Blood calcium dynamics after prophylactic treatment of subclinical hypocalcemia with oral or intravenous calcium

Total serum Ca dynamics and urine pH levels were evaluated after prophylactic treatment of subclinical hypocalcemia after parturition in 33 multiparous Jersey × Holstein crossbreed cows. Cows were blocked according to their calcemic status at the time of treatment [normocalcemic (8.0–9.9 mg/dL; n = 15) or hypocalcemic (5.0–7.9 mg/dL; n = 18)] and randomly assigned to 1 of 3 treatments: control [no Ca supplementation (n = 11)]; intravenous Ca [Ca-IV (n = 11), 500 mL of 23% calcium gluconate (10.7 g of Ca and 17.5 g of boric acid as a solubilizing agent; Durvet, Blue Springs, MO)]; or oral Ca [Ca-Oral (n = 11), 1 oral bolus (Bovikalc bolus, Boehringer Ingelheim, St. Joseph, MO) containing CaCl₂ and CaSO₄ (43 g of Ca) 2 times 12 h apart]. Total serum Ca levels were evaluated at 0, 1, 2, 4, 8, 12, 16, 20, 24, 36, and 48 h, and urine pH was evaluated at 0, 1, 12, 24, 36, and 48 h after treatment initiation. Total serum Ca levels were higher for Ca-IV than for control and Ca-Oral cows at 1, 2, and 4 h after treatment initiation, but lower than Ca-Oral cows at 20, 24, and 36 h and lower than control cows at 36 and 48 h. At 1 h after treatment initiation, when serum Ca levels for Ca-IV cows peaked (11.4 mg/dL), a greater proportion of Ca-IV (n = 8) cows had total serum Ca levels >10 mg/dL than control (n = 0) and Ca-Oral (n = 1) cows. At 24 h after treatment initiation, when Ca-IV cows reached the total serum Ca nadir (6.4 mg/dL), a greater proportion of Ca-IV (n = 10) cows had serum Ca levels <8 mg/dL than control (n = 5) and Ca-Oral (n = 2) cows. Treatment, time, and treatment × time interaction were significant for urine pH. Mean urine pH was lower for Ca-Oral cows (6.69) than for control (7.52) and Ca-IV (7.19) cows. Urine pH levels at 1 h after treatment were lower for Ca-IV cows compared with both control and Ca-Oral cows, a finding likely associated with the iatrogenic administration of boric acid added as a solubilizing agent of the intravenous Ca solution used. At 12, 24, and 36 h, urine pH levels were lower for Ca-Oral cows compared with both control and Ca-IV cows. This was expected because the oral Ca supplementation used (Bovikalc) is designed as an acidifying agent. Wide fluctuations in blood Ca were observed after prophylactic intravenous Ca supplementation. The implications for milk production and animal health, if any, of these transient changes in total serum Ca have yet to be evaluated.     

The effect of zeolite A supplementation in the dry period on periparturient calcium,phosphorus, and magnesium homeostasis

One potential way of preventing parturient hypocalcemia in the dairy cow is to feed dry cow rations very low in calcium (<20 g/d); but, because it is difficult to formulate rations sufficiently low in calcium, this principle has been almost abandoned. Recent studies have shown, however, that it is possible to prevent milk fever, as well as subclinical hypocalcemia, by supplementing the dry cow ration with sodium aluminium silicate (zeolite A), which has the capacity to bind calcium. The aim of this study was to further evaluate the effect, if any, of such supplementation on other blood constituents, feed intake, and milk production in the subsequent lactation. A total of 31 pregnant dry cows about to enter their third or later lactation were assigned as experimental or control cows according to parity and expected date of calving. The experimental cows received 1.4 kg of zeolite pellets per d (0.7 kg of pure zeolite A) for the last 2 wk of pregnancy. Blood samples were drawn from all cows 1 wk before the expected date of calving, at calving, at d 1 and 2 after calving, and 1 wk after calving. Additionally, a urine sample was drawn 1 wk before the expected date of calving. Zeolite supplementation significantly increased the plasma calcium level on the day of calving, whereas plasma magnesium as well as inorganic phosphate was suppressed. Serum 1,25(OH)2D was significantly increased 1 wk before the expected date of calving among the experimental cows, whereas there was no difference in the urinary excretion of the bone metabolite deoxypyridinoline between the two groups. Feed intake was decreased among the zeolite-treated cows during the last 2 wk of pregnancy. No effect was observed on milk yield, milk fat, and milk protein in the subsequent lactation. The mechanisms and interactions involved in zeolite supplementation are discussed in relation to the observed improvement in parturient calcium homeostasis and to the observed depression in blood magnesium and inorganic phosphate.     

Controlled trial of the effect of negative dietary cation-anion difference prepartum diets on milk production,reproductive performance,and culling of dairy cows

Our objective was to assess the effects of feeding negative dietary cation-anion difference (DCAD) prepartum diets on milk production, reproductive performance, and culling. Cows from 4 commercial farms in Ontario, Canada were enrolled in a pen-level controlled trial from November 2017 to April 2019. Close-up pens (1 per farm) with cows 3 wk before calving were randomly assigned to a negative DCAD (TRT; ?108 mEq/kg of dry matter; target urine pH 6.0–6.5) or a control diet (CON; +105 mEq/kg of dry matter with a placebo supplement). Each pen was fed TRT or CON for 3 mo (1 period), and then switched to the other treatment for the next period (4 periods per farm). Data from 15 experimental units (8 pen treatments in TRT and 7 in CON), with a total of 1,086 observational units (cows), were included. The effect of treatment on milk yield at the first 3 milk recording tests of lactation was assessed with linear regression models accounting for repeated measures. The risk of pregnancy at first artificial insemination and culling by 30, 60, and 305 d in milk (DIM) were analyzed with logistic regression models, and effects on time to first AI, pregnancy, and culling were assessed with Cox proportional hazards models. All models included treatment, parity, and their interactions, accounting for pen-level randomization and clustering of animals within farm with random effects, giving 10 degrees of freedom for treatment effects. Multiparous cows fed TRT produced more milk at the first (42.0 vs. 38.8 ± 1.2 kg/d) and second (44.2 vs. 41.7 ± 1.3 kg/d) milk tests. However, multiparous cows fed TRT tended to have 0.2 percentage units less milk fat content at these tests. Although multiparous cows fed TRT tended to have greater energy-corrected milk at the first test (least squares means ± standard error: TRT = 46.1 ± 0.9 vs. CON = 43.8 ± 1 kg/d), there were no differences observed in energy-corrected milk at the second or third tests. In primiparous cows, there was no effect of treatment on milk production. Multiparous cows fed TRT had greater pregnancy to first insemination (TRT = 42 ± 3 vs. CON = 32 ± 4%) and tended to have shorter time to pregnancy [hazard ratio (HR) = 1.20; 95% CI: 0.96–1.49]. In primiparous cows fed TRT, time to pregnancy was increased (HR = 0.76; 95% CI: 0.59–0.99). Culling by 30 DIM tended to be less in TRT (3.3 ± 1.1%) than CON (5.5 ± 1.8%). No effect of treatment on culling by 305 DIM was detected in primiparous cows, but in multiparous cows, the TRT diets decreased the odds of culling (21.3 ± 1.9 vs. 31.7 ± 2.8%) and daily risk of culling to 305 DIM (HR = 0.64; 95% CI: 0.46 to 0.89). Under commercial herd conditions, prepartum negative DCAD diets improved milk production and reproductive performance, and reduced culling risk in multiparous cows. In primiparous cows, TRT diets had no effect on milk yield or culling, but increased the time to pregnancy. Our results suggest that negative DCAD diets should be targeted to multiparous cows.     

Subclinical hypocalcemia,plasma biochemical parameters,lipid metabolism,postpartum disease,and fertility in postparturient dairy cows

A study was conducted to evaluate the potential association between Ca status at calving and postpartum energy balance, liver lipid infiltration, disease occurrence, milk yield and quality parameters, and fertility in Holstein cows. One hundred cows were assigned to 1 of 2 groups based on whole-blood ionized Ca concentration ([iCa]) on the day of calving [d 0; hypocalcemic [iCa] <1.0 mmol/L (n = 51); normocalcemic [iCa] ≥1.0 mmol/L (n = 49)]. Cows were blocked based on calving date and parity. Blood samples were collected approximately 14 d from expected calving date (d −14), the day of calving (d 0), and on d 3, 7, 14, 21, and 35 postpartum for measurement of plasma nonesterified fatty acid, iCa, total Ca, glucose, and total and direct bilirubin concentrations, and plasma aspartate aminotransferase and gamma glutamyl transferase activities. Liver biopsies were obtained from a subset of cows on d 0, 7, and 35 for quantification of lipid content. Milk samples were collected on d 3, 7, 14, 21, and 35 postpartum for measurement of somatic cell count and percentages of protein, fat, and solids-not-fat. Data for peak test-day milk yield, services per conception, and days open were obtained from Dairy Herd Improvement Association herd records. Disease occurrence was determined based on herd treatment records. Hypocalcemic cows had significantly higher nonesterified fatty acids on d 0. Hypocalcemic cows also had significantly more lipid in hepatocytes on d 7 and 35 postpartum. However, no statistically significant differences were observed between groups for plasma aspartate aminotransferase and gamma glutamyl transferase activities or total and direct bilirubin concentrations. Milk protein percentage was lower in hypocalcemic cows on d 21 and 35. However other milk quality variables (somatic cell count, milk fat percentage, and solids-not-fat) and milk yield variables (peak test-day milk yield and 305-d mature-equivalent 4% fat-corrected milk yield) did not differ between groups. No differences were observed between groups in the occurrence of clinical mastitis, ketosis, displaced abomasum, dystocia, retained placenta, metritis, or fertility measures (percentage cycling at 50–60 d postpartum, services per conception, or days open). These data suggest that early lactation fatty acid metabolism differs between cows with subclinical hypocalcemia and their normocalcemic counterparts.     

Applications of Metabolomics in Calcium Metabolism Disorders in Humans

The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, the present review highlights the potential of metabolomics in identifying the biomarkers of some of the most common endocrine disorders, such as primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), calcium deficiency, osteoporosis and vitamin D supplementation. Metabolites related to above-mentioned diseorders were grouped into specific classes and mapped into metabolic pathways. Furthermore, disturbed metabolic pathways can open up new directions for the in-depth exploration of the basic mechanisms of these diseases at the molecular level.     

Timothy hay with a low dietary cation-anion difference improves calcium homeostasis in periparturient Holstein cows

The current study was undertaken to evaluate the effects of feeding timothy (Phleum pratense L.) hay differing in dietary cation-anion difference (DCAD) on the capability of cows to maintain calcium homeostasis around parturition. We hypothesized that feeding low-DCAD timothy hay during the prepartum period would induce a mild metabolic acidosis prepartum and improve calcium homeostasis postpartum with no effect on dry matter intake. Forty-one dry pregnant Holstein cows entering their second lactation or greater were used in a randomized complete block design. Timothy hay was obtained from an established timothy stand under a pivot irrigation system. Low-DCAD timothy hay was produced by fertilizing the area between the second and third pivot towers at a rate of 224 kg of CaCl₂/ha, and control timothy hay (high DCAD) was grown on the area between the fourth and fifth pivot towers of the same field. The chloride concentration was 1.07 and 0.15% on a dry matter (DM) basis, and the DCAD was 1.2 and 21.6 mEq/100 g of DM for the low- and high-DCAD timothy hay, respectively. Experimental diets, containing timothy hay at 63% of dietary DM, were fed ad libitum starting 30 d before the expected calving date. The DCAD values were 1.6 vs. 14.5 mEq/100 g of DM for the low- and high-DCAD timothy-based diets, respectively. At the beginning of the study, urine pH and blood bicarbonate concentration averaged 8.22 ± 0.06 and 28.5 ± 0.3 mM, respectively. The low-DCAD timothy diet decreased urine pH compared with the high-DCAD timothy diet on d 21 (7.75 vs. 8.31), d 14 (7.69 vs. 8.22), and d 7 (7.50 vs. 8.19) before calving, and it also decreased the prepartum blood bicarbonate concentration by 2 mM. In addition, cows fed the low-DCAD timothy diet had greater blood ionized calcium concentration prepartum (1.22 vs. 1.19 mM), greater blood ionized calcium concentration at 0 and 8 h after calving, and similar prepartum dry matter intake. These results indicate that timothy hay differing in DCAD affects the acid-base balance of periparturient dairy cows, and that low-DCAD timothy hay improves calcium homeostasis postpartum with no negative effect on dry matter intake.     

Short communication: Effect of dietary phosphorus deprivation in late gestation and early lactation on the calcium homeostasis of periparturient dairy cows

Environmental concerns with P of animal origin polluting surface waters are leading to legal incentives aimed at reducing the dietary P content of dairy cow rations to the lowest possible level that does not negatively affect health and productivity. The objective of the present study was to determine the effect of feeding rations with low dietary P content in late gestation on the Ca homeostasis of the periparturient dairy cow. Eighteen multiparous dairy cows were either fed a P-deficient (0.15% P in dry matter antepartum and 0.20% P in dry matter postpartum) but otherwise balanced ration or a control ration with adequate P content (0.28% P in dry matter antepartum and 0.44% P in dry matter postpartum) during the last 4 wk of gestation until d 10 postpartum. Blood was obtained before initiation of P-deprivation (baseline) and ?10, ?2, +1, +3, and +10 d relative to parturition to be analyzed for plasma concentrations of Ca [Ca] and inorganic phosphate [Pi]. In addition, plasma concentrations of parathyroid hormone [PTH], the bone resorption marker CrossLaps [CTX], 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined in a subset of samples. Feeding a P-deficient diet for 4 wk antepartum positively affected the Ca homeostasis of periparturient cows. Clinical hypocalcemia occurred in 3/9 control and 0/9 P-deprived cows. [Calcium], [PTH], and plasma concentrations of vitamin D metabolites did not differ between groups until parturition, whereas [Pi] was decreased and [CTX] significantly increased in P-deprived animals. At parturition [PTH] was significantly greater in control cows compared with P-depleted cows. The P-deprived cows had significantly higher [Ca] than control cows on d +1 (2.46 ± 0.11 vs. 2.27 ± 0.41 mmol/L) and +2 (2.61 ± 0.13 vs. 2.35 ± 0.25 mmol/L). Plasma [CTX] was significantly higher in P-deprived than in control cows on d +2. Bone resorption and the typical increase in 1,25-dihydroxyvitamin D in periparturient P-deprived cows seemed to occur despite the smaller rise of [PTH], suggesting either greatly increased sensitivity to PTH or bone mobilization independent of PTH. Future studies must explore potentially negative effects of P-deprivation antepartum on health and productivity of the dairy cow in the following lactation.     

Effects of supplementation with ruminally protected choline on performance of multiparous Holstein cows did not depend upon prepartum caloric intake

Objectives were to evaluate the effect of prepartum energy intake on performance of dairy cows supplemented with or without ruminally protected choline (RPC; 0 or 17.3 g/d of choline chloride; 0 or 60 g/d of ReaShure, Balchem Corp., New Hampton, NY). At 47 ± 6 d before the expected calving date, 93 multiparous Holstein cows were assigned randomly to 1 of 4 dietary treatments in a 2 × 2 factorial arrangement. Cows were fed energy to excess [EXE; 1.63 Mcal of net energy for lactation/kg of dry matter (DM)] or to maintenance (MNE; 1.40 Mcal of net energy for lactation/kg of DM) in ad libitum amounts throughout the nonlactating period. The RPC was top-dressed for 17 ± 4.6 d prepartum through 21 d postpartum (PP). After calving, cows were fed the same methionine-balanced diet, apart from RPC supplementation, through 15 wk PP. Liver was biopsied at ?14, 7, 14, and 21 d relative to parturition. Cows fed EXE or MNE diets, respectively, consumed 40 or 10% more Mcal/d than required at 15 d before parturition. Cows fed the MNE compared with the EXE diet prepartum consumed 1.2 kg/d more DM postpartum but did not produce more milk (41.6 vs. 43.1 kg/d). Thus, PP cows fed the EXE diet prepartum were in greater mean negative energy balance, tended to have greater mean concentrations of circulating insulin, fatty acids, and β-hydroxybutyrate, and had greater triacylglycerol in liver tissue (8.3 vs. 10.7% of DM) compared with cows fed the MNE diet prepartum. Cows fed RPC in transition tended to produce more milk (43.5 vs. 41.3 kg/d) and energy-corrected milk (44.2 vs. 42.0 kg/d) without increasing DM intake (23.8 vs. 23.2 kg/d) during the first 15 wk PP, and tended to produce more milk over the first 40 wk PP (37.1 vs. 35.0 kg/d). Energy balance of cows fed RPC was more negative at wk 2, 3, and 6 PP, but mean circulating concentrations of fatty acids and β-hydroxybutyrate did not differ from those of cows not fed RPC. Despite differences in energy balance at 2 and 3 wk PP, mean concentration of hepatic triacylglycerol did not differ between RPC treatments. Feeding RPC reduced the daily prevalence of subclinical hypocalcemia from 25.5 to 10.5%, as defined by concentrations of total Ca of <8.0 mg/dL in serum in the first 7 d PP. Pregnancy at first artificial insemination tended to be greater for cows fed RPC (41.3 vs. 23.6%), but the proportion of pregnant cows did not differ by 40 wk PP. Heifers born from singleton calvings from cows fed RPC tended to experience greater daily gain between birth and 50 wk of age than heifers from cows not supplemented with RPC. Feeding RPC for approximately 38 d during the transition period tended to increase yield of milk for 40 wk regardless of amount of energy consumed during the pregnant, nonlactating period.     

Effects of prepartum dietary cation-anion difference on aspects of peripartum mineral and energy metabolism and performance of multiparous Holstein cows

The objectives of this study were to determine the effect of decreasing dietary cation-anion difference [DCAD; (Na⁺ + K⁺) ? (Cl^? + S^2?)] of the prepartum diet on aspects of mineral metabolism, energy metabolism, and performance of peripartum dairy cows. Multiparous Holstein cows (n = 89) were enrolled between 38 and 31 d before expected parturition and randomized to treatments in a completely randomized design (restricted to balance for previous 305-d mature equivalent milk production, parity, and body condition score) at 24 d before expected parturition. Treatments consisted of a low-K ration without anion supplementation [CON; n = 30, DCAD = +18.3 mEq/100 g of dry matter (DM)]; partial anion supplementation to a low-K ration (MED; n = 30, DCAD = +5.9 mEq/100 g of DM); and anion supplementation to a low-K ration to reach a targeted average urine pH between 5.5 and 6.0 (LOW; n = 29, DCAD = ?7.4 mEq/100 g of DM). Cows were fed a common postpartum diet and data collected through 63 d in milk. Urine pH (CON = 8.22, MED = 7.89, and LOW = 5.96) was affected quadratically by decreasing prepartum DCAD. A linear relationship between urine pH and urine Ca:creatinine ratio was observed (r = ?0.81). Plasma Ca concentrations in the postpartum period (d 0 to 14; CON = 2.16, MED = 2.19, and LOW = 2.27 mmol/L) were increased linearly with decreasing prepartum DCAD. A treatment by parity (second vs. third and greater) interaction for postpartum plasma Ca concentration suggested that older cows had the greatest response to the low DCAD diet and older cows fed LOW had decreased prevalence of hypocalcemia after calving. A quadratic effect of decreasing DCAD on prepartum DMI was observed (CON = 13.6, MED = 14.0, and LOW = 13.2 kg/d). Milk production in the first 3 wk postpartum was increased linearly with decreasing DCAD (CON = 40.8, MED = 42.4, and LOW = 43.9 kg/d) and DMI in this period also tended to linearly increase (CON = 20.2, MED = 20.9, and LOW = 21.3 kg/d). Overall, effects on intake and milk yield analyzed over wk 1 to 9 postpartum were not significant. This study demonstrates that feeding lower DCAD diets prepartum improves plasma Ca status in the immediate postpartum period and results in increased DMI and milk production in the 3 wk after parturition. Compared with no anion supplementation or lower levels of anion supplementation, greater improvements were observed with the lower DCAD feeding strategy, in which an average urine pH of 5.5 to 6.0 was targeted.     

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.