Combined effects of collagen type I alpha1 (COL1A1) Sp1 polymorphism and osteoporosis risk factors on bone mineral density in Turkish postmenopausal women

Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis. The collagen type I alpha1 (COL1A1) gene is suggested to be implicated in reduced bone mineral density (BMD) in osteoporosis. In the present study, the investigation of the effects of Sp1 polymorphic variants of COL1A1 gene on BMD values, and the determination of the association between COL1A1 Sp1 gene variants and osteoporosis risk factors in the context of gene–environment interaction in Turkish postmenopausal women were aimed. For the detection of COL1A1 Sp1 polymorphism, PCR-RFLP techniques have been used. BMD for lumbar spine (L1–L4) and hip (femoral neck and total hip) was measured by DXA. This study was carried out using a sample of 254 postmenopausal women. We observed a trend decrease in BMD values in the subjects with “ss” genotype having lower BMD of lumbar spine, femoral neck and total hip than those with “SS” and “Ss” genotype, however the differences did not reach statistical significance (P > 0.05). We also found that the frequencies of the BMD under mean values at the femoral neck (57.5%) and total hip (76.2%) increased considerably in the subjects carrying “Ss/ss” genotypes in combination of having family history of osteoporosis (61.5% for femoral neck) and smoking history (90.0% for total hip). This population-based study indicates that COL1A1 Sp1 polymorphism may contribute to the development of osteoporosis in combination of osteoporosis risk factors in Turkish postmenopausal women.     

Comparison of Methods to Assess Body Composition Changes during a Period of Weight Loss

Objective: To assess the accuracy of body composition measurements by air displacement plethysmography and bioelectrical impedance analysis (BIA) compared with DXA during weight loss. Research Methods and Procedures: Fifty‐six healthy but overweight participants, 34 women and 22 men (age, 52 ± 8.6 years; weight, 92.2 ± 11.6 kg; BMI, 33.3 ± 2.9 kg/m²) were studied in an outpatient setting before and after 6 months of weight loss (weight loss, 5.6 ± 5.5 kg). Subjects were excluded if they had initiated a new drug therapy within 30 days of randomization, were in a weight loss program, or took a weight loss drug within 90 days of randomization. Subjects were randomly assigned either to a self‐help program, consisting of two 20‐minute sessions with a nutritionist and provision of printed materials and other self‐help resources, or to attendance at meetings of a commercial program (Weight Watchers). Body composition was examined by each of the methods before and after weight loss. Results: BIA (42.4 ± 5.8%) underestimated percentage fat, whereas the BodPod (Siri = 51.7 ± 6.9%; Brozek = 48.5 ± 6.5%) overestimated percentage fat compared with DXA (46.1 ± 7.9%) before weight loss. Correlation coefficients for detecting changes in body composition between DXA and the other methods were relatively high, with Brozek Δfat mass (FM; r² = 0.63), Siri FM (r² = 0.65), tetrapolar BIA percentage fat (r² = 0.57), and Tanita FM (r² = 0.61) being the highest. Discussion: In conclusion, all of the methods were relatively accurate for assessing body composition compared with DXA, although there were biases. Furthermore, each of the methods was sensitive enough to detect changes with weight loss.     

Total and Regional Fat and Serum Cardiovascular Disease Risk Factors in Lean and Obese Children and Adolescents

Objective: This study was conducted to evaluate the association of total and central adiposity with serum cardiovascular disease (CVD) risk factors in lean and obese Portuguese children and adolescents. Research Methods and Procedures: A total of 87 girls (13.2 ± 1.6 years old, 29.9 ± 6.4% body fat [mean ± SD]) and 72 boys (13.2 ± 1.6 years old, 20.8 ± 9.9% body fat) volunteered for the study. Whole‐body composition and fat distribution, from DXA and anthropometry, and serum lipids, lipoproteins, and apolipoproteins were evaluated. Results: The sum of three trunk skinfolds (STS) was highly correlated with total trunk fat mass measured by DXA (p < 0.001). Body mass index, DXA‐measured percentage of body fat, trunk fat mass, STS, and the waist‐to‐height ratio were generally found to be associated with triacylglycerol, the ratio of total cholesterol (TC) to high density lipoprotein‐cholesterol (HDL‐C), low density lipoprotein‐cholesterol (LDL‐C), and apolipoprotein B levels, (significant age‐adjusted r between 0.16 and 0.27, p < 0.05). Body mass index, STS, and the waist circumference were also associated with HDL‐C (p < 0.05), whereas no body composition variable significantly correlated with TC or apolipoproteins A‐I. The STS was significantly correlated with HDL‐C (p < 0.01), TC/HDL‐C (p < 0.05), and apolipoproteins A‐I (p < 0.05) independently of whole‐body fatness. Obese subjects (n = 73) had higher TC, LDL‐C, TC/HDL‐C, and apolipoprotein B than did non‐obese subjects (n = 86), and significant associations between central adiposity and some lipid variables (triacylglycerol and HDL‐C) were found in obese children and adolescents that were not present in leaner individuals. Discussion: DXA‐ and anthropometry‐based whole‐body and central fat measures are associated with serum CVD risk factors in Portuguese boys and girls. Obese children and adolescents have a poorer lipid profile than do their leaner counterparts. Trunk skinfolds, which are easy to obtain even in large samples, predict CVD risk factors to the same extent as DXA‐based variables, in some cases, independently of total fatness.     

Raman spectroscopy predicts the link between claw keratin and bone collagen structure in a rodent model of oestrogen deficiency

Osteoporosis is a common disease characterised by reduced bone mass and an increased risk of fragility fractures. Low bone mineral density is known to significantly increase the risk of osteoporotic fractures, however, the majority of non-traumatic fractures occur in individuals with a bone mineral density too high to be classified as osteoporotic. Therefore, there is an urgent need to investigate aspects of bone health, other than bone mass, that can predict the risk of fracture. Here, we successfully predicted association between bone collagen and nail keratin in relation to bone loss due to oestrogen deficiency using Raman spectroscopy. Raman signal signature successfully discriminated between ovariectomised rats and their sham controls with a high degree of accuracy for the bone (sensitivity 89%, specificity 91%) and claw tissue (sensitivity 89%, specificity 82%). When tested in an independent set of claw samples the classifier gave 92% sensitivity and 85% specificity. Comparison of the spectral changes occurring in the bone tissue with the changes occurring in the keratin showed a number of common features that could be attributed to common changes in the structure of bone collagen and claw keratin. This study established that systemic oestrogen deficiency mediates parallel structural changes in both the claw (primarily keratin) and bone proteins (primarily collagen). This strengthens the hypothesis that nail keratin can act as a surrogate marker of bone protein status where systemic processes induce changes.     

Variogram-based evaluations of DXA correlate with vertebral strength,but do not enhance the prediction compared to aBMD alone

Ancillary evaluation of spinal Dual-energy X-ray Absorptiometry (DXA) via variogram-based texture evaluation (e.g., Trabecular Bone Score) is used for improving the fracture risk assessment, despite no proven relationship with vertebral strength. The purpose of this study was thus to determine whether classical variogram-based parameters (sill variance and correlation length) evaluated from simulated DXA scans could help predicting the in vitro vertebral strength.Experimental data of thirteen human full vertebrae (i.e., with posterior elements) and twelve vertebral bodies were obtained from two existing studies. Areal bone mineral density (aBMD) was calculated from 2D projection images of the 3D HR-pQCT scan of the specimens mimicking clinical DXA scans. Stochastic predictors, sill variance and correlation length, were calculated from their experimental variogram. Vertebral strength was measured as the maximum failure load of human vertebrae and vertebral bodies from mechanical tests.Vertebral strength correlated significantly with sill variance (r = 0.727) and correlation length (r = 0.727) for the vertebral bodies, and with correlation length (r = 0.593) for full vertebrae. However, the stochastic predictors improved the strength prediction made by aBMD alone by only 11% for the vertebral bodies while no improvement was observed for the full vertebrae.Despite a correlation, classical variogram parameters such as sill variance and correlation length do not enhance the prediction of in vitro vertebral strength beyond aBMD. It remains unclear why some variogram-based evaluations of DXA improve fracture prediction without a proven relationship with vertebral strength.     

A new geometric-based model to accurately estimate arm and leg inertial estimates

Segment estimates of mass, center of mass and moment of inertia are required input parameters to analyze the forces and moments acting across the joints. The objectives of this study were to propose a new geometric model for limb segments, to evaluate it against criterion values obtained from DXA, and to compare its performance to five other popular models. Twenty five female and 24 male college students participated in the study. For the criterion measures, the participants underwent a whole body DXA scan, and estimates for segment mass, center of mass location, and moment of inertia (frontal plane) were directly computed from the DXA mass units. For the new model, the volume was determined from two standing frontal and sagittal photographs. Each segment was modeled as a stack of slices, the sections of which were ellipses if they are not adjoining another segment and sectioned ellipses if they were adjoining another segment (e.g. upper arm and trunk). Length of axes of the ellipses was obtained from the photographs. In addition, a sex-specific, non-uniform density function was developed for each segment. A series of anthropometric measurements were also taken by directly following the definitions provided of the different body segment models tested, and the same parameters determined for each model. Comparison of models showed that estimates from the new model were consistently closer to the DXA criterion than those from the other models, with an error of less than 5% for mass and moment of inertia and less than about 6% for center of mass location.     

Long-term serotonin administration leads to higher bone mineral density, affects bone architecture, and leads to higher femoral bone stiffness in rats

New evidence suggests a control of bone mass by the central nervous system. We have previously shown that functional serotonin receptors are present in bone cells and that serotonin stimulates proliferation of osteoblast precursor cells in vitro. In the present study we investigated the effects of serotonin on bone tissue in vivo. Ten, 2-month-old female Sprague-Dawley rats were injected with serotonin subcutaneously (s.c.) (5 mg/kg) once daily for 3 months, controls received saline. Using microdialysis and HPLC, free circulating serotonin levels were measured. DXA scans were made after 3 months of serotonin administration. Bone architecture and mechanical properties were investigated by micro-computed tomography (microCT), histomorphometry, and mechanical testing. A long-lasting hyperserotoninemia with a >10-fold increase in serotonin appeared. Total body BMD was significantly higher (0.1976+/-0.0015 vs. 0.1913+/-0.0012 g/cm2) in rats receiving serotonin. Cortical thickness (Ct.Th) measured by microCT analysis was also higher, whereas trabecular bone volume (BV) was lower. Interestingly, the perimeter and cross-sectional moment of inertia (MOI), a proxy for geometrical bone strength, were the same in both groups. These data suggest that serotonin reduces resorption or/and increases apposition of endosteal bone. Mechanical testing showed that femoral stiffness was higher in serotonin-dosed animals. The energy absorption also seemed slightly, but not significantly higher. In conclusion, hyperserotoninemia led to a higher BMD, altered bone architecture and higher femural bone stiffness in growing rats, demonstrating that serotonin may have important effects on bone in vivo.     

Comparison of body composition methods in obese African-American women

Objective : To compare the accuracy of percentage body fat (%BF) estimates between bioelectrical impedance analysis (BIA) and DXA in obese African‐American women. Research Methods and Procedures : Fifty‐five obese African‐American women (mean age, 45 years; mean BMI, 38; mean %BF, 48%) were studied. BF was assessed by both BIA (RJL Systems BIA 101Q; RJL Systems, Clinton Township, MI) and DXA (Hologic QDR‐2000 Bone Densitometer; Hologic Inc., Bedford, MA). Generalized and ethnicity‐ and obese‐specific equations were used to calculate %BF from the BIA. Bland‐Altman analyses were used to compare the agreement between the BIA and the DXA, with the DXA serving as the criterion measure. Results : Two of the generalized equations provided consistent estimates across the weight range in comparison with the DXA estimates, whereas most of the other equations increasingly underestimated %BF as BF increased. One of the generalized and one of the ethnicity‐specific equations had mean differences that were not significantly different from the DXA value. Discussion : The findings show that the Lukaski equation provided the most precise and accurate estimates of %BF in comparison with the QDR 2000 and provide preliminary support for the use of this equation for obese African‐American women.