-)) is most effective for predicting milk fever risk. Decreased risk of milk fever is linear with DCAD, whereas the effect of DCAD on urinary pH is curvilinear. A pivotal role of providing dietary magnesium (Mg) before calving has been confirmed by meta-analysis, and a quadratic effect of Ca on milk fever risk was found with a peak occurring with dietary levels of 1.1-1.3% of dry matter. Risks of milk fever increase with increased dietary phosphorus (P) fed pre-calving and with increasing days of exposure to a pre-calving diet. Meta-analysis has revealed that the important roles of dietary Ca, Mg and P, as well as the duration of exposure to the pre-calving diet in milk fever control strategies are independent of DCAD. Studies on the effect of exposure to well designed pre-calving diets have shown that substantial improvements in production, reproduction and animal health can be made but further examination of the influence of the period of exposure to different diets is warranted.

Clinico-pathological findings in peripartum dairy cows fed anion salts lowering the dietary cation-anion difference: involvement of serum inorganic phosphorus, chloride and plasma estrogen concentrations in milk fever.

In our previous study, it was demonstrated that the administration of anion salts, which slightly lower the dietary cation-anion difference (DCAD), in the prepartum period is safe and effective for preventing milk fever in multiparous cows. In the present study, several clinico-pathological constituents in serum and urine, which might be related to milk fever, were analyzed using stored samples from the previous study to identify clinico-pathological parameters for easily evaluating the efficacy of lowering DCAD and to further investigate the mechanism by which lowering DCAD prevents milk fever. Among the parameters analyzed in the present study, inorganic phosphorus (iP) was involved in milk fever because the serum concentration and urinary excretion of iP were significantly higher in the group of primiparous cows (heifer group), which did not develop hypocalcemia, than those in other groups of multiparous cows. Serum chloride concentrations in the heifer group and the group of multiparous cows fed anion salts (anion group) tended to remain higher than those in other control groups of multiparous cows suggesting that serum chloride concentration may be utilized for evaluating the status of metabolic acidosis and the efficacy of lowerng DCAD in dairy cows fed anion salts. In addition, plasma estradiol-17beta concentration in the heifer group tended to be lower at parturition compared with that in other multiparous groups suggesting that estrogen known as a potent inhibitor of bone resorption may be involved in developing milk fever.

Preventive strategies and risk factors for milk fever in Danish dairy herds: a questionnaire survey.

Milk fever is a commonly recognized production disease in dairy cows around parturition. The aim of this questionnaire survey was therefore to investigate milk fever preventive strategies used in Danish dairy herds during 1998, to explore the reasons for choosing a specific strategy, and finally to evaluate possible risk factors for milk fever occurrences. A random sample of 230 milk producers (MP) was drawn from the Danish Cattle Database. A telephone interview (TI) was used to collect data. A sub-sample of 25% MPs was chosen by systematic random sampling and interviewed a second time (TI(2)). Descriptive analysis of all answers was performed. The agreement between TI(1) and TI(2) was evaluated using Cohen's kappa coefficient and the overall intra-MP agreement. Risk factors (such as housing systems or use of milk fever preventive strategies) for differences in milk fever incidences between herds were evaluated using logistic regression. This investigation revealed that Danish MPs focused on a few well-described milk fever preventive principles and other management methods, such as reduced milking and management of body condition. There was no significant difference in risk of developing milk fever using different prevention strategies (p=0.80). Furthermore, the logistic regression did not indicate an association between reported milk fever cases and the assessments of this as a problem or not (p=0.09). Tie stalls increased the risk of milk fever compared to loose housing systems (p=0.019). There was a significant difference in risk of milk fever between parities. The overall milk fever incidence risk was 3.0%.

Biomarkers for the activation of calcium metabolism in dairy cows: elevation of tartrate-resistant acid phosphatase activity by lowering dietary cation-anion difference is associated with the prevention of milk fever.

In our previous study, it was demonstrated that the administration of anion salts, which slightly lower the dietary cation-anion difference (DCAD), in the prepartum period is safe and effective for preventing milk fever in multiparous cows. In the present study, several biomarkers, which might show activation of Ca metabolism, were analyzed using stored samples in the previous study to investigate the mechanism of the preventive effect on milk fever by lowering DCAD. Changes in bone-specific alkaline phosphatase activity, osteocalcin and insulin-like growth factor I concentrations in serum were almost the same among the three groups of multiparous cows with or without the oral administration of anion salts, while the levels of these serum biomarkers in the group of primiparous cows (heifer group) were much higher compared with those in the three multiparous groups throughout the experimental period. Urinary deoxypyridinoline excretion was not a useful biomarker for dairy cows because it hardly changed during the peripartum period in all groups. However, serum tartrate-resistant acid phosphatase (TRAP) activity, which is known as a biomarker of osteoclast activity, was well associated with the administration of anion salts lowering DCAD because among the three multiparous groups, only the group of multiparous cows fed the anion salts (anion group) showed an increased level, which rose to the level in the heifer group, and was markedly higher than those in the other control groups of multiparous cows. The increased activity of serum TRAP in the anion group suggested that Ca in the plasma pool was mobilized smoothly from bone-bound Ca via mature osteoclasts at parturition, which might be due to prior activation under mild acidosis induced by slightly lowering DCAD. Therefore, TRAP was the best biomarker to monitor the activation of Ca metabolism in dairy cows fed anion salts.

Preventive effect of mildly altering dietary cation-anion difference on milk fever in dairy cows.

In the present study, we examined whether mildly altering dietary cation-anion difference (DCAD) contributes to the prevention of milk fever in dairy cows. Thirty multiparous cows and ten primiparous cows (heifer group) were used in this study and the multiparous cows were randomly divided into three groups of ten animals each (anion, non-anion and control groups). The cows in the anion group were given supplemental salts that slightly lowered DCAD. These salts consisted of 115 g of CaCO3, 42 g of CaHPO4, 65 g of MgSO4 x 7 H2O and 80 g of CaCl2 x 2 H2O as a daily dose for each cow, using a catheter from 21 days before the expected date of parturition until parturition. The cows in the non-anion group were given only the same Ca, Mg and ip supplement but no sulfate and chloride salts as that in the anion group. The cows in the control and heifer groups were not given any additional supplement. The incidence of hypocalcemia in the anion group decreased to approximately half of those in the non-anion and control groups, while the heifer group did not develop hypocalcemia at all. In addition, the number of days spent for the treatment of hypocalcemia and the number of drug bottles (calcium borogluconate solution) used for the treatment decreased to less than half in the anion group compared with those in the non-anion and control groups. At parturition, the serum Ca concentration in the control (6.2 +/- 1.9 mg/dl, mean +/- standard deviation) and non-anion groups (6.4 +/- 1.7 mg/dl) were significantly lower than that in the heifer group (8.3 +/- 0.4 mg/dl), and the level in the anion group was intermediate (7.3 +/- 1.3 mg/dl). The change in ionized Ca concentration was almost the same as that in serum Ca concentration, but only the concentration in the anion group tended to increase slightly from a week before parturition and was significantly higher than that in all other groups three days before parturition. Urinary pH in the anion group was maintained at a mildly acidic level (6.8-7.0) for the last two weeks before parturition, compared with those in the control (7.3-7.5) and non-anion groups (7.9-8.1), and similar to that in the heifer group (6.3-7.3). The urinary Ca excretion was the highest in the anion group among all groups during the prepartum period. There were no specific changes in the excretion of parathyroid hormone and 1,25-dihydroxyvitamin D in all groups of multiparous cows while the levels of these hormones remained low in the heifer group throughout the experimental period. The data in the present study indicates that the administration of anion salts that slightly lowered DCAD in the preparum period was effective for preventing milk fever in multiparous cows. Safe and mild metabolic acidosis induced by the anion salts could be evaluated by urinary pH (6.8-7.0), and might increase the responsiveness to Ca requirement at parturition through some complex mechanisms unrelated to the excretion of Ca-related hormones. In addition, it was clarified that primiparous cows have a high potential to respond to sudden Ca demand unrelated to hormone excretion, and their Ca metabolism was in some respects similar to that in multiparous cows fed anion salts. Therefore, manipulating mildly DCAD is expected to be an effective, safe and natural method for preventing milk fever in dairy cows.