The relationship between blood leptin level and bone density is specific to ethnicity and menopausal status

Leptin, the obesity hormone, has been linked to bone mineralization and tumorigenesis. In addition, both bone mineral density (BMD) and postmenopausal breast cancer are associated with obesity, but the interrelationships between obesity, leptin, BMD, and breast cancer are not yet clear. In particular, there is little published research comparing white and black women in terms of these variables. We obtained blood specimens for leptin analysis from a group of 320 breast cancer patients and controls with an ethnic composition of 49% white women and 51% black women. Distal and proximal radial BMD (DBMD and PBMD) were measured by dual-energy X-ray absorptiometry, and age- and ethnicity-specific standardized scores (Z-scores) were calculated for bone density. Blood leptin levels were determined by radioimmunoassay. Blood leptin level was not linked to breast cancer risk. Leptin levels were significantly higher in black women than in white women and were also significantly higher in obese and overweight women than in normal-weight women. Black women weighed more and had a higher body mass index (BMI) than white women. After controlling for BMI, leptin was correlated with DBMD ( r = .17; P < .05) and PBMD ( r = .21; P < .05) in whites, but not in blacks. Leptin was also correlated with both distal and proximal Z-scores in postmenopausal women ( r = .14 and .13; P < .05). Thus leptin may be a predictor for BMD in a population that is prone to have a low BMD, and this relationship is independent of the effect of body weight on leptin levels. Our results suggest that ethnicity and menopausal status should be considered when comparing results from different studies.     

Do Textiles Impact DXA Bone Density or Body Composition Results?

External artifacts can confound dual-energy X-ray absorptiometry (DXA) measurements. It is often accepted that garments free of metal do not affect DXA results; however, little data exist in this regard. It is plausible that some textiles absorb radiation and thereby alter DXA results. We hypothesized that some dense or synthetic textiles, for example, reflective materials, might alter DXA-measured bone and soft tissue mass. Hologic and GE Lunar spine phantoms and a Bioclinica prototype total body phantom were imaged on a GE Lunar iDXA and Prodigy densitometer. Each phantom was scanned 10 times to establish mean values. Subsequently, 2 layers of various fabrics were placed over the entire top surface of the phantom, and 10 scans were performed without repositioning. Samples of natural, synthetic, or embellished fabric (including those with reflective material) and of varying thickness were used. Wilcoxon signed rank tests were used to compare the means between bare phantom and textile-covered phantom. Significant differences were demonstrated often, depending on the scanner, phantom, and textile used. A polyester fabric with reflective strip consistently altered measurements. For example, this fabric increased measured mean lumbar spine bone mineral density and total body bone mineral content by 0.008?g/cm² and 3.6?g, respectively (p?<?0.01). Similarly, mean total body fat decreased (?173 g) and lean mass increased (+213 g; p?<?0.01). Fat and lean mass were also affected by metallic thread, wool, blend denim, and shiny polyester (p?<?0.05), and lean mass was affected by cotton denim and sweatshirt material (p?<?0.0003). In conclusion, textiles can affect DXA-measured bone mineral density and body composition results. Even small amounts of reflective material could alter mass measurements by ~25% of the least significant change. Clothing made of dense textiles (e.g., wool and denim) or those with reflective material and metallic thread should be avoided during DXA scanning.     

SGLT2抑制剂对2型糖尿病患者骨骼的影响

钠葡萄糖共转运体2(sodium-glucose cotransporter 2,SGLT2)抑制剂是一种新型降糖药物,其作用机理是通过抑制肾小管对尿糖的重吸收,以增加尿糖排泄降低血糖。近期来自国外的多个临床药物试验发现SGLT2抑制剂可能对2型糖尿病患者的骨代谢、骨密度以及骨折率产生影响。本文将通过复习国内外相关研究,尝试综述SGLT2抑制剂对2型糖尿病患者骨骼的影响。     

鲑鱼降钙素注射液与唑来膦酸钠注射液治疗绝经后骨质疏松症的临床疗效对比

目的对比鲑鱼降钙素注射液与唑来膦酸钠注射液在治疗绝经后骨质疏松症的临床疗效研究。方法本研究收集了2010年2月-2016年2月在南昌大学第三附属医院治疗的绝经后骨质疏松症患者82例,分为鲑鱼降钙素注射液治疗组(40例,治疗时间3个月/年,连续3年),唑来膦酸钠注射液组(42例,治疗时间1次/年,5 mg/次,连续3年)。同时口服碳酸钙D3(600 mg/d)、骨化三醇(0.25μg/d)。采集患者基线及治疗3年后骨密度(bone mineral density,BMD)、肾功能、血钙(blood calcium,BC)、血磷(blood phosphorus BP)、骨碱性膦酸酶(bone alkaline phosphatase,BALP);进行组间及治疗前后对照;以视觉模拟标度尺(visual analogue scale,VAS)评分评估骨痛情况,判定临床疗效;对比两组患者不良反应的发生人次及发生率。结果(1)对两组患者肾功能、血钙、血磷、骨碱性膦酸酶水平进行组间及治疗前后比较,差异均无统计学意义,P0.05;(2)两组患者治疗后骨痛评价:两组患者VAS评分均较治疗前降低,但鲑鱼降钙素组VAS评分较唑来膦酸钠组显著降低,差异有统计学意义,P0.05;(3)两组患者治疗后面积骨密度值较治疗前均显著升高,P0.05。唑来膦酸钠组患者腰椎、股骨颈骨密度升高幅度高于鲑鱼降钙素组,两组比较差异有统计学意义,P0.05;(4)在本研究中唑来膦酸钠组不良反应发生率低。结论唑来膦酸钠与鲑鱼降钙素治疗3年均有效提高了绝经后骨质疏松症患者的骨密度,其中唑来膦酸钠组优于鲑鱼降钙素组。两种治疗均有效减轻患者骨痛症状,鲑鱼降钙素组临床疗效优于唑来膦酸钠组。     

IL21R and PTH may underlie variation of femoral neck bone mineral density as revealed by a genome‐wide association study

Bone mineral density (BMD) measured at the femoral neck (FN) is the most important risk phenotype for osteoporosis and has been used as a reference standard for describing osteoporosis. The specific genes influencing FN BMD remain largely unknown. To identify such genes, we first performed a genome‐wide association (GWA) analysis for FN BMD in a discovery sample consisting of 983 unrelated white subjects. We then tested the top significant single‐nucleotide polymorphisms (SNPs; 175 SNPs with p < 5 × 10^?4) for replication in a family‐based sample of 2557 white subjects. Combing results from these two samples, we found that two genes, parathyroid hormone (PTH) and interleukin 21 receptor (IL21R), achieved consistent association results in both the discovery and replication samples. The PTH gene SNPs, rs9630182, rs2036417, and rs7125774, achieved p values of 1.10 × 10^?4, 3.24 × 10^?4, and 3.06 × 10^?4, respectively, in the discovery sample; p values of 6.50 × 10^?4, 5.08 × 10^?3, and 5.68 × 10^?3, respectively, in the replication sample; and combined p values of 3.98 × 10^?7, 9.52 × 10^?6, and 1.05 × 10^?5, respectively, in the total sample. The IL21R gene SNPs, rs8057551, rs8061992, and rs7199138, achieved p values of 1.51 × 10^?4, 1.53 × 10^?4, and 3.88 × 10^?4, respectively, in the discovery sample; p values of 2.36 × 10^?3, 6.74 × 10^?3, and 6.41 × 10^?3, respectively, in the replication sample; and combined p values of 2.31 × 10^?6, 8.62 × 10^?6, and 1.41 × 10^?5, respectively, in the total sample. The effect size of each SNP was approximately 0.11 SD estimated in the discovery sample. PTH and IL21R both have potential biologic functions important to bone metabolism. Overall, our findings provide some new clues to the understanding of the genetic architecture of osteoporosis. © 2010 American Society for Bone and Mineral Research     

运动疗法预防治疗绝经后骨质疏松症的应用进展

绝经后骨质疏松症以低骨密度为特征,是全球重要的公共健康问题。骨密度由多重因子决定。本文对绝经后骨质疏松症运动疗法的影响因素及其疗效等方面进行综述,探明预防治疗绝经后骨质疏松症的有效运动途径,为防治绝经后骨质疏松症提供理论依据,以期提高绝经后骨质疏松症妇女的生活质量。     

Biomonitoring equivalents for di-isononyl phthalate (DINP)

Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline such as a reference dose (RfD) or tolerable daily intake (TDI). BE values can be used as a screening tool for the evaluation of population-based biomonitoring data in the context of existing risk assessments. This study reviews available health based risk assessments and exposure guidance values for di-isononyl phthalate (DINP) from Health Canada, the United States Consumer Product Safety Commission (US CPSC), and the European Food Safety Authority (EFSA). Controlled dosing data reporting the urinary excretion fractions of major DINP metabolites following administration of labeled DINP are reviewed, and BE values corresponding to the available exposure guidance values are derived assuming chronic, steady-state intake and excretion at those exposure values. The BE values range from 1500 to 3600μg/L (1900-4600μg/g creatinine) based on the sum of three oxidative metabolites. Sources of uncertainty relating to both the basis for the BE values and their use in evaluation of biomonitoring data, including the transience of the biomarkers relative to exposure frequency, are discussed. The BE values derived here can be used as screening tools for evaluation of population biomonitoring data for DINP in the context of existing risk assessments and can assist in prioritization of the potential need for additional risk assessment efforts for DINP relative to other chemicals.     

Gene expression of biomarkers of nephrotoxicity in F344 rats co-exposed to melamine and cyanuric acid for seven days

A number of studies have demonstrated that co-exposure to low levels of melamine and cyanuric acid elicits renal toxicity due to the formation of melamine cyanurate crystals in the kidney nephrons. In this work, we investigated if co-exposure of rats to these compounds leads to alterations in the expression of the genes encoding kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), clusterin, osteopontin, and neutrophil gelatinase-associated lipocalin/lipocalin 2 (NGAL), which have been proposed as urinary biomarkers for nephrotoxicity. Six-week-old male and female F344 rats were fed ad libitum a diet fortified with 0 (control), 7, 23, 69, 229, or 694 ppm melamine and cyanuric acid (co-exposure groups), 1388 ppm melamine, or 1388 ppm cyanuric acid for seven days. Histopathology and clinical chemistry examination indicated marked toxicity only in the animals exposed to the two highest combined doses of melamine and cyanuric acid. Consistent with these observations, quantitative real-time polymerase chain reaction analysis of kidney tissue indicated increased expression of all genes analyzed relative to the control in both male and female rats fed daily with 229 or 694 ppm melamine and cyanuric acid. Exposure to lower levels of both compounds or to the individual compounds did not induce gene expression changes. These data indicate that quantifying the expression levels of the selected biomarker genes constitutes a useful endpoint to assess the combined toxicity of melamine and cyanuric acid in both male and female rats.     

Prenatal developmental toxicity studies on di-n-heptyl and di-n-octyl phthalates in Sprague-Dawley rats

This study evaluates the developmental toxicity of two dialkyl phthalate esters, di-n-heptyl phthalate (DHPP) and di-n-octyl (DnOP) phthalate, which have straight-alkyl side chains of seven and eight carbons, respectively. Sprague-Dawley rats were administered 0, 0.25, 0.50, or 1g/kg/day of DHPP or DnOP, by gavage, on gestation days 6-20. DHPP and DnOP had no adverse effect on maternal feed consumption and body weight gain, or on the incidence of post-implantation loss and fetal body weight. There was no increase in the incidence of fetal malformations or external and visceral variations, whatever treatment. A significant increase in rudimentary lumbar ribs was observed at all doses of DHPP and DnOP. The anogenital distance of the male fetuses was significantly decreased at the highest dose of DHPP. This parameter was not affected by DnOP. Thus, the lowest-observed-adverse-effect level (LOAEL) for developmental toxicity was 0.25 g/kg/day for DHPP and DnOP.