Anthony Kwok

European bone mineral density loci are also associated with BMD in East-Asian populations

Most genome-wide association (GWA) studies have focused on populations of European ancestry with limited assessment of the influence of the sequence variants on populations of other ethnicities. To determine whether markers that we have recently shown to associate with Bone Mineral Density (BMD) in Europeans also associate with BMD in East-Asians we analysed 50 markers from 23 genomic loci in samples from Korea (n = 1,397) and two Chinese Hong Kong sample sets (n = 3,869 and n = 785). Through this effort we identified fourteen loci that associated with BMD in East-Asian samples using a false discovery rate (FDR) of 0.05; 1p36 (ZBTB40, P = 4.3×10−9), 1p31 (GPR177, P = 0.00012), 3p22 (CTNNB1, P = 0.00013), 4q22 (MEPE, P = 0.0026), 5q14 (MEF2C, P = 1.3×10−5), 6q25 (ESR1, P = 0.0011), 7p14 (STARD3NL, P = 0.00025), 7q21 (FLJ42280, P = 0.00017), 8q24 (TNFRSF11B, P = 3.4×10−5), 11p15 (SOX6, P = 0.00033), 11q13 (LRP5, P = 0.0033), 13q14 (TNFSF11, P = 7.5×10−5), 16q24 (FOXL1, P = 0.0010) and 17q21 (SOST, P = 0.015). Our study marks an early effort towards the challenge of cataloguing bone density variants shared by many ethnicities by testing BMD variants that have been established in Europeans, in East-Asians.

High prevalence of asymptomatic vertebral fractures in Chinese women with systemic lupus erythematosus.

Objective. To investigate the prevalence of vertebral fractures and to identify risk factors associated with vertebral fractures in Chinese women with systemic lupus erythematosus (SLE). Methods. One hundred fifty-two consecutive patients with SLE were recruited in this cross-sectional study. Bone mineral density (BMD) measurements of the hip and spine were performed using the same dual energy X-ray absorptiometry (DEXA). Lateral radiographs of the spine (T5–L4) were assessed for vertebral fractures using a method described by Genant. Inflammatory and biochemical markers included C-reactive protein, receptor activator of nuclear factor-κB ligand, serum ß-CrossLaps assay for C-terminal telopeptides of type 1 collagen, and osteoprotegerin (OPG). Results. Asymptomatic vertebral fractures occurred in 20.4% of patients with SLE. Univariate analyses of variables associated with fractures were older age, higher body mass index (BMI), lower BMD spine, lower BMD hips, higher serum C3 and C4, longer estrogen exposure, higher levels of OPG, and the use of sunscreen. Multivariate analysis showed older age (p = 0.017), higher BMI (p < 0.036), and lower BMD of the spine were significantly associated with vertebral fractures in the thoracic and/or lumbar spine (odds ratio 1.068, 1.166, 0.005; p = 0.018, p = 0.025, p = 0.003, respectively). Conclusion. Asymptomatic vertebral fractures occur in 20.4% of patients with SLE and 30% of these patients have normal BMD. The current method using DEXA to predict the presence of vertebral fracture has limited value and there is a need for assessment of bone quality. Vertebral morphometry in patients with SLE is recommended and early therapeutic intervention is necessary to prevent vertebral fractures in patients with SLE.

Reduced bone perfusion in proximal femur of subjects with decreased bone mineral density preferentially affects the femoral neck.

Using dynamic contrast enhanced MR imaging, this study investigated perfusion of the proximal femur in subjects with normal BMD, low bone mass and osteoporosis. Study cohort comprised healthy elderly Hong Kong Chinese volunteers consisting of 107 males (74.4+/-4.2 years, mean+/-SD) and 135 females (73.9+/-4.3 years). Right proximal femur BMD measurement by DXA and MR perfusion imaging (maximum enhancement, E(max) and enhancement slope, E(slope)) of the femoral head, neck, and proximal shaft were carried out within a one month interval. Normal BMD, low bone mass and osteoporotic subjects accounted for 46.7%, 44.9%, and 8.4% of males; and 32.6%, 43.7%, and 23.7% of females. Perfusion indices showed that femoral head perfusion was less perfused compared to the femoral shaft (E(max) and E(slope) indices of head region=28% of shaft region). Compared with normal BMD subjects, E(max) of femoral head, neck, and proximal femur shaft were reduced by 15+/-5% (mean+/-standard error); 40+/-4%; 15+/-5% respectively for low bone mass subjects, and 36+/-4%; 50+/-6%; 47+/-6% respectively for osteoporotic subjects. E(slope) of femoral head, neck, and proximal femur shaft were reduced by 17+/-7%; 41+/-5%; 4+/-7% for low bone mass subjects and 50+/-5%, 62+/-5%, 34+/-8% for osteoporotic subjects. In low bone mass and osteoporotic subjects there was a tendency for perfusion in the femoral neck to reduce to a greater degree relative to that in the femoral head and shaft.

Structure and strength of the distal radius in female patients with rheumatoid arthritis: A case-control study

The purpose of this work was to investigate the volumetric bone mineral density (vBMD), bone microstructure, and mechanical indices of the distal radius in female patients with rheumatoid arthritis (RA). We report a cross‐sectional study of 66 middle‐aged female RA patients and 66 age‐matched healthy females. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual‐energy X‐ray absorptiometry (DXA). High‐resolution peripheral quantitative computed tomography (HR‐pQCT) was performed at the distal radius, yielding vBMD, bone microstructure, and mechanical indices. Cortical and trabecular vBMD were 3.5% and 10.7% lower, respectively, in RA patients than controls, despite comparable aBMD. Trabecular microstructural indices were –5.7% to –23.1% inferior, respectively, in RA patients compared to controls, with significant differences in trabecular bone volume fraction, separation, inhomogeneity, and structural model index. Cortical porosity volume and percentage were 128% and 93% higher, respectively, in RA patients, with stress being distributed more unevenly. Fourteen RA patients had exaggerated periosteal bone apposition primarily affecting the ulnovolar aspect of the distal radius. These particular patients were more likely to have chronic and severe disease and coexisting wrist deformity. The majority of the differences in density and microstructure between RA patients and controls did not depend on menstrual status. Recent exposure to glucocorticoids did not significantly affect bone density and microstructure. HR‐pQCT provides new insight into inflammation‐associated bone fragility in RA. It detects differences in vBMD, bone microstructure, and mechanical indices that are not captured by DXA. At the distal radius, deterioration in density and microstructure in RA patients involved both cortical and trabecular compartments. Excessive bone resorption appears to affect cortical more than trabecular bone at distal radius, particularly manifested as increased cortical porosity. Ulnovolar periosteal apposition of the distal radius is a feature of chronic, severe RA with wrist deformity.

Prevalence and sex difference of lumbar disc space narrowing in elderly chinese men and women: osteoporotic fractures in men (Hong Kong) and osteoporotic fractures in women (Hong Kong) studies.

OBJECTIVE Osteoporotic Fractures in Men (Hong Kong) and Osteoporotic Fractures in Women (Hong Kong) represent the first large-scale prospective population-based studies on bone health in elderly (age≥65 years) Chinese men (n=2,000) and women (n=2,000). We undertook the current study to investigate the prevalence of lumbar disc space narrowing in these subjects, and to identify the potential relationship between disc space narrowing and sex, bone mineral density (BMD), and other demographic and clinical data. METHODS On lumbar lateral radiographs, L1/L2-L4/L5 disc space was classified into 4 categories: 0=normal; 1=mild narrowing; 2=moderate narrowing; 3=severe narrowing. We compared demographic and clinical data between subjects with and those without total disc space narrowing scores≥3. RESULTS Disc space narrowing was more common in elderly women than in elderly men. The mean±SD disc space narrowing score for the 4 discs was 2.71±2.21 for men and 3.08±2.50 for women (P<0.0001). For the 3 age groups of 65-69 years, 70-79 years, and ≥80 years, the average disc space narrowing score increased with increasing age in both men and women, and to a greater degree in women than in men. The average disc space narrowing score differences between women and men were 0.12, 0.40, and 0.90, respectively, in the 3 age groups. For both men and women, a disc space narrowing score≥3 was associated with older age, higher spine and hip BMD, low back pain, and restricted leg mobility. CONCLUSION The prevalence and severity of disc space narrowing are higher in elderly women than in elderly men. With increasing age, disc space narrowing progresses at a greater rate in women than in men. A disc space narrowing score≥3 is associated with higher spine and hip BMD.

Bone Microarchitecture Assessment by High-Resolution Peripheral Quantitative Computed Tomography in Patients with Systemic Lupus Erythematosus Taking Corticosteroids

Objective. We assessed the relationship between vertebral fracture and bone microarchitecture in patients with systemic lupus erythematosus (SLE) on chronic corticosteroid therapy using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods. Fifty-nine Chinese women with SLE taking corticosteroid were selected to participate in a cross-sectional study. Vertebral fracture was confirmed semiquantitatively by lateral radiographs of the thoracic and lumbar spine. Density and microarchitecture at the distal radius were measured with HR-pQCT. Areal bone mineral density (aBMD) at hip and lumbar spine was measured by dual-energy x-ray absorptiometry (DEXA). Results. Twelve patients had vertebral fractures. The aBMD of spine or hip did not differ between those with and without vertebral fractures. Measures by HR-pQCT revealed that patients with vertebral fractures had significantly lower level of average bone density (p = 0.007), cortical bone density (p = 0.029), trabecular bone density (p = 0.024), trabecular bone volume to tissue volume (p = 0.023), and trabecular thickness (p = 0.011) than those without vertebral fractures. Independent explanatory variables associated with higher risk of vertebral fractures were older age (p = 0.013) and lower average cortical bone density (p = 0.029). Conclusion. Vertebral fracture in patients with SLE on chronic corticosteroid treatment was associated with alterations of bone density and microarchitectures measured by HR-pQCT and DEXA. However, alterations were more pronounced in measurements by HR-pQCT. Low cortical bone density and old age were significant predictors of vertebral fracture risk.

Inferior physical performance test results of 10,998 men in the MrOS Study is associated with high fracture risk

BACKGROUND most fractures are preceded by falls. OBJECTIVE the aim of this study was to determine whether tests of physical performance are associated with fractures. SUBJECTS a total of 10,998 men aged 65 years or above were recruited. METHODS questionnaires evaluated falls sustained 12 months before administration of the grip strength test, the timed stand test, the six-metre walk test and the twenty-centimetre narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.05 is a statistically significant difference. RESULTS fallers with a fracture performed worse than non-fallers on all tests (all P < 0.001). Fallers with a fracture performed worse than fallers with no fractures both on the right-hand-grip strength test and on the six-metre walk test (P < 0.001). A score below -2 standard deviations in the right-hand-grip strength test was associated with an odds ratio of 3.9 (95% CI: 2.1-7.4) for having had a fall with a fracture compared with having had no fall and with an odds ratio of 2.6 (95% CI: 1.3-5.2) for having had a fall with a fracture compared with having had a fall with no fracture. CONCLUSION the right-hand-grip strength test and the six-metre walk test performed by old men help discriminate fallers with a fracture from both fallers with no fracture and non-fallers.

Alterations of Bone Density, Microstructure, and Strength of the Distal Radius in Male Patients With Rheumatoid Arthritis: A Case-Control Study With HR-pQCT

In this cross‐sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age‐matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual‐energy X‐ray absorptiometry. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, –3.9% to –23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, –8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole‐bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro‐inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL‐6 and IL‐1β). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR‐pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in male RA patients and provides new insight into the microstructural basis of bone fragility accompanying chronic inflammation.

Prevalence of vertebral fracture in Asian men and women: Comparison between Hong Kong, Thailand, Indonesia and Japan

OBJECTIVES Little is known about the prevalence of vertebral fracture among Asians. This study investigated the prevalence of radiographically defined vertebral fracture, and identified associated risk factors in the aged population of four Asian countries. STUDY DESIGN In total, 1588 males and females aged ≥ 65 years were recruited from Hong Kong, Thailand, Indonesia and Japan. METHODS Standard X-rays for the spine were taken and vertebral heights were measured. Vertebral fracture was defined as a reduction of >3 standard deviations in vertebral height ratio. Bone mineral density (BMD) of the hip was measured by dual energy X-ray absorptiometry, and anthropometric measurements were taken in Hong Kong and Japan. Other relevant data were entered in a standard questionnaire. RESULTS The prevalence of vertebral fracture for both males and females was highest in Japan for younger (65-74 years) and older (≥ 75 years) age groups (36.6% and 37.6% for males; 18.8% and 28.7% for females). Lower hip BMD was associated with vertebral fracture in both sexes. Older age, lower quality of life score on Short Form-12 (physical), past longest occupation as a farmer, and history of cataract were significantly associated with vertebral fracture in females. However, smoking did not appear to be an important risk factor for vertebral fracture. CONCLUSIONS Radiographic assessments for vertebral fracture were performed in all four Asian countries. The prevalence of vertebral fracture was highest in Japan. Lower hip BMD, poorer physical condition and past longest occupation as a farmer were associated with vertebral fracture.

Determinants of bone mineral density in older postmenopausal Chinese women

Objective The study was performed to identify the risk factors of osteoporosis in older Chinese women. Methods Two thousand Chinese women aged above 65 years (65–98 years) were recruited. The subjects were interviewed by a structured questionnaire and had a physical examination. Bone mineral density (BMD) at the total hip and lumbar spine was measured by dual X-ray densitometry. Results On stepwise multiple regression, body weight, daily dietary calcium intake, history of diabetes mellitus and hypertension, and age of menopause were positively associated with BMD at total hip and spine. Age of menarche, duration of lactation and history of fracture at or after 50 years of age were significant negative predictors of BMD of total hip and spine. Age, current smoking, and history of gastrectomy were associated with lower BMD at the hip. Physical activity was associated with higher hip BMD. Tertiary education and alcohol consumption were associated with higher BMD at the spine. The explained variances of total hip BMD and spine BMD by these factors were 37.9% and 29.4%, respectively. Conclusion Lifestyle factors and medical history have significant influence on BMD in older postmenopausal Chinese women. The influence of gynecological and obstetric history was relatively small.