Vertebral Strength and Estimated Fracture Risk Across the BMI Spectrum in Women

Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor‐of‐risk (Φ), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher Φ reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.vBMD] and cross‐sectional area from quantitative computed tomography [QCT]), vertebral compressive loads, and Φ at L₄ in 176 women (65 anorexia nervosa, 45 lean controls, and 66 obese). Using biomechanical models, applied loads were estimated for: 1) standing; 2) arms flexed 90°, holding 5 kg in each hand (holding); 3) 45° trunk flexion, 5 kg in each hand (lifting); 4) 20° trunk right lateral bend, 10 kg in right hand (bending). We also investigated associations of Int.vBMD and vertebral strength with lean mass (from dual‐energy X‐ray absorptiometry [DXA]) and visceral adipose tissue (VAT, from QCT). Women with anorexia nervosa had lower, whereas obese women had similar, Int.vBMD and estimated vertebral strength compared with controls. Vertebral loads were highest in obesity and lowest in anorexia nervosa for standing, holding, and lifting (p < 0.0001) but were highest in anorexia nervosa for bending (p < 0.02). Obese women had highest Φ for standing and lifting, whereas women with anorexia nervosa had highest Φ for bending (p < 0.0001). Obese and anorexia nervosa subjects had higher Φ for holding than controls (p < 0.03). Int.vBMD and estimated vertebral strength were associated positively with lean mass (R = 0.28 to 0.45, p ≤ 0.0001) in all groups combined and negatively with VAT (R = –[0.36 to 0.38], p < 0.003) within the obese group. Therefore, women with anorexia nervosa had higher estimated vertebral fracture risk (Φ) for holding and bending because of inferior vertebral strength. Despite similar vertebral strength as controls, obese women had higher vertebral fracture risk for standing, holding, and lifting because of higher applied loads from higher body weight. Examining the load‐to‐strength ratio helps explain increased fracture risk in both low‐weight and obese women. © 2015 American Society for Bone and Mineral Research.     

The wear and tear on health: What is the role of occupation?

Health is well known to show a clear gradient by occupation. Although it may appear evident that occupation can affect health, there are multiple possible sources of selection that can generate a strong association, other than simply a causal effect of occupation on health. We link job characteristics to German panel data spanning 29 years to characterize occupations by their physical and psychosocial burden. Employing a dynamic model to control for factors that simultaneously affect health and selection into occupation, we find that selection into occupation accounts for at least 60% of the association. The effects of occupational characteristics such as physical strain and low job control are negative and increase with age: late‐career exposure to 1 year of high physical strain and low job control is comparable to the average health decline from ageing 16 and 6 months, respectively.     

Global malalignment in adolescent idiopathic scoliosis: the axial deformity is the main driver

European Spine Journal - To evaluate the global alignment of non-operated subjects with adolescent idiopathic scoliosis. A total of 254 subjects with AIS and 64 controls underwent low dose biplanar...     

Validation of the archimedes diabetes model

OBJECTIVE: To validate the Archimedes model of diabetes and its complications for a variety of populations, organ systems, treatments, and outcomes. RESEARCH DESIGN AND METHODS: We simulated a variety of randomized controlled trials by repeating in the model the steps taken for the real trials and comparing the results calculated by the model with the results of the trial. Eighteen trials were chosen by an independent advisory committee. Half the trials had been used to help build the model ("internal" or "dependent" validations); the other half had not. Those trials comprise "external" or "independent" validations. RESULTS: A total of 74 validation exercises were conducted involving different treatments and outcomes in the 18 trials. For 71 of the 74 exercises there were no statistically significant differences between the results calculated by the model and the results observed in the trial. Considering only the trials that were never used to help build the model-the independent or external validations-the correlation was r = 0.99. Including all of the exercises, the correlation between the outcomes calculated by the model and the outcomes seen in the trials was r = 0.99. When the absolute differences in outcomes between the control and treatment groups were compared, the correlation coefficient was r = 0.97. CONCLUSIONS: The Archimedes diabetes model is a realistic representation of the anatomy, pathophysiology, treatments, and outcomes pertinent to diabetes and its complications for applications that involve the populations, treatments, outcomes, and health care settings spanned by the trials.     

Earlier intervention in type 2 diabetes: the case for achieving early and sustained glycaemic control

In type 2 diabetes, the onset and progression of complications is significantly delayed by improving glycaemic control. However, the proportion of patients reaching and sustaining guideline recommendations for glycaemic targets remains unacceptably low. Recent clinical trials and predictive physiologically based mathematical simulations (Archimedes model) indicate that benefits can be enhanced with earlier intervention and timely achievement of glycaemic targets. This article reviews the evidence for early intervention, showing that intensive approaches, including earlier introduction of combination therapy, allow more patients to achieve glycaemic targets and hence reduce complications and delay disease progression.     

Effects of Estrogen Replacement on Bone Geometry and Microarchitecture in Adolescent and Young Adult Oligoamenorrheic Athletes: A Randomized Trial

Oligoamenorrheic athletes (OAs) have lower bone mineral density (BMD) and greater impairment of bone microarchitecture, and therefore higher fracture rates compared to eumenorrheic athletes. Although improvements in areal BMD (aBMD; measured by dual-energy X-ray absorptiometry) in OAs have been demonstrated with transdermal estrogen treatment, effects of such treatment on bone microarchitecture are unknown. Here we explore effects of transdermal versus oral estrogen versus no estrogen on bone microarchitecture in OA. Seventy-five OAs (ages 14 to 25 years) were randomized to (i) a 100-μg 17β-estradiol transdermal patch (PATCH) administered continuously with 200 mg cyclic oral micronized progesterone; (ii) a combined 30 μg ethinyl estradiol and 0.15 mg desogestrel pill (PILL); or (iii) no estrogen/progesterone (NONE) and were followed for 12 months. Calcium (≥1200 mg) and vitamin D (800 IU) supplements were provided to all. Bone microarchitecture was assessed using high-resolution peripheral quantitative CT at the distal tibia and radius at baseline and 1 year. At baseline, randomization groups did not differ by age, body mass index, percent body fat, duration of amenorrhea, vitamin D levels, BMD, or bone microarchitecture measurements. After 1 year of treatment, at the distal tibia there were significantly greater increases in total and trabecular volumetric BMD (vBMD), cortical area and thickness, and trabecular number in the PATCH versus PILL groups. Trabecular area decreased significantly in the PATCH group versus the PILL and NONE groups. Less robust differences between groups were seen at the distal radius, where percent change in cortical area and thickness was significantly greater in the PATCH versus PILL and NONE groups, and changes in cortical vBMD were significantly greater in the PATCH versus PILL groups. In conclusion, in young OAs, bone structural parameters show greater improvement after 1 year of treatment with transdermal 17β-estradiol versus ethinyl estradiol–containing pills, particularly at the tibia. © 2019 American Society for Bone and Mineral Research.     

Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase

相似文献