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Aim: Klotho, a key component of the endocrine fibroblast growth factor receptor—fibroblast growth factor axis, is a multi‐functional protein that impacts renal electrolyte handling. The physiological significance of Klotho will be highlighted in the regulation of calcium, phosphate, and potassium metabolism. Methods: In this review, we compare several murine models with different renal targeted deletions of Klotho and the insights into the molecular and physiological function that these models offer. Results: In vivo, Klotho deficiency is associated with severely impaired mineral metabolism, with consequences on growth, longevity and disease development. Additionally, we explore the perspectives of Klotho in renal pathology and vascular events, as well as potential Klotho treatment options. Conclusion: This comprehensive review emphasizes the use of Klotho to shed light on deciphering the renal molecular in vivo mechanisms in electrolyte handling, as well as novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Chronic kidney disease mineral bone disorder (CKD-MBD) is a complex clinical syndrome responsible for the accelerated cardiovascular mortality seen in individuals afflicted with CKD. Current approaches to therapy have failed to improve clinical outcomes adequately, likely due to targeting surrogate biochemical parameters as articulated by the guideline developer, Kidney Disease: Improving Global Outcomes (KDIGO). We hypothesized that using a Systems Biology Approach combining machine learning with mathematical modeling, we could test a novel approach to therapy targeting the abnormal movement of mineral out of bone and into soft tissue that is characteristic of CKD-MBD. The mathematical model describes the movement of calcium and phosphate between body compartments in response to standard therapeutic agents. The machine-learning technique we applied is reinforcement learning (RL). We compared calcium, phosphate, parathyroid hormone (PTH), and mineral movement out of bone and into soft tissue under four scenarios: standard approach (KDIGO), achievement of KDIGO guidelines using RL (RLKDIGO), targeting abnormal mineral flux (RLFLUX), and combining achievement of KDIGO guidelines with minimization of abnormal mineral flux (RLKDIGOFLUX). We demonstrate through simulations that explicitly targeting abnormal mineral flux significantly decreases abnormal mineral movement compared with standard approach while achieving acceptable biochemical outcomes. These investigations highlight the limitations of current therapeutic targets, primarily secondary hyperparathyroidism, and emphasize the central role of deranged phosphate homeostasis in the genesis of the CKD-MBD syndrome. NEW & NOTEWORTHY: Artificial intelligence is a powerful tool for exploration of complex processes but application to clinical syndromes is challenging. Using a mathematical model describing the movement of calcium and phosphate between body compartments combined with machine learning, we show the feasibility of testing alternative goals of therapy for Chronic Kidney Disease Mineral Bone Disorder while maintaining acceptable biochemical outcomes. These simulations demonstrate the potential for using this platform to generate and test hypotheses in silico rapidly, inexpensively, and safely. [ABSTRACT FROM AUTHOR]

Osteopontin (OPN) is a multi‐functional glycoprotein that coordinates the innate immune response, prevents nanocrystal formation in renal tubule fluid, and is a biomarker for kidney injury. OPN expression is markedly increased in cystic epithelial cells of polycystic kidney disease (PKD) kidneys; however, its role in PKD progression remains unclear. We investigated the in vitro effects of recombinant OPN on the proliferation of tubular epithelial cells from PKD and normal human kidneys and in vivo effects of OPN deletion on kidney cyst formation, fibrosis, and mineral metabolism in pcy/pcy mice, a non‐orthologous model of autosomal‐dominant PKD. In vitro studies revealed that OPN enhanced the proliferation of PKD cells but had no effect on normal kidney cells. Deletion of OPN in pcy/pcy mice significantly reduced kidney cyst burden; however, this was accompanied by increased fibrosis and no change in kidney function. The loss of OPN had no effect on kidney macrophage numbers, cyst epithelial cell proliferation, or apoptosis. Furthermore, there was no difference in kidney mineral deposition or mineral metabolism parameters between pcy/pcy mice with and without OPN expression. Global deletion of OPN reduced kidney cyst burden, while paradoxically exacerbating kidney fibrosis in mice with cystic kidney disease. [ABSTRACT FROM AUTHOR]

This study looked at how desalinated seawater, which has low minerals and high boron, could affect bone health. Prior research suggests that low mineral water may harm bone health and boron could be beneficial, but the overall impact on bone health is still unclear. Eighty-nine-week-old male Balb/C mice were allocated into eight groups and administered either tap water or purified water with varying boron concentrations (0, 5, 40, and 200 mg/L). They were kept in an environment mimicking tropical conditions (35–40 °C, 70–80% humidity) and underwent daily treadmill exercise for 13 weeks. At the 14th week, serum, femora, and lumbar vertebrae were collected for mineral metabolism, bone biomarker, microstructure, and biomechanics evaluation. Boron exposure improved bone formation, microstructure, and biomechanics initially but the benefits weakened with higher levels of exposure (p < 0.05). Co-exposure to purified water elevated serum boron but weakened the promotion of boron on bone minerals and the bone benefits of boron compared to tap water (p < 0.05). Thus, when studying the health effects of boron in desalinated seawater, it is crucial to look at various health effects beyond bone health. Furthermore, it is important to consider the mineral composition of drinking water when using boron for bone health benefits. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is prevalent in 25% of Americans. However, 25(OH)D may not be an accurate measure of vitamin D because the majority (85%-90%) of 25(OH)D is bound to vitamin D binding protein (VDBP), which varies by over 30% across individuals. Free 25(OH)D may be a better measure, but it is difficult to measure accurately and precisely. The existing free 25(OH)D estimating equation does not include VDBP phenotypes; therefore, new equations that include this variable may be more accurate. A total of 370 participants in the Health, Aging, and Body Composition Study, a cohort of healthy community-dwelling individuals aged 70-79 years old, underwent VDBP and vitamin D metabolite [25(OH)D, 24,25(OH)2D, 1,25(OH)2D, free 25(OH)D] measurements and were randomly allocated into equation development (two out of three) and internal validation (one out of three) groups. New equations were developed with multiple linear regression and were internally validated with Bland-Altman plots. The mean age was 75 ± 3 years, 53% were female, and the mean measured free 25(OH)D was 5.37 ± 1.81 pg/mL. Three equations were developed. The first equation included albumin, 25(OH)D3, 25(OH)D2, VDBP, 1,25(OH)2D3, and 24,25(OH)2D3. The second equation included all variables in Eq. (1) plus VDBP phenotypes. The third equation included albumin, 25(OH)D3, intact parathyroid hormone, and 1,25(OH)2D3. In internal validation, all three new equations predicted free 25(OH)D values within 30% and 15% of the measured free 25(OH)D concentrations in 76%-80% and 48%-52% of study participants, respectively. Equation (2) was the most precise, with a mean bias of 0.06 (95% limits of agreement -2.41 to 2.30) pg/mL. The existing equation estimated free 25(OH)D within 30% and 15% of measured free 25(OH)D in 43% and 22% of participants, respectively. Free 25(OH)D can be estimated with clinically available biomarkers as well as with more laboratory-intensive biomarkers with moderate precision. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Abstract Background Little information exists about vitamin D status in bitches with mammary tumors. Objectives To determine whether low plasma vitamin D concentrations are found in bitches with mammary tumors. Animals Eighty‐five client‐owned bitches with mammary tumors (n = 21 benign, n = 64 malignant) and 39 age‐matched healthy bitches. Methods Case‐control study. Plasma ionized and total calcium, phosphorus, magnesium, urea, creatinine, albumin, total proteins, alanine aminotransferase, alkaline phosphatase, parathyroid hormone (PTH), calcitriol (1,25‐dihydroxyvitamin D), and 25‐hydroxyvitamin D concentrations were measured in all bitches at the time of clinical diagnosis and before any treatments. Statistical analysis was performed to compare variables among groups (control, benign, and malignant). Results No significant differences were found when plasma 25‐hydroxyvitamin D concentrations in bitches with malignant (148.9 [59.9] ng/mL) and benign mammary tumors (150.1 [122.3] ng/mL) were compared with control group (129.9 [54.5] ng/mL). Parathyroid hormone was significantly higher in bitches with malignant (19.9 [20.5] pg/mL), and benign mammary tumors (14.6 [14.9] pg/mL) compared with control group (7.5 [7.5] pg/mL; P

Background. The study of the influence of "social" stress on biogenic elements involved in mineral metabolism and playing an important role in the life of the human body, the search for agents that have a leveling effect on their content, is an urgent problem of modern pharmacological science. Purpose. To study changes in the content of biogenic elements in the course of mineral metabolism in the blood serum of rats under conditions of "social" stress and under the influence of Scutellaria baicalensis Georgi extract. Materials and methods. Experimental studies were carried out on 96 mature male non-linear rats weighing 295±12.17 g at the age of 7-9 months. The first stage of the experiment involved the study of mineral metabolism in the norm. Individuals of the first group of animals were injected with water; the second was an extract of Scutellaria baicalensis Georgi (100 mg/kg/day); the third – medicinal product (MP) "Mebicar®" (25 mg/kg/day) and the fourth - MP "Phezam®" (45 mg/kg/day). At the second stage of the experiment, “social” stress was reproduced on animals, in groups of which aggressors and victims were identified after the formation of inter-male confrontations for 21 days. These individuals received the solutions used earlier (stage I) for two weeks. The content of sodium and potassium ions in plasma was determined by flame photometry; the level of total calcium - by the photometric method; the concentration of phosphorus and magnesium - by biochemical analysis; the amount of chloride ions - by mercurimetric titration. Statistical data processing was performed using the Statistica 10 package. Results. It was found that the introduction of the extract of Scutellaria baicalensis Georgi, MP "Mebikar®" and "Phezam®" normally does not affect the content of minerals in plasma. It has been shown that modeling of "social" stress in control animals with both dominant and submissive types of character contributes to a significant decrease in the concentration of calcium, phosphorus and magnesium ions compared with individuals of the intact group. A statistically significant difference in the content of chloride ions was proved only in the case of a group of victims. Comparable values of mineral metabolism parameters of the group that received the extract under stress conditions were obtained with the first stage of the experiment in the norm of both intact and experimental animals, as a result of which the leveling effect of the extract of Scutellaria baicalensis Georgi was substantiated. Statistically significant differences in the concentration of magnesium ions in the group of victims exposed to "social" stress under the influence of the type of behavior were determined. Conclusion. The analysis of the data obtained forms an idea of the mineral composition of blood plasma in normal conditions and under conditions of "social" stress. The results of the study characterize the extract of Scutellaria baicalensis Georgi as a remedy that has a leveling effect in conditions of anxiety-depressive state caused by inter-male confrontations.

Observational investigations recommend that mineral supplements were associated with a higher risk of polycystic ovary syndrome (PCOS) and its risk factors (insulin resistance, hyperandrogenism, and obesity), but the relationship with risk of PCOS, hyperandrogenism, obesity, and insulin resistance was unclear. This study was to investigate the potential causal impact of genetically predicted levels of magnesium (Mg), calcium (Ca), selenium (Se), zinc (Zn), iron (Fe), and omega-3 (ω-3) on polycystic ovary syndrome (PCOS) and its associated risk factors. A two-sample Mendelian randomization (MR) analysis was conducted. The genetic variations obtained from GWAS of individuals with European ancestry were found to be associated with the genetically predicted levels of Ca, Mg, Zn, Se, Fe, or ω-3. The data obtained from the FinnGen Consortium and MAGIC were utilized for the outcome of GWAS. The study found that there was a correlation between genetically predicted higher levels of Se and a reduced risk of insulin resistance, with a decrease of 2.2% according to random-effect IVW (OR 0.978, 95% CI 0.960–0.996, p = 0.015). The association between genetically determined mineral levels and PCOS was found to be limited, with an odds ratio (OR) ranging from 0.875 (95% CI: 0.637–1.202, p value = 0.411) for Ca. Limited scientific proof was found for the efficacy of other genetically determined mineral levels on hyperandrogenism, obesity, and insulin resistance. These findings suggested a causal relationship between genetically predicted higher levels of Se and a reduced risk of insulin resistance. Nonetheless, there is limited evidence supporting a causal association between various genetically determined mineral levels and the risk factors associated with PCOS. [ABSTRACT FROM AUTHOR]

Background: Little information exists about vitamin D status in bitches with mammary tumors. Objectives: To determine whether low plasma vitamin D concentrations are found in bitches with mammary tumors. Animals: Eighty‐five client‐owned bitches with mammary tumors (n = 21 benign, n = 64 malignant) and 39 age‐matched healthy bitches. Methods: Case‐control study. Plasma ionized and total calcium, phosphorus, magnesium, urea, creatinine, albumin, total proteins, alanine aminotransferase, alkaline phosphatase, parathyroid hormone (PTH), calcitriol (1,25‐dihydroxyvitamin D), and 25‐hydroxyvitamin D concentrations were measured in all bitches at the time of clinical diagnosis and before any treatments. Statistical analysis was performed to compare variables among groups (control, benign, and malignant). Results: No significant differences were found when plasma 25‐hydroxyvitamin D concentrations in bitches with malignant (148.9 [59.9] ng/mL) and benign mammary tumors (150.1 [122.3] ng/mL) were compared with control group (129.9 [54.5] ng/mL). Parathyroid hormone was significantly higher in bitches with malignant (19.9 [20.5] pg/mL), and benign mammary tumors (14.6 [14.9] pg/mL) compared with control group (7.5 [7.5] pg/mL; P <.01). Only the presence of mammary tumors (P <.01) and age (P =.04; adjusted R2 =.22) was significant in predicting PTH. Conclusions: Bitches with mammary tumors do not have low 25‐hydroxyvitamin D concentrations thus vitamin D supplementation is unlikely to be useful for prevention of mammary tumors in bitches. [ABSTRACT FROM AUTHOR]

The global derangement of mineral metabolism that accompanies chronic kidney disease (CKD-MBD) is a major driver of the accelerated mortality for individuals with kidney disease. Advances in the delivery of dialysis, in the composition of phosphate binders, and in the therapies directed towards secondary hyperparathyroidism have failed to improve the cardiovascular event profile in this population. Many obstacles have prevented progress in this field including the incomplete understanding of pathophysiology, the lack of clinical targets for early stages of chronic kidney disease, and the remarkably wide diversity in clinical manifestations. We describe in this review a novel approach to CKD-MBD combining mathematical modelling of biologic processes with machine learning artificial intelligence techniques as a tool for the generation of new hypotheses and for the development of innovative therapeutic approaches to this syndrome. Clinicians need alternative targets of therapy, tools for risk profile assessment, and new therapies to address complications early in the course of disease and to personalize therapy to each individual. The complexity of CKD-MBD suggests that incorporating artificial intelligence techniques into the diagnostic, therapeutic, and research armamentarium could accelerate the achievement of these goals. [ABSTRACT FROM AUTHOR]

Abstract Osteopontin (OPN) is a multi‐functional glycoprotein that coordinates the innate immune response, prevents nanocrystal formation in renal tubule fluid, and is a biomarker for kidney injury. OPN expression is markedly increased in cystic epithelial cells of polycystic kidney disease (PKD) kidneys; however, its role in PKD progression remains unclear. We investigated the in vitro effects of recombinant OPN on the proliferation of tubular epithelial cells from PKD and normal human kidneys and in vivo effects of OPN deletion on kidney cyst formation, fibrosis, and mineral metabolism in pcy/pcy mice, a non‐orthologous model of autosomal‐dominant PKD. In vitro studies revealed that OPN enhanced the proliferation of PKD cells but had no effect on normal kidney cells. Deletion of OPN in pcy/pcy mice significantly reduced kidney cyst burden; however, this was accompanied by increased fibrosis and no change in kidney function. The loss of OPN had no effect on kidney macrophage numbers, cyst epithelial cell proliferation, or apoptosis. Furthermore, there was no difference in kidney mineral deposition or mineral metabolism parameters between pcy/pcy mice with and without OPN expression. Global deletion of OPN reduced kidney cyst burden, while paradoxically exacerbating kidney fibrosis in mice with cystic kidney disease.

RATIONALE & OBJECTIVE: Posttransplant hyperparathyroidism is common, and treatment practices are poorly characterized. The goal of this study was to examine the incidence, associations, and outcomes of posttransplant parathyroidectomy and calcimimetic use in a cohort of Medicare-insured US kidney transplant recipients. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: We used the US Renal Data System to extract demographic, clinical, and prescription data from Medicare Parts A, B, and D-insured patients who received their first kidney transplant in 2007-2013. We excluded patients with pretransplant parathyroidectomy. PREDICTORS: Calendar year of transplantation and pretransplant patient characteristics. OUTCOME: (1) Incidence of and secular trends in parathyroidectomy and cinacalcet use in the 3 years after transplant; (2) 90-day outcomes after posttransplant parathyroidectomy and cinacalcet initiation. ANALYTICAL APPROACH: Temporal trends and pretransplant correlates of parathyroidectomy and cinacalcet use were assessed using proportional hazards models and multivariable Poisson regression, respectively. RESULTS: The inclusion criteria were met by 30,127 patients, of whom 10,707 used cinacalcet before transplant, 551 underwent posttransplant parathyroidectomy, and 5,413 filled≥1 prescription for cinacalcet. The rate of posttransplant parathyroidectomy was stable over time. By contrast, cinacalcet use increased during the period studied. Long dialysis vintage and pretransplant cinacalcet use were strongly associated with posttransplant parathyroidectomy and cinacalcet use. Roughly 1 in 4 patients were hospitalized within 90 days of posttransplant parathyroidectomy, with hypocalcemia-related diagnoses being the most common complication. Parathyroidectomy (vs cinacalcet initiation) was not associated with an increase in acute kidney injury. LIMITATIONS: We lacked access to laboratory data to help assess the severity of secondary/tertiary hyperparathyroidism. The cohort was limited to Medicare beneficiaries. CONCLUSIONS: Almost one-fifth of our study cohort was treated with parathyroidectomy and/or cinacalcet. Further studies are needed to establish the optimal treatment for posttransplant hyperparathyroidism.

Background. The presence of increased manganese concentrations in soils and water intakes areas for drinking and household purposes in a number of the Russian Federation subjects indicates the chronic influence of this metal on all segments of the population. This situation is aggravated by violation of the optimal nutrition principles, which leads to changes in the organism absorption of micronutrients. In this regard, the study of the elemental status of an organism against the background of manganese exposure is of particular importance.The aim. To study the effects of subchronic exposure to manganese on the mineral status of Wistar rats.Materials and methods. To conduct the study, 20 mature rats were selected, from which two groups were formed – control (n = 10) and experimental (n = 10). Animals in the control group received a general diet, animals in the experimental group received a diet with additional administration of manganese sulfate at a dose of 1433 mg/kg for 28 days. At the end of the preparatory period, blood and brain samples were taken to determine the content of chemical elements using inductively coupled plasma mass spectrometry and of metal-ligand manganese forms using high-performance liquid chromatography combined with inductively coupled plasma mass spectrometry.Results. It has been established that subchronic oral exposure to manganese leads to an increase in the content of this microelement in the blood serum and to a decrease in the levels of calcium, potassium, magnesium, iron and copper. In the cerebral cortex, the level of manganese, lead, mercury and strontium increases against the background of a decrease in iron and iodine levels. An increase in the gross content of manganese in blood serum leads to an overload of the main high-molecular carriers and initiates the formation of low-molecular forms of manganese.Conclusion. Subchronic oral exposure to manganese leads to the accumulation of this microelement in the body of animals and to the development of an imbalance of a number of macro- and microelements.

Previously, we demonstrated that prebiotics may provide a complementary strategy for increasing calcium (Ca) absorption in adolescents which may improve long-term bone health. However, not all children responded to prebiotic intervention. We determine if certain baseline characteristics of gut microbiome composition predict prebiotic responsiveness. In this secondary analysis, we compared differences in relative microbiota taxa abundance between responders (greater than or equal to 3% increase in Ca absorption) and non-responders (less than 3% increase). Dual stable isotope methodologies were used to assess fractional Ca absorption at the end of crossover treatments with placebo, 10, and 20 g/day of soluble corn fiber (SCF). Microbial DNA was obtained from stool samples collected before and after each intervention. Sequencing of the 16S rRNA gene was used to taxonomically characterize the gut microbiome. Machine learning techniques were used to build a predictive model for identifying responders based on baseline relative taxa abundances. Model output was used to infer which features contributed most to prediction accuracy. We identified 19 microbial features out of the 221 observed that predicted responsiveness with 96.0% average accuracy. The results suggest a simplified prescreening can be performed to determine if a subject's bone health may benefit from a prebiotic. Additionally, the findings provide insight and prompt further investigation into the metabolic and genetic underpinnings affecting calcium absorption during pubertal bone development. [ABSTRACT FROM AUTHOR]

The importance of maintaining proper magnesium intake and total body magnesium content in preserving human health remains underappreciated among medical professionals and laymen. This review aimed to show the importance of hypomagnesemia as a modifiable risk factor for developing disease processes. We searched the PubMed database and Google Scholar using the keywords 'magnesium', 'diabetes', 'cardiovascular disease', 'respiratory disease', 'immune system', 'inflammation', 'autoimmune disease', 'neurology', 'psychiatry', 'cognitive function', 'cancer', and 'vascular calcification'. In multiple contexts of the search terms, all reviews, animal experiments, and human observational data indicated that magnesium deficiency can lead to or contribute to developing many disease states. The conclusions of several in-depth reviews support our working hypothesis that magnesium and its supplementation are often undervalued and underutilized. Although much research has confirmed the importance of proper magnesium supply and tissue levels, simple and inexpensive magnesium supplementation has not yet been sufficiently recognized or promoted. [ABSTRACT FROM AUTHOR]

Abstract We conducted a systematic search across medical databases, including PubMed, Web of Science, EMBASE, and Cochrane Library, up to March 2023. A total of 1944 subjects or individuals from 17 studies were included in our final analysis. The correlation coefficient (r) between sKlotho and calcium was [0.14, (0.02, 0.26)], and a moderate heterogeneity was observed (I2 = 66%, P

Abstract Aims Abnormalities of mineral metabolism (MM) have been related to cardiovascular disorders. There are no reports on the prognostic role of MM after an acute coronary syndrome (ACS). We aim to assess the prognostic role of MM after an ACS. Methods and results Plasma levels of components of MM [fibroblast growth factor 23 (FGF23), calcidiol, parathormone, klotho, and phosphate], high‐sensitivity C‐reactive protein, and N‐terminal‐pro‐brain natriuretic peptide were measured in 1190 patients at discharge from an ACS. The primary outcome was a combination of acute ischaemic events, heart failure (HF) and death. Secondary outcomes were the separate components of the primary outcome. Age was 61.7 ± 12.2 years, and 77.1% were men. Median follow‐up was 5.44 (3.03–7.46) years. Two hundred and ninety‐four patients developed the primary outcome. At multivariable analysis FGF23 (hazard ratio, HR 1.18 [1.08–1.29], P 60 mL/min/1.73 m2. Conclusions FGF23 and other components of MM are independent predictors of HF and death after an ACS. This effect is homogeneous across different subgroups of population, and it is not limited to patients with chronic kidney disease.

Disorders of the mineral balance often determine the symptoms, the severity of the course and the prognosis of many diseases. Primary hyperparathyroidism (PHPT) is a common endocrine disease caused by increased secretion of parathyroid hormone as a result of primary damage to the parathyroid glands. Diagnosis of PHPT is often difficult. Clinical signs of PHPT appear months or years after the onset of the disease, however, the presence of hypercalcemia serves as an early indication of the disease of the thyroid gland. Often, patients are observed for a long time by related specialists (rheumatologists, traumatologists-orthopedists, oncologists), which gives rise to a lot of problems consisting in the lack of adequate treatment and its result, the progression of the disease, disability, and a decrease in the quality of life. Often, patients are observed for a long time by related specialists (rheumatologists, orthopedic traumatologists, oncologists) under the “masks” of various pathologies (osteoporosis, recurrent urolithiasis, etc.), which gives rise to a lot of problems, consisting in an erroneous diagnosis, lack of adequate treatment and its result, progression of the disease, disability, and a decrease in the quality of life. Late diagnosis of PHPT leads to the development of severe complications (osteoporetic fractures, renal failure) and an increased risk of premature death. A clinical case of late diagnosis of PHPT at the stage of pronounced bone complications of the disease, which proceeded under the guise of osteoarthritis, is considered. According to the results of laboratory and instrumental studies, the following were revealed: hypercalcemia, a significant increase in the concentration of PTH, adenoma of the left lower parathyroid gland, hyperparathyroid osteodystrophy, and a decrease in bone mineral density. Surgical treatment was performed – selective parathyroidectomy with the development of hypocalcemia in the early postoperative period, which was stopped by taking calcium supplements and active vitamin D metabolites and is designed to help practitioners of various specialties to understand the issues of diagnosis of PHPT and effective care for patients.

Relative abundance of fibroblast growth factor-23 (FGF23) measured by the C-terminal (cFGF23, which measures both intact FGF23 and C-terminal fragments) versus intact (iFGF23, measures only intact hormone) assays varies by kidney function in humans. Differential kidney clearance may explain this finding. We measured cFGF23 and iFGF23 in the aorta and bilateral renal veins of 162 patients with essential hypertension undergoing renal angiography. Using multivariable linear regression, we examined factors associated with aorta to renal vein reduction of FGF23 using both assays. Similar parameters and with addition of urine concentrations of cFGF23 and iFGF23 were measured in six Wistar rats. Mean ± standard deviation (SD) age was 54 ± 12 years, 54% were women, and mean creatinine clearance was 72 ± 48 mL/min/100 g. The human kidney reduced the concentrations of both cFGF23 (16% ± 12%) and iFGF23 (21% ± 16%), but reduction was higher for iFGF23. Greater kidney creatinine and PTH reductions were each independently associated with greater reductions of both cFGF23 and iFGF23. The greater kidney reduction of iFGF23 compared to cFGF23 appeared stable and consistent across the range of creatinine clearance evaluated. Kidney clearance was similar, and urine concentrations of both assays were low in the rat models, suggesting kidney metabolism of both cFGF23 and iFGF23. Renal reduction of iFGF23 is higher than that of creatinine and cFGF23. Our data suggest that FGF23 is metabolized by the kidney. However, the major cell types involved in metabolization of FGF23 requires future study. Kidney clearance of FGF23 does not explain differences in C-terminal and intact moieties across the range of kidney function. © 2022 American Society for Bone and Mineral Research (ASBMR).

We conducted a systematic search across medical databases, including PubMed, Web of Science, EMBASE, and Cochrane Library, up to March 2023. A total of 1944 subjects or individuals from 17 studies were included in our final analysis. The correlation coefficient (r) between sKlotho and calcium was [0.14, (0.02, 0.26)], and a moderate heterogeneity was observed (I2 = 66%, P < 0.05). The correlation coefficient (r) between Klotho and serum phosphate was [− 0.21, (− 0.37, − 0.04)], with apparent heterogeneity (I2 = 84%, P < 0.05). The correlation coefficient (r) between sKlotho and parathyroid hormone and vascular calcification was [− 0.23,(− 0.29, − 0.17); − 0.15, (− 0.23, − 0.08)], with no significant heterogeneity among the studies. (I2 = 40%, P < 0.05; I2 = 30%, P < 0.05). A significant correlation exists between low sKlotho levels and an increased risk of CKD–MBD in patients with CKD. According to the findings, sKlotho may play a role in alleviating CKD–MBD by lowering phosphorus and parathyroid hormone levels, regulating calcium levels, and suppressing vascular calcification. As analysis showed that sKlotho has an important impact on the pathogenesis and progression of CKD–MBD in CKD patients. Nonetheless, further comprehensive and high-quality studies are needed to validate our conclusions. [ABSTRACT FROM AUTHOR]

Androgen receptors are expressed in the kidney and serum testosterone is negatively associated with serum phosphate in males, suggesting a role of testosterone in renal phosphate handling. In this cross‐sectional study, we examined the association of serum total and free testosterone with acute phosphate and calcium excretion in males in response to an oral phosphate challenge. Thirty‐five healthy adult males with normal baseline testosterone levels consumed a 500 mg phosphorus drink and the urinary excretion of minerals, as well as levels of relevant circulating parameters, were assessed at baseline and hourly for 4 h. Serum total testosterone was positively associated with overall phosphate excretion (r = 0.35, p = 0.04) and calcium excretion (r = 0.44, p = 0.00) in response to the challenge. Serum free testosterone was positively associated with post‐challenge calcium excretion (r = 0.34, p = 0.048), but significance was not reached for phosphate excretion (r = 0.31, p = 0.07). Serum total and free testosterone were not associated with parathyroid hormone, fibroblast growth factor‐23, or vitamin D—key factors implicated in phosphate and calcium regulation. Overall, higher serum total testosterone levels in healthy middle‐aged males are associated with a greater capacity to acutely excrete phosphate and calcium after a single oral phosphate challenge, suggesting potential ramifications of testosterone deficiency related to mineral homeostasis. [ABSTRACT FROM AUTHOR]

The impact of pre-transplant parathyroid hormone (PTH) levels on early or long-term kidney function after kidney transplantation is subject of debate. We assessed whether severe hyperparathyroidism is associated with delayed graft function (DGF), deathcensored graft failure (DCGF), or all-cause mortality. In this single-center cohort study, we studied the relationship between PTH and other parameters related to bone and mineral metabolism, including serum alkaline phosphatase (ALP) at time of transplantation with the subsequent risk of DGF, DCGF and all-cause mortality using multivariable logistic and Cox regression analyses. In 1,576 kidney transplant recipients (51.6 ± 14.0 years, 57.3% male), severe hyperparathyroidism characterized by pre-transplant PTH ≥771 pg/ mL (>9 times the upper limit) was present in 121 patients. During 5.2 [0.2--30.0] years follow-up, 278 (15.7%) patients developed DGF, 150 (9.9%) DCGF and 432 (28.6%) died. A higher pre-transplant PTH was not associated with DGF (HR 1.06 [0.90--1.25]), DCGF (HR 0.98 [0.87--1.13]), or all-cause mortality (HR 1.02 [0.93--1.11]). Results were consistent in sensitivity analyses. The same applied to other parameters related to bone and mineral metabolism, including ALP. Severe pre-transplant hyperparathyroidism was not associated with an increased risk of DGF, DCGF or all-cause mortality, not supporting the need of correction before kidney transplantation to improve graft or patient survival. [ABSTRACT FROM AUTHOR]

This article examines the effects of chronic liver disease (CLD) on calcium homeostasis and bone mineral metabolism in Eastern India. The study reveals that individuals with CLD have lower levels of serum calcium and 25(OH) Vitamin D, as well as higher levels of intact parathyroid hormone compared to those without the disease. The severity of CLD is also linked to hypovitaminosis D and hypocalcemia. The study suggests that regular monitoring of these parameters is crucial for CLD patients to receive appropriate therapeutic interventions. However, it is important to note that the study's sample size and generalizability are limited. [Extracted from the article]

Studies have attempted to demonstrate the benefits of silicon on bone health using a wide range of Si amounts—provided in the diet or through supplementation—and several different animal species. Previous studies in humans have also demonstrated a positive correlation between Si intake and bone health measures. The aim of the current review is to determine the effective levels of Si intake or supplementation that influence bone health to better inform future study designs and guidelines. Articles were identified using one of two search terms: "silicon AND bone" or "sodium zeolite A AND bone". Articles were included if the article was a controlled research study on the effect of Si on bone health and/or mineral metabolism and was in English. Articles were excluded if the article included human subjects, was in vitro, or studied silica grafts for bone injuries. Silicon type, group name, Si intake from diet, Si supplementation amount, animal, and age at the start were extracted when available. Dietary Si intake, Si supplementation amount, and the amount of Si standardized on a kg BW basis were calculated and presented as overall mean ± standard deviations, medians, minimums, and maximums. Studies that left out animal weights, amount of food or water consumed, or nutrient profiles of the basal diet were excluded from these calculations. Standardized Si intakes ranged from 0.003 to 863 mg/kg BW, at times vastly exceeding current human Si intake recommendations (25 mg/d). The lack of data provided by the literature made definitively determining an effective threshold of supplementation for skeletal health difficult. However, it appears that Si consistently positively influences bone and mineral metabolism by around 139 mg Si/kg BW/d, which is likely unfeasible to attain in humans and large animal species. Future studies should examine this proposed threshold more directly and standardize supplemental or dietary Si intakes to kg BW for better study replication and translation. [ABSTRACT FROM AUTHOR]

Aims: Abnormalities of mineral metabolism (MM) have been related to cardiovascular disorders. There are no reports on the prognostic role of MM after an acute coronary syndrome (ACS). We aim to assess the prognostic role of MM after an ACS. Methods and results: Plasma levels of components of MM [fibroblast growth factor 23 (FGF23), calcidiol, parathormone, klotho, and phosphate], high‐sensitivity C‐reactive protein, and N‐terminal‐pro‐brain natriuretic peptide were measured in 1190 patients at discharge from an ACS. The primary outcome was a combination of acute ischaemic events, heart failure (HF) and death. Secondary outcomes were the separate components of the primary outcome. Age was 61.7 ± 12.2 years, and 77.1% were men. Median follow‐up was 5.44 (3.03–7.46) years. Two hundred and ninety‐four patients developed the primary outcome. At multivariable analysis FGF23 (hazard ratio, HR 1.18 [1.08–1.29], P < 0.001), calcidiol (HR 0.86 [0.74–1.00], P = 0.046), previous coronary or cerebrovascular disease, and hypertension were independent predictors of the primary outcome. The predictive power of FGF23 was homogeneous across different subgroups of population. FGF23 (HR 1.45 [1.28–1.65], P < 0.001) and parathormone (HR 1.06 1.01–1.12]; P = 0.032) resulted as independent predictors of HF. FGF23 (HR 1.21 [1.07–1.37], P = 0.002) and calcidiol (HR 0.72 [0.54–0.97), P = 0.028) were independent predictors of death. No biomarker predicted acute ischaemic events. FGF23 predicted independently the primary outcome in patients with estimated glomerular filtration rate > 60 mL/min/1.73 m2. Conclusions: FGF23 and other components of MM are independent predictors of HF and death after an ACS. This effect is homogeneous across different subgroups of population, and it is not limited to patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]

It is observed that there are physiological changes in the organism as a result of long-term training, but the mineral and hormonal effects of regular and submaximal exercises have not been fully revealed. This study was conducted to determine the effect of eightweek high-intensity training on mineral and thyroid hormone metabolism of badminton athletes. The research group consisted of 24 volunteer male athletes licensed in the badminton branch. Considering the badminton competition period, an eight-week, ninety-minute training program was applied to the research group, three days a week. Within the scope of the training, 10-15 minutes of warm-up time, 50-60 minutes of badminton training and studies to improve basic motoric features, and 5-10 minutes of cool-down exercises were made at the end of the training. Blood samples were taken from the athletes in the research group twice, before the start of the training program and at the end of the training. In the blood samples taken as a result of the training, the athletes; thyroid hormones (TSH, T3, T4), sodium, potassium, calcium, magnesium, levels were determined. The obtained data were analyzed using the SPSS 22 package program and the significance was accepted as p>0.05. As a result of the research, it was determined that there was a statistically significant difference between the thyroid hormone metabolism, TSH and T3 pre-post test values of the athletes (p<0.05), while there was no statistically significant difference between the T4 values and the pre-post test values (p>0.05). When the mineral levels of the athletes were evaluated as a result of the training, it was determined that there was a statistically significant difference in the Sodium, Potassium and Magnesium pre-post-test levels (p<0.05), while there was no statistically significant difference in the calcium pre-post-test level (p>0.05). As a result, it was observed that eight-week high-intensity training caused changes on the mineral and thyroid hormone metabolism of the athletes. In this context if the trainings to be applied are designed considering these physiological changes, it will positively affect the performance of the athlete. [ABSTRACT FROM AUTHOR]

This study looked at how desalinated seawater, which has low minerals and high boron, could affect bone health. Prior research suggests that low mineral water may harm bone health and boron could be beneficial, but the overall impact on bone health is still unclear. Eighty-nine-week-old male Balb/C mice were allocated into eight groups and administered either tap water or purified water with varying boron concentrations (0, 5, 40, and 200 mg/L). They were kept in an environment mimicking tropical conditions (35–40 °C, 70–80% humidity) and underwent daily treadmill exercise for 13 weeks. At the 14th week, serum, femora, and lumbar vertebrae were collected for mineral metabolism, bone biomarker, microstructure, and biomechanics evaluation. Boron exposure improved bone formation, microstructure, and biomechanics initially but the benefits weakened with higher levels of exposure (p < 0.05). Co-exposure to purified water elevated serum boron but weakened the promotion of boron on bone minerals and the bone benefits of boron compared to tap water (p < 0.05). Thus, when studying the health effects of boron in desalinated seawater, it is crucial to look at various health effects beyond bone health. Furthermore, it is important to consider the mineral composition of drinking water when using boron for bone health benefits.

Background. Sclerochoroidal calcification is an idiopathic rare benign lesion of the sclera or choroid characterized by histological deposition of calcium pyrophosphate. Taking into consideration its similar clinical manifestations with other diseases of the sclera, the most dangerous of which are malignant, timely verification of the diagnosis with the appointment of a further observation period is important.The aim. The description of a clinical case of sclerochoroidal calcification to improve the efficiency of disease detection through the use of multimodal diagnostics.Material and methods. A 62-year-old patient with complaints of “bright flashes” in her left eye for the past few months, who underwent a standard complex of ophthalmological examinations, supplemented according to indications by optical coherence tomography of peripapillary nerve fibers, macular zone, B-scan, Dopplerography in color Doppler mapping mode. Auxiliary diagnostic methods were magnetic resonance imaging of the orbits and extraocular muscles, computed tomography of the orbits and a biochemical blood test.Results. Considering the anamnesis, the absence of progression of complaints, the data of instrumental diagnostic methods, the absence of pathological blood flow in the area of both eyes formations, the correct diagnosis is most likely to be sclerochoroidal calcification of both eyes, despite the difficulties of the diagnostic process, which consisted in the absence of visualization of foci during ophthalmoscopy.Conclusion. Sclerochoroidal calcification is of interest to practicing ophthalmologists due to the difficulties of diagnostic search and differential diagnosis with malignant neoplasms. Modern medicine has a sufficient set of instrumental and laboratory research methods for making an accurate diagnosis.

The impact of pre-transplant parathyroid hormone (PTH) levels on early or long-term kidney function after kidney transplantation is subject of debate. We assessed whether severe hyperparathyroidism is associated with delayed graft function (DGF), death-censored graft failure (DCGF), or all-cause mortality. In this single-center cohort study, we studied the relationship between PTH and other parameters related to bone and mineral metabolism, including serum alkaline phosphatase (ALP) at time of transplantation with the subsequent risk of DGF, DCGF and all-cause mortality using multivariable logistic and Cox regression analyses. In 1,576 kidney transplant recipients (51.6 ± 14.0 years, 57.3% male), severe hyperparathyroidism characterized by pre-transplant PTH ≥771 pg/mL (>9 times the upper limit) was present in 121 patients. During 5.2 [0.2–30.0] years follow-up, 278 (15.7%) patients developed DGF, 150 (9.9%) DCGF and 432 (28.6%) died. A higher pre-transplant PTH was not associated with DGF (HR 1.06 [0.90–1.25]), DCGF (HR 0.98 [0.87–1.13]), or all-cause mortality (HR 1.02 [0.93–1.11]). Results were consistent in sensitivity analyses. The same applied to other parameters related to bone and mineral metabolism, including ALP. Severe pre-transplant hyperparathyroidism was not associated with an increased risk of DGF, DCGF or all-cause mortality, not supporting the need of correction before kidney transplantation to improve graft or patient survival.

The present study was performed to investigate yellow catfish manganese (Mn) requirement with Mn dioxide nanoparticles (MnO2NPs) as Mn source, and to evaluate effects of dietary Mn on growth performance, Mn metabolism and kidney health. Using MnO2NPs as the Mn sources, six experimental diets were formulated with dietary Mn levels at 1.67, 4.35, 7.37, 13.63, 26.06 and 50.37 mg Mn/kg diet, respectively, and fed to yellow catfish for 8 weeks. Yellow catfish growth performance and feed intake were the highest in the group of 13.63 mg Mn/kg diet, and the lowest in the group of 1.67 mg Mn/kg diet; and the feed conversion rate showed opposite trend with growth performance. Dietary Mn addition increased Mn content in the whole body, kidney and serum. The mRNA abundances of dmt1, zip8 and znt10 increased with the increase of dietary Mn level. Yellow catfish fed high dietary MnO2NPs level had higher mRNA abundances of dynamin1, dynamin2, cav1, cltc and eps15. Dietary Mn excess damaged the kidney histology. Yellow catfish fed the 13.63 mg Mn/kg diet had higher T-AOC, T-SOD, Mn-SOD, CAT activities, and mRNA levels of sod1, sod2 and cat (antioxidant response), but lower mRNA abundances of grp78, ire1, perk and atf4 (endoplasmic reticulum stress), tnfα, il1β and il6 (inflammatory response). The broken-line analysis of WG and the linear regression of whole-body Mn retention against dietary Mn levels showed that optimal Mn requirement was 12.57 mg Mn/kg diet and 8.33 mg Mn/kg diet, respectively, with MnO2NPs as Mn source. For the first time, we explored the effects of dietary MnO2 nanoparticles on growth performance, Mn uptake and metabolism, antioxidant responses, endoplasmic reticulum stress and inflammatory responses of the kidney, and determined the optimal dietary Mn requirement of yellow catfish fed MnO2 nanoparticles-added diet.

Context: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia. Objective: The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD). Methods: A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting. Results: Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed. Conclusion: This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD. [ABSTRACT FROM AUTHOR]

Cardio-renal syndrome is a clinical condition that has recently been well defined. In acute kidney disease, this interaction might trigger chronic processes determining the onset of cardiovascular events and the progression of chronic kidney disease. Moreover, the high mortality rate of acute kidney injury (AKI) is also linked to the fact that this condition is often complicated by dysfunctions of other organs such as lungs or heart, or is associated with septic episodes. In this context the role and the potential link between bone, heart and kidney is becoming an important topic of research. The aim of this review is to describe the cardiac alterations in the presence of AKI (cardiorenal syndrome type 3) and explore how bone can interact with heart and kidney in determining and influencing the trend of AKI in the short and long term. The main anomalies of mineral metabolism in patients with AKI will be reported, with specific reference to the alterations of fibroblast growth factor 23 and Klotho as a link between the bone–kidney–heart axis. [ABSTRACT FROM AUTHOR]

Copper is an essential dietary element with a crucial role in physiological regulation. However, the relationship between dietary copper intake and abdominal aortic calcification (AAC) remains uncertain. This study encompassed a cohort of 2535 adults aged over 40 years, derived from the National Health and Nutrition Examination Survey 2013–2014. Dietary copper intake from both food sources and supplements was assessed through two 24-h dietary recall interviews. AAC was measured by dual-energy X-ray absorptiometry and classified into 3 groups using the Kauppila score system. Multivariable logistic regression models were constructed to evaluate the association between dietary copper intake and AAC. Among the participants, a total of 771 individuals (30.4%) were diagnosed with AAC, of which 239 (9.4%) exhibited severe AAC. Higher dietary copper intake was significantly associated with a lower incidence of severe AAC. Specifically, for each 1 mg/day increase in dietary copper intake, the incidence of severe AAC decreased by 38% (odds ratios [OR] 0.62, 95% confidence intervals [CI] 0.39–0.98) after adjustment for relevant covariates. Moreover, individuals in the third tertile of copper intake had a 37% lower incidence of AAC compared to those in the first tertile [OR 0.63, 95% CI (0.43–0.95)]. However, no significant associations were found between supplemental copper intake or serum copper levels and AAC. This study demonstrates that lower dietary copper intake, rather than serum copper levels or supplement copper intake, is significantly associated with a higher prevalence of AAC in adults ≥40 years old in the United States. • High dietary copper intake was associated with a lower incidence of abdominal aortic calcification (AAC). • Supplemental copper intake and serum copper levels were not associated with AAC. • Increasing dietary copper intake, rather than copper supplements, could be a potential strategy to lower the incidence of AAC. [ABSTRACT FROM AUTHOR]

Context: Burosumab has been approved for the treatment of children and adults with X-linked hypophosphatemia (XLH). Real-world data and evidence for its efficacy in adolescents are lacking. Objective: To assess the effects of 12 months of burosumab treatment on mineral metabolism in children (aged <12 years) and adolescents (aged 12-18 years) with XLH. Design: Prospective national registry. Setting: Hospital clinics. Patients: A total of 93 patients with XLH (65 children, 28 adolescents). Main Outcome Measures: Z scores for serum phosphate, alkaline phosphatase (ALP), and renal tubular reabsorption of phosphate per glomerular filtration rate (TmP/GFR) at 12 months. Results: At baseline, patients showed hypophosphatemia (−4.4 SD), reduced TmP/GFR (−6.5 SD), and elevated ALP (2.7 SD, each P < .001 vs healthy children) irrespective of age, suggesting active rickets despite prior therapy with oral phosphate and active vitamin D in 88% of patients. Burosumab treatment resulted in comparable increases in serum phosphate and TmP/GFR in children and adolescents with XLH and a steady decline in serum ALP (each P < .001 vs baseline). At 12 months, serum phosphate, TmP/GFR, and ALP levels were within the age-related normal range in approximately 42%, 27%, and 80% of patients in both groups, respectively, with a lower, weight-based final burosumab dose in adolescents compared with children (0.72 vs 1.06 mg/kg, P < .01). Conclusions: In this real-world setting, 12 months of burosumab treatment was equally effective in normalizing serum ALP in adolescents and children, despite persistent mild hypophosphatemia in one-half of patients, suggesting that complete normalization of serum phosphate is not mandatory for substantial improvement of rickets in these patients. Adolescents appear to require lower weight-based burosumab dosage than children. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to investigate the changes in bone mineral metabolism caused by commonly used antiepileptic drugs in childhood epilepsies, and to evaluate the usability of Calcitriol Index and PTH Index, which are more practical and cost-effective parameters, in the follow-up of these patients. Materials and Methods: The study included 55 children who were newly diagnosed with idiopathic epilepsy and started on antiepileptic therapy (valproic acid, carbamazepine, phenobarbital) at our hospital's pediatric neurology clinic as the study group, and 32 healthy individuals with similar demographic characteristics as the control group. Calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) levels were studied in both groups before the medication initiation and at least 6-12 months after the treatment started, and PTH Index and Calcitriol Index were calculated. In the study patients, parathyroid hormone (PTH), 25-(OH)D3, osteocalcin levels were measured after the medication use and at the same dates in the control group. Results: When comparing the post-medication values and indices of the study patients with the control group, 8 cases showing signs of stage 2 rickets were identified. Considering these patients; the sensitivity, specificity, positive predictive, and negative predictive values of PTH and PTH Index were found to be high. No value correlation could be established between PTH Index and PTH, Calcitriol Index and Vitamin D. Conclusions: Antiepileptics affect bone mineral metabolism and biochemical changes occur. Using all biochemical parameters together in diagnosis and follow-up increases the diagnostic value. Although PTH Index does not reflect PTH levels, PTH and PTH Index may be considered valuable parameters in identifying osteopenic cases. [ABSTRACT FROM AUTHOR]

Aim: To compare the effectiveness and safety of various methods of professional teeth bleaching using light and chemical activation systems in an in vivo study. Materials and Methods: Teeth whitening was performed on 48 patients aged 20 to 35, divided into 4 groups. In patients of group 1 for dental bleaching a diode laser activation was used, group 2 -- LED/gel activation, group 3 -- chemical whitening with the following remineralization therapy, group 4 -- chemical whitening without remineralization therapy. The study of the effect of bleaching systems on the hard tooth tissues was carried out by index assessment, determination of biochemical parameters of an oral fluid. Results: Laser bleaching of the vital teeth was significantly more effective than the other methods with 95% confidence level and did not affect the structure of hard dental tissues and mineral exchange of the oral fluid. LED irradiation has a high whitening effect, but leads to dentin hypersensitivity and a decrease in phosphorus and alkaline phosphatase of oral fluid. Chemical bleaching causes a decrease in enamel resistance, the occurrence of tooth sensitivity, violation of mineral exchange of oral fluid, therefore; it requires combined use with local remotherapy. Conclusions: Laser teeth bleaching is the effective and safe method in management of discolored teeth. A positive result of its use can be considered an improvement of color change of the teeth by 3.33 shades compared to chemical bleaching, enamel stability, low values of dental hypersensitivity indices, no changes in biochemical parameters of the oral fluid. [ABSTRACT FROM AUTHOR]

BackgroundA better understanding of the pathophysiology involving coronary artery calcification (CAC) in patients on hemodialysis (HD) will help to develop new therapies. We sought to identify the differences in metabolomics profiles between patients on HD with and without CAC.MethodsIn this case-control study, nested within a cohort of 568 incident patients on HD, the cases were patients without diabetes with a CAC score >100 (n=51), and controls were patients without diabetes with a CAC score of zero (n=48). We measured 452 serum metabolites in each participant. Metabolites and pathway scores were compared using Mann-Whitney U tests, partial least squares-discriminant analyses, and pathway enrichment analyses.ResultsCompared with controls, cases were older (64±13 versus 42±12 years) and were less likely to be Black (51% versus 94%). We identified three metabolites in bile-acid synthesis (chenodeoxycholic, deoxycholic, and glycolithocholic acids) and one pathway (arginine/proline metabolism). After adjusting for demographics, higher levels of chenodeoxycholic, deoxycholic, and glycolithocholic acids were associated with higher odds of having CAC; comparing the third with the first tertile of each bile acid, the OR was 6.34 (95% CI, 1.12 to 36.06), 6.73 (95% CI, 1.20 to 37.82), and 8.53 (95% CI, 1.50 to 48.49), respectively. These associations were no longer significant after further adjustment for coronary artery disease and medication use. Per 1 unit higher in the first principal component score, arginine/proline metabolism was associated with CAC after adjusting for demographics (OR, 1.83; 95% CI, 1.06 to 3.15), and the association remained significant with additional adjustments for statin use (OR, 1.84; 95% CI, 1.04 to 3.27).ConclusionsAmong patients on HD without diabetes mellitus, chenodeoxycholic, deoxycholic, and glycolithocholic acids may be potential biomarkers for CAC, and arginine/proline metabolism is a plausible mechanism to study for CAC. These findings need to be confirmed in future studies.

Background25-Hydroxyvitamin D [25(OH)D] may be a poor marker of vitamin D status as it reflects differences in vitamin D binding protein (VDBP) between individuals. The vitamin D metabolite ratio [VMR, ratio of 24,25(OH)2D3 to 25(OH)D3] is a marker of vitamin D status that has been hypothesized to be independent of variability in VDBP. This hypothesis has not been directly evaluated.MethodsWe measured 25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3, and VDBP in 377 community-dwelling older adults that participated in the Health Aging and Body Composition Study. 24,25(OH)2D3 and 25(OH)D3 were used to calculate the VMR. We used linear regression to assess the relationship between VDBP with the VMR, 24,25(OH)2D3, 25(OH)D3, and 1,25(OH)2D3.ResultsParticipants had mean age 75 ± 3 years, 52% were female, 40% were black, and 24% had chronic kidney disease. VDBP concentrations were associated with sex, serum albumin, and VDBP phenotype in multivariable models. In fully adjusted models, each 1% higher VDBP was associated with a 0.92%[95% CI(0.37,1.49%)], 0.76% (0.39, 1.13%), and 0.57% (0.29, 0.85%), higher 24,25(OH)2D3, 25(OH)D3, and 1,25(OH)2D3. The VMR was independent of VDBP concentration, [0.16%(-0.11, 0.44) higher VMR per 1% higher VDBP, P = .25].ConclusionsThe VMR was independent of VDBP concentration, whereas VDBP was strongly directly associated with the individual vitamin D metabolite concentrations. Prior studies evaluating only 25(OH)D3 may have been confounded by absence of data on VDBP status. The VMR may serve as an important biomarker of vitamin D status and clinical outcomes that can be utilized in populations with a large spectrum of VDBP concentrations.

ABSTRACT Vitamin D deficiency is prevalent in 25% of Americans. However, 25(OH)D may not be an accurate measure of vitamin D because the majority (85%–90%) of 25(OH)D is bound to vitamin D binding protein (VDBP), which varies by over 30% across individuals. Free 25(OH)D may be a better measure, but it is difficult to measure accurately and precisely. The existing free 25(OH)D estimating equation does not include VDBP phenotypes; therefore, new equations that include this variable may be more accurate. A total of 370 participants in the Health, Aging, and Body Composition Study, a cohort of healthy community‐dwelling individuals aged 70–79 years old, underwent VDBP and vitamin D metabolite [25(OH)D, 24,25(OH)2D, 1,25(OH)2D, free 25(OH)D] measurements and were randomly allocated into equation development (two out of three) and internal validation (one out of three) groups. New equations were developed with multiple linear regression and were internally validated with Bland–Altman plots. The mean age was 75 ± 3 years, 53% were female, and the mean measured free 25(OH)D was 5.37 ± 1.81 pg/mL. Three equations were developed. The first equation included albumin, 25(OH)D3, 25(OH)D2, VDBP, 1,25(OH)2D3, and 24,25(OH)2D3. The second equation included all variables in Eq. (1) plus VDBP phenotypes. The third equation included albumin, 25(OH)D3, intact parathyroid hormone, and 1,25(OH)2D3. In internal validation, all three new equations predicted free 25(OH)D values within 30% and 15% of the measured free 25(OH)D concentrations in 76%–80% and 48%–52% of study participants, respectively. Equation (2) was the most precise, with a mean bias of 0.06 (95% limits of agreement −2.41 to 2.30) pg/mL. The existing equation estimated free 25(OH)D within 30% and 15% of measured free 25(OH)D in 43% and 22% of participants, respectively. Free 25(OH)D can be estimated with clinically available biomarkers as well as with more laboratory‐intensive biomarkers with moderate precision. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Fibroblast growth factor 23 (FGF23) is an important phosphaturic hormone, yet few studies have focused on FGF23 in children with primary nephrotic syndrome (PNS) and children who progressed to end-stage renal disease (ESRD). This cross-sectional study investigated the significance of changes in FGF23 levels in childhood PNS and children who progressed to ESRD. Of the 41 children included in the study, 17 had PNS with proteinuria and normal renal function (PNS group), 4 had ESRD (ESRD group), and 20 were healthy (control group). Following corticosteroid treatment, patients with PNS and proteinuria entered the remission phase. Serum levels of FGF23, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), and calcium were measured. It was found that FGF23 levels in the PNS and ESRD groups were higher than those in the control group, while serum 25-OH-D levels were lower. Serum PTH levels increased significantly in the ESRD group. In the control group, FGF23 levels were negatively correlated with serum PTH and positively correlated with serum 25-OH-D. FGF23 levels were positively correlated with serum calcium and corrected calcium levels in children with PNS during the remission phase. Increased FGF23 levels in children with PNS, particularly in children who progressed to ESRD. It was also confirmed that serum FGF23 levels begin to rise in children with PNS prior to Stage 1 chronic kidney disease. These findings indicated that increased FGF23 levels may be associated with the progression and severity of nephrosis in children, and that serum FGF23 levels were useful for early detection of abnormal mineral metabolism in children with PNS. [ABSTRACT FROM AUTHOR]

Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a unique bone and mineral phenotype. The impact of tolvaptan treatment on mineral metabolism and bone mineral density (BMD) is unknown. Methods We conducted an analysis in the Bern ADPKD Registry, a prospective observational cohort study. Mineral metabolism parameters were measured at baseline and every 12 months thereafter. BMD was determined by dual-energy X-ray absorptiometry at baseline and after 3 years. Multivariable mixed-effects regression models were applied to assess changes in mineral metabolism parameters and BMD associated with tolvaptan treatment. Results A total of 189 participants (122 without and 67 with subsequent tolvaptan treatment) were included in the analysis. During follow-up, tolvaptan treatment was associated with increased BMD at the femoral neck {β = 0.092 [95% confidence interval (CI) 0.001–0.183], P  = .047}. In addition, tolvaptan treatment was associated with higher plasma magnesium [β = 0.019 (95% CI 0.001–0.037), P  = .037], bicarbonate [β = 0.972 (95% CI 0.242–1.702), P  = .009] and urine pH [β = 0.214 (95% CI 0.056–0.372), P  = .008] and lower parathyroid hormone [β = −0.191 (95% CI −0.328 to −0.053), P  = .006], 1,25(OH)D3 [β = −0.126 (95% CI −0.235 to −0.164), P  = .024] and fractional urinary magnesium excretion [β = −0.473 (95% CI −0.622 to −0.324), P  < .001]. Conclusions Chronic tolvaptan treatment is associated with increased femoral BMD and significant changes in both mineral metabolism and acid–base parameters in ADPKD patients. [ABSTRACT FROM AUTHOR]

BackgroundPhosphate binders are commonly used in the treatment of patients with hyperphosphatemia. While phosphate binders are used to lower phosphate, the effects of specific phosphate binder types on vitamin D metabolism are unknown.MethodsWe performed a secondary analysis of the Phosphate Normalization Trial in which patients with moderate to advanced chronic kidney disease were randomized to receive either placebo, sevelamer carbonate, lanthanum carbonate or calcium acetate for 9 months. We evaluated changes in serum concentrations of vitamin D metabolites including 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the ratio of 24,25(OH)2D3 to 25-hydroxyvitamin D [the vitamin D metabolite ratio (VMR)] and the ratio of serum 1,25(OH)2D to 25-hydroxyvitamin D.ResultsCompared with placebo, randomization to the calcium acetate arm was associated with a 0.6 ng/mL (95% CI 0.2, 1) and 13.5 pg/ng (95% CI 5.5, 21.5) increase in 24,25(OH)2D and VMR, respectively, and a 5.2 pg/mL (95% CI 1.1, 9.4) reduction in 1,25(OH)2D. Randomization to sevelamer carbonate was associated with a 0.5 ng/mL (95% CI -0.9, -0.1) and 11.8 pg/ng (95% CI -20, -3.5) reduction in 24,25(OH)2D3 and VMR, respectively. There was no association of the sevelamer arm with the change in 1,25(OH)2D3, and randomization to lanthanum carbonate was not associated with a change in any of the vitamin D metabolites.ConclusionAdministration of different phosphate binders to patients with moderate to severe CKD results in unique changes in vitamin D metabolism.

Introduction Multifactoriality in the etiology of idiopathic scoliosis (IS) requires an integrated approach to diagnosis, while the regular examination of patients is limited to radiography, computed tomography without a detailed analysis of the data obtained on the state of the musculoskeletal system. The problem of complex diagnosis of IS is practically not covered by the literature including the syndromic approach to the rationale for the method of treatment and rehabilitation. Purpose of the study To define the concept of "syndromocomplex" of idiopathic scoliosis based on the study of the state of the spine, muscles, proximal femur, bone mineral density (BMD), mineral metabolism and bone metabolism using current diagnostic methods. Materials and methods The state of the spine (300 patients), proximal femur (57 patients), paravertebral (40 patients) and gluteal muscles (60 patients of the main group and 40 of the control group) were studied using the method of multislice computed tomography (MSCT) and magnetic resonance imaging (MRI), densitometry – BMD (40 patients of the main and 40 of control one), mineral metabolism and bone metabolism were studied by biochemical methods in 55 patients with IS. Results and discussion The study of patients with idiopathic scoliosis at different ages and with different grades of deformities in various parts of the musculoskeletal system revealed pronounced disorders in the shape of the vertebrae, including an increase in the frontal diameter, wedge shape with a significant difference in density along the convex and concave sides, structural changes in the vertebrae, manifested in a decrease in density, the presence of rarefaction zones, areas of maximum density at the top of the deformity, malnutrition and fatty degeneration of the paravertebral and gluteal muscles, a decrease in BMD, a decrease in the density of the femoral head, impaired mineral metabolism and bone metabolism. Conclusion Severe disorders in the shape, X-ray morphological changes in the vertebrae, malnutrition and fatty degeneration of the paravertebral and gluteal muscles, concomitant changes in BMD, hip joint, mineral metabolism and bone metabolism, are included in the concept of "syndromocomplex” of idiopathic scoliosis, underlie the tactical concept for diagnosis, treatment and further rehabilitation measures for patients with severe forms of scoliosis.

Using probiotic preparations and their complexes in poultry farming is an important step towards increasing poultry resistance and productivity, and thus producing environmentally friendly products. The purpose of the study was to investigate the effect of the complex action of symbiotic drugs and biocidal agents by investigating the clinical and biochemical parameters of blood and mineral metabolism in the body of broiler chickens under the conditions of their use according to the developed scheme. Hematologic, biochemical and immunologic blood parameters were explored by conventional methods, micro- and macroelements by optical emission spectrometry with inductively coupled plasma. Using the proposed complex of symbiotic and biocidal agents in the technology of rearing broiler chickens activates the processes of erythropoiesis, haemoglobin production, restoration of protein metabolism and normalisation of mineral status within physiological limits, which indicates the strengthening of the body's defences, increased resistance to stress factors and adverse environmental conditions, and will further have a positive effect on the growth and productivity of the target bird. The pronounced effect of the complex combination of drugs on the body of broiler chickens of experimental B is a better assimilation of many inorganic elements (by increasing the content of Calcium, Phosphorus, Cuprum, Ferrum and Selenium, Magnesium, Manganum); and, accordingly, causes the sustainable development of metabolic processes due to the prevalence of anabolic over catabolic processes (by increasing the level of total proteins against the background of a physiological increase in the number of globulin fractions; including the induction of the endogenous detoxification system – by reducing the level of production of toxic metabolites of purine metabolism: uric acid and creatinine; reduction of Chromium content; normalisation of transamination processes and deceleration of alkaline phosphatase activity) and immunobiological reactions (by enhancing erythropoiesis and haemoglobin production; induction of lysozyme, bactericidal and phagocytic activity), respectively. The proposed system of rearing young poultry using a complex of symbiotic preparations in combination with biocidal agents promotes the synergistic effect of the latter and their effective action on the body of experimental broiler chickens, which increases nonspecific resistance and restores metabolic reactions

Abstract Energy metabolism is a point of integration among the various organs and tissues of the human body, not only in terms of consumption of energy substrates but also because it concentrates a wide interconnected network controlled by endocrine factors. Thus, not only do tissues consume substrates, but they also participate in modulating energy metabolism. Soft mesenchymal tissues, in particular, play a key role in this process. The recognition that high energy consumption is involved in bone remodeling has been accompanied by evidence showing that osteoblasts and osteocytes produce factors that influence, for example, insulin sensitivity and appetite. Additionally, there are significant interactions between muscle, adipose, and bone tissues to control mutual tissue trophism. Not by chance, trophic and functional changes in these tissues go hand in hand from the beginning of an individual’s development until aging. Likewise, metabolic and nutritional diseases deeply affect the musculoskeletal system and adipose tissue. The present narrative review highlights the importance of the interaction of the mesenchymal tissues for bone development and maintenance and the impact on bone from diseases marked by functional and trophic disorders of adipose and muscle tissues. Arch Endocrinol Metab. 2022;66(5):611-20

Mineral and bone disorder biomarkers ‘normal ranges’ are controversial. The aim of the study was to evaluate the association between serum calcium (Ca), phosphate (P), intact parathyroid hormone (iPTH), and 25(OH) vitamin D levels and mortality risk, in a chronic kidney disease (CKD) grade (G) 3b-4 cohort. The Uruguayan National Renal Healthcare Program (NRHP-UY) CKD patients’ cohort, included between 1 October 2004 and 1 March 2020 and followed-up until 1 March 2021, was analyzed with the Ethics Committee approval. A total of 6473 patients were analyzed: 56% men, median age 73 (65–79) years, 55% on CKD G3b. At the end of the follow-up, 2459 (37.7%) patients had died (6.4/100 patient–year). There were iPTH data on 2013 patients (younger, with lower estimated glomerular filtration rate (eGFR) and lesser comorbidities). By bivariate Cox analysis the lowest death risk was observed with mean Ca between 9.01 and 10.25 mg/dl, P between 2.76 and 4.0 mg/dl, iPTH ≤ 105 pg/ml, and 25(OH) vitamin D >10 ng/ml. The multivariate Cox regression mortality risk adjusted to age, sex, CKD etiology, diabetes, smoking, cardiovascular comorbidity, blood pressure, proteinuria, eGFR, renin-angiotensin system blockers and vitamin D treatments, serum Ca, P, iPTH, and 25(OH) vitamin D (n = 964) showed that a higher mortality risk was associated with p > 4.00 mg/dl (HR 1.668, CI 95%: 1.201–2.317), iPTH >105 pg/ml (HR 1.386, CI 95%: 1.012–1.989), and 25(OH) vitamin D ≤ 10 ng/ml (HR 1.958, CI 95%: 1.238–3.098) and a lower mortality risk with 1,25(OH)2 vitamin D treatment (HR 0.639, CI 95%: 0.451–0.906). These data may contribute to the precise G3b-4 CKD-MBD biomarkers levels definition.

Objective: The aim of this study was to reach a consensus on an updated version of the recommendations for the diagnosis and Treat-to-Target management of osteoporosis that is effective and safe for individuals with chronic kidney disease (CKD) G4-G5D/kidney transplant. Methods: Delphi process was implemented (3 rounds) to establish a consensus on 10 clinical domains: (1) study targets, (2) risk factors, (3) diagnosis, (4) case stratification, (5) treatment targets, (6) investigations, (7) medical management, (8) monitoring, (9) management of special groups, (10) fracture liaison service. After each round, statements were retired, modified, or added in view of the experts’ suggestions, and the percent agreement was calculated. Statements receiving rates of 7–9 by more than 75% of experts’ votes were considered as achieving consensus. Results: The surveys were sent to an expert panel (n = 26), of whom 23 participated in the three rounds (2 were international experts and 21 were national). Most of the participants were rheumatologists (87%), followed by nephrologists (8.7%), and geriatric physicians (4.3%). Eighteen recommendations, categorized into 10 domains, were obtained. Agreement with the recommendations (rank 7–9) ranged from 80 to 100%. Consensus was reached on the wording of all 10 clinical domains identified by the scientific committee. An algorithm for the management of osteoporosis in CKD has been suggested. Conclusion: A panel of international and national experts established a consensus regarding the management of osteoporosis in CKD patients. The developed recommendations provide a comprehensive approach to assessing and managing osteoporosis for all healthcare professionals involved in its management.

Abstract Background Compelling evidence suggests that the fibroblast growth factor 23 (FGF23) / α-klotho axis is impaired in subjects with diabetes mellitus. We examined the relationship between parameters related to calcium/phosphate homeostasis, including FGF23 and α-klotho, and subclinical carotid atherosclerosis burden in type 1 diabetes mellitus (T1D) subjects. Methods This cross-sectional study involved 226 subjects with T1D and 147 age-, sex- and plaque-matched, non-diabetic (non-T1D) subjects, both with normal renal function. Carotid ultrasound was performed to determine the presence and burden of atheromatous plaques. Concentrations of the intact form of FGF23 and α-klotho were assessed by ELISA. Calcium, phosphate, parathyroid hormone, and vitamin D levels were also determined. Negative binomial regression models were used to examine relationship between parameters studied and subclinical carotid atherosclerosis. Results Only FGF23 was increased in T1D compared with non-diabetic subjects (> 2-fold; p