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As the population ages, osteoporosis-related fractures represent a major and costly public health concern that is associated with increased morbidity and mortality in the United States, particularly in postmenopausal women [1]. A Surgeon General’s Reported has pointed out the importance of early diagnosis and appropriate treatment of bone diseases [2]. Treatment is typically indicated based on a bone mineral density (BMD) value of osteoporosis or a prior fragility fracture. Of note, many fragility fractures occur in postmenopausal women with non-osteoporotic BMD values. More significantly, a prior fragility fracture, particularly a prevalent vertebral fracture (VF), is a strong predictor for the elevated risk of subsequent fractures [3-7]. Hence, early identification of VFs is of great importance for initiating pharmacological therapy in women who may not otherwise be treated in order to prevent future fractures. VFs are often subclinical which require additional efforts to identify these fractures [8]. Lateral dual-energy X-ray absorptiometry (DXA) scanning of the entire spine for vertebral fracture assessment (VFA) has been proposed by the International Society for Clinical Densitometry (ISCD) as an alternative of x-ray for the diagnosis of VFs [9]. Also, the National Osteoporosis Foundation (NOF) has provided guidelines when VFA should be performed [10]. However, the effectiveness of VFA as a screening tool for the identification of prevalent VFs is unclear and the cost-effectiveness of VFA is unknown, both limiting the implementation of VFA into routine care. Therefore, I conducted a systematic review and meta-analysis, the results of which have shown that the weighted pooled prevalence of VFA-detected VFs in asymptomatic women was 28%. Given that VFA is effective, I further evaluated the cost-effectiveness of VFA as a screening tool to reduce future osteoporotic fracture risk in U.S. postmenopausal women. The reference-case analysis has shown that VFA has the greatest cost-saving when the screening is initiated at age 65 years and with follow-up screening every 5 years. These findings support the NOF guidelines for the diagnostic use of VFA. There are some women with increased risk for secondary osteoporosis who may not be eligible for BMD or VFA screening due to their younger age, for example, women with human immunodeficiency virus (HIV) infection. Therefore, an accurate fracture risk assessment tool is an important component in the management of bone health in HIV-infected women. The interests of validating the predictive accuracy of FRAX® (a widely accepted fracture risk prediction tool in general population [11]) arose from the reported poor performance of FRAX in older HIV-infected men [12]. I validated FRAX performance in HIV-infected women using the Women’s Interagency HIV study (WIHS), suggesting that FRAX also underestimated fracture risk in HIV-infected women, but improved with the addition of DXA parameters. The results of the above studies demonstrate the potential role of VFA in reducing future fracture risk in women with prevalent VFs and the cost-effectiveness of incorporating VFA into routine screening for osteoporosis in postmenopausal women. Data were also provided for improving the fracture prediction in people with secondary osteoporosis using HIV infection as a model. These data may inform clinicians, policy makers and insurers on the benefit of including disease specific risk factors for fracture prediction and VF identification tools in the fight to prevent osteoporosis related fractures.

[Truncated abstract] The cost of managing osteoporotic fractures places a significant financial burden on the health-care system. To reduce the fracture burden, early identification of fracture risk is essential to allow early intervention. The limitations associated with dual-energy X-ray absorptiometry (DXA), such as limited sensitivity and specificity, cost, ionising radiation and accessibility, have resulted in the emergence of other technologies for assessing bone fragility. An example is the portable and non-ionising quantitative ultrasound (QUS) technology. The discriminatory power of quantitative ultrasonometry in fracture risk identification, either independently or in combination with other established risk factors, currently remains contentious. It is recommended that fracture risk assessment should not only focus on bone status, but also on the risk of falls. Additionally, it has been noted that disability arising from osteoporotic fractures, even when these fractures are not identified clinically, can translate into psychosocial symptoms and a poorer perception of health-related quality of life (HRQoL). The primary aim of the present study was to investigate if a composite model comprising: calcaneal QUS, falls risk and HRQoL assessments, can identify a group of elderly women at high risk of osteoporotic fracture from those at lower risk. One hundred and four community-dwelling women (mean age 71.3 ±5.8 years) were recruited for this study. These women underwent a series of tests that included: DXA bone mineral density (BMD) evaluation of the proximal femur and lumbar spine (L1 L4); calcaneal QUS measurement; spinal radiography; rasterstereographic back surface curvature (BSC) examination; and performance-based assessment of strength, mobility and balance. The women were classified into a `High Risk’group or a `Low Risk’ group using three separate classification criteria: i) low BMD, based on the World Health Organisation (WHO) recommended T-score of < -2.5, and⁄or a history of fragility fracture (Osteoporotic [OP] group versus Non-Osteoporotic [NOP] group); ii) presence of at least one radiographically identified prevalent vertebral fracture (Vertebral Fracture [VF] group versus Non-Vertebral Fracture [NVF] group); or iii) a history of either forearm or wrist fracture (Forearm/Wrist Fracture [WF] group versus Non-Forearm/Wrist Fracture [NWF] group)

The purpose of this paper is the development of a model to investigate possible causal relationships among some of the commonly reported risk factors for the development of osteoporosis and consequential hip fracture. Comparison of hip fracture incidence between women of primarily European descent, referred to in the literature as Caucasians, and Japanese women is made. Studies report the incidence of hip fractures among Japanese women is lower than among Caucasian women. Numerous factors related to the development of osteoporosis are significantly different between Japan and the United States. The model helps explain the interrelationships among the variables involved in this observed geographical variation in hip fracture incidence. / Department of Anthropology