Paul Lips

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (230)1385.32 Total impact

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    ABSTRACT: B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 μg) and folic acid (400 μg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (–1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. ClinicalTrials.gov Identifier: NCT00696514
    No preview · Article · Jan 2016 · Vascular Medicine
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    ABSTRACT: Background: Although vitamin D may have both protective and symptomatic effects in Parkinson's disease (PD), the evidence is scarce and not well understood. Also, 25-hydroxyvitamin D (vitamin D) is suggested to play a neuroprotective and neurotrophic role in the brain. Therefore, this review investigates the relationship between vitamin D and PD. Objective: Investigate the evidence for a relationship between vitamin D and PD by summarizing observational and interventional studies in humans, as well as relevant experimental studies. Methods: A systematic search was made in the Medline, Cochrane and Embase databases (from inception to March 2014). All identified titles were independently evaluated by two reviewers. Articles were selected based on the presence of PD-related outcome data. Included were observational studies (including genetic studies) and interventional studies in humans, as well as relevant animal studies. Results: A total of 20 studies (14 observational, 1 interventional and 5 rodent studies) were selected for analysis. Eight observational studies showed that serum 25(OH) D levels tend to be low in PD. One observational study indicated that low serum 25(OH) D may worsen automatic postural responses and one interventional study suggested that vitamin D supplementation can prevent worsening (based on the Hoehn and Yahr rating scale). Studies in rodent models of PD showed a protective effect of vitamin D treatment on dopaminergic neurons in the substantia nigra. Results of genetic studies on the association between vitamin D receptor polymorphisms and the risk of PD were contradictory. Conclusion: The literature supports possible protective and symptomatic effects of vitamin D in PD. However, more observational and interventional studies in humans are needed to confirm and further elucidate the suggested beneficial effect of vitamin D on PD.
    No preview · Article · Jan 2016
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    ABSTRACT: Observational studies suggest that low concentrations of serum 25-hydroxyvitamin D (25(OH)D) and high concentrations of parathyroid hormone (PTH) are associated with a higher risk of mortality. The aim of this study was to examine whether 25(OH)D and PTH concentrations are independently associated with overall and disease-specific (cardiovascular and cancer-related) mortality in a large, prospective population-based cohort of older adults. Data from 1317 men and women (65-85 years) of the Longitudinal Aging Study Amsterdam were used. Cox proportional hazard analyses were used to examine whether 25(OH)D and PTH at baseline were associated with overall mortality (with a follow-up of 18 years) and disease-specific mortality (with a follow-up of 13 years). Compared to persons in the reference category of ≥75 nmol/L, persons with serum 25(OH)D <25 nmol/L (HR 1.46; 95% CI: 1.12-1.91) and 25-49.9 nmol/L (HR 1.24; 95%CI: 1.01-1.53) had a significantly higher risk of overall mortality, as well as men with baseline PTH concentrations ≥7pmol/L (HR 2.54 (95% CI: 1.58-4.08), compared to the reference category of <2.33pmol/L. The relationship of 25(OH)D with overall mortality was partly mediated by PTH. Furthermore, men with PTH concentrations of ≥7pmol/L (HR 3.22; 95% CI: 1.40-7.42) had a higher risk of cardiovascular mortality, compared to the reference category. No significant associations of 25(OH)D or PTH with cancer-related mortality were observed. Both 25(OH)D and PTH should be considered as important health markers.
    No preview · Article · Dec 2015 · The Journal of steroid biochemistry and molecular biology
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    ABSTRACT: Introduction: Vitamin D is essential for bone health since it stimulates the intestinal absorption of calcium and phosphorus from the gut, both necessary for bone mineralization. However, vitamin D deficiency is highly prevalent among several non-Western immigrant populations in the Netherlands. To date, there are no data available of the vitamin D status in the Chinese population residing in the Netherlands. Therefore, an observational study was performed to determine 25-hydroxyvitamin D (25OH)D concentrations and to assess potential determinants of low vitamin D status. Methods: Subjects, aged 18 years and older, with a Chinese background and residing in the Netherlands were invited to participate in the study. A questionnaire was used to assess general characteristics and lifestyle habits. Fasting blood samples were obtained in March 2014 to measure serum 25(OH)D concentration, and analysed by liquid chromatography tandem mass spectrometry. Results: 418 subjects participated in the study, 104 men and 314 women. The mean age for both men and women was 56 years. Serum 25(OH)D concentration <50 nmol/L was more prevalent in men than in women (67.9% and 53.1%, respectively; p=0.008). The percentage of serum 25(OH)D concentration<25nmol/L in men and women was 5.8% and 10.9%, respectively. Multiple logistic regression analysis, adjusted for age and gender, revealed that non-use of vitamin D supplements and fewer days per week of physical activity were significant predictors of serum 25(OH)D levels below 50nmol/L. Conclusions: Within the Chinese population living in the Netherlands, serum 25(OH)D concentration was below 50nmol/L in 68% of men and 53% of women. Use of vitamin D supplements by Chinese people in the Netherlands was highly protective against low 25(OH)D levels.
    No preview · Article · Dec 2015 · The Journal of steroid biochemistry and molecular biology
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    ABSTRACT: Background: Depressive symptoms and decreased physical functioning are interrelated conditions and common in older persons, causing significant individual and societal burden. Evidence suggests that vitamin D supplementation may be beneficial for both mental and physical functioning. However, previous randomized controlled trials have yielded inconsistent results and often had suboptimal designs. This study examines the effect of vitamin D supplementation on both depressive symptoms and physical functioning in a high-risk population of older persons with low vitamin D status. Methods/design: The D-Vitaal study is a randomized, double-blind, placebo-controlled trial investigating the effects of a daily dose of 1200 IU vitamin D3 versus placebo for one year on depressive symptoms and physical functioning (primary outcomes) in older adults. Participants (N = 155, age 60-80 years) were recruited from the general population. Eligibility criteria included the presence of depressive symptoms, ≥1 functional limitation and serum 25-hydroxyvitamin D levels between 15 and 50/70 nmol/L (depending on season). Secondary outcomes include incidence of major depressive disorder, anxiety symptoms, health-related quality of life, cognitive function and cost-effectiveness of the intervention. Discussion: With this study, we aim to elucidate the effects of vitamin D supplementation on depressive symptoms and physical functioning in older persons who are at high risk of developing more substantial mental and physical problems. If effective, vitamin D supplementation can be a preventive intervention strategy that is easy to implement in the primary care setting. Trial registration: Netherlands Trial Register NTR3845 . Registered 6 February 2013.
    Full-text · Article · Dec 2015 · BMC Geriatrics
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    ABSTRACT: The Department of Nutrition for Health and Development of the World Health Organization (WHO) in collaboration with the Executive Committee of the 18th Vitamin D Workshop (VDW), organised a joint symposium on the prevention and consequences of vitamin D deficiency in pregnant women and children, convening experts on vitamin D, clinicians and policy-makers. The overall aim was to identify priority areas for research and to discuss the need for global options for policy, with a focus on the prevention of rickets in infants and children and vitamin D deficiency in pregnant women. The scope and purpose were (i) to present the WHO research strategy for health, addressing vitamin D-related public health problems and the process for the development of evidence-informed guidelines in general and how vitamin D interventions in diverse populations could be prioritised; (ii) to provide an overview of vitamin D status in children and pregnant and lactating women across the world; (iii) to review the health risks associated with vitamin D deficiency in children and in pregnant women and their offspring; (iv) to understand the aetiology of vitamin D deficiency in pregnant women and children; (v) to identify and interpret biomarkers to assess vitamin D status and to consider possible clinical and biochemical screening tools for determining the prevalence of nutritional rickets in at risk groups or communities; and (vi) to provide an overview of policies and recommendations on vitamin D across the world. The format of the symposium was a composite of comprehensive scientific presentations and a panel debate with international experts on WHO guidelines, nutritional rickets, nutritional policy and consequences of vitamin D deficiency during pregnancy. This paper summarizes the content and outcomes of the panel debate.
    No preview · Article · Nov 2015 · The Journal of steroid biochemistry and molecular biology
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    ABSTRACT: Advanced glycation endproducts (AGEs) are a heterogeneous group of compounds formed nonenzymatically by glycation and oxidation of proteins. AGEs are suggested as one of the major agents in the pathogenesis and progression of diabetic-associated microvascular and macrovascular complications.
    Full-text · Article · Nov 2015
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    ABSTRACT: Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12-50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 IU vitamin D3, or to placebo with 600 IU vitamin D3. Physical performance (range 0-12) and handgrip strength (kg) were measured at baseline and after 2 years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95 % CI 0.9-1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95 % CI 1.1-1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons >80 years. These effects should be further tested in future studies.
    Full-text · Article · Sep 2015 · Calcified Tissue International
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    ABSTRACT: Background Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties. Vitamin D deficiency is a common problem in patients with COPD. Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients. However, subgroup analyses suggested protective effects in vitamin D deficient patients. Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients. Methods/Design We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study. The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L). Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period. Visits will be performed at baseline, at 6 months and at 12 months after randomisation. Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure. Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken. The primary outcome will be exacerbation rate. Discussion This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients. Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation. Secondly, the immunomodulatory effects of vitamin D on host immune response of COPD patients and underlying mechanisms will be studied. Finally, the effects on physical functioning will be examined. Trial registration This trial is registered in ClinicalTrials.gov, ID number NCT02122627. Date of Registration April 2014.
    Full-text · Article · Sep 2015 · BMC Pulmonary Medicine
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    ABSTRACT: Background/objectives: The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults. Methods/subjects: Serum 25-hydroxyvitamin D (25(OH)D) was measured in 2857 adults aged ≥65 years. Sun exposure was assessed with a structured questionnaire (n=1012), vitamin D intake using a Food Frequency Questionnaire (n=596), and data on genetic variation that may affect 25(OH)D status was obtained for 4 genes, DHCR7 (rs12785878), CYP2R1 (rs10741657), GC (rs2282679), and CYP24A1 (rs6013897) (n=2530). Results: Serum 25(OH)D concentrations <50nmol/L were observed in 45% of the population; only 6% of these participants used vitamin D supplements. Sun exposure (being outside daily during summer: 66±25nmol/L vs not being outside daily during summer: 58±27nmol/L, P=0.02) and vitamin D intake (per unit μg/day during winter/spring: 3.1±0.75nmol/L, P<0.0001) were associated with higher 25(OH)D concentrations. Major allele carriers of SNPs related to DHCR7, CYP24A1, and GC, as well as CYP2R1 minor allele carriers had the highest 25(OH)D concentrations. Together, sun (R(2)=0.29), vitamin D intake (R(2)=0.24), and genes (R(2)=0.28) explained 35% (R(2)=0.35) of the variation in 25(OH)D concentrations during summer/autumn period, when adjusted for age, sex, BMI, education, alcohol consumption, smoking, physical activity, and self-rated health status (n=185). Conclusion: The investigated determinants explained 35% of 25(OH)D status. Of the three main determinants under study, sun exposure still appeared to be an important determinant of serum 25(OH)D in older individuals, closely followed by genes, and vitamin D intake. Given the low frequency of vitamin D supplement use in this population, promoting supplement use may be an inexpensive, easy, and effective strategy to fight vitamin D deficiency.
    No preview · Article · Aug 2015 · The Journal of steroid biochemistry and molecular biology
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    ABSTRACT: Elevated systemic levels of pro-inflammatory cytokines are thought to be involved in the pathogenesis of osteoporosis. Our objective was to investigate whether low grade systemic inflammation was associated with bone markers, bone quality, bone mass and fracture risk in a population of older persons. Serum interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were measured in 1287 participants of the Longitudinal Aging Study Amsterdam (LASA), a population based study in a representative sample of older men and women (age 76±6.7years). Bone quality was measured by quantitative ultrasound measurements (QUS) at baseline and after 3years at the calcaneus, and bone mineral density was measured by dual-energy x-ray absorptiometry (DXA) at the spine and hip in a subpopulation. Furthermore, the bone markers osteocalcin (OC) and urinary excretion of deoxypyridinoline (DPD) were determined. Incident clinical fractures were recorded during 6years of follow-up. Multivariable regression analyses revealed higher IL-6 and ESR levels were associated with lower quantitative ultrasound values in older men (β=-0.98; 95%CI -57.72- -6.42, p<0.05) and (β=-0.221; 95%CI -15.39- -3.27, p<0.05) respectively at baseline, but not in women. No significant associations were found between inflammatory markers and bone markers, bone loss at the spine or hips, fracture rate or time to fracture. Elevated inflammatory markers are associated with impaired bone quality in older men, but not in women. No associations were found with the risk for fractures. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jul 2015 · Bone
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    ABSTRACT: Hyperhomocysteinemia is an important cardiovascular risk indicator in the oldest old, and is associated with elevated arterial stiffness in this age group. Since several intervention trials reported a lack of benefit of B-vitamin supplementation on cardiovascular outcomes, we aimed to investigate the effect of B-vitamin supplementation on arterial stiffness and atherosclerosis in hyperhomocysteinemic elderly patients. The B-PROOF study is a double-blind, randomized controlled trial, including 2919 elderly aged at least 65 years, with hyperhomocysteinemia (12-50 μmol/l), treated with B-vitamins (500 μg vitamin B12 and 400 μg folic acid) or placebo for 2 years. In a subgroup (n = 569), the effect of B-vitamins on pulse wave velocity (PWV) was investigated as a measurement of arterial stiffness. To measure atherosclerosis, carotid intima-media thickness (IMT) measures had been used. Incidents of cardiovascular and cerebrovascular events were determined via structured questionnaires, and blood pressure was also measured. Compared to placebo, B-vitamin supplementation lowered serum homocysteine by 3.6 μmol/l (P < 0.001). Analysis of covariance showed no effect of supplementation on PWV levels, and this was not different for patients without increased arterial stiffness at baseline. Furthermore, no effect on carotid IMT was observed. Vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly patients have no effect on PWV or carotid IMT. Further research will still be necessary to unravel the effects and pathways of homocysteine-lowering treatment on cardiovascular outcomes.
    Full-text · Article · Jun 2015 · Journal of Hypertension

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  • No preview · Article · May 2015
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    ABSTRACT: Introduction Patients with differentiated thyroid cancer (DTC) are treated with (near)-total thyroidectomy followed by remnant ablation. Optimal radioiodine-131 (131I) uptake is achieved by withholding thyroid hormone (THW), pretreatment with recombinant human Thyrotropin Stimulating Hormone (rhTSH) is an alternative. Six randomized trials have been published comparing THW and rhTSH, however comparison is difficult because an uniform definition of ablation success is lacking. Using a strict definition, we performed an observational study aiming to determine the efficacy of rhTSH as preparation for remnant ablation. Patients and Methods Adult DTC patients with, tumor stage T1b to T3, Nx, N0 and N1, M0 were included in a prospective multicenter observational study with a fully sequential design, using a stopping rule. All patients received remnant ablation with 131I using rhTSH. Ablation success was defined as no visible uptake in the original thyroid bed on a rhTSH stimulated 150 MBq 131I whole body scan (WBS) 9 months after remnant ablation, or no visible uptake in the original thyroid bed on a post therapeutic WBS when a second high dose was necessary. Results After interim analysis of the first 8 patients, the failure rate was estimated to be 69% (90% confidence interval (CI) 20-86%) and the inclusion of new patients had to be stopped. Final analysis resulted in an ablation success in 11 out of 17 patients (65%, 95% CI 38-86%). Conclusion According to this study, the efficacy of rhTSH in the preparation of 131I ablation therapy is inferior, when using a strict definition of ablation success. The current lack of agreement as to the definition of successful remnant ablation, makes comparison between different ablation strategies difficult. Our results point to the need for an international consensus on the definition of ablation success, not only in routine patient’s care but also for scientific reasons. Trial Registration Dutch Trial Registration NTR2395
    Full-text · Article · Mar 2015 · PLoS ONE
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    ABSTRACT: Beyond the established roles of vitamin D in bone and mineral homeostasis, we are becoming increasingly aware of its diverse effects in skeletal muscle. Subjects with severe vitamin D deficiency or mutations of the vitamin D receptor develop generalized atrophy of muscle and bone, suggesting coordinated effects of vitamin D in musculoskeletal physiology. At a mechanistic level, vitamin D exerts wide-ranging effects in muscle and bone calcium handling, differentiation and development. Vitamin D also modulates muscle and bone-derived hormones, facilitating cross-talk between these tissues. In this review, we discuss emerging evidence that vitamin D regulates bone and muscle in a direct, integrated fashion, positioning the vitamin D pathway as a potential therapeutic target for musculoskeletal diseases. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Mar 2015 · Bone
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    ABSTRACT: Objectives: First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance. Design, setting, and participants: Associations were studied using cross-sectional data of 776 (3 domains) up to 2722 (1 domain) Dutch community-dwelling older adults, aged 65 years or older. Measurements: Serum 25(OH)D, plasma glucose, and insulin concentrations were obtained. Cognitive performance was assessed with an extensive cognitive test battery. Prevalence ratios (PRs) were calculated to quantify the association between 25(OH)D and cognition; poor performance was defined as the worst 10% of the distribution of the cognitive scores. Results: The overall median MMSE score was 29 (IQR 28-30). Higher serum 25(OH)D was associated with better attention and working memory, PR 0.50 (95% CI 0.29-0.84) for the third serum 25(OH)D tertile, indicating a 50% lower probability of being a poor performer than participants in the lowest tertile. Beneficial trends were shown for 25(OH)D with executive function and episodic memory. Serum 25(OH)D was not associated with plasma glucose or insulin. Plasma insulin only modified the association between serum 25(OH)D and executive function (P for interaction: .001), suggesting that the improvement in executive function with high 25(OH)D concentrations is stronger in participants with high plasma insulin concentrations compared with those with low plasma insulin concentrations. Conclusion: Higher 25(OH)D concentrations significantly associated with better attention and working memory performance. This study does not demonstrate an interplay between serum 25(OH)D and glucose homeostasis in the association with cognitive performance.
    No preview · Article · Mar 2015 · Journal of the American Medical Directors Association

Publication Stats

17k Citations
1,385.32 Total Impact Points

Institutions

  • 2001-2015
    • VU University Medical Center
      • • Department of Internal Medicine
      • • Department of Epidemiology and Biostatistics
      • • Department of Endocrinology
      • • Department of Pediatrics
      Amsterdamo, North Holland, Netherlands
  • 1989-2015
    • VU University Amsterdam
      • • Faculty of Human Movement Sciences
      • • Academic Centre for Dentistry Amsterdam (ACTA)
      • • IHS-Institute of Health Sciences
      • • Department of Nuclear Medicine and PET research
      Amsterdamo, North Holland, Netherlands
  • 1991-2010
    • University of Amsterdam
      • Department of Endocrinology
      Amsterdamo, North Holland, Netherlands
  • 2006
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
    • National Institute on Aging
      Baltimore, Maryland, United States
  • 1991-2001
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Endocrinology and Metabolism
      Amsterdam, North Holland, Netherlands
  • 1988
    • Slotervaart Ziekenhuis Amsterdam
      Amsterdamo, North Holland, Netherlands