Osteoporosis alters bone mass and composition ultimately increasing the fragility of primarily cancellous skeletal sites; however, effects of osteoporosis on tissue-level mechanical properties of cancellous bone are unknown. Dual-energy x-ray absorptiometry (DXA) scans are the clinical standard for diagnosing osteoporosis though changes in cancellous bone mass and mineralization are difficult to separate using this method. The goal of this study was to investigate possible difference in tissue-level properties with osteoporosis as defined by donor T-scores. Spine segments from Caucasian female cadavers (58–92 yrs) were used. A T-score for each donor was calculated from DXA scans to determine osteoporotic status. Tissue level composition and mechanical properties of vertebrae adjacent to the scan region were measured using nanoindentation and Raman spectroscopy. Based on T-scores, six samples were in the Osteoporotic group (58–74 yrs) and four samples were in the Not Osteoporotic group (65–92 yrs). The indentation modulus and mineral to matrix ratio (mineral:matrix) were lower in the Osteoporotic group than the Not Osteoporotic group. Mineral:matrix ratio decreased with age (r2 = 0.35, p = 0.05), and the indentation modulus increased with a real bone mineral density (aBMD) (r2 = 0.41, p = 0.04)