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Nutritional Calcium Supply Dependent Calcium Balance, Bone Calcification and Calcium Isotope Ratios in Rats

ABSTRACT: Serum calcium isotopes (δ44/42Ca) have been suggested as a non-invasive and sensitive Ca balance marker. Quantitative δ44/42Ca changes associated with Ca flux across body compartment barriers relative to the dietary Ca and the correlation of δ44/42CaSerum with bone histology are unknown. We analyzed Ca and δ44/42Ca by mass-spectrometry in rats after two weeks of standard-Ca-diet (0.5%) and after four subsequent weeks of standard- and of low-Ca-diet (0.25%). In animals on a low-Ca-diet net Ca gain was 61 ± 3% and femur Ca content 68 ± 41% of standard-Ca-diet, bone mineralized area per section area was 68 ± 15% compared to standard-Ca-diet. δ44/42Ca was similar in the diets, and decreased in feces and urine and increased in serum in animals on low-Ca-diet. δ44/42CaBone was higher in animals on low-Ca-diet, lower in the diaphysis than the metaphysis and epiphysis, and unaffected by gender. Independent of diet, δ44/42CaBone was similar in the femora and ribs. At the time of sacrifice, δ44/42CaSerum inversely correlated with intestinal Ca uptake and histological bone mineralization markers, but not with Ca content and bone mineral density by µCT. In conclusion, δ44/42CaBone was bone site specific, but mechanical stress and gender independent. Low-Ca-diet induced marked changes in feces, serum and urine δ44/42Ca in growing rats. δ44/42CaSerum inversely correlated with markers of bone mineralization.

SUBMITTER: Rott J

PROVIDER: S-EPMC9322359 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We assessed the potential of Calcium (Ca) isotope fractionation measurements in blood (δ44/42CaBlood) and urine (δ44/42CaUrine) as a new biomarker for the diagnosis of osteoporosis. One hundred post-menopausal women aged 50 to 75 years underwent dual-energy X-ray absorptiometry (DXA), the gold standard for determination of bone mineral density. After exclusion of women with kidney failure and vitamin D deficiency (<25 nmol/l) 80 women remained in the study. Of these women 14 fulfilled the standard diagnostic criteria for osteoporosis based on DXA. Both the δ44/42CaBlood (p < 0.001) and δ44/42CaUrine (p = 0.004) values were significantly different in women with osteoporosis (δ44/42CaBlood: -0.99 ± 0.10‰, δ 44/42CaUrine: +0.10 ± 0.21‰, (Mean ± one standard deviation (SD), n = 14)) from those without osteoporosis (δ44/42CaBlood: -0.84 ± 0.14‰, δ44/42CaUrine: +0.35 ± 0.33‰, (SD), n = 66). This corresponded to the average Ca concentrations in morning spot urine samples ([Ca]Urine) which were higher (p = 0.041) in those women suffering from osteoporosis ([Ca]Urine-Osteoporosis: 2.58 ± 1.26 mmol/l, (SD), n = 14) than in the control group ([Ca]Urine-Control: 1.96 ± 1.39 mmol/l, (SD), n = 66). However, blood Ca concentrations ([Ca]Blood) were statistically indistinguishable between groups ([Ca]Blood, control: 2.39 ± 0.10 mmol/l (SD), n = 66); osteoporosis group: 2.43 ± 0.10 mmol/l (SD, n = 14) and were also not correlated to their corresponding Ca isotope compositions. The δ44/42CaBlood and δ44/42CaUrine values correlated significantly (p = 0.004 to p = 0.031) with their corresponding DXA data indicating that both Ca isotope ratios are biomarkers for osteoporosis. Furthermore, Ca isotope ratios were significantly correlated to other clinical parameters ([Ca]Urine, ([Ca]Urine/Creatinine)) and biomarkers (CRP, CTX/P1NP) associated with bone mineralization and demineralization. From regression analysis it can be shown that the δ44/42CaBlood values are the best biomarker for osteoporosis and that no other clinical parameters need to be taken into account in order to improve diagnosis. Cut-off values for discrimination of subjects suffering from osteoporosis were - 0.85‰ and 0.16‰ for δ44/42CaBlood and δ44/42CaUrine, respectively. Corresponding sensitivities were 100% for δ44/42CaBlood and ~79% for δ44/42CaUrine. Apparent specificities were ~55% for δ44/42CaBlood and ~71%. The apparent discrepancy in the number of diagnosed cases is reconciled by the different methodological approaches to diagnose osteoporosis. DXA reflects the bone mass density (BMD) of selected bones only (femur and spine) whereas the Ca isotope biomarker reflects bone Ca loss of the whole skeleton. In addition, the close correlation between Ca isotopes and biomarkers of bone demineralization suggest that early changes in bone demineralization are detected by Ca isotope values, long before radiological changes in BMD can manifest on DXA. Further studies are required to independently confirm that Ca isotope measurement provide a sensitive, non-invasive and radiation-free method for the diagnosis of osteoporosis.

Project description:Latin America is an important contributor to the worldwide beef business, but in general, there are limited studies considering strategies to reduce nitrogen contamination in their production systems. The study's goal was to assess the effect of two nutritional strategies to balance energy and protein supply in fattening heifers on performance, ruminal metabolism, and carcass characteristics. A total of 24 crossbred heifers (initial body weight 'BW 'of 372 ± 36 kg) were used to create two blocks (based on live weight) of two pens each, that were equipped with individual feeders. Within each block, half of the animals were assigned to a diet based on tabular Crude Protein (CP) requirements denominated Crude Protein Diet 'CPD' but without a ruminal degradable protein balance. The other half received a diet denominated Metabolizable Protein Diet 'MPD', formulated with the metabolizable protein system, balanced for the ruminal degradable protein. Both diets had the same ingredients and as well as similar synchrony indexes (0.80 and 0.83, respectively). For nitrogen concentration in feces and urine as well as microbial crude protein synthesis, a total of 12 heifers (three per pen) were randomly selected to collect samples. The dataset was analyzed as a randomized complete block design with a 5% significance. No diet × time interaction was observed for Average Daily Gain 'ADG' (p = 0.89), but there was an effect of the time on ADG (p ? 0.001). No differences were observed neither for final weight, dry matter intake 'DMI', and feed conversion rate (p > 0.05). Heifers fed with CPD showed greater cold carcass weight (p = 0.041), but without differences in ribeye area, backfat thickness, pH, dressing %, and marbling (p > 0.05). Differences between diets were observed for the in vitro parameters as well as for the Total Volatile Fatty Acids 'VFA' and NH3 (p < 0.05). Total N concentrations (urine + feces) of heifers fed with MDP was lower than in those fed with the CPD (p < 0.01), but no differences were observed in microbial protein, purine derivatives, and creatinine (p > 0.05). We conclude that the combination of synchrony and the metabolizable protein system achieve greater efficiency in the use of nitrogen, without negatively affecting animals' performance or the quality of the carcass.

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Nutritional Calcium Supply Dependent Calcium Balance, Bone Calcification and Calcium Isotope Ratios in Rats

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