The benchmark dose approach in food risk assessment: Is it applicable and worthwhile?

The benchmark dose (BMD) approach is being increasingly used in the area of food risk assessment because it offers several advantages compared to the conventional no-observed-adverse-effect-level approach. The aim of this work was to check the applicability of the BMD approach on toxicity data available from pesticides, mycotoxins and natural toxins.     

骨密度测量仪器的技术与发展

综述了目前进行骨密度分析的不同技术与仪器。同时讨论了这些方法在精确度、测量部位、测量的便利性、灵敏度和辐射危害等方面的特性。     

Osteoporosis Risk in Premenopausal Women

Although clinically significant bone loss and fractures in healthy premenopausal women are rare, more women are seeking evaluation for osteoporosis from their health care providers. As pharmacists are in an ideal position to influence the management of premenopausal women with osteoporosis, it is important that pharmacists understand the available data on bone loss, fractures, and risk factors and secondary causes for osteoporosis, as well as when to recommend testing and treatment in premenopausal women. Limited data are available; therefore, we conducted a MEDLINE search of the literature from January 1993-August 2008. Studies evaluating bone loss, fractures, and fracture risk in healthy premenopausal women were targeted and summarized; most recommendations are based on expert opinion. A small but statistically significant loss in bone mineral density of 0.25-1%/year by dual-energy x-ray absorptiometry is seen healthy premenopausal women; the clinical significance of this is unknown. Whereas absolute fracture risk is low, premenopausal fractures appear to increase postmenopausal fracture risk by 1.5-3-fold. Risk factors for low bone density appear to be similar between pre- and postmenopausal women. Bone density screening in healthy premenopausal women is not recommended, but bone mineral density testing is advisable for those who have conditions or who receive drug therapy that may cause secondary bone loss. Lifestyle modification emphasizing bone-healthy habits such as adequate calcium and vitamin D nutrition, regular exercise, limitation of caffeine and alcohol consumption, and avoidance of tobacco are essential to the management of osteoporosis risk. The efficacy and safety of osteoporosis drugs have not been adequately demonstrated in premenopausal women. Therefore, pharmacologic interventions cannot be recommended in young women with low bone mass but may be considered in those having a more significant fracture risk, such as those with a previous low-trauma fracture or an identified secondary cause for bone loss.     

Vertebral Fracture Risk in Diabetic Elderly Men: The MrOS Study

Type 2 diabetes (T2DM) is associated with a significant increase in risk of nonvertebral fractures, but information on risk of vertebral fractures (VFs) in subjects with T2DM, particularly among men, is lacking. Furthermore, it is not known whether spine bone mineral density (BMD) can predict the risk of VF in T2DM. We sought to examine the effect of diabetes status on prevalent and incident vertebral fracture, and to estimate the effect of lumbar spine BMD (areal and volumetric) as a risk factor for prevalent and incident morphometric vertebral fracture in T2DM (n = 875) and nondiabetic men (n = 4679). We used data from the Osteoporotic Fractures in Men (MrOS) Study, which enrolled men aged ≥65 years. Lumbar spine areal BMD (aBMD) was measured with dual‐energy X‐ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT). Prevalence (7.0% versus 7.7%) and incidence (4.4% versus 4.5%) of VFs were not higher in T2DM versus nondiabetic men. The risk of prevalent (OR, 1.05; 95% CI, 0.78 to 1.40) or incident vertebral‐fracture (OR, 1.28; 95% CI, 0.81 to 2.00) was not higher in T2DM versus nondiabetic men in models adjusted for age, clinic site, race, BMI, and aBMD. Higher spine aBMD was associated with lower risk of prevalent VF in T2DM (OR, 0.55; 95% CI, 0.48 to 0.63) and nondiabetic men (OR, 0.66; 95% CI, 0.5 to 0.88) (p for interaction = 0.24) and of incident VF in T2DM (OR, 0.50; 95% CI, 0.41 to 0.60) and nondiabetic men (OR, 0.54; 95% CI, 0.33 to 0.88) (p for interaction = 0.77). Results were similar for vBMD. In conclusion, T2DM was not associated with higher prevalent or incident VF in older men, even after adjustment for BMI and BMD. Higher spine aBMD and vBMD are associated with lower prevalence and incidence of VF in T2DM as well as nondiabetic men. © 2017 American Society for Bone and Mineral Research.     

Characteristics of regional bone quality in cervical vertebrae considering BMD: Determining a safe trajectory for cervical pedicle screw fixation

This study aimed to report the mechanical strength and characteristics of the lateral mass and pedicle considering BMD for the safe insertion of pedicle screws in the subaxial cervical level. We evaluated BMD and Hounsfield unit (HU) values of cortical bones at the lateral mass and pedicle of C3‐7 from CT images in 99 patients. Patients were divided into three groups (Group A, T‐score ≥ ?1; Group B, ?2.5 < T‐score < ?1.0; Group C, T‐score ≤ ?2.5). The HU numbers of cortical bone in the vertebral canal (medial wall of the lateral mass; cHU), posterior wall of the transverse foramen (fHU), and medial wall, lateral wall, and trabecular area of the pedicle (mHU, lHU, and pHU, respectively) were measured on the CT images in the middle of the pedicle. A mechanical study was also performed to measure cortical bone strength using 10 fresh cadavers. The cHU and mHU values in Group C were higher than lHU and fHU in Groups A and B, and there was a wide gap between the pHU value and other areas. The penetrating force also had a close correlation with HU number. The mean penetrating force of the medial wall of the lateral mass and the posterior wall of the transverse foramen were 210.08 ± 110.46 and 50.51 ± 46.09 N, respectively. The cortical bones in the vertebral canal and medial wall of the pedicle were stronger than the lateral wall and the trabecular area. The cHU and mHU in the osteoporotic group were higher than fHU and pHU in the normal group. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:217–223, 2018.

     

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.     

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。     

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