Bone mineral density enhances use of clinical risk factors in predicting ten-year risk of osteoporotic fractures in Chinese men: the Hong Kong Osteoporosis Study.

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.

Clinical risk factor assessment had better discriminative ability than bone mineral density in identifying subjects with vertebral fracture.

UNLABELLED: 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. INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Ten-year fracture probability in Hong Kong Southern Chinese according to age and BMD femoral neck T-scores.

UNLABELLED: This study estimated the 10-year probability of osteoporotic fracture in Hong Kong Southern Chinese based on a simplified model of the recently developed WHO fracture risk prediction tool (FRAX). Thus, the data provides further insights into potential development of a population-specific FRAX model for Hong Kong in the future. INTRODUCTION: The purpose of this paper was to estimate the 10-year probability of osteoporotic fracture in Hong Kong (HK) Southern Chinese according to age and bone mineral density (BMD) T-score at the femoral neck based on the methodology of the FRAX risk assessment tool calibrated to the epidemiology of HK. METHODS: Hip fracture data was obtained from the Clinical Data Analysis Reporting System (CDAS) of the Hospital Authority of HK and population size and death rates were taken from the HK Government Census and Statistics Department. Fracture probability was calculated using the cut-off values for T-scores derived from the NHANES III data for Caucasian women aged 20-29 years for BMD at the femoral neck. RESULTS: In this study, the 10-year probability of osteoporotic fracture in HK Southern Chinese increased markedly with increasing age and decreasing femoral neck BMD T-scores in both women and men. Interestingly, at low T-scores, the increase in 10-year probability of osteoporotic fracture in women with age was greater than in men. Fracture probabilities were substantially higher than those from mainland China. CONCLUSIONS: Based on this evidence, and until we have HK Southern Chinese population-specific information, we recommend the application of the Caucasian risk profile to calculate the absolute fracture risk for HK Southern Chinese subjects.

Loss of [3H]4-DAMP binding to muscarinic receptors in the orbitofrontal cortex of Alzheimer's disease patients with psychosis.

RATIONALE: Neuropsychiatric behaviours in Alzheimer's disease (AD) patients have been associated with neocortical alterations of presynaptic cholinergic and muscarinic M2 receptor markers. In contrast, it is unclear whether non-M2 muscarinic receptors have a role to play in AD behavioural symptoms. OBJECTIVES: To correlate the alterations of neocortical postsynaptic muscarinic receptors with clinical features of AD. MATERIALS AND METHODS: [(3)H]4-DAMP were used in binding assays with lysates of Chinese hamster ovary (CHO) cells stably transfected with M1-M5 receptors. [(3)H]4-DAMP was further used to measure muscarinic receptors in the postmortem orbitofrontal cortex of aged controls and AD patients longitudinally assessed for cognitive decline and behavioural symptoms. RESULTS: [(3)H]4-DAMP binds to human postmortem brain homogenates and M1-, M3-, M4- and M5-transfected CHO lysates with subnanomolar affinity. Compared to the controls, the [(3)H]4-DAMP binding density is reduced only in AD patients with significant psychotic symptoms. The association between reduced [(3)H]4-DAMP binding and psychosis is independent of the effects of dementia severity or neurofibrillary tangle burden. CONCLUSIONS: This study suggests that the loss of non-M2 muscarinic receptors in the orbitofrontal cortex may be a neurochemical substrate of psychosis in AD and provides a rationale for further development of muscarinic receptor ligands in AD pharmacotherapy.