Pharmacological and Non-Pharmacological Agents versus Bovine Colostrum Supplementation for the Management of Bone Health Using an Osteoporosis-Induced Rat Model

Osteoporosis is defined by loss of bone mass and deteriorated bone microarchitecture. The present study compared the effects of available pharmacological and non-pharmacological agents for osteoporosis [alendronate (ALE) and concomitant supplementation of vitamin D (VD) and calcium (Ca)] with the effects of bovine colostrum (BC) supplementation in ovariectomized (OVX) and orchidectomized (ORX) rats. Seven-month-old rats were randomly allocated to: (1) placebo-control, (2) ALE group (7.5 μg/kg of body weight/day/5 times per week), (3) VD/Ca group (VD: 35 μg/kg of body weight/day/5 times per week; Ca: 13 mg/kg of body weight/day/3 times per week), and (4) BC supplementation (OVX: 1.5 g/day/5 times per week; ORX: 2 g/day/5 times per week). Following four months of supplementation, bone microarchitecture, strength and bone markers were evaluated. ALE group demonstrated significantly higher Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC and significantly lower Ct.Pr, Tb.Pr, Tb.Sp, Ct.BMD and Tb.BMD, compared to placebo (p < 0.05). BC presented significantly higher Ct.Pr, Ct.BMD, Tb.Pr, Tb.Sp, and Tb.BMD and significantly lower Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC compared to ALE in OVX rats (p < 0.05). OVX rats receiving BC experienced a significant increase in serum ALP and OC levels post-supplementation (p < 0.05). BC supplementation may induce positive effects on bone metabolism by stimulating bone formation, but appear not to be as effective as ALE

Bovine colostrum supplementation improves bone metabolism in an osteoporosis-induced animal model

Osteoporosis is characterized by bone loss. The present study aims to investigate the effects of bovine colostrum (BC) on bone metabolism using ovariectomized (OVX) and orchidectomized (ORX) rat models. Twenty-seven-week-old Wistar Han rats were randomly assigned as: (1) placebo control, (2) BC supplementation dose 1 (BC1: 0.5 g/day/OVX, 1 g/day/ORX), (3) BC supplementation dose 2 (BC2: 1 g/day/OVX, 1.5 g/day/ORX) and (4) BC supplementation dose 3 (BC3: 1.5 g/day/OVX, 2 g/day/ORX). Bone microarchitecture, strength, gene expression of VEGFA, FGF2, RANKL, RANK and OPG, and bone resorption/formation markers were assessed after four months of BC supplementation. Compared to the placebo, OVX rats in the BC1 group exhibited significantly higher cortical bone mineral content and trabecular bone mineral content (p < 0.01), while OVX rats in the BC3 group showed significantly higher trabecular bone mineral content (p < 0.05). ORX rats receiving BC dose 2 demonstrated significantly higher levels of trabecular bone mineral content (p < 0.05). Serum osteocalcin in the ORX was pointedly higher in all BC supplementation groups than the placebo (BC1: p < 0.05; BC2, BC3: p < 0.001). Higher doses of BC induced significantly higher relative mRNA expression of OPG, VEGFA, FGF2 and RANKL (p < 0.05). BC supplementation improves bone metabolism of OVX and ORX rats, which might be associated with the activation of the VEGFA, FGF2 and RANKL/RANK/OPG pathways.EC -European Commission(778277

Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B trial): protocol for a mixed-methods process evaluation of a randomised controlled trial

Introduction An association between deep sedation and adverse short-term outcomes has been demonstrated although this evidence has been inconsistent. The A2B (alpha-2 agonists for sedation in critical care) sedation trial is designed to determine whether the alpha-2 agonists clonidine and dexmedetomidine, compared with usual care, are clinically and cost-effective. The A2B intervention is a complex intervention conducted in 39 intensive care units (ICUs) in the UK. Multicentre organisational factors, variable cultures, perceptions and practices and the involvement of multiple members of the healthcare team add to the complexity of the A2B trial. From our pretrial contextual exploration it was apparent that routine practices such as type and frequency of pain, agitation and delirium assessment, as well as the common sedative agents used, varied widely across the UK. Anticipated challenges in implementing A2B focused on the impact of usual practice, perceptions of risk, ICU culture, structure and the presence of equipoise. Given this complexity, a process evaluation has been embedded in the A2B trial to uncover factors that could impact successful delivery and explore their impact on intervention delivery and interpretation of outcomes. Methods and analysis This is a mixed-methods process evaluation guided by the A2B intervention logic model. It includes two phases of data collection conducted during and at the end of trial. Data will be collected using a combination of questionnaires, stakeholder interviews and routinely collected trial data. A framework approach will be used to analyse qualitative data with synthesis of data within and across the phases. The nature of the relationship between delivery of the A2B intervention and the trial primary and secondary outcomes will be explored. Ethics and dissemination All elements of the A2B trial, including the process evaluation, are approved by Scotland A Research Ethics Committee (Ref. 18/SS/0085). Dissemination will be via publications, presentations and media engagement. Trial registration number NCT03653832

Nutraceutical Supplementation Based on Colostrum as Osteoporosis Treatment: A Pilot Study

Introduction: Naturally based treatments for osteoporosis are currently limited. The purpose of this investigation was to ascertain whether bovine colostrum supplementation can improve bone health in humans. Methods: In total 63 individuals volunteered in a 4-month supplementation project. They were stratified into three groups: 1) healthy post-menopausal women (n = 24); 2) individuals with osteopenia (n = 25); 3) people with osteoporosis (n = 14). Participants of each group were randomly assigned into two experimental sub-groups: a) the bovine colostrum (BC) supplementation (200 mL/day; 5 days/week); b) the placebo sub-group. Before and after the 4-month supplementation, blood samples were obtained and bone mineral density (BMD) was measured. Dual-Energy X-ray Absorptiometry (DXA) was performed on three different anatomical sites: lumbar spine (LS), left femur neck (FN), and left forearm (Arm). Bone health markers (bone alkaline phosphatase (BAP), osteocalcin, C-terminal telopeptide (CTX-I), deoxypyridinoline (DPD)) as well as immunological markers (interleukin 6 (IL6) and immunoglobulin E (IgE)), were assessed in blood serum with enzyme immunoassays, at baseline and 4-months after BC supplementation. Results: No significant changes were found in bone densitometry factors (p > 0.05), for all studied blood parameters and their calculated effect sizes. Conclusions: It is concluded that, as studied herein, BC does not seem to affect human bone health. This pilot study though warrant the need for further research into the efficacy of BC in patients with osteoporosis

Identifying determinants for the application of physical or chemical restraint in the management of psychomotor agitation on the critical care unit

Aims and objectives: To identify key determinants, which lead to the decision to apply physical or chemical restraint on the critical care unit. Background: Psychomotor agitation and hyperactive delirium are frequently cited as clinical rationale for initiating chemical and physical restraint in critical care. Current restraint guidance is over a decade old, and wide variations in nursing and prescribing practice are evident. It is unclear whether restraint use is grounded in evidence‐based practice or custom and culture. Study design: Integrative review. Method: Seven health sciences databases were searched to identify published and grey literature (1995–2019), with additional hand‐searching. The systematic deselection process followed PRISMA guidance. Studies were included if they identified physical or chemical restraint as a method of agitation management in adult critical care units. Quality appraisal was undertaken using Mixed Methods Appraisal Tool. Data were extracted, and thematic analysis undertaken. Results: A total of 23 studies were included. Four main themes were identified: the lack of standardised practice, patient characteristics associated with restraint use, the struggle in practice and the decision to apply restraint. Conclusions: There are wide variations in restraint use despite the presence of international guidance. Nurses are the primary decision‐makers in applying restraint and report that caring for delirious patients is physically and psychologically challenging. The decision to restrain can be influenced by the working environment, patient behaviours and clinical acuity. Enhanced clinical support and guidance for nurses caring for delirious patients is indicated. Relevance to clinical practice: Delirium and agitation pose a potential threat to patient safety and the maintenance of life‐preserving therapies. Restraint is viewed as one method of preserving patient safety. However, use appears to be influenced by previous adverse experiences and subjective patient descriptors, rather than robust evidence‐based knowledge. The need for a precise language to describe restraint and quantify when it becomes necessary is indicated

Un calostro bovino neuroprotector atenúa la apoptosis inducida por dexametasona en células osteoblásticas MC3T3-E1

Este estudio ha sido financiado por la Unión Europea mediante una MSCA-RISE-Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE) (Grant agreement ID: 778277). El proyecto, en toda su extensión, ha pretendido crear una colaboración intersectorial (instituciones académicas e industriales) para intercambiar conocimientos y experiencias con la finalidad de crear un producto nutracéutico innovador, basado en el calostro, para prevenir la osteoporosis. La osteoporosis constituye un importante problema de salud pública. Se prevé un aumento importante de la carga económica de las fracturas osteoporóticas en la Unión Europea hasta 2025. Estas estimaciones pueden indicar una ineficacia de los tratamientos farmacológicos actuales para la osteoporosis. Por tanto, se necesitan agentes innovadores para reducir la carga de la osteoporosis. El calostro es un agente prometedor frente a la pérdida de masa ósea ya que contiene componentes que intervienen directamente en el metabolismo óseo. Sin embargo, la posibilidad de su uso como agente nutracéutico para la osteoporosis sólo ha recibido atención dentro de la comunidad científica. Los conocimientos sobre los efectos del calostro en el metabolismo óseo aún no se han trasladado al mercado y, la industria, aunque posee los conocimientos para el desarrollo de productos, carece de experiencia en investigación. En definitiva, lo que dificulta la creación de un producto innovador basado en el calostro para la prevención de la osteoporosis es la ausencia de una colaboración intersectorial. Concretamente, la osteoporosis inducida por glucocorticoides (OIG) es una de las formas secundarias más frecuentes de osteoporosis. La OIG se debe en parte al proceso de apoptosis que experimentan los osteoblastos y osteocitos. Para el presente estudio se desarrolló un modelo celular de apoptosis exponiendo a una línea celular osteoblástica, MC3T3-E1, al glucorticoide dexametasona (DEX) en un rango de concentraciones en el medio de cultivo desde 0 hasta 700 μM. El daño inducido por la DEX se estudió en presencia y ausencia de tratamiento con un calostro bovino (0,1-5,0 mg/mL) con el fin de conocer la posible protección que puede ejercer frente a la apoptosis celular inducida por el glucocorticoide. El calostro evitó la disminución de la viabilidad celular y el aumento de la activación de la caspasa-3 y del estrés oxidativo causados por la exposición a DEX. Las células, tras el tratamiento con calostro junto con DEX, mostraron niveles más altos de p-ERK1/2 y niveles más bajos de Bcl-XL, Bax y Hsp70. Nuestros datos apoyan la noción de que el calostro puede ser capaz de reducir la apoptosis inducida por DEX posiblemente a través de la activación de la vía ERK y la modulación del sistema Hsp70. Proporcionamos pruebas preliminares de cómo el calostro bovino, como producto lácteo complejo y multicomponente, además de su acción neuroprotectora, puede afectar a la supervivencia de las células osteoblásticas sometidas a apoptosis. Estos resultados prueban que este calostro posee capacidad reductora de la apoptosis inducida por DEX, posiblemente a través de la activación de la vía ERK y la modulación del sistema Hsp70.Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0–700 μM). Colostrum co-treated with DEX was executed at 0.1–5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.MSCA-RISE-Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE) grant funded by the European UnionDepto. de Farmacología, Farmacognosia y BotánicaFac. de FarmaciaTRUEpu