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Esta actualización de las Guías incorpora la información más relevante aparecida durante los 7 años trascurridos desde la publicación de la versión anterior, especialmente en cuanto a procedimientos diagnósticos y opciones terapéuticas. Entre los primeros, merece la pena destacar la incorporación del TBS y la detección de fracturas vertebrales por densitometría. Entre los tratamientos, se consideran los nuevos fármacos anabólicos, los estudios comparativos de eficacia en osteoporosis grave, las pautas de actuación tras la suspensión de los antirresortivos y otros esquemas de tratamiento secuencial y combinado. Teniendo en cuenta todo ello, se actualizan los esquemas de tratamiento recomendados.

Esta versión actualizada de la Guía de osteoporosis de la SEIOMM (Sociedad Española de Investigación en Osteoporosis y Metabolismo Mineral) incorpora la información más relevante publicada en los últimos 7 años, desde la Guía de 2015, con estudios de imagen, como la valoración de la fractura vertebral y el análisis del índice trabecular óseo. Además, los avances terapéuticos incluyen los nuevos fármacos anabólicos, los estudios comparativos de la eficacia de los fármacos y la terapia secuencial y combinada. Por ello se actualizan también las recomendaciones de los tratamientos.

Objetivo: La principal consecuencia de la osteoporosis es la fractura por fragilidad asociada a elevada morbimortalidad. La predicción de la misma puede ayudar a identificar la población de mayor riesgo y establecer medidas de prevención. El objetivo de este estudio fue valorar la utilidad de diversos factores en su prevención comparando la densidad mineral ósea (DMO), el cálculo del riesgo absoluto de fractura con la herramienta FRAX® con y sin DMO, y los datos clínicos. Material y método: Se realizó un estudio longitudinal de 8 años de duración en una población de mujeres postmenopáusicas, osteoporóticas y no osteoporóticas. A todas ellas se les realizó una historia clínica protocolizada, DMO de columna y cadera, y el FRAX con y sin DMO. A los 8 años se identificaron las fracturas existentes. Además de realizar una estadística paramétrica y no paramétrica con SPSS 21.1, se realizó un método del árbol de clasificación y regresión (CART) para evaluar las posibles interacciones entre los factores de riesgo de fractura. Resultados: Se incluyeron 276 pacientes postmenopáusicas cuya edad media al inicio del estudio fue de 61,08±8,43 años y un índice de masa corporal (IMC) de 25,67±4,04. El 56,5% de las pacientes (n=156) fueron diagnosticadas de osteoporosis antes del inicio de nuestro estudio, y todas ellas fueron tratadas. Pasados los 8 años de seguimiento, 72 pacientes (24,6%) sufrieron fractura y 17 (6,2%) también sufrieron una segunda fractura. Los resultados del análisis CART nos mostraron que el principal factor de riesgo para sufrir una fractura osteoporótica tras 8 años de seguimiento fue el haber sufrido fracturas previas. Entre las pacientes que habían sufrido una fractura previa, el tener una DMO del cuello femoral menor de 0,67 fue el principal factor de riesgo. Conclusiones: La utilización de un procedimiento estadístico binario (CART), en una cohorte de pacientes nos permite identificar a los pacientes con mayor riesgo de fracturas en función de parámetros clínicos y de pruebas complementarias sencillas de realizar y establecer medidas terapéuticas más eficaces.

Introducción: La relación entre osteoporosis e hipertensión arterial no está claramente establecida, habiéndose descrito en ésta última alteraciones del metabolismo del calcio que podrían explicar su asociación. Nuestro objetivo fue establecer la relación entre el polimorfismo A986S del receptor sensor del calcio (CaSR) y la presencia de fracturas clínicas osteoporóticas en un grupo de pacientes hipertensos.Material: Estudio de cohortes prospectivo observacional en 71 pacientes hipertensos, desde 2001 hasta junio de 2014. Obtuvimos datos sociodemográficos y clínicos, incluyendo fracturas osteoporóticas clínicas. El polimorfismo del CaSR se analizó con técnicas moleculares. Analizamos los datos con SPSS 15.0 (p

Objetivo: La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad ampliamente distribuida y con elevada morbimortalidad, asociada a patologías importantes, entre las que está incluida la osteoporosis. El objetivo de este estudio fue evaluar la prevalencia de fracturas vertebrales en los pacientes con enfermedad pulmonar obstructiva crónica y determinar algunos factores que favorecen el riesgo de fractura en estos pacientes, especialmente la severidad de la EPOC y el empleo y dosis de corticoides inhalados. Material y método: Estudio retrospectivo, observacional y trasversal donde se incluyeron pacientes ingresados en el Hospital Universitario Río Hortega durante el año 2006, diagnosticados de EPOC que tuvieran una radiografía lateral de tórax. Se incluyó un grupo control, sin EPOC, de edad y sexo similares, ingresados en el Servicio de Medicina Interna durante el mismo periodo. La fractura vertebral se determinó por Morphoxpress®. Resultados: Se incluyeron 115 pacientes con EPOC y 87 pacientes controles, observándose una elevada prevalencia de fractura vertebral en pacientes con EPOC, aunque sin mostrar diferencias estadísticamente significativas con el grupo control. Sin embargo, si consideramos únicamente fracturas moderadas-severas (Tipo II y III de Gennant), sí existe una mayor prevalencia que se relaciona con la severidad de la enfermedad, medida por el descenso del VEMS (Volumen espiratorio máximo en el primer segundo de espiración forzada). No hemos encontrado relación entre la prevalencia de fracturas, los diversos tipos de tratamiento y la morbilidad determinada por el número de ingresos. Conclusión: Nuestro estudio muestra la tendencia de los pacientes con EPOC a presentar una elevada prevalencia de fracturas vertebrales asociándose las mismas con la severidad del EPOC y la gravedad de las propias fracturas vertebrales. No encontramos relación entre los diferentes corticoides inhalados, de forma individual o agrupada, y la presencia de fracturas. Tampoco encontramos relación entre número de fracturas vertebrales y número de reagudizaciones, tratamiento con broncodilatadores, corticoides, oxigenoterapia crónica domiciliaria, o diagnóstico y el tratamiento previo de osteoporosis.

Introduction: The telmisartan is an angiotensin II receptor blocker (ARB) with a few own characteristics that it allows us to obtain a few additional benefits. It displays the ability to act as a partial agonist of PPARgamma. On the other hand, PPAR gamma intervenes in the control of bone remodelling though with not concordant results. The objective of this study to value the effect of telmisartan on bone markers in hypertensive patients. Subjects: A sample of 31 hypertensive patients with hypertension were included. The dose of telmisartan was of 80 mg/24 h and the period of follow-up was 12 weeks. The control group included 32 hypertensive patients treated before with IECA (enalapril-20 mg/24 h - or quinapril - 40 mg/24 hours). The following parameters were determined P1NP, [beta]-CTX, 25OHD and PTH , osteocalcin, insulin and adiponectin. Results: The patients treated with Telmisartan shown a significantly decrease in systolic blood pressure (156 ± 19 mmHg vs 133 ± 15 mmHg, p = 0.001) and diastolic blood pressure (92 ± 9 mmHgvs 82 ± 6 mmHg, p = 0.01) . Changes were not observed in other parameter, PTHi (48 ± 22 pg/ml vs 45 ± 22 pg/ml, p > 0.05) and 25-vitamin D (21 ± 10 ng/ml vs 25 ± 8 ng/ml, p > 0.05), CTX (0.195 ± 0.12 ng/ml vs 0.221 ± 0.13 ng/ml, p > 0.05), PINP (39 ± 20 ng/ml vs 40 ± 19 ng/ml, p > 0.05), osteocalcin (11 ± 9 ng/ml vs 11 ± 5 ng/ml, p > 0.05), glucose, adiponectin, insulin and HOMA. When the patients divided in two groups depending on the levels of vitamin D (insufficient and not insufficient), with a cut of 20 ng/ml, there was changes on bone markers but a decrease of the glucose was observed in patients with levels of vitamin D over 20 ng/ml (135 ± 53 mg/dl vs 119 ± 39 mg/dl, p = 0.01). The patients treated with IECAS decreases the systolic blood pressure but the diastolic blood pressure values of arterial systolic does not show changes. Conclusions: Telmisartan has a neutral effect to level of the bone markers of bone remodelling. [ABSTRACT FROM AUTHOR]

Background: The objective of study was to evaluate the evolution of lymphocyte population in patients with tularemia before initiating treatment and 1 year later and to evaluate their prognostic value.Patients and Methods: The patients were diagnosed of tularemia by compatible clinical manifestations and by an elevated titer of antibodies against Francisella tularensis (>1/160), seroconversion or isolation of F. tularensis in a clinical sample. The control group consisted of asymptomatic patients with chronic ischemic heart disease with negative serology against F. tularensis and Chlamydia pneumoniae. The patients were treated with streptomycin or ciprofloxacin. The following cell populations were determined by FACSCAN cytometer: T lymphocytes, helper T lymphocytes, suppressor T lymphocytes, activated T lymphocytes, T lymphocytes with NK activity, B lymphocytes, and NK cells. The progression was evaluated using clinical criteria.Results: During the initial determination, the patients presented statistically significant elevated values of total lymphocytes, T lymphocytes, activated T lymphocytes, and T lymphocytes with NK activity. The values had become normal 1 year after termination of treatment. There were no differences between those patients with a poor response to treatment and those with a positive one.Conclusions: Patients with tularemia initially presented a high total lymphocyte count, T lymphocytes, activated lymphocytes, and T lymphocytes with natural killer activity. The cell populations lack value as a prognostic marker. [ABSTRACT FROM AUTHOR]

Las funciones clásicas del hueso son el mantenimiento de la homeostasis fosfo-cálcica, la reparación de los daños así como un efecto estructural que permite la locomoción y protege los órganos vitales. Los recientes descubrimientos de las nuevas funciones del hueso en la regulación del metabolismo energético sugieren que el hueso puede ser un órgano endocrino. En la última década, en diferentes estudios genéticos y moleculares realizados en ratones, han determinado que la osteocalcina aumenta la secreción de insulina y la sensibilidad a ésta, a través de la elevación de la secreción de adiponectina, estimula la proliferación y el mejor funcionamiento de las células beta, promueve la reducción de masa grasa y el incremento del consumo de energía. Estos hallazgos demuestran la existencia de una regulación recíproca entre el hueso y el metabolismo energético, mediada por la osteocalcina. El reconocimiento del papel metabólico de la osteocalcina, supone un descubrimiento importante en el campo de la Osteología y la Endocrinología posibilitando nuevas terapias en la prevención y tratamiento de enfermedades metabólicas como la diabetes mellitus, la sarcopenia, la obesidad y la osteoporosis.

BACKGROUND: Angiotensin II regulates the production of adipokines. The objective was to study the effect of treatment with telmisartan versus olmesartan in hypertensive obese and overweight patients. SUBJECTS: A sample of 65 overweight and obese patients with mild to moderate hypertension was analyzed in a prospective way with a randomized trial. Patients were randomized to telmisartan (80 mg/day) or olmesartan (40 mg/day) for 3 months. Weight, body mass index, blood pressure, basal glucose, insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, HOMA, QUICKI, leptin and adiponectin were determined at basal time and after 3 months of treatment. RESULTS: Sixty five patients gave informed consent and were enrolled in the study. Patients treated with telmisartan had a significative decrease of glucose 10.53 mg/dl (CI 95%: 2.6-18.5), insulin 2.51 mUI/L (CI 95%: 2.07-7.17) and HOMA 1.08 (CI 95%: 0.39-2.55). Patients treated with olmesartan had a significative decrease of total cholesterol 20.2 mg/dl (CI 95%: 5.8-34.9) and LDL cholesterol 22.6 mg/dl (CI 95%: 9.7-35.6). Only leptin levels have a significant decrease in telmisartan group 7.39 ng/ml (CI 95%: 1.47-13.31). CONCLUSION: Telmisartan improved blood pressure, glucose, insulin, HOMA and leptin in hypertensive diabetic patients. Olmesartan improved blood pressure and lipid levels. [ABSTRACT FROM AUTHOR]

Background and objective: To adjust the Impact Factor (IF) provided by the Institute for Scientific Information (ISI) is necessary for improving bibliometric analysis among the various areas of knowledge. Our objective was to evaluate two parameters (the maximum and the median value of each subject area) for IF adjustment using the original (not corrected) IF as the reference method in a tertiary hospital biomedical investigation model. Material and method: We retrieved articles from Hospital Universitario 'Del Río Hortega' from Valladolid (Spain) for the period 1999-2004 as data source. We have describe the characteristics of the followed IF distributions: IF Corrected by the Maximum value (IFCORMAX), IF Corrected by the Median value (IFCORMED) and IF without adjustments (IF). Besides, we have analyzed both the inter-annual and the inter-subject differences obtained by the three methods. Results: The three analyzed IF series shown not normal distributions that are positively skewed. The IF adjusted by the median showed the highes coefficient of variation (CV = 357.3%). The IF adjusted by the Maximum value increased the 'weight' of journals with the highest not corrected IF for each subject category. Inter-annual differences were similarly estimated by the three methods. The IF adjusted by the median increased the inter-subject difference from 7.3% to 12.4%. Conclusions: Our results suggests that IF adjusted by the maximum value of each discipline is the best method to correct the ISI-IF values, because journals with the high IF are always rewarded, while IF adjusted by the median infra-estimated most of them. [ABSTRACT FROM AUTHOR]

Background/objective: Optimal vitamin D levels are required for bone health and proper functionality of the nervous, musculoskeletal and immune systems. The objective of this study was to assess the efficacy and safety profiles of new weekly calcifediol formulations with the potential to improve adherence and outcome., Methods: A Phase II-III, double-blind, randomized, multicentre trial (EudraCT 2020-001099-14 and NCT04735926). Subjects were randomized 2:2:1 to calcifediol 75 µg, 100 µg and placebo. 25(OH)D levels were measured at 4, 16, 24, 32 and 52 weeks. The main outcome was the percentage of subjects who achieved a response defined as 25(OH)D levels ≥20 ng/mL and/or ≥30 ng/mL at week 16., Results: 398 subjects (51.1 ± 15.96 years, 74.2% females, 98.7% Caucasian) with plasma 25(OH)D levels between 10 and 20 ng/mL were randomized. A total of 376 subjects completed 16 weeks of treatment, and 355 subjects completed the study. Six patients withdrew due to an adverse event, all unrelated to treatment. At week 16, 93.6% and 74.4% of subjects receiving calcifediol 75 µg achieved response levels of ≥20 ng/mL and ≥30 ng/mL, respectively. The calcifediol 100 µg group showed 98.7% and 89.9% of responders for ≥20 ng/mL and ≥30 ng/mL, respectively. Both calcifediol groups showed superiority over placebo at each response level at all time points analyzed ( p < 0.0001). Calcifediol treatments increased 25(OH)D levels from baseline to week 24 and remained stable thereafter. The frequency of treatment-emergent adverse events was balanced between groups., Conclusions: New weekly calcifediol 75 and 100 µg formulations showed an effective and sustained response with a good long-term safety profile.

Competing Interests: The authors have no potential conflicts of interest to disclose.

This study explores the genetic factors associated with atypical femoral fractures (AFF), rare fractures associated with prolonged anti-resorptive therapy. AFF are fragility fractures that typically appear in the subtrochanteric or diaphyseal regions of the femur. While some cases resemble fractures in rare genetic bone disorders, the exact cause remains unclear. This study investigates 457 genes related to skeletal homeostasis in 13 AFF patients by exome sequencing, comparing the results with osteoporotic patients ( n = 27) and Iberian samples from the 1000 Genomes Project ( n = 107). Only one AFF case carried a pathogenic variant in the gene set, specifically in the ALPL gene. The study then examined variant accumulation in the gene set, revealing significantly more variants in AFF patients than in osteoporotic patients without AFF ( p = 3.7 × 10 -5 ), particularly in ACAN, AKAP13, ARHGEF3, P4HB, PITX2, and SUCO genes, all of them related to osteogenesis. This suggests that variant accumulation in bone-related genes may contribute to AFF risk. The polygenic nature of AFF implies that a complex interplay of genetic factors determines the susceptibility to AFF, with ACAN, SUCO, AKAP13, ARHGEF3, PITX2, and P4HB as potential genetic risk factors. Larger studies are needed to confirm the utility of gene set analysis in identifying patients at high risk of AFF during anti-resorptive therapy.

Metabolic bone diseases cover a broad spectrum of disorders that share alterations in bone metabolism that lead to a defective skeleton, which is associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, with TP53 being one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of TP53 is a genetic factor associated with several pathologies, including cancer, stroke, and osteoporosis. Here, we aim to analyze the influence of the TP53 Arg72Pro SNP on bone mass in humanized Tp53 Arg72Pro knock-in mice. This work reports on the influence of the TP53 Arg72Pro polymorphism in bone microarchitecture, OPG expression, and apoptosis bone status. The results show that the proline variant of the TP53 Arg72Pro polymorphism (Pro72-p53) is associated with deteriorated bone tissue, lower OPG/RANK ratio, and lower apoptosis in bone tissue. In conclusion, the TP53 Arg72Pro polymorphism modulates bone microarchitecture and may be a genetic biomarker that can be used to identify individuals with an increased risk of suffering metabolic bone alterations.

Introduction: social media is increasingly used in medical education, but its real educational effectiveness is unclear. In this study we assess the effectiveness of Twitter threads (TTS) in improving electrocardiogram (ECG) basic reading skills (ECGBRS)., Materials and Methods: Seven TTS describing ECGBRS were published from October 28, 2021, to November 24, 2021. Tests were used to assess medical students ECGBRS pre and post intervention. All third and sixth-year medical students were invited to participate. Sixty-three students were enrolled (33 third year and 30 sixth year). Nine (14.3%) participants dropped out., Results: Sixth year medical students had higher ECGBRS at baseline. The number of correct items increased after the Twitter intervention; median correct pre-test items were 20 out of 56, (interquartile range (IQR) 14-23), and median post-test were 29 out of 56, (IQR 21-36) (p < 0.001). The improvement in sixth year students was greater than for third year students; 10 more correct items (IQR 4-14) vs. 7 (IQR 1-14) items (p = 0.045). The more TTS followed, the greater the improvement in ECGBRS (p = 0.004). The QRS axis calculation was the ECG reading skill with the lowest scores. Most medical students were definitely (35%) or very probably (46%) interested in repeating another on-line learning experience and found the TTS extremely (39%) or very (46%) interesting., Conclusions: The use of specifically designed TTS was associated with improvement in medical students' interpretation of ECGs. The effectiveness of the threads was higher in the final years of medical school when basic skills had already been acquired., Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01885-x., Competing Interests: Competing interestsAll authors declare that they have no conflict of interest., (© The Author(s) under exclusive licence to International Association of Medical Science Educators 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Hypoxia may be associated with alterations in bone remodeling, but the published results are contradictory. The aim of this study was to characterize the bone morphometry changes subject to hypoxia for a better understanding of the bone response to hypoxia and its possible clinical consequences on the bone metabolism. This study analyzed the bone morphometry parameters by micro-computed tomography (μCT) in rat and guinea pig normobaric hypoxia models. Adult male and female Wistar rats were exposed to chronic hypoxia for 7 and 15 days. Additionally, adult male guinea pigs were exposed to chronic hypoxia for 15 days. The results showed that rats exposed to chronic constant and intermittent hypoxic conditions had a worse trabecular and cortical bone health than control rats (under a normoxic condition). Rats under chronic constant hypoxia were associated with a more deteriorated cortical tibia thickness, trabecular femur and tibia bone volume over the total volume (BV/TV), tibia trabecular number (Tb.N), and trabecular femur and tibia bone mineral density (BMD). In the case of chronic intermittent hypoxia, rats subjected to intermittent hypoxia had a lower cortical femur tissue mineral density (TMD), lower trabecular tibia BV/TV, and lower trabecular thickness (Tb.Th) of the tibia and lower tibia Tb.N. The results also showed that obese rats under a hypoxic condition had worse values for the femur and tibia BV/TV, tibia trabecular separation (Tb.Sp), femur and tibia Tb.N, and BMD for the femur and tibia than normoweight rats under a hypoxic condition. In conclusion, hypoxia and obesity may modify bone remodeling, and thus bone microarchitecture, and they might lead to reductions in the bone strength and therefore increase the risk of fragility fracture.

Purpose: To examine the response to anti-osteoporotic treatment, considered as incident fragility fractures after a minimum follow-up of 1 year, according to sex, age, and number of comorbidities of the patients., Methods: For this retrospective observational study, data from baseline and follow-up visits on the number of comorbidities, prescribed anti-osteoporotic treatment and vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression and an artificial network model., Results: Logistic regression showed that the probability of reducing fractures for each anti-osteoporotic treatment considered was independent of sex, age, and the number of comorbidities, increasing significantly only in males taking vitamin D (OR = 7.918), patients without comorbidities taking vitamin D (OR = 4.197) and patients with ≥ 3 comorbidities taking calcium (OR = 9.412). Logistic regression correctly classified 96% of patients (Hosmer-Lemeshow = 0.492) compared with the artificial neural network model, which correctly classified 95% of patients (AUC = 0.6)., Conclusion: In general, sex, age and the number of comorbidities did not influence the likelihood that a given anti-osteoporotic treatment improved the risk of incident fragility fractures after 1 year, but this appeared to increase when patients had been treated with risedronate, strontium or teriparatide. The two models used classified patients similarly, but predicted differently in terms of the probability of improvement, with logistic regression being the better fit., (© 2022. The Author(s).)

Background and aims: The relationship between obesity and bone metabolism is controversial. In recent decades, the protective role of obesity in the development of osteoporosis is questioned. The aims of this study are the following: to evaluate the differences in bone turnover markers between postmenopausal women with and without obesity and to compare the risk of fracture at five years between these groups. Methods: An observational longitudinal prospective cohort study of postmenopausal women with obesity (O) (body mass index (BMI) > 30 kg/m2) and non-obesity (NoO) (BMI < 30 kg/m2) is designed. 250 postmenopausal women are included in the study (NoO: 124 (49.6%) and O: 126 (50.4%)). It measures epidemiological variables, dietary variables (calcium intake, vitamin D intake, smoking, alcohol consumption, and physical activity), biochemicals (β-crosslap, type I procollagen amino-terminal peptide (P1NP), 25OH-vitamin D, and parathyroid hormone (PTH)), anthropometric variables, and fracture data five years after the start of the study. The mean age is 56.17 (3.91) years. Women with obesity showed lower levels of vitamin D (O: 17.27 (7.85) ng/mL, NoO: 24.51 (9.60) ng/mL; p < 0.01), and higher levels of PTH (O: 53.24 (38.44−65.96) pg/mL, NoO: 35.24 (25.36−42.40) pg/mL; p < 0.01). Regarding the bone formation marker (P1NP), it was found to be high in women without obesity, O: 45.46 (34.39−55.16) ng/mL, NoO: 56.74 (45.34−70.74) ng/mL; p < 0.01; the bone resorption marker (β-crosslap) was found to be high in women with obesity, being significant in those older than 59 years (O: 0.39 (0.14) ng/mL, NoO 0.24 (0.09) ng/mL; p < 0.05). No differences are observed in the risk of fracture at 5 years based on BMI (OR = 0.90 (95%CI 0.30−2.72); p = 0.85). Conclusions: Postmenopausal women with obesity showed lower levels of bone formation markers; older women with obesity showed higher markers of bone resorption.

Bone is crucial for the support of muscles and the protection of vital organs, and as a reservoir of calcium and phosphorus. Bone is one of the most metabolically active tissues and is continuously renewed to adapt to the changes required for healthy functioning. To maintain normal cellular and physiological bone functions sufficient oxygen is required, as evidence has shown that hypoxia may influence bone health. In this scenario, this review aimed to analyze the molecular mechanisms involved in hypoxia-induced bone remodeling alterations and their possible clinical consequences. Hypoxia has been associated with reduced bone formation and reduced osteoblast matrix mineralization due to the hypoxia environment inhibiting osteoblast differentiation. A hypoxic environment is involved with increased osteoclastogenesis and increased bone resorptive capacity of the osteoclasts. Clinical studies, although with contradictory results, have shown that hypoxia can modify bone remodeling.

The most widely accepted etiopathogenesis hypothesis of the origin of osteoporosis and its complications is that they are a consequence of bone aging and other environmental factors, together with a genetic predisposition. Evidence suggests that oxidative stress is crucial in bone pathologies associated with aging. The aim of this study was to determine whether genetic variants in oxidative stress-related genes modified the risk of osteoporotic fracture. We analysed 221 patients and 354 controls from the HORTEGA sample after 12-14 years of follow up. We studied the genotypic and allelic distribution of 53 SNPs in 24 genes involved in oxidative stress. The results showed that being a carrier of the variant allele of the SNP rs4077561 within TXNRD1 was the principal genetic risk factor associated with osteoporotic fracture and that variant allele of the rs1805754 M6PR, rs4964779 TXNRD1, rs406113 GPX6, rs2281082 TXN2 and rs974334 GPX6 polymorphisms are important genetic risk factors for fracture. This study provides information on the genetic factors associated with oxidative stress which are involved in the risk of osteoporotic fracture and reinforces the hypothesis that genetic factors are crucial in the etiopathogenesis of osteoporosis and its complications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Osteoporosis and obesity are major public health problems that are closely correlated, as they share various features, including a genetic predisposition. A genetic correlation between obesity and osteoporosis due to the biological common pathways of bone and fat metabolism, which implies pleiotropic genes regulating has been described. The objective of our study was to analyse whether polymorphisms in obesity-related genes modify the risk of osteoporotic bone fracture., Methods: We studied 575 subjects from the Hortega Study. The subjects were followed-up for 12-14 years. 202 subjects were overweight, 143 obese and 221 had bone fractures. The distribution of 39 genetic variants in 22 obesity-related genes were studied., Results: The results showed a relationship between polymorphisms in the FTO and NEGR1 genes and the susceptibility to osteoporotic fracture. The variant genotype of the rs2568958 NEGR1 polymorphism and the rs6499649, rs3751812, and rs8044769 genetic variants in FTO were associated with susceptibility to bone fracture. In the best of our knowledge, this is the first time that these variants in NEGR1 and FTO genes have been associated with the susceptibility to osteoporotic bone fracture, supporting the hypothesis that the NEGR1 and FTO genes might be candidates for osteoporosis and bone fracture., Conclusions: In conclusion, this study associates obesity-related polymorphisms in the NEGR1 and FTO genes with osteoporotic bone fracture, reinforcing the hypothesis that obesity and bone metabolism are closely correlated genetically., Competing Interests: The authors declare no conflict of interest. RUM and JLPC are serving as guest editors in this journal. We declare that RUM and JLPC had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to AG., (© 2022 The Author(s). Published by IMR Press.)

The vitamin D receptor (VDR), a member of the nuclear receptor superfamily of transcriptional regulators, is crucial to calcitriol signalling. VDR is regulated by genetic and environmental factors and it is hypothesised that the response to vitamin D supplementation could be modulated by genetic variants in the VDR gene. The best studied polymorphisms in the VDR gene are Apal (rs7975232), BsmI (rs1544410), Taql (rs731236) and Fokl (rs10735810). We conducted a systematic review and meta-analysis to evaluate the response to vitamin D supplementation according to the BsmI, TaqI, ApaI and FokI polymorphisms. We included studies that analysed the relationship between the response to vitamin D supplementation and the genotypic distribution of these polymorphisms. We included eight studies that enrolled 1038 subjects. The results showed no significant association with the BsmI and ApaI polymorphisms ( p = 0.081 and p = 0.63) and that the variant allele (Tt+tt) of the TaqI polymorphism and the FF genotype of the FokI variant were associated with a better response to vitamin D supplementation ( p = 0.02 and p < 0.001). In conclusion, the TaqI and FokI polymorphisms could play a role in the modulation of the response to vitamin D supplementation, as they are associated with a better response to supplementation.

Background: There are few clinical data on retinal involvement after acute exposure to high concentrations mercury and the available reports are based on a small number of patients suffering chronic exposure. The purpose of this paper is to report findings in workers acutely exposed to very high concentrations of mercury vapor with the aim of providing data on a possible direct retinal involvement., Methods: Twenty-nine patients and 16 controls were evaluated in a comparative case series. Mercury levels in blood and urine samples, visual acuity (VA), contrast sensitivity (CS), visual field (VF), color discrimination and optical coherence tomography (OCT) were recorded. The pattern reversal visual-evoked potentials (PRVEP), full-field and multifocal electroretinography (ffERG/mfERG), pattern electroretinography (PERG), systemic symptoms, presence of erethism, and electromyography (EMG) were also gathered. A descriptive analysis was performed. The correlations between variables also were studied. In addition, electrophysiological data from those patients with deeper VF defects (group 1) were compared with a normal control group., Results: Twenty-six workers exhibited symptoms of erethism. The EMG showed sensorimotor polyneuropathy and multiple mononeuropathy. The VA was slightly affected in 48.27% (n = 14) of subjects. Loss of CS in at least one of four spatial frequencies and color vision alterations occurred in 96.5% (n = 28) and 44.8% (n = 13), respectively. VF alterations were identified in 72.4% (n = 21) patients. No morphologic changes were seen in the OCT scans. Latencies over 100 milliseconds and reduced amplitudes of P100 were found in the PRVEP (p < 0.05). The reduced amplitude of the b wave at the ffERG, of the P50 at the PERG and of the P1 wave at the mfERG results (p < 0.05) suggested that the outer retina was involved. Significant negative correlations among blood mercury levels, VA, and ffERG were observed., Conclusions: In this case series, showed that acute exposure to mercury vapor had a hazardous effect on the visual system. Although neurologic and visual pathway involvement was clearly demonstrated, the differences found compared to control support the existence of a direct functional retinal damage and participation in impaired vision in mercury poisoning., (© 2021. The Author(s).)

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Purpose: To report the ocular surface pathology of patients suffering from acute/subacute mercury vapor intoxication., Design: Cross-sectional study., Participants: Male workers intoxicated with inorganic mercury referred for ophthalmic involvement and healthy control subjects., Methods: The following tests were performed: dry eye (DE)-related symptoms indicated by the ocular surface disease (OSDI) index questionnaire; tear osmolarity; analysis of 23 tear cytokine concentrations and principal component and hierarchical agglomerative cluster analyses; tear break-up time (T-BUT); corneal fluorescein and conjunctival lissamine green staining; tear production by Schirmer and tear lysozyme tests; mechanical and thermal corneal sensitivity (non-contact esthesiometry); and corneal nerve analysis and dendritic cell density by in vivo confocal microscopy (IVCM)., Results: Twenty-two out of 29 evaluated patients entered the study. Most had DE-related symptoms (OSDI values > 12), that were severe in 63.6% of them. Tear osmolarity was elevated (>308 mOsms/L) in 83.4% of patients (mean 336.23 (28.71) mOsm/L). Corneal and conjunctival staining were unremarkable. T-BUT was low (<7 s) in 22.7% of patients. Schirmer test and tear lysozyme concentration were low in 13.6% and 27.3% of cases, respectively. Corneal esthesiometry showed patient mechanical (mean 147.81 (53.36) mL/min) and thermal thresholds to heat (+2.35 (+1.10) °C) and cold (-2.57 (-1.24) °C) to be significantly higher than controls. Corneal IVCM revealed lower values for nerve density (6.4 (2.94) n/mm 2 ), nerve branching density (2 (2.50) n/mm 2 ), and dendritic cell density (9.1 (8.84) n/mm 2 ) in patients. Tear levels of IL-12p70, IL-6, RANTES, and VEGF were increased, whereas EGF and IP-10/CXCL10 were decreased compared to controls. Based on cytokine levels, two clusters of patients were identified. Compared to Cluster 1, Cluster 2 patients had significantly increased tear levels of 18 cytokines, decreased tear lysozyme, lower nerve branching density, fewer dendritic cells, and higher urine mercury levels., Conclusions: Patients suffering from systemic mercury intoxication showed symptoms and signs of ocular surface pathology, mainly by targeting the trigeminal nerve, as shown by alterations in corneal sensitivity and sub-basal nerve morphology.

Background: Insulin may play a key role in bone metabolism, where the anabolic effect predominates. This study aims to analyze the relationship between insulin resistance and bone quality using the trabecular bone score (TBS) and three-dimensional dual-energy X-ray absorptiometry (3D-DXA) in non-diabetic postmenopausal women by determining cortical and trabecular compartments., Methods: A cross-sectional study was conducted in non-diabetic postmenopausal women with suspected or diagnosed osteoporosis. The inclusion criteria were no menstruation for more than 12 months and low bone mass or osteoporosis as defined by DXA. Glucose was calculated using a Hitachi 917 auto-analyzer. Insulin was determined using an enzyme-linked immunosorbent assay (EIA). Insulin resistance was estimated using a homeostasis model assessment of insulin resistance (HOMA-IR). DXA, 3D-DXA, and TBS were thus collected. Moreover, we examined bone parameters according to quartile of insulin, hemoglobin A1C (HbA1c), and HOMA-IR., Results: In this study, we included 381 postmenopausal women. Women located in quartile 4 (Q4) of HOMA-IR had higher values of volumetric bone mineral density (vBMD) but not TBS. The increase was higher in the trabecular compartment (16.4%) than in the cortical compartment (6.4%). Similar results were obtained for insulin. Analysis of the quartiles by HbA1c showed no differences in densitometry values, however women in Q4 had lower levels of TBS. After adjusting for BMI, statistical significance was maintained for TBS, insulin, HOMA-IR, and HbA1c., Conclusions: In non-diabetic postmenopausal women there was a direct relationship between insulin resistance and vBMD, whose effect is directly related to greater weight. TBS had an inverse relationship with HbA1c, insulin, and insulin resistance unrelated to weight. This might be explained by the formation of advanced glycosylation products (AGEs) in the bone matrix, which reduces bone deformation capacity and resistance, as well as increases fragility.

La obesidad interfiere con el metabolismo óseo a través de factores mecánicos, hormonales e inflamatorios. El principal tratamiento de dicha enfermedad es la dieta, modificación de la cantidad y tipo de alimento. Este tratamiento nutricional tiene una influencia sobre el metabolismo óseo en dos sentidos: modifica el efecto del sobrepeso y la obesidad sobre el hueso e interviene directamente en el turnoveróseo a través de las características de los nutrientes utilizados. Esta revisión analiza la evidencia del efecto sobre el hueso del descenso de peso y del patrón dietético utilizado. Por otra parte, se valorarán las modificaciones que se pueden realizar en la dieta indicada en un paciente obeso para prevenir la pérdida ósea, a corto y largo plazo, y disminuir el riesgo de fractura.

Objective: Angiotensin-converting enzyme (ACE) has been related to cardiovascular physiology and bone remodeling. Our aim was to assess the relationship among ACE polymorphisms, cardiovascular risk, and osteoporotic fractures., Material and Methods: We prospectively enrolled 71 patients with hypertension from 2001 to 2014. Sociodemographic and medical data were collected. Comorbidity was evaluated with Charlson index. Densitometric studies on lumbar spine were performed. ACE polymorphism was analyzed by polymerase chain reaction. Data were analyzed using SPSS 15.0 (p value <0.05)., Results: Homozygous deletion (DD) genotype was described in 32.4% of patients, homozygous insertion (II) in 19.7%, and heterozygous insertion/deletion (ID) in 47.9%. On stratifying data by ACE polymorphism, we observed that DD carriers demonstrated neither greater cardiovascular risk factors (30.4% vs. 33.3%, p=0.4) and higher comorbidity (34.8% vs. 22.9%, p=0.3) nor higher osteoporotic fracture incidence (17.4% vs. 16.8%, p=0.9). In women, no significant differences were observed between DD homozygous individuals and ID+II subjects., Conclusion: It is unclear whether DD genotype is an independent risk factor for cardiovascular disease. In contrast to our expectations, we found no relationship among the DD genotype, cardiovascular risk, and osteoporotic fracture incidence.

Studies have established a relationship between hypothalamic-pituitary dysfunction and the onset of liver damage, which may occasionally progress to cirrhosis. Patients with hypopituitarism can develop a metabolic syndrome-like phenotype. Insulin resistance is the main pathophysiological axis of metabolic syndrome and is the causal factor in the development of nonalcoholic fatty liver disease (NAFLD). We present the case of a young patient with liver cirrhosis of unknown aetiology that was finally attributed to panhypopituitarism.

Aim: To evaluate the role of balance and gait disorders, comorbidities and laboratory abnormalities in the occurrence of falls in an institutionalized elderly population., Methods: We made a non-interventional, prospective, observational study in elderly institutionalized people. Comorbidities and information on treatments were obtained. Function and cognition were measured using the Katz Index, the Tinetti Balance and Gait, lower extremity function tests and the Mini-Mental test. At the inclusion, the analytical was made including cystatin C. Falls were recorded for 20 months after inclusion., Results: Patients with falls were older (85 ± 7 vs. 82 ± 8, p = 0.04) and more often female (88 vs. 12 %, p = 0.01). Dyslipidemia, hypertension and antihypertensive treatment were associated with an increased risk of falls. Cystatin C was higher in patients with falls (0.96 ± 0.21 vs. 1.12 ± 0.29, p = 0.02). Functional tests showed differences in the Tinetti balance test (15 ± 2 vs. 13 ± 3, p = 0.04) and lower extremity function balance test (2.8 ± 1.2 vs. 2.2 ± 1.2, p = 0.05). The Mini-Mental State Examination (MMSE) scores were worse in patients with falls (22 ± 4 vs. 25 ± 4, p = 0.01). Only female status (6.2, p = 0.03), the MMSE scores (1.2, p = 0.02) and cystatin C (5.3, p = 0.02) were independent risk factors for falls after logistic regression., Conclusions: Female sex, cognitive impairment and cystatin C were risk factors for falls in non-dependent institutionalized elderly people.

We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic and epigenetic mechanisms involved. β-Catenin gene expression and nuclear levels were analyzed by real time PCR and confocal immunofluorescence. Increased nuclear β-catenin was found in osteoblasts isolated from patients with osteoarthritis (99 ± 4 units vs. 76 ± 12, p=0.01, n=10), without differences in gene transcription, which is consistent with a post-translational down-regulation of β-catenin and decreased Wnt pathway activity. Twenty four single nucleotide polymorphisms (SNPs) of genes showing differential expression between fractures and osteoarthritis (WNT4, WNT10A, WNT16 and SFRP1) were analyzed in DNA isolated from blood of 853 patients. The genotypic frequencies were similar in both groups of patients, with no significant differences. Methylation of Wnt pathway genes was analyzed in bone tissue samples (15 with fractures and 15 with osteoarthritis) by interrogating a CpG-based methylation array. Six genes showed significant methylation differences between both groups of patients: FZD10, TBL1X, CSNK1E, WNT8A, CSNK1A1L and SFRP4. The DNA demethylating agent 5-deoxycytidine up-regulated 8 genes, including FZD10, in an osteoblast-like cell line, whereas it down-regulated other 16 genes. In conclusion, Wnt activity is reduced in patients with hip fractures, in comparison with those with osteoarthritis. It does not appear to be related to differences in the allele frequencies of the Wnt genes studied. On the other hand, methylation differences between both groups could contribute to explain the differences in Wnt activity., (© 2013.)

Some patients sustain fractures while on antiresorptives. Whether this represents an inadequate response (IR) to treatment or a chance event has not been elucidated. We performed a study to identify which patients are more likely to fracture while on treatment. This is a multicentric, cross-sectional study of postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals, classified as adequate responders (ARs) if on treatment with antiresorptives for 5 years with no incident fractures or inadequate responders (IRs) if an incident fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary osteoporosis, and previous anti-osteoporosis treatment other than the assessed were exclusion criteria. Clinical, demographic, analytical, dual-energy X-ray absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTx™) and structural/fractal analyses of distal radius were performed. A total of 179 women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years) were included. History of prior fracture (p = 0.005), two or more falls in the previous year (p = 0.032), low lumbar spine bone mineral density (BMD) (p = 0.02), 25 hydroxyvitamin D (p = 0.017), and hip ImaTx fracture load index (p = 0.004) were associated with IR. In the logistic regression models a fracture before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47-8.82; p = 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI, 1.55-9.77; p = 0.004) significantly increased risk for IR, while increased ImaTx fracture load (OR, 0.96; 95% CI, 0.93-0.99; p = 0.006; per every 100 units) was protective, although the latter became not significant when all three variables were fitted into the model. Therefore, we can infer that severity of the disease, with microarchitectural and structure deterioration, as shown by previous fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher risk of inadequate response to antiresorptives. More potent regimes should be developed and adequate supplementation implemented to solve this problem., (Copyright © 2012 American Society for Bone and Mineral Research.)

Background and Aims: To determine mortality and predisposing factors in patients with fracture of the proximal femur, one year after the initial fracture, in a tertiary hospital in Castile and Leon (Spain)., Methods: Observational case-control study. Patients aged ≥65 years admitted to the orthopedic surgery department of the Rio Hortega Hospital, a tertiary care hospital with approximately 560 beds, due to non-traumatic hip fracture between September 2005 and November 2006, were included. An age-matched control group of 81 institutionalized patients with similar characteristics was recruited. A protocolized telephone interview and a review of hospital medical records was made at 12 months followup., Results: Of the 170 patients recruited, the final analysis was made in 139: 121 (87.1%) women and 18 (12.9%) men. The control group was formed of 81 patients: 64 (79%) women and 17 (21%) men. Mortality was 41.7% in the study group and 2.5% in controls (p; 0.001). Mortality was 31% in month 1, 24.1% between months 2 and 6 and 29.3% between months 6 and 12 (in 15.6% the date of death was unknown). Factors associated with mortality were: age >86 years (p; 0.024); prior cognitive deterioration (p; 0.011); prior locomotor disorder (p; 0.047); male gender (p; 0.017); heart disease (p; 0.042)., Conclusions: Patients with hip fracture, had substantially higher mortality than comparable healthy people, and mortality was highest in the first six months after fracture. Age and prior comorbidities were associated with excess mortality.

Osteoclasts are specialized cells that initiate the process of bone resorption, which has two phases, dissolution of the mineral component and degradation of the organic matrix, in which cathepsin K plays a key role. Cathepsin K inhibitors, which block the activity of cathepsin on bone resorption lacunae, may be a new therapeutic option in osteoporosis. Odanacatib is a nonpeptidic biaryl inhibitor of cathepsin K. Two studies have evaluated the efficacy and safety of odanacatib, a phase I study to determine the dose and a phase II study of safety and efficacy. Due to the long half-life of odanacatib and the similar effects of different doses on bone remodeling markers, a weekly dosage was chosen for the phase II trail, with the best results being obtained with a dose of 50 mg. At 36 months, increases in bone mineral density similar to those produced by other powerful antiresorptive drugs (zoledronate and denosumab) were observed but there were differences in the behaviour of bone remodeling markers. Data on fractures from the phase III trial currently in development are required to confirm these possible advantages.

Background: Despite their great impact, few genetic association studies have used hip fractures as an endpoint. However, the association of two polymorphisms on intron 4 of estrogen receptor alpha (ESR1) with hip fractures was recently reported in a Chinese population. The aim of this study was to investigate whether such association is also present in Caucasians., Methods: We analyzed those two SNPs and another neighbour SNP located on the exon 4 of ESR1 in 787 patients with hip fractures and 953 controls from Spain., Results: The allelic frequencies differed markedly from those reported in Asian populations. Nevertheless, haplotypes including the rs3020314 and rs1884051 loci in intron 4 showed a significant association with hip fractures (omnibus test p = 0.006 in the whole group and 0.00005 in women). In the sex-stratified analysis, the association was significant in females, but not in males. In women, the CA haplotype appeared to have a protective influence, being present in 6.5% of the controls, but only in 3% of patients with fractures (odds ratio 0.39; 95% confidence interval 0.26-0.59; estimated population preventive fraction 3.5%). The inclusion of the rs1801132 SNP of exon 4 further increased the statistical significance of the association (odds ratio 0.17; 95% CI 0.08-0.37; p = 0.00001). Each SNP appeared to contribute independently to the association. No genotype-related differences in gene expression were found in 42 femoral bone samples., Conclusions: This study confirms the association of some polymorphisms in the region of exon 4/intron 4 of ESR1 and hip fractures in women. However, there are marked differences in allele frequencies between Asian and Caucasian populations.

Adequate vitamin D levels are necessary for good vascular health. 1,25-dihydroxycholecalciferol activates CYP3A4, an enzyme of the cytochrome P450 system, which metabolizes atorvastatin to its main metabolites. The objective of this study was to evaluate the response of cholesterol and triglycerides to atorvastatin according to vitamin D levels. Sixty-three patients with acute myocardial infarction treated with low and high doses of atorvastatin were included. Levels of total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol were measured at baseline and at 12 months of follow-up. Baseline levels of 25-hydroxyvitamin D (25-OHD) were classified as deficient (<30 nmol/L), insufficient (30-50 nmol/L), and normal (>50 nmol/L). In patients with 25-OHD <30 nmol/L, there were no significant changes in levels of total cholesterol (173 +/- 47 mg/dL versus 164 +/- 51 mg/dL), triglycerides (151 +/- 49 mg/dL versus 177 +/- 94 mg/dL), and LDL cholesterol (111 +/- 48 mg/dL versus 92 45 +/- mg/dL); whereas patients with insufficient (30-50 nmol/L) and normal vitamin D (>50 nmol/L) had a good response to atorvastatin. We suggest that vitamin D concentrations >30 nmol/L may be required for atorvastatin to reduce lipid levels in patients with acute myocardial infarction.

Background: A polymorphism (1359 G/A) of the CB1 gene has been described, it was reported as a common polymorphism in European populations. The aim of our study was to investigate the influence of this polymorphism of CB1 receptor gene on obesity anthropometric parameters, cardiovascular risk factors and adipocytokines in morbid obese patients., Design: A population of 66 morbid obese patients was analyzed. An indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure, a serial assessment of nutritional intake with 3 days written food records and biochemical analysis (lipid profile, adipocytokines, insulin, CRP and lipoprotein-a) were performed. The statistical analysis was performed for the combined G1359A and A1359A as a group and wild type G1359G as second group, with a dominant model., Results: Thirty eight patients (57.6%) had the genotype G1359G (wild type group) and 28 (42.4%) patients G1359A (40.0%) (mutant type group). Weight (117.4 +/- 17.4 kg vs 109.4 +/- 13.8 kg: p < 0.05), BMI (45.4 +/- 4.7 vs 43.3 +/- 3.4: p < 0.05), fat mass (60.1 +/- 13.4 kg vs 53,6 +/- 12.8 kg: p < 0.05), waist circumference (126.3 +/- 10.8 cm vs 122.9 +/- 12.6 cm: p < 0.05), C reactive protein (11.2 +/- 8.8 mg/dl vs 7.8 +/- 4.6 mg/dl: p < 0.05), insulin (23.5 +/- 19.8 mUI/L vs 18.4 +/- 17.1 mUI/L: p < 0.05) and HOMA (6.46 +/- 6.2 vs 4.70 +/- 4.6: p < 0.05) were lowers in patients with G1359A genotype. No differences were detected between groups in other parameters., Conclusion: The mutant genotype G1359A is associated with a better cardiovascular profile (weight, BMI, fat mass, waist circumference, insulin, HOMA and c reactive protein) than wild type group.

Objectives: To evaluate the effect of atorvastatin on bone mass and markers of bone remodeling in patients with acute coronary syndrome according to the Lys656Asn leptin receptor gene polymorphism., Methods: Sixty-two patients with acute coronary syndrome were included. Patients were allocated to low and high doses of atorvastatin according to baseline levels of cholesterol and triglycerides and the index of vascular risk and were studied at hospital admission and at 12 months. Cholesterol, triglycerides, total calcium, phosphorus, magnesium, osteocalcin and urinary deoxypyridinoline were determined in all patients at baseline and at 12 months of follow up. Densitometric studies were conducted in the lumbar spine and hip. Patients with a T-score<-2.5 were considered osteoporotic. The Lys656Asn leptin receptor gene polymorphism was determined by PCR., Results: Forty-two patients were Lys/Lys homozygotic and 20 Lys/Asn heterozygotic. The prevalence of osteoporosis was 31% for the Lys/Lys genotype and 27% for the Lys/Asn genotype with no significant differences between groups. There was a significant increase in bone mineral density in the lumbar spine (1.117 +/- 0.24 versus 1.135 +/- 0.24, P = 0.008) in patients with the Lys/Lys genotype., Conclusion: Atorvastatin increases lumbar spine bone mineral density only in patients with the Lys/Lys genotype of the Lys656Asn polymorphism.

Nocardia farcinica is an infrequent infection that usually appears in patients with predisposing conditions, especially in immunosuppressed patients, although it has also been found in healthy individuals. Its importance as a new pathogen has been recognized only in recent years. Mainly, it affects the lung, indistinguishable from other types of pneumonia in the clinical and radiological characteristics. The main reason for detection is therapeutic failure.

Numerous phosphocalcium alterations associated with bone mineral density in hypertension have been described, but very few studies assess them. This study assesses bone mass in hypertensive postmenopausal women and the hypertension influence determining both calcium homeostasis and bone turnover markers. Blood and urine samples were analysed for calcium metabolism-related parameters. Densitometry studies were conducted in the lumbar spine (L2-L4). Hypertensive osteoporotic women--selected from 82 women, with 22% osteoporosis prevalence, similar to the rate for the same age in the Spanish population--had significantly higher levels of body mass index (29+/-4 vs 26+/-4, P=0.019), calciuria (293+/-146 vs 210+/-116 mg/24 h, P=0.023) and calcium/creatinine ratio (0.33+/-0.2 vs 0.22+/-0.1 P=0.003) vs hypertensive nonosteoporotic women. No relation was found between systolic and diastolic blood pressure with bone mass. However, there was a negative osteocalcin correlation (r=-0.386, P=0.0001, and r=-0.242, P=0.033). Calciuria is associated with bone mass decrease in hypertensive women, and there is no relation between bone mass and blood pressure.