Rescuing Loading Induced Bone Formation at Senescence

The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential

Anemia in relation to body mass index and waist circumference among Chinese women

Extent: 3 p.BACKGROUND: This study aimed to investigate the relationship of anemia and body mass index among adult women in Jiangsu Province, China. Data were collected in a sub-national cross-sectional survey, and 1,537 women aged 20 years and above were included in the analyses. Subjects were classified by body mass index (BMI) categories as underweight, normal weight, overweight and obese according to the Chinese standard. Central obesity was defined as a waist circumference ≥ 80 cm. Anemia was defined as hemoglobin concentration < 12 g/dl. Prevalence ratios (PRs) of the relationship between anemia and BMI or waist circumference were calculated using Poisson regression. FINDINGS: Overall, 31.1% of the Chinese women were anemic. The prevalence of overweight, obesity and central obesity was 34.2%, 5.8% and 36.2%, respectively. The obese group had the highest concentrations of haemoglobin compared with other BMI groups. After adjustment for confounders, overweight and obese women had a lower PR for anemia (PR: 0.72, 95% CI: 0.62-0.89; PR: 0.59, 95% CI: 0.43-0.79). Central obesity was inversely associated with anemia. CONCLUSION: In this Chinese population, women with overweight/obesity or central obesity were less likely to be anemic as compared to normal weight women. No measures are required currently to target anemia specifically for overweight and obese people in China.Yu Qin, Alida Melse-Boonstra, Xiaoqun Pan, Baojun Yuan, Yue Dai, Jinkou Zhao, Michael B. Zimmermann, Frans J. Kok, Minghao Zhou and Zumin Sh