Clinical and outcome comparison of genetically positive vs. negative patients in a large cohort of suspected familial hypocalciuric hypercalcemia.

OBJECTIVE: Biochemical suspicion of familial hypocalciuric hypercalcemia (FHH) might provide with a negative (FHH-negative) or positive (FHH-positive) genetic result. Understanding the differences between both groups may refine the identification of those with a positive genetic evaluation, aid management decisions and prospective surveillance. We aimed to compare FHH-positive and FHH-negative patients, and to identify predictive variables for FHH-positive cases. DESIGN: Retrospective, national multi-centre study of patients with suspected FHH and genetic testing of the CASR, AP2S1 and GNA11 genes. METHODS: Clinical, biochemical, radiological and treatment data were collected. We established a prediction model for the identification of FHH-positive cases by logistic regression analysis and area under the ROC curve (AUROC) was estimated. RESULTS: We included 66 index cases, of which 30 (45.5%) had a pathogenic variant. FHH-positive cases were younger (p = 0.029), reported more frequently a positive family history (p < 0.001), presented higher magnesium (p < 0.001) and lower parathormone levels (p < 0.001) and were less often treated for hypercalcemia (p = 0.017) in comparison to FHH-negative cases. Magnesium levels showed the highest AUROC (0.825, 95%CI: 0.709-0.941). The multivariate analysis revealed that family history and magnesium levels were independent predictors of a positive genetic result. The predictive model showed an AUROC of 0.909 (95%CI: 0.826-0.991). CONCLUSIONS: The combination of magnesium and a positive family history offered a good diagnostic accuracy to predict a positive genetic result. Therefore, the inclusion of magnesium measurement in the routine evaluation of patients with suspected FHH might provide insight into the identification of a positive genetic result of any of the CaSR-related genes.

Impact of nutritional and educational support on home enteral nutrition.

BACKGROUND: Home Enteral Nutrition (HEN) is used to prevent or correct malnutrition in outpatients. Due to the complexity of this process, the indication, follow-up, and results of an educational program of HEN patients was evaluated. METHODS: A prospective, observational, real-life, multicenter study was performed in 21 Spanish Hospital. Patients receiving HEN by nasogastric tube or ostomy were included. The following variables were collected: age, gender, HEN indication, type of formula, nutritional requirements, laboratory variables, complications, and quality standards of the educational program. To calculate the energy and protein requirements, the FAO/WHO/UNU formula was used considering the adjusted weight of the patients. All data were analyzed using SPSS.24. RESULTS: 414 patients were included. Most conditions diagnosed were neurodegenerative diseases (64.8%). 100 (25.3%) were diabetic. The mean weight was 59.3 ± 10.4 kg and BMI 22.6 ± 3.2. Moderate protein-calorie malnutrition was predominant at baseline (46.4%). Improvement in nutritional status at six months was recorded in more than 75% of patients (p < 0.05). Tolerance problems, diarrhea and abdominal distension fell between the 3- and 6-month visits (p < 0.05). Patients who received intermittent EN had fewer tolerance-related effects (OR 0.042; 95% CI 0.006-0.279) and less diarrhoea (OR 0.042; 95% CI 0.006-0.279). At the baseline and 6-month visits, compliance with the educational measures proposed by the prescriber was ≥ 99%. CONCLUSION: The nutritional assessment to prescribe individualized HEN to each patient, together with educational measures and training in the proper use of this treatment for both patients and trainers, improves nutritional status and reduces the onset of adverse events.

Guide of management of alterations in mineral and bone metabolism during gestation and lactation.

OBJECTIVE: To provide practical recommendations for the management of mineral and bone metabolism alterations in pregnancy and lactation. PARTICIPANTS: Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition. METHODS: Recommendations were formulated according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. A systematic search was carried out in Medline of the available evidence for each pathology. Papers in English with publication date until 29 February 2020 were included. A methodologist resolved the differences that arose during the process of reviewing the literature and formulating recommendations. The recommendations were discussed and approved by all members of the Working Group. CONCLUSIONS: The document establishes practical recommendations based on evidence about the management of mineral and bone metabolism disorders in pregnancy and lactation.

Guide of management of alterations in mineral and bone metabolism during gestation and lactation / Guía de manejo de las alteraciones del metabolismo mineral y óseo en la gestación y la lactancia

Objective: To provide practical recommendations for the management of mineral and bone metabolism alterations in pregnancy and lactation. Participants: Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition. Methods: Recommendations were formulated according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. A systematic search was carried out in Medline of the available evidence for each pathology. Papers in English with publication date until 29 February 2020 were included. A methodology resolved the differences that arose during the process of reviewing the literature and formulating recommendations. The recommendations were discussed and approved by all members of the Working Group. Conclusions: The document establishes practical recommendations based on evidence about the management of mineral and bone metabolism disorders in pregnancy and lactation.

Objetivo: Proporcionar unas recomendaciones prácticas para el manejo de las alteraciones del metabolismo mineral y óseo en la gestación y la lactancia. Participantes: Miembros del Grupo de Metabolismo Mineral de la Sociedad Española de Endocrinología y Nutrición. Métodos:Las recomendaciones se formularon de acuerdo con el sistema Grading of Recommendations Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en Medline de la evidencia disponible para cada patología. Se revisaron artículos escritos en inglés con fecha de inclusión hasta 29 de febrero del 2020. Un metodólogo resolvió las diferencias que surgieron durante el proceso de revisión de bibliografía y formulación de recomendaciones. Tras la formulación de las recomendaciones éstas se discutieron en una reunión conjunta del Grupo de Trabajo. Conclusiones: El documento establece unas recomendaciones prácticas basadas en la evidencia acerca del manejo de las alteraciones del metabolismo mineral y óseo en la gestación y la lactancia.

Nuevas tecnologías en la evaluación de la fragilidad ósea y su aplicación en Endocrinología / New technologies in the evaluation of bone fragility and its application in Endocrinology

La medición de la densidad mineral ósea mediante la absorciometría radiológica de doble energía es la técnica de elección para la valoración ósea y un predictor importante del riesgo de fractura. Sin embargo, la mayoría de las fracturas por fragilidad ocurren en personas sin osteoporosis densitométrica, especialmente en enfermedades endocrinológicas. Las herramientas para la estimación del riesgo de fracturas como FRAX han mejorado la sensibilidad diagnóstica aunque no consideran otras características óseas adicionales. La investigación de la microarquitectura ósea supone una mejoría en el abordaje de estos pacientes. En este documento elaborado por miembros del grupo de trabajo de Metabolismo Mineral y Óseo de la Sociedad Española de Endocrinología y Nutrición se revisan los nuevos avances en absorciometría radiológica de doble energía y otras técnicas más complejas para el estudio de la microarquitectura ósea así como los datos disponibles en diabetes tipo 2 y patología paratiroidea

Bone mineral density using dual-energy X-ray absorptiometry is the gold standard for the assessment of bone and an important predictor of fracture risk. However, most fragility fractures occur in people without densitometric osteoporosis, especially in endocrinological diseases. Fracture risk estimation tools such as FRAX have improved diagnostic sensitivity but do not include additional skeletal features. Bone microarchitecture research represents an improvement in the treatment of these patients. In this document members of the Mineral and Bone Metabolism Working Group of the Spanish Society of Endocrinology and Nutrition review new advances in dual-energy X-ray absorptiometry and other complex techniques for the study of bone microarchitecture as well as the available data on type 2 diabetes and parathyroid pathology

New technologies in the evaluation of bone fragility and its application in Endocrinology. / Nuevas tecnologías en la evaluación de la fragilidad ósea y su aplicación en Endocrinología.

Bone mineral density using dual-energy X-ray absorptiometry is the gold standard for the assessment of bone and an important predictor of fracture risk. However, most fragility fractures occur in people without densitometric osteoporosis, especially in endocrinological diseases. Fracture risk estimation tools such as FRAX have improved diagnostic sensitivity but do not include additional skeletal features. Bone microarchitecture research represents an improvement in the treatment of these patients. In this document members of the Mineral and Bone Metabolism Working Group of the Spanish Society of Endocrinology and Nutrition review new advances in dual-energy X-ray absorptiometry and other complex techniques for the study of bone microarchitecture as well as the available data on type 2 diabetes and parathyroid pathology.

Trastornos del fosfato y actitud clínica ante situaciones de hipofosfatemia e hiperfosfatemia / Phosphate disorders and clinical management of hypophosphatemia and hyperphosphatemia

La concentración sérica de fósforo oscila entre 2,5 y 4,5 mg/dl (0,81-1,45 mmol/l) en adultos, con niveles más altos en la infancia, la adolescencia y durante la gestación. El fosfato intracelular está implicado en el metabolismo intermediario y otras funciones celulares esenciales, mientras que el extracelular es fundamental para la mineralización de la matriz ósea. La fosforemia se mantiene en un estrecho rango mediante la regulación de la absorción intestinal, la redistribución y la reabsorción tubular renal de fósforo. La hipofosfatemia y la hiperfosfatemia son situaciones clínicas frecuentes, aunque, en la mayoría de las ocasiones, se trata de alteraciones leves y poco sintomáticas. Sin embargo, pueden presentarse cuadros agudos y severos que requieren tratamiento específico. En este documento elaborado por miembros del Grupo de Trabajo de Metabolismo Mineral y Óseo de la Sociedad Española de Endocrinología y Nutrición se revisan los trastornos del fosfato y se proporcionan algoritmos de manejo clínico de la hipofosfatemia y la hiperfosfatemia

Serum phosphorus levels range from 2.5 and 4.5 mg/dL (0.81-1.45 mmol/L) in adults, with higher levels in childhood, adolescence, and pregnancy. Intracellular phosphate is involved in intermediary metabolism and other essential cell functions, while extracellular phosphate is essential for bone matrix mineralization. Plasma phosphorus levels are maintained within a narrow range by regulation of intestinal absorption, redistribution, and renal tubular absorption of the mineral. Hypophosphatemia and hyperphosphatemia are common clinical situations, although changes are most often mild and oligosymptomatic. However, acute and severe conditions that require specific treatment may occur. In this document, members of the Mineral and Bone Metabolism Working Group of the Spanish Society of Endocrinology and Nutrition review phosphate disorders and provide algorithms for adequate clinical management of hypophosphatemia and hyperphosphatemia

Phosphate disorders and clinical management of hypophosphatemia and hyperphosphatemia. / Trastornos del fosfato y actitud clínica ante situaciones de hipofosfatemia e hiperfosfatemia.

Serum phosphorus levels range from 2.5 and 4.5mg/dL (0.81-1.45 mmol/L) in adults, with higher levels in childhood, adolescence, and pregnancy. Intracellular phosphate is involved in intermediary metabolism and other essential cell functions, while extracellular phosphate is essential for bone matrix mineralization. Plasma phosphorus levels are maintained within a narrow range by regulation of intestinal absorption, redistribution, and renal tubular absorption of the mineral. Hypophosphatemia and hyperphosphatemia are common clinical situations, although changes are most often mild and oligosymptomatic. However, acute and severe conditions that require specific treatment may occur. In this document, members of the Mineral and Bone Metabolism Working Group of the Spanish Society of Endocrinology and Nutrition review phosphate disorders and provide algorithms for adequate clinical management of hypophosphatemia and hyperphosphatemia.

Circulating levels of sclerostin are associated with cardiovascular mortality.

Cardiovascular diseases are a health problem throughout the world, especially in people with diabetes. The identification of cardiovascular disease biomarkers can improve risk stratification. Sclerostin is a modulator of the Wnt/ß-catenin signalling pathway in different tissues, and it has recently been linked to vascular biology. The current study aimed to evaluate the relationship between circulating sclerostin levels and cardiovascular and non-cardiovascular mortality in individuals with and without type 2 diabetes. We followed up a cohort of 130 participants (mean age 56.8 years; 48.5% females; 75 with type 2 diabetes; 46 with prevalent cardiovascular disease) in which serum sclerostin levels were measured at the baseline. Time to death (both of cardiovascular and non-cardiovascular causes) was assessed to establish the relationship between sclerostin and mortality. We found that serum sclerostin concentrations were significantly higher in patients with prevalent cardiovascular disease (p<0.001), and independently associated with cardiovascular mortality (p = 0.008), showing sclerostin to be a stronger predictor of mortality than other classical risk factors (area under the curve = 0.849 vs 0.823). The survival analysis showed that an increase of 10 pmol/L in the serum sclerostin level resulted in a 31% increase in cardiovascular mortality. However, no significant association was observed between sclerostin levels and non-cardiovascular mortality (p = 0.346). From these results, we conclude that high sclerostin levels are related to mortality due to cardiovascular causes. The clinical implication of these findings is based on the possible use of serum sclerostin as a new biomarker of cardiovascular mortality risk in order to establish preventive strategies.

Higher Levels of Serum 25-Hydroxyvitamin D Are Related to Improved Glucose Homeostasis in Women with Postmenopausal Osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMO) is associated with other comorbidities such as impaired glucose homeostasis and cardiovascular disease. Vitamin D insufficiency is highly prevalent and may be a common link between these disorders. However, the relationship between circulating 25-hydroxyvitamin D [25(OH)D] and insulin resistance in women with PMO has not been well evaluated. The aim of this study was to assess the relationship between circulating levels of 25(OH)D and parameters of glucose homeostasis in a cohort of women with PMO to establish a serum concentration threshold of 25(OH)D for improved glycemic parameters. MATERIALS AND METHODS: This cross-sectional study included 40 women with PMO. We measured 25(OH)D serum levels and glucose homeostasis parameters (glucose and insulin levels, insulin sensitivity, and ß-secretion index HOMA2-%S and HOMA2-%B, respectively). Anthropometric, biochemical, and clinical parameters and bone markers were also evaluated. RESULTS: Circulating levels of 25(OH)D were related to glucose parameters (negatively with HOMA2-%B and insulin levels and positively with HOMA2-%S) in women with PMO, resulting in an indicator of insulin sensitivity independent of age, body mass index, percent body fat, and undercarboxylated osteocalcin. Patients with serum 25(OH)D ≥45 ng/mL showed lower HOMA2-%B values and insulinemia and greater HOMA2-%S. CONCLUSIONS: Our results support the hypothesis that circulating 25(OH)D levels are related to improved glucose homeostasis in women with PMO. However, this relationship was apparent only in the presence of high circulating levels of 25(OH)D.

Documento de consenso de osteoporosis del varón / Consensus document on osteoporosis in males

Objetivo: Proporcionar unas recomendaciones prácticas para la evaluación y tratamiento de la osteoporosis del varón. Participantes. Miembros del Grupo de Metabolismo Mineral de la Sociedad Española de Endocrinología y Nutrición. Métodos: Las recomendaciones se formularon de acuerdo con el sistema Grading of Recommendations, Assessment, Development and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en Medline de la evidencia disponible sobre la osteoporosis del varón usando las siguientes palabras claves asociadas: osteoporosis, men, fractures, bone mineral density, treatment, hypogonadism y prostate cancer. Se revisaron artículos escritos en inglés y español con fecha de inclusión hasta el 30 de agosto del 2017; cada tema fue revisado por 2 personas del grupo. Tras la formulación de las recomendaciones, estas se discutieron en una reunión conjunta del grupo de trabajo. Conclusiones: El documento establece unas recomendaciones prácticas basadas en la evidencia acerca del diagnóstico, evaluación y tratamiento de la osteoporosis del varón y situaciones especiales como el hipogonadismo y el tratamiento con terapia de déficit androgénico en el carcinoma de próstata

Objective: To provide practical recommendations to assess and treat osteoporosis in males. Participants. Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. Methods: Recommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in Medline (PubMed) using the following associated terms: «osteoporosis», «men», «fractures», «bone mineral density», «treatment», «hypogonadism», and «prostate cancer». Papers in English and Spanish with publication date before 30 August 2017 were included. Current evidence for each disease was reviewed by 2 group members. Finally, recommendations were discussed in a meeting of the working group. Conclusions: The document provides evidence-based practical recommendations for diagnosis, assessment, and management of osteoporosis in men and special situations such as hypogonadism and prostate cancer

Recommended vitamin D levels in the general population. / Recomendaciones de vitamina D para la población general.

OBJECTIVE: To provide recommendations based on evidence on the management of vitaminD deficiency in the general population. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. METHODS: Recommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the term VitaminD and the name of each issue. Papers in English and Spanish with publication date before 17 March 2016 were included. Recommendations were jointly discussed by the Working Group. CONCLUSIONS: This document summarizes the data about vitaminD deficiency in terms of prevalence, etiology, screening indications, adequate levels and effects of supplementation on bone and non-skeletal health outcomes.

Recomendaciones de vitamina D para la población general / Recommended vitamin D levels in the general population

Objetivo: Proporcionar recomendaciones basadas en la evidencia sobre el manejo del déficit de vitaminaD en población general. Participantes: Miembros del Grupo de Trabajo de Osteoporosis y Metabolismo Mineral de la SEEN. Métodos: Se empleó el sistema Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en Medline de la evidencia disponible para vitaminaD y el título de cada capítulo. Se revisaron artículos escritos en inglés con fecha de inclusión hasta 17 de marzo del 2016. Tras la formulación de las recomendaciones, estas se discutieron de manera conjunta en el grupo de trabajo. Conclusiones: Este documento resume los datos acerca del déficit de vitaminaD en lo que respecta a su prevalencia, etiología, indicaciones de cribado, niveles adecuados y efectos de la suplementación a nivel óseo y extraóseo (AU)

Objective: To provide recommendations based on evidence on the management of vitaminD deficiency in the general population. Participants: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. Methods: Recommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the term VitaminD and the name of each issue. Papers in English and Spanish with publication date before 17 March 2016 were included. Recommendations were jointly discussed by the Working Group. Conclusions: This document summarizes the data about vitaminD deficiency in terms of prevalence, etiology, screening indications, adequate levels and effects of supplementation on bone and non-skeletal health outcomes (AU)

Relationship between myostatin and irisin in type 2 diabetes mellitus: a compensatory mechanism to an unfavourable metabolic state?

Myostatin and irisin are two myokines related to energy metabolism, acting on skeletal muscle and recently suggested on adipose tissue in mice. However, the exact role of these myokines in humans has not been fully established. Our aim was to evaluate the relationship between serum levels of myostatin and irisin in type 2 diabetes mellitus patients and non-diabetic controls and to explore its links with metabolic parameters. Case-control study including 73 type 2 diabetes mellitus patients and 55 non-diabetic subjects as control group. Circulating myostatin and irisin levels were measured by enzyme-linked immunosorbent assays. Type 2 diabetes mellitus patients showed significantly lower myostatin levels (p = 0.001) and higher irisin levels (p = 0.036) than controls. An inverse relationship was observed between myostatin and irisin levels (p = 0.002). Moreover, in type 2 diabetes mellitus patients, after adjusting by confounder factors, myostatin was negatively related to fasting plasma glucose (p = 0.005) and to triglyceride levels (p = 0.028) while irisin showed a positive association with these variables (p = 0.017 and p = 0.006 respectively). A linear regression analysis showed that irisin and fasting plasma glucose levels were independently associated to myostatin levels and that myostatin and triglyceride levels were independently associated to irisin concentrations in type 2 diabetes mellitus patients. Our results suggest that serum levels of myostatin and irisin are related in patients with type 2 diabetes. Triglyceride and glucose levels could modulate myostatin and irisin concentrations as a compensatory mechanism to improve the metabolic state in these patients although further studies are needed to elucidate whether the action of these myokines represents an adaptative response.

Osteocalcina: nexo de unión entre homeostasis ósea y metabolismo energético / Osteocalcin: A link between bone homeostasis and energy metabolism

La investigación en modelos animales ha demostrado el papel de la osteocalcina, marcador de formación ósea, en la regulación del metabolismo energético. Estos trabajos han dado lugar a un nuevo concepto del hueso como órgano endocrino mediante la secreción de osteocalcina, que actúa incrementando la secreción de insulina, disminuyendo la glucosa plasmática, así como aumentando la sensibilidad a la insulina y el gasto energético. Los resultados en humanos han sido diversos y en ocasiones contradictorios. Por otro lado, los fármacos antirresortivos frente a la osteoporosis disminuyen los niveles de osteocalcina mientras que los osteoanabólicos la incrementan. No obstante, no se han investigado los efectos de estas terapias sobre el metabolismo energético (AU)

Research in animal models has demonstrated the role of osteocalcin, a bone formation marker, in regulation of energy metabolism. Those studies have led to a new concept of the bone acting as an endocrine organ by secreting osteocalcin, which acts by increasing insulin secretion, lowering plasma glucose, and increasing insulin sensitivity and energy expenditure. Results in humans have been conflicting. On the other hand, antiresorptive drugs used against osteoporosis decrease osteocalcin levels, while anabolic drugs increase osteocalcin levels. However, the effects of these therapies on energy metabolism have not been investigated (AU)

Osteocalcin: a link between bone homeostasis and energy metabolism.

Research in animal models has demonstrated the role of osteocalcin, a bone formation marker, in regulation of energy metabolism. Those studies have led to a new concept of the bone acting as an endocrine organ by secreting osteocalcin, which acts by increasing insulin secretion, lowering plasma glucose, and increasing insulin sensitivity and energy expenditure. Results in humans have been conflicting. On the other hand, antiresorptive drugs used against osteoporosis decrease osteocalcin levels, while anabolic drugs increase osteocalcin levels. However, the effects of these therapies on energy metabolism have not been investigated.