The Extraglycemic Effect of SGLT-2is on Mineral and Bone Metabolism and Bone Fracture.

Type 2 diabetes mellitus (T2DM) is a risk factor for osteoporosis. The effects of T2DM and anti-diabetic agents on bone and mineral metabolism have been observed. Sodium-glucose co-transporter 2 inhibitors (SGLT-2is) promote urinary glucose excretion, reduce blood glucose level, and improve the cardiovascular and diabetic nephropathy outcomes. In this review, we focused on the extraglycemic effect and physiological regulation of SGLT-2is on bone and mineral metabolism. SGLT-2is affect the bone turnover, microarchitecture, and bone strength indirectly. Clinical evidence of a meta-analysis showed that SGLT-2is might not increase the risk of bone fracture. The effect of SGLT-2is on bone fracture is controversial, and further investigation from a real-world study is needed. Based on its significant benefit on cardiovascular and chronic kidney disease (CKD) outcomes, SGLT-2is are an outstanding choice. Bone mineral density (BMD) and fracture risk evaluation should be considered for patients with a high risk of bone fracture.

El déficit de vitamina D en pacientes con espondiloartritis en un hospital de Castilla-La Mancha / Vitamin D deficiency in patients with spondylarthritis in a Spanish (Castilla-La Mancha) hospital

RESUMEN Introducción: Las espondiloartritis son un grupo de enfermedades inflamatorias crónicas con afectación principalmente del esqueleto axial y también de articulaciones periféricas. En cuanto al metabolismo óseo de estos pacientes, se ha observado en algunos estudios que existen niveles más bajos de vitamina D en pacientes con espondiloartritis. Objetivo: Estimar la prevalencia de déficit/insuficiencia de vitamina D, el metabolismo fosfocálcico y sus implicaciones en una cohorte de pacientes con espondiloartritis. Metodología: Estudio observacional, descriptivo y transversal. Se llevó a cabo una revisión retrospectiva de la base de datos de pacientes con espondiloartritis que fueron atendidos en las consultas externas del Servicio de Reumatología del Hospital General Universitario de Ciudad Real entre junio del 2018 y junio del 2019. Las variables se describieron usando medidas de frecuencia o medidas de tendencia central/dispersión según correspondiera. Resultados: Se analizaron 115 pacientes, de los cuales 64 fueron hombres y 51 mujeres, con una edad media de 45,97 años (± 13,41 DE). Del total de los pacientes, 59 presentaron espon dilitis anquilosante, 24 artropatía psoriásica, 9 artritis asociada a enfermedad inflamatoria intestinal, 12 espondiloartritis axial no radiográfica y 11 artritis reactiva. Los niveles de vitamina D fueron de 23,81 ng/ml (±10,5 DE), con un 77,4% de los pacientes con cifras de déficit/insuficiencia de vitamina D. Agrupados por el subtipo de espondiloartritis y según las cifras de déficit/insuficiencia de vitamina D, 45 pacientes tenían espondilitis anquilo sante, 19 artropatía psoriásica, 9 artritis asociada a enfermedad inflamatoria intestinal, 7 espondiloartritis axiales no radiográficas y 9 artritis reactivas. Además, el déficit de vita mina D (< 20 ng/ml) se presentaba la mayoría de las veces en las estaciones de primavera e invierno, con 31 y 26 pacientes respectivamente. Conclusiones: Una optimización de los niveles de vitamina D puede implicar una mejoría en la situación clínica del paciente, medida tanto por BASDAI y DAPSA como por PCR y VSG. En consecuencia, se recomienda la monitorización y suplementación de vitamina D en pacientes con hipovitaminosis D.

ABSTRACT Introduction: Spondyloarthritis is a group of chronic inflammatory diseases that mainly affect the axial skeleton, and also the peripheral joints. In bone metabolism studies on these patients, it has been observed that there are lower levels of vitamin D in patients with spondyloarthritis. Objective: To estimate the prevalence of vitamin D deficiency / insufficiency, as well as calcium/ phosphate metabolism and their implications in a cohort of patients with spondyloarthritis. Methodology: Observational, descriptive, and cross-sectional study. A retrospective review of the databases was carried out on patients with spondyloarthritis who were treated in the outpatient clinics of the Rheumatology Department of the General University Hospital of Ciudad Real between June 2018 and June 2019. Variables are described using frequency and central tendency / dispersion measurements as appropriate. Results: The study included 115 patients, of whom 64 were men and 51 women, with a mean age of 45.97 years (± 13.41 SD). They included 59 patients with ankylosing spondylitis, 24 with psoriatic arthropathy, 9 arthritis associated with inflammatory bowel disease, 12 non-radiographic axial spondylarthritis, and 11 reactive arthritis. Vitamin D levels were 23.81 ng/ml (± 10.5 SD), with 77.4% of patients with vitamin D deficiency / insufficiency levels. Grouped by the spondylarthritis subtype, and according to vitamin D deficiency / insufficiency, 45 patients had ankylosing spondylitis, 19 psoriatic arthropathy, 9 arthritis associated with inflammatory bowel disease, 7 non-radiographic axial spondyloarthritis, and 9 reactive arthritis. Furthermore, vitamin D deficiency (< 20 ng/ml) mainly occurred in the spring and winter seasons, with 31 and 26 patients, respectively. Conclusions: An optimization of vitamin D levels may lead to an improvement in the clinical situation of the patients, as measured by both BASDAI and DAPSA, as well as by PCR and ESR. Therefore, vitamin D monitoring and supplementation is recommended in patients with vitamin D deficiency.

The Role of Diet in Bone and Mineral Metabolism and Secondary Hyperparathyroidism.

Bone disorders are a common complication of chronic kidney disease (CKD), obesity and gut malabsorption. Secondary hyperparathyroidism (SHPT) is defined as an appropriate increase in parathyroid hormone (PTH) secretion, driven by either reduced serum calcium or increased phosphate concentrations, due to an underlying condition. The available evidence on the effects of dietary advice on secondary hyperparathyroidism confirms the benefit of a diet characterized by decreased phosphate intake, avoiding low calcium and vitamin D consumption (recommended intakes 1000-1200 mg/day and 400-800 UI/day, respectively). In addition, low protein intake in CKD patients is associated with a better control of SHPT risk factors, although its strength in avoiding hyperphosphatemia and the resulting outcomes are debated, mostly for dialyzed patients. Ultimately, a consensus on the effect of dietary acid loads in the prevention of SHPT is still lacking. In conclusion, a reasonable approach for reducing the risk for secondary hyperparathyroidism is to individualize dietary manipulation based on existing risk factors and concomitant medical conditions. More studies are needed to evaluate long-term outcomes of a balanced diet on the management and prevention of secondary hyperparathyroidism in at-risk patients at.

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up / Biomarcadores del metabolismo mineral óseo (FGF-23, fetuína-A) y calcificaciones vasculares como herramientas predictivas de muerte cardiovascular de pacientes en diálisis, a 10 años de seguimiento

Abstract Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary stud ies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Resumen Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad car diovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p<0.001). El mejor punto de corte fue de 5 (sensibili dad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up.

Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary studies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad cardiovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p < 0.001). El mejor punto de corte fue de 5 (sensibilidad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Transcriptomics: a Solution for Renal Osteodystrophy?

PURPOSE OF REVIEW: The molecular mechanisms of the bone disease associated with chronic kidney disease (CKD), called renal osteodystrophy (ROD), are poorly understood. New transcriptomics technologies may provide clinically relevant insights into the pathogenesis of ROD. This review summarizes current progress and limitations in the study and treatment of ROD, and in transcriptomics analyses of skeletal tissues. RECENT FINDINGS: ROD is characterized by poor bone quality and strength leading to increased risk of fracture. Recent studies indicate permanent alterations in bone cell populations during ROD. Single-cell transcriptomics analyses, successful at identifying specialized cell subpopulations in bone, have not yet been performed in ROD. ROD is a widespread poorly understood bone disease with limited treatment options. Transcriptomics analyses of bone are needed to identify the bone cell subtypes and their role in the pathogenesis of ROD, and to develop adequate diagnosis and treatment strategies.

Factors and Outcome of Renal Osteodystrophy-Associated Initial Fragility Fracture in End-Stage Renal Disease Patients.

BACKGROUND: Renal osteodystrophy has caused increased risk of fragility fracture in end-stage renal disease (ESRD) patients. However, risk factors and outcome of ESRD patients with fragility fracture remain uncharacterized. We aimed to assess these parameters in ESRD patients. SUMMARY: This retrospective case-control study analyzed 354 ESRD patients (initial fragility fracture [FF] group, n = 59; control group, n = 295). Pre-dialysis blood hemoglobin, serum albumin, lipid, calcium, phosphorus, alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) were collected. All procedures performed involving human participants were in accordance with the ethical standards of the institutional committee of The First Affiliated Hospital of Chongqing Medical University (IRB approval number 216-82), and informed consent was obtained from all participants. There were higher prevalence rates of primary hypertension and diabetes, higher serum ALP, corrected calcium, and lower serum total cholesterol, low-density lipoprotein, lipoprotein-α, and iPTH in the FF group. Fractures were more likely to occur in the higher level of corrected calcium as well as in the lower iPTH group. High corrected calcium (p = 0.010, OR = 11.308, 95% CI: 1.770-72.242) and serum ALP (p = 0.000, OR = 1.007, 95% CI: 1.004-1.011) were independent risk factors of fragility fracture. The incidence of all-cause mortality and cardiovascular (CV) events in ESRD patients with fragility fracture was higher than in those without fracture. KEY MESSAGES: Patients with hypertension, diabetes, excessive suppression of PTH, and poor nutritional status are more prone to fractures. Serum corrected calcium and ALP were independent risk factors of fragility fracture. Patients with initial fragility fracture had more CV events and higher mortality.

¿Puede establecerse hoy un valor de fosfatemia como indicador de calidad del tratamiento dialítico? / Can a phosphatemia value be established today as an indicator of the quality of the dialysis treatment?

INTRODUCCIÓN: El trastorno del metabolismo óseo y mineral constituye una grave complicación de la IRC. Respecto al fósforo, las nuevas Guías KDIGO sugieren disminuirla hiperfosfatemia, sin recomendar un valor determinado. Sin embargo, en Argentina se continúa utilizando como indicador de calidad dialítica (IndCalDial) un valor de fósforo igual o inferior a 5 mg.dl. Nuestro objetivo fue evaluar si un valor fijo de fosfatemia es válido como IndCalDial. MATERIAL Y MÉTODOS: Se realizó un estudio multicéntrico, de corte transversal. Se incluyeron pacientes mayores de 18 años, con más de 90 días en hemodiálisis crónica. Se tabularon datos demográficos y de laboratorio. Según el reactivo empleado en la determinación de fósforo, en 4 centros el límite superior de referencia fue 4.5 mg.dl (Grupo F4.5) y en tres 5.6 mg.dl (Grupo F5.6). RESULTADOS: Se incluyeron 334 pacientes. Edad, sexo, porcentaje con FAV, diabéticos, tiempo en diálisis, Kt/V, Hemoglobina y Albúmina, resultaron semejantes a los del Registro Nacional de Diálisis. La mediana de fosfatemia fue 5.2 mg.dl, (rango: 2.3 a 10.6). Los pacientes hiperfosfatémicos fueron más jóvenes y presentaron mejores niveles de Albúmina. De considerarse como IndCalDial: Fósforo menor a 5 mg.dl, 21 pacientes del Grupo F4.5 (n=154) con fosfatemia entre 4.5 y 5.0 mg.dl no recibirían tratamiento, mientras que en el Grupo F5.6 (n=180), 32 pacientes con fosfatemia entre 5.1 y 5.6 mg.dl deberían recibir tratamiento, a pesar de presentar normofosfatemia. CONCLUSIONES: Debería estandarizarse la determinación de fosfatemia, previo a utilizar un valor fijo como IndCalDial

¿podemos hablar hoy de un valor de fósforo como indicador de la calidad del tratamiento dialítico? / Can we speak today of a phosphorus value as an indicator of dialysis treatment quality?

Introducción: El trastorno del metabolismo óseo y mineral constituye una grave complicación de la insuficiencia renal crónica. Respecto al fósforo, las nuevas Guías KDIGO sugieren disminuir la hiperfosfatemia, sin recomendar un valor determinado. Sin embargo, en Argentina se utiliza como indicador de calidad dialítica (IndCalDial) un valor de fósforo igual o inferior a 5 mg/dL. Nuestro objetivo fue evaluar si dicho objetivo es actualmente válido como IndCalDial. Material y métodos: Estudio multicéntrico, de corte transversal. Se incluyeron pacientes mayores de 18 años, con más de 90 días en hemodiálisis. Se tabularon datos demográficos y de laboratorio, comparándose normofosfatémicos contra hiperfosfatémicos. Según el método, en 3 centros el límite superior de referencia fue 4.5 mg/dL y en cuatro 5.6 mg/dL, éstos últimos se analizaron como grupo separado F 5.6. Resultados: Se incluyeron 333 pacientes. Edad, sexo, porcentaje FAV, diabéticos, tiempo en diálisis, Kt/V, Hemoglobina y Albumina, fueron semejantes a los datos del registro. La mediana de fosfatemia fue 5.2 mg/dL, (rango: 2.3 a 10.6). Los pacientes hiperfosfatémicos presentaron menor edad, menos tiempo en diálisis y cifras mayores de hemoglobina y Albumina. En el grupo F 5.6 (n = 203), según KDIGO sólo el 33.7 % necesitaría tratamiento. De aplicarse el IndCalDial (fósforo menor a 5 mg/dL), el porcentaje sería de 55%, es decir, un 21.3% de pacientes normofosfatémicos deberían ser tratados. Conclusiones: Debería estandarizarse la determinación de fosfatemia, previo a utilizar un valor fijo como IndCalDial.

Introduction: Bone and mineral metabolism disorder is a serious complication of Chronic Kidney Disease. Concerning phosphorus, the new KDIGO Guidelines suggest a reduction of hyperphosphatemia, but they do not recommend a specific value. However, in Argentina, a phosphorus value of 5 mg/dL or less is used as a dialysis quality indicator (DiaQualInd). Our objective was to evaluate whether this goal is currently valid as a DiaQualInd. Methods: A multicentric, cross-sectional study was conducted. Patients older than 18 were included, with more than 90 days undergoing hemodialysis. Demographic and laboratory data were tabulated, comparing normophosphatemic with hyperphosphatemic values. According to this method, in 3 centers the upper reference limit was 4.5 mg/dL and in 4 centers it was 5.6 mg/dL. The latter were analyzed as a separate group (F 5.6). Results: There were 333 patients included in this study. Age, sex, AVF percentage, diabetes, time on dialysis, Kt/V, hemoglobin and albumin were similar to the registry data. The median phosphatemia was 5.2 mg/dL, (range: 2.3 to 10.6). The hyperphosphatemic patients were the youngest, spent less time on dialysis and showed higher hemoglobin and albumin values. In group F 5.6 (n = 203), according to KDIGO only 33.7% would need treatment. If this DiaQualInd were to be applied (phosphorus lower than 5 mg/dL), the percentage would be 55%, that is, 21.3% of normophosphatemic patients should be treated. Conclusions: Phosphatemia determination should be standardized before using a fixed value such as DiaQualInd

The interrelation between FGF23 and glucose metabolism in humans.

AIMS: Different studies point to a link between glucose metabolism and Fibroblast Growth Factor 23 (FGF23), an osteocyte-derived phosphaturic hormone. We aimed to investigate in humans the effect of (I) a glucose load and (II) a hyperinsulinemic-euglycemic clamp on FGF23 concentrations and conversely (III) the effect of a diet-induced increase in FGF23 concentration on glucose and insulin concentrations. METHODS: Plasma cFGF23 concentrations were measured during: I. an oral glucose tolerance test in eight adults with impaired glucose tolerance and vitamin D deficiency and II. a hyperinsulinemic-euglycemic clamp in nine healthy adults. III. Serum glucose and insulin concentrations were measured in nine healthy adults receiving a single-day phosphate-enriched or -restricted diet. RESULTS: I. A glucose load decreased FGF23 and phosphate concentrations. II. The hyperinsulinemic-euglycemic clamp decreased phosphate concentrations, but did not affect FGF23 concentrations. III. Fasting insulin and glucose concentrations remained unchanged after a diet-induced increase in FGF23 concentration. CONCLUSIONS: An oral glucose load in vitamin D deficient patients with impaired glucose metabolism decreased FGF23 concentrations, which cannot be attributed to changes in insulin concentration. Thus, bone may react rapidly after glucose loading by alternating FGF23 secretion. A diet-induced increase in FGF23 concentrations did not affect fasting glucose or insulin levels.

Characterization of an Animal Model to Study Risk Factors and New Therapies for the Cardiorenal Syndrome, a Major Health Issue in Our Aging Population.

BACKGROUND: The cardiorenal syndrome (CRS) is a major health problem in our aging population. The term was introduced to cover disorders of the kidneys and heart, whereby dysfunction of one organ may induce dysfunction of the other. As the natural history of the CRS is mostly slow, hence difficult to explore in clinical trials, adequate animal models combining cardiovascular and renal disease are required. Therefore, we developed and characterized a usable model for CRS type 4, i.e. chronic kidney disease (CKD) causing cardiac dysfunction. METHODS: CKD was induced in rats by supplementing the diet with adenine. During 8 weeks, several aspects of CRS were studied: CKD, mineral-bone disorder (MBD), cardiovascular disease, and (iron-deficiency) anemia. Hereto, the following parameters were monitored: serum creatinine, calcium, phosphate, FGF23, dynamic bone parameters, aortic Ca deposits, heart weight, serum NT-proANP, Hct, Hb, reticulocytes, spleen iron, and serum hepcidin. RESULTS: Animals developed a severe CKD together with a disturbed mineral balance as reflected by the increased serum creatinine and phosphorus levels and decreased serum calcium levels; and in association herewith aberrations in hormonal levels of FGF-23. In turn, the well-known and highly undesirable complications of CKD, i.e. high turnover bone disease and pathological vessel calcification were induced. Furthermore (iron-deficiency) anemia developed quickly. CONCLUSION: The animal model described in this article in many aspects mimics the human situation of the CRS type 4 and will be useful to concomitantly evaluate the effects of new treatment strategies on the various aspects of CRS.

O sistema endocrinológico vitamina D / The vitamin D endocrine system

O sistema endocrinológico vitamina D é constituído por um grupo de moléculas secosteroides derivadas do 7-deidrocolesterol, incluindo a forma ativa 1,25-diidroxi-vitamina D (1,25(OH)2D), seus precursores e metabólitos, sua proteína transportadora (DBP), seu receptor nuclear (VDR) e as enzimas do complexo do citocromo P450 envolvidas nos processos de ativação e inativação dessas moléculas. Os efeitos biológicos da 1,25(OH)2D são mediados pelo VDR, um fator de transcrição ativado por ligante, presente em quase todas as células humanas, e que pertence à família de receptores nucleares. Além dos clássicos papéis de reguladora do metabolismo do cálcio e da saúde óssea, as evidências sugerem que a 1,25(OH)2D module direta ou indiretamente cerca de 3 por cento do genoma humano, participando do controle de funções essenciais à manutenção da homeostase sistêmica, tais como crescimento, diferenciação e apoptose celular, regulação dos sistemas imunológico, cardiovascular e musculoesquelético, e no metabolismo da insulina. Pela influência crítica que esse sistema exerce em vários processos do equilíbrio metabólico sistêmico, é importante que os ensaios laboratoriais utilizados para sua avaliação apresentem alta acurácia e reprodutibilidade, permitindo que sejam estabelecidos pontos de corte que, além de serem consensualmente aceitos, expressem adequadamente o grau de reserva de vitamina D do organismo e reflitam os respectivos impactos clínico-metabólicos na saúde global do indivíduo.

The vitamin D endocrine system comprises a group of 7-dehydrocholesterol-derived secosteroid molecules, including its active metabolite 1,25-dihydroxy-vitamin D (1,25(OH)2D), its precursors and other metabolites, its binding protein (DBP) and nuclear receptor (VDR), as well as cytochrome P450 complex enzymes participating in activation and inactivation pathways of those molecules. The biologic effects of 1,25(OH)2D are mediated by VDR, a ligand-activated transcription factor which is a member of the nuclear receptors family, spread in almost all human cells. In addition to its classic role in the regulation of calcium metabolism and bone health, evidence suggests that 1,25(OH)2D directly or indirectly modulates about 3 percent of the human genome, participating in the regulation of chief functions of systemic homeostasis, such as cell growth, differentiation and apoptosis, regulation of immune, cardiovascular and musculoskeletal systems, and insulin metabolism. Given the critical influence of the vitamin D endocrine system in many processes of systemic metabolic equilibrium, the laboratory assays available for the evaluation of this system have to present high accuracy and reproducibility, enabling the establishment of cutoff points that, beyond being consensually accepted, reliably express the vitamin D status of the organism, and the respective clinical-metabolic impacts on the global health of the individual.

Effect of oligofructose-enriched inulin on bone metabolism in girls with low calcium intakes

In the present clinical study, the effect of oligofructose-enriched inulin was studied on bone metabolism in girls from 9 to 12 years old, with low habitual calcium intakes, who attended public schools. Two calcium-enriched formulations, supplemented with oligofructose-enriched inulin (test drink) or without (standard drink) were made. Sixty pre-pubertal girls were randomized into a double-blind and crossover design, divided into three groups and received one daily portion of either the standard drink (group 1) or test drink (group 2) during 11 weeks, followed by a three-week washout period. Group control did not receive any supplementation. Biochemical evaluations of serum calcium, intact parathyroid hormone - iPTH - and bone alkaline phosphatase - BAP - were performed at baseline and after 4, 8 and 11 weeks of each intervention period. In group 1, a significant increase in serum calcium and BAP and a reduction of iPTH were observed after consumption of the test drink.

No presente ensaio clínico, o efeito de oligofrutose enriquecida com inulina foi estudado no metabolismo ósseo de meninas de 9 a 12 anos com baixa ingestão habitual de cálcio, matriculadas em escolas públicas. Duas formulações foram suplementadas ou não (bebida padrão) com oligofrutose enriquecida com inulina (bebida teste). Sessenta meninas pré-púberes foram aleatorizadas em estudo duplo cego crossover e divididas em três grupos e receberam uma porção diária da bebida padrão (grupo 1) ou teste (grupo 2) durante 11 semanas, seguidos por um período de intervalo de três semanas. O grupo controle não recebeu nenhuma suplementação. As avaliações bioquímicas de cálcio sérico, paratormônio intacto - PTHi e fosfatase alcalina fração óssea - FAO foram executadas ao início e após 4, 8 e 11 semanas de cada período de intervenção. No grupo 1, um aumento significante no cálcio sérico e FAO e uma redução no PTHi foram observadas após o consumo da bebida teste.