Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

CORRELATIONS OF SERUM VITAMIN D WITH METABOLIC PARAMETERS IN ADULT OUTPATIENTS WITH DIFFERENT DEGREES OF OVERWEIGHT / OBESITY COMING FROM AN URBAN COMMUNITY.

OBJECTIVE: To describe the correlations between serum 25(OH) vitamin D and anthropometric and metabolic parameters in adult outpatients of both sexes with different BMI coming from an urban community. SUBJECTS AND METHODS: 264 subjects referred for obesity assessment participated - 109 men and 155 women (20-60 years). Body weight and height, waist circumference (WC), blood pressure were recorded. Body composition was assessed by bioelectrical impedance (BIA) on a Tanita BC 420 MA analyzer (Tanita Inc., Japan). Serum 25(OH)D Total, Insulin, High-sensitivity C-reactive protein, blood glucose, total, HDL-cholesterol and triglycerides were measured. The insulin resistance index was calculated (HOMA-IR). Participants with BMI>25.0 kg/m2 underwent standard 75 g OGTT. Statistical analysis was performed on an IBM SPSS Statistics 19.0 for Windows platform (Chicago, IL). RESULTS: Normal weight was found in 27.2 % of the participants, 24.6 % had overweight, 29.2 % -class I obesity, and 18.9 % - class II or III. Vitamin D was weakly and inversely correlated to different variables in the whole group - such as weight, WC, WC/Height, % body fat and HOMA-IR index (r=-0.231, -0.283, -0.307, -0.339, -0.328 respectively, all p<0.001). Building subgroups based on BMI led to loss of significance. Backward analysis revealed Total-C/LDL-C ratio, and LDL-C/HDL-C ratio as strongest predictors of serum vitamin D (p=0.001; R2=0.204). CONCLUSION: The association of vitamin D with blood pressure, plasma lipids, glucose and insulin is very weak on an individual level. However, several obesity indices (WC, WC/height ratio, % Body fat from BIA) might be used as a screening tool for subjects at risk for vitamin D deficiency.

Medication-taking behaviour in Bulgarian women with postmenopausal osteoporosis treated with denosumab or monthly oral bisphosphonates.

Persistence with osteoporosis therapy is critical for fracture risk reduction. This observational study evaluated medication-taking behaviour of women with postmenopausal osteoporosis receiving denosumab or oral ibandronate in real-world clinical practice in Bulgaria. Compared with ibandronate, densoumab was associated with a lower discontinuation rate and greater increases in bone mineral density. PURPOSE: Persistence with osteoporosis therapy is critical for fracture risk reduction and the effectiveness of such treatments may be reduced by low persistence. Alternative therapies such as denosumab may improve persistence. This study aimed to describe medication-taking behaviour in women with osteoporosis, prescribed denosumab or oral ibandronate, in Bulgarian clinical practice. METHODS: This retrospective, observational, multicentre chart review (with up to 24 months follow-up) enrolled postmenopausal women initiating 6-monthly denosumab injection or monthly oral ibandronate treatment for osteoporosis between 1 October 2011 and 30 September 2012. RESULTS: Overall, 441 women were enrolled (224 had initiated denosumab, 217 had initiated ibandronate). At baseline, more women in the denosumab group than in the ibandronate group had a previous fracture (25.5 vs 17.5%; p = 0.043) and past exposure to osteoporosis therapy (19.6 vs 12.0%; p = 0.028). At 24 months, 4.5% of women receiving denosumab had discontinued therapy compared with 56.2% of women receiving ibandronate. Median time to discontinuation was longer in the denosumab group (729 days; interquartile range (IQR), 728.3-729.0) than in the ibandronate group (367 days; IQR, 354.0-484.8; p < 0.001). At 24 months, there were significantly greater changes in BMD T-scores at the lumbar spine (p < 0.001) and femoral neck (p < 0.001) in patients receiving denosumab than in those receiving ibandronate. At 24 months, persistence with denosumab was 98.7%. CONCLUSION: This real-world study demonstrates there is a low discontinuation rate and high persistence with denosumab. Denosumab was associated with greater BMD increases than ibandronate, which could reduce fracture risk.

WHOLE BODY AND REGIONAL BONE MINERAL CONTENT AND DENSITY IN WOMEN AGED 20-75 YEARS.

BACKGROUND: Dual-energy X-ray absorptiometry (DXA) allows measurement of whole body (WB) and regional bone mineral content (BMC) and density (BMD). OBJECTIVE: To measure WB and regional bone area, BMC and BMD (arms, legs, ribs and pelvis) in women of different ages. SUBJECTS AND METHODS: 140 women participated (age range 20-75 yrs). Three subgroups were built: 20-44 yr (30 premenopausal women), 45-59 (80 women), and 60-75 (30 women). WB DXA was performed on a Hologic QDR 4500 A bone densitometer (Hologic Inc., Bedford MA). WB BMD T-scores were calculated by using the manufacturer-provided and the NHANES 1999-2004 reference databases, while the WB BMC Z-scores - based on the latter. Statistical analysis was performed on an IBM SPSS Statistics 19.0 for Windows platform (Chicago, IL). RESULTS: WB BMC and BMD Z-scores were consistently lower than the reference databases showing a difference of about 0.4 - 0.5 SD. The arms, legs and ribs lost more BMC after the age of 50-55, while the pelvis - much earlier. The total decreases in BMC were highest in the pelvis (26.36 %), followed by the arms (16.81 %) and whole body (15.91 %), while the bone area decreased mostly in the pelvis (13.23 %). CONCLUSION: The age-related declines in regional BMC, bone areas and BMD follow different patterns in appendicular and axial bones.

Estimation of lumbar spine bone mineral density by dual-energy X-ray absorptiometry: standard anteroposterior scans vs sub-regional analyses of whole-body scans.

Dual-energy X-ray absorptiometry of the lumbar spine (anteroposterior (AP) L(1)-L(4) DXA) is one of the standards for testing bone density (BMD). Whole-body (WB) DXA scanning allows analysis of the L-spine (WB-LS). The objective of this study was (i) to predict the AP L(1)-L(4) BMD from the WB-LS BMD, and (ii) to compare WB and AP L(1)-L(4) T-scores. 132 women participated in the study (age, 50.84+/-9.69 years; range, 21-74 years). AP L(1)-L(4) BMD was measured on a Hologic QDR 4500-A densitometer, and was followed by a WB scan. Linear regression analyses and curve estimations were performed for area, bone mineral content (BMC), BMD and T-scores. Precision errors for BMD from AP scans and WB-LS scans were 1.37% and 1.65%, respectively. The best linear correlations were found for BMD, followed by the T-scores (R = 0.882 and 0.871; p<0.001). A power model for BMC (R(2) = 0.630) and a model S for BMD and the scanned area (R(2) = 0.841 and 0.539) were built. Discordant classification between AP L(1)-L(4) and WB T-scores was found in 12.73% and 19.09% cases, respectively. WB T-score cut-off values of -2.35 and -0.90 produced the best sensitivity-to-specificity ratio in the diagnosis of lumbar spine osteoporosis and low bone mass. In conclusion, WB-LS analysis may provide data for the indirect estimation of spinal BMD.

Body composition analysis by leg-to-leg bioelectrical impedance and dual-energy X-ray absorptiometry in non-obese and obese individuals.

AIM: The aim of this study is to compare total weight, % body fat (% BF), fat mass (FM) and fat-free mass (FFM) measured by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). METHODS: This cross-sectional study included 159 women (mean age: 49.1 +/- 10.0 years) and 124 men (mean age: 51.4 +/- 8.0 years) subdivided according to sex and body mass index (BMI): BMI < 30 kg/m(2) (66 women and 50 men); BMI 30-35 kg/m(2) (53 women and 44 men) and BMI > or = 35 kg/m(2) (40 women and 30 men). Bioelectrical impedance was performed in the fasting state on a Tanita TBF-215 leg-to-leg analyser (Tanita, Tokyo, Japan). Whole-body DXA scans were performed on a Hologic QDR 4500 A bone densitometer (Hologic, Bedford, MA, USA). Total weight, % BF, FM and FFM were tested for intermethod differences. Linear regression and correlation analysis was performed. Limits of agreement and Bland-Altman plots were built. RESULTS: DXA-derived body composition parameters were not significantly different from BIA estimates and were highly correlated (e.g. for FFM, r = 0.82-0.95). In lean individuals, BIA tended to produce lower values for FM and % BF and higher ones for FFM in comparison with DXA. This trend was reversed at BMI > 35 kg/m(2). The correlations decreased with increasing BMI. The limits of agreement were much better in men than in women and increased with increasing BMI in both sexes. CONCLUSIONS: Compared with DXA, the leg-to-leg Tanita TBF-215 analyser accurately assessed body composition in a heterogeneous group of both sexes. In the very obese women (BMI > 35 kg/m(2)), BIA measurements should be viewed with caution.

[Bone density measurement: quantitative ultrasound of the calcaneus and distal radius. A comparison with dual spectrum X-ray absorptiometry]. / Knochendichtemessung: Quantitativer Ultraschall am Kalkaneus und distalen Radius. Ein Vergleich mit der Zwei-Spektren-Röntgen-Absorptiometrie.

BACKGROUND AND OBJECTIVE: Quantitative ultrasound (QUS) has been successfully used for more than a decade in predicting the risk of osteoporotic fractures. However, the "gold standard" in the diagnosis of osteoporosis is dual-energy X-ray absorptiometry (DXA). The aim of this study was to perform QUS at the calcaneus and distal radius, as well as DXA over the lumbar spine and proximal femur in women and to compare both QUS results with the DXA ones. PATIENTS AND METHODS: 230 postmenopausal Bulgarian women, aged between 42 and 80 years, took part in this study. QUS was performed ar the calcaneus and the radius. At the calcaneus the "quantitative ultrasound index" (QUI) was used, but at the radius the speed of sound (SOS) T-scores (SD's under the mean value for young healthy adults) were calculated. RESULTS: The highest accuracy was observed at the radius (coefficient of variance 0.59 %), followed by that for the total hip (0.95 %). The lowest mean T-scores were found at the lumbar spine (-1.94), followed by the calcaneus (-1.85) und radius (-1.74). The correlation coefficients between calcaneal QUI and BMD of the lumbar spine and proximal femur were 0,285 and 0.442 (p=0.059 and 0.001, respectively); the corresponding values for radial SOS were 0.201 and 0.061 (p=0.019 and 0.513, respectively: no significant difference). T-scores of -1.0 for the Sahara device and of -0.5 for the Sunlight device identified women without spinal osteoporosis with a 90% probability. CONCLUSIONS: Women with normal bone density of the proximal femur were better identified using transverse QUS at the calcaneus. Both QUS techniques (transverse and axial) are well suited for identifying women without osteoporosis of the lumbar spine.

Mixed-valence cytoplasmic iron granules are linked to anaerobic respiration.

Intracellular granules containing ferric and ferrous iron formed in Shewanella putrefaciens CN32 during dissimilatory reduction of solid-phase ferric iron. It is the first in situ detection at high resolution (150 nm) of a mixed-valence metal particle residing within a prokaryotic cell. The relationship of the internal particles to Fe(III) reduction may indicate a respiratory role.

Bone mineral density changes in women with systemic lupus erythematosus.

The aim of this study was to analyse the heterogeneity of bone mineral density (BMD) reduction across measurement sites in female systemic lupus erythematosus (SLE) patients on glucocorticoid (CS) treatment. The study population consisted of two subgroups: 32 women at a mean (SD) age of 43.2 (12.0) years, SLE duration of 13.4 (6.2) years, treated with a mean cumulative prednisone dose of 34.4 g; and 16 women at a mean age of 36.1 (9.0) years, SLE duration of 3.2 (2.0) years, never treated with glucocorticoids (control group). The participants underwent a standardised interview, medical record review, blood sampling and BMD examination of the lumbar spine, femoral neck and distal forearm by dual-energy X-ray absorptiometry. CS-treated participants were supplemented with daily calcium (1200 mg) and vitamin D (500 UI). During the study mean daily glucocorticoid dose was 10 mg prednisone equivalent. The controls did not receive either corticosteroids or calcium and vitamin D. BMD and laboratory parameters were re-examined at the end of the second year. At baseline 22 (68.7%) of the CS-treated participants had osteoporosis at least at one major site, compared to 18.8% of the controls. The BMD reduction was proportional to the trabecular bone content at the specific measurement site. At baseline mean T scores in the CS-treated group were the highest at the forearm (-1.03 +/- 1.13), followed by the hip (-1.32 +/- 1.26), AP spine (-1.87 +/- 1.46) and lateral spine (-2.90 +/- 1.50). At follow-up lateral spine bone loss was 5.54% per year, the total hip and the forearm lost 3.59% and 0.33%, respectively, compared to annual losses of 1.02% (AP spine), 1.30% (lateral spine), 0.83% (total hip) and 0.11% (forearm) in the control group. The heterogeneity of BMD reduction in our SLE population emphasises the need for the targeted use of bone densitometry in steroid-treated patients. Attention should be paid to trabecular-rich sites, and fracture risk should be specifically determined.

Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency.

The objective of this study was to assess the effects of oral testosterone supplementation therapy on glucose homeostasis, obesity and sexual function in middle-aged men with type 2 diabetes and mild androgen deficiency. Forty-eight middle-aged men, with type 2 diabetes, (visceral) obesity and symptoms of androgen deficiency, were included in this open-label study. Twenty-four subjects received testosterone undecanoate (TU; 120 mg daily, for 3 months); 24 subjects received no treatment. Body composition was analyzed by bio-impedance. Parameters of metabolic control were determined. Symptoms of androgen deficiency and erectile dysfunction were scored by self-administered questionnaires. TU had a positive effect on (visceral) obesity: statistically significant reduction in body weight (2.66%), waist-hip ratio (-3.96%) and body fat (-5.65%); negligible changes were found in the control group. TU significantly improved metabolic control: decrease in blood glucose values and mean glycated hemoglobin (HbA1c) (from 10.4 to 8.6%). TU treatment significantly improved symptoms of androgen deficiency (including erectile dysfunction), with virtually no change in the control group. There were no adverse effects on blood pressure or hematological, biochemical and lipid parameters, and no adverse events. Oral TU treatment of type 2 diabetic men with androgen deficiency improves glucose homeostasis and body composition (decrease in visceral obesity), and improves symptoms of androgen deficiency (including erectile dysfunction). In these men, the benefit of testosterone supplementation therapy exceeds the correction of symptoms of androgen deficiency and also includes glucose homeostasis and metabolic control.

Prevalence of low forearm bone density in a Bulgarian female referral population.

Osteoporosis is one of the leading causes of morbidity and mortality in the elderly population. The prevalence of osteoporosis and osteopenia in Bulgaria is unknown except for preliminary data. We tried to determine retrospectively the prevalence of osteopenia and osteoporosis in a referral female population; 8869 consecutive Bulgarian women (age 20-87 years) were included. Information about known risk factors for low bone mass was recorded. Forearm bone mineral density was measured at the distal radius+ulna site by single X-ray absorptiometry (DTX-100 device). T- and Z-scores were calculated from Bulgarian reference data. In the total study sample 15.16% had osteoporosis and 28.8% had osteopenia. In women aged 50 years and over the corresponding prevalence was 20.45% and 32.5%. Age-adjusted prevalence of osteoporosis and osteopenia started rising after age 55 years. Corresponding mean T-scores also declined and the osteoporosis threshold of -2.5 SD was reached in the age group 70-74 years. Z-scores in all age groups were between 0 and -0.6, thus excluding major selection bias. This is the first large-scale Bulgarian study designed to look for the prevalence of osteopenia and osteoporosis in a referral population. It may become the starting point for future screening and intervention strategies in our country.

Separate assessment of forearm cortical and trabecular bone density from standard densitometry data.

BACKGROUND: Cortical and trabecular bone are different bone components. Their mineral density cannot be measured directly by areal bone densitometry. AIM: To introduce a method for assessment of pure radial cortical and trabecular bone density based on standard densitometry data. METHOD: The study included 418 healthy females (aged 20-83 years, body mass index between 19 and 30) free of previous fractures and conditions or drugs affecting bone metabolism; as well as a group of 64 age-matched females with early menopause. Forearm bone density was measured by single X-ray absorptiometry and calculated separately for cortical and trabecular bone. Age-adjusted bone density curves were built. RESULTS: Peak bone density was found to occur between 30 and 34 years of age and was 0.561 g/cm2 for cortical and 0.281 g/cm2 for trabecular bone. In comparison, lowest values were registered between 70 and 74 years of age; cortical bone density reduced by 26% and trabecular density by 44%. Both bone density profiles through life reflected the earlier peri- and postmenopausal (mainly trabecular) and later senile (cortical bone also involved) changes in bone mass. A step-wise pattern of trabecular bone reduction was registered with acceleration around 45, 55 and 65 years. The effects of early menopause on trabecular and cortical bone were tested in the prematurely menopausal women. CONCLUSIONS: The ability of our model to discriminate between natural and premature menopause was moderate. Although hypothetical (based on calculations from integral densitometry data rather than on direct measurements), our method could differentiate between cortical and trabecular osteopenia and may prove helpful in assessing the type of osteoporosis, in making therapy choices and monitoring response to therapy based on forearm bone density.

XAFS studies of gold and silver-gold nanoparticles in aqueous solutions.

The x-ray absorption fine structure (XAFS) of colloidal Au and Au/Ag nanoparticles (3.5nm and 20nm mean diameter) in an aqueous solution has been investigated. Size dependent alloying was observed upon deposition of Ag on Au core. Ag forms distinct layers around the 20 nm Au nanoparticles. In contrast, random mixing is found for Ag deposited on 3.5nm Au particles.

XAFS determination of the bacterial cell wall functional groups responsible for complexation of Cd and U as a function of pH.

Bacteria, which are ubiquitous in near-surface geologic systems, can affect the distribution and fate of metals in these systems through adsorption reactions between the metals and bacterial cell walls. Recently, Fein et al. (1997) developed a chemical equilibrium approach to quantify metal adsorption onto cell walls, treating the sorption as a surface complexation phenomenon. However, such models are based on circumstantial bulk adsorption evidence only, and the nature and mechanism of metal binding to cell walls for each metal system have not been determined spectroscopically. The results of XAFS measurements at the Cd K-edge and U L3-edge on Bacillus subtilis exposed to these elements show that, at low pH, U binds to phosphoryl groups while Cd binds to carboxyl functional groups.

Diagnostic discrepancies between two closely related forearm bone density measurement sites.

At the present time the diagnosis of osteoporosis is based on the use of T-scores. Measurements at different skeletal sites or of different regions of interest may result in diagnostic discrepancies. In this study, we tried to demonstrate that bone mineral density (BMD)values at the closely related forearm sites may lead to diagnostic uncertainty, and to assess the degree of site heterogeneity across different age groups. The study consisted of 2348 women (age 20-83) referred for bone densitometry. Forearm BMD was measured at the distal and ultradistal sites by single X-ray absorptiometry (DTX-100 device). T-scores were calculated from Bulgarian reference data. Diagnostic disagreement between sites was found in 19.3% of all women. In 7.7% of all cases, the difference between T-scores at the two sites exceeded 1. The discrepancies were more pronounced after age 60. This corresponds well to the different onset and rates of trabecular and cortical bone losses as well as to their different distribution along the forearm. We encourage the separate assessment of cortical and trabecular bone densities or measurements at axial sites in case forearm sites yield conflicting results or low-normal BMD values.