Vitamin D metabolism and extraskeletal outcomes: an update

ABSTRACT Vitamin D deficiency is a general health problem affecting individuals at all stages of life and on different continents. The musculoskeletal effects of vitamin D are well known. Its deficiency causes rickets, osteomalacia, and secondary hyperparathyroidism and increases the risk of fractures. Clinical and experimental evidence suggests that vitamin D performs multiple extraskeletal functions. Several tissues unrelated to calcium and phosphate metabolism express vitamin D receptor (VDR) and are directly or indirectly influenced by 1,25(OH)2D (calcitriol). Some also express the enzyme 1 alpha-hydroxylase (CYP27B1) and produce 1,25(OH)2D, inducing autocrine or paracrine effects. Among the pleiotropic effects of vitamin D are the regulation of cell proliferation and differentiation, hormone secretion, and immune function. In this review, we outline vitamin D physiology and the outcomes of recent large RCTs on its potential extraskeletal effects. Those studies exhibit a need for continued clinical analysis to elucidate whether vitamin D status can influence extraskeletal health. Longer longitudinal follow-up and standardized assays are crucial to better assess potential outcomes.

Low serum 25-hydroxy vitamin D levels are associated with aggressive breast cancer variants and poor prognostic factors in patients with breast carcinoma

ABSTRACT Objective: This study was conducted to assess the serum 25-hydroxy (OH) vitamin D levels in patients with breast cancer compared to healthy controls and to identify its association with aggressive breast cancer phenotypes. Materials and methods: Serum 25-OH vitamin D levels of 78 breast cancer patients and 78 matched healthy controls were estimated using ELISA. The cases and controls were matched with respect to age, menopausal status, parity, weight, height and co-morbidities. Prognostic factors like grade of tumour, hormone receptor status, HER2 neu status and lymphovascular invasion were compared with 25-OH vitamin D levels. Results: The mean serum 25-OH vitamin D levels of cases were significantly lower compared to the controls (22.33 ± 8.19 vs. 37.41 ± 12.9 ng/mL; p = 0.0001). Patients with higher grades of tumour, non-luminal types of breast cancer and breast cancers with estrogen receptor negativity had significantly lower serum 25-OH vitamin D levels than their opposing groups. Patients with excellent and good Nottingham's prognostic Index (NPI) had significantly higher serum 25-OH vitamin D levels than the moderate and poor NPI groups. Conclusion: Newly diagnosed breast cancer patients have significantly lower serum 25-OH vitamin D levels than healthy controls. Lower level of serum 25-OH vitamin D correlates with aggressive breast cancer phenotypes.

Vitamin D level in patients with pterygium / Níveis de vitamina D em pacientes com pterígio

ABSTRACT Purpose: To evaluate blood vitamin D level in patients with pterygium. Methods: This prospective study, compared 58 eyes of 58 healthy individuals (control group) with 63 eyes of 63 patients with pterygium (study group). Subjects were stratified by time spent indoors or outdoors. Participants were given comprehensive ophthalmic examinations; blood 25-hydroxyvitamin D (nmol/L) was assayed. Results: Vitamin D level was significantly higher in men with pterygium than without it (p=0.020), but the difference was not significant in women (p=0.86). In the pterygium group, vitamin D level was significantly increased in participants with outdoor activity (p=0.010). In the control group, vitamin D levels did not differ significantly with indoor and outdoor activity (p=0.126). Conclusion: Vitamin D level in participants with pterygium was significantly increased only in men and in those with more outdoor activity.

RESUMO Objetivo: Avaliar os níveis sanguíneos de vitamina D em pacientes com pterígio. Métodos: Neste estudo prospectivo e comparativo, foram incluídos 58 olhos de 58 indivíduos saudáveis (grupo controle) e 63 olhos de 63 pacientes com pterígio (grupo de estudo). Os indivíduos também foram categorizados quanto ao tempo foi gasto dentro de casa ou ao ar livre. Todos os participantes foram submetidos a exames oftálmicos e avaliações de nível sanguíneo 25-hidroxivitamina D (nmol/L). Resultados: O nível de vitamina D foi significativamente maior em pacientes masculinos com pterígio do que aqueles sem pterígio (p=0,020). Não houve diferença significativa entre mulheres do grupo de estudo e controle (p=0,86). No grupo pterígio, o nível de vitamina D foi significativamente maior no subgrupo com atividade ao ar livre (p=0,010). No grupo controle, o nível de vitamina D não foi significativamente diferente entre a atividade interna e ao ar livre (p=0,126). Conclusão: Os achados deste estudo revelaram que o nível de vitamina D nos casos de pterígio foi significativamente maior apenas nos homens e nos casos com maior atividade ao ar livre.

Women with recurrent spontaneous abortion have decreased 25(OH) vitamin D and VDR at the fetal-maternal interface

Immunological mechanisms have been proposed to underlie the pathogenesis of recurrent spontaneous abortion (RSA). Vitamin D has a potent immunomodulatory effect, which may affect pregnancy outcome. The objective of this study was to investigate 25-hydroxyvitamin D [25(OH) D] concentration and vitamin D receptor (VDR) expression in the decidual tissues of RSA patients. Thirty women with RSA (RSA group) and thirty women undergoing elective abortion (control group) were recruited during 2016 from gynecology outpatient clinics. We measured 25(OH) D, interleukin (IL)-17, IL-23, transforming growth factor β (TGF-β), VDR and 1-α-hydroxylase (CYP27B1) in decidual tissues collected during the abortion procedure. In the RSA group, 25(OH) D and TGF-β were significantly decreased while IL-17 and IL-23 were significantly increased compared with the control group. VDR expression was significantly decreased in the RSA group compared with the control group. Logistic regression analysis showed a significant negative correlation between 25(OH) D in decidual tissues and RSA. These results indicated that vitamin D concentrations in the decidua are associated with inflammatory cytokine production, suggesting that vitamin D and VDR may play a role in the etiology of RSA.

Type II Vitamin D Dependent Rickets: A Case Report.

Vitamin D-dependent rickets Type II is a rare autosomal recessive disorder. Alopecia of the scalp or the body is seen in some families with Vitamin D-dependent rickets Type II. We report a child with this disease, and review the salient features of this disease with emphasis on the associated alopecia. Due to lack of facilities for estimation of 1, 25(OH)2 D and parathyroid hormone, alopecia remains the only clue to the diagnosis of this rare syndrome in association with resistant rickets.

Vitamina D e análogos para o controle do hiperparatireodismo secundário / Vitamin D and analogues in the aontrol of secondary hyperparathyroidism

A vitamina D participa (d)o metabolismo mineral e sua deficiência está associada com doenças extra-ósseas Estudos têm evidenciado hipovitaminose Dna população geral e em renais crônicos. Na progressão da doença renal crônica (DRC), a redução dos níveis de calcitriol, hipocalcemia e hiperfosfatemiasão fatores causais do hiperparatireoidismo secundário (HPTS). Utilizamos o calcitriol para o manejo do HPTS e da hipovitaminose D per se também devemser enfatizadas. Novos análogos da vitamina D, desenvolvidos para substituírem o calcitriol devido à hipercalcemia e hiperfosfatemia associadas ao seuuso, não se mostraram superiores no controle do HPTS. O estado de conhecimento atual sugere a realização de estudos randomizados, controlados ecom amostragem maior para comparar efetividade e segurança entre estes análogos e o calcitriol. Assim, estes estudos poderiam sinalizar para um melhor controle mineral e da doença óssea e resultar em um impacto favorável na morbi-mortalidade na DRC.

Vitamin D has been reported as pivotal for mineral metabolism and bone health, and its deficiency has also been associated with non-skeletal diseases.Many studies have shown high prevalence of vitamin D deficiency in general population as well as in chronic kidney disease (CKD) patients. In CKD progression, low calcitriol levels, hypocalcemia and hyperphosphatemia have all been implicated in the genesis of the secondary hyperparathyroidism (SHPT).In addition to calcitriol supplementation for SHPT management, emphasis should be given to the diagnosis and treatment of vitamin deficiency itself. Newvitamin D analogs were developed in an attempt to overcome the hypercalcemia and hyperphosphatemia that can follow calcitriol treatment but currentknowledge does not allow any conclusion about superiority of new analogs. Large randomized controlled trials studies are needed to compare efficacy and safety of these analogs and calcitriol. These studies could promote a better understanding of mineral metabolism and bone disease control, and result in a favorable impact on morbidity and mortality of CKD patients.