Nutrients and Dietary Patterns Related to Osteoporosis

Osteoporosis is a common chronic disease characterized by a decrease in bone mineral density, impaired bone strength, and an increased risk of fragility fractures. Fragility fractures are associated with significant morbidity, mortality and disability and are a major public health problem worldwide. The influence of nutritional factors on the development and progression of this disease can be significant and is not yet well established. Calcium intake and vitamin D status are considered to be essential for bone metabolism homeostasis. However, some recent studies have questioned the usefulness of calcium and vitamin D supplements in decreasing the risk of fractures. The adequate intake of protein, vegetables and other nutrients is also of interest, and recommendations have been established by expert consensus and clinical practice guidelines. It is important to understand the influence of nutrients not only in isolation but also in the context of a dietary pattern, which is a complex mixture of nutrients. In this review, we evaluate the available scientific evidence for the effects of the main dietary patterns on bone health. Although some dietary patterns seem to have beneficial effects, more studies are needed to fully elucidate the true influence of diet on bone fragility.Instituto de Salud Carlos III PI18/01235European Union (EU

Vitamin D Status, Calcium Intake and Risk of Developing Type 2 Diabetes: An Unresolved Issue

The relationship between vitamin D status, calcium intake and the risk of developing type 2 diabetes (T2D) is a topic of growing interest. One of the most interesting non-skeletal functions of vitamin D is its potential role in glucose homeostasis. This possible association is related to the secretion of insulin by pancreatic beta cells, insulin resistance in different tissues and its influence on systemic inflammation. However, despite multiple observational studies and several meta-analyses that have shown a positive association between circulating 25-hydroxyvitamin D concentrations and the risk of T2D, no randomized clinical trials supplementing with different doses of vitamin D have confirmed this hypothesis definitively. An important question is the identification of what 25-hydroxyvitamin D levels are necessary to influence glycemic homeostasis and the risk of developing T2D. These values of vitamin D can be significantly higher than vitamin D levels required for bone health, but the currently available data do not allow us to answer this question adequately. Furthermore, a large number of observational studies show that dairy consumption is linked to a lower risk of T2D, but the components responsible for this relationship are not well established. Therefore, the importance of calcium intake in the risk of developing T2D has not yet been established. Although there is a biological plausibility linking the status of vitamin D and calcium intake with the risk of T2D, well-designed randomized clinical trials are necessary to answer this important question

Obesity and Bone Health: A Complex Relationship

Recent scientific evidence has shown an increased risk of fractures in patients with obesity, especially in those with a higher visceral adipose tissue content. This contradicts the old paradigm that obese patients were more protected than those with normal weight. Specifically, in older subjects in whom there is a redistribution of fat from subcutaneous adipose tissue to visceral adipose tissue and an infiltration of other tissues such as muscle with the consequent sarcopenia, obesity can accentuate the changes characteristic of this age group that predisposes to a greater risk of falls and fractures. Other factors that determine a greater risk in older subjects with obesity are chronic proinflammatory status, altered adipokine secretion, vitamin D deficiency, insulin resistance and reduced mobility. On the other hand, diagnostic tests may be influenced by obesity and its comorbidities as well as by body composition, and risk scales may underestimate the risk of fractures in these patients. Weight loss with physical activity programs and cessation of high-fat diets may reduce the risk. Finally, more research is needed on the efficacy of anti-osteoporotic treatments in obese patients.Instituto de Salud Carlos IIIEuropean Commission CD20/00022 PI18-00803 PI21-01069 PI18-01235European CommissionJunta de Andalucia PI-0268-201

Osteoglycin as a Potential Biomarker of Mild Kidney Function Impairment in Type 2 Diabetes Patients

Osteoglycin (OGN) could be a biomarker of mild kidney function impairment in type 2 diabetes (T2D). Our study aimed to determine the association between serum OGN and impaired kidney function risk in T2D patients and to analyze its potential role as an estimator of kidney disturbances in this population. This cross-sectional study included 147 T2D patients (65 ± 8 years, 58.5% males), and 75 healthy controls (63 ± 10 years, 36% males). Circulating OGN levels were determined by ELISA. Linear regression modeling was performed to determine the variables influencing circulating OGN, and an ROC curve was plotted to assess the usefulness of OGN as an estimator of diabetic kidney disease risk. Circulating OGN was significantly increased in T2D patients compared to controls (18.41 (14.45–23.27) ng/mL vs. 8.74 (7.03–12.35) ng/mL; p < 0.001). We found a progressive increase in serum OGN according to the severity of kidney impairment in T2D patients (normal kidney function: 16.14 (12.13–20.48) ng/mL; mildly impaired kidney function: 19.15 (15.78–25.90) ng/mL; moderate impaired kidney function: 21.80 (15.06–29.22) ng/mL; p = 0.006). Circulating OGN was an independent estimator of mildly impaired kidney function risk in T2D patients. We suggest that serum OGN could act as an albuminuria-independent biomarker of incipient kidney dysfunction in T2D patients.Junta de Andalucía grants (PI-0207-2016 and PI0268-2019)Instituto de Salud Carlos III grants (PI18-00803 and PI18-01235)European Regional Development Fund (FEDER)Instituto de Salud Carlos III (FI19/00118; CD20/00022

Mechanisms Involved in the Relationship between Vitamin D and Insulin Resistance: Impact on Clinical Practice

This research was funded by the Institute of Health Carlos III grants (PI18-00803 and PI18-01235), co-funded by the European Regional Development Fund (FEDER) and Junta de Andalucia (PI-0268-2019). In addition, V.C.-B. and C.G.-F. are funded by postdoctoral fellowships from the Junta de Andalucia and Institute of Health Carlos III respectively (RH-0141-2020; CD20/00022).Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extraskeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association.Institute of Health Carlos III grants PI18-00803 PI18-01235European Commission Junta de Andalucia PI-0268-2019Instituto de Salud Carlos III RH-0141-2020 CD20/0002

Cardiorespiratory fitness and bone turnover markers in adults with metabolic syndrome: the mediator role of inflammation

The relationship between inflammatory markers and bone turnover in adults is well known, whilst a negative association between cardiorespiratory fitness (CRF) and inflammatory markers has also been described. Hence, we tested whether the association between CRF and bone turnover markers is mediated by inflammatory markers in adults with metabolic syndrome. A total of 81 adults (58.5±5.0 yrs, 62.7% women) were included in the analysis. CRF was measured by the six-minute walking test. Serum interleukine (IL)-1β, IL-6, IL-10, tumor necrosis factor alpha, high-sensitivity c-reactive protein (hsCRP) and vascular endothelial growth factor, collagen type I cross-linked C-telopeptide, procollagen type I N-terminal propeptide (P1NP) and total osteocalcin were assessed using a sensitive ELISA kit. Body composition was assessed by dual-energy x-ray absorptiometry. Partial correlation was used to test the relationship between CRF, inflammatory markers and bone turnover markers, controlling for sex, lean mass and fat mass. Boot-strapped mediation procedures were performed and indirect effects with confidence intervals not including zero were interpreted as statistically significant. CRF was positively correlated with P1NP levels (r=0.228, p=0.044) and osteocalcin levels (r=0.296, p=0.009). Furthermore, CRF was positively correlated with IL-1β levels (r=0.340, p=0.002) and negatively correlated with hsCRP levels (r=-0.335, p=0.003), whereas IL-1β levels were positively correlated with P1NP levels (r=0.245, p=0.030) and hsCRP levels were negatively correlated with P1NP levels (r=-0.319, p=0.004). Finally, the association between CRF and P1NP levels was totally mediated by hsCRP (PM=39.9). Therefore, CRF benefits on bone formation could be dependent on hsCRP concentrations in this population.Heart and Diseases Foundation (Fondation 234 Coeur et Artères) 59200 Loos, Franc

Circulating Undercarboxylated Osteocalcin as Estimator of Cardiovascular and Type 2 Diabetes Risk in Metabolic Syndrome Patients

Undercarboxylated osteocalcin (ucOC) could be a biomarker of glucose disturbances and cardiovascular risk. Our study aimed to determine the association between serum levels of ucOC and cardiovascular risk in metabolic syndrome (MetS) patients and to analyse its potential role as estimator of type 2 diabetes (T2D) risk in this population. This cross-sectional study included 235 patients with MetS, 53.2% women, aged 55–75 years. Circulating ucOC levels were measured by ELISA. Cardiovascular risk was determined as Z-score of the diagnostic criteria for MetS (CV-ZS). Linear regression model was performed to analyse the association between circulating ucOC and CV-ZS. A receiver operating curve (ROC) was performed to analyse the usefulness of ucOC as T2D risk estimator. Patients above the CV-ZS median showed signifcant lower ucOC levels. We found an inverse association between ucOC levels and CV-ZS in MetS patients without T2D. Patients with ucOC levels below the 25th percentile showed worse cardiometabolic profle and higher cardiovascular and T2D risk. The area under the curve performed better when ucOC levels were included along with the classic T2D risk factors. The measurement of circulating ucOC could be a useful tool to identify increased cardiovascular and T2D risk in MetS patients without T2D.Junta de Andalucia PI-0207-2016European Union (EU) PI18-00803 PI18-0123

The Influence of the Mediterranean Dietary Pattern on Osteoporosis and Sarcopenia

Diet is a modifiable factor in bone and muscle health. The Mediterranean diet (MedDiet) is rich in nutrients and contains key bioactive components with probable protective effects on muscle and bone deterioration. Osteoporosis (OP) and sarcopenia are diseases that increase frailty and susceptibility to fracture, morbidity and mortality. Therefore, it is necessary to combat them in the population. In this regard, MedDiet adherence has proven to be beneficial to bone mineral density (BMD), muscle mass, physical function, OP and sarcopenia. Hence, this diet is proposed as a therapeutic tool that could slow the onset of osteoporosis and sarcopenia. However, there is doubt about the interaction between the MedDiet, strength and fracture risk. Perhaps the amount of EVOO (extra virgin olive oil), fruits, vegetables and fish rich in anti-inflammatory and antioxidant nutrients ingested has an influence, though the results remain controversiaInstitute of Health Carlos III grants (PI21-01069, PI18-01235 and CIBERFES)European Regional Development Fund (FEDER)Junta de Andalucía (PI- 0268-2019)Junta de Andalucía and Institute of Health Carlos III, respectively (RH-0141-2020; CD20/00022

Systematic Review of Therapeutic Physical Exercise in Patients with Amyotrophic Lateral Sclerosis over Time

Background: the main objective of this study was to analyze the potential short-, medium- and long-term effects of a therapeutic physical exercise (TFE) programme on the functionality of amyotrophic lateral sclerosis (ALS) patients, measured with the Revised Amyotrophic Lateral Sclerosis Functional Scale (ALSFRS-R) scale. Methods: a systematic review of the PubMed, SCOPUS, Cochrane, Scientific Electronic Library Online (Scielo), Physiotherapy Evidence Database (PEDro), Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Medical Literature Analysis and Retrieval System Online (MEDline) databases was carried out. The information was filtered using the following Medical Subjects Heading (MeSH) terms: "Amyotrophic lateral sclerosis", "Physical Therapy", and "Physical and Rehabilitation Medicine". The internal validity of the selected documents was evaluated using the PEDro scale. The study included clinical trials published in the last 5 years in which one of the interventions was therapeutic physical exercise in patients with ALS, using the ALSFRS-R as the main outcome variable and functional variables as secondary variables. Results: 10 clinical trials were analyzed, with an internal validity of 5-7 points. The TFE groups showed significant short-, medium- and long-term differences, obtaining a mean difference of 5.8 points compared to the 7.6 points obtained by the control groups, at six months, measured with ALSFRS-R. In addition, the participants showed significant improvements in functional abilities in the short, medium and long terms. Conclusions: Therapeutic physical exercise could contribute to slowing down the deterioration of the musculature of patients with ALS, thus facilitating their performance in activities of daily living, based on the significant differences shown by these individuals in the short, medium and long term both in subjective perception, measured with ALSFRS-R, and functional capacities

Association between lifestyle factors and thyroid function in young euthyroid adults

This work is part of a PhD thesis conducted within the framework of the Biomedicine Doctoral Studies Program of the University of Granada, Spain. This study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), by the Retos de la Sociedad program (DEP2016-79512-R), European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU13/04365 and FPU19/01609), the Fundación Iberoamericana de Nutrición (FINUT), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)-and Plan Propio de Investigación 2018-the Programa Contratos-Puente and Contratos Perfeccionamiento de Doctores, the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF; ref. SOMM17/6107/UGR), and the Fundación Alfonso Martín Escudero (grant awarded to GSD).Data availability The datasets generated and/or analyzed during this study are available upon reasonable request. Clinical trial registry: NCT02365129 (ClinicalTrials.gov).Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://doi.org/10.26599/FSHW.2022.9250022.Purpose The present work examines the associations of dietary habits, sedentarism, physical activity (PA) levels and sleep habits, with thyroid function in young euthyroid adults. Methods A total of 105 young euthyroid adults participated in this cross-sectional study. Thyroid function was determined in fasting conditions (> 6 h). Dietary habits were measured by a food frequency questionnaire and three non-consecutive 24 h recalls, and different dietary intake and patterns were then estimated. The time spent in sedentary, PA levels and sleep habits were objectively measured using a wrist-worn accelerometer. Results Energy and carbohydrate intake were positively associated with thyroid stimulating hormone (TSH) (β = 0.222; R2 = 0.102; P = 0.022 and β = 0.425; R2 = 0.129; P = 0.007, respectively) whereas fat intake was negatively associated with TSH (β = −0.428; R2 = 0.137; P = 0.004). Energy intake was also positively associated with free triiodothyronine (β = 0.277; R2 = 0.137; P = 0.004). Further, adherence to the Mediterranean diet was negatively related to TSH and free thyroxine (FT4) (β = −0.221; R2 = 0.113; P = 0.020 and β = −0.268; R2 = 0.071; P = 0.007, respectively). Vigorous-intensity and overall PA were negatively associated with FT4 (β = −0.227; R2 = 0.052; P = 0.022 and β = −0.204; R2 = 0.042; P = 0.041, respectively). In contrast, no associations were found between sleep parameters and thyroid function. Conclusions Lifestyle factors such as dietary intake and PA levels seems to be related to thyroid function even in young euthyroid adults.Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393)Retos de la Sociedad program (DEP2016-79512-R)European Regional Development Funds (ERDF)Spanish Ministry of Education (FPU13/04365 and FPU19/01609)Fundación Iberoamericana de Nutrición (FINUT)Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022)AstraZeneca HealthCare FoundationUniversity of Granada Plan Propio de Investigación 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)-and Plan Propio de Investigación 2018-the Programa Contratos-Puente and Contratos Perfeccionamiento de DoctoresJunta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF; ref. SOMM17/6107/UGR)Fundación Alfonso Martín Escuder