Search

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]

Reports on the alpha-antitrypsin deficiency observed in a female patient suffering from discoid lupus erythematosus. Association of the disease with cutaneous disorders caused by the disease; Factors attributed to the condition.

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.

Background: In vitro studies have shown that genistein inhibits the CYP240 enzyme, which is involved in the degradation of 1,25-dihydroxycholecalciferol and its precursor 25-hydroxycholecalciferol, and increases their plasma levels. However, no clinical studies have primarily assessed the synergistic effect of isoflavones on vitamin D levels. The aim of this study was to evaluate the possible additive effect of genistein supplementation on vitamin D levels, calcium metabolism and bone remodeling markers in healthy postmenopausal women during the spring-summer months. Patients and methods: We made a prospective, double-blind study with 150 healthy postmenopausal women that were randomized to three groups. One received placebo, another received calcium (1000 mg/day) and vitamin D (cholecalciferol, 800 U/day) and the third received calcium (1000 mg/day), vitamin D (cholecalciferol, 800 U/day) and genistein (90 mg/day). The study period was from May to September (spring-summer). Vitamin D, PTH, CTX and P1NP were determined by electrochemiluminescence at baseline and after 12 weeks. Results: Vitamin D levels increased in all groups: placebo (23±9 ng/ml vs. 29±10 ng/ml, p<0.05), calcium+vitamin D (26±10 ng/ml vs. 33±8 ng/ml, p<0.05) and calcium+vitamin D+genistein (24±9 ng/ml vs. 31±8 ng/l, p<0.05) without between-group differences. At study end, the percentage of women with vitamin D <20 ng/ml (11%) and <30 ng/ml (39%) had fallen without between-group differences. The effects on calcium metabolism and bone remodeling markers were similar between groups: rises in vitamin D were significantly linked to reductions in PTH, CTX and P1NP. Conclusion: Adding genistein to supplementation with calcium and vitamin D provided not additional changes in vitamin D levels, calcium metabolism or bone remodeling markers in healthy Spanish postmenopausal women during the spring-summer months.

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.)

Purpose: To evaluate the effect of different non-osteoporotic drugs on the increase or decrease in the risk of incident fragility fractures (vertebral, humerus or hip) in a cohort of patients diagnosed with osteoporosis on active anti-osteoporotic therapy., Methods: For this retrospective longitudinal study, baseline and follow-up data on prescribed non-osteoporotic treatments and the occurrence of vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression models. The drugs evaluated with a possible beneficial effect were thiazides and statins, while the drugs evaluated with a possible harmful effect were antiandrogens, aromatase inhibitors, proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, GnRH agonists, thyroid hormones, and oral and inhaled corticosteroids., Results: Logistic regression analyses indicated that no treatment significantly improved fracture risk, with the only treatments that significantly worsened fracture risk being letrozole (OR = 0.18, p-value = 0.03) and oral corticosteroids at doses ≤ 5 mg/day (OR = 0.16, p-value = 0.03) and > 5 mg/day (OR = 0.27, p-value = 0.04)., Conclusion: The potential beneficial or detrimental effects of the different drugs evaluated on fracture risk are masked by treatment with anabolic or antiresorptive drugs that have a more potent action on bone metabolism, with two exceptions: letrozole and oral corticosteroids. These findings may have important clinical implications, as patients receiving these treatments are not fully protected by bisphosphonates, which may imply the need for more potent anti-osteoporotic drugs such as denosumab or teriparatide., (© 2023. The Author(s).)

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).)

Acute carbon monoxide (CO) intoxication may result in delayed neurological sequelae, which can include amnesia, ataxia, aphasia, emotional lability, disorientation, dysphagia, and other manifestations. A 27-year-old man reported symptoms of aphasia with agraphia and alexia in a review after CO intoxication. The patient received outpatient speech therapy, as well as repeated sessions of hyperbaric oxygen for 15 days, interspersing speech therapy with hyperbaric oxygen therapy for two months. After this period of combined treatment the aphasic symptomatology remitted, and oral and written language was normal. The complete disappearance of aphasia with agraphia and alexia confirms the efficacy of the combined intervention. More data from large clinical studies are needed to assess the outcomes of hyperbaric oxygen treatment in patients with delayed neurological sequelae after CO intoxication, but this case suggests it may be a good therapeutic option in combination with specific speech therapy., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

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).)

This updated version of the Spanish Society for Research in Osteoporosis and Mineral Metabolism (SEIOMM) osteoporosis guides incorporate the most relevant information published in the last 7 years, since the 2015 guides, with imaging studies, such as vertebral fracture assessment and bone trabecular score analysis. In addition, therapeutic advances include new anabolic agents, comparative studies of drug efficacy, and sequential and combined therapy. Therefore, therapeutic algorithms are also updated., (Copyright © 2022 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

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.

This study was carried out to analyze the evolution of the quality indicators in the Spanish National Hip Fracture Registry, after disseminating a series of recommendations based on available clinical practice guidelines to the participating hospitals. Six of the seven proposed quality indicators showed a significant improvement., Purpose: The Spanish National Hip Fracture Registry (RNFC) arises from the need to know the process and improve the quality of care. Our goal was to analyze the changes in the RNFC's quality indicators after an intervention based on disseminating specific recommendations among the participating hospitals, following available clinical practice guidelines., Methods: Study comparing before and after performing an intervention in hospitals participating in the RNFC. Data from the hospitals that registered cases in 2017, and that kept registering cases in 2019. Seven quality indicators were chosen, and a standard to be achieved for each indicator was proposed. The intervention consisted in the dissemination of 25 recommendations with practical measures to improve each quality indicator, based on available clinical practice guidelines, by drafting and publishing a scientific paper and sending it via email and printed cards. Fulfilment of each quality indicator was measured after carrying out the intervention., Results: Forty-three hospitals registered 2674 cases between January and May, 2017, and 8037 during 2019. The quality indicators chosen and the degree of compliance were (all with p<0.05): (1) surgery ≤48 h increased from 38.9 to 45.8%; (2) patients mobilised on the first postoperative day increased from 58.9 to 70.3%; (3) patients with anti-osteoporotic medication at discharge increased from 34.5 to 49.8%; (4) patients with calcium supplements at discharge increased from 48.7 to 62.8%; (5) patients with vitamin D supplements at discharge increased from 71.5 to 84.7%; (6) patients developing a grade >2 pressure ulcer during admission decreased from 6.5 to 5.0%; (7) patients able to move on their own at 1 month fell from 58.8 to 56.4%. More than 48% of hospitals improved the proposed indicators., Conclusion: Establishing quality indicators and standards and intervening through the dissemination of specific recommendations to improve these indicators achieved an improvement in hospital performance results on a national level., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

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).)

Background: Denosumab is a monoclonal antibody approved for the treatment of postmenopausal osteoporosis. The withdrawal of denosumab produces an abrupt loss of bone mineral density and may cause multiple vertebral fractures (MVF)., Objective: The objective of this study is to study the clinical, biochemical, and densitometric characteristics in a large series of postmenopausal women who suffered MVF after denosumab withdrawal. Likewise, we try to identify those factors related to the presence of a greater number of vertebral fractures (VF)., Patients and Methods: Fifty-six patients (54 women) who suffered MVF after receiving denosumab at least for three consecutive years and abruptly suspended it. A clinical examination was carried out. Biochemical bone remodelling markers (BBRM) and bone densitometry at the lumbar spine and proximal femur were measured. VF were diagnosed by magnetic resonance imaging MRI, X-ray, or both at dorsal and lumbar spine., Results: Fifty-six patients presented a total of 192 VF. 41 patients (73.2%) had not previously suffered VF. After discontinuation of the drug, a statistically significant increase in the BBRM was observed. In the multivariate analysis, only the time that denosumab was previously received was associated with the presence of a greater number of VF (P = .04)., Conclusions: We present the series with the largest number of patients collected to date. 56 patients accumulated 192 new VF. After the suspension of denosumab and the production of MVF, there was an increase in the serum values of the BBRM. The time of denosumab use was the only parameter associated with a greater number of fractures., (© 2021 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.)

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.

The study aimed to achieve expert consensus to optimize secondary fracture prevention in Spain. Relevant gaps in current patient management were identified. However, some aspects were considered difficult to apply. Future efforts should focus on those items with greatest divergences between importance and feasibility., Purpose: To establish a Spanish multidisciplinary expert consensus on secondary fracture prevention., Methods: A two-round Delphi consensus was conducted, guided by a Scientific Committee. The 43-item study questionnaire was designed from a literature review and a subsequent multidisciplinary expert group (n = 12) discussion. The first-round questionnaire, using a 7-point Likert scale, assessed the experts' opinion of the current situation, their wish for items to happen, and their prognosis that items would be implemented within 5 years. Items for which consensus was not achieved were included in the second round. Consensus was defined as ≥ 75% agreement or ≥ 75% disagreement. A total of 102 experts from 14 scientific societies were invited to participate., Results: A total of 75 (response rate 73.5%) and 69 (92.0%) experts answered the first and second Delphi rounds, respectively. Participants mean age was 51.8 years [standard deviation (SD): 10.1 years]; being 24.0% rheumatologists, 21.3% primary care physicians, 14.7% geriatricians, 8.0% internal medicine specialists, 8.0% rehabilitation physicians, and 8.0% gynecologists. Consensus was achieved for 79.1% of items (wish, 100%; prognosis, 58.1%). Effective secondary prevention strategies identified as requiring improvement included: clinical report standardization, effective hospital primary care communication (telephone/mail and case managers), health-related quality of life (HRQoL) questionnaires use, and treatment compliance monitoring (prognosis agreement 33.3%, 47.8%, 18.8%, and 55.1%, respectively)., Conclusion: A consensus was reached by health professionals in their wish to implement strategies to optimize secondary fracture prevention; however, they considered some difficult to apply. Efforts should focus on those items with currently low application and those with greatest divergence between wish and prognosis.

Osteoporosis is the most common bone disorder worldwide and is associated with a reduced quality of life with important clinical and economic consequences. The most widely accepted etiopathogenic hypothesis on the origin of osteoporosis and its complications is that they are a consequence of the synergic action of environmental and genetic factors. Bone is constantly being remodelled through anabolic and catabolic pathways in which inflammation, the NF-kB pathway and the renin-angiotensin-aldosterone system (RAAS) are crucial. The aim of our study was to determine whether polymorphisms in genes implicated in inflammation, the NF-kB pathway and RAAS modified the risk of osteoporotic fracture. We analysed 221 patients with osteoporotic fracture and 354 controls without fracture from the HORTEGA sample after 12-14 years of follow up. In addition, we studied the genotypic distribution of 230 single nucleotide polymorphisms (SNPs) in genes involved in inflammation, NF-kB pathway and RAAS. Our results showed that be carrier of the C allele of the rs2228145 IL6R polymorphism was the principal genetic risk factor associated with osteoporotic fracture. The results also showed that variant genotypes of the rs4762 AGT, rs4073 IL8, rs2070699 END1 and rs4291 ACE polymorphisms were important genetic risk factors for fracture. The study provides information about the genetic factors associated with inflammation, the NF-kB pathway and RAAS, 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., Competing Interests: Declaration of competing interest The authors report no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)