Ling Oei
Erasmus University Rotterdam
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Featured researches published by Ling Oei.
European Journal of Epidemiology | 2012
Lili Ma; Ling Oei; Lindi Jiang; Karol Estrada; Huiyong Chen; Zhen Wang; Qiang Yu; M.C. Zillikens; Xin Gao; Fernando Rivadeneira
Type 2 diabetes mellitus (T2DM) influences bone metabolism, but the relation of T2DM with bone mineral density (BMD) remains inconsistent across studies. The objective of this study was to perform a meta-analysis and meta-regression of the literature to estimate the difference in BMD (g/cm2) between diabetic and non-diabetic populations, and to investigate potential underlying mechanisms. A literature search was performed in PubMed and Ovid extracting data from articles prior to May 2010. Eligible studies were those where the association between T2DM and BMD measured by dual energy X-ray absorptiometry was evaluated using a cross-sectional, cohort or case–control design, including both healthy controls and subjects with T2DM. The analysis was done on 15 observational studies (3,437 diabetics and 19,139 controls). Meta-analysis showed that BMD in diabetics was significantly higher, with pooled mean differences of 0.04 (95% CI: 0.02, 0.05) at the femoral neck, 0.06 (95% CI: 0.04, 0.08) at the hip and 0.06 (95% CI: 0.04, 0.07) at the spine. The differences for forearm BMD were not significantly different between diabetics and non-diabetics. Sex-stratified analyses showed similar results in both genders. Substantial heterogeneity was found to originate from differences in study design and possibly diabetes definition. Also, by applying meta-regression we could establish that younger age, male gender, higher body mass index and higher HbA1C were positively associated with higher BMD levels in diabetic individuals. We conclude that individuals with T2DM from both genders have higher BMD levels, but that multiple factors influence BMD in individuals with T2DM.
Journal of Bone and Mineral Research | 2016
Eugene McCloskey; Anders Odén; Nicholas C. Harvey; William D. Leslie; Didier Hans; Helena Johansson; Reinhard Barkmann; Stephanie Boutroy; Jacques P. Brown; Roland Chapurlat; Yuki Fujita; Claus-C. Glüer; David Goltzman; Masayuki Iki; Magnus Karlsson; Andreas Kindmark; Mark A. Kotowicz; Norio Kurumatani; Timothy Kwok; Oliver Lamy; Jason Leung; Kurt Lippuner; Östen Ljunggren; Mattias Lorentzon; Dan Mellström; Thomas Merlijn; Ling Oei; Claes Ohlsson; Julie A. Pasco; Fernando Rivadeneira
Trabecular bone score (TBS) is a gray‐level textural index of bone microarchitecture derived from lumbar spine dual‐energy X‐ray absorptiometry (DXA) images. TBS is a bone mineral density (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 their combined performance by adjusting the FRAX probability for TBS. We utilized individual‐level data from 17,809 men and women in 14 prospective population‐based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow‐up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35–1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10‐year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24–1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65–1.87 versus 1.70, 95% CI 1.60–1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.
Diabetes Care | 2013
Ling Oei; M. Carola Zillikens; Abbas Dehghan; Gabriëlle H.S. Buitendijk; Martha C. Castaño-Betancourt; Karol Estrada; Lisette Stolk; Edwin H. G. Oei; Joyce B. J. van Meurs; Joseph A M J L Janssen; Albert Hofman; Johannes P.T.M. van Leeuwen; Jacqueline C. M. Witteman; Huibert A. P. Pols; André G. Uitterlinden; Caroline C. W. Klaver; Oscar H. Franco; Fernando Rivadeneira
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 12.2 years). At baseline, 420 participants with type 2 diabetes were classified by glucose control (according to HbA1c calculated from fructosamine), resulting in three comparison groups: adequately controlled diabetes (ACD; n = 203; HbA1c <7.5%), inadequately controlled diabetes (ICD; n = 217; HbA1c ≥7.5%), and no diabetes (n = 3,715). Models adjusted for sex, age, height, and weight (and femoral neck BMD) were used to test for differences in bone parameters and fracture risk (hazard ratio [HR] [95% CI]). RESULTS The ICD group had 1.1–5.6% higher BMD, 4.6–5.6% thicker cortices, and −1.2 to −1.8% narrower femoral necks than ACD and ND, respectively. Participants with ICD had 47–62% higher fracture risk than individuals without diabetes (HR 1.47 [1.12–1.92]) and ACD (1.62 [1.09–2.40]), whereas those with ACD had a risk similar to those without diabetes (0.91 [0.67–1.23]). CONCLUSIONS Poor glycemic control in type 2 diabetes is associated with fracture risk, high BMD, and thicker femoral cortices in narrower bones. We postulate that fragility in apparently “strong” bones in ICD can result from microcrack accumulation and/or cortical porosity, reflecting impaired bone repair.
PLOS Genetics | 2014
John P. Kemp; Carolina Medina-Gomez; Karol Estrada; Beate St Pourcain; Denise H. M. Heppe; Nicole M. Warrington; Ling Oei; Susan M. Ring; Claudia J. Kruithof; Nicholas J. Timpson; Lisa E. Wolber; Sjur Reppe; Kaare M. Gautvik; Elin Grundberg; Bing Ge; Bram C. J. van der Eerden; Jeroen van de Peppel; Matthew A. Hibbs; Cheryl L. Ackert-Bicknell; Kwangbom Choi; Daniel L. Koller; Michael J. Econs; Frances M. K. Williams; Tatiana Foroud; M. Carola Zillikens; Claes Ohlsson; Albert Hofman; André G. Uitterlinden; George Davey Smith; Vincent W. V. Jaddoe
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 BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (re = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (re = 0.20–0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n∼9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01×10−37), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31×10−14). In addition, we report a novel association between RIN3 (previously associated with Pagets disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4×10−10). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.
European Radiology | 2013
Ling Oei; Fernando Rivadeneira; Felisia Ly; Stephan J. Breda; M. Carola Zillikens; Albert Hofman; André G. Uitterlinden; Gabriel P. Krestin; Edwin H. G. Oei
AbstractBackgroundOsteoporosis is the most common metabolic bone disease; vertebral fractures are the most common osteoporotic fractures.MethodsSeveral radiological scoring methods using different criteria for osteoporotic vertebral fractures exist. Quantitative morphometry (QM) uses ratios derived from direct vertebral body height measurements to define fractures. Semi-quantitative (SQ) visual grading is performed according to height and area reduction. The algorithm-based qualitative (ABQ) method introduced a scheme to systematically rule out non-fracture deformities and diagnoses osteoporotic vertebral fractures based on endplate depression. The concordance across methods is currently a matter of debate.ResultsThis article reviews the most commonly applied standardised radiographic scoring methods for osteoporotic vertebral fractures, attaining an impartial perspective of benefits and limitations. It provides image examples and discusses aspects that facilitate large-scale application, such as automated image analysis software and different imaging investigations. It also reviews the implications of different fracture definitions for scientific research and clinical practice.ConclusionAccurate standardised scoring methods for assessing osteoporotic vertebral fractures are crucial, considering that differences in definition will have implications for patient care and scientific research. Evaluation of the feasibility and concordance among methods will allow establishing their benefits and limitations, and most importantly, optimise their effectiveness for widespread application.Key Points• Several scoring methods using different criteria for assessing osteoporotic vertebral fractures exist. • Standardised osteoporotic vertebral fracture assessment should be applicable to different radiological investigations. • Accurate assessment of osteoporotic vertebral fractures is essential for proper patient management. • Optimising feasibility of scoring methods enables widespread use in scientific research. • Assessment of concordance between methods is important for application in patient care.
Current Osteoporosis Reports | 2015
Ling Oei; Fernando Rivadeneira; M. Carola Zillikens; Edwin H. G. Oei
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 studies in animal models and humans. Compared to control subjects, decreased bone mineral density (BMD) has been observed in type 1 diabetes mellitus, while on average, higher BMD has been found in type 2 diabetes; nonetheless, patients with both types of diabetes are seemingly at increased risk of fractures. Conventional diagnostics such as DXA measurements and the current fracture risk assessment tool (FRAX) risk prediction algorithm for estimating risk of osteoporotic fractures are not sufficient in the case of diabetes. A deterioration in bone microarchitecture and an inefficient distribution of bone mass with insufficiency of repair and adaptation mechanisms appear to be factors of relevance. A highly complex and heterogeneous molecular pathophysiology underlies diabetes-related bone disease, involving hormonal, immune, and perhaps genetic pathways. The detrimental effects of chronically elevated glucose levels on bone should be added to the more well-known complications of diabetes.
Journal of Medical Genetics | 2014
Ling Oei; Yi-Hsiang Hsu; Unnur Styrkarsdottir; Bert H.J. Eussen; Annelies de Klein; Marjolein J. Peters; Bjarni V. Halldórsson; Ching-Ti Liu; Nerea Alonso; Stephen Kaptoge; Gudmar Thorleifsson; Göran Hallmans; Lynne J. Hocking; Lise Bjerre Husted; Karen Jameson; Marcin Kruk; Joshua R. Lewis; Millan S. Patel; Serena Scollen; Olle Svensson; Stella Trompet; Natasja M. van Schoor; Kun Zhu; Brendan M. Buckley; C Cooper; Ian Ford; David Goltzman; Jesús González-Macías; Bente Langdahl; William D. Leslie
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. Method We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. Results A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10−5). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk. Conclusions These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
Journal of Bone and Mineral Research | 2012
Ching-Ti Liu; Karol Estrada; Laura M. Yerges-Armstrong; Najaf Amin; Evangelos Evangelou; Guo Li; Ryan L. Minster; Melanie A. Carless; Candace M. Kammerer; Ling Oei; Yanhua Zhou; Nerea Alonso; Zoe H. Dailiana; Joel Eriksson; Natalia Garcia-Giralt; Sylvie Giroux; Lise Bjerre Husted; R. I. Khusainova; Theodora Koromila; Annie Waichee Kung; Joshua R. Lewis; Laura Masi; Simona Mencej-Bedrač; Xavier Nogués; Millan S. Patel; Janez Prezelj; J. Brent Richards; Pak Chung Sham; Tim D. Spector; Liesbeth Vandenput
Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene‐by‐sex autosomal interactions genome‐wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome‐wide meta‐analysis of gene‐by‐sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single‐nucleotide polymorphisms (SNPs; p < 1 × 10−5) in an additional set of 24,763 individuals. Gene‐by‐sex interaction and sex‐specific effects were examined in these 12 SNPs. We detected one novel genome‐wide significant interaction associated with LS‐BMD at the Chr3p26.1‐p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10−5; female effect = −0.007 and p = 3.3 × 10−2), and 11 suggestive loci associated with either FN‐ or LS‐BMD in discovery cohorts. However, there was no evidence for genome‐wide significant (p < 5 × 10−8) gene‐by‐sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome‐wide significant evidence for gene‐by‐sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene‐by‐sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP.
Bone | 2014
Ling Oei; Karol Estrada; Emma L. Duncan; Claus Christiansen; Ching-Ti Liu; Bente Langdahl; Barbara Obermayer-Pietsch; José A. Riancho; Richard L. Prince; Natasja M. van Schoor; E. McCloskey; Yi-Hsiang Hsu; Evangelos Evangelou; Evangelia E. Ntzani; David Evans; Nerea Alonso; Lise Bjerre Husted; Carmen Valero; José L. Hernández; Joshua R. Lewis; Stephen Kaptoge; Kun Zhu; L. Adrienne Cupples; Carolina Medina-Gomez; Liesbeth Vandenput; Ghi Su Kim; Seunghun Lee; Martha C. Castaño-Betancourt; Edwin H. G. Oei; Josefina Martinez
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 comprising 329 cases and 2,666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at P<5x10-8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6 x 10-8. However, the association was not significant across 5,720 cases and 21,791 controls from 14 studies. Fixed-effects meta analyses summary estimate was 1.06 (95% CI: 0.98-1.14; P=0.17), displaying high degree of heterogeneity (I2=57%; Qhet p= 0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (P=0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size > 1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions are needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.
PLOS ONE | 2015
Taulant Muka; Katerina Trajanoska; Jessica C. Kiefte-de Jong; Ling Oei; André G. Uitterlinden; Albert Hofman; Abbas Dehghan; M. Carola Zillikens; Oscar H. Franco; Fernando Rivadeneira
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 (RSI-3), a prospective population based cohort, were available (mean follow-up 6.7 years). MS was defined according to the recent harmonized definition. HBG parameters were measured at the third round visit whereas FN-BMD was assessed at the third round and 5 years later. Incident fractures were identified from medical registry data. After correcting for age, body mass index (BMI), lifestyle factors and medication use, individuals with MS had lower bone width (β = -0.054, P = 0.003), lower cortical buckling ratio (β = -0.81, P = 0.003) and lower odds of having osteoporosis (odds ratio =0.56, P = 0.007) in women but not in men. Similarly, MS was associated with higher FN-BMD only in women (β = 0.028, P=0.001). In the analyses of MS components, the glucose component (unrelated to diabetes status) was positively associated with FN-BMD in both genders (β = 0.016, P = 0.01 for women and β = 0.022, P = 0.004 for men). In men, waist circumference was inversely associated with FN-BMD (β = -0.03, P = 0.004). No association was observed with fracture risk in either sex. In conclusion, women with MS had higher FN-BMD independent of BMI. The glucose component of MS was associated with high FN-BMD in both genders, highlighting the need to preserve glycemic control to prevent skeletal complications.