Low handgrip strength is a predictor of osteoporotic fractures: Cross-sectional and prospective evidence from the Hong Kong Osteoporosis Study

Handgrip strength (HGS) is a potentially useful objective parameter to predict fracture since it is an indicator of general muscle strength and is associated with fragility and propensity to fall. Our objective was to examine the association of HGS with fracture, to evaluate the accuracy of HGS in predicting incident fracture, and to identify subjects at risk of fracture. We analyzed a cross-sectional cohort with 2,793 subjects (1,217 men and 1,576 women aged 50-101 years) and a subset of 1,702 subjects which were followed for a total of 4,855 person-years. The primary outcome measures were prevalent fractures and incident major fragility fractures. Each standard deviation (SD) reduction in HGS was associated with a 1.24-fold increased odds for major clinical fractures even after adjustment for other clinical factors. A similar result was obtained in the prospective cohort with each SD reduction in HGS being associated with a 1.57-fold increased hazard ratio of fracture even after adjustment for clinical factors. A combination of HGS and femoral neck bone mineral density (FN BMD) T-score values (combined T-score), together with other clinical factors, had a better predictive power of incident fractures than FN BMD or HGS T-score alone with clinical factors. In addition, combined T-score has better sensitivity and specificity in predicting incidence fractures than FN BMD alone. This study is the first study to compare the predictive ability of HGS and BMD. We showed that HGS is an independent risk factor for major clinical fractures. Compared with using FN BMD T-score of -2.5 alone, HGS alone has a comparable predictive power to BMD, and the combined T-score may be useful to identify extra subjects at risk of clinical fractures with improved specificity. © The Author(s) 2011.published_or_final_versionSpringer Open Choice, 21 Feb 201

Ethnic difference of clinical vertebral fracture risk

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. Introduction: 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. Methods: 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. Results: 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. Conclusions: 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. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Multiscale Modeling of Red Blood Cell Mechanics and Blood Flow in Malaria

Red blood cells (RBCs) infected by a Plasmodium parasite in malaria may lose their membrane deformability with a relative membrane stiffening more than ten-fold in comparison with healthy RBCs leading to potential capillary occlusions. Moreover, infected RBCs are able to adhere to other healthy and parasitized cells and to the vascular endothelium resulting in a substantial disruption of normal blood circulation. In the present work, we simulate infected RBCs in malaria using a multiscale RBC model based on the dissipative particle dynamics method, coupling scales at the sub-cellular level with scales at the vessel size. Our objective is to conduct a full validation of the RBC model with a diverse set of experimental data, including temperature dependence, and to identify the limitations of this purely mechanistic model. The simulated elastic deformations of parasitized RBCs match those obtained in optical-tweezers experiments for different stages of intra-erythrocytic parasite development. The rheological properties of RBCs in malaria are compared with those obtained by optical magnetic twisting cytometry and by monitoring membrane fluctuations at room, physiological, and febrile temperatures. We also study the dynamics of infected RBCs in Poiseuille flow in comparison with healthy cells and present validated bulk viscosity predictions of malaria-infected blood for a wide range of parasitemia levels (percentage of infected RBCs with respect to the total number of cells in a unit volume).United States. National Institutes of Health (Grant R01HL094270)National Science Foundation (U.S.). (Grant CBET-0852948)Singapore-MIT Alliance for Research and Technology Cente

Discriminative value of FRAX for fracture prediction in a cohort of Chinese postmenopausal women

We followed 2,266 postmenopausal Chinese women for 4.5 years to determine which model best predicts osteoporotic fracture. A model that contains ethnic-specific risk factors, some of which reflect frailty, performed as well as or better than the well-established FRAX model. Introduction: Clinical risk assessment, with or without T-score, can predict fractures in Chinese postmenopausal women although it is unknown which combination of clinical risk factors is most effective. This prospective study sought to compare the accuracy for fracture prediction using various models including FRAX, our ethnic-specific clinical risk factors (CRF) and other simple models. Methods: This study is part of the Hong Kong Osteoporosis Study. A total of 2,266 treatment naïve postmenopausal women underwent clinical risk factor and bone mineral density assessment. Subjects were followed up for outcome of major osteoporotic fracture and receiver operating characteristic (ROC) curves for different models were compared. The percentage of subjects in different quartiles of risk according to various models who actually fractured was also compared. Results: The mean age at baseline was 62.1 ± 8.5 years and mean follow-up time was 4.5 ± 2.8 years. A total of 106 new major osteoporotic fractures were reported, of which 21 were hip fractures. Ethnic-specific CRF with T-score performed better than FRAX with T-score (based on both Chinese normative and National Health and Nutrition Examination Survey (NHANES) databases) in terms of AUC comparison for prediction of major osteoporotic fracture. The two models were similar in hip fracture prediction. The ethnic-specific CRF model had a 10% higher sensitivity than FRAX at a specificity of 0.8 or above. Conclusion: CRF related to frailty and differences in lifestyle between populations are likely to be important in fracture prediction. Further work is required to determine which and how CRF can be applied to develop a fracture prediction model in our population. © 2011 International Osteoporosis Foundation and National Osteoporosis Foundation.link_to_subscribed_fulltex

Post-genome wide association studies and functional analyses identify association of MPP7 gene variants with site-specific bone mineral density

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 (Pmeta = 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. © The Author 2011. Published by Oxford University Press. All rights reserved.link_to_subscribed_fulltex