There is a fundamental lack of knowledge in identifying HIV infected individuals at high risk of fracture, and determining the effectiveness of treatment. Osteoporosis is usually diagnosed using DXA that provides an estimate of areal bone mineral density (BMD) computed for skeleton sites prone to fracture such as the femoral neck and the lumbar vertebrae. While DXA is non-invasive and convenient, it is not an accurate measurement of bone quality and strength and there is increasing awareness that bone geometry and microarchitecture are of key importance as risks factors for osteoporotic fractures. Studies have reported an increased incidence of fragility fractures in HIV infected subjects despite healthy BMD. Hence, our central hypothesis is that: 1) HIV-infected patients will have greater defects in trabecular microstructure and topology as well as cortical structure and porosity than HIV uninfected subjects, independent of BMD and 2) these defects will be more severe in subjects with fragility fractures. Our long-term goal is to establish sensitive risk assessment tools using state-of?the art imaging techniques to accurately predict fracture risk in HIV-infected persons and to identify who may most benefit from preventative treatments. The objective of this one-year proposal is to apply novel 3D high-resolution imaging methods to quantitatively assess bone quality in a group of HIV-infected patients and controls, and to determine whether HIV-infected patients may be particularly affected. The primary analysis for the specific aims will be analysis of variance (ANOVA) that uses each bone mineral density (BMD), structure, topology and mechanical parameters as the dependent variables and use the three study groups as independent variables. The proposed research is significant, because it is expected to expand our understanding of how HIV metabolism and treatments affect bone quality and how fracture prevention efforts can be improved in an aging HIV positive population.