G. Bondi

IGF-1, the Cross Road of the Nutritional, Inflammatory and Hormonal Pathways to Frailty

The decline in functional capacity is a heterogeneous phenomenon in the elderly. An accelerated ageing determines a frail status. It results in an increased vulnerability to stressors for decreased physiological reserves. The early identification of a frail status is essential for preventing loss of functional capacity, and its clinical consequences. Frailty and mobility limitation result from an interplay of different pathways including multiple anabolic deficiency, inflammation, oxidative stress, and a poor nutritional status. However, the age-related decline in insulin-like growth factor 1 (IGF-1) bioactivity deserves special attention as it could represent the ideal crossroad of endocrine, inflammatory, and nutritional pathways to frailty. Several minerals, namely magnesium, selenium, and zinc, appear to be important determinants of IGF-1 bioactivity. This review aims to provide an overview of the potential usefulness of nutrients modulating IGF-1 as potential therapeutic targets in the prevention of mobility limitation occurring in frail older subjects.

Use of proton pump inhibitors is associated with lower trabecular bone density in older individuals

Proton pump inhibitors (PPIs) are highly effective in the treatment of upper gastrointestinal acid-related conditions and are fast becoming one of the most frequently prescribed treatments in adult or older persons. Recent data show that long-term use of PPIs in older subjects is associated with important undesirable effects, including a higher risk of osteoporotic fractures. The mechanisms of this association are unclear and the relationship between the use of PPIs and parameters of bone mass and geometry has never been fully explored. This study investigates the relationship between the chronic use of PPIs and the parameters of bone mass (cortical and trabecular bone mineral density - vBMDc and vBMDt) and bone geometry (cortical and trabecular cross sectional area - tCSA and cCSA) in older individuals. The study population consisted of 1038 subjects (452 men and 586 women) 65years or older, selected from the InCHIANTI study, with complete information on computerized tomography performed at tibial level (pQCT) and on medications. Participants were classified as PPI users and nonusers based on self-report of PPI use over the last 15days, with PPI users (36 subjects, 14 men and 22 women) making up 3.4% of the study population (mean age 75.7±7.4years). The relationship between use of PPIs and pQCT bone parameters was tested by multivariate linear regression analysis adjusted for age, sex and several clinical factors and/or statistically confounding variables identified by partial correlation coefficient and Spearman partial rank order correlation coefficients, as appropriate (age, sex, BMI, caloric intake, IGF-1, IL-6, calcium, estradiol, bioavailable testosterone, vitamin D, parathyroid hormone, cross-sectional muscle area, and level of physical activity). PPI users showed age- and sex-adjusted lower vBMDt than nonusers (180.5±54.8 vs. 207.9±59.4, p=0.001). The inverse association between PPI use and vBMDt remained almost unchanged after adjustment for multiple confounders. There was no statistically significant difference in vBMDc, tCSA and cCSA between PPI users and nonusers. In community dwelling older persons, the use of PPIs is inversely associated with vBMDt, an early marker of the osteoporotic process. These findings suggest that PPI use might increase the risk of fractures in older subjects through its detrimental effects on trabecular bone.

Relationship between use of proton pump inhibitors and igf system in older subjects

Objectivesto investigate the effects of proton pump inhibitors (PPIs) on the insulin-like-growth factor 1(IGF-1) system in the elderly.Designcross-sectional.SettingInCHIANTI study.Participants938 older subjects (536 women, 402 men, mean age 75.7±7.4 years).Measurementscomplete data on age, sex, BMI, liver function, medications, dietary intake, IGF-1, IGF-binding protein-1 and -3 (IGFBP-1, IGFBP-3).ResultsParticipants were categorized by PPI use, identifying 903 PPI non users and 35 users. After adjusting for age, male PPI users (107.0 ± 69.6 vs 127.1 ± 55.8, p<0.001) and female PPI users (87.6 ± 29.1 vs 107.6 ± 52.3, p=0.03) had lower IGF-1 levels than non-users. IGFBP-1 levels were similar in the two groups in both sexes. In whole population, after adjustment for age and sex, PPI users had lower IGF-1 levels 81.9 [61.1–113.8] than nonusers 110 [77.8–148.6], p=0.02. After further adjustment for BMI, albumin, liver function, C-reactive protein, Interleukin-6, number of medications, ACE-inhibitors use, caloric intake, protein intake, physical activity, glycemia, and IGFBP-1, the use of PPIs remained significantly and negatively associated with IGF-1 levels (β±SE=−19.60±9.83, p=0.045).ConclusionUse of PPIs was independently and negatively associated with IGF-1 levels.

PP096-SUN: Inverse Relationship Between Carotenoids and Estradiol Levels in Older Women: Implication for Estrogen-Dependent Cancers?

Rationale: The HSCT patients have a tendency to lower serum vitamin D (VD). There is an important role in the regulation of VD and lymphocyte function T. The VD has an immunomodulatory effect that correlates with an increased incidence of Chronic GVHD and may increase mortality in this group of patients. Additionally, serum vitamin D levels are related to bacterial infection, ICU and relapse after HSCT. Objective: Analyse the relationship between disability and serum levels of vitamin D and risk of developing Acute GVHD. Methods: Retrospective study in Oncology and Hematology Department of the Albert Einstein Hospital (HIAE), with 19 patients (10 women, 9 men), adults (>18 years) who underwent HSCT, 42% of allogeneic related, 37% of unrelated allogeneic and 21% haploidential. The mean age was 46 years (±16) and weight 67 kg (±17). Of these patients, 59% had normal body mass index (BMI) (kg/m2), 21% overweight, 5% obese and 16% malnutrition. The exam for measurement of serum vitamin D (25-hydroxyvitamin D) was requested at the time of admission of the patient before the start of HSCT. The results of serum VD were classified into 50 nmol/ml normal. Results: There was a significant and negative correlation between BMI and serum levels of VD (rp = 0.5). 53% of patients had GVHD, but there was no significant relationship of the same with the other variables. There was a trend GVHD in the presence of low serum vitamin D also present in 53% of cases. Conclusion: GVHD is a disease with a high risk for patients undergoing HSCT, having great impact on the quality of life. Overweight and obese patients who have lower levels of VD should be better monitored, as tending to a higher risk of developing this complication.