Serum Phosphate Is Associated With Fracture Risk: The Rotterdam Study and MrOS.

Extreme phosphate levels (P) have been associated with mineralization defects and increased fracture risk. Whether P within normal range is related to bone health in the general population is not well understood. To investigate the association of P with bone mineral density (BMD) and fracture risk, we assessed two population-based cohorts: the Dutch Rotterdam Study (RS-I, RS-II, RS-III; n = 6791) and the US Osteoporotic Fractures in Men (MrOS; n = 5425) study.

A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus.

Background: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.

Aim: To identify CNVs associated with osteoporotic bone fracture risk.

High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: the Rotterdam Study.

Objective: Individuals with type 2 diabetes have increased fracture risk despite higher bone mineral density (BMD). Our aim was to examine the influence of glucose control on skeletal complications.

Research Design And Methods: Data of 4,135 participants of the Rotterdam Study, a prospective population-based cohort, were available (mean follow-up 12.

Mild hyponatremia as a risk factor for fractures: the Rotterdam Study.

Recent studies suggest that mild hyponatremia is associated with fractures, but prospective studies are lacking. We studied whether hyponatremia is associated with fractures, falls, and/or bone mineral density (BMD). A total of 5208 elderly subjects with serum sodium assessed at baseline were included from the prospective population-based Rotterdam Study.

Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis.

Background: The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis.

Methods: In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively.

An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits.

Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits.

Interactions between dietary vitamin E intake and SIRT1 genetic variation influence body mass index.

Background: Genetic variation in SIRT1 has been associated with body mass index (BMI) and risk of obesity. SIRT1 may be influenced by diet.

Objective: We studied the gene-diet interaction on BMI at the SIRT1 locus.

The T-13910C polymorphism in the lactase phlorizin hydrolase gene is associated with differences in serum calcium levels and calcium intake.

The C-variant of a T-13910C polymorphism (rs4988235; NT_022135.15:g.25316568G > A) upstream of the lactase phlorizin hydrolase (LPH) gene causes lactose intolerance.

A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22.

Objective: To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study.

Methods: We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2 OA phenotypes were analyzed in 14,938 OA cases and approximately 39,000 controls.

Vitamin D receptor: a new risk marker for clinical restenosis after percutaneous coronary intervention.

Objective: Restenosis is the main drawback of percutaneous coronary intervention (PCI). Inherited factors may explain part of the risk of restenosis. Recently, the vitamin D receptor (VDR) has been shown to be involved not only in bone metabolism but also in modulating immune responses and cell proliferation.

The role of body mass index, insulin, and adiponectin in the relation between fat distribution and bone mineral density.

Despite the positive association between body mass index (BMI) and bone mineral density (BMD) and content (BMC), the role of fat distribution in BMD/BMC remains unclear. We examined relationships between BMD/BMC and various measurements of fat distribution and studied the role of BMI, insulin, and adiponectin in these relations. Using a cross-sectional investigation of 2631 participants from the Erasmus Rucphen Family study, we studied associations between BMD (using dual-energy X-ray absorptiometry (DXA]) at the hip, lumbar spine, total body (BMD and BMC), and fat distribution by the waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and DXA-based trunk-to-leg fat ratio and android-to-gynoid fat ratio.

Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture.

Background: Osteoporosis is a highly heritable trait. Many candidate genes have been proposed as being involved in regulating bone mineral density (BMD). Few of these findings have been replicated in independent studies.

Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.

Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.

SIRT1 genetic variation is related to BMI and risk of obesity.

Objective: SIRT1 has pleiotropic metabolic functions. We investigated whether SIRT1 genetic variation is associated with obesity.

Research Design And Methods: In 6,251 elderly subjects from the prospective, population-based Rotterdam Study, three single nucleotide polymorphisms (SNPs) in the SIRT1 gene were studied in relation to BMI and risk of obesity (BMI > or =30 kg/m(2)) and prospectively with BMI change after 6.

Vitamin D status, bone mineral density, and the development of radiographic osteoarthritis of the knee: The Rotterdam Study.

Objective: To study the association between baseline vitamin D status, bone mineral density (BMD), and the development of radiographic osteoarthritis (ROA) of the knee in a large population-based cohort of men and women.

Methods: A sample of 1248 subjects (728 women and 520 men) was drawn from the Rotterdam Study, a prospective population-based cohort study of the elderly. At baseline, vitamin D dietary intake was determined, and BMD and 25-hydroxy vitamin D (25(OH)D) serum levels were measured.

Osmomediated natriuresis in humans: the role of vasopressin and tubular calcium sensing.

Background: The aim was to investigate the unknown mechanism of osmomediated natriuresis. This is the phenomenon by which hypertonic saline (HS) produces a larger natriuresis than isotonic saline (IS), despite the same sodium content.

Methods: Seven healthy volunteers first received HS and then IS (both 3.

Vitamin D binding protein genotype and osteoporosis.

Osteoporosis is a bone disease leading to an increased fracture risk. It is considered a complex multifactorial genetic disorder with interaction of environmental and genetic factors. As a candidate gene for osteoporosis, we studied vitamin D binding protein (DBP, or group-specific component, Gc), which binds to and transports vitamin D to target tissues to maintain calcium homeostasis through the vitamin D endocrine system.

Loci at chromosomes 13, 19 and 20 influence age at natural menopause.

We conducted a genome-wide association study for age at natural menopause in 2,979 European women and identified six SNPs in three loci associated with age at natural menopause: chromosome 19q13.4 (rs1172822; -0.4 year per T allele (39%); P = 6.

Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size.

Recent genome-wide (GW) scans have identified several independent loci affecting human stature, but their contribution through the different skeletal components of height is still poorly understood. We carried out a genome-wide scan in 12,611 participants, followed by replication in an additional 7,187 individuals, and identified 17 genomic regions with GW-significant association with height. Of these, two are entirely novel (rs11809207 in CATSPER4, combined P-value = 6.

SIRT1 genetic variation and mortality in type 2 diabetes: interaction with smoking and dietary niacin.

SIRT1 protects cells against oxidative stress and aging. Its activity may be modulated by dietary niacin (vitamin B3) intake. We studied the association of SIRT1 genetic variation with mortality in subjects with increased oxidative stress (type 2 diabetes and smokers) in relation to dietary niacin.

A simple risk score for the assessment of absolute fracture risk in general practice based on two longitudinal studies.

The aim of this prospective study was to develop a risk score, based on putative risk factors in current guidelines, which can be used to identify women at high risk of fractures in general practice. The study sample included 4157 women >/=60 yr of age (mean +/- SD: 74.1 +/- 9.

The interleukin-6-174 G/C promoter polymorphism and arterial stiffness; the Rotterdam Study.

Arterial stiffness normally increases with age and has been established as a precursor of cardiovascular disease. Interleukin-6 is a pleiotropic inflammatory cytokine with an important role in the inflammatory cascade, such as up-regulation of C-reactive protein (CRP). The interleukin-6-174-G/C promoter polymorphism appears to influence levels of inflammatory markers, which have been shown to be associated with arterial stiffness.