Anthony W.L. Kwok

Bio: Anthony W.L. Kwok is an academic researcher from The Chinese University of Hong Kong. The author has contributed to research in topics: Osteoporosis & Bone mineral. The author has an hindex of 25, co-authored 55 publications receiving 1355 citations.

Prevalence and risk factors of radiographic vertebral fractures in elderly Chinese men and women: results of Mr. OS (Hong Kong) and Ms. OS (Hong Kong) studies

Abstract: This study investigated the prevalence of radiographic vertebral fractures using Genant’s semiquantitative (SQ) scoring system in elderly Chinese men (n = 2,000; mean age, 72.4 years) and women (n = 2,000; mean age, 72.6 years). Vertebral deformities had similar prevalence in elderly men (14.9 %) and women (16.5 %). Majority of the deformities in men were mild (9.9 %, grade = 1). The prevalence of vertebral fractures (grade ≥ 2) was 5.0 % among men and 12.1 % among women. Vertebral fracture is a serious consequence of osteoporosis and is often under-diagnosed. Researches on different ethnicities and territories to estimate the prevalence of vertebral fractures and to identify the risk factors are necessary. Mr. OS (Hong Kong) and Ms. OS (Hong Kong) represent the first large-scale cohort studies ever conducted on bone health in elderly Chinese men (n = 2,000) and women (n = 2,000). The current study investigated the prevalence of radiographic vertebral fractures in these subjects using Genant’s SQ scoring system and identified risk factors for vertebral fractures. The radiographs of all men (mean age, 72.4 years) and women (mean age, 72.6 years) were obtained. Six hundred twenty-seven subjects (15.7 %) had at least one vertebral deformity (SQ grade ≥ 1), including 297 men (14.9 %) and 330 women (16.5 %, p = 0.151). Three hundred forty-two participants (8.6 %) were defined as having at least one vertebra fracture (SQ grade ≥ 2), consisted of 100 men (5.0 %) and 242 women (12.1 %, p < 0.001). Older age, lower bone mineral density, lower physical activity, lower grip strength, fracture history, and low back pain were significantly associated with higher vertebral fracture rate for both men and women. Vertebral deformity had similar prevalence in older men and women, while vertebral fracture was more common in women. Majority of deformities in men was mild. The vertebral deformity prevalence of women from this study is similar to previous reports of other East Asian women and Latin American women.

Relationship between gender, bone mineral density, and disc degeneration in the lumbar spine: a study in elderly subjects using an eight-level MRI-based disc degeneration grading system.

Abstract: The study cohort comprised 196 females and 163 males. Lumbar spine bone mineral density (BMD) and magnetic resonance imaging (MRI) were acquired. Females had more severe disc degeneration than males. Lumbar spine lower BMD was associated with less severe disc degeneration. Lumbar disc spaces were more likely to be narrower when vertebral BMD was higher. The purpose of this paper is to study the relationship between gender, BMD, and disc degeneration in the lumbar spine. The study cohort comprised 196 females and 163 males (age range 67–89 years) with no age difference between the two groups. Lumbar spine BMD was measured with dual X-ray densitometry, and MRI was acquired at 1.5 T. A subgroup of 48 males had additional lumbar vertebral quantitative computerized tomography densitometry. Lumbar disc degeneration was assessed using a MRI-based eight-level grading system. Female subjects had more severe disc degeneration than male subjects. After removing age effect, a positive trend was observed between T-score and severity of lumbar disc degeneration. This was significant in female subjects while not significant in male subjects. Lumbar disc spaces were more likely to be narrowed when vertebral BMD was higher. These observations were more significant in the midlumbar region (L3/4 and L4/5) and less so at the thoracolumbar junction. Female subjects tended to have slightly more severe lumbar disc degeneration than male subjects. Lower lumbar spine BMD was associated with less severe disc degeneration.

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

Abstract: 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.

Prevalence and risk factors of lumbar spondylolisthesis in elderly Chinese men and women.

Abstract: Objective A screening survey for osteoporotic fractures in men and women in Hong Kong represents the first large-scale prospective population-based study on bone health in elderly (≥65 years) Chinese men and women. This study aims to identify the prevalence and potential risk factors of lumbar spondylolisthesis in these subjects.

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

Abstract: Intervertebral disc degeneration is a common musculoskeletal condition. It can progress to disc herniation, spinal canal stenosis, and, in conjunction with facet joint arthrosis, degenerative spondylolisthesis. The factors initiating and influencing the progression of disc degeneration remain unclear. Nevertheless, there is a general agreement that spinal mechanical stress accelerates the progression of disc degeneration. Young men are more susceptible to disc degeneration than are young women, most likely due to increased mechanical stress and physical injury. Disc degeneration becomes apparent in men in the second decade of life, at almost a decade earlier than in women (1,2). The severity of age-matched disc degeneration is also generally greater in young and middle-aged men (1,2). In a recent MR imaging-based survey of young adults 20–22 years, lumbar disc degeneration was significantly more frequent in men (3). While young and middle-aged men are more likely to have lumbar disc degeneration than women, two recent population based studies indicated that this trend is reversed in elderly subjects, with women tending to have more severe lumbar disc degeneration than men. In a radiographic study of subjects 55 years and older, de Schepper et al (4) found that disc space narrowing (DSN) was more prevalent in women than men. Using an MR-based disc degeneration grading system, Wang et al. showed that elderly female subjects had more severe disc degeneration than elderly male subjects at all lumbar levels (5,6). It has been postulated that a decrease in estrogen level may be important with regard to accelerated disc degeneration in post-menopausal women (7). Mr Os (Hong Kong) and Ms OS (Hong Kong) represent the first large scale prospective cohort studies ever conducted on bone health in Asian men and women. Two thousand Chinese elderly men and two thousand Chinese elderly women were studied to determine the relationship between anthropometric, lifestyle, medical and other factors with bone mineral density (BMD) at the hip and spine. The purpose of this current study is four-fold: 1) to determine the prevalence of radiographic lumbar DSN in elderly Chinese men and women; 2) to confirm whether DSN is more prevalent in elderly Chinese women than men and how this changes among different age groups; 3) to investigate the relationship between DSN and BMD; and 4) to identify potential risk factors for lumbar DSN in Chinese population. Radiographic DSN is a manifestation of late stage disc degeneration.

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

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.

The JAK-STAT Pathway: Impact on Human Disease and Therapeutic Intervention*

Abstract: The Janus kinase (JAK)–signal transducer of activators of transcription (STAT) pathway is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules. This pathway provides an elegant and remarkably straightforward mechanism whereby extracellular factors control gene expression. It thus serves as a fundamental paradigm for how cells sense environmental cues and interpret these signals to regulate cell growth and differentiation. Genetic mutations and polymorphisms are functionally relevant to a variety of human diseases, especially cancer and immune-related conditions. The clinical relevance of the pathway has been confirmed by the emergence of a new class of therapeutics that targets JAKs.

The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations

Abstract: Lifestyle choices influence 20–40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years—a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one’s genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach.