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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.

Summary: 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., Introduction: 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., Methods: 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)., Results: 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., Conclusions: Our results suggest POSTN as a candidate gene for BMD variation and vertebral fracture risk.

Unlabelled: 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.

Unlabelled: 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.

Unlabelled: This prospective study aimed to determine the risk factors and the 10-year probability of osteoporotic fracture in Southern Chinese men. The findings show substantial population differences in fracture incidence and risk prediction compared to the FRAX(TM) model, and the addition of BMD information to clinical risk factor assessment improved fracture risk prediction in Chinese men., Introduction: Clinical risk factors with or without bone mineral density (BMD) measurements are increasingly recognized as reliable predictors of fracture risk. Prospective data on fracture incidence in Asian men remain sparse. This prospective study aimed to determine the risk factors and the 10-year absolute fracture risk in Southern Chinese men., Methods: This is a part of the Hong Kong Osteoporosis Study. One thousand eight hundred ten (1,810) community-dwelling, treatment-naive men aged 50 years or above were evaluated. Baseline demographic characteristics, clinical risk factors and BMD were recorded. Ten-year risk of osteoporotic fracture was calculated using Cox proportional hazards models., Results: The mean age of subjects was 68.0 ± 10.3 years. After a mean follow-up period of 3.5±2.9 years (range 1 to 14 years), 37 incident low-trauma fractures were recorded. The incidence for all osteoporotic fractures and hip fractures was 635/100,000 and 123/100,000 person-years, respectively. The most significant predictors of osteoporotic fracture were history of fall (RR 14.5), femoral neck BMD T-score < -2.5 (RR 13.8) and history of fracture (RR 4.4). Each SD reduction in BMD was associated with a 1.8 to 2.6-fold increase in fracture risk. Subjects with seven clinical risk factors and BMD T-score of -1 had an absolute 10-year risk of osteoporotic fracture of 8.9%, but this increased to 22.7% if they also had a femoral neck BMD T-score of -2.5., Conclusions: These findings show substantial population differences in fracture incidence and risk prediction. The addition of BMD information to clinical risk factor assessment improved fracture risk prediction in Chinese men.