Dickkopf1 (DKK1), metabolismo óseo y enfermedad ateroesclerótica en pacientes con diabetes mellitus tipo 2 / Serum dickkopf1 (DKK1), bone metabolism and atherosclerotic disease in patients with type 2 diabetes

Objetivos: La diabetes mellitus tipo 2 (DM2) se asocia a un incremento del riesgo de fracturas y de enfermedades cardiovasculares. Los objetivos de nuestro estudio fueron evaluar los niveles séricos de Dickkopf-1 (DKK1) en una cohorte de pacientes con DM2 y analizar su relación con el metabolismo óseo y la enfermedad ateroesclerótica (EA). Pacientes y métodos: Se estudiaron 126 sujetos: 72 pacientes con DM2 (edad media de 58,2±6 años) y 54 sujetos no diabéticos (edad media de 55,4±7 años). Se midió DKK1 mediante ensayo de inmunoabsorción ligado a enzimas (ELISA, Biomedica Gruppe), se determinó la densidad mineral ósea (DMO) mediante absorciometría dual de rayos X (DXA), se registró la presencia de EA (enfermedad cerebrovascular, enfermedad arterial periférica, cardiopatía isquémica) y se evaluó el grosor de la íntima-media (GIM, ultrasonografía doppler) y la calcificación aórtica (radiología simple). Resultados: No se encontraron diferencias significativas en DKK1 entre diabéticos y no diabéticos. Las concentraciones séricas de DKK1 fueron significativamente mayores en las mujeres de la muestra total (24,3±15,2 vs. 19,6±10,2 pmol/L, p=0,046) y del grupo DM2 (27,5±17,2 vs. 19,8±8,9 pmol/L, p=0,025). Hubo una correlación positiva entre DKK1 y DMO lumbar en la muestra total (r=0,183, p=0,048). Sin embargo, no se encontraron diferencias en función del diagnóstico de osteoporosis o presencia de fracturas vertebrales morfométricas. Los valores de DKK1 fueron significativamente mayores en los pacientes con DM2 y EA (26,4±14,5 pmol/L vs. 19,1±11,6 pmol/L, p=0,026) y también en pacientes con GIM anormal (26,4±15,1 pmol/L vs. 19,8±11,3 pmol/L, p=0,038). En el análisis de la curva ROC para evaluar la utilidad de DKK1 como un marcador de alto riesgo de EA, el área bajo la curva fue de 0,667 (intervalo de confianza -IC- del 95%: 0,538-0,795; p=0,016). Una concentración de 17,3 pmol/L o superior mostró una sensibilidad del 71,4% y una especificidad del 60% para identificar un mayor riesgo de EA. Conclusiones: Los niveles circulantes DKK1 son más altos en los diabéticos con EA y se asocian con un GIM patológico. Por tanto, consideramos que DKK1 puede estar implicado en la enfermedad vascular de los pacientes con DM2 (AU)

Background and objectives: Type 2 diabetes (T2DM) is a risk factor for osteoporotic fractures and cardiovascular disease. The aims of our study were to evaluate serum Dickkopf-1(DKK1) levels in a cohort of T2DM patients and to analyze its relationships with bone metabolism and atheroesclerotic disease (AD). Patients and methods: We studied 126 subjects: T2DM patients (n: 72, mean age 58,2±6 years) and non-diabetic subjects (n: 54, mean age 55,4±7 years). DKK-1 was measured by enzyme-linked immunosorbent assay (ELISA, Biomedica Gruppe). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). The presence of AD (cerebrovascular disease, peripheral arterial disease, ischemic heart disease) was recorded. Intima-media thickness (IMT) was determined by doppler ultra- sonography and aortic calcification by evaluation of lateral view conventional X-rays. Results: We did not find significant differences in DKK1 between groups. Serum DKK1 concentrations were significantly higher in females in total sample (24,3±15,2 vs 19,6±10,2 pmol/L, p=0,046) and in T2DM group (27,5±17,2 vs 19,8±8,9 pmol/L, p=0,025). There was a positive correlation between serum DKK1 and LS BMD in total sample (r=0,183, p=0,048). However, we did not find a significant relationship with osteoporosis diagnosis or morphometric vertebral fractures. Serum DKK1 was significantly higher in T2DM patients with AD (26,4±14,5 pmol/L vs 19,1±11,6 pmol/L, p=0,026) and also in patients with abnormal IMT (26,4±15,1 pmol/L vs 19,8±11,3 pmol/L, p=0,038). In the ROC curve analysis to evaluate the usefulness of DKK-1 as a marker for high risk of AD, the area under the curve was 0,667 (95% confidence interval: 0,538-0,795; p=0,016). A concentration of 17,3 pmol/L or higher showed a sensitivity of 71,4% and a specificity of 60% to identify an increased risk of AD. Conclusions: Circulating DKK1 levels are higher in T2DM with AD and are associated with an abnormal IMT in this cross-sectional study. DKK1 may be involved in vascular disease of T2DM patients (AU)

Actualización de las recomendaciones para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales. Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN / Update of recommendations for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology

Objetivo: Actualizar las recomendaciones previas formuladas por el Grupo de trabajo de osteoporosis y metabolismo mineral de la Sociedad Española de Endocrinología y Nutrición (SEEN) para la evaluación y el tratamiento de la osteoporosis asociada a diferentes enfermedades endocrinas y alteraciones nutricionales. Participantes: Miembros del Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN. Métodos: Las recomendaciones se formularon de acuerdo al 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 PubMed de las nuevas acerca de cada enfermedad usando las siguientes palabras clave asociadas al nombre de cada proceso patológico: AND osteoporosis, fractures, bone mineral density, bone markers y treatment. Se revisaron artículos escritos en inglés con fechas de inclusión comprendidas entre el 18 de octubre de 2011 y el 30 de octubre de 2014. Tras la formulación de las recomendaciones estas se discutieron de forma conjunta por el Grupo de trabajo.Conclusiones: Esta actualización resume los nuevos datos acerca de la evaluación y tratamiento de la osteoporosis en las enfermedades endocrinas y nutricionales que se asocian a baja masa ósea o a un aumento del riesgo de fractura.(AU)

Objective: To update previous recommendations developed by the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition for the evaluation and treatment of osteoporosis associated to different endocrine and nutritional diseases. 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 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 terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date between 18 October 2011 and 30 October 2014 were included. The recommendations were discussed and approved by all members of the Working Group. Conclusions: This update summarizes the new data regarding evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions.(AU)

Serum osteoprotegerin: bone or cardiovascular marker in Type 2 diabetes males?

BACKGROUND: The role of osteoprotegerin (OPG) as a marker of cardiovascular disease (CVD) in Type 2 diabetes (T2DM) is not well established. Moreover, the relationship between OPG, osteoporosis, and vertebral fractures in T2DM remains to be elucidated. AIM: To determine the role of serum OPG in the prediction of CVD and bone disease in T2DM males. SUBJECTS AND METHODS: Cross-sectional study with 68 males, 43 with T2DM and 25 subjects without diabetes. We measured: serum OPG by inmunoassay, the presence of CVD (coronary heart disease, cerebrovascular and peripheral artery disease), surrogate markers of CVD [intima- media thickness (IMT) and aortic calcification] and bone disease (bone mineral density and prevalent vertebral fractures). RESULTS: OPG serum levels (in pmol/l) were significantly higher in T2DM males with abnormal IMT (5.12 ± 1.59 vs 3.76 ± 1.98), carotid plaque (5.46 ± 1.67 vs 4.20 ± 1.81), aortic calcification (5.91 ± 1.39 vs 4.07 ± 1.76), hypertension (5.11 ± 1.86 vs 3.81 ± 1.47), and peripheral artery disease (6.24 ± 1.64 vs 4.21 ± 1.63, p < 0.05 for all comparisons). In the logistic regression analysis (after adjustment for age and main cardiovascular risk factors), serum OPG (per 1 pmol/l increase in OPG) was associated with increased risk of abnormal IMT [odds ratio (OR) 1.84, confidence interval (CI) 1.21-2.79, p = 0.004), carotid plaque (OR 1.71, CI 1.13-2.58, p = 0.012), aortic calcification (OR 2.21, CI 1.27-3.84, p = 0.05) and peripheral artery disease (OR 4.02, CI 1.65-9.8 p = 0.002). However, OPG were not related to bone mass or vertebral fractures. CONCLUSIONS: Our results suggest that in T2DM males OPG serum concentrations constitute a marker of CVD, but not a marker of bone disease.

Enfermedad cardiovascular, osteoporosis y riesgo de fractura / Cardiovascular disease, osteoporosis and risk of fracture

Hombre de 60 años, administrativo, que consulta para valoración de posible osteoporosis. Fumador de 10 cigarrillos/día y bebedor esporádico. A los 52 años y tras una caída accidental presentó una fractura de Colles en muñeca derecha, que curó sin complicaciones. Su madre padeció a los 78 años una fractura de cadera. El enfermo pesaba 89,4 kg y medía 165cm (IMC: 32,8 kg/m2). La densitometría ósea mostró en columna lumbar T-score -2,4 (CL) y en fémur T-score -1,9. Hace un año tuvo un infarto agudo de miocardio, por lo que sigue tratamiento con una estatina, beta-bloqueante y enalapril. En resumen, se trata de un varón con antecedente de fractura por fragilidad, con valores de densidad mineral ósea (DMO) lumbar cercanos a los establecidos como diagnósticos de osteoporosis y que además presenta enfermedad cardiovascular. ¿Cómo debe ser evaluado y tratado este enfermo?(AU)

A 60-year-old man, who did administrative work, consulted for evaluation of the presence of osteoporosis. He smoked ten cigarettes a day and drank alcohol occasionally. Eight years ago he suffered a Colle's fracture in his right arm after an incidental fall, which resolved without complications. His mother had a hip fracture when she was 78 years old. The patient weighed 89.4 kg and his height was 165cm (BMI 38 kg/m2). The DXA showed a T-score -2.4 at lumbar spine and -1.9 at femoral neck. He had suffered a myocardial infarction one year ago and is presently taking statin, a beta-blocker and enalapril. In summary, this is a male with a background of fracture due to fragility, with lumbar BMD close to those established as diagnostic of osteoporosis and he also has cardiovascular disease. How should this patient be evaluated and treated?(AU)

Relationship between serum levels of osteocalcin and atherosclerotic disease in type 2 diabetes.

AIMS: To analyze the relationship between serum levels of osteocalcin and parameters of atherosclerosis in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study of 78 patients with T2DM evaluated intima-media thickness, and the prevalence of coronary heart disease, atherosclerotic plaques and aortic calcifications. Serum osteocalcin levels were also determined by radioimmunoassay. RESULTS: The patients' mean age was 57.8±6.4 years (duration of diabetes: 13.4 years; mean HbA(1c) level: 8.01%), and 37.2% had coronary heart disease, 56% had an abnormal intima-media thickness, 26.9% had carotid plaques and 32.1% had aortic calcifications. Coronary heart disease was associated with higher levels of osteocalcin in male vs female patients (1.95±1.36 vs 0.93±0.86 ng/mL, respectively; P=0.006). Also, higher concentrations of osteocalcin were found in female patients with vs without abnormal intima-media thicknesses (2.17±1.84 vs 1.25±0.67 ng/mL, respectively; P=0.042), carotid plaques (2.86±2.10 vs 1.43±1.09 ng/mL, respectively; P=0.03) and aortic calcifications (2.85±1.97 vs 1.26±0.83 ng/mL, respectively; P=0.002). Serum osteocalcin levels were associated with coronary heart disease on multivariate logistic regression (odds ratio: 2.27, 95% confidence interval: 1.21-4.25; P=0.01). CONCLUSION: In T2DM patients, serum osteocalcin levels were associated with parameters of atherosclerosis, suggesting that osteocalcin is involved not only in bone metabolism, but also in atherosclerotic disease.

[Cardiovascular disease, osteoporosis and risk of fracture]. / Enfermedad cardiovascular, osteoporosis y riesgo de fractura.

A 60-year-old man, who did administrative work, consulted for evaluation of the presence of osteoporosis. He smoked ten cigarettes a day and drank alcohol occasionally. Eight years ago he suffered a Colle's fracture in his right arm after an incidental fall, which resolved without complications. His mother had a hip fracture when she was 78 years old. The patient weighed 89.4 kg and his height was 165 cm (BMI 38 kg/m(2)). The DXA showed a T-score -2.4 at lumbar spine and -1.9 at femoral neck. He had suffered a myocardial infarction one year ago and is presently taking statin, a beta-blocker and enalapril. In summary, this is a male with a background of fracture due to fragility, with lumbar BMD close to those established as diagnostic of osteoporosis and he also has cardiovascular disease. How should this patient be evaluated and treated?

Regulación del proceso de remodelado óseo / Regulation of bone remodeling processes

El hueso es un tejido metabólicamente activo que experimenta un continuo proceso de remodelado, lo que confiere al esqueleto su capacidad regenerativa y de adaptación funcional. Aunque en los últimos años se ha producido un gran avance en el conocimiento de los factores que intervienen en la regulación del proceso de remodelado, aún quedan por aclarar muchos aspectos dado que esta regulación es compleja ya que integra diversos estímulos como son factores mecánicos, hormonales, citoquinas y factores de crecimiento. Por otra parte, el mayor conocimiento existente sobre las vías y moléculas que intervienen en su regulación abre la posibilidad de futuros tratamientos en el campo de las enfermedades metabólicas óseas

The bone is a metabolically active tissue that undergoes continuous regeneration, which bestows the skeleton its regenerative and functional adaptation capacity. Although there have been significant advances in our understanding of the mechanism of the bone remodeling process in recent years, there is still much to learn on many aspects since the regulation of bone remodeling is a complex process. It integrates different stimuli such as mechanical and hormonal factors, cytokines and growth factors. On the other hand, better understanding of the cellular and molecular events involved in the bone remodeling process could help in futures treatments in the field of bone metabolic diseases

Encuesta sobre práctica clínica en el hiperparatiroidismo primario / Survey on clinical practice in primary hyperparathyroidism

Una reciente conferencia de consenso, promovida por los National Institutes of Health y la Endocrine Society, ha establecido un conjunto de recomendaciones para el tratamiento del hiperparatiroidismo primario en la práctica clínica. Sin embargo, no se conoce los grados de conocimiento y de cumplimiento de estas recomendaciones por parte de los endocrinólogos españoles. En este artículo se revisan las recomendaciones del consenso y se presenta una encuesta elaborada por el Grupo de Trabajo de Metabolismo Mineral Óseo de la SEEN

A recent consensus conference, promoted by the National Institutes of Health and the Endocrine Society, has established a set of recommendations for the management of primary hyperparathyroidism in clinical practice. However, the degree of awareness of and compliance with these recommendations by Spanish endocrinologists is unknown. The present article reviews the consensus recommendations and presents a survey designed by the Working Group for Bone Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition

Neurofibromatosis tipo 1 y feocromocitoma / Type 1 neurofibromatosis and pheochromocytoma

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