Annie W C Kung

Hong Kong Hospital Authority, Hong Kong, Hong Kong

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Publications (133)653.54 Total impact

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    ABSTRACT: Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10,336 individuals from European and Asian origin, we discovered that variants >100 Kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels.
    Human Molecular Genetics 07/2014; · 7.69 Impact Factor
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    ABSTRACT: 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 determinants of heel broadband ultrasound attenuation (BUA, n=14,260), velocity of sound (VOS, n=15,514) and BMD (n=4,566) in 13 discovery cohorts. Independent replication involved 7 cohorts with GWA data (in silico n=11,452) and new genotyping in 15 cohorts (de novo n=24,902). In combined random effects meta-analysis of the discovery and replication cohorts, 9 SNPs had genome-wide significant (p<5×10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708), and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (p<8.23×10(-14)). In meta-analyses involving 25 cohorts with up to 14,985 fracture cases, six of 10 SNPs associated with heel bone properties at p<5×10(-6) also had the expected direction of association with any fracture (p<0.05), including 3 SNPs with p<0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007), and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
    Human Molecular Genetics 01/2014; · 7.69 Impact Factor
  • E Cheung, C-L Cheung, A W C Kung, K C B Tan
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    ABSTRACT: A total of 2,266 postmenopausal Chinese women were followed for 4.5 years to determine the incidence of new fractures. The positive predictive value, negative predictive value, sensitivity and specificity of different treatment strategies were compared. Using a fixed optimal threshold calculated from receiver operating characteristics (ROC) curve had the highest sensitivity but lowest specificity. There is no specific intervention threshold based on FRAX to guide treatment for Asian populations. This prospective study sought to determine the impact of applying different intervention thresholds to a cohort of Chinese postmenopausal women. This study was part of the Hong Kong Osteoporosis Study. A total of 2,266 treatment-naïve postmenopausal women underwent clinical risk factor and BMD assessments. The subjects were followed to assess fractures. We calculated the FRAX probability of major osteoporotic fractures corresponding to women with prior fractures but no other clinical risk factors. Different treatment strategies which include treating women with prior fractures, women with age-specific FRAX probability corresponding to those with prior fractures, women with osteoporosis as well as women with FRAX probability above a fixed cut-off based on optimizing sensitivity and specificity on the ROC curve were compared. The mean age at baseline was 62.1 ± 8.5 years, and the mean follow-up time was 4.5 ± 2.8 years. One hundred six new major osteoporotic fractures were reported. An optimal (FRAX, with BMD) cut-off point of 9.95 % was identified. All strategies had negative predictive value of >90 %. Using a fixed cut-off had the highest sensitivity (62.3 %) but lowest specificity (73.5 %) and positive predictive value (10.3 %). Using a fixed cut-off would direct treatment from younger women with lower absolute risk to elderly women with higher absolute risk. Targeting only women with prior fractures is unlikely to reduce fracture burden. Other treatment strategies with higher sensitivity need to be considered but they have different shortcomings.
    Osteoporosis International 11/2013; · 4.04 Impact Factor
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    ABSTRACT: Context:Gremlin 2 (GREM2) is a regulator of osteoblast differentiation and osteogenesis. A recent genome-wide association study identified GREM2 as a novel susceptibility gene for trabecular volumetric bone mineral density (BMD).Objective:We investigated whether GREM2 gene variants were associated with areal BMD in southern Chinese people.Research Design and Methods:We genotyped 108 single-nucleotide polymorphisms (SNPs) in 417 cases (defined as BMD Z-score ≤-1.28) and 359 controls (defined as BMD Z-score ≥+1). Multivariable logistic regression using an additive model was used to evaluate the association. The most associated SNPs of BMD at the spine, femoral neck, and total hip was then replicated in an additional 454 cases and 401 controls.Results:Twelve, 13, and 14 SNPs showed nominal association with BMD at the spine, femoral neck, and total hip, respectively. The minor alleles of rs9728351 (odds ratio [OR] = 2.56; 95% confidence interval [CI] = 1.33-4.92), rs11588607 (OR = 1.65; 95% CI = 1.14-2.4), and rs4454537 (OR = 1.87; 95% CI = 1.22-2.86) were associated with the low BMD at the spine, femoral neck, and total hip, respectively. Among these SNPs most associated with BMD, rs4454537 was successfully replicated in an independent cohort (OR = 1.59; 95% CI = 1.05-2.4). Meta-analysis showed that the minor allele of rs4454537 was associated with low total hip BMD with an OR of 1.72 (95% CI = 1.28-2.31) (P = 3.2 × 10(-4); Pcorrected = .043).Conclusions:The minor allele of rs4454537 is significantly associated with low BMD at the total hip of southern Chinese people. Our study further suggests GREM2 as a novel susceptibility gene for osteoporosis.
    The Journal of Clinical Endocrinology and Metabolism 07/2013; · 6.31 Impact Factor
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    ABSTRACT: Population-based studies have revealed a decline in the incidence of age-adjusted hip fractures in southern Chinese women during the past decade. To determine whether there was a secular change in population characteristics that accounted for this decline, we compared the bone mineral density (BMD) and lifestyle habits of two cohorts of women who were more than 50 years of age and who were recruited from 1995 to 2000 and 2005 to 2010. The BMD levels in the 2005-2010 cohort were significantly higher at the spine and hip and ranged from 3.6 to 17.8 % among the different age groups. Additionally, a significantly lower prevalence of subjects with osteoporosis and osteopenia was observed. Longer reproductive years, higher levels of physical activity, higher estradiol and 25(OH) vitamin D levels, and lower alkaline phosphatase levels were found in the 2005-2010 cohort. After adjusting for bone-determining factors, significant differences were detected in the BMD levels at the lumbar spine, femoral neck, and total hip (4.17, 9.02, and 9.34 %, respectively) in women >50 years of age but not in women ≤50 years of age. The secular increase in BMD and healthier lifestyles most likely led to the decline in the incidence of age-adjusted fractures.
    Journal of Bone and Mineral Metabolism 04/2013; · 2.22 Impact Factor
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    ABSTRACT: BACKGROUND: A vast amount of literature describes the incidence of fracture as a risk for recurrent osteoporotic fractures in western and Asian countries. Osteoporosis evaluation and treatment after a low-trauma fracture, however, has not been well characterized in postmenopausal women in Asia. The purpose of this study was to characterize patient and health system characteristics associated with the diagnosis and management of osteoporosis among postmenopausal women hospitalized with a fragility fracture in Asia. METHODS: Patient surveys and medical charts of postmenopausal women (N=1,122) discharged after a fragility hip fracture from treatment centers in mainland China, Hong Kong, Singapore, South Korea, Malaysia, Taiwan, and Thailand between July 1, 2006 and June 30, 2007 were reviewed for bone mineral density (BMD) measurement, osteoporosis diagnosis, and osteoporosis treatment. RESULTS: The mean (SD) age was 72.9 (11.5) years. A BMD measurement was reported by 28.2% of patients, 51.5% were informed that they had osteoporosis, and 33.0% received prescription medications for osteoporosis in the 6 months after discharge. Using multivariate logistic regression analyses, prior history of fracture decreased the odds of a BMD measurement (OR 0.63, 95% CI 0.45-0.88). Having a BMD measurement increased the odds of osteoporosis diagnosis (OR 10.1, 95% CI 6.36-16.0), as did having health insurance (OR 4.95, 95% CI 1.51-16.21 for private insurance with partial self-payment relative to 100% self-payment). A history of fracture was not independently associated with an osteoporosis diagnosis (OR 0.80, 95% CI 0.56-1.15). Younger age reduced the odds of receiving medication for osteoporosis (OR 0.59, 95% CI 0.36-0.96 relative to age >=65), while having a BMD measurement increased the odds (OR 1.79, 95% CI 1.23-2.61). CONCLUSIONS: Osteoporosis diagnosis and treatment in Asian countries were driven by BMD measurement but not by fracture history. Future efforts should emphasize education of general practitioners and patients about the importance of fracture.
    BMC Women's Health 02/2013; 13(1):7. · 1.66 Impact Factor
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    ABSTRACT: Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of thyrotoxicosis. We conducted a genome-wide association study (GWAS) and a replication study with a total of 123 southern Chinese with TPP (cases) and 1,170 healthy controls and identified a susceptibility locus on chromosome 17q24.3 near KCNJ2 (rs312691: odds ratio (OR) = 3.3; P(meta-analysis) = 1.8 × 10(-14)). All subjects with TPP also had Graves' disease, and subsequent TPP versus Graves' disease comparison confirmed that the association at 17q24.3 was specific to TPP. The area under the curve (AUC) of rs312691 genotype for risk prediction of TPP in subjects with Graves' disease was 0.73. Expression quantitative trait locus (eQTL) analysis identified SNPs in the region flanking rs312691 (±10 kb) that could potentially affect KCNJ2 expression (P = 0.0001). Our study has identified a susceptibility locus associated with TPP and provides insight into the causes of TPP.
    Nature Genetics 08/2012; 44(9):1026-9. · 35.21 Impact Factor
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    ABSTRACT: Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
    Nature Genetics 04/2012; 44(5):491-501. · 35.21 Impact Factor
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    ABSTRACT: The prevalence of chronic diseases has risen along with increased longevity. Co-occurrence of two or more chronic diseases in an individual (multimorbidity) is prevalent and poses a huge burden to individuals and the society. However, determinants of multimorbidity are largely unknown. Handgrip strength is a general indicator of muscle strength and linked with premature mortality. However, its role in multimorbidity has never been evaluated. To investigate the relationships between handgrip strength and multiple chronic diseases and multimorbidity, and to assess the usefulness of age and handgrip as a marker of chronic diseases and multimorbidity in a community dwelling sample of men and women, we analyzed a cross-sectional cohort with 1,145 subjects (748 men and 397 women) aged 50 years and older living in Hong Kong. Low handgrip strength was significantly associated with increased odds of having five and three chronic diseases in men and women, respectively, after controlling for age, body mass index, history of smoking, educational level, marital level and comorbidity. Multivariable-adjusted handgrip strength was significantly decreased with the number of chronic diseases in men (trend, P = 0.001), but the trend in women was marginal (trend, P = 0.06). Conversely, multivariable-adjusted age was significantly increased with the number of chronic diseases in women (trend, P = 0.033), but not in men (trend, P = 0.118). In conclusion, handgrip strength is associated with multiple chronic diseases and multimorbidity in men and women after adjustment of confounding factors. It shows a linear trend of association with the number of chronic diseases in men, but not in women. Since handgrip strength is a biomarker of multiple physiological systems, its augmentation may be a feasible strategy to improve general health and decrease likelihood of having multiple chronic diseases and hence, premature mortality.
    Age 02/2012; · 6.28 Impact Factor
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    ABSTRACT: Periostin (POSTN) as a regulator of osteoblast differentiation and bone formation may affect susceptibility to osteoporosis. This study suggests POSTN as a candidate gene for bone mineral density (BMD) variation and vertebral fracture risk, which could better our understanding about the genetic pathogenesis of osteoporosis and will be useful in clinic in the future. The genetic determination of osteoporosis is complex and ill-defined. Periostin (POSTN), an extracellular matrix secreted by osteoblasts and a regulator of osteoblast differentiation and bone formation, may affect susceptibility to osteoporosis. We adopted a tag-single nucleotide polymorphism (SNP) based association method followed by imputation-based verification and identification of a causal variant. The association was investigated in 1,572 subjects with extreme-BMD and replicated in an independent population of 2,509 subjects. BMD was measured by dual X-ray absorptiometry. Vertebral fractures were identified by assessing vertebral height from X-rays of the thoracolumbar spine. Association analyses were performed with PLINK toolset and imputation analyses with MACH software. The top imputation finding was subsequently validated by genotyping. Interactions between POSTN and another BMD-related candidate gene sclerostin (SOST) were analyzed using MDR program and validated by logistical regression analyses. The putative transcription factor binding with target sequence was confirmed by electrophoretic mobility shift assay (EMSA). Several SNPs of POSTN were associated with BMD or vertebral fractures. The most significant polymorphism was rs9547970, located at the -2,327 bp upstream (P = 6.8 × 10(-4)) of POSTN. Carriers of the minor allele G per copy of rs9547970 had 1.33 higher risk of vertebral fracture (P = 0.007). An interactive effect between POSTN and SOST upon BMD variation was suggested (P < 0.01). A specific binding of CDX1 to the sequence of POSTN with the major allele A of rs9547970 but not the variant G allele was confirmed by EMSA. Our results suggest POSTN as a candidate gene for BMD variation and vertebral fracture risk.
    Osteoporosis International 01/2012; 23(7):1877-87. · 4.04 Impact Factor
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    ABSTRACT: Our previous genome-wide association study (GWAS) in a Hong Kong Southern Chinese population with extreme bone mineral density (BMD) scores revealed suggestive association with MPP7, which ranked second after JAG1 as a candidate gene for BMD. To follow-up this suggestive signal, we replicated the top single-nucleotide polymorphism rs4317882 of MPP7 in three additional independent Asian-descent samples (n= 2684). The association of rs4317882 reached the genome-wide significance in the meta-analysis of all available subjects (P(meta)= 4.58 × 10(-8), n= 4204). Site heterogeneity was observed, with a larger effect on spine than hip BMD. Further functional studies in a zebrafish model revealed that vertebral bone mass was lower in an mpp7 knock-down model compared with the wide-type (P= 9.64 × 10(-4), n= 21). In addition, MPP7 was found to have constitutive expression in human bone-derived cells during osteogenesis. Immunostaining of murine MC3T3-E1 cells revealed that the Mpp7 protein is localized in the plasma membrane and intracytoplasmic compartment of osteoblasts. In an assessment of the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of transcriptional factor GATA2 to the risk allele 'A' but not the 'G' allele of rs4317882. An mRNA expression study in human peripheral blood mononuclear cells confirmed that the low BMD-related allele 'A' of rs4317882 was associated with lower MPP7 expression (P= 9.07 × 10(-3), n= 135). Our data suggest a genetic and functional association of MPP7 with BMD variation.
    Human Molecular Genetics 12/2011; 21(7):1648-57. · 7.69 Impact Factor
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    ABSTRACT: Serum osteoprotegerin (OPG) level is a key biomarker for numerous traits of clinical importance like diabetes, coronary artery disease, blood pressure, lipid profile, and cancers, but its genetic basis remains poorly understood. We estimated the heritability (h(2)) of serum OPG level in 1442 southern Chinese subjects from 306 families. The h(2) for unadjusted OPG was 0.62 for females and 0.17 for males; and for age-adjusted OPG, 0.75 for females and 0.37 for males. Adjustment for lifestyle factors including calcium and phytoestrogen intake, exercise, smoking, and alcohol consumption exerted only a modest effect on the h(2). In conclusion, we confirmed that circulating OPG is a heritable trait and there is a significant difference in heritability between sexes.
    Annals of Human Genetics 09/2011; 75(5):584-8. · 2.22 Impact Factor
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    ABSTRACT: In this 2-year extension of a 3-year study, bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higher-risk women. Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated. This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years. A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year, randomized, double-blind, placebo-controlled, phase 3 trial. In the core study (N = 7,492), subjects received bazedoxifene 20 or 40 mg/day, raloxifene 60 mg/day, or placebo. The raloxifene arm was discontinued after 3 years; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years. Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo. Endpoints included incidence of new vertebral fractures (primary) and non-vertebral fractures, and changes in bone mineral density (BMD) and bone turnover markers. At 5 years, the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg (4.5%) and 40/20 mg (3.9%) versus placebo (6.8%; P < 0.05), with relative risk reductions of 35% and 40%, respectively. Non-vertebral fracture incidence was similar among groups. In a subgroup of higher-risk women (n = 1,324; femoral neck T-score ≤-3.0 and/or ≥ 1 moderate or severe or ≥ 2 mild vertebral fracture[s]), bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo (37%; P = 0.06); combined data for bazedoxifene 20 and 40/20 mg reached statistical significance (34% reduction; P < 0.05). Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo (P < 0.05) and was generally safe and well tolerated. The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women.
    Osteoporosis International 07/2011; 23(1):351-63. · 4.04 Impact Factor
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    ABSTRACT: We previously used five freely available bioinformatics tools (Prioritizer, Geneseeker, PROSPECTR and SUSPECTS, Disease Gene Prediction, and Endeavour) to analyze the thirteen well-replicated osteoporosis susceptibility loci and identify a subset of most likely candidate osteoporosis susceptibility genes (Huang et al. in J Hum Genet 53:644-655, 2008). In the current study, we experimentally tested the association between bone mineral density (BMD) and the 9 most likely candidate genes [LAMC2(1q25-q31), MATN3(2p24-p23), ITGAV(2q31-q32), ACVR1(2q23-q24), TDGF1(3p21.31), EGF(4q25), IGF1(12q22-q23), ZIC2(13q32), BMP2(20p12)] which were pinpointed by 4 or more bioinformatics tools. Forty tag SNPs in nine candidate genes were genotyped in a southern Chinese female case-control cohort consisting of 1643 subjects. Single- and multi-marker association analyses were performed using logistic regression analysis implemented by PLINK. Potential transcription factor binding sites were predicted by MatInspector. The strongest association was observed between rs10178256 (MATN3) and trochanter (P < 0.001) and total hip BMD (P = 0.002). The SNP rs6214 (IGF1) showed consistent association with BMD at all the four measured skeletal sites (P = 0.005-0.044). Prediction of transcription factor binding suggested that the minor allele G of rs10178256 might abolish the binding of MESP1 and MESP2 which play vital roles in bone homeostasis, whereas the minor allele G of rs6214 might create an additional binding site for XBP1, a constitutive regulator of endoplasmic reticulum stress response. Our data suggested that variants in MATN3 and IGF1 were involved in BMD regulation in southern Chinese women.
    Journal of Bone and Mineral Metabolism 06/2011; 29(6):709-16. · 2.22 Impact Factor
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    Johnny S H Kwan, Annie W C Kung, Pak C Sham
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    ABSTRACT: Selective genotyping can increase power in quantitative trait association. One example of selective genotyping is two-tail extreme selection, but simple linear regression analysis gives a biased genetic effect estimate. Here, we present a simple correction for the bias.
    Behavior Genetics 05/2011; 41(5):776-9. · 2.61 Impact Factor
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    ABSTRACT: Heart failure occurs in 6% of hyperthyroid patients. Nonetheless, only half of those with hyperthyroidism-related heart failure have impaired left ventricular (LV) systolic function. Thus, diastolic dysfunction may play an important role in the pathogenesis. We performed serial echocardiographic examinations in 70 consecutive patients with hyperthyroidism (39 ± 2 years, 47 women) to determine their diastolic function and repeated the examinations 6 months after achieving a euthyroid state. All patients had normal LV systolic function, but diastolic dysfunction was detected in 22 cases (mild: 3, moderate: 15 and severe: 4). The prevalence of diastolic dysfunction increased with age from 17·9 % in patients <40 years to 100% in those >60 years. Increasing age was the only independent predictor for diastolic dysfunction in hyperthyroid patients. After achievement of a euthyroid state, most patients (16/22, 72%) had completely normalized diastolic function: 100% of patients <40 years, 33·3 % of those ≥ 60 years. Further analyses revealed significant age-related differences in the cardiovascular response to hyperthyroidism. Among patients <40 years, hyperthyroidism resulted in a marked reduction in total peripheral vascular resistance, increased cardiac output and enhanced diastolic function as determined by E'. No such significant change in total peripheral vascular resistance or cardiac output was observed in hyperthyroid patients ≥ 40 years. In addition, hyperthyroidism was associated with reduced E', signifying diastolic dysfunction in older hyperthyroid patients. Hyperthyroidism is associated with diastolic dysfunction, particularly in older patients. It is partly reversible following achievement of a euthyroid state.
    Clinical Endocrinology 05/2011; 74(5):636-43. · 3.40 Impact Factor
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    ABSTRACT: Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. This study observed that Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians, but the vertebral fracture rates were higher, resulting in a high vertebral-to-hip fracture ratio. As a result, estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. The aim of this study was to report the incidence of clinical vertebral fractures among the Chinese and to compare the vertebral-to-hip fracture risk to other ethnic groups. Four thousand, three hundred eighty-six community-dwelling Southern Chinese subjects (2,302 women and 1,810 men) aged 50 or above were recruited in the Hong Kong Osteoporosis Study since 1995. Baseline demographic characteristics and medical history were obtained. Subjects were followed annually for fracture outcomes with a structured questionnaire and verified by the computerized patient information system of the Hospital Authority of the Hong Kong Government. Only non-traumatic incident hip fractures and clinical vertebral fractures that received medical attention were included in the analysis. The incidence rates of clinical vertebral fractures and hip fractures were determined and compared to the published data of Swedish Caucasian and Japanese populations. The mean age at baseline was 62 ± 8.2 years for women and 68 ± 10.3 years for men. The average duration of follow-up was 4.0 ± 2.8 (range, 1 to 14) years for a total of 14,733 person-years for the whole cohort. The incidence rate for vertebral fracture was 194/100,000 person-years in men and 508/100,000 person-years in women, respectively. For subjects above the age of 65, the clinical vertebral fracture and hip fracture rates were 299/100,000 and 332/100,000 person-years, respectively, in men, and 594/100,000 and 379/100,000 person-years, respectively, in women. Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians. At the age of 65 or above, the hip fracture rates for Asian (Hong Kong Chinese and Japanese) men and women were less than half of that in Caucasians, but the vertebral fracture rate was higher in Asians, resulting in a high vertebral-to-hip fracture ratio. The incidences of vertebral and hip fractures, as well as the vertebral-to-hip fracture ratios vary in Asians and Caucasians. Estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate.
    Osteoporosis International 04/2011; 23(3):879-85. · 4.04 Impact Factor
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    ABSTRACT: myo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1(-/-)) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1(-/-) embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1(-/-) mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1(-/-) mice and strengthened bone structure in SMIT1(+/+) mice. Although MI content was much lower in SMIT1(-/-) mesenchymal cells (MSCs), the I(1,4,5)P(3) signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2011; 26(3):582-90. · 6.04 Impact Factor
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    ABSTRACT: This study evaluated the characteristics of patients with vertebral fractures and examined the discriminative ability of clinical risk factors. The findings provide further insights into possible development of a simple, cost-effective scheme for fracture risk assessment using clinical risk factors to identify high-risk patients for further evaluation. Vertebral fractures are the most common complication of osteoporosis. The aim of this study was to evaluate the characteristics of patients with vertebral fractures and to determine the discriminative ability of bone mineral density (BMD) and other clinical risk factors. Postmenopausal Southern Chinese women (2,178) enrolled in the Hong Kong Osteoporosis Study since 1995 were prospectively followed up for fracture outcome. Subjects (1,372) with lateral spine radiographs were included in this study. Baseline demographic, BMD, and clinical risk factor information were obtained from a structured questionnaire. Subjects (299; 22%) had prevalent vertebral fractures. The prevalence of vertebral fractures increased with increasing age, number of clinical risk factors, and decreasing BMD. The odds of having a prevalent vertebral fracture per SD reduction in BMD after adjustment for age in Hong Kong Southern Chinese postmenopausal women was 1.5 for the lumbar spine and femoral neck. Analysis of the receiver operating characteristic curve revealed that bone mineral apparent density did not enhance fracture risk prediction. Subjects with ≥ 4 clinical risk factors had 2.3-fold higher odds of having a prevalent vertebral fracture while subjects with ≥ 4 clinical risk factors plus a low BMD (i.e., femoral neck T-score < -2.5) had 2.6-fold. Addition of BMD to clinical risk factors did not enhance the discriminative ability to identify subjects with vertebral fracture. Based on these findings, we recommend that screening efforts should focus on older postmenopausal women with multiple risk factors to identify women who are likely to have a prevalent vertebral fracture.
    Osteoporosis International 02/2011; 22(2):667-74. · 4.04 Impact Factor

Publication Stats

2k Citations
653.54 Total Impact Points

Institutions

  • 2005–2013
    • Hong Kong Hospital Authority
      • Department of Medicine and Geriatrics
      Hong Kong, Hong Kong
  • 1987–2013
    • The University of Hong Kong
      • • Li Ka Shing Faculty of Medicine
      • • Department of Medicine
      • • Department of Pathology
      Hong Kong, Hong Kong
  • 1990–2011
    • Queen Mary Hospital
      Hong Kong, Hong Kong
  • 2010
    • University of Florence
      Florens, Tuscany, Italy
    • Tung Wah Group of Hospitals
      Hong Kong, Hong Kong