Disorders Of Mineral Metabolism Research Articles

Vitamin D Status in Supplemented Hemodialysis Patients

Introduction: Chronic kidney disease (CKD) causes decreased activity of the enzyme 1-alpha-hydroxylase and calcitriol deficiency with mineral and bone metabolism disorders or secondary hyperparathyroidism. Anticipation of the occurrence of these complications implies the systematic supplementation of all hemodialysis patients, with monitoring of biological parameters. It is in this context that this study was carried out, the general objective of which was to establish the profile of vitamin D concentration in hemodialysis and Ivorian public sector supplemented patients in Abidjan. Patients and Methods: In a cross-sectional study conducted from September to December 2022, we included 89 patients with end-stage CKD treated with hemodialysis at the CNPTIR in Cocody. The collection of epidemio-clinical data was done on the basis of a questionnaire on the one hand and the patients' medical records on the other. The vitamin D concentration was determined by the ELFA immunoassay method on mini Vidas (BIOMERIEUX). Results: The mean age of the patients was 45 ± 13 and 65.17% of them were men. 55.06% of the patients had been treated with dialysis for at least 5 years. 48.31% of the patients had regular supplementation treatment. Of the two types of vitamin D supplementation, 94.38% of the study population was supplemented with cholecalciferol compared to 18% for alfacalcidol with 12% of patients included, using both types. From a biological point of view, it appears that the average concentration of vitamin D in the patients was 26.9 ng/mL, and only 16% have a concentration of less than 20 mg/mL, corresponding to an deficiency vitamin D status. Conclusion: At the end of this cross-sectional study, it emerged that the average in adult hemodialysis subjects followed at the CNPTIR in Cocody had an insufficient vitamin D status. And 37% of the study population with normal vitamin D status. However, these results could be improved by better accessibility to the products, and regular compliance with supplementation.

Phosphate metabolism: its impact on disorders of mineral metabolism.

Regulatory molecules typically work cooperatively to ensure the efficient functioning of hormonal systems. Examples include LH and FSH in reproductive biology, insulin and glucagon in glucose metabolism. Similarly, calcium and phosphorus are important regulators of skeletal homeostasis. In the circulation, these molecules are under the control of PTH, 1,25(OHD), and FGF23. In turn, these hormones depend upon a mutual and complex interplay among themselves. For example, alterations in calcium metabolism influence phosphorus homeostasis, as occurs in primary hyperparathyroidism (PHPT). Not as well recognized is the influence that abnormalities in phosphorus metabolism can have on calcium homeostasis. In this review, we call attention to the impact that abnormalities in phosphorus can have on calcium metabolism.

Association between proteinuria and mineral metabolism disorders in chronic kidney disease: the Japan chronic kidney disease database extension (J-CKD-DB-Ex)

Chronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR.

Osteopenia and osteoporosis in patients after bariatric surgery: mechanisms of development, course and prognosis

In recent decades, the medical community around the world has been searching for ways to combat morbid obesity, and despite the variety of methods and techniques, great progress has been noted in recent years in the field of bariatric surgery. Despite its effectiveness, bariatric surgery still has a large number of questions related to the effectiveness of certain methods, their long-term results and the choice of surgery. The purpose of this literature review: to consider the mechanisms of formation, development and course of osteopenia and osteoporosis after bariatric surgery, as well as the frequency of their occurrence depending on the type of bariatric procedure (sleeve gastrectomy, Roux-en-Y gastric bypass, gastric banding, biliopancreatic diversion). To achieve this goal, a literature search on this issue was conducted on the PubMed, eLIBRARY.RU, Google scholar platforms. The material was summarized and analyzed in order to find previously unexplored links in the pathogenesis of osteopenia and osteoporosis and, in general, the mechanisms of mineral metabolism disorders in the postoperative period in patients who underwent bariatric surgeries of varying volumes.

Causal association of serum calcium, phosphate, vitamin D, parathyroid hormone, and FGF23 with the risk of aortic stenosis

Abstract Aim Disorders of mineral metabolism, including elevated levels of serum calcium, phosphate, 25-hydroxyvitamin D (25OH-VitD), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), have been reported in patients with calcific aortic valve stenosis (CAVS). However, evidence of the causal role of mineral metabolism in CAVS is still lacking. We aimed to investigate the causality between mineral metabolism and CAVS. Methods A systematic pipeline combining Mendelian randomization (MR), Steiger directionality test, colocalization analysis, protein-protein network, and enrichment analysis was applied to investigate the causal effect. Genome-wide association study (GWAS) and protein quantitative trait loci data for mineral metabolism markers were extracted from large-scale meta-analyses. Summary statistics for CAVS were obtained from two independent GWAS datasets as discovery and replication cohorts (n=374,277 and 653,867). Results In MR analysis, genetic mimicry of serum FGF23 elevation was associated with increased CAVS risk [ORdiscovery=3.081 (1.649-5.760), Pdiscovery=4.21×10-4; ORreplication=2.280 (1.461-3.558), Preplication=2.82×10-4] without evidence of reverse causation (Psteiger=7.21×10-98). Strong colocalisation association with CAVS was observed for FGF23 expression in the blood (PP.H4 = 0.96). Additionally, we identified some protein-protein interactions between FGF23 and known CAVS causative genes. Serum calcium, phosphate, 25OH-VitD, and PTH failed to show causal effects on CAVS at Bonferroni-corrected significance (all P>0.05/5=0.01). Conclusions Elevated serum FGF23 level is a causal risk factor for CAVS, and its mechanism of action in CAVS development may be independent of its function in regulating mineral metabolism. Hence, FGF23 may serve as a circulating marker and a promising preventive target for CAVS, warranting further investigation.

7336 Decades In The Dark: The Long Road To Diagnosing And Treating Hypophosphatasia

Abstract Disclosure: V.A. Mendpara: None. G. Madrigal Loria: None. L.Z. Khan: None. Background: Hypophosphatasia (HPP) is a rare bone disorder that results from deficient activity of the tissue non-specific isoenzyme alkaline phosphatase (ALP).[1] This case highlights a patient whose diagnosis of this treatable genetic condition was significantly delayed for almost two decades, despite receiving care at a prominent academic institution. The patient's persistently low ALP levels in routine lab tests were overlooked by multiple clinicians, leading to a delay in her care and eventual treatment. Case presentation: A 61-year-old Caucasian woman presented at the endocrinology clinic with complaints of severe fatigue, generalized pain, multiple childhood fractures, and ongoing dental issues. The rheumatology clinic to which she was referred for polyarthralgia diagnosed her with Hypophosphatasia (HPP) after noting chronically low alkaline phosphatase (ALP) levels from her previous charts ranging from 15 to 24 U/L (normal range: 34 to 123 U/L) over two decades. Her serum calcium, parathyroid hormone (PTH), and 25-hydroxy vitamin D levels were within normal ranges. A DEXA scan revealed normal bone density, effectively ruling out osteoporosis. Further investigation showed elevated Vitamin B6 levels at 219.6 nmol/L (normal range: 20.0 to 125.0 nmol/L), raising suspicion for HPP. The patient's family history provided additional insight, with her mother having a history of short stature and fractures and her son experiencing premature tooth loss at the age of 2. A genetic evaluation identified a heterozygous pathogenic variant in the ALPL gene (c.881A>C, p.Asp294Ala), confirming the diagnosis of autosomal dominant HPP. Initiating treatment with Asfotase alfa, a medication targeting HPP, resulted in a marked improvement in the patient's symptoms. Discussion: This case shows the diagnostic complexities of HPP, stressing the significance of actively screening for this condition via ALP levels in routine laboratory testing or during osteoporosis evaluations. The diagnostic process is critical to distinguish HPP from primary osteoporosis, as treatment and potential risks differ significantly. Inadvertent use of bisphosphonates can worsen hypomineralization and lead to atypical femoral fractures in HPP patients. Asfotase alfa enzyme replacement therapy, available since 2015, offers a targeted approach by replacing the enzyme defect, thereby mitigating symptoms. Heightened awareness among healthcare providers of HPP in adults holds the potential to enhance diagnosis rates and facilitate improved treatment outcomes for this highly treatable condition.[1] Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition. ASBMR. Presentation: 6/2/2024

Features of hear microelement composition in children with type 1 diabetes mellitus

Objective: Assessment of the characteristics of the microelement composition of the hair of children with type 1 diabetes mellitus (T1DM) to develop recommendations for diet correction. Material and methods. The study involved children with T1 DM (n=28) and practically healthy children from the comparison group (n=56) aged 3-5 years living in the Omsk region. The elemental composition of hair was analyzed by atomic emission and mass spectrometry with inductively coupled argon plasma. The research materials were subjected to statistical processing using nonpara-metric criteria. Results. The elemental profile of hair of children with T1 DM has been determined. Significant differences were found in the amounts of microelements in hair: lower values of beryllium (p=0.0001), chromium (p=0.003), lithium (p=0.005), vanadium (p=0.005), selenium (p=0.043), and large amounts of cuprum (p=0.025), phosphorus (p=0.001) in the hair of children with diabetes in comparison with the group of practically healthy ones. In the group of children with T1DM, there was a smaller proportion of people with insufficient magnesium (p=0.003), phosphorus (p=0.001), and cuprum (p=0.001). The severity of mineral metabolism disorders (MMD) was less in the group of children with T1DM: 53.6% of children were classified as having no MMD or having minor MMD. Conclusions. The elemental composition of the hair of children with T1DM was characterized by higher amounts of phosphorus and cuprum, lower content of chromium, selenium, beryllium, lithium and vanadium. The proportion of children with insufficient supply of magnesium, phosphorus, cuprum was higher in the comparison group. The degree of MMD in the group of children with T1 DM was generally less.

Genetic association of serum calcium, phosphate, vitamin D, parathyroid hormone, and FGF23 with the risk of aortic stenosis

Disorders of mineral metabolism, including elevated levels of serum calcium, phosphate, 25-hydroxyvitamin D (25OH-VitD), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), have been reported in patients with calcific aortic valve stenosis (CAVS). However, evidence of the causal role of mineral metabolism in CAVS is still lacking. In this study, we employed a systematic pipeline combining Mendelian randomization (MR), Steiger directionality test, colocalization analysis, protein-protein network, and enrichment analysis to investigate the causal effect of mineral metabolism on CAVS. Genome-wide association study (GWAS) and protein quantitative trait loci data for mineral metabolism markers were extracted from large-scale meta-analyses. Summary statistics for CAVS were obtained from two independent GWAS datasets as discovery and replication cohorts (n = 374,277 and 653,867). In MR analysis, genetic mimicry of serum FGF23 elevation was associated with increased CAVS risk [ORdiscovery = 3.081 (1.649–5.760), Pdiscovery = 4.21 × 10−4; ORreplication = 2.280 (1.461 – 3.558), Preplication = 2.82 × 10−4] without evidence of reverse causation (Psteiger= 7.21 × 10−98). Strong colocalisation association with CAVS was observed for FGF23 expression in the blood (PP.H4 = 0.96). Additionally, we identified some protein-protein interactions between FGF23 and known CAVS-associated genes. Serum calcium, phosphate, 25OH-VitD, and PTH failed to show causal effects on CAVS at Bonferroni-corrected significance (all P > 0.05/5 = 0.01). In conclusion, elevated serum FGF23 level may act as a causal risk factor for CAVS, and its mechanism of action in CAVS development may be independent of its function in regulating mineral metabolism. Hence, FGF23 may serve as a circulating marker and a promising preventive target for CAVS, warranting further investigation.

Persistent uncertainties in optimal treatment approaches of secondary hyperparathyroidism and hyperphosphatemia in patients with chronic kidney disease.

This review is a critical analysis of treatment results obtained in clinical trials conducted in patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT), hyperphosphatemia, or both. Patients with CKD have a high mortality rate. The disorder of mineral and bone metabolism (CKD-MBD), which is commonly present in these patients, is associated with adverse outcomes, including cardiovascular events and mortality. Clinical trials aimed at improving these outcomes by modifying CKD-MBD associated factors have most often resulted in disappointing results. The complexity of CKD-MBD, where many players are closely interconnected, might explain these negative findings. We first present an historical perspective of current knowledge in the field of CKD-MBD and then examine potential flaws of past and ongoing clinical trials targeting SHPT and hyperphosphatemia respectively in patients with CKD.

The Importance of Determining the Level of Bone Metabolism Markers and Vitamin D in the First Year of Life in the Kazakh Population.

The research aimed to determine the importance of vitamin D and markers of bone metabolism in the overall assessment of bone mineralization during a child's first year of life. The 198 children were selected by screening all infants seen at our pediatric clinic over a 2-year period from 2020-2022 and including those who met the eligibility criteria of being aged 0 to 1 year, healthy with no chronic conditions, and not on vitamin D supplementation. Children were divided into 3 groups depending on the content of vitamin D in the blood serum: sufficient, insufficient, and deficient. The markers of bone tissue status included: markers of mineral metabolism (calcium, phosphorus, parathyroid hormone, calcitonin), a marker of bone formation (osteocalcin), resorption marker (deoxypyridinoline). Laboratory values were obtained at the time of study enrollment during the initial study visit. Labs were not repeated during the course of the study. A quarter of the infants exhibited vitamin D deficiency at enrollment with serum 25OHD concentrations below 20 ng/mL, which showed a positive correlation with serum calcium and phosphorus -concentrations and a negative correlation with PTH, while osteocalcin and deoxypyridinoline concentrations remained consistent regardless of vitamin D status. The study's practical significance allows for the recommendation of using vitamin D -concentrations as a marker to detect bone formation and mineral metabolism disorders in children during their first year of life. By identifying and addressing these issues early on, the health care system aims to ensure better musculoskeletal health for children.

Environmental and Genetic Determinants of Ankylosing Spondylitis.

Exposure to heavy metals and lifestyle factors like smoking contribute to the production of free oxygen radicals. This fact, combined with a lowered total antioxidant status, can induce even more damage in the development of ankylosing spondylitis (AS). Despite the fact that some researchers are looking for more genetic factors underlying AS, most studies focus on polymorphisms within the genes encoding the human leukocyte antigen (HLA) system. The biggest challenge is finding the effective treatment of the disease. Genetic factors and the influence of oxidative stress, mineral metabolism disorders, microbiota, and tobacco smoking seem to be of great importance for the development of AS. The data contained in this review constitute valuable information and encourage the initiation and development of research in this area, showing connections between inflammatory disorders leading to the pathogenesis of AS and selected environmental and genetic factors.

Food habits of Ukrainian adolescents with obesity

Introduction and objective: There is currently a significant increase in the prevalence of obesity among children worldwide. The aim of the study was to analyse the diet and eating habits of adolescents depending on the presence of obesity and demonstrate the impact of incorrect eating habits on lipid and mineral metabolism disorders. Materials and methods: The study involved 133 adolescents aged 12–17 years: 101 adolescents with obesity and 32 healthy children in the control group. The study plan provided for a combination of standard clinical and anamnestic evaluations, including a study of eating habits, and laboratory-instrumental research. Results: In adolescents with obesity, violations of the regularity of eating (p < 0.001), as well as the habit of snacking on bakery products and sweets during the day (p < 0.01) and late dinner (p < 0.001) were significantly more common compared to the control group. Adolescents with obesity consumed sweets, bakery products, fast food products, chips, crackers significantly more often, and vegetables less frequently, compared to their peers in the control group, every day or several times a week (p < 0.05). Adolescents with obesity had significantly lower levels of zinc and magnesium compared to the control group (p < 0.05). Conclusions: The study revealed the problem of irrational and unbalanced nutrition in adolescents with obesity. The obtained data may become the basis for timely correction of the diet of obese adolescents, which will prevent the development of disorders of the gastrointestinal tract, and halt the progression of the underlying disease.

Current therapeutic approach of chronic kidney disease-mineral and bone disorder.

Chronic kidney disease (CKD) has emerged as one of the leading noncommunicable diseases affecting >10% of the population worldwide. Bone and mineral disorders are a common complication among patients with CKD resulting in a poor life quality, high fracture risk, increased morbidity and cardiovascular mortality. According to Kidney Disease: Improving Global Outcomes, renal osteodystrophy refers to changes in bone morphology found in bone biopsy, whereas CKD-mineral and bone disorder (CKD-MBD) defines a complex of disturbances including biochemical and hormonal alterations, disorders of bone and mineral metabolism and extraskeletal calcification. As a result, the management of CKD-MBD should focus on the aforementioned parameters, including the treatment of hyperphosphatemia, hypocalcemia, abnormal PTH and vitamin D levels. Regarding the bone fragility fractures, osteoporosis and renal osteodystrophy, which constitute the bone component of CKD-MBD, anti-osteoporotic agents constitute the mainstay of treatment. However, a thorough elucidation of the CKD-MBD pathogenesis is crucial for the ideal personalized treatment approach. In this paper, we review the pathology and management of CKD-MBD based on the current literature with special attention to recent advances.

#2061 Perirenal fat thickness as a potential marker for cardiovascular risk in chronic kidney disease: the influence of vitamin D analogs

Abstract Background and Aims Patients with CKD show high cardiovascular complication rates. There are classical cardiovascular risk factors, such as obesity, dyslipidemia, and diabetes; however, other cardiovascular disease risk factors are associated with mineral metabolism disorders (phosphorus, hyperparathyroidism, etc.) typically appear in CKD. Due to their pleiotropic effects, vitamin D analogs, such as cholecalciferol, calcitriol, or paricalcitol, have proven effective in controlling bone mineral disease secondary to CKD and cardiovascular pathologies. On the other hand, visceral adiposity has been shown as a risk factor in the general population and in patients with CKD. Specifically, the fat deposited in regions such as the epicardium generates a complex autocrine and paracrine hormonal mechanism that has been associated with cardiovascular complications. Although it has not been widely evaluated, the adipose tissue surrounding the kidneys (perirenal fat [PRF]) could provide additional information of interest in the CKD population. The aim of the study is to assess the relationship between cardiovascular disease, PRF, and the effect of therapeutic interventions for bone and mineral metabolism in patients with CKD. Method This prospective observational and cross-sectional study was designed to evaluate the usage of vitamin D analogs in patients with CKD, focusing on cardiovascular history and PRF accumulation. All the patients were evaluated at the outpatient clinic in Consuelo Hospital in Valencia Spain (January-November 2022). Eighty-three patients with different grades of CKD (G1A1 to G5A3 not on dialysis) were included and follow-up for 24 months. All the patient's data from electronic medical and analytical records were entered into a protocol sheet. The patients that meet the inclusion criteria (eGFR ≤90 or>15 ml/min/1.73 m2; age ≥18 years at the time of signing informed consent, and a life expectancy higher than 1 year) were eligible to participate in the study. As exclusion criteria, patients with an active inflammatory process such as infection, active cancer, or other inflammatory states were excluded beyond those mentioned in inclusion. Patients with an AKI, ADPKD, or CKD requiring RRT were also excluded. Patients were discriminated according to their history of cardiovascular disease (coronary artery disease, stroke, and peripheral vascular disease) and the use of Vitamin D analogs (Cholecalciferol, Calcitriol, and Paricalcitol). The thickness of the PRF was measured in centimeters (cm) through a B-mode ultrasound with a 3.5-MHz convex transductor (Alpinion®; Alpinion Medical Systems, Korea). Patients underwent a bilateral renal ultrasound, and the kidneys were measured anteroposteriorly, transversally, and longitudinally. PRF was measured in the distal third between the cortex and the hepatic border and/or spleen. Results The mean age of the patients was 58.3 ± 16 years. Patients with a cardiovascular disease history showed significantly higher levels of urea (62.0 vs 45.2 mg/dl, p < 0.05), uric acid (5.5 vs 4.3 mg/dl; p < 0.03), intact parathyroid hormone (iPTH) (186.2 vs 65.2 pcg/dl; p0.05) and decreased eGFR (53.55 vs 89.00 ml/min/1.73 mts2). The mean PRF thickness (0.99 vs 0.80 cm; SD ± 0.30; p0.05) was also observed to be elevated with respect to the group who had no previous cardiovascular events (Fig. 1). Moreover, this group showers higher levels (1.2 vs 7.1; p < 0.005) of CRP. Those patients on oral treatment with Paricalcitol (1 mcg/day) had lesser PRF accumulation than those treated with Cholecalciferol (1000 IU/day) or Calcitriol (0.5 mcg/day) (p < 0.05) (Fig. 2). It was not adjusted for confounding factors such as weight, height, or BMI. Conclusion These results show a close relationship between the presence of cardiovascular disease history and a higher accumulation of PRF. The mechanisms by which paricalcitol could influence the decrease in PRF are so far unknown, however, some studies have shown an association between PTH elevation and obesity. Finally, achieving a decrease in the latter could reduce visceral adipose tissue, thus reducing the cardiovascular risk in CKD-affected patients.

#1552 The role of osteocytes in bone remodeling: comparison between biopsies from patients with osteitis fibrosa and mixed uremic osteodystrophy disease

Abstract Background and Aims Osteocytes represent about 95% of bone cells. They are located in mineralized bone tissue and connect with each other, with osteoblasts, osteoclasts, blood vessels and bone marrow cells. These cells express several proteins that regulate phosphorus-calcium metabolism and bone remodeling. Disorders of mineral metabolism resulting from chronic kidney disease – mineral bone disorder (CKD-MBD) alter tissue function leading to histological changes known as renal osteodystrophy (ROD). ROD is classified: in high turnover – osteitis fibrosa (OF) and mixed uremic osteodystrophy (MUO) and low turnover – adynamic bone disease and osteomalacia. The participation of osteocytes proteins in ROD pathogenesis is not fully explained. The aim of this study was to evaluate the expression of osteocytic proteins in bone biopsies from patients with OF and MUO and analyze clinical, biochemical and bone histomorphometric results. Method We evaluated patients with CKD on hemodialysis, who underwent bone biopsy to elucidate the diagnosis of ROD. Static and dynamic parameters by histomorphometry, including quantification of osteocytes, and the expression of proteins by immunohistochemistry (Sclerostin; Nuclear factor Kappa B ligand – RANKL; Osteoprotegerin – OPG; Dickkopf-related protein 1 - DKK1; Fibroblast growth factor 23 - FGF23; Dentin matrix protein 1 - DMP1; Matrix extracellular phosphoglycoprotein – MEPE; Phosphate regulatory gene with homologies to endopeptidases on the X chromosome – PHEX; podoplanin - E11; and CD44). Results We included 47 patients (24 with OF and 23 with MUO). Table 1 describes the results from the comparison between both groups. Patients with MUO were older and had lower serum P levels compared to patients with OF. Histomorphometric results showed that the structural parameter trabecular number was greater in patients with OF. The formation parameters, as osteoid volume, thickness and surface were greater in patients with MUO. Regarding mineralization, these patients also have lower bone formation rate, and mineralizing surface and a longer mineralization lag time. The expression of osteocytic proteins in both groups showed that DMP-1 was approximately 50% lower, near to statistical significance (p = 0.07) and RANKL was 23% lower in patients with MUO. In Table 2 are described the association found between proteins and histomorphometric parameters. The majority of the proteins involved in bone remodeling are negatively associated with histomorphometric parameters. Conclusion The clinical symptoms of CKD-BMD in patients with OF and MD are similar, and, except for serum P levels, other biochemical parameters did not contribute to differentiate Of and MUO. Bone biopsy, despite being an invasive procedure, revealed differences between the two pathologies, which could better guide clinical treatment, such as, vitamin D supplementation and VD analogs in patients with MUO who present an increase in osteoid parameters, which could improve bone mineralization. Regarding the expression of proteins in osteocytes, we found few differences between the two groups. However, several associations were observed between the expression of these proteins and structural, formation, reabsorption and mineralization parameters in high turnover bone disease.

Exploring the Causal Effects of Mineral Metabolism Disorders on Telomere and Mitochondrial DNA: A Bidirectional Two-Sample Mendelian Randomization Analysis

The aim of this study was to assess the causal relationships between mineral metabolism disorders, representative of trace elements, and key aging biomarkers: telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN). Utilizing bidirectional Mendelian randomization (MR) analysis in combination with the two-stage least squares (2SLS) method, we explored the causal relationships between mineral metabolism disorders and these aging indicators. Sensitivity analysis can be used to determine the reliability and robustness of the research results. The results confirmed that a positive causal relationship was observed between mineral metabolism disorders and TL (p < 0.05), while the causal relationship with mtDNA-CN was not significant (p > 0.05). Focusing on subgroup analyses of specific minerals, our findings indicated a distinct positive causal relationship between iron metabolism disorders and both TL and mtDNA-CN (p < 0.05). In contrast, disorders in magnesium and phosphorus metabolism did not exhibit significant causal effects on either aging biomarker (p > 0.05). Moreover, reverse MR analysis did not reveal any significant causal effects of TL and mtDNA-CN on mineral metabolism disorders (p > 0.05). The combination of 2SLS with MR analysis further reinforced the positive causal relationship between iron levels and both TL and mtDNA-CN (p < 0.05). Notably, the sensitivity analysis did not indicate significant pleiotropy or heterogeneity within these causal relationships (p > 0.05). These findings highlight the pivotal role of iron metabolism in cellular aging, particularly in regulating TL and sustaining mtDNA-CN, offering new insights into how mineral metabolism disorders influence aging biomarkers. Our research underscores the importance of trace element balance, especially regarding iron intake, in combating the aging process. This provides a potential strategy for slowing aging through the adjustment of trace element intake, laying the groundwork for future research into the relationship between trace elements and healthy aging.

Incidence and Prevalence of Fibrous Dysplasia/McCune-Albright Syndrome: A Nationwide Registry-Based Study in Denmark.

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic disorder. Incidence and prevalence are not well-studied. Epidemiological research is complicated by the rarity of FD/MAS, absence of registries, heterogeneous presentation, and possibly asymptomatic phenotype. FD/MAS may present with FGF23-mediated hypophosphatemia, of which the epidemiology is also unclear. Evaluate incidence and prevalence of FD/MAS and FD/MAS-related hypophosphatemia. This cohort study based on the nationwide Danish National Patient Registry from 1995-2018, included patients identified by ICD-10 codes M85.0 (monostotic FD [MFD]) and Q78.1 (polyostotic FD [PFD]/MAS). Incidence rates and prevalence were calculated and stratified by sex, age, calendar period, and diagnosis code. Cases were screened for FD-associated hypophosphatemia by diagnosis code E.83 (disorder of mineral metabolism) and dispatched vitamin D analogues. A total of 408 patients were identified, 269 with MFD (66%), 139 with PFD/MAS (34%), comparable between sexes. Incidence of FD/MAS demonstrated increasing secular trend with a rate of 3.6 per 1 000 000 person-years (95% CI: 2.9, 4.5) in 2015-2018. Incidence peaked between age 11 and 20. Prevalence of FD/MAS increased over time to 61.0 (95% CI: 54.6, 67.4) per 1 000 000 persons in 2018. The incidence rate of MFD was 1.5-fold that of PFD/MAS in the first decade, rising to 2.5-fold in the last decade. No FD/MAS cases were registered with diagnosis code or treatment for hypophosphatemia. FD/MAS is rare, diagnosis peaks during adolescence without sex predominance, and MFD is most prevalent. Hypophosphatemia may be underdiagnosed and undertreated, or it may be underregistered, comparing this study to literature.

VITAMIN D, CALCIUM, AND PHOSPHORUS STATUS IN CHILDREN WITH SPINA BIFIDA

Introduction. Children with spina bifida (SB) are at the highest risk of developing vitamin and mineral deficiencies, including vitamin D, due to a sedentary lifestyle, prolonged indoor stays, and dietary peculiarities. The aim of our study was to determine the dietary intakes of vitamin D, calcium, and phosphorus in children with spina bifida and the concentration of these nutrients in the serum of children with SB. Materials and Methods. The study included 20 children aged 2 to 17 years with congenital neural tube defect (spina bifida). The control group consisted of 67 healthy children aged 6 to 17 years. To determine the dietary intakes of vitamin D, calcium and phosphorus, children or their parents were surveyed using a questionnaire containing questions about the amount of consumption of certain food products over the week. The total amount of vitamin D, calcium, and phosphorus in the weekly diet were calculated, as well as their average daily intakes with food and overall. The concentration of 25-OH vitamin D, calcium, and phosphorus in the blood serum was determined using an enzyme immunoassay. Results. Among the examined children with SB, girls predominated (70.0%). Physical development delay and undernutrition were identified in 3 (15.0%), overweight - in 6 (30.0%) children. Most children with SB exhibited clinical manifestations of mineral metabolism disorders: body proportion disturbances (55.0%), posture disorders (40.0%), scoliosis and/or chest deformity (50.0%), caries (40.0%). Despite the presence of dairy, meat, and fish products in the weekly diet of all children with SB, their quantity was insufficient to meet the daily needs for vitamin D, calcium, and phosphorus. Inadequate intake of vitamin D from food occurred in 70.0% of children, calcium deficiency in 90.0%, phosphorus deficiency in 80.0%, with the alimentary provision of calcium and phosphorus in children with SB being significantly lower than in healthy children (p=0.0027 and p=0.0047, respectively). Optimal levels of vitamin D in the blood serum were observed in only 10.0% of children with SB, which was twice less than in healthy children, while its deficiency was observed 1.5 times more often in children with SB than in healthy children. Half of the patients with SB had reduced calcium levels, and 70.0% had reduced phosphorus levels. Conclusions. The study results demonstrate a wide prevalence of vitamin D deficiency and insufficiency (in 90.0%), calcium and phosphorus deficiency in children with SB, indicating the need for additional intake of these nutrients alongside dietary and lifestyle corrections. Further research on a larger cohort of patients with supplementation regimens is necessary to reduce the risk of complications and improve the quality of life for children with SB.

Polypharmacy in acute and chronic kidney diseases

The prevalence for chronic kidney disease (CKD) has steadily increased over the past decades. It is agradually progressive disease that is associated with several comorbidities including cardiovascular diseases, hypertension, anemia, disorders of bone and mineral metabolism, electrolyte imbalance and acid-base abnormalities. All these comorbidities require adequate medication. Therefore, patients with CKD have a high risk for polypharmacy, which is defined as five or more medications daily. Polypharmacy causes agreatly increased risk for adverse drug effects and severe drug-drug interactions, which if not closely controlled and the individual doses adapted to the decreased renal function during the progression of the CKD, can result in increased morbidity and mortality. Therefore, several aspects of the medication need to be considered and constantly addressed. This article summarizes the problems arising from inadequate polypharmacy in CKD patients, including undesired adverse drug effects, drug interactions, the complexity of medication plans, treatment burden and nonadherence to the treatment. Furthermore, the most important steps to identify patients with inadequate polypharmacy are discussed, whereby complications can also be avoided and the benefits of the medication can be increased. Finally, the polypharmacy in acute kidney injury is dealt with.

Bone Disorders in Pediatric Chronic Kidney Disease: A Literature Review.

Intense changes in mineral and bone metabolism are frequent in chronic kidney disease (CKD) and represent an important cause of morbidity and reduced quality of life. These disorders have conventionally been defined as renal osteodystrophy and classified based on bone biopsy, but due to a lack of bone biopsy data and validated radiological methods to evaluate bone morphology in children, it has been challenging to effectively assess renal osteodystrophy in pediatric CKD; the consequence has been the suboptimal management of bone disorders in children. CKD-mineral and bone disorder (CKD-MBD) is a new expression used to describe a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is a triad of biochemical imbalances in calcium, phosphate, parathyroid hormone, and vitamin D; bone deformities and soft tissue calcification. This literature review aims to explore the pathogenesis, diagnostic approach, and treatment of CKD-MBD in children and the effects of renal osteodystrophy on growing skeleton, with a specific focus on the biological basis of this peculiar condition.