Project Summary/Abstract Most patients who fracture have non-osteoporotic bone mineral density. Often, the result of a fracture is devastating and results in substantial morbidity and health care costs. One cause of fragility in these patients is poor bone quality that subsequently contributes to higher risk for fracture. Yet few techniques are available to accurately assess bone quality in the clinic. Dual energy x-ray absorptiometry (DXA) is the most used clinical surrogate for fracture risk, but DXA does not account for bone quality and thus overestimates bone health. OsteoProbe® enables the measurement of bone quality in human patients and has been FDA cleared. The OsteoProbe® quantifies bone material quality as a measure termed bone material strength index (BMSi) at the tibia through a rapid microindentation process. A significant and highly predictive relationship has been demonstrated between tibial BMSi and fracture occurrence at multiple skeletal sites. BMSi has also been shown to be strongly predictive of bone strength at the femoral neck. The ongoing SBIR Phase II study is investigating the relationship between OsteoProbe measurements at the tibia and bone strength at these clinically relevant skeletal sites on post-menopausal cadavers. We hypothesize that OsteoProbe® measurements will also prove valuable for HIV patients who are at higher risk of fracture but do not have low BMD. The proposal aims to: (1) Contrast DEXA and BMSi as predictors of true bone strength between HIV+ and HIV- populations across multiple skeletal sites, and (2) Determine the microstructural and tissue-level changes in HIV bone that is detectable by the OsteoProbe, compared with those of the normal aging population. We hypothesize that HIV+ bones will exhibit impairments at lower length scales that differentially affects BMSi than non-HIV bones.