Alleles of RUNX2/CBFA1 gene are associated with differences in bone mineral density and risk of fracture.

The aim of this study was to determine if DNA polymorphism within runt-related gene 2 (RUNX2)/core binding factor A1 (CBFA1) is related to bone mineral density (BMD). RUNX2 contains a glutamine-alanine repeat where mutations causing cleidocranial dysplasia (CCD) have been observed. Two common variants were detected within the alanine repeat: an 18-bp deletion and a synonymous alanine codon polymorphism with alleles GCA and GCG (noted as A and G alleles, respectively). In addition, rare mutations that may be related to low BMD were observed within the glutamine repeat. In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The effect was maximal at the ultradistal (UD) radius (p = 0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture, suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis.     

Beta-adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: Geelong Osteoporosis Study.

This population-based study documented beta-blocker use in 59/569 cases with incident fracture and 112/775 controls. OR for fracture associated with beta-blocker use was 0.68 (95%CI, 0.49-0.96). Beta-blockers were associated with higher BMD at the total hip (2.5%) and UD forearm (3.6%) after adjusting for age, anthropometry, and thiazide use. Beta-blocker use is associated with reduced fracture risk and higher BMD. INTRODUCTION: Animal data suggests that bone formation is under beta-adrenergic control and that beta-blockers stimulate bone formation and/or inhibit bone resorption. MATERIALS AND METHODS: We evaluated the association between beta-blocker use, bone mineral density (BMD), and fracture risk in a population-based study in Geelong, a southeastern Australian city with a single teaching hospital and two radiological centers providing complete fracture ascertainment for the region. Beta-blocker use was documented for 569 women with radiologically confirmed incident fractures and 775 controls without incident fracture. Medication use and lifestyle factors were documented by questionnaire. RESULTS: Odds ratio for fracture associated with beta-blocker use was 0.68 (95% CI, 0.49-0.96) for any fracture. Adjusting for age, weight, medications, and lifestyle factors had little effect on the odds ratio. Beta-blocker use was associated with a higher BMD at the total hip (2.5%, p = 0.03) and ultradistal forearm (3.6%, p = 0.04) after adjustment for age, anthropometry, and thiazide use. CONCLUSION: Beta-blockers are associated with a reduction in fracture risk and higher BMD.     

Biological function of CD40 on human endothelial cells: costimulation with CD40 ligand and interleukin-4 selectively induces expression of vascular cell adhesion molecule-1 and P-selectin resulting in preferential adhesion of lymphocytes

The expression of adhesion molecules on vascular endothelial cells determines the pattern of migration and extravasation of leucocytes in inflammation and immunity. Here we show that costimulation with CD40 ligand (CD40L) and interleukin (IL)-4 (or IL-13) gives rise to a unique pattern of adhesion molecule expression by human umbilical vein endothelial cells (HUVEC). CD40 ligation alone enhanced expression of vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and E-selectin whereas IL-4 and IL-13 increased expression of VCAM-1 and P-selectin but not ICAM-1 or E-selectin. When IL-4 and CD40L were combined there was an additional increase of both VCAM-1 and P-selectin, but ICAM-1 and E-selectin were both inhibited. The combined effects of IL-4 and CD40L signalling were not the result of altered response kinetics, enhanced sensitivity of the endothelium, or increased expression of CD40 or the IL-4 receptor. The rise in VCAM-1 expression induced by combined IL-4 and CD40L stimulation was slower and more sustained than with tumour necrosis factor-alpha (TNF-alpha) and occurred only on a subset (75-80%) of the endothelial cell population compared to 100% with TNF-alpha. Costimulation with IL-4 and CD40L increased adhesion of T cells and B cells above levels obtained with either signal alone, but decreased adhesion of neutrophils. Furthermore, CD40 and IL-4 synergistically increased IL-6 but decreased IL-8 production by HUVEC. These results show that interactions between IL-4 and CD40 on endothelial cells give rise to specific patterns of adhesion molecule expression and cytokine production that may have important implications for lymphocyte and neutrophil migration and function at sites of inflammation.     

New Acceptor–Donor–Acceptor Systems Based on Bis-(Imino-1,8-Naphthalimide)

In this paper, six novel symmetrical bis-(imino-1,8-naphthalimides) differing in core and N-substituent structure were synthesized, and their thermal (TGA, DSC), optical (UV-Vis, PL), electrochemical (DPV, CV) properties were evaluated. The compounds were stable to 280 °C and could be transferred into amorphous materials. Electrochemical investigations showed their ability to occur reductions and oxidations processes. They exhibited deep LUMO levels of about −3.22 eV and HOMO levels above −5.80 eV. The optical investigations were carried out in the solutions (polar and non-polar) and in films and blends with PVK:PBD. Bis-(imino-1,8-naphthalimides) absorbed electromagnetic radiation in the range of 243–415 nm and emitted light from blue to yellow. Their capacity for light emission under voltage was preliminarily tested in devices with an active layer consisting of a neat compound and a blend with PVK:PBD. The diodes emitted green or red light.     

β-blockers reduce bone resorption marker in early postmenopausal women

Background: There is evidence to suggest that β-blockers used in the management of cardiovascular disease may also modulate bone metabolism and reduce bone fragility.

Aim: The study aimed to determine the association between β-blocker use, serum markers of bone turnover and bone loss in early postmenopausal women.

Subjects and methods: In this observational study, we evaluated β-blocker exposure in association with serum levels of C-telopeptide and bone-specific alkaline phosphatase, and rates of bone loss. β-blocker use, concomitant therapy and lifestyle were documented for 197 women (50–59 years), 175 of whom had changes in whole body bone mineral density monitored over a 2–year period.

Results: Twenty-four β-blocker users were identified at baseline. After controlling for concomitant use of hormone therapy, C-telopeptide levels were 6.7% lower among β-blocker users (p?=?0.02). No association was detected between bone-specific alkaline phosphatase and β-blocker use. Analysis of 15 β-blocker users and 152 non-users identified 2 years post-baseline showed that levels of C-telopeptide but not bone-specific alkaline phosphatase were predictors of adjusted rates of bone loss (p?=?0.008 and p>0.05, respectively). Adjusted rates of bone loss were??0.001?±?0.026?g?cm^?2 over 2 years for the users and??0.004?±?0.025?g?cm^?2 over 2 years for non-users, but this difference was not significant.

Conclusion: β-blockers might suppress bone resorption with relative preservation of bone formation. A study with greater power is required to determine whether β-blocker use is associated with lower rates of bone loss.

Résumé. Arrière plan: Il semble que les β-bloquants employés pour le traitement des maladies cardiaques, puissant aussi moduler le métabolisme osseux et réduire la fragilité de l'os.

But: Cette étude a pour objet de déterminer l'association de l'usage des β-bloquants avec les marqueurs sériques du remplacement osseux et la perte osseuse juste après la ménopause.

Sujets et méthodes:.On a évalué l'exposition aux β-bloquants en association avec les niveaux sériques de C-telopeptide et l'alcaline phosphatase osseuse spécifique ainsi qu'avec les taux de perte osseuse. L'utilisation de β-bloquants, la thérapie concomitante et le mode de vie ont été enregistrés pour 197 femmes âgée de 50 à 59 ans, parmi lesquelles 175 ont subi un contrôle suivi des changements de leur densité minérale osseuse totale sur une période de deux ans.

Résultats: 34 utilisateurs de β-bloquants ont été identifiés comme base de référence. Après contrôle de l'emploi concomitant d'une thérapie hormonale, les niveaux de C-telopeptides sont de 6,7% plus bas chez les utlilisateurs de β-bloquants (p?=?0,02). On ne trouve pas d'association entre l'alcaline-phosphatase et l'utilisation de β-bloquants. L'analyse de 15 utilisateurs de β-bloquants et de 152 non utilisateurs identifiés deux ans après la base de référence, montre que les niveaux de C-telopeptides mais non pas l'alcaline phosphatase, sont prédicateurs des taux ajustés de perte osseuse (respectivement p?=?0,008 et p?=?0,05)). Les taux ajustés de perte osseuse sur 2 ans sont de??0,001?±?0,026 g/cm^?2 pour les utilisateurs et??0,004?±?0,025?g/cm^?2 pour les non utilisateurs, mais cette différence n'est pas significative.

Conclusion: Les β-bloquants pourraient supprimer la résorption osseuse par une préservation relative de la formation de l'os. Une étude de plus vaste envergure est nécessaire afin de déterminer si les β-bloquants sont associés à des taux plus faibles de perte osseuse.

Zusammenfassung. Hintergrund: Es gibt deutliche Hinweise darauf, dass die Einnahme von β-Blockern bei der Behandlung kardiovaskulärer Erkrankungen auch den Knochenstoffwechsel beeinflussen und zu erhöhter Knochenbrüchigkeit führen können.

Ziel: Die Studie zielte auf die Bestimmung der Beziehung zwischen Einnahme von β-Blockern, Serummarkern des Knochenumsatzes und Knochenverlusts bei Frauen kurz nach der Menopause.

Probanden und Methoden: In dieser Beobachtungsstudie beurteilten wir den Zustand unter Einnahme β-Blockern in Verbindung mit Serumspiegeln von C-Telopeptiden und knochenspezifischer alkalischer Phosphatase, und Knochenabbauraten. Die Einnahme von β-Blockern, Begleittherapie und Lebensumstände wurden bei 197 Frauen (50–59 Jahre) dokumentiert, von denen 175 Veränderungen der Ganzkörperknochendichte über einen Beobachtungszeitraum von 2 Jahren aufwiesen.

Ergebnisse: Zu Beginn wurden 24 Patienten identifiziert, die β-Blocker einnahmen. Nach rechnerischem Ausschluss von Effekten, die sich durch begleitende Hormonbehandlung ergeben könnten, zeigten Patienten, die β-Blocker einnahmen, um 6,7% niedrigere C-Telopeptidspiegel (p?=?0,02). Es fand sich keine Beziehung zwischen knochenspezifischer alkalischer Phosphatase und der Einnahme von β-Blockern. Die Analyse von 15 Patienten, die β-Blocker einnahmen, und 152 Personen, die dies über einen Zeitraum von 2 Jahren nach Studienbeginn nicht taten, zeigte, dass C-Telopeptidspiegel, nicht aber die knochenspezifische alkalische Phosphatase ein Kriterium war, um korrigierte Knochenabbauraten vorherzusagen (p?=?0,008, bzw. p?>?0,05). Korrigierte Knochen-abbauraten waren –0,001?±?0,026?g?cm^?2 über 2 Jahre für Patienten, die β-Blocker einnahmen, und –0,004?±?0,025?g?cm^?2 über 2 Jahre für solche, die keine β-Blocker einnahmen, aber diese Differenz war nicht signifikant.

Zusammenfassung: β-Blocker können die Knochenresorption supprimieren, wobei die Knochenformation im Prinzip beibehalten wird. Eine Untersuchung mit größerer power ist notwendig, um zu klären, ob die Einnahme von β-Blockern mit erniedrigten Knochenabbauraten vergesellschaftet ist.

Resumen. Antecedentes: Existen evidencias que sugieren que los ß-bloqueantes usados en el tratamiento de la enfermedad cardiovascular también pueden modular el metabolismo óseo y reducir la fragilidad de los huesos.

Objetivos: El estudio trata de determinar la asociación entre el uso de ß-bloqueantes, los marcadores séricos de remodelado y la pérdida ósea, en mujeres postmenopaúsicas tempranas.

Sujetos y métodos: En este estudio de observación, evaluamos la exposición a ß-bloqueantes en asociación con los niveles séricos del telopéptido C y de la fosfatasa alcalina óseo-específica, y las tasas de pérdida ósea. La utilización de ß-bloqueantes, la terapia concomitante y el estilo de vida se documentaron en 197 mujeres (de 50 a 59 años), 175 de las cuales habían tenido cambios en la densidad mineral ósea de todo el cuerpo monitorizados durante un periodo de 2 años.

Resultados: Inicialmente se identificaron veinticuatro usuarias de ß-bloqueantes. Tras controlar el uso conjunto de la terapia hormonal, los niveles del telopéptido C fueron un 6,7% menores entre las usuarias de ß-bloqueantes (p?=?0,2). No se detectó ninguna asociación entre la fosfatasa alcalina óseo-específica y el uso de ß-bloqueantes. El análisis de 15 usuarias de ß-bloqueantes y de 152 no usuarias, identificadas durante 2 años después del inicio, mostró que los niveles del telopéptido C, pero no los de la fosfatasa alcalina óseo-específica, eran predictores de las tasas ajustadas de pérdida ósea (p?=?0,008 y p?>?0,05, respectivamente). Las tasas ajustadas de pérdida ósea fueron de –0,001?±?0,026?g?cm^?2 tras 2 años en las usuarias y de –0,004?±?0,025?g?cm^?2 tras 2 años en las no usuarias, aunque esta diferencia no fue significativa.

Conclusión: Los β-bloqueantes podrían suprimir la resorción del hueso con una relativa preservación de la formación ósea. Se requiere un estudio con mayor potencia para determinar si el uso de ß-bloqueantes está asociado con tasas más bajas de pérdida ósea.     

Oral contraceptives and bone mineral density: A population-based study

OBJECTIVE: We sought to test the hypothesis that exposure to oral contraceptives protects the skeleton. STUDY DESIGN: Multiple regression techniques were used to analyze data for a random sample of 710 Australian women (age range, 20-69 years). Bone mineral density was measured at the lumbar spine, proximal femur, whole body, and distal forearm. Oral contraceptive exposure was assessed by a questionnaire. RESULTS: Women exposed to oral contraceptives had a 3.3% greater mean bone mineral density adjusted for body mass index and age at the lumbar spine (partial r (2) = 0.009; P =.014). Adjusted mean vertebral bone mineral density was 3.3% greater for premenopausal women (partial r (2) = 0.008; P <.05), but the effect did not reach significance among postmenopausal women. Higher bone mineral density was associated with increased duration of exposure, with a mean increase of 3.2% associated with the first 5 years and a further 0.2% with >/=5 years of exposure. No association was detected at other sites. CONCLUSION: Exposure to oral contraceptives may be associated with higher lumbar spine bone mineral density.     

Three-dimensional photoelastic stress analysis of the ferrule effect in cast post and cores

The effect of a metal collar on stress distribution with cast post and cores was studied by using three-dimensional photoelastic models of maxillary canine teeth of average dimensions. Standardized parallel post and cores were cemented into the models, with half of the samples incorporating a 1.5 mm metal collar. A 400 gm load was applied to the cingulum of the cores and stresses were frozen in the models. The posts were removed, the teeth were sectioned, and stresses were measured with a circular polariscope. In both groups the greatest stress concentration was found at the lingual apex of the post. On a point by point basis, stresses were higher in the collared specimens. Variation in stress magnitude among five preselected points was greater within the noncollared group.     

Prevalence of mood and anxiety disorder in self reported irritable bowel syndrome (IBS). An epidemiological population based study of women

Background  

Irritable bowel syndrome (IBS) is commonly regarded as a functional disorder, and is hypothesized to be associated with anxiety and depression. This evidence mainly rests on population-based studies utilising self-report screening instruments for psychopathology. Other studies applying structured clinical interviews are generally based on small clinical samples, which are vulnerable to biases. The extant evidence base for an association between IBS and psychopathology is hence not conclusive. The aim of this study was therefore to re-examine the hypothesis using population-based data and psychiatric morbidity established with a structured clinical interview.     

Area-based socioeconomic status and mood disorders: cross-sectional evidence from a cohort of randomly selected adult women

Objective

Data suggest there are established socio-economic disparities associated with mental health although most research has focused on individual-level indicators of socio-economic position. The aim of this study was to investigate the association between mood disorders and area-based socio-economic status (SES), and whether both ends of the SES continuum experienced increased odds for a mood disorder.

Methods

Using a clinical interview (SCID-I/NP), psychiatric history was ascertained in a population-based sample of 1095 women (20–93 years) from the Barwon Statistical Division, south-eastern Australia. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics 2006 census data for the region and categorised into three groupings of low, mid, and upper SES. The Index of Economic Resources (IER), Index of Education and Occupation (IEO), and Index of Relative Socioeconomic Advantage/Disadvantage (IRSAD) were utilised. Lifestyle factors were self-reported.

Results

For IER, the low SES group had a 2.0-fold increased odds of a current mood disorder compared to the mid group, after adjustment for physical activity and current anxiety (OR = 2.0, 95% CI 1.0–4.1, p = 0.05). This pattern was similarly observed for IEO (OR = 1.8, 95% CI 0.9–3.7, p = 0.1) and IRSAD (OR = 1.6 95% CI 0.8–3.4, p = 0.2). Those within the upper SES group showed a non-significant increase in the odds of a current mood disorder compared to the mid-group; IER (OR = 1.4, 95% CI 0.8–2.5, p = 0.3), IEO (OR = 1.2, 95% CI 0.07–2.3, p = 0.5) and IRSAD (OR = 1.2, 95% CI 0.7–2.1, p = 0.6).

Conclusions

Women in the low SES category were most likely to have a mood disorder. Furthermore, being in an upper SES group may not be protective against mood disorders.     

Morphometric vertebral fractures of the lower thoracic and lumbar spine, physical function and quality of life in men

Summary  The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly documented. We found that MVFs of the lower thoracic and lumbar spine were associated with poor quality of life and impaired physical function in men. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry. Introduction  Vertebral fractures are sentinel events for osteoporosis. We aimed to compare quality of life and physical function in men with and without MVF. Methods  Using morphometric X-ray absorptiometry (T10–L4), MVFs were identified in a random sample of men aged 20–93 years. Moderate and severe wedge, biconcave or compression deformities (>25% reduction in any vertebral height) were classified as MVFs. Results  Of 1,147 men, MVFs were identified in 64. No MVFs were detected for men in their twenties. Prevalence was 1.5% for 30–39 years, 1.4% 40–49 years, 3.2% 50–59 years, 4.7% 60–69 years, 10.0% 70–79 years and 14.6% 80+ years. Among 555 men aged 60+ years, those with MVFs were twice as likely to have quality of life scores in the lowest tertile (age-adjusted OR = 2.35, 95%CI 1.24–4.45). MVFs were associated with lower mean age-adjusted physical activity scores [11.3 (95%CI 9.0–13.8) vs 14.0 (13.2–14.9), P = 0.04] and longer mean age-adjusted ‘Up-&-Go’ times [9.5 (8.9, 10.1) vs 8.9 (8.8, 9.1) s, P = 0.06]. Conclusion  Despite most men being unaware of their condition, MVFs were associated with poor quality of life and impaired physical function. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry because detection of MVFs has important implications for osteoporosis management in men.