Vitamin D Review: The Low Hanging Fruit for Human Health

Vitamin D is an important hormone that is known for the regulation of calcium and phosphate metabolism. Vitamin D deficiency leads to rickets in children and osteoporosis in adults leading to poor bone mineralisation and can also lead to serious dental complications in the same population. Recent studies have shown vitamin D to work as a hormone needed not only in bone and teeth but also in other body organs from intrauterine life up to old age. It has been demonstrated that Vitamin D has various effects on biological processes that deal with cell growth, differentiation, cell death, immune regulation, DNA stability, and neuronal growth. Despite being readily formed in the body through the intervention of the sun, patients are still found to have low vitamin D levels. We review studies done to show how vitamin D works.

A comparative study on the effect of calcitriol and cinacalcet on hyperparathyroidism in hemodialysis patients; a double-blinded randomized clinical trial

Introduction:Chronic kidney disease (CKD) has lots of complication like calcium and phosphate metabolism disorders, hyperparathyroidism, vitamin D deficiency and metabolic acidosis. Objectives: The aim of this study was to determine and compare the effect of calcitriol and cinacalcet on hyperparathyroidism in hemodialysis patients due to end-stage renal disease (ESRD). Patients and Methods: This study was a double-blinded randomized clinical trial, which was conducted on 60 hemodialysis patients in 2017-2018. The patients were randomly assigned to two groups of 30 patients, which one group was treated with cinacalcet and the other group was treated with calcitriol. During this study, phosphorus, calcium and iPTH were measured. Results: The results showed that in the group treated with cinacalcet, the amount of calcium [t(22)=0.294, P>0.05] and the amount of phosphorus [t(22)=1.87, P>0.05] did not change significantly while iPTH values before and after the study had statistically significant difference [t(22)=4.37, P<0.05]. In group treated with calcitriol, the calcium, phosphorus and iPTH values did not change significantly (P>0.05). Calcium changes in the cinacalcet group compared to the calcitriol group [t (47) =-1.14, P>0.05] and also, the amount of phosphorus changes [t (47) =-1.022, P>0.05] was not statistically significant. The iPTH changes were not statistically significant between the two groups however iPTH in the calcitriol group was higher than the cinacalcet group [t (47) =-1.13, P>0.05]. Conclusion: In contrast to calcitriol, cinacalcet significantly reduced iPTH and did not significantly change calcium and phosphorus levels. Trial Registration: The trial was registered by Iranian Registry of Clinical Trials (IRCT) (identifier: IRCT20190702044076N1; https://en.irct.ir/trial/40547, Ethical code# IR.SKUMS.REC.1397.026).

Vitamin D Intoxication and Nephrocalcinosis in a Young Breastfed Infant

Numerous studies were performed assessing the benefits and side effects of vitamin D. Vitamin D helps in regulating the calcium and phosphate metabolism leading to a healthy mineral and bone development. Vitamin D intoxication is an uncommon event that leads to hypercalcemia which can be associated with both immediate and late morbidities that can cause severe renal complications. Here, we present a case of a 4-month-old girl with a history of decreased feed and activity due hypercalcemia and high vitamin D level, which led to nephrocalcinosis. The patient received IV fluids, IV diuretics, methylprednisolone, and bisphosphonate in order to normalize the calcium level in blood. With clear verbal and written instructions for the dosage and administration of vitamin D supplements, as well as clear warnings of the potential risks of overdose, vitamin D intoxication could be an easily avoidable condition.

Pleiotropic effects of vitamin D3

Introduction: Vitamin D belongs to the group of fat-soluble vitamins. cholecalciferol (D3) and ergocalciferol (D2) are the most important forms. Vitamin D is associated with a regulatory role in calcium and phosphate metabolism. In recent years, there has been attention to its pleiotropic action. Aim: The aim of the study was to present the general characteristics of vitamin D and explore its relation with polycystic ovary syndrome (PCOS), endometriosis, pain management, insulin resistance, influenza and chronic kidney disease (CKD).Description: VDR receptor has been detected in the cells of the intestines, bones, kidneys, heart, brain, prostate, breast, ovaries, skin. In the ovaries, vit. D3 affects the production of progesterone, estradiol or estrone which suggest its important role in the folliculogenesis and ovulation. Women with PCOS have significantly lower levels of vitamin D3 compared to healthy women. It has been suggested that the deficiency of this vitamin may be related to infertility. Research show that vit. D3 may affect the mechanisms of the inflammatory and nocyceptive pain perception. A significant connection has also been found between vit. D3 and the metabolism of the adipose tissue and insulin secretion. Vitamin D3 deficiency may increase the risk of development of obesity and insulin resistance as well as CKD.Summary: The observation of statistically significant correlation between the reduced level of vit. D3 and occurrence of numerous diseases indicates the need for further research to explain the mechanisms in which D3 deficiency may contribute to development of these diseases. This knowledge is important for the development of new prevention and treatment methods of the diseases mentioned in this article.

Progressive valvular calcifications with critical aortic stenosis in a 25-year-old woman with end-stage renal disease on haemodialysis: a case report

Background The increased risk of cardiovascular morbidity and mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) seems particularly pronounced in patients with concomitant aortic and mitral valvular calcifications. Valvular calcification (VC) is accelerated in patients with CKD and even more so with ESRD and haemodialysis (HD) due to premature endothelial cell dysfunction. Mineral and bone disorder (CKD-MBD) is a common complication of CKD/ESRD and may play a pivotal role in VC. Case summary A 25-year-old woman with congenital hypoplastic kidneys and ESRD on HD from the age of 19 was admitted to the emergency department suffering from chest pain and dyspnoea. Transthoracic echocardiogram (TTE) revealed critical aortic stenosis (AS) with indexed aortic valve area 0.4 cm2/m2, a mean gradient 58 mmHg and a moderate mitral stenosis with a mean gradient 6–8 mmHg developed over the course of 2 years, as a normal TTE was performed at that time. During HD, the patient had longstanding alterations in calcium and phosphate metabolism including secondary hyperparathyroidism that eventually progressed into tertiary hyperparathyroidism. Efforts were made to treat CKD-MBD but patient compliance was low. Subtotal parathyroidectomy was performed 6 months prior to admission. The patient had dual mechanical valve replacement. Discussion Valvular calcification is common in patients with CKD/ESRD and in particular in patients on HD. Rapid progression of valve disease in this case may be related to the combination of low patient adherence and sustained disturbed calcium and phosphate metabolism with tertiary hyperparathyroidism. Transthoracic echocardiogram should be performed in patients on HD even with minor suspicion of VC and in patients with low adherence and disturbance of calcium and phosphate metabolism.

FGF23: A Review of Its Role in Mineral Metabolism and Renal and Cardiovascular Disease

FGF23 is a hormone secreted mainly by osteocytes and osteoblasts in bone. Its pivotal role concerns the maintenance of mineral ion homeostasis. It has been confirmed that phosphate and vitamin D metabolisms are related to the effect of FGF23 and its excess or deficiency leads to various hereditary diseases. Multiple studies have shown that FGF23 level increases in the very early stages of chronic kidney disease (CKD), and its concentration may also be highly associated with cardiac complications. The present review is limited to some of the most important aspects of calcium and phosphate metabolism. It discusses the role of FGF23, which is considered an early and sensitive marker for CKD-related bone disease but also as a novel and potent cardiovascular risk factor. Furthermore, this review gives particular attention to the reliability of FGF23 measurement and various confounding factors that may impact on the clinical utility of FGF23. Finally, this review elaborates on the clinical usefulness of FGF23 and evaluates whether FGF23 may be considered a therapeutic target.

Features of the clinical course of nephrolithiasis in patients with hyperparathyroidism

Aim. To assess the incidence of kidney stone disease and to identify its clinical course in patients with primary hyperparathyroidism. Methods. 48 medical records of patients hospitalized with primary hyperparathyroidism were retrospectively analyzed. The average age of the patients was 57 [53; 61] years. The medical history, complaints upon admission, the clinical presentation, the results of laboratory test and instrumental examination were studied in evaluating the medical records. The patients were divided into the group with nephrolithiasis (n=33) and the group without nephrolithiasis (n=15). The differences between the two groups were tested for statistical significance by the MannWhitney U test. Results. Among patients with primary hyperparathyroidism, nephrolithiasis was detected in 69% of patients, of which 90% were women in the postmenopausal period. The course of the kidney stone disease in these patients was characterized by frequent recurrence with a predominance of bilateral renal impairment (62%). The duration of nephrolithiasis before the diagnosis of primary hyperparathyroidism was 6 [1; 19] years, and this complication was often the first manifestation of the disease. According to the instrumental examination of kidney in patients with nephrolithiasis, small stones up to 5 mm in diameter were detected in 42% of cases, asymptomatic kidney stones in 15% of cases. A severe complication of primary hyperparathyroidism staghorn calculi were found in 2 (10%) patients. The patients in the group with nephrolithiasis showed higher serum calcium (p=0.022) and parathyroid hormone (p=0.007) levels compared with patients in the group without nephrolithiasis. Conclusion. Nephrolithiasis is a common complication of primary hyperparathyroidism; the presence of nephrolithiasis is associated with more significant changes in calcium and phosphate metabolism and is also characterized by a frequent asymptomatic course, thus requiring attention of specialists to this type of complications in primary hyperparathyroidism.

Molecular mechanosensors in osteocytes

Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the major responsive cells in force adaptation due to mechanical stimulation. Mechanically induced bone formation and adaptation, disuse-induced bone loss and skeletal fragility are mediated by osteocytes, which sense local mechanical cues and respond to these cues in both direct and indirect ways. The mechanotransduction process in osteocytes is a complex but exquisite regulatory process between cells and their environment, between neighboring cells, and between different functional mechanosensors in individual cells. Over the past two decades, great efforts have focused on finding various mechanosensors in osteocytes that transmit extracellular mechanical signals into osteocytes and regulate responsive gene expression. The osteocyte cytoskeleton, dendritic processes, Integrin-based focal adhesions, connexin-based intercellular junctions, primary cilium, ion channels, and extracellular matrix are the major mechanosensors in osteocytes reported so far with evidence from both in vitro and in vitro studies. This review aims to give a systematic introduction to osteocyte mechanobiology, provide details of osteocyte mechanosensors, and discuss the roles of osteocyte mechanosensitive signaling pathways in the regulation of bone homeostasis.