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Vanderschueren D.,Catholic University of Leuven | Laurent M.R.,Gerontology and Geriatrics | Laurent M.R.,Laboratory of Molecular Endocrinology | Laurent M.R.,Catholic University of Leuven | And 7 more authors.
Endocrine Reviews | Year: 2014

Sex steroids are chief regulators of gender differences in the skeleton, and male gender is one of the strongest protective factors against osteoporotic fractures. This advantage in bone strength relies mainly on greater cortical bone expansion during pubertal peak bone mass acquisition and superior skeletal maintenance during aging. During both these phases, estrogens acting via estrogen receptor-α in osteoblast lineage cells are crucial for male cortical and trabecular bone, as evident from conditional genetic mouse models, epidemiological studies, rare genetic conditions, genome-wide meta-analyses, and recent interventional trials. Genetic mouse models have also demonstrated a direct role for androgens independent of aromatization on trabecular bone via the androgen receptor in osteoblasts and osteocytes, although the target cell for their key effects on periosteal bone formation remains elusive. Low serum estradiol predicts incident fractures, but the highest risk occurs in men with additionally low T and high SHBG. Still, the possible clinical utility of serum sex steroids for fracture prediction is unknown. It is likely that sex steroid actions on male bone metabolism rely also on extraskeletal mechanisms and cross talk with other signaling pathways. We propose that estrogens influence fracture risk in aging men via direct effects on bone, whereas androgens exert an additional antifracture effect mainly via extraskeletal parameters such as muscle mass and propensity to fall. Given the demographic trends of increased longevity and consequent rise of osteoporosis, an increased understanding of how sex steroids influence male bone health remains a high research priority. © 2014 by the Endocrine Society.


Willems J.M.,Gerontology and Geriatrics | Den Elzen W.P.J.,Public Health and Primary Care | Vlasveld L.T.,Hematology | Vlasveld L.T.,Bronovo Hospital | And 5 more authors.
Age and Ageing | Year: 2012

Background: in older persons, anaemia is associated with a number of unfavourable outcomes. In approximately 30% of older persons with anaemia, the cause of the anaemia is unexplained. We assessed the clinical differences between subjects with explained and unexplained anaemia and investigated whether these subjects have different mortality patterns compared with subjects without anaemia. Design: observational prospective follow-up study. Setting: the Leiden 85-plus study.Participants: four hundred and ninety-one persons aged 86 years.Methods: the study population was divided in three groups: (i) no anaemia (reference group, n = 377), (ii) explained anaemia (iron deficiency, folate deficiency, vitamin B12 deficiency, signs of myelodysplastic syndrome or renal failure, n = 74) and (iii) unexplained anaemia, (n = 40). Mortality risks were estimated with Cox-proportional hazard models. Results: haemoglobin levels were significantly lower in subjects with explained anaemia than in subjects with unexplained anaemia (P < 0.01). An increased risk for mortality was observed in subjects with explained anaemia [HR: 1.93 (95% CI: 1.47-2.52), P < 0.001], but not in subjects with unexplained anaemia [HR: 1.19 (95% CI: 0.85-1.69), P = 0.31]. Adjusted analyses (sex, co-morbidity, MMSE, institutionalised and smoking) did not change the observed associations for both explained and unexplained anaemic subjects.Conclusion: older subjects with unexplained anaemia had similar survival compared with non-anaemic subjects. Increased mortality risks were observed in subjects with explained anaemia compared with non-anaemic subjects. © The Author 2012. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.


Sala M.,Leiden University | de Roos A.,Leiden University | Blauw G.J.,Gerontology and Geriatrics | Middelkoop H.A.M.,Clinical Neuropsychology | And 9 more authors.
BMC Neurology | Year: 2015

Background: The purpose of this study is to investigate whether changes in brain microstructure, detected by magnetization transfer imaging, are associated with cognition in older subjects at increased risk for vascular disease. Methods: One hundred ninety three nondemented subjects (105 men, mean age 77 ± 3 years) from the Prospective Study of Pravastatin in the Elderly at Risk were included. To assess cross-sectional associations between magnetization transfer ratio (MTR) peak height and cognitive test scores, general linear model multivariate analysis was performed. Models were adjusted for age, sex, education level, vascular risk factors, individual white matter lesion volume, and brain atrophy. A repeated measures general linear model was used to investigate whether MTR peak height relates to cognitive test performance at baseline and 3.3-year follow-up. Results: Cross-sectionally, MTR peak height was associated with performance on the STROOP test (unstandardized β = -0.27, p = 0.045), delayed Picture Word Learning (PWL) test (β = 0.48, p = 0.007), and the Letter Digit Coding test (β = 1.1, p = 0.006). Repeated measures general linear model analysis showed that individuals with low MTR peak height at baseline performed worse on the STROOP test compared to subjects with intermediate MTR peak height (mean time to complete the test at baseline and follow-up, lower versus middle tertile of MTR peak height: 61.6 versus 52.7 s, p = 0.019) or compared to subjects with high MTR peak height (p = 0.046). Similarly, low MTR peak height was associated with worse performance on the immediate (lower versus middle tertile, p = 0.023; lower versus higher tertile, p = 0.032) and delayed PWL test (lower versus middle, p = 0.004; lower versus higher, p = 0.012) at baseline and follow-up testing. Conclusions: MTR peak height is associated with cognitive function in older subjects at increased risk for vascular disease. © 2015 Sala et al.


Bastiaannet E.,Leiden University | Portielje J.E.A.,HAGA Hospital | Van De Velde C.J.H.,Leiden University | De Craen A.J.M.,Gerontology and Geriatrics | And 7 more authors.
Oncologist | Year: 2011

Back ground. The number of elderly women with breast cancer is increasing and will become a major health concern. However, little is known about the optimal treatment for this age group. The aim of this study was to describe time trends for the overall Dutch breast cancer cohort with an emphasis on differences between young and elderly patients. Methods. All adult female patients diagnosed in 1995- 2005 were selected from the Netherlands Cancer Registry. Relative excess risks for death (adjusted for stage, histology, treatment, and grade) were estimated using a multivariate generalized linear model with a Poisson distribution, based on collapsed relative survival data, using exact survival times. Results. Overall, 127,805 patients were included. Treatment of patients aged ≥75 years changed significantly over time: they received less surgery, more adjuvant hormonal treatment and chemotherapy, and more hormonal treatment without surgery. In contrast to younger patients, the relative survival did not improve significantly over time for elderly patients. With increasing age, the observed- expected death ratio decreased to almost 1.0. Conclusion. Survival for elderly patients with breast cancer did not improve significantly. Observed- expected death ratios in the elderly are close to 1, indicating that excess mortality is low. Elderly patients with breast cancer have a higher risk for over treatment and under treatment, with a delicate therapeutic balance between breast cancer survival gain and potential toxicities. To improve breast cancer survival in the elderly, a critical reappraisal is needed of costs and benefits of hormonal as well as other treatments, and better selection of patients who can benefit from available therapies is warranted. The Oncologist 2011. © AlphaMed Press.


PubMed | Gerontology and Geriatrics
Type: Journal Article | Journal: Age and ageing | Year: 2012

in older persons, anaemia is associated with a number of unfavourable outcomes. In approximately 30% of older persons with anaemia, the cause of the anaemia is unexplained. We assessed the clinical differences between subjects with explained and unexplained anaemia and investigated whether these subjects have different mortality patterns compared with subjects without anaemia.observational prospective follow-up study.the Leiden 85-plus study.four hundred and ninety-one persons aged 86 years.the study population was divided in three groups: (i) no anaemia (reference group, n=377), (ii) explained anaemia (iron deficiency, folate deficiency, vitamin B12 deficiency, signs of myelodysplastic syndrome or renal failure, n=74) and (iii) unexplained anaemia, (n=40). Mortality risks were estimated with Cox-proportional hazard models.haemoglobin levels were significantly lower in subjects with explained anaemia than in subjects with unexplained anaemia (P<0.01). An increased risk for mortality was observed in subjects with explained anaemia [HR: 1.93 (95% CI: 1.47-2.52), P<0.001], but not in subjects with unexplained anaemia [HR: 1.19 (95% CI: 0.85-1.69), P=0.31]. Adjusted analyses (sex, co-morbidity, MMSE, institutionalised and smoking) did not change the observed associations for both explained and unexplained anaemic subjects.older subjects with unexplained anaemia had similar survival compared with non-anaemic subjects. Increased mortality risks were observed in subjects with explained anaemia compared with non-anaemic subjects.


PubMed | Leiden University, Clinical Neuropsychology and Gerontology and Geriatrics
Type: | Journal: BMC neurology | Year: 2015

The purpose of this study is to investigate whether changes in brain microstructure, detected by magnetization transfer imaging, are associated with cognition in older subjects at increased risk for vascular disease.One hundred ninety three nondemented subjects (105 men, mean age 773years) from the Prospective Study of Pravastatin in the Elderly at Risk were included. To assess cross-sectional associations between magnetization transfer ratio (MTR) peak height and cognitive test scores, general linear model multivariate analysis was performed. Models were adjusted for age, sex, education level, vascular risk factors, individual white matter lesion volume, and brain atrophy. A repeated measures general linear model was used to investigate whether MTR peak height relates to cognitive test performance at baseline and 3.3-year follow-up.Cross-sectionally, MTR peak height was associated with performance on the STROOP test (unstandardized = -0.27, p=0.045), delayed Picture Word Learning (PWL) test (=0.48, p=0.007), and the Letter Digit Coding test (=1.1, p=0.006). Repeated measures general linear model analysis showed that individuals with low MTR peak height at baseline performed worse on the STROOP test compared to subjects with intermediate MTR peak height (mean time to complete the test at baseline and follow-up, lower versus middle tertile of MTR peak height: 61.6 versus 52.7s, p=0.019) or compared to subjects with high MTR peak height (p=0.046). Similarly, low MTR peak height was associated with worse performance on the immediate (lower versus middle tertile, p=0.023; lower versus higher tertile, p=0.032) and delayed PWL test (lower versus middle, p=0.004; lower versus higher, p=0.012) at baseline and follow-up testing.MTR peak height is associated with cognitive function in older subjects at increased risk for vascular disease.

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