External validation of the Garvan nomograms for predicting absolute fracture risk: The Tromso study

Background: Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decision making. This study aimed to evaluate and validate the predictive performance of the Garvan Fracture Risk Calculator in a Norwegian cohort. Methods: The analysis included 1637 women and 1355 aged 60+ years from the Tromsø study. All incident fragility fractures between 2001 and 2009 were registered. The predicted probabilities of non-vertebral osteoporotic and hip fractures were determined using models with and without BMD. The discrimination and calibration of the models were assessed.Reclassification analysis was used to compare the models performance. Results: The incidence of osteoporotic and hip fracture was 31.5 and 8.6 per 1000 population in women, respectively; in men the corresponding incidence was 12.2 and 5.1. The predicted 5-year and 10-year probability of fractures was consistently higher in the fracture group than the non-fracture group for all models. The 10-year predicted probabilities of hip fracture in those with fracture was 2.8 (women) to 3.1 times (men) higher than those without fracture. There was a close agreement between predicted and observed risk in both sexes and up to the fifth quintile. Among those in the highest quintile of risk, the models over-estimated the risk of fracture. Models with BMD performed better than models with body weight in correct classification of risk in individuals with and without fracture. The overall net decrease in reclassification of the model with weight compared to the model with BMD was 10.6% (p = 0.008) in women and 17.2% (p = 0.001) in men for osteoporotic fractures, and 13.3% (p = 0.07) in women and 17.5% (p = 0.09) in men for hip fracture. Conclusions: The Garvan Fracture Risk Calculator is valid and clinically useful in identifying individuals at high risk of fracture. The models with BMD performed better than those with body weight in fracture risk prediction

Genetic polymorphisms are associated with serum levels of sex hormone binding globulin in postmenopausal women

<p>Abstract</p> <p>Background</p> <p>Estrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the <it>SHBG </it>gene on serum SHBG, bone mineral density (BMD), and osteoporotic fractures.</p> <p>Methods</p> <p>Four biallelic polymorphisms of the <it>SHBG </it>gene were studied by means of Taqman assays in 753 postmenopausal women. BMD was measured by DXA and serum SHBG was measured by ELISA.</p> <p>Results</p> <p>Age, body weight, and two polymorphisms of the <it>SHBG </it>gene (rs6257 and rs1799941 [A/G]) were significantly associated with serum SHBG in unadjusted and age- and weight-adjusted models. Alleles at the rs1799941 locus showed the strongest association with serum SHBG (p = 0.0004). The difference in SHBG levels between women with AA and GG genotypes at the rs1799941 locus was 39%. There were no significant differences in BMD across SHBG genotypes. The genotypes showed similar frequency distributions in control women and women with vertebral or hip fractures.</p> <p>Conclusion</p> <p>Some common genetic variants of the <it>SHBG </it>gene, and particularly an A/G polymorphism situated in the 5' region, influence serum SHBG levels. However, a significant association with BMD or osteoporotic fractures has not been demonstrated.</p

Comparison of plasma endothelin levels between osteoporotic, osteopenic and normal subjects

BACKGROUND: It has been demonstrated that endothelins (ET) have significant roles in bone remodeling, metabolism and physiopathology of several bone diseases. We aimed to investigate if there was any difference between the plasma ET levels of osteoporotic patients and normals. METHODS: 86 patients (70 women and 16 men) with a mean age of 62.6 (ranges: 51–90) years were included in this study. Patients were divided into groups of osteoporosis, osteopenia and normal regarding reported T scores of DEXA evaluation according to the suggestions of World Health Organization. According to these criteria 19, 43 and 24 were normal, osteopenic and osteoporotic respectively. Then total plasma level of ET was measured in all patients with monoclonal antibody based sandwich immunoassay (EIA) method. One-way analysis of variance test was used to compare endothelin values between normals, osteopenics and osteoporotics. RESULTS: Endothelin total plasma level in patients was a mean of 98.36 ± 63.96, 100.92 ± 47.2 and 99.56 ± 56.6 pg/ml in osteoporotic, osteopenic and normal groups respectively. The difference between groups was not significant (p > 0.05). CONCLUSION: No significant differences in plasma ET levels among three groups of study participants could be detected in this study

Relationships between heavy metal concentrations in three different body fluids and male reproductive parameters: a pilot study

<p>Abstract</p> <p>Background</p> <p>Animal studies have shown the reproductive toxicity of a number of heavy metals. Very few human observational studies have analyzed the relationship between male reproductive function and heavy metal concentrations in diverse biological fluids.</p> <p>Methods</p> <p>The current study assessed the associations between seminal and hormonal parameters and the concentration of the 3 most frequent heavy metal toxicants (lead, cadmium and mercury) in three different body fluids. Sixty one men attending infertility clinics that participated in a case-control study to explore the role of environmental toxins and lifestyles on male infertility were analyzed. Concentration of lead, cadmium and mercury were measured in blood and seminal plasma and whole blood using anodic stripping voltammetry and atomic absorption spectrophotometry. Serum samples were analyzed for follicle-stimulating hormone, luteinizing hormone and testosterone. Semen analyses were performed according to World Health Organization criteria. Mann-Whitney test and Spearman's rank correlations were used for unadjusted analyses. Multiple linear regression models were performed controlling for age, body mass index and number of cigarettes per day.</p> <p>Results</p> <p>There were no significant differences between cases and controls in the concentrations of heavy metals in any of the three body fluids. In multivariate analyses using all subjects no significant associations were found between serum hormone levels and metal concentrations. However there was a significant positive association between the percentage of immotile sperms and seminal plasma levels of lead and cadmium.</p> <p>Conclusions</p> <p>Our results suggest that the presence of lead and cadmium in the reproductive tract of men may be related to a moderate alteration of their seminal parameters.</p

Bone trait ranking in the population is not established during antenatal growth but is robustly established in the first postnatal year

Efforts to understand the pathophysiology of bone fragility must focus on bone traits during growth. We hypothesized that variance in individual trait ranking in the population distribution is established by genetic factors and is reflected in foetal trait ranking in early pregnancy, but intrauterine factors modify trait ranking in late pregnancy, followed by the reinstating of this ranking during the first postnatal year. Thus, relations with paternal factors are present in early pregnancy but are then lost and subsequently reinstated postnatal. We recruited 399 healthy pregnant women aged 20-42 years from The Mercy Hospital for Woman in Melbourne, Australia. Foetal femur length (FL) and knee-heel length (KHL) were measured by ultrasound during gestation, and FL, KHL, body length and weight were measured in neonates, infants, and parents. The z-scores were calculated using Royston models. Pearson correlation was used to assess tracking and linear mixed models to test the associations. Correlations between FL and KHL z-scores of the same trait at 20 and 30 weeks gestation, at birth, and at 12 and 24 months of age (r = 0.1-0.3) and of body length and weight at birth, and 6, 12 and 24 months (r = 0.3-0.5) became more robust after 6-12 months (r = 0.4-0.8). FL and KHL z-scores at 20 weeks gestation accounted for 4-5% of total variance, while FL, KHL, body length and weight z-scores at birth accounted for 13-26% of total variance in the same traits at 24 months. Maternal FL and KHL were associated with foetal FL and KHL at 20 and 30 weeks, but there were no such associations for paternal FL and KHL with foetal traits during gestation. Both maternal and paternal traits were associated with infant traits. Tracking in traits is not established antenatal but is robustly established at 6-12 months of age

Fracture risk and height: An association partly accounted for by cortical porosity of relatively thinner cortices

The fulltext of this publication will be made publicly available after relevant embargo periods have lapsed and associated copyright clearances obtained.Taller women are at increased risk for fracture despite having wider bones that better tolerate bending. Because wider bones require less material to achieve a given bending strength, we hypothesized that taller women assemble bones with relatively thinner and more porous cortices because excavation of a larger medullary canal may be accompanied by excavation of more intracortical canals. Three-dimensional images of distal tibia, fibula, and radius were obtained in vivo using high-resolution peripheral quantitative computed tomography (HRpQCT) in a twin study of 345 females aged 40 to 61 years, 93 with at least one fracture. Cortical porosity 100 µm, and microarchitecture, were quantified using Strax1.0, a new algorithm. Multivariable linear and logistic regression using generalized estimating equation (GEE) methods quantified associations between height and microarchitecture and estimated the associations with fracture risk. Each standard deviation (SD) greater height was associated with a 0.69 SD larger tibia total cross-sectional area (CSA), 0.66 SD larger medullary CSA, 0.50 SD higher medullary CSA/total CSA (i.e., thinner cortices relative to the total CSA due to a proportionally larger medullary area), and 0.42 SD higher porosity (all p < 0.001). Cortical area was 0.45 SD larger in absolute terms but 0.50 SD smaller in relative terms. These observations were confirmed by examining trait correlations in twin pairs. Fracture risk was associated with height, total CSA, medullary CSA/total CSA, and porosity in univariate analyses. In multivariable analyses, distal tibia, medullary CSA/total CSA, and porosity predicted fracture independently; height was no longer significant. Each 1 SD greater porosity was associated with fracture; odds ratios (ORs) and 95% confidence intervals (CIs) are as follows: distal tibia, OR = 1.55 (95% CI, 1.11-2.15); distal fibula, OR = 1.47 (95% CI, 1.14-1.88); and distal radius, OR = 1.22 (95% CI, 0.96-1.55). Taller women assemble wider bones with relatively thinner and more porous cortices predisposing to fracture

Architecture of cortical bone determines in part its remodelling and structural decay

The fulltext of this publication will be made publicly available after relevant embargo periods have lapsed and associated copyright clearances obtained.Bone remodelling accelerates and becomes unbalanced after menopause; less bone is deposited than resorbed from the surface of canals traversing the cortex. The canals enlarge so the intracortical surface area enlarges. We hypothesized that cortical bone with a larger internal surface area, due to more or larger canals, is more liable to being remodelled, further enlarging the internal surface area and facilitating more remodelling and structural deterioration. For 95 monozygotic twin pairs aged 40-61 years, we measured internal cortical surface areas and structure of the distal tibia using high resolution peripheral computed tomography, and three circulating bone remodelling markers. Using principal component (PC) analyses, we identified one summary measure of intracortical and endocortical bone surface areas, cortical porosity and volumetric bone mineral density (structure PC), and one summary measure of bone remodelling markers (remodelling PC). We applied a twin regression analysis (Inference on Causation by Examination of Familial Confounding; ICE FALCON) to assess consistency with a causal component in the association between a predictor (X) and an outcome (Y) by testing if the regression coefficient for the X value of the co-twin decreases after adjusting for the X value of the twin herself. With Y = remodelling PC, the regression coefficient for structure PC in the co-twin was 0.29 (p < 0.001) before, and 0.18 (p = 0.03) after, adjusting for her own structure PC (40% lower; p = 0.06). With Y = structure PC, the regression coefficient for remodelling PC in the co-twin was 0.17 (p = 0.01) before, and 0.20 (p < 0.001) after, adjusting for her own remodelling PC (22% higher; p = 0.7). The structure of bone, its surface area to bone matrix volume configuration, might contribute in part to its own remodelling and deterioration, but not vice versa