Ling Oei

Erasmus MC | Erasmus MC · Department of Internal Medicine

Background & Objective: Low bone mineral density and dementia commonly co-occur in the elderly, with bone loss accelerating in dementia patients due to physical inactivity and poor nutrition. However, uncertainty persists over the extent to which bone loss already exists prior to the onset of dementia. Therefore, we investigated how dementia risk w...

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE (“GEnomics of MusculoSkeletal Traits translational Network”) Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to c...

Worldwide, there are millions of people who have been diagnosed with osteoporosis, a bone disease that increases the risk of fracture due to low bone mineral density and deterioration of bone architecture. In the US alone, there are approximately ten million men and women diagnosed with osteoporosis and this number is still growing. Diagnosis is ma...

Introduction: Individuals with type 2 diabetes mellitus (T2DM) are at an increased risk of developing fractures, despite higher mean BMI and BMD. Recently, clinically-relevant sub-groups of T2DM have been characterised using biomarkers of glycemic metabolism. Aim: Characterise T2DM sub-groups in a population-based setting and test for differences i...

Purpose of Review The purpose of this review is to summarize the recently published evidence concerning vertebral fracture risk in individuals with diabetes mellitus. Recent Findings Vertebral fracture risk is increased in individuals with T2DM. The presence of vertebral fractures in T2DM is associated with increased non-vertebral fracture risk an...

In this review we discuss skeletal adaptations to the demanding situation of pregnancy and lactation. Calcium demands are increased during pregnancy and lactation, and this is effectuated by a complex series of hormonal changes. The changes in bone structure at the tissue and whole bone level observed during pregnancy and lactation appear to largel...

Objective: We aimed to assess whether individuals with type 2 diabetes (T2D) have increased risk of vertebral fractures (VFs) and to estimate nonvertebral fracture and mortality risk among individuals with both prevalent T2D and VFs. Research design and methods: A systematic PubMed search was performed to identify studies that investigated the r...

Genetic susceptibility, together with old age, female sex, and low bone mineral density (BMD) are amongst the strongest determinants of fracture risk. Tmost recent large-scale genome-wide association study (GWAS) meta-analysis has yielded fifteen loci. This review focuses on the advances in the research of genetic determinants of fracture risk. We...

Until recently there has been little evidence available to validate any method by which to make an accurate diagnosis of an osteoporotic vertebral fractures (OVF) from plain radiographs. In part this reflects a lack of a completely satisfactory “gold standard” but primarily relates to an absence of well‐designed prospective studies in this context....

Background The relation between sex hormone-binding globulin (SHBG) and vertebral fracture (VFx) is unclear. We examined whether SHBG is associated with bone mineral density at lumbar spine (LS-BMD), trabecular bone score (TBS) and prevalent VFx. Methods Data of 6,224 men and women participants in the third visit of the first cohort (I-3) and the...

Objectives To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk. Design Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach. Setting 25 cohorts from Europe, United States, east Asia, and Australia with genome wide g...

Web appendix: Supplementary note and full list of authorship details

Dear Prof. Civitelli, We thank Dr Gilchrist and colleagues for their letter entitled “Osteoporotic vertebral fracture prevalence varies widely” in which they outline their experience with clinical health ontology applied on a shared repository of clinical notes, radiological images and reports. The purpose of their effort is to “assess whether pati...

Fracture incidence needs to be evaluated over time to assess the impact of the enlarging population burden of fractures (due to increase in lifespan) and the efficacy of fracture prevention strategies. Therefore, we aimed to evaluate the association of femoral neck bone mineral density (FN-BMD) measured using dual-energy X-ray absorptiometry (DXA)...

Dear Dr. Civitelli, In discussing such advances, they include spinal morphometry, and specifically refer to and illustrate the Genant semi‐quantitative (GSQ) paradigm,² although also referring to the algorithm‐based qualitative (ABQ) method³ of vertebral evaluation in the diagnosis of osteoporotic vertebral fractures (OVF). Although in its day the...

Objectives To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. Methods Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 contr...

Accurate diagnosis of vertebral osteoporotic fractures is crucial for the identification of individuals at high risk of future fractures. Different methods for radiological assessment of vertebral fractures exist, but a gold standard is lacking. The aim of our study was to estimate statistical measures of agreement and prevalence of osteoporotic ve...

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated wi...

Osteoporosis is characterized by a decreased bone mass and quality resulting in an increased fracture risk. Quantitative imaging methods are critical in the diagnosis and follow-up of treatment effects in osteoporosis. Prior radiographic vertebral fractures and bone mineral density (BMD) as a quantitative parameter derived from dual-energy X-ray ab...

Genome-wide association studies (GWAS) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (N = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associate...

Background: Fracture risk is increased in Type 2 diabetes (T2D) individuals. Bone mineral density (BMD) is inversely associated with fracture risk but paradoxically high in T2D individuals. Trabecular bone score (TBS) reflects bone microarchitecture and predicts fracture risk. Objective: We aimed to compare mean lumbar spine TBS (LS-TBS) and lumbar...

Background: The relation between sex hormone-binding globulin (SHBG) and vertebral fracture (VFx) is unclear. Aim: To examine whether SHBG is associated with bone mineral density at lumbar spine (LS-BMD), trabecular bone score (TBS) and prevalent VFx. Methods: Data of 6224 men and women participants in the third visit of the first cohort (I-3) and...

Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine t...

Our understanding of the genetic control of skeletogenesis and bone remodeling is increasing, and in addition to various nongenetic risk factors, a positive family history confers an increased risk of fracture. Vertebral fractures are the most common osteoporotic fractures and they are often a first manifestation of osteoporosis. This review presen...

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants,...

Our understanding of the genetic control of skeletogenesis and bone remodeling is expanding, and normally, bone resorption and bone formation are well balanced through regulation by hormones, growth factors, and cytokines. Osteoporosis is considered a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissu...

The association between metabolic syndrome (MS) and bone health remains unclear. We aimed to study the association between MS and hip bone geometry (HBG), femoral neck bone mineral density (FN-BMD), and the risk of osteoporosis and incident fractures. Data of 2040 women and 1510 men participants in the third visit (1997–1999) of the Rotterdam Study...

In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8 % in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. This study a...

Signaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms influence receptor function. We show that these polymorphisms are not associated with fracture risk or bone mineral density in the UCP, Rotterdam Study, and GEFOS cohorts. Signaling through the beta-...

Diabetes and osteoporosis are both common diseases with increasing prevalences in the aging population. There is increasing evidence corroborating an association between diabetes mellitus and bone. This review will discuss the disease complications of diabetes on the skeleton, highlighting findings from epidemiological, molecular, and imaging studi...

The association between metabolic syndrome (MS) and bone health remains unclear. We aimed to study the association between MS and hip bone geometry (HBG), femoral neck bone mineral density (FN-BMD), and the risk of osteoporosis and incident fractures. Data of 2040 women and 1510 men participants in the third visit (1997-1999) of the Rotterdam Study...

The potential for personalized sequencing to individually optimize medical treatment in diseases such as cancer and for pharmacogenomic application is just beginning to be realized, and the utility of sequencing healthy individuals for managing health is also being explored. The data produced requires additional advancements in interpretation of va...

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BM...

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinant...

Context: Low bone mineral density (BMD) has been associated with increased all-cause mortality. Cause-specific mortality studies have been controversial. Objective: The aim of the study was to investigate associations between BMD and all-cause mortality and in-depth cause-specific mortality. Design and Setting: We studied two cohorts from the pro...

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged > 55 years; and comp...

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by x-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinant...

Although the baby growing in its mother's womb needs calcium for skeletal development osteoporosis and fractures very rarely occur during pregnancy. A 27-year old woman in the seventh month of her first pregnancy contracted mid-thoracic back pain after lifting an object. The pain was attributed to her pregnancy, but remained post-partum. Her past m...

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. To identify CNVs associated with osteoporotic bone fracture r...

Serum high-sensitivity C-reactive protein (CRP) is an inflammatory biomarker. We investigated the relationship between CRP and bone health in the Rotterdam Study. Serum high-sensitivity CRP was associated with fracture risk and lower femoral neck bending strength. Mendelian randomization analyses did not yield evidence for this relationship being c...

PURPOSE Scheuermann’s disease is a form of osteochondrosis of the spine, characterized by increased posterior rounding of the thoracic spine in association with structural deformity of the vertebral elements. Although the etiology remains largely unknown, there is evidence that genetic factors play a role. A Danish twin study has found a heritabili...

A 56-year-old man was treated with bisphosphonates following incidental findings of vertebral deformities on a chest radiograph taken for cough. After re-evaluation with DEXA and spinal radiographs he was diagnosed with Scheuermann's disease, not osteoporosis. His gastrointestinal symptoms resolved after bisphosphonates were stopped. A 42-year-old...

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and compri...

Osteoporotic vertebral fractures are an increasingly active area of research. Oftentimes assessments are performed by software-assisted quantitative morphometry. Here, we will discuss multi-functionality of these data for research purposes. A team of trained research assistants processed lateral spine radiographs from the population-based Rotterdam...

We explored the role of transient receptor potential vanilloid 4 (TRPV4) in murine bone metabolism and association of TRPV4 gene variants with fractures in humans. Urinary and histomorphometrical analyses demonstrated reduced osteoclast activity and numbers in male Trpv4−/− mice, which was confirmed in bone marrow-derived osteoclast cultures. Osteo...

Study design: Observational population-based study. Objective: To determine the prevalence of radiographical Scheuermann disease in a Dutch population and evaluate the consistency of diagnostic criteria. Summary of background data: Scheuermann disease is a form of osteochondrosis characterized by increased posterior rounding of the thoracic sp...

Background: The baby growing in its mother’s womb needs calcium for skeletal development. Maternal osteoporosis has been attributed to pregnancy in some cases. Presenting problem: A 27-year-old woman in the 7th month of her first pregnancy complained of mid-thoracic back pain after lifting a non-heavy object. The pain remained with differing intens...

Purpose: Patello-femoral (PF) cartilage damage can cause severe knee pain and result in increasing disability. The purpose of this study was to identify factors associated with grade 4 defects of the patello-femoral joint. Methods: A cohort of 2601 patients (average age¼45, range, 18 to 83) who underwent knee arthroscopy for knee pathology were stu...

Diuretics can cause changes in calcium levels due to renal effects. Moreover, calcium levels can also vary as a result of changes in intestinal absorption and in the activity of osteoclastic cells. A marker of osteoclastic bone-resorption activity is the level of urinary free deoxypyridinoline (FDP). Deoxypyridinoline (DP) acts as a cross-link betw...