Does Vitamin D Insufficiency Influence Prebiotic Effect on Calcium Absorption and Bone Retention?

Higher calcium (Ca) absorption would partially compensate for Ca intake below requirements for bone health. Previously, we found that GOS/FOS prebiotic mixture (PM) increases Ca absorption in the colon and retention in bone. Ca absorption and retention are regulated by vitamin D (VD). Hence, it is relevant to explore whether VD insufficiency influences the effect of the PM in the colon. The effect of the PM on Ca, phosphate (IP), and magnesium (Mg) absorption and retention under conditions of VD sufficiency and insufficiency (VDInsuff) was compared using a preclinical model of VDInsuff and low bone mass. Ovariectomized rats were fed isocaloric semisynthetic diets according to AIN-93 M. The diets varied in Ca (0.5% or 0.3%), VD [100 IU% (+ D) or 0 IU% (- D)], and PM (2.5% or 0%) content. The following eight groups were studied: + D0.5; + D0.3; + DPM0.5; + DPM0.3; - D0.5; - D0.3; - DPM0.5; and - DPM0.3. Irrespective of Ca content, VDInsuff did not affect the prebiotic effect of the PM on caecum pH, lactobacillus colony growth, or Mg absorption but significantly decreased its effect on colonic crypt length and cell/crypt and Ca and IP absorption. The PM failed to counterbalance the pro-inflammatory effect of VDInsuff. Moreover, bone retention i.e., bone mineral content and density, bone volume, and bone quality parameters were significantly lower (p < 0.05) and bone turnover significantly was higher (p < 0.05). Although the PM is a useful tool to improve mineral absorption and bone retention, it would seem important to monitor VD nutritional status to ensure the full prebiotic effect in the large intestine.

Reducing medication errors for adults in hospital settings.

BACKGROUND: Medication errors are preventable events that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional or patient. Medication errors in hospitalised adults may cause harm, additional costs, and even death. OBJECTIVES: To determine the effectiveness of interventions to reduce medication errors in adults in hospital settings. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers on 16 January 2020.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) and interrupted time series (ITS) studies investigating interventions aimed at reducing medication errors in hospitalised adults, compared with usual care or other interventions. Outcome measures included adverse drug events (ADEs), potential ADEs, preventable ADEs, medication errors, mortality, morbidity, length of stay, quality of life and identified/solved discrepancies. We included any hospital setting, such as inpatient care units, outpatient care settings, and accident and emergency departments. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care (EPOC) Group. Where necessary, we extracted and reanalysed ITS study data using piecewise linear regression, corrected for autocorrelation and seasonality, where possible.  MAIN RESULTS: We included 65 studies: 51 RCTs and 14 ITS studies, involving 110,875 participants. About half of trials gave rise to 'some concerns' for risk of bias during the randomisation process and one-third lacked blinding of outcome assessment. Most ITS studies presented low risk of bias. Most studies came from high-income countries or high-resource settings. Medication reconciliation -the process of comparing a patient's medication orders to the medications that the patient has been taking- was the most common type of intervention studied. Electronic prescribing systems, barcoding for correct administering of medications, organisational changes, feedback on medication errors, education of professionals and improved medication dispensing systems were other interventions studied. Medication reconciliation Low-certainty evidence suggests that medication reconciliation (MR) versus no-MR may reduce medication errors (odds ratio [OR] 0.55, 95% confidence interval (CI) 0.17 to 1.74; 3 studies; n=379). Compared to no-MR, MR probably reduces ADEs (OR 0.38, 95%CI 0.18 to 0.80; 3 studies, n=1336 ; moderate-certainty evidence), but has little to no effect on length of stay (mean difference (MD) -0.30 days, 95%CI -1.93 to 1.33 days; 3 studies, n=527) and quality of life (MD -1.51, 95%CI -10.04 to 7.02; 1 study, n=131).  Low-certainty evidence suggests that, compared to MR by other professionals, MR by pharmacists may reduce medication errors (OR 0.21, 95%CI 0.09 to 0.48; 8 studies, n=2648) and may increase ADEs (OR 1.34, 95%CI 0.73 to 2.44; 3 studies, n=2873). Compared to MR by other professionals, MR by pharmacists may have little to no effect on length of stay (MD -0.25, 95%CI -1.05 to 0.56; 6 studies, 3983). Moderate-certainty evidence shows that this intervention probably has little to no effect on mortality during hospitalisation (risk ratio (RR) 0.99, 95%CI 0.57 to 1.7; 2 studies, n=1000), and on readmissions at one month (RR 0.93, 95%CI 0.76 to 1.14; 2 studies, n=997); and low-certainty evidence suggests that the intervention may have little to no effect on quality of life (MD 0.00, 95%CI -14.09 to 14.09; 1 study, n=724).  Low-certainty evidence suggests that database-assisted MR conducted by pharmacists, versus unassisted MR conducted by pharmacists, may reduce potential ADEs (OR 0.26, 95%CI 0.10 to 0.64; 2 studies, n=3326), and may have no effect on length of stay (MD 1.00, 95%CI -0.17 to 2.17; 1 study, n=311).  Low-certainty evidence suggests that MR performed by trained pharmacist technicians, versus pharmacists, may have little to no difference on length of stay (MD -0.30, 95%CI -2.12 to 1.52; 1 study, n=183). However, the CI is compatible with important beneficial and detrimental effects. Low-certainty evidence suggests that MR before admission may increase the identification of discrepancies compared with MR after admission (MD 1.27, 95%CI 0.46 to 2.08; 1 study, n=307). However, the CI is compatible with important beneficial and detrimental effects. Moderate-certainty evidence shows that multimodal interventions probably increase discrepancy resolutions compared to usual care (RR 2.14, 95%CI 1.81 to 2.53; 1 study, n=487). Computerised physician order entry (CPOE)/clinical decision support systems (CDSS) Moderate-certainty evidence shows that CPOE/CDSS probably reduce medication errors compared to paper-based systems (OR 0.74, 95%CI 0.31 to 1.79; 2 studies, n=88).  Moderate-certainty evidence shows that, compared with standard CPOE/CDSS, improved CPOE/CDSS probably reduce medication errors (OR 0.85, 95%CI 0.74 to 0.97; 2 studies, n=630). Low-certainty evidence suggests that prioritised alerts provided by CPOE/CDSS may prevent ADEs compared to non-prioritised (inconsequential) alerts (MD 1.98, 95%CI 1.65 to 2.31; 1 study; participant numbers unavailable). Barcode identification of participants/medications Low-certainty evidence suggests that barcoding may reduce medication errors (OR 0.69, 95%CI 0.59 to 0.79; 2 studies, n=50,545). Reduced working hours Low-certainty evidence suggests that reduced working hours may reduce serious medication errors (RR 0.83, 95%CI 0.63 to 1.09; 1 study, n=634). However, the CI is compatible with important beneficial and detrimental effects. Feedback on prescribing errors Low-certainty evidence suggests that feedback on prescribing errors may reduce medication errors (OR 0.47, 95%CI 0.33 to 0.67; 4 studies, n=384). Dispensing system Low-certainty evidence suggests that dispensing systems in surgical wards may reduce medication errors (OR 0.61, 95%CI 0.47 to 0.79; 2 studies, n=1775). AUTHORS' CONCLUSIONS: Low- to moderate-certainty evidence suggests that, compared to usual care, medication reconciliation, CPOE/CDSS, barcoding, feedback and dispensing systems in surgical wards may reduce medication errors and ADEs. However, the results are imprecise for some outcomes related to medication reconciliation and CPOE/CDSS. The evidence for other interventions is very uncertain. Powered and methodologically sound studies are needed to address the identified evidence gaps. Innovative, synergistic strategies -including those that involve patients- should also be evaluated.

Development of physical activity and food built environment quality indicators for chronic diseases in Argentina.

Although obesity and non-communicable disease (NCD) prevention efforts to-date have focused mainly on individual level factors, the social and physical environments in which people live are now widely recognized as important social determinants of health. Obesogenic environments promote higher dietary energy intakes and sedentary behaviors, thus contributing to the obesity/NCD burden. To develop quality indicators (QIs) for measuring food and physical activity (PA)-built environments in municipalities. A literature review was conducted. Based on the best practices identified from this review, a draft set of candidate QI was retrieved. The initial 67 QIs were then evaluated by a modified Delphi panel of multidisciplinary health professionals (n = 40) to determine their relevance, validity, and feasibility in 3 rounds of voting and threaded discussion using a modified RAND/University of California, Los Angeles Appropriateness Methodology. Response rate for the panel was 89.4%. All final 42 QIs were rated as highly relevant, valid, and feasible (median rating ≥ 7 on a 1-9 scale), with no significant disagreement. The final QI set addresses for the PA domain: (i) promotion of PA; and (ii) improvements in the environment to strengthen the practice of PA; and for Food environment domain: (i) promotion of healthy eating; (ii) access to healthy foods; and (iii) promotion of responsible advertising. We generated a set of indicators to evaluate the PA and food built environment, which can be adapted for use in Latin American and other low- and middle-income countries.

The built environment has a considerable effect on health indicators such as physical activity, eating behavior, and community. There is considerable research evidence demonstrating a direct relationship between our built environments and our health. In Argentina, the Healthy Municipalities and Communities Program focuses in health promotion interventions. It was developed to seek collaboration among community members, local government authorities and other stakeholders in order to improve quality of life. However, up to date, there has not been a homogenous measure to evaluate how well a particular locality or a whole municipality supports the health and wellbeing its residents. The proposed study aims to develop a set of local valid and common measures in order to evaluate what is happening within a particular municipality. A designated group of local experts will select a set of final measures trough out an iterative multistage process in order to combine opinion into group consensus. We will ask the panel to rate, discuss and re-rate the proposed measures (based on the existing evidence). This will study provide an evaluative tool to inform policy making and program implementation, and to guide programs and initiatives aimed at combating obesogenic environments in municipalities and communities.

A review of assessment indicators used by Healthy Municipalities and Communities Program in Latin America and the Caribbean region.

The Healthy Municipalities and Communities Strategy (HMCS) was developed by the Pan American Health Organization in 1990. Evaluation and monitoring are fundamental components of health promotion policies. The aim of this study is to explore the indicators used in Latin America and the Caribbean (LAC) countries to assess the performance of HMCS. We searched MEDLINE, EMBASE, LILACS, BVSDE and Google Advanced Search for documents published between January 2000 and April 2016. We included only documents with assessment indicators of the strategy. All articles were independently assessed for eligibility by pairs of reviewers. We classified the indicators with a supporting framework proposed by O'Neill and Simard (Choosing indicators to evaluate Healthy Cities projects: a political task? Health Promot Int 2006, 21, 145-152.). Local level indicators figured far more prominently among countries and were distributed both in projects and specific activities. Regarding the evolution of the HMCS, indicators were reported in the five levels of analysis (local projects and activities, provincial, national and international networks). Empowerment was represented through the presence of active community organizations and different methods of community participation (forums, open hearing and participation maps). Public policies (such as for tobacco cessation) and bylaws adherence and changes in school's curricula regarding healthy eating were frequently mentioned. However, this review demonstrated that impact indicators related to lifestyle changes or built environment are not clearly defined and there is a lack of indicators to measure progress in achieving change in long-term outcomes in LAC. We highlight the importance of designing validated indicators for measuring the impact of health promotion policies in partnership with each country involved.

Effect of Adding a Galacto-Oligosaccharides/Fructo-Oligosaccharides (GOS/FOS®) Mixture to a Normal and Low Calcium Diet, on Calcium Absorption and Bone Health in Ovariectomy-Induced Osteopenic Rats.

Menopause is associated with bone loss. Prebiotics increase Ca, inorganic phosphorus (Pi), and Mg absorption, improving bone health. These increases would supply an extra amount of minerals, decreasing bone resorption and possibly reversing ovariectomy-induced bone loss. The present experimental study sought to evaluate the effect of adding a prebiotic GOS/FOS® mixture to a normal or a low Ca diet on Ca, Pi, and Mg absorption, in osteopenic rats. Four groups of n = 8 rats each were OVX, and 8 rats were SHAM operated. All rats were fed a commercial diet for 45 days. They were then fed one of the following diet for 45 days: C-0.5%: SHAM fed AIN 93 M containing 0.5%Ca; O-0.5% and O-0.3%: OVX rats fed AIN 93 M, containing 0.5% or 0.3%Ca, respectively; GF-0.5% and GF-0.3%: OVX rats fed AIN 93 M, containing 0.5% or 0.3%Ca+ 2.5% GOS/FOS®, respectively. At the end of the experimental time point, Ca, P, and MgAbs% was significantly higher in GF-0.5% and GF-0.3% as compared to the remaining groups (p < 0.01). Irrespective of diet Ca content, CTX decreased whereas femur Ca and P content, tibia BV/TV and GPC.Th, lumbar spine and proximal tibia BMD, bone strength, bone stiffness, and elastic modulus increased in the GF-0.5% and GF-0.3% groups as compared to O-0.5% and O-0.3%, respectively (p < 0.05). This prebiotic mixture would be a useful tool to prevent the increase in bone loss associated with menopause and aging.

Comparison of self-reported and directly measured weight and height among women of reproductive age: a systematic review and meta-analysis.

INTRODUCTION: The use of self-report as a strategy for collecting data on women's weight and height is widespread in both clinical practice and epidemiological studies. This study aimed to compare self-reported and directly measured weight and height among women of reproductive age. MATERIAL AND METHODS: In July 2015 we searched MEDLINE, EMBASE, COCHRANE, CINHAL, LILACS and gray literature. We included women of reproductive age (12-49 years old) independently of their weight or height at the time of the study. Women with any condition that implies regular tracking of their weight (for example, eating disorder) were excluded. Two reviewers independently selected, extracted and assessed the risk of bias of the studies. We used REVMAN 5.3 to perform the meta-analysis. Heterogeneity was assessed using the I2 statistic. RESULTS: Following eligibility assessment, 21 studies of 18 749 women met the inclusion criteria. The results of the meta-analysis showed an underestimation of weight by -0.94 kg (95% CI -1.17 to -0.71 kg; p < 0.0001; I2  = 0%) in the overall sample and an overestimation of height by 0.36 cm (95% CI 0.20-0.51; p < 0.0001; I2  = 35%) based on self-reported vs. directly measured values. CONCLUSION: This review shows that self-reported weight and height of women of reproductive age differs slightly from direct measures. We consider that the magnitude at which self-reported data over- or underestimates the real value, is negligible regarding clinical and research use.

Argentine consensus recommendations for lung cancer screening programmes: a RAND/UCLA-modified Delphi study.

BACKGROUND: Lung cancer (LC) screening improves LC survival; the best screening method in terms of improving survival is low-dose CT (LDCT), outpacing chest X-ray and sputum cytology. METHODS: A consensus of experts in Argentina was carried out to review the literature and generate recommendations for LC screening programmes. A mixed-method study was used with three phases: (1) review of the literature; (2) modified Delphi consensus panel; and (3) development of the recommendations. The Evidence to Decision (EtD) framework was used to generate 13 evaluation criteria. Nineteen experts participated in four voting rounds. Consensus among participants was defined using the RAND/UCLA method. RESULTS: A total of 16 recommendations scored ≥7 points with no disagreement on any criteria. Screening for LC should be performed with LDCT annually in the population at high-risk, aged between 55 and 74 years, regardless of sex, without comorbidities with a risk of death higher than the risk of death from LC, smoking ≥30 pack-years or former smokers who quit smoking within 15 years. Screening will be considered positive when finding a solid nodule ≥6 mm in diameter (or ≥113 mm3) on baseline LDCT and 4 mm in diameter if a new nodule is identified on annual screening. A smoking cessation programme should be offered, and cardiovascular risk assessment should be performed. Institutions should have a multidisciplinary committee, have protocols for the management of symptomatic patients not included in the programme and distribute educational material. CONCLUSION: The recommendations provide a basis for minimum requirements from which local institutions can develop their own protocols adapted to their needs and resources.

[Is daily supplementation with vitamin D2 equivalent to daily supplementation with vitamin D3 in the elderly?]. / Es equivalente la suplementación diaria con vitamina D2 o vitamina D3 en adultos mayores?

The equivalence of cholecalciferol (D3) and ergocalciferol (D2) as well as their corresponding doses and administration route remain controversial to date. The aim of this study was to compare the effectiveness of daily supplementation with 800 IU of D2 (drops) and D3 (pills) on 25-hydroxivitamin D (25OHD) levels (= 30 ng/ml). Twenty-one ambulatory postmenopausal women from Buenos Aires City with a mean (X ± SD) age of 77.1 ± 6.8 years were included. The participants were randomly assigned to one of the following groups: GD2 (n = 13): 800 IU (drops) and GD3 (n = 8): 800 IU (pills). Serum 25OHD levels were measured (RIA-DIASORIN) at baseline, and at 7, 28 and 45 days. Nineteen out of twenty one women showed deficient levels of 25OHD at baseline (< 20 ng/ml): GD2: 14.0 ± 4.8 ng/ml and GD3: 13.2 ± 4.9 ng/ml (NS). Whereas only GD3 exhibited an increase (≈ 25%) at 7 days, both groups showed a significant increase at the end of the study. However, neither attained adequate 25OHD levels (GD2: 17.4 ± 5.5 vs. GD3:22.9 ± 4.6 ng/ml; p < 0.001). Administration of 800 IU of vitamin D3 during 45 days was more effective than D2 in increasing 25OHD, but both failed to achieve adequate levels of 25OHD (= 30 ng/ml). but neither succeeded in achieving adequate levels of 25OHD (= 30 ng/ml).

A subset of low density granulocytes is associated with vascular calcification in chronic kidney disease patients.

Inflammation is central to chronic kidney disease (CKD) pathogenesis and vascular outcomes, but the exact players remain unidentified. Since low density granulocytes (LDGs) are emerging mediators in inflammatory conditions, we aimed to evaluate whether LDGs may be altered in CKD and related to clinical outcomes as biomarkers. To his end, LDGs subsets were measured in peripheral blood by flow cytometry and confocal microscopy in 33 CKD patients undergoing peritoneal dialysis and 15 healthy controls (HC). Analyses were replicated in an additional cohort. DEF3 (marker of early granulopoiesis) gene expression on PBMCs was quantified by qPCR. Total CD15+ LDGs and both CD14lowCD16+ and CD14-CD16- subsets were expanded in CKD. The relative frequency of the CD14-CD16- subpopulation was higher among the CD15+ pool in CKD. This alteration was stable over-time. The increased CD14-CD16-CD15+ paralleled Kauppila scores and DEF3 expression, whereas no association was found with CD14lowCD16+ CD15+. Both subsets differed in their CD11b, CD10, CD35, CD31, CD62L, IFNAR1 and CD68 expression, FSC/SSC features and nuclear morphology, pointing to different origins and maturation status. In conclusion, LDGs were expanded in CKD showing a skewed distribution towards a CD14-CD16-CD15+ enrichment, in association with vascular calcification. DEF3 expression in PBMC can be a marker of LDG expansion.

MicroARN circulantes y su potencialidad como futuros biomarcadores óseos / Circulating microRNAs and their potential use as future bone biomarkers / MicroRNAs circulantes e a sua potencialidade como futuros biomarcadores ósseos

Resumen El remodelamiento óseo es ejercido por la actividad de osteoblastos y osteoclastos y puede evaluarse por marcadores bioquímicos de formación y resorción ósea. Sin embargo, el nivel de los marcadores óseos está sometido a una enorme cantidad de variables y, además, carece o presenta escaso valor pronóstico. Los microARN (miARN) fueron recientemente estudiados como una alternativa potencial para ser utilizados como nuevos marcadores óseos. Los miARN son pequeñas moléculas de ARN no codificantes (15-25 nucleótidos) que, a través de la inhibición o degradación de ARN mensajeros, modifican una serie de funciones biológicas. Los miARN específicos de hueso ejercen funciones reguladoras sobre factores transcripcionales involucrados en la osteoblastogénesis y osteoclastogénesis, modificando el remodelamiento óseo. La mayoría de los miARN permanecen dentro de la célula, pero algunos son liberados a la circulación donde pueden ser dosados. Los miARN circulantes presentan gran estabilidad en fluidos biológicos, lo que los hace potenciales candidatos a ser utilizados como nuevos biomarcadores óseos. Cambios en el patrón normal de miARN circulantes específicos de hueso reflejarán modificaciones en el metabolismo óseo y señalan el posible inicio o progresión de enfermedades óseas, como la osteoporosis. Si bien es promisorio, el uso en la práctica clínica de los miARN específicos circulantes como nuevos biomarcadores óseos, ello implica primeramente cumplir con una serie de requisitos que permitan estandarizar las condiciones preanalíticas, analíticas y posanalíticas de estas moléculas. La presente revisión brinda información reciente sobre los estudios clínicos tendientes a determinar el posible uso de los miARN circulantes como nuevos biomarcadores óseos, ya que cuentan con elevada sensibilidad y especificidad diagnósticas, valor predictivo positivo y valor predictivo negativo.

Abstract Osteoblasts and osteoclasts activity determines the level of the bone remodelling process which can be assessed by biochemical markers of bone formation and resorption. However, bone marker levels are subject to a series of variables resand, furthermore, they lack or have little prognostic values. MicroRNAs (miRNAs) were recently studied as a potential alternative to be used as new bone biomarkers. The miRNAs are endogenous small noncoding RNA molecules (15-25 nucleotides) that regulate many biological functions by inhibiting or degrading specific messenger RNAs. Bone-specific miRNAs exert regulatory functions on key transcriptional factors involved in osteoblastogenesis and osteoclastogenesis, modifying the bone remodelling process. Most miRNAs remain within the cell, but some of them are released into circulation. Circulating miRNAs show great stability in biological fluids, which makes them excellent candidates to be used as new bone biomarkers. Modifications in the normal pattern of bone-specific circulating miRNA might reflect changes in bone metabolism, signalling the possible onset or progression of bone diseases, such as osteoporosis. Although promising, the use of specific circulating miRNAs as new bone biomarkers in clinical practice implies fulfilling a series of requirements that lead to standardising the pre-analytical, analytical and post-analytical conditions of these molecules. The present review gives an overview on the clinical studies related to the possible use of specific circulating miRNAs as new bone biomarkers.

Resumo A remodelação óssea é exercida pela atividade dos osteoblastos e osteoclastos e pode ser avaliada para a medição dos marcadores bioquímicos de formação e reabsorção óssea. No entanto, o nível dos marcadores ósseos está sujeito a grande quantidade de variáveis e, além disso, carece ou tem pouco valor prognóstico. Os microARN (miARN) foram estudados recentemente como uma alternativa potencial para serem utilizados como novos marcadores ósseos. Os MicroRNAs (miRNAs) são pequenas moléculas de RNA não codificantes (15-25 nucleotídeos) que, através da inibição ou degradação de RNA mensageiros modificam uma série de funções biológicas. Os miRNAs específicos de osso exercem funções reguladoras sobre fatores transcricionais envolvidos na osteoblastogênese e na osteoclastogênese, modificando o processo de remodelação óssea. A maioria dos miRNAs permanece dentro da célula, mas de RNA mensageiros alguns são liberados na circulação, onde podem ser determinados bioquimicamente. Os miRNAs circulantes apresentam grande estabilidade em fluidos biológicos, o que os torna excelentes candidatos para serem usados como novos biomarcadores ósseos. Mudanças no padrão normal de miRNA circulantes específicos do osso mostrarão mudanças no metabolismo ósseo, sinalizando o possível início ou progressão de doenças ósseas, como osteoporose. Embora promissor, o uso de miRNAs específicas circulantes na prática clínica como novos biomarcadores ósseos, implica primeiramente, atender uma série de requisitos que permitem padronizar as condições pré-analíticas, analíticas e pós-analíticas dessas moléculas. A presente revisão fornece informações recentes sobre estudos clínicos destinados a determinar o possível uso dos miRNAs circulantes como novos biomarcadores ósseos, visto que contam com elevada sensibilidade e especificidade diagnósticas, valor preditivo positivo e valor preditivo negativo.

Vitamina D y embarazo: una experiencia piloto / Vitamin D and pregnancy: a pilot experience

La insuficiencia de vitamina D (VD) en el embarazo se relaciona con una mayor incidencia de cesáreas, preeclampsia y partos prematuros. Objetivo: evaluar si el grado de insuficiencia de VD se asocia a mayor número de cesáreas y evaluar la correlación entre la 25 hidroxivitamina D (25OHD) materna y en sangre del cordón del recién nacido. Las mujeres (n=127) se dividieron según sus niveles de 25OHD (ng/mL):G1:<20 (deficiencia), G2:20-30 (insuficiencia), G3:>30 (suficiencia). Se registraron edad; edad gestacional (EG); índice de masa corporal (IMC); tensión arterial sistólica y diastólica; tipo de parto y la estación del año en que se tomó la muestra. Se determinaron calcemia (ng/mL); 25OHD; parathormona intacta (pg/mL); fosfatasa alcalina ósea (UI/L) y crosslaps (pg/mL). La edad media fue de 26±6 años y la EG de 35,8±2,7 semanas, sin diferencias entre grupos. El porcentaje de cesáreas fue mayor en G1 que en G2 y G3 (31,3%, 21,4% y 25%, respectivamente; p<0,05). El mayor porcentaje de muestras se tomó en primavera (p<0,05). No se observaron diferencias en las demás variables maternas estudiadas. La 25OHD materna correlacionó positivamente con los valores de la sangre de cordón de sus respectivos recién nacidos (r= 0,67; p<0,0001). Independientemente de la época del año y del IMC, se observó que un porcentaje significativo de las mujeres embarazadas estudiadas tenía niveles de 25OHD inferiores a 30 ng/mL. Conclusión: evidenciamos que la deficiencia de VD materna se asoció al número de cesáreas. Asimismo, los niveles séricos de 25OHD en sangre de cordón umbilical correlacionaron significativamente con los maternos. (AU)

Vitamin D (VD) insufficiency in pregnancy is associated with a higher incidence of cesarean section, preeclampsia, and preterm delivery. Objective: to evaluate if the degree of VD insufficiency is associated with the incidence of cesarean section and to determine the correlation between maternal and newborn cord blood 25-hydroxy VS (25OHD). Women (n=127) were divided according to their 25OHD levels (ng/mL): G1:<20 (deficiency), G2:20-30 (insufficiency), G3:>30 (sufficiency). Age; gestational age (GA); body mass index (BMI); systolic and diastolic blood pressure (mmHg); type of delivery and the season of the year in which the sample was taken were recorded. Calcemia (ng/mL); 25OHD; intact parathormone (pg/mL); bone alkaline phosphatase (IU/L) and Crosslaps (pg/mL) levels were determined. Mean age was 26±6 years and GA was 35.8±2.7 weeks with no differences among groups. The % of cesarean sections was higher in G1 than in G2 and G3 (31.3%, 21.4% and 25%; p<0.05). The highest % of samples were taken in spring (p<0.05). No differences were observed in the other maternal variables studied. Maternal serum 25OHD levels correlated positively with those of cord blood from their respective newborns (r=0.67; p<0.0001). Regardless the season of the year and BMI, a high % of the studied pregnant women presented 25OHD levels lower than 30 ng/ml. Conclusion: we found that maternal VD deficiency is associated with the number of cesarean sections. In addition, 25OHD levels in the newborn significantly correlate with maternal serum levels. (AU)

A pilot study on the impact of body composition on bone and mineral metabolism in Parkinson's disease.

The impact of body composition on bone and mineral metabolism in Parkinson's disease (PD) was evaluated. Body fat mass, lean mass, bone mineral content, and bone mineral density (BMD) were measured by DXA in 22 PD patients and 104 controls. Female patients exhibited reduced body mass index, fat mass, and BMD compared to controls (p<0.05). Significant positive correlation was found between 25 OHD levels and BMC. Diminished bone mass in women with PD was found to be associated with alterations in body composition and low 25 OHD levels.

A pilot study of body composition and bone mineral density in healthy men from Argentina.

A precise assessment of bone mineral density (BMD) and body composition can be performed using dual-energy X-ray absorptiometry (DXA). Values of body composition for males would be useful to evaluate the occurrence of alterations in body composition in a number of diseases. The objectives of this study were to establish BMD and body composition values in healthy men and to analyze age-related changes. BMD and body composition of total body and subareas were determined in 116 healthy men (aged 20-79 yr) using DXA. Comparison between 20-29- and 70-79-yr-old men showed that older subjects were shorter (p<0.03), and had a higher body mass index (p<0.01). Fat mass increased (+46.7%; p<0.001) especially in the trunk. Lean mass (LM) decreased (-9.4%; p<0.05) mainly in the arms and legs. Bone mineral content (BMC) and BMD decreased (-15.3% [p<0.001], -6.3% [p<0.05], respectively). Correlation was observed between BMC and LM (r=0.7, p<0.01). Values of BMD and body composition in healthy men were obtained. A relation was observed between bone mass and body composition, suggesting that the age-related decrease in LM may be associated to bone mass loss. Further studies should be conducted to elucidate the role of body composition in the occurrence of osteoporosis in men.

Absorción mineral y retención ósea en ratas normales en crecimiento por el consumo de un yogur experimental reducido en lactosa que contiene galactooligosacáridos (GOS) / Mineral absorption and bone retention in normal growing rats by consumption of an experimental lactose-reduced yogurt containing galactooligosaccharides (GOS)

Introducción: Los GOS son prebióticos naturales presentes en la leche materna que pue-den obtenerse enzimáticamente a partir de la lactosa de leche de vaca durante la fabricación de yogur. El producto lácteo resultante será reducido en lactosa y contendrá prebióticos y bacterias potencialmente probióticas. Sin embargo, mantendrá la baja relación Ca/Pi que aporta la leche de vaca, lo que podría alterar el remodelamiento óseo y la mineralización. Objetivo: comparar si un yogur reducido en lactosa que contiene GOS (YE) ofrece ventajas adicionales respecto de un yogur regular sin GOS (YR) sobre las absorciones (Abs) de Ca y Pi, retención y calidad ósea durante el crecimiento normal. Al destete, ratas machos fueron divididas en 3 grupos alimentados con AIN ́93-G (C), YE o YR durante 28 días. Resultados: YE mostró el mayor aumento de lactobacilos fecales; producción de ácidos grasos de cadena corta especialmente p, profundidad de las criptas colónicas y menor pH cecal. El %AbsCa y %AbsPi aumentó en el siguiente órden: YE> YR> C (p < 0,05). El contenido de Ca y Pi en fémur, la densidad y contenido mineral óseos y los parámetros biomecánicos fueron similares en YE y C, mientras que YR mostró valores significativa-mente menores (p < 0,05). Conclusiones: YE aumentó las Abs y biodisponibilidad de minerales, alcanzando la retención y calidad ósea de C. El aumento en las Abs observado en YR no logró obtener la retención y calidad ósea de C. Conclusión: YE habría contrarrestado el efecto negativo del mayor aporte de Pi de la leche de vaca y sería una buena estrategia para lograr el pico de masa ósea y calidad del hueso adecuados, especialmente en individuos intolerantes a la lactosa. (AU)

Breast milk contains an optimal calcium/phosphate (Ca/Pi) ratio and GOS. These natural prebiotics can be enzymatically produced via cow's milk lactose inyogurt manufacture. This milk product is low in lactose and contains prebiotics and potentially probiotic bacteria but maintains a low Ca/Pi ratio that could alter bone remodeling and mineralization. We evaluated if a lactose-reduced yogurt containing GOS (YE) offers additional advantages over regular yogurt without GOS (YR) on Ca and Pi absorption (Abs), bone retention and quality during normal growth. Weaning male rats were divided into 3 groups fed AIN'93-G (C), YE or YR for 28 days. Results: YE showed the highest increase in fecal lactobacilli; short-chain fatty acids production, especially propionate and butyrate; intestine crypt depth, and the lowest cecal pH. AbsCa% and AbsPi% increased in this order: YE> YR> C (p <0.05). Ca and Pi content in femur, bone density and mineral content, and biomechanical parameters were similar in YE and C, while YR showed the significantly lowest value (p < 0.05). Conclusions: YE increased mineral Abs reaching the retention and bone quality of C. Although YR increased Abs, bone retention and quality did not achieve C values. Seemingly, YE compensated for the negative effect of the higher Pi supply and would be a good strategy to achieve adequate peak bone mass and bone quality, especially in lactose intolerant individuals. (AU)

Efectos de la administración local de PTH 1-34 a bajas dosis en un modelo experimental de periodontitis: estudio piloto / Local effects of low dose of PTH 1-34 on experimental periodontitis: pilot study

La periodontitis es una patología inflamatoria que aumenta la resorción de hueso alveolar (HA), pérdida de la inserción dentaria y posible exfoliación. Evaluamos el efecto de la administración intermitente de bajas dosis de parathormona (PTH) 1-34 sobre la recuperación de la masa ósea pérdida en un modelo experimental de periodontitis inducida por una ligadura periodontal (LP) con hilo de algodón alrededor de la pieza dentaria. Las ratas fueron divididas luego de 5 días en instaurada la periodontitis en: CT LP sin trata-miento y PTH LP tratados con 0,2 µg/kg PTH 1-34 subcutánea local, tres veces por semana por 17 días. El control absoluto fue un tercer grupo sin LP (CT). Se estudiaron parámetros antropométricos, bioquímicos e histomosfométricos en tibias y hemimandibulas. La calcemia, fosfatemia, CTX sérico, PTHi y vo-lumen óseo (BV/TV%) de tibias fueron similares en los tres grupos. El BV/TV% del HA fue significativamente menor en PTH LP respecto de CT pero mayor que CT LP (p<0.05). La pérdida ósea de HA porcentual fue significativamente mayor en CT LP (p<0.05). La altura del ligamento periodontal fue significativamente menor en PTH LP que en CT (p<0.05) y mayor respecto de CT LP, sin alcanzar diferencias significativas. Los resultados del presente estudio piloto sugieren que la administración intermitente de PTH en bajas dosis y durante un periodo de tiempo corto disminuye la progresión de la enfermedad periodontal sin generar efectos sistémicos. Como no se logró regenerar totalmente el tejido periodontal se requieren estudios adicionales. (AU)

Periodontitis is an inflammatory chronic disease with high prevalence in adults that induces a progressive alveolar bone (AB) loss leading to tooth loss. Experimental periodontitis can be induced in rats by cotton ligature placement (LP) in the gingival sulcus around the molar teeth. The biofilm accumulation and disruption of the gingival epithelium lead to bone resorption. We investigated whether intermittent administration of a low dose of PTH 1-34 may recover the alveolar bone loss in the experimental periodontitis induced in female Wistar rats. Animals were randomly divided in two groups which were subcutaneously injected with: saline solution (CT LP) or 0,2 µg/kg PTH 1-34 (PTH LP) three times per week during 17 days. Unligated rats were taken as healthy controls (CT). Anthropometric, biochemical and histologic analysis of tibia and hemimandible were done. No differences in serum calcium, phosphorus, CTX, PTHi or subchondral tibia bone volume (BV/TV%) were observed between the three groups. AB BV/TV% was significantly lower in PTH LP than in CT but higher than in CT LP (p<0.05). The highest percentage of AB loss was observed in CT LP. The height of periodontal ligament was lower in PTH LP than in CT (p<0.05) but not significantly higher than CT LP.The increase in AB loss by experimental periodontitis appears to be corrected by the intermittent administration of low doses of PTH without systemic effect. As the recovery of periodontal tissue was only partial, additional studies should be done.

Importancia de la Vitamina D en la época del COVID-19 / Importance of Vitamin D in the time of COVID-19

"Los coronavirus pertenecen a una gran familia de virus (Coronaviridae) que infectan aves y varios mamíferos. El coronavirus actualmente denominado SARS-CoV-2, fue descubierto en diciembre de 2019 en Wuhan, provincia de Hubei, China, y es el agente causal de la epidemia de neumonía atípica actual" (COVID-19; Coronavirus Disease 2019). Los casos más graves presentan un síndrome de dificultad respiratoria aguda que puede conducir a la muerte. La vitamina D (VD), además del efecto bien conocido y positivo sobre la salud ósea y la homeostasis del calcio, tiene efecto pleiotrópico en varios órganos, con distribución casi universal del receptor de VD y de las enzimas de metabolización de 25 hidroxivitamina D (25OHD) en las células del organismo. Estas acciones extraesqueléticas dependen de la síntesis en dichas células del metabolito activo 1,25 dihidroxivitamina D por regulación paracrina y autocrina, dependiente de niveles circulantes óptimos de 25OHD. Por sus acciones inmunomoduladora, antiinflamatoria, antimicrobiana, reguladora del sistema renina-angiotensina-aldosterona, favorecedora de la indemnidad del epitelio respiratorio y la homeostasis redox celular, la VD podría tener efecto protector en la infección por COVID-19. Entre los grupos de riesgo para COVID-19 figuran los adultos mayores, obesos, diabéticos, hipertensos, con afecciones cardiovasculares, patologías con mayor incidencia en individuos con hipovitaminosis VD. La suplementación con VD, para alcanzar niveles óptimos de 25OHD de 40-60 ng/ml, podría reducir la incidencia, severidad y riesgo de muerte en la actual pandemia por COVID-19, como medida complementaria mientras se desarrollan la vacuna y otras medicaciones específicas. (AU)

Coronaviruses belong to a large family of viruses (Coronaviridae) that infect birds and various mammals. The novel coronavirus currently known as SARS-CoV-2 was discovered in December 2019 in Wuhan, Hubei province, China and is the causal agent of the current atypical pneumonia epidemic (COVID-19: Coronavirus Disease 2019); The most severe cases present with acute respiratory distress syndrome that can lead to death. Vitamin D (VD) has a pleiotropic effect on several organs, in addition to its wellknown and positive effect on bone health and calcium homeostasis, with an almost universal distribution of the VD receptor and the metabolites of 25hydroxyvitamin D (25OHD) in all cells of the body. These extra-skeletal actions depend on the synthesis of the active metabolite 1,25dihydroxyvitamin D in the cells depending on the optimal circulating levels of 25OHD and though paracrine and autocrine regulation. Due to its immunomodulatory, anti-inflammatory, antimicrobial, and regulatory actions on the renin angiotensin aldosterone system, which favors the compensation of the respiratory epithelium and cellular redox homeostasis, the VD could have a protective effect on COVID-19 infection. Among the risk groups for COVID-19 are obese, diabetic, and hypertensive patients, subjects with cardiovascular conditions, and elderly people. All these pathologies show a higher incidence in individuals with VD hypovitaminosis. VD supplementation, to achieve optimal 25OHD levels of 40-60 ng/ml, could reduce the incidence, severity, and risk of death in the current COVID-19 pandemic, as a complementary measure while the vaccine and other specific therapies are being developed. (AU)

Micro-ARNs y células óseas / Micro RNAs and bone cells

Los micro-ARNs (miARNs) son pequeñas moléculas de ARN no codificante (de aproximadamente 15-25 nucleótidos), que regulan la expresión de genes involucrados en numerosas funciones biológicas, a través de la inhibición o degradación de un ARN mensajero diana. La homeostasis ósea se mantiene por el balance entre la formación osteoblástica y la resorción osteoclástica. La sobreexpresión o inhibición de miARNs específicos afecta la proliferación, diferenciación y actividad de osteoblastos, osteocitos y osteoclastos. Estas acciones son llevadas a cabo modulando la expresión de distintos factores transcripcionales y moléculas de señalización de las vías esenciales para la osteoblastogénesis u osteoclastogénesis. Estos efectos modifican el balance entre la formación y la resorción, determinando cambios en la homeostasis ósea. Esta revisión enumera una serie de miARNs que participan en la homeostasis ósea. Profundizando en el conocimiento de los mecanismos por medio de los cuales los miARNs actúan sobre el hueso, podrían revelarse nuevos usos potenciales futuros, entre los que se encuentran su utilidad como nuevos biomarcadores óseos o como agentes terapéuticos para el tratamiento de trastornos metabólicos óseos, pérdida de masa ósea o enfermedades óseas. (AU)

MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules (of approximately 15­25 nucleotides), which regulate the expression of genes controlling numerous biological functions, through the inhibition or degradation of the target messenger RNA. Bone homeostasis is maintained by a balance between osteoblastic bone formation and osteoclastic bone resorption. The overexpression or inhibition of specific miRNAs affects cell proliferation, differentiation and activity of osteoblast, osteocytes and osteoclast. This action is done by modulating the expression of different transcription factors and signaling molecules of the most relevant pathways of osteoblastogenesis or osteoclastogenesis. This effect is able to modify the balance between bone formation and resorption, determining changes in bone homeostasis. The present review is an overview of a series of miRNAs involved in bone homeostasis. An in depth knowledge of the mechanisms by which miRNAs act on bone may reveal potential uses in the future as new bone biomarkers or therapeutic agents for treating metabolic bone disorders, bone loss and bone diseases. (AU)

Rol de la osteocalcina más allá del hueso / Role of osteocalcin beyond bone

Los hallazgos osteológicos se intensi!caron en los últimos años. Se demostró que el esqueleto se comporta, además de sus funciones clásicas, como un órgano de secreción endocrina que sintetiza al menos dos hormonas: el factor de crecimiento de !broblastos 23 (FGF-23) y la osteocalcina (Ocn). La Ocn es un péptido pequeño que contiene 3 residuos de ácido glutámico. Estos residuos se carboxilan postraduccionalmente, quedando retenida en la matriz ósea. La forma decarboxilada en el primer residuo de ácido glutámico (GluOcn) fue reportada por poseer efectos biológicos; la resorción ósea es el mecanismo clave para su bioactivación. La presente revisión se centra en los conocimientos actuales sobre la función hormonal de la Ocn. A la fecha se reporta que la Ocn regularía el metabolismo energético aumentando la proliferación de células ` pancreáticas, y la secreción de insulina y de adiponectina. Sobre el músculo esquelético actuaría favoreciendo la absorción y el catabolismo de nutrientes. La función reproductiva masculina estaría regulada mediante el estímulo a las células de Leydig para sintetizar testosterona; en el desarrollo cerebral y la cognición, la Ocn aumentaría la síntesis de neurotransmisores monoaminados y disminuiría el neurotransmisor inhibidor GABA. Si bien son indispensables mayores evidencias para dilucidar los mecanismos reguladores por medio de los cuales actuaría la Ocn, los resultados enumerados en los distintos estudios experimentales establecen la importancia de este novedoso integrante molecular. Dilucidar su rol dentro de estos procesos interrelacionados en seres humanos abriría la posibilidad de utilizar a la Ocn en el tratamiento de enfermedades endocrino-metabólicas. (AU)

Osteological !ndings have intensi!ed in recent years. The skeleton behaves as an endocrine secretion organ that synthesizes at least two hormones: osteocalcin (Ocn) and !broblast growth factor 23 (FGF-23). Ocn is a small peptide that contains 3 glutamic acid residues. After translation, these residues are carboxylated to make possible its retention into the bone matrix. Decarboxylation on the !rst glutamic acid residue (GluOcn) has been reported to have biological effects. Bone resorption is the key mechanism for its bioactivation. This review focuses on current knowledge on Ocn hormonal function. It has been reported that Ocn regulates energy metabolism by increasing the proliferation of pancreatic ` cells, and the secretion of insulin and adiponectin. On the skeletal muscle, it may act by favoring the absorption and catabolism of nutrients. Male reproductive function might be regulated by stimulating Leydig cells to synthesize testosterone. Regarding brain development and cognition, Ocn would increase monoamine neurotransmitters synthesis and decrease inhibitory neurotransmitter GABA. Although more evidence is needed to elucidate the regulatory mechanisms of Ocn, different experimental studies establish the importance of this novel molecular mediator. Clarifying its role within interrelated processes in humans, might open the possibility of using Ocn in different treatments of endocrine-metabolic diseases. (AU)

Caso clínico: hipofosfatasia de la niñez. Seguimiento clínico / Clinical case: childhood hypophosphatasia. Clinical follow-up

La hipofosfatasia (HP) es una enfermedad congénita, causada por mutaciones con pérdida de función en el gen ALPL que codifica la isoenzima no específica de tejido de la fosfatasa alcalina (TNSALP). Su expresión clínica es muy variable, desde casos de muerte intraútero por alteración grave de la mineralización ósea, hasta casos solo con caída prematura de la dentición. Se presenta el caso clínico de un varón al que se le diagnosticó odontohipofosfatasia a los 30 meses por pérdida temprana de piezas dentarias y niveles anormalmente bajos de fosfatasa alcalina, sin signos de raquitismo ni deformidades óseas. Durante su seguimiento, hasta los 13 años, presentó síntomas compatibles con HP infantil leve, como cansancio al caminar, incoordinación en la marcha y dolor en miembros inferiores que aumentaban con la actividad física. Ante la aparición de edema bimaleolar y poca respuesta al tratamiento con calcitonina y antiinflamatorios, se descartaron patologías infecciosas o reumáticas o ambas y se diagnosticó, por biopsia de tibia y peroné, periostitis sin detección de cristales de pirofosfato. Los controles radiológicos durante su evolución mostraron ensanchamiento metafisario en muñeca, falta de remodelado de metacarpianos, hojaldrado perióstico en tibia y peroné e hipomineralización en metáfisis tibiales, con "lenguas radiolúcidas" características de HP. Como conclusión, la hipofosfatasia debe considerarse como una entidad clínica para descartar en niños que presentan pérdida temprana de dientes. La presencia de este cuadro clínico es en general suficiente para realizar el diagnóstico de HP de la niñez. (AU)

Hypophosphatasia (HP) is a congenital disease, caused by mutations with loss of function in the gene ALPL that encodes the non-specific tissue isoenzyme of alkaline phosphatase (TNSALP). Its clinical expression displays considerable variability, from cases of intrauterine death due to severe alteration of bone mineralization, to cases with only early loss of teeth. We report the case of a male, diagnosed as odontohypophosphatasia at 30 months of age due to early loss of teeth and abnormally low levels of alkaline phosphatase, without signs of rickets or bone deformities. During follow-up, up to 13 years of age, he presented symptoms consistent with mild infantile HP such as tiredness when walking, lack of gait coordination, and pain in lower limbs, especially after physical activity. Due to the appearance of bimalleolar edema and poor response to treatment with calcitonin and anti-inflammatory drugs, infectious and / or rheumatic pathologies were ruled out. Periostitis without pyrophosphate crystal detection was diagnosed by tibial and fibular biopsy. Radiological controls during follow up showed metaphyseal wrist enlargement, lack of remodeling of metacarpals, periosteal flaking in the tibia and fibula and hypomineralization in the tibial metaphysis, with "radiolucent tongues"; characteristic of HP. In conclusion, hypophosphatasia should be considered as a clinical entity in children who present early loss of teeth. The presentation of this clinical case is generally sufficient to make the diagnosis of childhood HP. (AU)