Concerted Action of Androgens and Mechanical Strain Shifts Bone Metabolism from High Turnover into an Osteoanabolic Mode

Adhesion of bone cells to the extracellular matrix is a crucial requirement for osteoblastic development and function. Adhesion receptors connect the extracellular matrix with the cyto-skeleton and convey matrix deformation into the cell. We tested the hypothesis that sex hormones modulate mechanoperception of human osteoblastic cells (HOB) by affecting expression of adhesion molecules like fibronectin and the fibronectin receptor. Only dihydrotestosterone (DHT), but not 17β-estradiol, stimulated fibronectin (137%) and fibronectin receptor (252%) protein expression. The effects of deformation strain on HOB metabolism were investigated in a FlexerCell® strain unit. Cyclically applied strain (2.5% elongation) increased DNA synthesis (125%) and interleukin-6 (IL-6) production (170%) without significantly affecting alkaline phosphatase (AP) activity, type I collagen (PICP), or osteoprotegerin (OPG) secretion. 10 nM DHT pretreatment abolished the mitogenic response of HOB to strain and increased AP activity (119%), PICP (163%), and OPG production (204%). In conclusion, mechanical strain stimulates bone remodeling by increasing HOB mitosis and IL-6 production. DHT enhances the osteoanabolic impact of deformation strain by increasing bone formation via increased AP activity and PICP production. At the same time, bone resorption is inhibited by decreased IL-6 and increased OPG secretion into the bone microenvironment

FS7BJ Multiple prevalent fractures in relation to macroscopic bone architecture in patients with cystic fibrosis

Background: The relative risk for bone fractures in patients with cystic fibrosis (CF) and its relationship to macroscopic bone architecture assessed by pQCT and DXA are incompletely defined. Methods: In a cross-sectional study of 43 CF patients (age, 17.8 +/- 6.2 years), rate and location of fractures, bone mass, density, geometry, and strength of the radius as well as forearm muscle size were investigated. Results: The fracture rate in CF was 9.2-fold higher compared to an age-matched German control population. The probability of remaining free of any fracture in CF patients at 25 years was reduced to 39.8% compared to 84.6% in controls (P < 0.001). Assessment of macroscopic bone architecture by DXA and pQCT allowed the differentiation of patients with multiple prevalent fractures with a high sensitivity (up to 100%) and specificity (up to 94.3%). Conclusions: Bone densitometry is a useful tool for noninvasive assessment of fracture risk in CF patients. (C) 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved

Mindful sensation seeking: an examination of the protective influence of selected personality traits on risk sport-specific stress

Stress often has a negative influence on sports performance. Stress-induced decreases in performance can be especially disastrous for risk sports athletes, who often put their life at risk when practicing their sport. Therefore, it is of great importance to identify protective factors in stressful situations in risk sports. On average, risk sports athletes score extremely high on the personality trait sensation seeking. At the same time, theoretical considerations about dispositional mindfulness suggest that mindful athletes can handle stress more effectively. The main goal of this experiment is to examine the influence of sensation seeking and mindfulness on the stress response to a risk sport-specific stressor. To induce stress, 88 male students completed the Heidelberg Risk Sport-Specific Stress Test (HRSST) which utilizes fear of falling as the stressful event during a climbing exercise. Psychological (anxiety) and physiological (cortisol) responses were measured at multiple time points before and after the HRSST to determine the severity of the stress response. In reaction to the stressor, a significant increase in self-reported state anxiety, but no significant increase in cortisol were observed. The mindfulness subscale external observation correlated positively with anxiety in the climbing wall, sensation seeking and the anxiety scales after the jump correlated negatively and sensation seeking predicted anxiety subscales after the jump in hierarchical regression analyses. However, mindfulness did not predict anxiety measures. Neither sensation seeking nor mindfulness correlated significantly with cortisol levels. The results suggest that high sensation seekers perceive a risk sport-specific stressor as less stressful. The missing physiological response might be explained by the Cross-Stressor-Adaptation-Hypothesis and particularities of the sample. Good internal observers might be especially aware of their need of stimulation and new experiences, which in turn might explain the higher experience-seeking scores. Future studies should further examine the role of mindfulness in stressful situations and the interaction of its subscales with sensation seeking. The current experiment offers new possibilities for adjoining research fields at the interface between sports sciences, psychology and medicine: The findings can be transferred to high risk professions such as police officers, firefighters and military forces (e.g., for selection processes or for interventions)

Können gut selbstregulierte High-Sensation Seeker besser mit sportspezifischen Stress umgehen?

Die Konstrukte Sensation Seeking (SS) und Selbstregulation haben besondere Relevanz für den Sport. Forschungsarbeiten zum SS legen nahe, dass Sportler mit einem hoch ausgeprägtem SS-Motiv (High Sensation Seeker; HSS) in risikoreichen Situationen weniger mit Angst reagieren (Breivik, 1999) und weniger das Stresshormon Cortisol ausschütten (Frenkel et al., under review), als diejenigen, die ein schwach ausgeprägtes SS-Motiv (Low Sensation Seeker; LSS) aufweisen. Eine Erklärung hierfür liefert das Konzept des Optimalen Niveaus der Katecholamine (Zuckerman, 1996). Zudem gilt Selbstregulation als essenzielle Fähigkeit zum adaptiven Umgang mit Stress. Sowohl der Zustand selbstregulatorischer Beeinträchtigung (Ego-Depletion; Baumeister et al., 1998) als auch die Fähigkeit zur Selbstkontrolle (Englert & Bertrams, 2012) gelten als relevant für sportliche Leistungen. Zum Zusammenhang zwischen Ego-Depletion und Stresserleben gibt es im sportspezifischen Kontext bislang keine Studien. Der Zusammenhang zwischen SS und Selbstregulation wird daher erstmalig in einem Laborexperiment untersucht. Das Ziel der vorliegenden Studie besteht darin, zu prüfen, ob die momentan verfügbare Selbstkontrollkraft und Sensation Seeking das Ausmaß der Stressreaktion auf einen sportspezifischen Stressreiz beeinflussen. Mit Hilfe der SSS-V wurden aus der Gesamtstichprobe (N = 149 Sportneigungsfachschüler) zwei Extremgruppen (HSS vs. LSS) rekrutiert (n= 35). Die Probanden wurden randomisiert einer Depletion- bzw. einer Non-Depletion-Bedingung zugeteilt. Die Stressinduktion erfolgte mit Hilfe eines sportspezifischen Stressparadigmas, dem „Heidelberg Sport Stress Test“. Hierbei wird die Stressreaktion bei einer Kletteraufgabe mit einem „Sprung ins Seil“ mit einem Fall von ca. drei Meter induziert. Physiologische (Speichelcortisol, Herzratenvariabilität) und psychologische Variablen (u. a. Zustandsangst mit WAI-S) wurden mehrmals erhoben. Ferner wurden als behaviorale Variab-len Kletterdauer und -verhalten (Videoanalyse) erfasst. Die Auswertung erfolgte varianzanalytisch [2x2x3 (bzw.4/5/6/7) ANOVAs/ANCOVAS mit Messwiederholung; univariate ANOVAs Posthoc)]. Die experimentelle Manipulation der Selbstkontrollkraft und die Stressinduktion durch das Kletterparadigma waren erfolgreich. Aus deskriptivstatistischer Sicht sind alle psychologischen und behavioralen Ergebnisse hypothesenkonform, alle physiologischen Ergebnisse ergaben jedoch Veränderungen entgegen der Hypothesen. Bezüglich des Affektes (viermalig erhoben) wurden Zeit und Interaktion zweiter Ordnung (LSS vs. HSS) signifikant: HSS zeigen nach dem Sprung ins Seil einen höheren positiven Affekt. Andere signifikante Interaktionen zweiter oder dritter Ordnung liegen nicht vor. Die Diskrepanz der Ergebnisse zwischen psychologischen und physiologischen Variablen sowie einige Limitationen der Studie (u. a. Stichprobengröße, Dichotomisierung anhand SS) machen weitere Untersuchungen notwendig. An der Schnittstelle zwischen Sportwissenschaften, Psychologie und Medizin lässt die vorliegende Studie protektive Einflüsse der Dispositionen Sensation Seeking und Selbstregulation vermuten. Die Studie hat Relevanz für die Entwicklung effizienter Interventionsmethoden sowohl zur Stressprävention als auch zur Optimierung selbstregulatorischer Ressourcen

Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial

OBJECTIVE To evaluate whether the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Patients with T2D ( = 84) (HbA 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS EMPA treatment resulted in a placebo-corrected absolute of -1.8% (95% CI -3.4, -0.2%; = 0.02) and relative change in LFC of -22% (-36, -7%; = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change -2.5 kg [-3.7, -1.4 kg]; < 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (-74 mol/L [-108, -42 mol/L]; < 0.001) and high-molecular-weight adiponectin (36% [16, 60%]; < 0.001) levels from 0 to 24 weeks. CONCLUSIONS EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D